Enhanced CoQsol-10 by BRI Nutrition

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Serving Size 1 Softgel(s)

Ingredients	Amount Per Serving
Vitamin E	100 IU
Vitamin A	2334 IU
Coenzyme Q-10 (CoQ10)	100 mg

Other Ingredients

Gelatin, Magnesium Stearate (Alt. Name: Mg Stearate), Calcium Carbonate (Alt. Name: Ca Carbonate, CaCO3)

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Below is general information about the effectiveness of the known ingredients contained in the product Enhanced CoQsol-10. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COENZYME Q10 (Coenzyme Q-10)

LIKELY EFFECTIVE

Coenzyme Q10 deficiency. Taking coenzyme Q10 orally improves symptomatic deficiency. Details: Rare cases of acquired coenzyme Q10 deficiency with symptoms of weakness, fatigue, and seizures have been reported (8160,8161). In adults, deficiency can be treated with coenzyme Q10 orally, 150-2400 mg daily in up to three divided doses. In children, 30 mg/kg, or 60-250 mg daily in up to three divided doses has been used (8160,8161,89417). Data from several multinational disease registries has also evaluated the use of coenzyme Q10 in patients with primary coenzyme Q10 deficiency, a rare genetic disorder. This data indicates that patients who take coenzyme Q10 supplements have a mean reduction of 88% in proteinuria at 12 months when compared with patients who do not take coenzyme Q10. In patients under 18 years of age with primary deficiency and chronic kidney disease at baseline, taking coenzyme Q10 supplements is associated with a 5-year survival without kidney failure of 62%, compared with 19% for those not taking coenzyme Q10 (108956).
Mitochondrial myopathies. Taking coenzyme Q10 orally seems to reduce symptoms in some patients with genetic and acquired mitochondrial dysfunction. Details: A specific coenzyme Q10 formulation (UbiQGel, Tishcon Corporation) has been evaluated for mitochondrial myopathies, including MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome, Kearns-Sayre syndrome, and MERRF (myoclonus epilepsy with ragged red fibers). Typical doses are 150-160 mg, or 2 mg/kg, daily, gradually increasing to 3000 mg daily in some cases. The onset of action is slow, with maximal effects around 6 months (8159,8162,8163,8912,11050,44240,97905).

POSSIBLY EFFECTIVE

Congestive heart failure (CHF). Oral coenzyme Q10 may provide benefit to patients with CHF by improving some, but not all, measures of disease severity when given in combination with conventional therapy. Details: Population research has found that CHF is associated with low coenzyme Q10 levels that correlate with severity of disease, and may be a predictor of mortality risk (44059,44220). A 2017 meta-analysis of clinical research shows that taking coenzyme Q10 30-300 mg, or 2 mg/kg, orally daily in two or three divided doses for up to 2 years, in addition to conventional therapy, improves exercise capacity, reduces hospitalizations, and reduces mortality by about 30% when compared with placebo. Other clinical research shows that adding oral coenzyme Q10 seems to improve quality of life and decrease symptoms of CHF such as dyspnea, peripheral edema, enlarged liver, and insomnia in patients with mild to severe (New York Heart Association (NYHA) class II-IV) CHF (6037,6038,6407,6408,6409,8909,12170,43967,43971,44042)(44277,44288,44289,44304,44334,44352,95610,96542). Additional clinical research shows that taking coenzyme Q10 30 mg daily for 1 year in addition to standard care reduces the incidence of atrial fibrillation by about 73% when compared with standard care alone in patients with NYHA class II-IV CHF (95609). However, not all evidence is positive. Some research suggests that coenzyme Q10 does not improve objective measures of CHF, including left ventricular ejection fraction (LVEF), cardiac output, or NYHA classification (5090,5248,6037,6038,43904,43932,96542,43932,97902). It is possible that the benefit of coenzyme Q10 depends on the dose and duration, the severity of CHF, and the specific conventional therapies taken concurrently (43973). A meta-analysis of 11 small, low-quality studies concludes that coenzyme Q10 probably reduces risk of all-cause and cardiovascular mortality, and of hospital admission for CHF, but data on improvement in LVEF or exercise capacity and the risk for myocardial infarction and stroke are inconclusive. However, the included studies used a range of coenzyme Q10 doses, varying concurrent therapy, short follow-up periods, and variable measures of treatment effect (108954). In patients with CHF with preserved ejection fraction (HFpEF) and a LVEF of 50% or greater, taking coenzyme Q10 600 mg daily for 12 weeks reduces B-type natriuretic peptide levels and improves Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, level of vigor, and LVEF when compared with placebo (108959).
Diabetic neuropathy. When taken alone or as add-on treatment with pregabalin, most research suggests that oral coenzyme Q10 reduces symptoms in patients with diabetes and neuropathy. Details: Clinical research shows that taking coenzyme Q10 400 mg orally daily for 12 weeks significantly improves nerve conduction and symptoms of neuropathic pain when compared with placebo in diabetic patients with polyneuropathy (44217). The beneficial effects of coenzyme Q10 have also been investigated as an add-on treatment in patients taking pregabalin 150 mg daily. Clinical research shows that taking coenzyme Q10 100 mg three times daily for 8 weeks reduces pain severity and sleep interference due to pain when compared with placebo. The proportion of patients taking coenzyme Q10 with a decline in pain of at least 50% was 47%, compared with 27% of those taking placebo. Despite these findings, there was no difference in patient global improvement (109391). However, some research disagrees. One clinical trial shows that taking coenzyme Q10 (Health Burst) 200 mg daily for 12 weeks does not affect neuropathic symptoms, including pain, sensations, and strength, when compared with placebo (109386).
Fibromyalgia. Oral coenzyme Q10 seems to improve both physical and psychological symptoms of this condition. Details: Clinical research in women with fibromyalgia shows that taking coenzyme Q10 300-400 mg orally daily for 40 days to 3 months improves pain by 24% to 56%, fatigue by 22% to 47%, sleep disturbances by 33%, morning tiredness by 56%, and tender points by 44% when compared with placebo. Patients also experience an improvement in psychological symptoms, including depression and anxiety (89416,97912,97913).
Ischemia-reperfusion injury. Oral or intravenous coenzyme Q10 may help reduce hypoxic damage during cardiac bypass or vascular surgery. Details: Clinical research shows that taking coenzyme Q10, 150-300 mg orally daily in up to 3 divided doses for 1-2 weeks before cardiac bypass or vascular surgery, or 5 mg/kg IV two hours prior to surgery, reduces hypoxic damage during the surgery (11902,11903,44031,44294). However, coenzyme Q10 has no effect on cardiac function or troponin levels (11904,44292).
Migraine headache. The American Academy of Neurology considers oral coenzyme Q10 to be possibly effective for migraine prevention in adults. Its benefit in children is unclear. Details: Two small open-label, non-randomized clinical trials in adults show that taking coenzyme Q10 100-150 mg daily decreases the frequency of headaches by up to 50% when compared with baseline or control, although it can take up to 3 months to see benefit (8135,95608). Higher quality research suggests a smaller benefit. A meta-analysis of small randomized controlled trials in adults shows that taking coenzyme Q10 alone or with other supplements reduces migraine attacks by 1.5 times per month and reduces duration of migraines by about 12 minutes when compared with control (105070). In children and adolescents, some clinical research shows that taking coenzyme Q10 orally, as 100 mg daily or 1-3 mg/kg daily, for 12-16 weeks does not improve headache frequency, severity, or duration when compared with placebo. However, it may reduce migraine frequency in children with low coenzyme Q10 levels (15256,44197). However, another clinical study shows that taking coenzyme Q10 daily is less effective than amitriptyline after one month, but as effective after 3 months, for improving headache frequency, severity, or duration, as well as quality of life. In this study, the dose of coenzyme Q10 was based on weight; 30 mg daily for children weighing less than 30 kg and 60 mg daily for children weighing at least 30 kg (109388).
Multiple sclerosis (MS). Oral coenzyme Q10 seems to reduce fatigue and depression associated with MS. Details: Clinical research shows that taking coenzyme Q10 500 mg orally daily for 3 months reduces fatigue and depression in patients with MS when compared with placebo (96539).
Muscular dystrophy. Oral coenzyme Q10 seems to improve physical performance in patients with muscular dystrophy of various forms. Details: Two small clinical studies show that taking coenzyme Q10 orally 100 mg daily for 3 months seems to improve physical performance when compared with placebo in some patients with various muscular dystrophies (2127).
Myocardial infarction (MI). Oral coenzyme Q10 seems to reduce cardiac events and improve survival in patients who have had an MI. It is unclear if coenzyme Q10 improves survival in patients after cardiac arrest. Details: One small clinical study in patients with acute MI shows that starting coenzyme Q10 60 mg twice daily within 72 hours of the MI appears to significantly reduce the risk of cardiac events, including non-fatal MI and cardiac death, by 52% when administered for 28 days and by 45% when administered for up to one year (10152,44330). Also, a small clinical study in patients with recent MI who received cardiopulmonary resuscitation, shows that administering a 250 mg loading dose of coenzyme Q10 solution followed by 150 mg three times daily through a nasogastric tube for 5 days improves the 3-month survival rate by 134% when compared with placebo (43935). However, another clinical study in a similar patient population conducted to replicate these results shows that administering coenzyme Q10 300 mg in 50 mL of Ensure every 12 hours for 7 days does not improve in-hospital mortality or neurological outcomes when compared with placebo (105068).
Peyronie disease. Coenzyme Q10 taken orally may reduce Peyronie disease severity. Details: Clinical research shows that, in patients with early chronic Peyronie disease, taking coenzyme Q10 (Kaneka Nutrients, Osaka) 300 mg orally daily for 24 weeks reduces new plaque formation and plaque size and improves erectile function when compared with placebo. Additionally, disease progression is slowed in about 76% of patients (44180).

POSSIBLY INEFFECTIVE

Alzheimer disease. Coenzyme Q10 appears to be ineffective for improving cognition. Details: One clinical study shows that taking coenzyme Q10 1200 mg orally daily for 16 weeks does not improve cognition scores when compared with placebo in patients with Alzheimer disease (19206).
Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Oral coenzyme Q10 does not attenuate functional decline in ALS patients. Details: Clinical research shows that taking coenzyme Q10 2700 mg orally daily for 9 months does not significantly attenuate a decline in ALS functioning scores when compared with placebo (44131). Higher doses, up to 3000 mg daily, have been tolerated by patients with ALS for 5 months, although the effect on ALS functioning at this dose is not known (43955).
Chemotherapy-related fatigue. Oral coenzyme Q10 does not seem to help with fatigue due to chemotherapy. Details: Clinical research shows that taking coenzyme Q10 100 mg orally three times daily for 24 weeks does not reduce chemotherapy-related fatigue or improve quality of life when compared with placebo in breast cancer patients undergoing chemotherapy with or without radiation (89420).
Diabetes. Most clinical research does not show any benefit with oral coenzyme Q10 in patients with type 1 or type 2 diabetes. However, some research suggests a possible benefit on insulin resistance. Details: Although a recent meta-analysis and some individual clinical research shows that coenzyme Q10 modestly reduces fasting glucose levels and glycated hemoglobin (HbA1c) in patients with type 1 or type 2 diabetes, most clinical research shows that coenzyme Q10 has no clinically meaningful effect on these parameters (456,492,2126,9890,96544,97911,97918,99636,11877,17704,44023,103778,109389). However, a recent meta-analysis in patients with type 1 or type 2 diabetes shows that improvements in insulin resistance may be clinically meaningful when compared with placebo (109389). In people with type 2 diabetes and nephropathy requiring hemodialysis, coenzyme Q10 120 mg orally daily for 12 weeks does not improve blood glucose levels, HbA1c, or lipid levels when compared with placebo, although it is associated with a decrease in serum insulin levels and insulin resistance (99636).
Parkinson disease. Most clinical research does not show any benefit with the use of oral coenzyme Q10 in patients with Parkinson disease. Details: While some conflicting evidence exists (8938,15255), a large clinical trial and a meta-analysis of 8 small clinical studies in patients with Parkinson disease show that taking coenzyme Q10 300-2400 mg daily for up to 2 years does not improve Parkinson disease symptoms at any stage of the disease, or slow progression of the disease, when compared with placebo (89421,95610). In addition, a clinical study in patients with mid-stage Parkinson disease shows that taking a specific nanoparticulate coenzyme Q10 supplement (Nanoquinon, MSE Pharmazeutilka) 100 mg orally three times daily does not reduce symptoms when compared with placebo (15395).
Post-polio syndrome. Muscle function in people with post-polio syndrome is not improved by oral coenzyme Q10. Details: Clinical research shows that taking coenzyme Q10 100 mg twice daily for 12 weeks does not improve muscle strength when compared with baseline, nor does it improve muscle function or muscle endurance when compared with placebo, in patients with post-polio syndrome (44054). Other clinical research shows that taking coenzyme Q10 100 mg daily for 60 days does not improve levels of fatigue when compared with placebo in patients with post-polio syndrome (97917).

LIKELY INEFFECTIVE

Athletic performance. There is some evidence that exercise can deplete coenzyme Q10 and that supplementation will prevent this depletion. However, there is no evidence that taking coenzyme Q10 is beneficial. Details: Clinical research shows that taking coenzyme Q10 orally does not improve aerobic or anaerobic power or perceived exertion in athletes and non-athletes (2109,2110,8911,44122,44227). While some evidence suggests coenzyme Q10 slightly improves tolerance to higher workloads, more research is needed to tell if coenzyme Q10 is effective for this purpose (8911). One clinical study shows that taking coenzyme Q10 300 mg orally daily for 8 days reduces exercise-induced fatigue when compared with placebo (44006); other research shows that doses of 100-200 mg do not have this effect (44122,44233,44299). Taking the ubiquinol form of coenzyme Q10 200 mg orally daily for one month prevents exercise-induced coenzyme Q10 depletion and decreases levels of reactive oxygen species in blood mononuclear cells in young male athletes performing an intense long-distance run. However, it does not affect physical performance or markers of muscle damage (99429).
Huntington disease. The ubiquinol form of coenzyme Q10 does not seem to improve function in people with this condition. Details: Ubiquinol, a reduced form of coenzyme Q10, has been evaluated for use in Huntington disease (11873). However, a large, high-quality study shows that taking coenzyme Q10 2.4 grams orally daily for up to 5 years does not slow the progression or functional decline in patients with Huntington disease (96538). Other studies using doses up to 600 mg daily also show no benefit (1357,8940).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Age-related macular degeneration (AMD). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with early AMD shows that taking a specific combination product (Phototrop, Sigma-tau Health Science Ltd.) containing coenzyme Q10 10 mg, acetyl-L-carnitine 100 mg, and omega-3 fatty acids 530 mg orally daily for 12 months seems to reduce the percentage of patients who experience deterioration of vision by about 50%, and the percentage who have reduced light sensitivity by about 39%, when compared with placebo (43946). The effects of coenzyme Q10 alone are unclear.
Aging. Although there has been interest in using oral coenzyme Q10 for aging, there is insufficient reliable information about the clinical effects of coenzyme Q10 for this purpose.
Angina. There is some limited clinical evidence that coenzyme Q10 can improve exercise tolerance and symptoms in people with this condition. Details: Preliminary clinical research shows that taking coenzyme Q10 50 mg three times daily orally for 4 weeks improves exercise tolerance in people with angina by about 18% (2121). Also, taking 60 mg once daily for 4 weeks improves heart failure scores, angina symptoms, and heart volume when compared to baseline in patients with stable angina (44336). The validity of these findings is limited by the lack of a comparator group.
Anthracycline cardiotoxicity. Evidence on the use of coenzyme Q10 to protect against anthracycline cardiotoxicity in adults and children is conflicting. Details: Preliminary clinical research in children aged 3-12 years shows that taking coenzyme Q10 orally 100 mg twice daily might protect against anthracycline cardiotoxicity (44279). However, evidence from larger clinical trials evaluating patients aged 16-77 years is conflicting. Results from one of these studies suggests that intravenous administration of coenzyme Q10 1 mg/kg daily the day before, the day of, and for 2 days after anthracycline treatment does not protect against cardiotoxicity (44267). Differences between the studies may be due to methodological problems, or differences in doses, route of administration, and age of participants.
Asthma. Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of coenzyme Q10 (Q-Gel, Tishcon Corporation) 120 mg, vitamin E 400 mg, and vitamin C 250 mg orally daily in addition to conventional anti-asthmatic therapy for 16 weeks might reduce the dosage of corticosteroids required by patients with mild to moderate asthma. However, it does not appear to improve lung function any more than standard therapy alone (43969).
Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral coenzyme Q10 is beneficial in children with ADHD. Details: A small clinical study in children aged 6-16 years with ADHD who are unresponsive to atomoxetine therapy shows that taking coenzyme Q10 1-3 mg/kg with atomoxetine 0.5-1.8 mg/kg daily for 6 months improves parent-rated symptoms of ADHD, particularly hyperactivity-related symptoms, when compared with placebo plus atomoxetine (107449).
Autism spectrum disorder. It is unclear if the ubiquinol form of coenzyme Q10 taken orally is beneficial in children aged 3-6 years with this condition. Details: A small clinical study in children aged 3-6 years suggests that taking the reduced form of coenzyme Q10, ubiquinol (Li-QH, Tishcon Corporation), 50 mg orally once daily for one week followed by 50 mg twice daily for 11 weeks, improves symptoms of autism spectrum disorder, including communication with parents, ability to play with friends, verbal communication, sleeping, food rejection, aggressiveness, and self-harm, when compared with baseline, per parent assessment (89419). The validity of these findings is limited by the small study size, the use of parent assessment, and the lack of a comparator group.
Benign prostatic hyperplasia (BPH). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with BPH shows that taking coenzyme Q10 100 mg plus L-carnitine daily for 8 weeks modestly decreases prostate volume and improves sexual performance when compared with placebo. There was no effect on prostate symptoms, prostate specific antigen levels, or quality of life. All patients were also taking finasteride 5 mg daily (113226). It is unclear if these effects are due to coenzyme Q10, L-carnitine, or the combination.
Bipolar disorder. It is unclear if oral coenzyme Q10 is beneficial for bipolar disorder in older adults. Details: Preliminary clinical research in people 55 years of age or older with bipolar disorder shows that taking coenzyme Q10 800 mg orally daily for 4 weeks improves symptoms of depression when compared with baseline (95606). The validity of this finding is limited by the lack of a comparator group.
Breast cancer. Low coenzyme Q10 levels may be associated with an increased risk of breast cancer. The benefit of coenzyme Q10 supplementation is unclear. Details: Population research in Chinese women has found that low plasma coenzyme Q10 levels are associated with an increased risk of breast cancer (44194).
Cancer. Low coenzyme Q10 levels may increase the risk of cancer development and progression. Details: Population research has found that low coenzyme Q10 levels are associated with increased risk of metastatic melanoma (43959). Preliminary clinical research suggests that taking coenzyme Q10 150 mg twice daily along with vitamins A, C, and E, selenomethionine, beta-carotene, and folic acid extends survival time by 40% when compared with predicted survival in patients with end-stage cancer from various different primary sites (44159). It is unclear if this effect is due to coenzyme Q10, other ingredients, or the combination.
Cardiovascular disease (CVD). It is unclear whether oral coenzyme Q10 has a role in preventing complications from CVD. Details: Preliminary clinical research shows that taking coenzyme Q10 300 mg 2 hours prior to an elective percutaneous coronary intervention does not reduce periprocedural myocardial injury or prevent major adverse cardiac events during one month of follow-up (96543). Other clinical research shows that taking a combination of coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg twice daily plus organic selenium yeast tablets (SelenoPrecise, Pharma Nord) 200 mcg daily for 4-5 years reduces the risk of death from CVD by 7% when compared with placebo in elderly people living in Sweden (92904). This benefit appears to persist even after supplement discontinuation, with an 18% reduction at 10 years and an 11% reduction at 12 years (96546,97466,97906). In this same trial, post-hoc subgroup analyses in patients with elevated baseline D-dimer levels and/or hypertension or ischemic heart disease shows that taking this combination reduces cardiovascular mortality when compared with placebo (105874). It is unclear if these benefits are due to coenzyme Q10, selenium, or the combination.
Cataracts. It is unclear if coenzyme Q10-containing eye drops are beneficial in patients undergoing cataract surgery. Details: Clinical research suggests that administering an ophthalmic solution containing coenzyme Q10 and vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate twice daily for 9 months increases the speed of nerve regeneration when compared with saline solution in post-cataract surgery patients (44228).
Cerebellar ataxia. It is unclear if coenzyme Q10 is beneficial for this condition. Details: Preliminary clinical research in patients with cerebellar ataxia shows that coenzyme Q10 30 mg/kg daily for 2 years improves ataxia scores by 48%, posture scores by 63%, and kinetic function scores by 37% when compared with baseline, but only in patients who are coenzyme Q10 deficient (44177). The validity of these findings is limited by the lack of a comparator group.
Chronic fatigue syndrome (CFS). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with CFS shows that taking coenzyme Q10 200 mg plus NADH 20 mg daily for 8 weeks does not improve measures of fatigue, sleep, or quality of life when compared with placebo (107448).
Chronic obstructive pulmonary disease (COPD). It is unclear if coenzyme Q10 is beneficial for improving exercise tolerance in people with COPD. Details: Preliminary clinical research suggests that taking coenzyme Q10 90 mg daily for 8 weeks reduces lactate production during anaerobic exercise in people with COPD, but does not improve oxygen consumption or exercise performance, when compared with baseline (44293). The validity of these findings is limited by the lack of a comparator group.
Cocaine dependence. Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients with cocaine dependence shows that taking a combination of coenzyme Q10 200 mg and L-carnitine 500 mg orally daily for 8 weeks does not reduce cocaine use when compared with placebo, as measured by urine benzoylecgonine levels and self-reported usage (43940).
Coronavirus disease 2019 (COVID-19). It is unclear if oral coenzyme Q10 is beneficial for patients with persistent symptoms after COVID-19 infection. Details: Clinical research in individuals with previous confirmed COVID-19 infection and continued symptoms lasting more than 12 weeks shows that taking coenzyme Q10 (Pharma Nord) 100 mg five times daily for 6 weeks does not reduce the number or severity of symptoms when compared with placebo. The most common symptoms were concentration problems, mental and physical fatigue, headache, and/or muscle weakness (109392).
Critical illness (trauma). It is unclear if oral coenzyme Q10 is beneficial in patients hospitalized due to acute trauma. Details: Preliminary clinical research in patients who are mechanically ventilated due to acute trauma and have low baseline coenzyme Q10 plasma levels shows that taking sublingual coenzyme Q10 (Nutri Q10, Nutri Century) 400 mg daily for 7 days reduces the duration of intensive care stay, mechanical ventilation, and hospitalization by 4 days, 2 days, and 6 days, respectively, when compared with placebo. Patients taking coenzyme Q10 also demonstrated larger improvements in organ function scores and coma scores than those taking placebo (105875).
Cyclic vomiting syndrome (CVS). Limited evidence suggests oral coenzyme Q10 may reduce episodes of CVS. Details: Preliminary clinical research shows that taking coenzyme Q10 10 mg/kg orally twice daily is comparable to amitriptyline 0.5-1 mg/kg/day for reducing the number of CVS episodes in both children and adults (17703).
Diabetic nephropathy. Although there has been interest in using oral coenzyme Q10 for diabetic nephropathy, there is insufficient reliable information about the clinical effects of coenzyme Q10 for this purpose.
Dilated cardiomyopathy. Very small clinical studies suggest that children and adolescents with dilated cardiomyopathy may benefit from oral coenzyme Q10. Details: Preliminary clinical research in children with dilated cardiomyopathy suggests that taking coenzyme Q10 3-10 mg/kg daily, divided into 2-3 doses for up to 9 months, improves ejection fraction and New York Heart Association (NYHA) classification when compared to baseline (12199,13223). Also, in people under 20 years of age, taking a specific oral liquid formulation of coenzyme Q10 (QuinoMit Q10 Fluid, MSE Pharmazeutika GmbH), 10 mg/kg daily for 24 weeks produces a small increase in ejection fraction and improves NYHA class from II to I in 30% of patients (99427). The validity of these findings is limited by the lack of comparator groups.
Dry eye. Ophthalmic coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research has evaluated the use of a specific eye drop (VisuXL, Visufarma) containing coenzyme Q10 and cross-linked hyaluronic acid, in a 1:1 ratio with alpha-tocopherol polyethylene glycol succinate. One study in menopausal women receiving antidepressants shows that placing 1 drop in each eye twice daily for 8 weeks reduces dry eye severity by 17% and improves tear break-up time when compared to 5 drops daily of carmellose eye drops (104553). In addition, another study in adults with mild to moderate dry eye shows that placing 1 drop in each eye four times daily for 12 weeks reduces dry eye severity by 14% and decreases some laboratory markers of dry eye when compared to hyaluronic acid alone. Both groups demonstrated similar improvement in meibomian gland function and tear break-up time (97909). The effect of coenzyme Q10 when used alone is unclear.
Dry mouth. It is unclear if oral ubiquinol or ubiquinone improves salivary secretion. Details: Preliminary clinical research suggests that taking coenzyme Q10, as the reduced ubiquinol form or as the oxidized ubiquinone form, 100 mg orally daily for one month, improves salivary secretion by 72% to 82% when compared with baseline in patients with dry mouth (44191). The validity of these findings is limited by the lack of a comparator group.
Erectile dysfunction (ED). It is unclear if oral coenzyme Q10 is beneficial in patients with ED. Details: A small, open-label study in patients with hypertension and complaints of ED shows that taking coenzyme Q10 200 mg daily for 3 months along with current antihypertensive therapy does not improve symptoms of ED when compared with antihypertensive therapy alone (107447).
Fatigue. It is unclear if oral coenzyme Q10 is beneficial for reducing fatigue. Details: A meta-analysis of low- to moderate-quality clinical research in mixed populations shows that taking coenzyme Q10 modestly reduces feelings of fatigue when compared with placebo. This improvement was consistent between groups of healthy individuals and individuals with fatigue related to disease. However, a sub-group analysis shows that benefits are limited to studies in which coenzyme Q10 was studied as a single ingredient. Doses of coenzyme Q10 ranged from 60 mg to 500 mg daily for 4-12 weeks with treatment effects appearing to be both dose- and duration-dependent (109387).
Friedreich ataxia. Oral coenzyme Q10 has been evaluated in combination with vitamin E; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking coenzyme Q10 (Bio-Quinon Q10, Pharma Nord) 200 mg orally twice daily plus vitamin E (Bio-E-Vitamin, Pharma Nord) 1050 IU twice daily for 47 months improves measures of cardiovascular function by 20% when compared with baseline. However, it does not improve posture or gait, or prevent deterioration of posture, gait, speech, or eye function, when compared with baseline (43943,44064). It is unclear if these benefits are due to coenzyme Q10, vitamin E, or the combination. Also, the validity of these findings is limited by the lack of a comparator group.
Hearing loss. There is conflicting evidence regarding the effects of oral coenzyme Q10 on hearing loss of various etiologies. Details: Some clinical research shows that taking coenzyme Q10 terclatrate (Qter), a water-soluble formulation of coenzyme Q10, 160 mg orally daily for 30 days improves hearing thresholds when compared to baseline in patients with age-related hearing loss (44171,44184). However, taking coenzyme Q10 terclatrate 200 mg daily for 7 days does not significantly improve hearing thresholds when compared with placebo in patients with noise-induced hearing loss (44143). Also, combining coenzyme Q10 with conventional steroid therapy for 2 weeks does not improve hearing when compared with steroid therapy alone in patients with sudden sensorineural hearing loss (44185).
Hepatitis C. It is unclear if oral coenzyme Q10 is beneficial in patients with this condition. Details: Clinical research shows that taking coenzyme Q10 up to 80 mg orally daily for 28 days does not reduce serum liver enzymes when compared with placebo in patients with chronic hepatitis C who are unresponsive to conventional treatment (44172).
Hyperlipidemia. There is conflicting evidence regarding the effects of coenzyme Q10 on cholesterol levels in adults. However, any changes are unlikely to be clinically meaningful. Details: A meta-analysis of 50 moderate-quality clinical trials shows that taking coenzyme Q10 has small beneficial effects on levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides when compared with a control, usually placebo (109394). However, whether coenzyme Q10 produces clinically meaningful changes is unclear. In a subgroup of patients with dyslipidemia, coenzyme Q10 does not seem to have significant beneficial effects on total cholesterol (109394). Also, previous individual clinical trials and meta-analyses in specific populations, including studies in which lipoprotein A was measured, as well as populations with diabetes, coronary artery disease, and others, have not shown beneficial effects on plasma lipids (17704,44187,96545,97918,109394). The effect of coenzyme Q10 on lipoprotein A has also been investigated. Individual studies and a meta-analysis show that taking coenzyme Q10 slightly reduces plasma levels of lipoprotein A when compared with placebo (17704,44187,96545). Most studies have used doses of 100-500 mg daily for 4-24 weeks (17704,44187,96545,96547,97910,109394). Coenzyme Q10 has also been studied in combination with other ingredients. A moderate-sized, open-label clinical study in adults with mild hypercholesterolemia and low cardiovascular disease risk shows that taking a combination product containing coenzyme Q10 2 mg, red yeast rice, grape seed extract, olive tree leaf extract, and B vitamins (Arichol, Epsilon Health) daily for 8 weeks reduces total cholesterol and LDL cholesterol, but not HDL cholesterol or triglycerides, when compared with placebo (111559). The validity of this effect is limited by a lack of blinding. It is unclear if this effect is due to coenzyme Q10, other ingredients, or the combination.
Hypertension. Most research suggests that oral coenzyme Q10 may reduce systolic blood pressure (SBP), but not diastolic blood pressure (DBP). Details: Most clinical research shows that taking coenzyme Q10 100-900 mg orally daily in divided doses, either alone or with conventional medications, for up to 12 weeks significantly lowers SBP (2122,3365,9890,17702,17650,17651,44343,109393). One meta-analysis of moderate quality clinical research in patients with cardiometabolic disorders shows that supplementation with coenzyme Q10, especially 100-200 mg daily for at least 12 weeks, reduces SBP by 5 mmHg (109393). However, some studies show conflicting results. Most clinical research shows that coenzyme Q10 supplementation does not reduce DBP (8907,96541,109393). Also, a meta-analysis of two clinical studies (17651,44211) shows that taking coenzyme Q10 100-200 mg orally daily has no significant effect on blood pressure when compared with placebo (95607). Conflicting results may be due to differences in the severity of hypertension at baseline, adjustments made to conventional medications during studies, and the presence of a variety of concomitant conditions. Some data also suggest that effects may be greater in people with low baseline levels of coenzyme Q10 (2122,17650,17651).
Hypertrophic cardiomyopathy. It is unclear if oral coenzyme Q10 is beneficial for this condition. Details: A very small clinical study of 7 patients suggests that taking coenzyme Q10 (Vitaline) 120-240 mg orally daily with the goal of raising blood levels above 2 mcg/mL, might improve symptoms of hypertrophic cardiomyopathy, including dyspnea and fatigue, and decrease cardiac wall thickness, when compared to baseline (11031). The validity of these findings is limited by the small size of the study and the lack of a comparator group.
Infertility. It is unclear if oral coenzyme Q10 helps women undergoing assisted reproductive technology (ART) treatment. Details: A meta-analysis of 5 small clinical studies in infertile women undergoing ART treatment shows that although coenzyme Q10 increases the odds of clinical pregnancy more than 2-fold, it does not seem to affect the rate of live births or miscarriages when compared with placebo or no treatment (103780).
Kidney failure. Oral coenzyme Q10 has been reported to improve renal function in people with kidney failure, but not in those with less severe kidney disease. Details: Preliminary clinical research in patients with kidney failure shows that taking coenzyme Q10 180 mg orally daily for 28 days improves blood urea nitrogen, serum creatinine, and creatinine clearance when compared with placebo (44347). However, other clinical research in patients with less severe kidney disease shows that taking coenzyme Q10 200 mg daily for 8 weeks does not significantly improve kidney function parameters, including urinary albumin, total protein, or glomerular filtration rate, when compared with placebo (44128).
Lichen planus. It is unclear if topical coenzyme Q10 is beneficial for oral lichen planus. Oral coenzyme Q10 has not been studied for this condition. Details: A small clinical study in patients with oral lichen planus conducted in Egypt shows that applying topical coenzyme Q10 (ubiquinol) 120 mg as a mucoadhesive tablet 3 times daily for 4 weeks does not improve pain scores or lesion size when compared with topical corticosteroid paste (111617).
Male Infertility. Oral coenzyme Q10 may improve some measures of sperm function in males with infertility, but there is no convincing evidence that it can increase pregnancy rates. Details: One small clinical study in males with idiopathic asthenozoospermia shows that coenzyme Q10 200 mg orally daily for 6 months improves sperm motility when compared with baseline (12169). The validity of this finding is limited by the lack of a comparator group. Coenzyme Q10 has also been studied in males with idiopathic oligoasthenoteratozoospermia, but results are conflicting. Studies have used coenzyme Q10 or its reduced form, ubiquinol, in doses of 200-300 mg orally daily for 26 weeks. Sperm density and motility are increased when compared with placebo, but pregnancy rates do not seem to improve (17413,89422). Three studies have used coenzyme Q10 200-400 mg orally daily for 12-26 weeks, with two reporting increased sperm concentration and motility when compared to baseline, but the other finding no improvements when compared with placebo (44190,102008,107444). Coenzyme Q10 has also been investigated in combination with other ingredients. In one preliminary clinical trial, taking coenzyme Q10 10 mg and vitamin E 100 mg three times daily for 3 months modestly increases levels of testosterone and improves progressive sperm motility and morphology when compared with baseline. However, taking an L-carnitine nutrient complex 15 grams twice daily was more effective for increasing testosterone and for improving sperm parameters (109390). Other small and preliminary clinical studies have investigated the effects of a specific combination product providing coenzyme Q10 20 mg twice daily for 6 months, along with acetyl-L-carnitine, L-carnitine, selenium, zinc, vitamin C, folic acid, vitamin B12, and citric acid (Proxeed Plus). Taking this combination product has been shown to improve measures of sperm quality such as sperm count, sperm concentration, total motility, and progressive motility when compared to baseline. The effect on sperm volume and morphology is unclear. Most research has been conducted in patients with oligoasthenozoospermia, although some benefit has also been shown in patients with varicocele-related infertility, especially those with more severe varicocele (102017,107395,111296). The validity of these findings is limited by the lack of comparator group. Also, it is unclear if these effects are due to coenzyme Q10, other ingredients, or the combination.
Maternally inherited diabetes mellitus and deafness (MIDD). It is unclear if oral coenzyme Q10 is beneficial for MIDD. Details: One small clinical study shows that taking coenzyme Q10 150 mg orally daily for 3 years might prevent progressive insulin secretory defect, exercise intolerance, and hearing loss when compared with baseline in people with this rare form of diabetes (2125).
Metabolic syndrome. It is unclear if oral coenzyme Q10 is beneficial in patients with metabolic syndrome. Details: A small clinical study in patients with metabolic syndrome receiving healthy dietary recommendations shows that taking coenzyme Q10 60 mg daily for 12 weeks does not have beneficial effects on blood glucose, cholesterol, waist circumference, or blood pressure when compared with placebo (109284).
Myocarditis. It is unclear if oral coenzyme Q10 is beneficial in patients with acute viral myocarditis. Details: A small observational study in Chinese patients with acute viral myocarditis has found that taking coenzyme Q10 10 mg and trimetazidine 20 mg three times daily for 2 weeks, along with standard care, is associated with higher rates of resolution and improved quality of life when compared with coenzyme Q10 plus standard care alone (107443). While coenzyme Q10 alone appeared to improve symptoms and markers of cardiac function when compared to baseline in some patients, the validity of these findings is limited by a lack of placebo control.
Nonalcoholic fatty liver disease (NAFLD). Coenzyme Q10 may reduce liver enzymes and the severity of NAFLD. Details: Preliminary clinical research in adults with NAFLD shows that taking coenzyme Q10 100 mg orally daily for 12 weeks reduces the clinical grade of NAFLD and decreases plasma levels of liver enzymes when compared with placebo (97907).
Obesity. Oral coenzyme Q10 does not seem to improve weight loss in adults. Details: A meta-analysis of small, highly heterogeneous clinical trials shows that taking coenzyme Q10 100-300 mg daily for up to 24 weeks does not reduce weight or body mass index when compared with placebo. However, the included studies were not designed to assess for weight loss and involved patients with type 2 diabetes, metabolic syndrome, kidney disease, liver disease, rheumatoid arthritis, and other conditions (105067).
Periodontitis. Data on the effects of oral or topical coenzyme Q10 are conflicting. It is unclear if coenzyme Q10 is beneficial for periodontitis. Details: Some very small, low-quality studies suggest that taking coenzyme Q10 orally, 50 mg daily for 3 weeks, might be beneficial for periodontitis (8917,8918). Preliminary research with topical coenzyme Q10 suggests it is ineffective (2107,2108). However, a meta-analysis of 11 clinical trials evaluating coenzyme Q10 topical gel shows reductions in plaque index, bleeding index, pocket index, clinical attachment level, and gingival index when compared with placebo gel or scaling and root planing alone. The greatest effects are seen when coenzyme Q10 gel is applied directly into the periodontal pocket daily for at least six weeks in combination with scaling and root planing (108958). The validity of these findings is limited by a high risk of bias and the overall low quality of the included studies. Coenzyme Q10 has also been studied in combination with other ingredients for periodontitis. A small clinical study in patients with moderate or advanced periodontitis shows that taking a supplement containing 30 mg of coenzyme Q10 in addition to alpha-lipoic acid, cranberry extract, grapeseed extract, selenium, vitamin C, vitamin E, and zinc twice daily for 8 weeks in addition to standard nonsurgical therapy does not improve periodontal indices including bleeding on probing, gingival recession, plaque index, or inflammation, among others, when compared with placebo (111708).
Physical performance. It is unclear if oral coenzyme Q10 improves physical performance in older adults with chronic kidney disease (CKD). Details: A small clinical study in mostly older adults with CKD shows that taking coenzyme Q10 1200 mg daily for 6 weeks does not improve measures of physical exercise endurance including aerobic capacity, total work, and work efficiency when compared with placebo (111558). The validity of these effects is limited by the small sample size and short study duration.
Polycystic ovary syndrome (PCOS). Most clinical studies suggest that oral coenzyme Q10 modestly improves symptoms in patients with PCOS. Details: A meta-analysis of clinical trials in patients with PCOS shows that taking coenzyme Q10 modestly improves measures of glycemic response, as well as plasma lipids and some sex hormones, when compared with placebo (109384). However, any changes are small and the clinical relevance is unclear. Also, although nine studies were included in the review, the number of studies included for each endpoint was much lower. Most clinical studies included in the analysis used 100-200 mg daily for 8-12 weeks (107446,109384). An additional small clinical study also shows that taking coenzyme Q10 (Nature Made) 100 mg orally daily for 12 weeks reduces fasting plasma glucose, insulin, and total cholesterol and improves insulin sensitivity when compared with placebo. This study also found that taking coenzyme Q10 reduces alopecia by about 33% and acne by 48% when compared with placebo (97914). Another small clinical study shows that taking coenzyme Q10 100 mg daily for 12 weeks reduces depression, anxiety, and hirsutism when compared with placebo (107446).
Prader-Willi syndrome (PWS). It is unclear if oral coenzyme Q10 is beneficial in patients with PWS. Details: Preliminary clinical research in children with Prader-Willi syndrome shows that taking coenzyme Q10 2.5 mg/kg orally daily for one year improves psychomotor development similarly to growth hormone therapy, although this might reflect natural changes in the condition occurring over time (44005).
Pre-eclampsia. Taking coenzyme Q10 orally seems to reduce the rate of pre-eclampsia in women at risk for the condition. Details: Clinical research shows that taking coenzyme Q10 (Q-absorb, Jarrow Formulas) 100 mg orally twice daily during pregnancy, starting at 20 weeks gestation and continuing until term, reduces the rate of pre-eclampsia by about 44% when compared with placebo in women at risk for developing this condition (17201).
Schizophrenia. It is unclear if oral coenzyme Q10 improves symptoms in patients with schizophrenia or schizoaffective disorder. Details: A small clinical study in patients with schizophrenia or schizoaffective disorder shows that taking coenzyme Q10 300 mg daily for 6 months does not improve attention, working memory, negative symptoms, mood disorders, or quality of life when compared with placebo (105069). This finding is limited by insufficient power and poor protocol adherence, with only 61% of the participants taking at least 90% of the study treatment.
Sepsis. There is no strong evidence that coenzyme Q10 is helpful in the management of sepsis or septic shock. Details: Patients with septic shock have been shown to have low levels of coenzyme Q10, but the effects of supplementation are unclear. Some preliminary clinical research shows that taking coenzyme Q10 100 mg orally twice daily for 7 days reduces the risk of in-hospital mortality by 69% and improves markers of inflammation, but does not reduce length of ICU stay, when compared with conventional treatment alone (102548). However, other preliminary research shows that taking coenzyme Q10 as ubiquinol 200 mg twice daily for 7 days has no effect on inflammatory or vascular endothelial biomarkers, mortality, or length of stay when compared with placebo (96540). Both studies were small and likely underpowered to detect a meaningful change in clinical outcomes.
Statin-induced myalgia. There is conflicting evidence regarding the effects of oral coenzyme Q10 on statin-associated muscular adverse effects, such as myalgia. Details: Some clinical research shows that taking coenzyme Q10 (Q-Sorb softgel, Nature's Bounty) 100 mg orally daily for 30 days reduces pain intensity when compared with baseline or vitamin E control in patients with statin-induced myalgia (16008,44345). Other clinical research shows that taking coenzyme Q10 (MGC Company) 50 mg orally twice daily for 30 days reduces muscle pain and pain interference with daily activities by 30% to 40% when compared with placebo (95604). One small study in adults with statin-induced myalgia shows that taking liquid coenzyme Q10 (Q-Factor, Giellepi S.p.A) 100 mg orally daily for 3 months modestly reduces pain scores, but not plasma creatine kinase (CK) levels, when compared with placebo (102007). Other clinical research shows that taking coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg twice daily, with or without selenium, for 3 months, reduces muscle pain and weakness, cramps, and tiredness when compared with placebo (92909). However, not all studies have shown benefit. Meta-analyses of several small randomized controlled trials show that taking coenzyme Q10 100-600 mg daily for 1-3 months does not improve muscle pain, statin tolerability, or plasma CK activity in patients with statin-induced myalgia when compared with placebo (95602,103781,106050). However, the validity of these results is limited by small population size and high heterogeneity. Other clinical research shows that taking coenzyme Q10 60 mg twice daily for 3 months does not improve muscle pain when compared with placebo (44218). Also, taking coenzyme Q10 (Q-Gel, Tishcon Corporation) 200 mg daily for 12 weeks does not affect myalgia scores when compared with placebo in patients taking simvastatin (44346). Additionally, taking high doses of coenzyme Q10 600 mg daily for 8 weeks does not affect the incidence, severity, or time to onset of statin-induced myalgia when compared with placebo in patients taking simvastatin (95603). Reasons for these conflicting findings are not entirely clear. The inconsistent results do not appear to be related to the dose of coenzyme Q10 or plasma CK levels. About 50% of patients who experience statin-induced myalgia will tolerate a statin re-challenge with a lower or equivalent dose of the same or alternative statin after a statin-free interval, which is a higher response rate than seen in currently available studies with the use of coenzyme Q10. Taking coenzyme Q10 for 30 days may be a reasonable option if other attempts to improve tolerance have failed. If a significant improvement in pain related to statin use is not seen after 30 days of taking coenzyme Q10, it is unlikely to be beneficial (96548).
Statin-induced myopathy. There is conflicting evidence regarding the effects of coenzyme Q10 on statin-associated muscular adverse effects, including myopathy. Details: Clinical research shows that taking coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg orally twice daily, with or without selenium, for 3 months, reduces muscle weakness and pain, cramps, and tiredness when compared with placebo in patients with statin-induced myopathy due to atorvastatin, fluvastatin, rosuvastatin, or simvastatin (92909). Preliminary clinical research also shows that taking coenzyme Q10 60 mg orally four times daily decreases the rate of dose-limiting statin-induced myopathy in patients taking high-dose lovastatin as an investigational treatment for cancer (11899,11900). However, when coenzyme Q10 (Myoquinon, Pharma Nord,) 400 mg orally daily is used in combination with selenium for 12 weeks, it does not affect atorvastatin-induced myopathy when compared with placebo (92908).
Toxin-induced liver damage. Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients being treated with anti-tuberculosis drugs shows that taking coenzyme Q10 200 mg, acetyl-L-carnitine 250 mg, and alpha-lipoic acid 250 mg twice daily for 2 weeks reduces the risk of drug-induced liver injury by 73% when compared with placebo (107445). It is unclear if these findings are due to coenzyme Q10, other ingredients, or the combination.
Ulcerative colitis. It is unclear if oral coenzyme Q10 is beneficial in patients with ulcerative colitis. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking oral coenzyme Q10 (Nutri Q10, Nutri Century Company) 100 mg twice daily for 8 weeks modestly improves ulcerative colitis disease activity and quality of life scores when compared with placebo. Taking coenzyme Q10 also reduces systolic and diastolic blood pressure by 4 mmHg and 2 mmHg, respectively, when compared with placebo (106049). The clinical relevance of these changes is unclear.
Wrinkled skin. It is unclear if topical application of coenzyme Q10 cream can reduce wrinkles. Details: A small clinical study shows that applying a coenzyme Q10 1% cream to the skin twice daily for 5 months reduces objective wrinkle scores when compared to baseline (44082). The validity of this finding is limited by the lack of a comparator group. More evidence is needed to rate coenzyme Q10 for these uses.

(Read more about COENZYME Q10)

VITAMIN A

EFFECTIVE

Vitamin A deficiency. Oral vitamin A is effective for treatment and prevention of vitamin A deficiency. Details: Clinical and observational research in children shows that taking vitamin A orally is effective for preventing and improving symptoms of vitamin A deficiency, including xerophthalmia, night blindness, and Bitot's spots (82329,82689,82710,90773). Vitamin A deficiency can occur due to abnormal storage and transport of vitamin A in people with abetalipoproteinemia, protein deficiency, diabetes mellitus, hyperthyroidism, fever, liver disease, and cystic fibrosis (7135). However, research suggests that supplementation with vitamin A may not be necessary for most newborns with vitamin A deficiency. An observational study in newborns with vitamin A levels of 0.43-0.59 mcmol/L or >0.59 mcmol/L found that vitamin A levels increased naturally over the first six months of life, regardless of oral vitamin A supplementation. However, in infants with very low vitamin A levels (<0.43 mcmol/L), vitamin A supplementation was associated with significant increases in vitamin A levels at 6 months of age when compared with no supplementation, suggesting that only newborns with very low vitamin A levels should receive oral vitamin A (107298).

POSSIBLY EFFECTIVE

Aging skin. Topical vitamin A (retinol) formulations seem to improve symptoms of aging skin, such as wrinkles and mottled pigmentation. Details: The vitamin A analog tretinoin (Renova) is a prescription drug approved by the U.S. Food and Drug Administration for adjunctive use in reducing fine wrinkles, hyperpigmentation, and tactile roughness of aging facial skin (103711). However, this drug is not interchangeable with non-prescription, commercially available vitamin A products, which have not been as extensively evaluated in clinical research. Although research evaluating non-prescription topical vitamin A shows benefit for reducing wrinkles, most studies have been small and used different formulations. One small study in adults over 40 years of age shows that applying a pea size amount of 0.075% retinol cream to the face daily for 26 weeks seems to reduce deep and fine wrinkling when compared with placebo. Applying a lower dose of 0.04% retinol cream for 13 weeks seems to reduce fine wrinkling to a lesser degree, with no effect on deep wrinkles, when compared with placebo cream (104458). Another small clinical study in adults over 80 years of age shows that applying 2 mL of retinol 0.4% lotion to the upper arm up to 3 times weekly for 24 weeks reduces visible wrinkles when compared with placebo (94683). Two small studies in females ages 33 to 65 show that applying retinol 0.15%, 0.3% and 0.5% in liquid crystal formulation once daily to the face for 2-3 months improves skin pigmentation, elasticity, and wrinkles when compared with baseline (103680,104464). The validity of these two studies is limited by the lack of a comparator treatment. Topical vitamin A is frequently combined with other ingredients in commercial formulations; however these combinations have rarely been studied. A small clinical study in adults over 35 years with skin aging shows that applying a cream containing retinol 0.5%, niacinamide, resveratrol, and hexylresorcinol seems to improve wrinkling and skin tone when compared with baseline (104455). Another small preliminary clinical trial in adults ages 35-65 years with periorbital lines and wrinkles shows that applying a cream containing retinol modestly improves dryness, puffiness, redness, and darkness when compared with baseline. The retinol was conjugated with lactic acid, and the cream contained other nutrient and herbal ingredients It was applied around the eyes each evening, sometimes used in combination with another product each morning (109747).
Bronchopulmonary dysplasia. Intramuscular vitamin A may reduce the risk of bronchopulmonary dysplasia (BPD) in very low birth weight infants when given at a dose of 5000 IU three times weekly for 28 days. Lower doses do not seem to be effective. It is unclear if enteral vitamin A is beneficial for BPD. Details: A meta-analysis of 6 clinical trials in premature infants shows that intramuscular administration of vitamin A every other day or three times weekly for 28 days reduces the risk of BPD by around 33% when compared with control (107297). The results from this meta-analysis are primarily driven by a modestly sized clinical trial in very low birth weight infants which shows that intramuscular administration of vitamin A 5000 IU three times weekly for 28 days reduces the risk of BPD by 15% when compared with a sham control (82195). A subgroup analysis of this trial suggests that infants with the lowest BPD risk estimate based on gestational age, birth weight, sex, ethnicity, and oxygen levels 24 hours after birth appear to benefit more from vitamin A therapy than those with higher BPD risk estimates (107296). Previous research in this area utilized a lower dose of only 2000 IU every other day for 28 days, and showed no significant improvement in the rate of BPD (82331,82613). The evaluation of a higher dose was prompted by research noting that the lower doses evaluated in these earlier studies were unable to achieve serum retinol concentrations above 25 mcg/dL, while doses at or above 5000 IU three times weekly could reach this level (82731). Enteral vitamin A has also been investigated. Meta-analyses of two clinical trials show that supplementation with vitamin A at an average of 5,000 IU daily, staring within four days of birth, does not reduce the incidence of BPD when compared with placebo (109750,109753).
Diarrhea. Vitamin A seems to reduce the incidence of diarrhea in young children. However, it is unclear if oral vitamin A while breastfeeding is beneficial for preventing diarrhea in nursing infants. Details: A meta-analysis of clinical research in children up to age 5 shows that vitamin A supplementation reduces the incidence of diarrhea by 15% and mortality related to diarrhea by 12% when compared with control, usually placebo or no supplementation (109755). However, one small clinical trial in breastfeeding parents shows that supplementation of vitamin A 1800 IU and ergocalciferol (vitamin D2) 600 IU daily for 2 months does not reduce the risk of diarrhea in the nursing infants when compared with placebo (107293).
Measles. High-dose oral vitamin A seems to reduce mortality from measles in children under 2 years of age and may also reduce the incidence of measles in children up to 5 years of age. Details: Meta-analyses of clinical research show that taking vitamin A does not reduce mortality in children with measles when all ages and/or doses are considered (82373,82502,95055,109755). However, in children with measles who are less than 2 years of age, taking vitamin A 200,000 IU orally for at least two doses seems to reduce mortality by up to 83% when compared with placebo (82373,82502). Also, taking vitamin A seems to reduce the incidence of measles in children ages 6 months to 5 years (95055,109755).
Night vision. Oral vitamin A as retinyl palmitate seems to reduce night blindness during pregnancy in malnourished patients. Details: Clinical research shows that taking vitamin A (as retinyl palmitate) 23,000 IU weekly before and during pregnancy reduces pregnancy-related night blindness by 37% in malnourished patients (6154). Some evidence suggests that zinc supplements might potentiate the effects of vitamin A in restoring sight in zinc-deficient pregnant patients affected by night blindness (8630).
Oral leukoplakia. High-dose oral vitamin A seems to reduce oral leukoplakia lesions in patients that chew tobacco and/or betel nut. Details: Clinical research in patients with tobacco and/or betel nut chewing habits shows that taking oral vitamin A 200,000-300,000 IU weekly for 6-12 months seems to result in remission of leukoplakia lesions in over 50% of participants when compared with placebo (34674,82617). However, it is unknown if vitamin A prevents the development of oral cancer from oral leukoplakia lesions.
Overall mortality. In children at risk for vitamin A deficiency, oral vitamin A seems to reduce mortality. However, it does not seem to reduce mortality in healthy adults. Details: Despite previous debate on whether the programs supplying high-dose vitamin A in low- and middle-income countries with prevalent vitamin A deficiency are safe and effective for reducing child mortality, most experts, including World Health Organization, recommend high-dose vitamin A supplementation for those children (95055,95724,97170,109755). In 2010, a meta-analysis of 17 trials involving over 194,000 patients, showed that vitamin A supplementation reduces all-cause mortality by about 24% in children 6 months to 5 years of age (82559). However, some research published after this meta-analysis shows conflicting results (90773,90777). In fact, the largest clinical trial conducted to date (Deworming and Enhanced Vitamin A; DEVTA), which was published after the analysis and involved one million preschool children, suggests that high-dose vitamin A supplementation does not reduce mortality (90773). However, this trial was limited due to under-resourcing and undetermined patient consent and treatment compliance (90773). Furthermore, in 2017, a meta-analysis including the DEVTA trial along with 46 additional studies involving over 1.2 million preschool children, shows that vitamin A supplementation does reduce all-cause mortality by 12% when compared with control (95055). This meta-analysis was updated in 2022 with no additional studies or changes in conclusions (109755). Adult mortality is not reduced by vitamin A supplementation. In fact, some evidence even shows that vitamin A supplementation increases mortality when administered to healthy adult patients or those with a stabilized disease (15305,34622,90775).
Postpartum complications. Oral vitamin A seems to reduce postpartum diarrhea and mortality in malnourished patients. Details: A large clinical study in malnourished pregnant patients in Nepal shows that taking vitamin A (as retinyl palmitate) 23,000 IU weekly before, during, and after pregnancy reduces the occurrence of blood and mucus in the stool by 93% and the occurrence of diarrhea by up to 90% during the first 6 months postpartum when compared with placebo (2581). Another clinical study in the same population shows that taking vitamin A (as retinyl palmitate) 23,000 IU weekly before and during pregnancy reduces pregnancy-related mortality by 40% when compared with placebo (6153).
Retinitis pigmentosa. Oral vitamin A supplementation in children with retinitis pigmentosa seems to slow retinal function decline. Details: Observational and clinical research in children with retinitis pigmentosa shows that taking an age-adjusted dose of vitamin A, up to a maximum dose of 15,000 IU daily, modestly attenuates the decline in retinal function when compared with control (83,97167,103677).
Ulcerative colitis. Oral vitamin A supplementation in patients with ulcerative colitis seems to improve clinical response and mucosal healing. Details: A clinical study in adults with symptomatic ulcerative colitis despite treatment with 5-aminosalicylic acid shows that taking vitamin A 25,000 IU daily for 2 months reduces disease severity and increases the rate of clinical response and mucosal healing when compared with placebo. The number needed to treat (NNT) for clinical response is 3; the NNT for mucosal healing is 5 (100329).
Wrinkled skin. Topical vitamin A (retinol) formulations seem to improve photodamage and wrinkles. Details: The vitamin A analog tretinoin (Renova) is a prescription drug approved by the U.S. Food and Drug Administration for adjunctive use in reducing fine wrinkles, hyperpigmentation, and tactile roughness of facial skin (103711). This drug is not interchangeable with non-prescription, commercially available vitamin A products, which have not been as extensively evaluated in clinical research. Still, some research in females ages 35-65 with moderately wrinkled and photoaged skin suggests that commercially available retinol formulations might reduce wrinkles and skin roughness similarly to tretinoin. One study used retinol serum starting at a concentration of 0.25% and increased to 1% over 3 months, compared with tretinoin cream 0.025% gradually increased to 0.1% (103671), while another study compared a gradual release tri-retinol 1.1% cream applied daily for 3 months to tretinoin 0.025% cream (104456). Commercial retinol also seems to be beneficial when compared with placebo. A small study in adults over 40 years old with photodamaged skin shows that applying stabilized retinol 0.1% to the face daily for one year improves wrinkles and mottled pigmentation in over 50% of the participants when compared with a placebo treatment (104463).

POSSIBLY INEFFECTIVE

Atopic disease. Supplementation with oral vitamin A does not seem to reduce the risk of atopy. Details: Clinical research in infants born in Guinea-Bissau shows that a single dose of vitamin A does not reduce the incidence of atopy when compared with placebo (90779,90780). Furthermore, giving a single dose of vitamin A to some infants, such as low birth weight infants and infants given Bacille Calmette-Guerin (BCG) vaccination, was associated with increased atopy and wheeze (90779).
Fetal and premature infant mortality. Giving oral vitamin A to malnourished adults during pregnancy and postpartum does not seem to reduce fetal, early infant, or first year mortality. Giving oral or intramuscular vitamin A to the infant also does not seem to reduce mortality in most patients. Details: Most meta-analyses of clinical research in malnourished patients suggest that vitamin A supplementation during pregnancy or postpartum does not reduce fetal, early infant, or first year mortality (6152,34601,34602,34627,82479,82566,82567,90774,90776,90782,90784,95057,109750,109753). Also, giving vitamin A supplements or intramuscular vitamin A to low birth weight infants does not appear to reduce mortality in these patients (82195,82431,82498,90778,90781,95053,107296,107297). Furthermore, vitamin A supplementation in term infants from low or middle income countries also does not appear to reduce the risk of mortality at 6 or 12 months of age when compared with placebo (95054,103674). Some evidence from a meta-analysis of clinical research shows that vitamin A supplementation may reduce the risk of mortality at 6 months in Asian infants, although it appears to increase the risk of mortality at 6 months in studies conducted in Africa. It also appears to increase the risk of mortality in female term infants by 12 months (95054).
Intestinal parasite infection. Oral high-dose vitamin A does not seem to prevent reinfection with intestinal parasites. Details: Clinical research in children living in Malaysia that were given albendazole 400 mg daily for 3-4 days for parasitic worms, shows that adding a single dose of vitamin A 200,000 IU does not help to prevent reinfection when compared with placebo (90772).
Melanoma. Oral vitamin A in patients with resected melanoma does not seem to improve survival and disease recurrence. Details: A clinical study in patients with completely resected melanoma shows that taking vitamin A 100,000 IU daily for 18 months does not increase disease-free survival when compared with no supplementation (82670).
Miscarriage. Oral vitamin A given to the mother does not prevent miscarriage or stillbirth. Details: A meta-analysis of clinical research shows that maternal supplementation with oral vitamin A, either alone or in combination with other vitamins, prior to or during early pregnancy does not reduce the risk of miscarriage or stillbirth when compared with control (104462).
Sepsis. Most research shows that oral vitamin A does not reduce the risk of sepsis in premature infants. Details: A meta-analysis of three clinical trials in premature infants shows that providing supplemental enteral vitamin A 1500-5000 IU daily, starting within four days of birth, does not reduce the incidence of sepsis when compared with placebo (109753).
Tuberculosis. Oral vitamin A does not seem to improve tuberculosis disease duration or mortality. Details: Low levels of vitamin A are common in patients with tuberculosis. However, taking vitamin A 2000 IU to 200,000 IU by mouth for 2-24 months does not improve symptoms, decrease disease duration, or reduce mortality when compared with placebo in these patients (82570,103668,109754). This may be due to the fact that vitamin A levels may normalize following the initiation of tuberculosis treatment, even without additional vitamin A supplementation.

LIKELY INEFFECTIVE

Head and neck cancer. Oral vitamin A taken for 2 years does not seem to improve survival or prevent head and neck cancer recurrence. Details: A large clinical study n patients with a history of head and neck cancer shows that taking vitamin A as retinyl palmitate 300,000 IU daily for 1 year, and followed by 150,000 IU daily for another year, does not reduce the risk of second primary tumors or tumor recurrence when compared with placebo. Also, vitamin A does not seem to improve survival or event-free survival (1710).
HIV transmission. Oral vitamin A does not reduce vertical HIV transmission risk. There is some concern that vitamin A might increase HIV transmission through breast milk. Details: Observational and intervention research shows that taking vitamin A orally does not decrease the risk of HIV transmission to the fetus during pregnancy, to newborns during delivery, or to infants during early breast-feeding (6376,82470,95059). Preliminary clinical research also shows that vitamin A supplementation of pregnant adults with HIV infection might increase the risk of HIV transmission to their babies through breast milk (9801).
Lower respiratory tract infections. Oral vitamin A does not reduce the risk for lower respiratory tract infections in children. It is unclear if supplementation of oral vitamin A while breast-feeding reduces the risk of lower respiratory tract infections in nursing infants. Details: Taking vitamin A by mouth does not prevent or reduce symptoms of lower respiratory tract infections, such as cough and fever, in children (82288,82443). Furthermore, some research shows that vitamin A is associated with a slight increase in the risk of respiratory tract infections when administered to children with adequate nutritional status (82288). Additionally, one small clinical trial in breast-feeding parents shows that supplementation of vitamin A 1800 IU and ergocalciferol (vitamin D2) 600 IU daily for 2 months does not reduce the risk of febrile illness or respiratory tract infections in the nursing infants when compared with placebo (107293).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Acne. Although prescription vitamin A analogs are approved to treat acne, it is unclear if non-prescription topical vitamin A products help with acne symptoms. Details: The high-dose vitamin A analogs adapalene (Differin) and tazarotene (Tazorac) are prescription drugs approved by the US Food and Drug Administration for the treatment of acne (103712,103713). These drugs are not interchangeable with non-prescription, commercially available vitamin A products, such as retinol, which have not been extensively evaluated in clinical research. A small preliminary clinical trial in adolescents and young adults with mild to moderate acne shows that applying topical benzoyl peroxide 2.5% each morning and a topical retinol plus salicylic acid product each evening for 12 weeks modestly improves acne severity and other measures of complexion when compared with baseline. All patients also used the same cleanser twice daily (109748). The validity of this finding is limited by the lack of a comparator group.
Alcohol-related liver disease. Oral vitamin A has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with acute alcoholic hepatitis shows that taking vitamin A in combination with coenzyme Q10 and other vitamins and minerals daily for 6 months does not improve survival when compared with placebo (61392).
Asthma. It is unclear if oral vitamin A is beneficial for preventing asthma in children. Details: An observational study in children has found that higher dietary intake of vitamin A is associated with a lower risk of asthma. Children in the highest quartile of vitamin A intake (median of 2267 IU daily) at 7 years of age had improved lung function and 32% lower odds of asthma at 11-14 years of age when compared with children in the lowest quartile of vitamin A intake (median of 870 IU daily) (107291).
Atopic dermatitis (eczema). It is unclear if supplementation of oral vitamin A while breast-feeding is beneficial for preventing eczema in nursing infants. Details: One small clinical trial in breast-feeding parents shows that supplementation of vitamin A 1800 IU and ergocalciferol (vitamin D2) 600 IU daily for 2 months does not reduce the risk of eczema in the nursing infants when compared with placebo (107293).
Autism spectrum disorder. It is unclear if oral vitamin A is beneficial for improving symptoms of autism. Details: Children with autism spectrum disorder are at increased risk for vitamin A deficiency, and vitamin A levels have been inversely associated with autism symptoms. Preliminary clinical research shows that taking a single dose of vitamin A 200,000 IU slightly improves emotional response, communication, and other symptoms when compared to baseline (97168). The lack of a control group limits the validity of these findings. Another preliminary clinical study in children with autism and vitamin A deficiency shows that taking vitamin A 50,000 IU weekly for 6 months, but not as a single dose of 200,000 IU, seems to improve social impairment scores when compared with control. Controls were children with autism without vitamin A deficiency that did not take a supplement (104459).
Breast cancer. Although vitamin A intake has been associated with a reduced risk for breast cancer, it is unclear if vitamin A supplements are beneficial. Details: Epidemiological evidence has found an association between high intake of vitamin A and a reduced risk of breast cancer. A meta-analysis of epidemiological research has found that the adults with the highest intake of vitamin A, either from diet alone or also from supplements, reduces the odds of developing breast cancer by 16% when compared with the lowest intake (1444,34610,109752). However, the effects of supplemental vitamin A, specifically, are unclear.
Cataracts. It is unclear if oral vitamin A is beneficial for cataract prevention. Details: A large-scale population-based study has found that high dietary intake of vitamin A is associated with a reduced risk of nuclear cataracts (6378). Also, other population research has found that the highest dietary intake of vitamin A is associated with a 17% lower risk of cataracts when compared with the lowest intakes (90786). However, there is conflicting evidence regarding the association between blood levels of vitamin A and the risk of cataracts (90786,90944). It is not known if supplemental vitamin A is beneficial.
Cervical cancer. It is unclear if oral vitamin A is beneficial for cervical cancer prevention. Details: A meta-analysis of clinical research shows that increased vitamin A levels in the blood or higher vitamin A intakes are associated with a reduced risk of cervical cancer. However, this effect is observed when both forms of vitamin A, either retinol or carotenoids, are considered. When only the retinol form is considered, vitamin A supplementation does not seem to reduce the risk of cervical cancer (34613,109752). Also, a meta-analysis of epidemiological research has found that vitamin A intake, either from diet alone or supplements, does not affect the risk of cervical cancer (109752).
Chemotherapy-induced diarrhea. It is unclear if oral vitamin A helps to prevent diarrhea caused by chemotherapy. Details: A very small clinical study in children receiving chemotherapy shows that taking vitamin A orally does not seem to prevent GI adverse effects, including diarrhea and mouth pain, when compared with control (9802).
Child development. Oral vitamin A might improve growth and development in children with vitamin A deficiency, but not in those with good nutritional status. Details: Supplementing with vitamin A 60 mg for up to 9 years does not promote or improve child growth in children with appropriate nutritional status (20132). However, in children with vitamin A deficiency, supplementation with vitamin A may improve growth (82246).
Chronic obstructive pulmonary disease (COPD). There is limited evidence on the oral use of vitamin A in patients with emphysema. Details: Observational research has found that consuming recommended amounts of vitamin A in the diet is associated with 33% lower odds of developing emphysema (103678).
Colorectal adenoma. Oral vitamin A has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination supplement containing selenium, zinc, vitamin A, vitamin C, and vitamin E orally daily for 5 years or until the recurrence of an adenoma reduces the risk of recurrent large-bowel adenomas by about 40% when compared with placebo in patients with large-bowel adenomas (92903). It is not clear if this benefit is due to vitamin A or other constituents.
Colorectal cancer. It is unclear if oral vitamin A is beneficial for colorectal cancer prevention. Details: Taking vitamin A alone or in combination with beta-carotene does not seem to reduce the risk of colorectal cancer (12185).
Coronary artery bypass graft (CABG) surgery. It is unclear if oral vitamin A improves recovery after CABG surgery. Details: Preliminary clinical research shows that taking vitamin A 5000 IU daily (as retinol palmitate) for 21 days starting on the day of CABG surgery reduces time in intensive care after surgery by 46% to 69% compared to a control group not given vitamin A (90783). Supplementation with vitamin A also improves total hospitalization time for those patients with adequate zinc status (90783).
Coronavirus disease 2019 (COVID-19). It is unclear if oral vitamin A is beneficial for the treatment of mild to moderate COVID-19. Details: Clinical research in COVID-19 outpatients treated with hydroxychloroquine shows that taking vitamin A 25,000 IU daily for 10 days modestly reduces the number of patients with symptoms of fever, body ache, and fatigue when compared with placebo. However, there was no effect on the number of patients with cough, shortness of breath, lack of appetite, chest pain, diarrhea, loss of smell, or headache (109745).
Depression. It is unclear if oral vitamin A is beneficial for depression. Details: A meta-analysis of observational research has found that dietary intake of vitamin A is inversely associated with depression. The highest intake of vitamin A was associated with a 17% reduced risk of depression when compared with the lowest intake. Also, vitamin A intake was lower in individuals with depression (109743). The effect of vitamin A supplementation is unclear.
Esophageal cancer. It is unclear if oral vitamin A is beneficial for esophageal cancer prevention. Details: Observational research has found that higher beta-carotene and vitamin A intake is associated with a reduced risk of esophageal cancer (34551,103675). However, evidence from higher-quality clinical research shows that taking vitamin A in combination with beta-carotene does not reduce the risk of esophageal cancer (12185).
Gastric cancer. It is unclear if oral vitamin A is beneficial for gastric cancer prevention. Details: Taking vitamin A alone and in combination with beta-carotene does not seem to reduce the risk of gastric cancer (12185).
Glaucoma. It is unclear if oral vitamin A is beneficial for glaucoma prevention. Details: A meta-analysis of observational research has found that a high dietary intake of vitamin A is associated with a 37% reduced risk of glaucoma when compared with a low intake (109742).
HIV/AIDS. It is unclear if oral vitamin A is beneficial for improving HIV/AIDs outcomes. Details: A meta-analysis of clinical trials and population research shows that maternal vitamin A supplementation of mothers with poor vitamin A status at baseline does not influence child or maternal mortality, hospitalization rate, or HIV/AIDS progression. However, pediatric vitamin A supplementation seems to decrease mortality rates in children with HIV/AIDS when compared with placebo (34529,95059).
HIV/AIDS-related diarrhea. It is unclear if oral vitamin A is beneficial for preventing diarrhea associated with HIV. Details: A large clinical trial shows that taking vitamin A can decrease the rate of diarrhea-specific mortality by up to 92% in vitamin A-deficient children with or without HIV/AIDS (1465). However, a meta-analysis of clinical research shows that taking vitamin A does not significantly reduce diarrhea-specific mortality when only children with HIV/AIDS are considered (82511). But vitamin A does appear to reduce overall mortality in these children by 50% to 63% (1465,82511).
Human papillomavirus (HPV). It is unclear if topical or oral vitamin A is beneficial for the resolution of genital warts caused by HPV. Details: A meta-analysis of small clinical trials in patients with genital warts suggests that the oral prescription drugs isotretinoin and etretinate might promote resolution of warts when compared with baseline. However, the topical prescription drug tretinoin 0.05% cream does not seem to help (104460). These drugs are not interchangeable with non-prescription, commercially available vitamin A products, such as retinol.
Infant development. It is unclear if intramuscular vitamin A improves the development of low birth weight infants. Details: A meta-analysis of clinical research shows that giving intramuscular vitamin A to very low birth weight infants reduces the risk of chronic lung disease at 36 weeks postmenstrual age by about 13% compared to control (95053). Preliminary clinical research also shows that giving intramuscular vitamin A along with inhaled nitric oxide gas for 3 weeks to low birth weight infants on mechanical ventilation might improve mental development at one year in some of these patients when compared with inhaled nitric oxide gas alone (90778). However, a meta-analysis of clinical research shows that intramuscular vitamin A does not improve neurodevelopment in very low birth weight infants (95053).
Iron deficiency anemia. It is unclear if oral vitamin A is beneficial for the prevention or treatment of anemia due to iron deficiency. Details: Some research in children and pregnant adults without anemia shows that taking vitamin A increases plasma levels of hemoglobin and ferritin, and may reduce the risk of developing anemia (9518,34627). However, another study in pregnant patients, half of whom had anemia at baseline and half of whom did not have anemia, shows that taking 3000 mcg retinol orally in combination with iron and folate does not improve hemoglobin or erythropoietin concentrations when compared with taking iron and folate (9188). In preterm infants with existing anemia, taking vitamin A 5000 IU and vitamin B complex 40 mg daily improves serum ferritin, hemoglobin, and reticulocyte levels and reduces the need for blood transfusions when compared with taking either vitamin alone. Taking vitamin A alone, however, does not improve these outcomes (100330).
Leukemia. It is unclear if oral vitamin A is beneficial for leukemia prevention. Details: Preliminary clinical research in adults with chronic myelogenous leukemia shows that taking a specific vitamin A product (Aquasol, Armour Pharmaceuticals) 50,000 IU orally daily in combination with busulfan therapy does not significantly increase progression-free survival or overall survival when compared with busulfan alone. Furthermore, supplementation with vitamin A plus busulfan seems to increase the percentage of patients who experience grade 2 toxicity by about 5-fold when compared with busulfan alone (82652).
Liver cancer. It is unclear if oral vitamin A is beneficial for liver cancer prevention. Details: Population research has found that vitamin A supplementation or serum levels of vitamin A are not associated with the risk of liver cancer (97169).
Lung cancer. It is unclear if oral vitamin A is beneficial for lung cancer treatment or prevention. Details: Population research has found that increased dietary intake of vitamin A is not associated with a reduced risk of lung cancer (35628). Furthermore, supplementation with vitamin A and beta-carotene seems to increase the risk of lung cancer in smokers or those exposed to asbestos (2642,34675). A large clinical trial in patients with existing lung cancer shows that vitamin A 300,000 IU daily for one year followed by 150,000 IU daily for a second year does not increase survival (1710). However, some clinical research shows that high-dose vitamin A 300,000 IU daily following curative lung cancer resection reduces the risk of new primary tumors in patients heavily exposed to tobacco (7875).
Malaria. It is unclear if oral vitamin A is beneficial for reducing symptoms of malaria in young children. Details: Taking vitamin A orally seems to help decrease symptoms of malaria in children less than 3 years of age living in endemic areas (1464). However, other clinical research shows that single doses of vitamin A 100,000 to 200,000 IU do not improve coma resolution, convulsions, fever, parasite clearance, or mortality in infants and children less than 5 years of age with cerebral malaria (90785).
Multiple sclerosis-related fatigue. It is unclear if oral vitamin A is beneficial for reducing fatigue in patients with multiple sclerosis. Details: Preliminary clinical research in patients with relapsing-remitting multiple sclerosis receiving interferon beta-1a shows that taking vitamin A 25,000 IU (as retinyl palmitate) (Zahravi Pharmaceutical) daily for 6 months followed by 10,000 IU daily for 6 months, improves physical, cognitive, and psychosocial fatigue when compared with placebo (95052).
Necrotizing enterocolitis (NEC). A meta-analysis of several small clinical trials suggests that intramuscular vitamin A does not seem to prevent NEC. Details: A meta-analysis of 3 small clinical studies in very low birth weight infants shows that intramuscular administration of vitamin A 1500-5000 IU every other day or three times weekly for 28 days does not reduce the risk of NEC when compared with a control (107297).
Non-Hodgkin lymphoma. It is unclear if oral vitamin A is beneficial for non-Hodgkin lymphoma prevention. Details: Population research has found that intake of vitamin A at levels above 2330 mcg daily is associated with a 17% lower risk of non-Hodgkin lymphoma when compared with those whose daily intake of vitamin A is less than 642 mcg per day (90945).
Nonmelanoma skin cancer. It is unclear if oral vitamin A is beneficial for nonmelanoma skin cancer prevention. Details: Observational research over 26 years found that higher dietary vitamin A intake is associated with a 12% reduced risk for cutaneous squamous cell carcinoma in healthy patients when compared with lower vitamin A intake (101673).
Oral clefts. It is unclear if oral vitamin A is beneficial for oral cleft prevention. Details: A meta-analysis of observational research has found that periconceptional use of vitamin A, from diet and/or supplements, is associated with a 13% reduced incidence of cleft lip alone or with a cleft palate, but is not associated with the risk of cleft palate alone, in the child (109751).
Osteoarthritis. Oral vitamin A has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with osteoarthritis shows that taking a specific product containing vitamin A in combination with selenium, vitamin C, and vitamin E (Selenium ACE, Carls-Berghs Farmaceutiska AB) does not appear to alleviate symptoms when compared with placebo (74449).
Ovarian cancer. It is unclear if oral vitamin A is beneficial for ovarian cancer prevention. Details: Most observational research has found that increased dietary intake of vitamin A is associated with a reduced risk of developing ovarian cancer (9193,103679,109752). The most recent meta-analysis of epidemiological research has found that adults with the highest intake of vitamin A, either from diet alone or supplements, reduces the odds of developing ovarian cancer by 19% when compared with the lowest intake (109752).
Pancreatic cancer. It is unclear if oral vitamin A is beneficial for pancreatic cancer prevention. Details: A meta-analysis of observational research has found that higher intake of vitamin A is associated with a reduced risk of pancreatic cancer; however, this benefit appears to be limited to only hospital-based cases and studies conducted in Europe (95060). In contrast, a meta-analysis of clinical research shows that taking vitamin A in combination with beta-carotene does not reduce the risk of pancreatic cancer (12185).
Parkinson disease. It is unclear if oral vitamin A prevents Parkinson disease development. Details: Population research has found that blood levels or dietary intake of vitamin A are not associated with the risk of Parkinson disease (91164).
Photoreactive keratectomy. Oral vitamin A has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking a specific product (Evitex capsules, Alcon) containing vitamin A along with vitamin E seems to improve healing after photoreactive keratectomy. High dose (50,000 to 75,000 IU) vitamin A in the form of retinol palmitate taken daily with vitamin E (alpha-tocopheryl nicotinate) 460-590 mg daily seems to accelerate re-epithelialization, reduce haze formation, and improve visual acuity in patients undergoing laser surgery for myopia (348).
Pneumonia. Oral vitamin A does not seem to prevent mortality related to pneumonia in children. However, it is unclear if vitamin A reduces symptom severity and hospitalization in children. Details: Clinical research in children living in developing countries shows that taking vitamin A orally does not prevent mortality related to pneumonia (1466,82362,82504,82717,109749). However, the evidence related to symptom duration and severity is mixed. A large study and early meta-analyses show that vitamin A does not prevent pneumonia or decrease the severity or length of hospitalization in children with pneumonia (1466,82362,82504,82717). A more recent meta-analysis also shows that giving vitamin A to children at or below 5 years of age does not affect the duration of hospitalization (109755). The best evidence to date comes from a recent meta-analysis of randomized clinical trials. This meta-analysis shows that, when given in combination with conventional therapy to children up to 10 years of age, vitamin A reduces the duration of symptoms including fever, cough, lung rale, and shortness of breath, as well as the duration of hospitalization and time to a negative X-ray, when compared with conventional therapy alone (109749). However, the number of trials evaluating each endpoint is small and more research is needed to confirm these findings.
Prematurity. It is unclear if vitamin A reduces the duration of hospitalization for premature infants. Details: A meta-analysis of four randomized controlled trials in preterm infants shows that providing supplemental enteral vitamin A 1500-5000 IU daily, starting within four days of birth, does not reduce the duration of hospitalization when compared with placebo (109750).
Prostate cancer. It is unclear if oral vitamin A is beneficial for prostate cancer prevention. Details: Observational studies suggest that dietary intake of vitamin A is not associated with a reduced risk of prostate cancer (14134).
Psoriasis. It is unclear if topical vitamin A is beneficial for psoriasis symptoms. Details: The vitamin A analog tazarotene (Tazorac) is a prescription drug that is approved by the U.S. Food and Drug Administration to treat stable plaque psoriasis covering up to 20% body surface area (103713). This drug is not interchangeable with non-prescription, commercially available vitamin A products, such as retinol.
Radiation proctopathy. It is unclear if oral vitamin A is beneficial for reducing chronic radiation proctopathy symptoms. Details: A small clinical study in patients experiencing chronic radiation proctopathy caused by pelvic radiotherapy shows that taking retinol palmitate 10,000 IU daily for 90 days might reduce rectal symptoms when compared with placebo (82350).
Retinopathy of prematurity. Most small studies show that oral or intramuscular vitamin A does not reduce the risk of retinopathy of prematurity (ROP). Details: A meta-analysis of 4 small clinical studies in very low birth weight infants shows that intramuscular administration of vitamin A 2000-10,000 IU every other day or three times weekly, or oral vitamin A 2000 IU daily, for 28 days does not reduce the risk of ROP when compared with a control (107297). Another meta-analysis of clinical research shows that providing supplemental enteral vitamin A 1500 IU or an average of 5000 IU daily, starting within four days of birth, does not reduce the incidence of severe ROP (109750,109753). However, a very small clinical study in preterm infants, which was not included in the meta-analysis, shows that receiving retinol palmitate drops 3000 IU/kg daily for 28 days reduces the risk of ROP by 88% when compared with no treatment (103672).
Urinary tract infections (UTIs). It is unclear if adding oral vitamin A to antibiotic therapy is beneficial for symptoms of acute pyelonephritis in young females. Details: A small clinical study in females 2-12 years of age with a first occurrence of acute pyelonephritis shows that taking vitamin A 1500 units/kg daily for 10 days in conjunction with antibiotics decreases the duration of fever by about 1.3 days and reduces urinary frequency by about 1.5 episodes per day when compared to taking placebo with antibiotics. Taking vitamin A might also reduce the occurrence of moderate or severe renal scarring after 6 months when compared with placebo (100327). The validity of these findings is limited by small study size and a high dropout rate.
Warts. It is unclear if topical or oral vitamin A improves the resolution of viral warts. Details: A meta-analysis of observational and clinical research in patients with viral warts suggests that receiving prescription oral retinoids (isotretinoin, acitretin, etretinate) seems to produce a 61% rate of wart resolution. Prescription topical retinoids seems to produce a 64% rate of wart resolution (104461). These drugs are not interchangeable with non-prescription, commercially available vitamin A products, such as retinol. More evidence is needed to rate vitamin A for these uses.

(Read more about VITAMIN A)

VITAMIN E

EFFECTIVE

Ataxia with vitamin E deficiency (AVED). Oral vitamin E is effective for treating vitamin E deficiency due to the genetic disorder AVED. Details: This genetic disorder occurs when the gene that produces alpha-tocopherol transfer protein (alpha-TTP) is defective. This causes severe vitamin E deficiency. Symptoms such as cerebellar ataxia, dysarthria, absence of deep tendon reflexes, and sensory loss usually appear between 4 and 18 years of age. Vitamin E supplements are used in the treatment of AVED (13498,101437,101438).
Vitamin E deficiency. Oral vitamin E is effective for preventing or treating vitamin E deficiency and associated conditions. Details: Taking vitamin E orally is effective for preventing and treating vitamin E deficiency (4844). However, vitamin E deficiency is rare in humans. It most commonly occurs in people with malabsorption disorders such as abetalipoproteinemia; cystic fibrosis; gastrectomy; hepatic-biliary tract disease including chronic cholestasis, hepatic cirrhosis, biliary atresia, and obstructive jaundice; in infants receiving formula with insufficient vitamin E; intestinal diseases including celiac and tropical sprue; and regional enteritis (4844,104411).

POSSIBLY EFFECTIVE

Alzheimer disease. Oral vitamin E might slow functional decline in some patients with this condition. However, it does not seem to prevent Alzheimer disease onset. Details: A clinical study in patients with moderate Alzheimer disease shows that taking all-rac-alpha-tocopherol (synthetic vitamin E) 2000 IU daily for 2 years might be similar to selegiline (Eldepryl), and superior to placebo, for slowing cognitive decline. Benefit was only apparent when outcomes were adjusted for baseline Mini-Mental State Examination (MMSE) scores. This study is limited by attrition bias, or incomplete outcome reporting (4635,97070). Another clinical study in patients with mild-to-moderate Alzheimer disease shows that taking all-rac-alpha-tocopherol 2000 IU daily reduces the annual rate of decline in activities of daily living by 19% when compared with placebo. This translates to a delay in disease progression of 6.2 months. This is comparable to the effect of acetylcholinesterase inhibitors (e.g., rivastigmine) in this population. Despite these positive findings, the World Health Organization (WHO) recommends against the use of vitamin E for the management of dementia due to the increased risk for adverse effects with the extended use of high-dose vitamin E (104823). Interestingly, the combination of vitamin E and memantine (Namenda) 20 mg per day is not superior to placebo in this population. Researchers speculate that this lack of effectiveness may be due to an interaction between vitamin E and memantine, but this proposed interaction has not been validated in research (19060,97070). Vitamin E supplementation doesn't seem to prevent Alzheimer disease or slow progression of mild cognitive impairment. Patients with mild cognitive impairment who take vitamin E 2000 IU daily for 3 years progress to Alzheimer disease at the same rate as those who take placebo (13060,97070). Furthermore, although population research has found that greater intake of foods high in vitamin E is associated with a lower risk of developing Alzheimer disease (34597,90082), taking vitamin E supplements does not seem to help. Evidence from a large clinical study that was later converted into an observational study shows that taking vitamin E 400 IU orally daily does not prevent Alzheimer disease when compared with placebo in cognitively intact men (93570). However, this study is limited by the fact that the participants were well-educated and were assessed for dementia in their 60s; the prevalence of dementia is typically low in this age group (93571).
Beta-thalassemia. Oral vitamin E seems to be beneficial for children with this condition. Details: A small clinical study in children with beta-thalassemia and low vitamin E plasma concentrations shows that taking vitamin E orally seems to correct erythrocyte membrane abnormalities when compared with control (4642). Another small clinical trial in children 5-18 years of age with beta-thalassemia shows that taking an age-based dose of vitamin E (alpha-tocopherol) 200-600 mg daily for 4 weeks seems to increase haptoglobin levels, suggesting reduced hemolysis, when compared with placebo (104412).
Dysmenorrhea. Oral vitamin E seems to reduce pain in adults with dysmenorrhea. Details: Small clinical studies in younger adults with primary dysmenorrhea show that taking vitamin E 200-500 IU daily, starting 2 days before menstruation and continuing through the first 3 days of bleeding for 2-4 cycles, decreases the severity and duration of pain and reduces blood loss when compared with placebo (10361,14432,99367). One study also shows that taking vitamin E 200 IU with fish oil provides better pain relief when compared with taking either vitamin E or omega-3 fatty acids alone (99367). A meta-analysis of 8 small clinical studies, including those described above, in individuals with dysmenorrhea shows that taking vitamin E reduces the severity of pain when compared with placebo (112170).
Exercise-induced muscle damage. Oral vitamin E seems to modestly reduce exercise-induced muscle damage. Details: A meta-analysis of 17 very small clinical studies in trained and untrained adults shows that taking vitamin E 300-1200 IU daily for up to 12 weeks reduces markers of exercise-induced muscle damage, including creatine kinase and lactate dehydrogenase, when compared with placebo. Vitamin E appears to be most beneficial in athletes and at doses under 500 IU daily (112160). However, a small clinical study in endurance-trained runners, not included in the analysis above, shows that taking vitamin E (as alpha-tocopherol) 235 mg and vitamin C 1000 mg 2 hours prior to an exercise protocol does not reduce delayed onset muscle soreness or improve markers of exercise-induced muscle damage when compared with placebo (109961).
Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Oral vitamin E seems to be beneficial in patients with G6PD deficiency. Details: Individual clinical studies evaluating the use of vitamin E in patients with G6PD deficiency show mixed results (4682,4683,4684). However, a meta-analysis of 6 small clinical studies in patients with G6PD deficiency shows that taking vitamin E improves hemoglobin levels and reduces reticulocyte levels when compared with placebo in the setting of both acute and chronic hemolysis (112164).
Intracranial hemorrhage. Oral vitamin E might reduce the risk of intracranial hemorrhage in premature infants. Details: Clinical research shows that giving premature neonates vitamin E orally might reduce the risk of intracranial hemorrhage when compared with control (4655,85074).
Intraventricular hemorrhage. Oral vitamin E might reduce the risk of intraventricular hemorrhage in premature infants. Intravenous vitamin E does not provide this benefit. Details: A meta-analysis of the available clinical research shows that oral, but not intravenous, administration of vitamin E can reduce the risk for intraventricular hemorrhage in premature neonates when compared with control. However, it might not reduce the risk for severe (grade III-IV) intraventricular hemorrhage. Additionally, high serum levels of vitamin E have been associated with an increased risk for sepsis in premature infants (85062).
Nitrate tolerance. Oral vitamin E might reduce tolerance to nitrates. Details: Nitrate tolerance might involve increased vascular superoxide anion production, and antioxidants may help prevent this (4705). Clinical research in patients with ischemic heart disease shows that taking vitamin E 447-894 IU daily can help prevent nitrate tolerance when compared with placebo (4705,11543).
Nonalcoholic steatohepatitis (NASH). Oral vitamin E seems to improve outcomes in patients with NASH. Details: Clinical studies and meta-analyses in adults with NASH shows that taking vitamin E 800 IU daily for up to 24 months improves liver enzymes, hepatic fibrosis, steatosis, and lobular inflammation (14005,17517,97077,104413). Taking vitamin E 400-1200 IU in children with NASH also seems to improve liver enzyme levels after 4-10 months of treatment (89). Furthermore, a small study in patients with NASH shows that taking vitamin E 800 IU daily for 1 year seems to improve liver histology to a similar degree as taking telmisartan 40 mg daily (104405). In fact, practice guidelines by the American Association for the Study of Liver Diseases (AASLD) recommend taking vitamin E 800 IU daily as a first-line therapy in non-diabetic adults with biopsy-proven NASH. However, vitamin E isn't recommended in NASH patients with diabetes, cirrhosis, or cryptogenic cirrhosis (98130).
Premenstrual syndrome (PMS). Oral vitamin E seems to improve PMS symptoms. Details: Clinical research in adults with PMS shows that taking vitamin E 400-600 IU daily for 3 cycles reduce subjective reports of symptoms, including anxiety, craving, and depression, when compared with placebo (4719,4720). Another small clinical study in Japanese patients with PMS shows that taking vitamin E, as gamma-tocopherol 180 mg, twice daily for 7 days during the luteal phase of 2 consecutive cycles reduces fatigue, irritability, and leg swelling when compared with placebo (112337).
Tardive dyskinesia. Oral vitamin E might attenuate worsening of tardive dyskinesia in patients taking antipsychotic medications. Details: Small clinical studies suggest that taking vitamin E orally improves Abnormal Involuntary Movement Scale (AIMS) scores in patients with tardive dyskinesia. It seems to be more effective in higher doses and in people who have had tardive dyskinesia for less than 5 years (3942,3943,3944,3945,3946,3948,85323). Both RRR-alpha-tocopherol (natural vitamin E) and unspecified forms were used in clinical trials. However, some conflicting findings have been reported. A meta-analysis suggests that vitamin E does not improve symptoms of tardive dyskinesia when compared with placebo; however, taking vitamin E seems to prevent the deterioration of symptoms when compared with placebo (97079).

POSSIBLY INEFFECTIVE

Age-related macular degeneration (AMD). Oral vitamin E does not seem to slow AMD progression. Details: Results from clinical trials and meta-analyses of clinical trials show that vitamin E when taken alone or in combination with other antioxidants does not prevent the development (4667,7303,7304,34625) or progression of AMD (34633). In contrast, taking vitamin E 400 IU orally with elemental zinc 80 mg, vitamin C 500 mg, and beta-carotene 15 mg daily does seem to be beneficial. When taken for 5 years, this combination reduces visual acuity loss and reduces the risk of progression of AMD by 25% in patients with advanced AMD (7303,11326). A 10-year follow-up on this study confirmed these findings (90069). It is not known if this combination is beneficial for people with less advanced macular disease or for preventing AMD. Additionally, it is not clear if this benefit is due to vitamin E, the other ingredients, or the combination.
Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Oral vitamin E does not seem to slow ALS progression. Details: Clinical research in patients with ALS shows that taking alpha-tocopherol 1490 IU daily for up to 12 months in addition to riluzole does not influence survival or motor function when compared with riluzole alone. However, these patients seem to be less likely to progress to a more severe disease state from a milder disease state (83180). Additionally, a large population study has found that dietary intake of vitamin E is not associated with risk of developing ALS (90087).
Angina. Oral vitamin E does not seem to reduce angina symptoms. Details: Clinical research shows that taking vitamin E orally may have some effect on endothelial dysfunction, but does not improve angina in nonsmokers or smokers, when compared with placebo (3896,4634,4649,4650,4651,4652).
Atherosclerosis. Oral vitamin E does not seem to reduce atherosclerosis progression. Details: Taking RRR-alpha-tocopherol (natural vitamin E) orally does not appear to have any effect on atherosclerosis progression or mortality in patients with atherosclerosis when compared with placebo (3899,3936). However, there is preliminary evidence that a combination of vitamin E and vitamin C might help prevent the progression of atherosclerosis in men, particularly smokers and cardiac transplant patients (1918).
Atopic dermatitis (eczema). Oral vitamin E does not seem to reduce eczema symptoms. Details: Clinical research shows that taking vitamin E 600 IU in combination with selenium daily for 12 weeks does not improve symptoms of atopic eczema when compared with placebo or selenium alone (74456). Also, while some clinical research shows that taking 600 IU of all-rac-alpha-tocopherol (synthetic vitamin E) daily for 60 days with vitamin D 1600 IU improves overall atopic dermatitis symptoms, pruritus, and erythema when compared with placebo, taking vitamin E alone does not seem to have this effect. However, vitamin E alone does improve hard, leathery skin symptoms and dryness when compared with placebo (84491).
Breast cancer-related hot flashes. Oral vitamin E does not seem to reduce hot flashes related to breast cancer. Details: Clinical research shows that taking vitamin E 800 IU daily for 4 weeks does not reduce hot flashes in females who have had breast cancer when compared with placebo (454).
Bronchopulmonary dysplasia. Oral vitamin E does not seem to reduce the risk for bronchopulmonary dysplasia in premature infants. Details: Clinical research in premature infants weighing less than 1500 grams at birth shows that taking vitamin E orally does not prevent bronchopulmonary dysplasia when compared with placebo (4657,85062).
Cataracts. Oral vitamin E does not seem to reduce cataract risk. Details: Some population research has found that dietary and supplemental vitamin E intake is associated with a reduced risk of developing age-related cataracts (4208,4663,4665,4759). However, other population research has not found this association (2395,4664,92902). Additionally, higher quality evidence from clinical trials and a meta-analysis consistently shows that vitamin E, taken alone or with other vitamins, does not prevent the progression of age-related cataracts or decrease vision loss when compared with control (4666,7304,34626).
Chemotherapy-induced peripheral neuropathy. Oral vitamin E does not seem to reduce peripheral neuropathy due to chemotherapy. Details: Although some small, low-quality clinical studies and a meta-analysis of these studies suggest that vitamin E 600 mg daily for 3 months might be beneficial for preventing chemotherapy-induced peripheral neuropathy induced by cisplatin, carboplatin, or oxaliplatin when compared with placebo (10366,85117,90072), these studies have found no effect with lower doses of vitamin E or in those receiving paclitaxel chemotherapy (107862). In addition to the low methodological quality of the studies, the validity of these finding is limited by high heterogeneity, as the studies included patients with several different cancer types. Also, a large, high-quality clinical study shows that taking vitamin E 400 mg daily is not beneficial for preventing peripheral neuropathy induced by taxanes or platinum analogues when compared with placebo (101457). The American Society of Clinical Oncology does not recommend the use of vitamin E for the prevention or management of chemotherapy-induced peripheral neuropathy (101434).
Colorectal cancer. Oral vitamin E does not seem to reduce colorectal cancer risk. Details: Some population research has found that intake of vitamin E and multivitamins is associated with a reduced risk of colorectal cancer (1047). Some preliminary clinical research also shows that taking vitamin E orally in combination with other vitamins might have a protective effect in patients with a history of colorectal adenomas (3954,3956,92903). However, higher quality evidence from larger clinical trials and meta-analyses of clinical research consistently show that taking vitamin E supplements alone, or in combination with other vitamins, does not prevent colorectal cancer incidence or recurrence when compared with control (3953,3955,3957,12185,13036,13131,34594,90361). Despite this conflicting research, the US Food and Drug Administration (FDA) approved a qualified health claim in 2009 regarding vitamin E and colorectal cancer risk. However, the FDA has determined that it is highly unlikely that vitamin E supplements reduce the risk of colorectal cancer (102332).
Congestive heart failure (CHF). Oral vitamin E does not seem to reduce CHF symptoms or prevent CHF development. Details: Clinical research in adults with New York Heart Association (NYHA) functional class III or IV heart failure shows that taking vitamin E (RRR- α tocopherol) 500 IU orally daily for 12 weeks does not improve prognostic or functional indices of CHF or quality of life measurements when compared with placebo (3906). Additionally, population research shows that taking vitamin E 600 IU every other day does not affect the risk of developing heart failure in healthy females 45 years or older when compared with placebo (90068).
Head and neck cancer. Oral vitamin E does not seem to reduce the risk of head and neck cancer recurrence. In fact, it might increase recurrence risk. Details: A large clinical trial in patients with stage I or II head and neck cancer shows that taking all-rac-alpha-tocopherol (synthetic vitamin E) 400 IU daily, during radiation therapy and for 3 years after the end of radiation therapy, does not reduce the risk of recurrence of the first tumor or development of a second primary tumor when compared with placebo. In fact, there is some concern that patients taking vitamin E seem to have an increased risk of tumor recurrence or a second primary tumor when compared with patients taking placebo (13055). Advise patients with head and neck cancer to avoid taking vitamin E supplements in doses of 400 IU/day or more.
Hypertension. Oral vitamin E does not seem to reduce blood pressure. Details: A clinical study in patients with hypertension who are receiving conventional treatment shows that taking vitamin E 300 mg daily orally for 3-4 years does not lower blood pressure when compared with control (5210).
Intrauterine growth restriction (IUGR). Oral vitamin E during pregnancy does not seem to reduce IUGR risk. Details: A meta-analysis of clinical research shows that taking vitamin E along with other ingredients throughout pregnancy does not reduce the risk for IUGR when compared with placebo (97075).
Liver disease. Oral vitamin E does not seem to reduce liver disease-associated mortality. Details: A meta-analysis of clinical research shows that taking vitamin E does not reduce all-cause-or liver related-mortality or morbidity in patients with liver diseases, including autoimmune liver diseases, viral hepatitis, alcoholic liver disease, or cirrhosis (34608). Additional clinical research in male smokers over 50 years old shows that taking vitamin E 75 IU orally, alone or with beta-carotene 20 mg orally, daily for 5-8 years does not reduce the risk of mortality due to chronic liver disease when compared with placebo (91383).
Oral leukoplakia. Oral vitamin E does not seem to reduce the risk for oral leukoplakia in male smokers. Details: Although there is some conflicting evidence (3951,4708), the largest randomized controlled trial indicates that supplementation with all-rac-alpha-tocopherol (synthetic vitamin E) 55.6 IU daily for 5-7 years has no effect on the incidence of oral lesions in male cigarette smokers when compared with placebo (3951).
Osteoarthritis. Oral vitamin E does not seem to be beneficial for osteoarthritis treatment or prevention. Details: Taking vitamin E 500 IU daily for 6 months does not seem to decrease symptoms of pain or stiffness in patients with osteoarthritis when compared with placebo (5264). Additional clinical research show that taking vitamin E 500 IU daily for up to 2 years does not slow cartilage loss when compared with placebo (13066). Population research has shown that taking vitamin E supplements does not reduce the risk of developing osteoarthritis or slow the progression of existing osteoarthritis (5881).
Pancreatic cancer. Oral vitamin E does not seem to reduce pancreatic cancer risk. Details: Taking vitamin E supplements alone or in combination with other antioxidants such as beta-carotene and vitamin C does not reduce the risk of developing pancreatic cancer (12185,85147). Taking all-rac-alpha-tocopherol (synthetic vitamin E) 55.6 IU daily for 5 to 8 years also does not seem to reduce the incidence of or mortality from carcinoma of the pancreas in male smokers (3961).
Parkinson disease. Oral vitamin E does not seem to reduce Parkinson disease symptoms or progression, although the risk of developing the disease may decrease with increased dietary vitamin E intake. Details: Observational research has found that dietary vitamin E intake might be associated with a decreased occurrence of Parkinson disease (4712). A meta-analysis of 12 studies evaluating the risk of developing Parkinson disease has found that the highest daily intake of vitamin E is associated with a 20% lower risk than those with the lowest intake (107858). However, clinical research in patients with stage I or II Parkinson disease shows that taking all-rac-alpha-tocopherol (synthetic vitamin E) 2000 IU daily for up to 24 months doesn't seem to have any benefit when compared with baseline or control (4709,4710,4711,85318).
Pharyngeal cancer. It is unclear if oral vitamin E reduces the risk of developing cancer of the pharynx. Details: A sub-group analysis of a large-scale clinical trial (The HOPE Trial) in patients with diabetes or cardiovascular disease suggests that taking RRR-alpha-tocopherol (natural vitamin E) 400 IU daily for about 7 years is not linked with a reduced risk of developing oral or pharyngeal cancer when compared with placebo (13036).
Pre-eclampsia. Oral vitamin E does not seem to reduce pre-eclampsia risk. Details: The majority of clinical research shows that taking a combination of vitamins E and C, at the same doses, does not reduce the risk of pre-eclampsia in low-, moderate-, or high-risk patients, when compared with placebo or no treatment. Also, the risk of gestational hypertension might increase in some cases, although results are inconsistent (83312,83356,83383,83472,83474,97075,97059). Other researchers using vitamin E in combination with vitamin C and allopurinol beginning at 24-32 weeks gestation found the combination similar to placebo (4718). However, some clinical research suggests that taking a combination of vitamin E 400 IU and vitamin C 1000 mg daily reduces the risk of proteinuric hypertension in high-risk patients when started in weeks 16-22 of pregnancy (3236).
Preterm labor. Oral vitamin E does not seem to reduce risk for premature labor. Details: A meta-analysis of clinical research shows that taking vitamin E along with other ingredients throughout pregnancy does not reduce the risk for preterm labor when compared with placebo (97075).
Prostate cancer. Oral vitamin E does not seem to reduce the risk of prostate cancer. Details: A meta-analysis of over 30 large clinical trials and observational studies shows that neither dietary nor supplemental vitamin E reduces the risk of prostate cancer when compared with a control (112159). However, individual study results are mixed. Population research on the use of dietary or supplemental vitamin E intake for prostate cancer risk reduction is conflicting (12872,14124,12873,15607). Although one large-scale study in smokers found that taking 55.6 IU daily of all-rac-alpha-tocopherol (synthetic vitamin E) reduced the risk of prostate cancer and mortality (3959,11303), most large-scale randomized, controlled trials show that vitamin E is not beneficial. A sub-group analysis of a large-scale clinical study (The HOPE trial) in patients with diabetes or cardiovascular disease suggests that taking 400 IU of RRR-alpha-tocopherol (natural vitamin E) daily for about 7 years is not linked with a decreased risk of developing prostate cancer when compared with placebo (13036). Another large scale study (Physician's Health Study II) shows that taking vitamin E 400 IU every other day for an average of 8 years does not reduce the risk of prostate cancer when compared with placebo (16708,90097). Similarly, another large clinical study (The SU.VI.MAX study) shows that a combination of vitamin E (alpha-tocopherol) 44.7 IU, vitamin C 120 mg, beta-carotene 6 mg, selenium 100 mcg, and zinc 20 mg daily for an average of 8 years does not reduce the risk of prostate cancer overall when compared with placebo (14135). A fourth large-scale clinical trial (The SELECT trial) in men over the age of 50 years shows that taking all-rac-alpha-tocopherol (synthetic vitamin E) 400 IU daily, alone or in combination with selenium 200 mcg daily, for an average of about 5.5 years does not reduce prostate cancer risk when compared with placebo (16707). Also, an extension of this initial study found that taking vitamin E alone was associated with a 17% increased of developing prostate cancer (17688).
Respiratory tract infections. Oral vitamin E does not seem to reduce respiratory infections in most patients. However, there's some evidence that it might reduce incidence of the common cold in patients living in long-term care facilities. Details: Taking oral vitamin E 298 IU daily, alone or in supplemental multivitamin form, does not appear to decrease the incidence, duration, or severity of upper or lower respiratory infections in elderly persons when compared with placebo (10788,12094). However, some research shows that taking vitamin E reduces the incidence of the common cold in elderly long-term care patients when compared with placebo (12094). More evidence is needed to determine how effective vitamin E might be for reducing the incidence of the common cold.
Retinitis pigmentosa. Oral vitamin E does not seem to reduce retinitis pigmentosa and related visual decline. Details: Taking all-rac-alpha-tocopherol (synthetic vitamin E) orally does not appear to slow visual decline is people with retinitis pigmentosa and has been associated with more rapid loss of visual acuity, although the validity of the study with these findings has been questioned (83,84,85,86,87,88).
Scarring. Topical vitamin E does not seem to improve scar appearance. Details: Some clinical research shows that applying ointment containing vitamin E topically does not reduce surgical wound scarring when compared with a placebo ointment (4721,4722).
Stillbirth. Oral vitamin E does not seem to reduce risk of a stillborn baby. Details: A meta-analysis of clinical research shows that taking vitamin E along with other ingredients during pregnancy does not reduce the risk for stillbirth when compared with placebo (97075).

LIKELY INEFFECTIVE

Breast cancer. Oral vitamin E does not reduce breast cancer risk. Details: Some evidence suggests that higher serum levels of vitamin E might be associated with a reduced risk of breast cancer (10132). However, increasing vitamin E intake from the diet or supplements does not seem to reduce the risk of developing breast cancer (4658,4659,85147,112334). Also, a large-scale randomized trial in patients with diabetes or cardiovascular disease shows that patients who take 400 IU of RRR-alpha-tocopherol (natural vitamin E) daily do not have a reduced risk of developing breast cancer (13036). In other large-scale studies, females who take RRR-alpha-tocopherol (natural vitamin E) 600 IU every other day for up to 10 years also do not have a lower risk of developing breast cancer (13131,34580).
Cancer. Oral vitamin E does not reduce the risk of cancer in most patients. Details: Some research suggests that a combination of vitamin E 44.7 IU daily with vitamin C, beta-carotene, selenium, and zinc does not lower the overall risk of cancer, although it might reduce the risk of cancer when only males are evaluated (14109). However, clinical research from a large scale study (Physician's Health Study II) shows that taking vitamin E 400 IU every other day for an average of 8 years does not reduce the overall risk of cancer in males when compared with placebo (16708,90097). Also, clinical research published in a meta-analysis shows that taking vitamin E does not reduce the overall risk of cancer (85147). In 2003, the US Food and Drug Administration (FDA) approved a qualified health claim regarding antioxidant vitamins, such as vitamin E and overall cancer risk. However, the FDA has determined that the evidence is limited and inconclusive (102334). The US Preventive Services Task Force (USPSTF) states that there is no net benefit to supplementation with vitamin E for the prevention of cancer in general and therefore recommends against its use (108641,112166).
Cardiovascular disease (CVD). Most evidence shows that oral vitamin E does not reduce the risk for CVD events or complications. Details: Most clinical research in various populations shows that taking vitamin E supplements orally is not effective for preventing heart disease or adverse cardiovascular outcomes such as myocardial infarction (MI), stroke, hospitalizations for unstable angina, morbidity, or cardiovascular death (12492,12493,13036,14108,66140,83050,85084,85224). The US Preventive Services Task Force (USPSTF) states that there is no net benefit to supplementation with vitamin E for the prevention of CVD in general and therefore recommends against its use (108641,112166). With few exceptions (3357,3936), large-scale controlled clinical trials show that vitamin E supplements offer no benefit for primary prevention in healthy or high-risk patients (3907,3935,3937,13036,13131), or for secondary prevention of heart disease and cardiovascular events such as MI, stroke, and death (3896,3899,13036). While one analysis of clinical research found that in mostly healthy patients 70 years or younger without CVD, vitamin E supplementation reduces the risk of cardiovascular mortality, the authors performed more than 20 statistical tests and did not adjust for multiple comparisons. Therefore, it possible that the positive effect was due to chance. This analysis was also limited because it excluded adults older than 70 years of age and adults that are more likely to suffer an exacerbation from a chronic condition. Furthermore, the analysis showed that vitamin E supplementation does not reduce the risk of all-cause mortality or the risk of CVD compared with placebo or no intervention (97078). There's additional conflicting evidence. One large-scale trial shows that healthy females who take RRR-alpha-tocopherol (natural vitamin E) 600 IU every other day for up to 10 years also do not have a lower risk of major cardiovascular events but might have a 24% lower risk of cardiovascular death when compared with placebo (13131). This finding is contradictory to previous findings. One notable limitation of this trial is a lack of systematic assessment of the use of statins or other cardiovascular therapies by the participants throughout the 10-year period. Meta-analyses of clinical trials involving patients with type 2 diabetes and the haptoglobin 2-2 genotype show that taking vitamin E, up to 600 IU daily for up to 8 years, reduces the incidence of non-fatal myocardial infarction and death due to CVD (85179,85221). Because these meta-analyses included only specific patients, the generalizability of the results is questionable. There is debate about whether some forms of vitamin E might work differently than others. Some people suggest that RRR-alpha-tocopherol (natural vitamin E) is more effective than all-rac-alpha-tocopherol (synthetic vitamin E). This has not been verified by studies. A meta-analysis of vitamin E studies indicates that there is no significant difference in cardiovascular outcomes based on the form of vitamin E used (13132). The FDA has refused to allow labeling claims for vitamin E supplements for prevention of CVD (3939). A Science Advisory from the American Heart Association also states that the evidence doesn't justify use of antioxidants such as vitamin E for reducing the risk of CVD (12142). Advise patients not to rely on vitamin E supplements for preventing heart disease.
Fetal and premature infant mortality. Oral vitamin E does not seem to reduce death in preterm infants. Details: Meta-analyses of clinical research show that taking vitamin E throughout pregnancy does not affect morbidity or mortality in preterm infants when compared with placebo (85074,97075).
Fibrocystic breast disease. Oral vitamin E does not improve fibrocystic breast disease in most patients. Details: Clinical research shows that taking alpha-tocopherol 150 IU, 300 IU, or 600 IU daily for 2-3 months does not improve subjective or objective measures of fibrocystic breast disease when compared with placebo (4660,4661,4662).
Lung cancer. Oral vitamin E does not seem to reduce lung cancer risk. Details: Taking all-rac-alpha-tocopherol (synthetic vitamin E) 55.6 IU daily for 5-8 years is not associated with a lower risk of developing lung cancer for male smokers (3949). A sub-group analysis of a large scale clinical trial in patients with diabetes or cardiovascular disease who take RRR-alpha-tocopherol (natural vitamin E) 400 IU daily for about 7 years do not have a lower risk of developing lung cancer when compared with placebo (13036). In another large-scale study, females who take RRR-alpha-tocopherol (natural vitamin E) 600 IU every other day for up to 10 years also do not have a lower risk of developing lung cancer (13131). Meta-analyses of clinical research suggest taking vitamin E as alpha-tocopherol for up to approximately 10 years does not prevent lung cancer or reduce the incidence of lung cancer mortality when compared with placebo (34632,85147).
Overall mortality. Oral vitamin E does not seem to reduce the risk of mortality from all causes. Details: Although some population research suggests that increased dietary vitamin E intake is associated with reduced overall mortality (98260), most meta-analyses of clinical research in adults show that taking vitamin E supplements for at least 1 year does not affect all-cause mortality (34622,85164,85200). Furthermore, when only high quality clinical trials were analyzed, mortality was increased by 3% in adults taking vitamin E when compared with control (34622).
Prematurity. Oral vitamin E does not seem to reduce the risk of premature birth and complications. Details: Clinical research shows that vitamin E does not improve blood parameters or prevent the development of anemia in premature infants (4648,10362). One clinical study in premature infants weighing less than 1500 grams at birth shows that giving vitamin E 25 IU daily for six weeks does not improve hemoglobin concentration, reticulocyte counts, or platelet counts when compared with placebo (4648). Another clinical study in premature infants weighing less than 1250 grams at birth shows that giving vitamin E 50 IU daily for eight weeks does not increase the response to erythropoietin and iron when compared with placebo (10362).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Aging skin. Topical vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in Asian females aged 30-65 years shows that applying a specific liquid product, (Antioxidant and Collagen Booster Serum, Max Biocare Pty Ltd.) containing vitamin E 1%, vitamin C 20%, and red raspberry leaf cell culture extract 0.0005%, to the face nightly for 8 weeks, in addition to regular facial skin products, improves skin color, elasticity, radiance, smoothness, and appearance of wrinkles when compared with regular facial skin products alone (102355).
Anemia of chronic disease. Small clinical studies suggest that oral vitamin E might improve response to anemia treatment in patients on chronic hemodialysis. Details: Two small studies in adults and children on chronic hemodialysis have shown improved response to erythropoietin with vitamin E supplementation (4640,4647). In one study, children given vitamin E 22.4 IU/kg in combination with erythropoietin had significantly increased hemoglobin and hematocrit levels after 2 weeks of combination treatment, compared with eight and five weeks in patients receiving erythropoietin alone (4640). In a study of adults, concurrent supplementation with vitamin E 745 IU daily allowed dose reductions of erythropoietin from an average of 93 U/kg/week to 74 U/kg/week with the same resultant hemoglobin levels (4647).
Anthracycline cardiotoxicity. Oral vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with breast cancer receiving doxorubicin and cyclophosphamide chemotherapy shows that taking vitamin E 600 mg three times daily and L-carnitine 3000 mg by intravenous infusion on day 1 followed by 300 mg by mouth four times daily thereafter for 3 weeks reduced the risk of cardiovascular events by 63% and improved laboratory markers of cardiotoxicity when compared with chemotherapy alone (112338). It is unclear if these findings are due to vitamin E, L-carnitine, or the combination.
Anxiety. It is unclear if oral vitamin E is beneficial in patients with anxiety. Details: A meta-analysis of 5 mostly small clinical studies in patients without anxiety shows that taking vitamin E 200-400 IU daily for up to 10 weeks does not improve anxiety symptom scores when compared with placebo (112158). It is unclear if these findings can be generalized to patients with anxiety disorders.
Asthma. It is unclear if oral vitamin E is beneficial for asthma treatment or prevention. Details: There is inconsistent evidence about the role of vitamin E in asthma. Some population research has found that increased dietary intake of vitamin E is associated with a lower risk of asthma; however taking vitamin E supplements are not associated with decreased risk (6058,15006). Low vitamin E intake also appears to be associated with an increased risk of asthma (315,401,422). A small clinical study in children with asthma suggests that adding vitamin E 74.5 IU by mouth daily to fluticasone treatment for 8 weeks may decrease cough, wheezing, and dyspnea when compared with baseline (90077). This study was limited because it did not compare the vitamin E intervention to the control group.
Atopic disease. It is unclear if oral vitamin E reduces the risk of atopic disease in infants. Details: Population research has found that increased maternal vitamin E intake isn't associated with decreased odds of developing eczema, food allergy, wheeze, allergic sensitization, or any allergic disease in infants (90098).
Bladder cancer. It is unclear if oral vitamin E reduces bladder cancer risk. Details: A meta-analysis of clinical research shows that the highest intake of vitamin E is associated with a reduced risk for bladder cancer when compared to the lowest intake in patients followed for more than 10 years. This benefit was not seen in those followed for less than 10 years. This effect appears to be dose-dependent, although it is not clear how much vitamin E intake is required to reduce bladder cancer risk. Additionally, it is not clear whether this benefit differs for dietary or supplemental intake of vitamin E (101435). In 2009, the US Food and Drug Administration (FDA) approved a qualified health claim regarding vitamin E and bladder cancer risk. However, the FDA has determined that it is highly unlikely that vitamin E supplements reduce the risk of bladder cancer (102332). Some population research also shows that regular use of vitamin E supplements for more than 10 years is associated with a reduced risk of bladder cancer mortality; however, use for less than 10 years is not associated with reduced mortality (9839).
Burns. It is unclear if topical vitamin E is beneficial for healing of burn wounds. Details: A small clinical study in patients with moderate and deep burn wounds (25% to 67%) shows that applying a specific alpha-tocopherol product (Filme Olio) daily seems to reduce infection and improve healing when compared with usual treatment (104407).
Chemotherapy-related infection. It is unclear if oral vitamin E is beneficial in patients with infection due to chemotherapy. Details: Observational research suggests that greater dietary intake of vitamin E may lower the incidence of infection in children undergoing chemotherapy for lymphoblastic leukemia (11997).
Chronic fatigue syndrome (CFS). Although there is interest in using oral vitamin E for CFS, there is insufficient reliable information about the clinical effects of vitamin E for this condition.
Cisplatin-associated ototoxicity. It is unclear if oral vitamin E is beneficial for preventing ototoxicity due to cisplatin. Details: A small clinical study in patients receiving cisplatin for solid tumors shows that taking a specific vitamin E supplement (Rigentex, Bracco) as alpha-tocopherol 400 IU daily for 3 months attenuates hearing loss when compared with placebo (97082).
Colistin-induced nephrotoxicity. It is unclear if oral vitamin E is beneficial for preventing nephrotoxicity due to colistin. Details: A small clinical study in patients receiving colistin therapy shows that taking vitamin E (alpha-tocopherol) 400 IU orally daily for the duration of colistin therapy does not reduce the incidence or duration of acute kidney injury when compared with colistin alone (107867).
Contrast induced nephropathy. It is unclear if oral or intravenous vitamin E is beneficial in patients with nephropathy due to contrast dye. Details: A small clinical study in patients receiving elective computer-assisted tomography with nonionic radiocontrast agents shows that receiving vitamin E 3218 IU emulsion in 0.45% saline intravenously infused at the rate of 1 mL/kg/hr over 24 hours does not decrease the risk of contrast agent-induced nephropathy when compared with normal saline alone (90081). However, oral vitamin E may modestly reduce the risk of contrast induced nephropathy. A clinical trial shows that taking vitamin E as alpha-tocopherol 522 IU or gamma-tocopherol 447 IU orally daily, starting 5 days prior to the procedure and continuing 2 days post-procedure, results in a 9% to 10% lower incidence of contrast induced acute kidney injury when compared with standard treatment with normal saline (90096). Another clinical study shows that taking a single dose of vitamin E 1490 IU orally before elective coronary angiography reduces the risk of contrast induced kidney injury by 7% when compared with placebo (97074).
Coronary artery bypass graft (CABG) surgery. It is unclear if oral vitamin E is beneficial for recovery after CABG. Details: When taking vitamin E orally with vitamin C and allopurinol two days prior to CABG and one day postoperatively, patients had fewer perioperative infarctions and lower creatine kinase-MB release (4699); however, this benefit was not found when using vitamin E alone or in combination with vitamin C without allopurinol (4697,4698).
Critical illness (trauma). An analysis of several small clinical studies suggests that oral or intravenous vitamin E is not beneficial in patients admitted to the intensive care unit (ICU). Details: A meta-analysis of 5 small clinical studies in patients admitted to the ICU shows that administration of oral or intravenous vitamin E 400-3000 IU daily for up to 4 weeks does not decrease the length of hospital or ICU stay or reduce the risk of mortality when compared with control (112335). The validity of these findings is limited by a high degree of heterogeneity among the studies, which included differences in vitamin E dosing, duration of therapy, and reasons for ICU admission.
Dementia. It is unclear if oral vitamin E is beneficial for dementia prevention; the available research is conflicting. Details: A longitudinal cohort study in Japanese adults aged 40 years or older at baseline who were followed for a median of about 20 years, shows that total daily dietary intake of vitamin E is inversely associated with the risk of developing dementia, with a hazard ratio of about 0.8 for the highest compared with lowest quartiles of intake (107857). In a longitudinal cohort study of males aged 71-93 years, consuming supplemental vitamin E and vitamin C decreased the risk of developing vascular and mixed or other dementias; however, there was no protective effect for Alzheimer dementia (4636). Evidence from clinical research that evolved into an observational study shows that taking vitamin E 400 IU daily does not decrease the incidence of dementia in males 60 years or older (93570). However, the results from this study are limited by selection bias due to the high education levels and relatively young age of the participants, limitations with case ascertainment, and problems with follow-up (93570,93571). Also, these studies did not distinguish between different forms of vitamin E (4636,93570).
Depression. It is unclear if oral vitamin E is beneficial in patients with depression. Details: A meta-analysis of 7 mostly small clinical studies in patients without major depressive disorder shows that taking vitamin E 400-2000 IU daily for up to 6 months modestly improves depression symptom scores when compared with placebo (112158). It is unclear if these findings can be generalized to patients with depression.
Developmental coordination disorder (DCD). Oral vitamin E has only been evaluated in combination with other ingredients for DCD; its effect when used alone is unclear. Details: A small clinical study in children with developmental coordination disorder (DCD), also known as dyspraxia, shows that taking vitamin E orally, in combination with evening primrose oil, thyme oil, and fish oils, for 4 months seems to improve movement when compared with control (5708). The effects of vitamin E alone on DCD are unclear.
Diabetes. It is unclear if oral vitamin E is beneficial for the treatment or prevention of diabetes. Details: Population research has found that higher vitamin E dietary intake is associated with a lower risk of developing type 2 diabetes (14004). However, individual clinical studies in patients with existing diabetes show mixed results (13496,13497,90095,90099,98259). A meta-analysis of 36 small clinical studies in patients with diabetes suggests that vitamin E may slightly improve some measures of glycemic control. In patients with type 2 diabetes, vitamin E seems to reduce glycated hemoglobin (HbA1c) by around 0.2% and improve insulin resistance, but not fasting blood glucose, when compared with placebo. In patients with type 1 diabetes, vitamin E seems to reduce HbA1c by around 0.8%, but does not improve fasting blood glucose, when compared with placebo (112161). The validity of this analysis is limited by a high degree of heterogeneity across the studies, including differences in vitamin E dose, treatment duration, concomitant medications, patient populations, and study designs.
Diabetic foot ulcers. Oral vitamin E has only been evaluated in combination with other ingredients for diabetic foot ulcers; its effect when used alone is unclear. Details: A small clinical study in adults with a grade 3 diabetic foot ulcer shows that taking vitamin E 400 IU and magnesium oxide 250 mg daily for 12 weeks reduces ulcer length, width, and depth when compared with placebo (101436). A small clinical study in adults with non-healing diabetic foot ulcers being treated with a platelet-rich plasma fibrin glue dressing shows that taking vitamin E 200 IU and vitamin C 12.5 mg orally twice daily for 8 weeks increases the rate of ulcer healing when compared with placebo. In those receiving vitamins, 46% of wounds closed completely, compared with 17% of those receiving placebo (107870). It is not clear if the effects seen in these studies are due to vitamin E, the other nutrients, or the combinations.
Diabetic nephropathy. It is unclear if oral vitamin E is beneficial in patients with diabetes and impaired kidney function. Details: A meta-analysis of clinical research in adults with diabetic nephropathy shows that taking vitamin E 600-1200 mg daily, alone or with other antioxidants, modestly reduces urinary albumin excretion when compared with placebo or no treatment, but seems to have no effect on glomerular filtration rate (GFR) (97069). A small clinical study in patients with diabetic nephropathy shows that taking a specific tocotrienol-rich vitamin E supplement (Tocovid SupraBio, Hovid Nutriworld) 200 mg twice daily for 12 weeks seems to modestly reduce serum creatinine, with a corresponding increase in GFR, when compared with placebo. According to a sub-group analysis, these improvements remain statistically significant in patients with low tocopherol levels (less than 42 mcmol/L) at baseline, but not in those with higher levels at baseline (103010). Another small clinical study shows that taking this same supplement regimen for 12 months reduces serum creatinine levels and improves GFR at 8 months, but not 12 months, when compared with placebo. In a subgroup analysis of patients with stage 3 chronic kidney disease, these benefits persisted at 12 months when compared with placebo (107390).
Diabetic neuropathy. It is unclear if oral vitamin E is beneficial for improving diabetic neuropathy symptoms. Details: A small clinical trial in patients with uncontrolled type 2 diabetes and neuropathy shows that taking a specific vitamin E supplement (Evion) 400 IU daily for 12 weeks modestly decreases neuropathic pain scores when compared to baseline (90091). Another very small clinical trial shows that taking vitamin E 1341 IU daily for 6 months improves nerve conduction in diabetic neuropathy when compared with placebo (4724).
Down syndrome. Oral vitamin E does not seem to slow cognitive decline in patients with this condition. Details: A clinical study in patients over 50 years old with Down syndrome shows that taking vitamin E 1000 IU twice daily for 3 years does not slow cognitive decline when compared with placebo (97076).
Endometriosis. Oral vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with endometriosis and pelvic pain shows that taking vitamin E 800 IU and vitamin C 1000 mg daily for 8 weeks improves dysmenorrhea, dyspareunia, and chronic pelvic pain scores when compared with placebo (106622).
Extravasation. Topical vitamin E has only been evaluated in combination with dimethylsulfoxide (DMSO); its effect when used alone is unclear. Details: A very small clinical study in patients receiving chemotherapy shows that applying vitamin E topically, in combination with DMSO, seems to prevent skin ulceration after chemotherapy extravasation (4668).
Gastric cancer. It is unclear if oral vitamin E is beneficial for preventing gastric cancer or reducing associated mortality. Details: Population studies have found that increasing dietary vitamin E intake by 22.4 IU daily is associated with a 21% decreased risk of gastric cancer (3360,90083). However, clinical trials have not found that vitamin E supplements reduce gastric cancer risk (3960,4676,4677,12185). Studies evaluating vitamin E in combination with other supplements have been inconsistent. In one large-scale clinical trial a specific combination of vitamin E 100 IU with selenium 37.5 mcg and vitamin C 250 mg twice daily for about 7 years did not reduce risk of gastric cancer in patients from Shandong Province in China where there is a very high prevalence of gastric cancer (14447,90085). In another large-scale clinical study of 29,584 people in China, the combination of oral vitamin E, beta-carotene, and selenium over 5 years did reduce total mortality, total cancer mortality, and stomach cancer mortality (4679). A meta-analysis of clinical research shows that taking vitamin E plus beta-carotene with or without vitamin C does not reduce gastric cancer incidence (12185).
Glomerulosclerosis. It is unclear if oral vitamin E reduces proteinuria due to glomerulosclerosis in children. Details: A very small clinical study in children with focal segmental glomerulosclerosis who are refractory to standard medical management shows that taking vitamin E 200 IU daily orally might reduce proteinuria when compared with baseline (4675). The validity of this finding is limited by a lack of control group.
Granuloma annulare. Although there is interest in using topical vitamin E for granuloma annulare, there is insufficient reliable information about the clinical effects of vitamin E for this condition.
Helicobacter pylori. Oral vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in patients with Helicobacter pylori dyspepsia without ulcers shows that taking vitamin E 200 IU and vitamin C 500 mg by mouth twice daily for 30 days in addition to standard triple therapy increases eradication rates by 37% when compared with triple therapy alone (90094). It is not clear if this benefit is due to vitamin E, vitamin C, or the combination.
Huntington disease. It is unclear if oral vitamin E improves Huntington disease symptoms. Details: A small clinical study shows that taking RRR-alpha-tocopherol (natural vitamin E) might improve symptoms in patients with early Huntington disease, but this benefit is not seen in patients with more advanced disease when compared with placebo (4686).
IgA nephropathy. It is unclear if oral vitamin E is beneficial for IgA nephropathy in children. Details: A small clinical study in children with IgA nephropathy shows that taking vitamin E (400 IU for those weighing less than 30 kg; 800 IU for those weighing more than 30 kg) improves urinary protein to creatinine ratio, but not glomerular filtration rate, creatinine clearance, or hematuria, when compared with placebo (85063).
Infertility. It is unclear if oral vitamin E improves pregnancy rates in females with infertility of unknown cause. Details: A small clinical study in females experiencing implantation failure shows that taking vitamin E 400 IU daily for 12 weeks improves endometrial thickness when compared with placebo (99852). Vitamin E has also been studied in combination with selenium. In a small clinical study in patients with premature ovarian insufficiency (POI), taking vitamin E 400 IU with selenium 200 mcg orally daily for 90 days increases anti-Mullerian hormone index, antral follicle count, and mean ovarian volume after 12 months of follow-up when compared with placebo (107866). It is unclear if these improvements correlate to higher pregnancy or live birth rates.
Inflammatory bowel disease (IBD). Although there is interest in using oral vitamin E for IBD, there is insufficient reliable information about the clinical effects of vitamin E for this condition.
Insomnia. It is unclear if oral vitamin E is beneficial in patients with insomnia. Details: A moderate-sized clinical study in postmenopausal patients with chronic insomnia shows that taking vitamin E 400 IU daily for 1 month improves sleep quality ratings and reduces the need for sedative medications when compared with placebo (112163).
Intermittent claudication. It is unclear if oral vitamin E improves intermittent claudication symptoms. Details: A large clinical study in male smokers with intermittent claudication shows that taking all-rac-alpha-tocopherol (synthetic vitamin E) 50 mg orally daily for about 3.7 years does not appear to have any effect when used alone or in combination with beta-carotene for treating symptoms or disease progression when compared with placebo (4732). However, according to poor-quality clinical research included in a meta-analysis, taking vitamin E 447-2384 IU daily for up to 18 months appears to reduce symptoms of intermittent claudication (85023).
Lice. Topical synthetic vitamin E might be beneficial for head lice eradication. Details: A small clinical study in children and adults with head lice shows that topical application of a specific tocopheryl acetate 20% spray (LiceKO, Panin SRL) once, and then again 7 days later, is more effective for eliminating lice when compared with permethrin 1% cream rinse (90067).
Male infertility. An analysis of several small, low-quality clinical studies suggests that oral vitamin E might improve pregnancy rates and measures of sperm health in males with infertility. Details: Several small clinical studies in males with infertility show conflicting results (3583,4695,107865). However, a meta-analysis of 7 small, low-quality clinical trials shows that taking vitamin E 300-600 IU for 12-48 weeks increases pregnancy rates by 86% and modestly improves sperm count, concentration, motility, and vitality, but does not seem to increase semen volume, when compared with a control (109461). Vitamin E has also been used in combination with other nutrients with unclear results. Small studies show that taking vitamin E 800 mg daily with vitamin C 1000 mg daily for 8 weeks doesn't seem to improve sperm functionality (4696), while vitamin E 400 IU plus selenium 200 mcg daily for at least 100 days improves sperm functionality, but not fertilization rates, when compared with baseline (3585). In another small clinical study in infertile males undergoing varicocelectomy, taking vitamin E 400 IU, selenium 200 mcg, and folic acid 5 mg daily for 6 months improved sperm count and motility when compared with control (102968). Another small clinical study shows that taking vitamin E 100 mg and coenzyme Q10 10 mg three times daily for 3 months modestly increases levels of testosterone and improves progressive sperm motility and morphology when compared to baseline. However, taking an L-carnitine nutrient complex 15 grams twice daily was more effective for increasing testosterone and improving sperm parameters (109390). However, it is unclear if any of these combination therapies increases live birth rates.
Melanoma. It is unclear if oral vitamin E is beneficial for reducing melanoma risk. Details: A sub-group analysis of a large-scale clinical trial in patients with diabetes or cardiovascular disease suggests that taking RRR-alpha-tocopherol (natural vitamin E) 400 IU daily for about 7 years is not linked with a reduced risk of developing melanoma when compared with placebo (13036).
Menopausal symptoms. It is unclear if oral vitamin E is beneficial for reducing menopausal symptoms such as hot flashes. Details: A small clinical study in postmenopausal patients shows that taking vitamin E 200 IU twice daily for 8 weeks reduces hot flashes, but does not affect other menopausal symptoms or anxiety, when compared with placebo. The improvement in hot flashes was no longer present 4 weeks after the intervention (102969). However, a meta-analysis of 3 small clinical studies in postmenopausal patients, including the study above, shows that taking vitamin E 400 IU daily for 8 weeks does not reduce hot flash frequency when compared with placebo (111460).
Methotrexate toxicity. It is unclear if oral vitamin E reduces the risk of liver toxicity due to methotrexate. Details: An observational study in patients taking methotrexate for rheumatoid arthritis has found that taking vitamin E 400 mg twice daily for 3 months is associated with reductions in serum glutamic pyruvic transaminase (SGPT) and serum glutamic-oxaloacetic transaminase (SGOT) levels when compared with no supplementation. This suggests a reduction in liver injury in the treatment group (104414).
Muscular dystrophy. Small clinical studies suggest that oral vitamin E may not improve muscular dystrophy symptoms or progression. Details: Small clinical studies in patients with myotonic or Duchenne muscular dystrophy show that taking vitamin E along with penicillamine or selenium doesn't appear to slow disease progression or improve symptoms when compared with placebo (4703,4704).
Nocturnal leg cramps. It is unclear if oral vitamin E reduces leg cramps in veterans or in patients on hemodialysis. Details: A small clinical study in adults undergoing hemodialysis shows that taking vitamin E 400 IU at bedtime for 2 months seems to reduce the frequency of nocturnal leg cramps when compared with placebo (4701). However, another small clinical study in male veterans shows that taking vitamin E 800 IU at bedtime for 4 weeks does not reduce cramp frequency or severity or reduce sleep disturbances when compared with placebo (4702).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral vitamin E is beneficial in adults or children with NAFLD. Details: One meta-analysis of studies assessing both NAFLD patients and patients in whom NAFLD progressed to nonalcoholic steatohepatitis (NASH) shows that taking vitamin E 100-800 IU daily for 1-24 months improves liver enzyme levels, hepatic steatosis, and lobular inflammation when compared with control. However, taking vitamin E does not appear to improve hepatic fibrosis in these patients (97077). Methodological limitations such as publication bias and unclear calculations limit the reliability of these results. Another meta-analysis of 8 small clinical trials in adults with NAFLD shows that taking vitamin E 400-800 IU daily for up to 24 weeks improves liver enzyme levels when compared with placebo (112336). Vitamin E has also been evaluated in children with NAFLD. A meta-analysis of studies in this population shows that taking vitamin E 15-900 IU daily for up to 24 months reduces total and low-density lipoprotein (LDL) cholesterol levels, but does not affect liver enzyme levels, measures of insulin resistance, body mass index (BMI), ballooning degeneration of the liver, or liver fibrosis when compared with placebo (107861). Until additional data showing its benefit becomes available, practice guidelines by the American Association for the Study of Liver Diseases (AASLD) state that vitamin E is not recommended in patients with NAFLD without liver biopsy (98130).
Obesity. It is unclear if oral vitamin E is beneficial for improving weight loss. Details: A meta-analysis of 24 small clinical studies shows that taking oral vitamin E, 67-900 mg daily does not affect weight, body mass index (BMI), or waist circumference in adults with obesity. In fact, in people with a normal BMI, vitamin E seems to increase body weight (107859).
Oral mucositis. It is unclear if oral or topical vitamin E is beneficial in patients with oral mucositis from chemotherapy or radiotherapy. Details: Vitamin E has been evaluated in both chemotherapy- and radiation-induced mucositis. A small clinical study in children with chemotherapy-induced oral mucositis shows that a specific vitamin E product (Evion Paediatric Drops, Merck Limited) 200 IU applied topically in three divided doses daily for 1 week improves healing, pain, and the ability to eat when compared with placebo (94585). However, another small clinical study in patients receiving radiotherapy for head and neck cancer shows that taking vitamin E 1000 mg once daily with pentoxifylline 400 mg twice daily does not reduce the incidence or severity of oral mucositis and dysphagia when compared with control (102972).
Osteopenia. It is unclear if oral vitamin E helps slow the progression of osteopenia. Details: A small clinical study in postmenopausal adults with osteopenia who are taking calcium and vitamin D supplements shows that taking vitamin E (mixed tocopherols) 400 IU daily for 12 weeks prevents the increase in serum C-terminal telopeptide, a marker of bone resorption, seen with placebo over that same time period (107868).
Osteoporosis. It is unclear if oral vitamin E helps to reduce complications of osteoporosis such as fractures. Details: Observational research has found that vitamin E supplementation is associated with a 22% lower risk of hip fracture and a 14% lower risk of all fractures in elderly females with osteoporosis (90086). Additional observational research has found that higher dietary vitamin E intake is also associated with a 34% reduced risk of fractures in adults at risk for osteoporosis (104415).
Peyronie disease. It is unclear if oral vitamin E reduces Peyronie disease symptoms. Details: A small clinical study in patients with Peyronie disease shows that taking vitamin E 894 IU daily in addition to conservative treatment for 6 months does not improve pain, but may reduce plaque, when compared with using conservative treatment alone. Conservative treatment included verapamil 10 mg biweekly injection and iontophoresis, blueberries 160 mg orally daily, propolis 600 mg orally daily, and topical diclofenac 4% twice daily (90090). It is not clear if this effect is due to vitamin E, the other interventions, or the combination.
Photoreactive keratectomy. Oral vitamin E has only been evaluated for recovery after photoreactive keratectomy in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients undergoing laser surgery for myopia shows that taking vitamin A (retinol palmitate) 50,000-75,000 units with vitamin E (alpha-tocopheryl nicotinate) 343 IU daily seems to accelerate re-epithelialization, reduce haze formation, and improve visual acuity when compared with placebo (348).
Physical performance. It is unclear if oral vitamin E improves physical performance in the elderly. Details: Population research has found that increasing intake of dietary vitamin E is associated with increased physical performance and muscle strength in elderly people (14006).
Polycystic ovary syndrome (PCOS). Analyses of small clinical studies suggest that oral vitamin E may modestly reduce lipid levels in patients with PCOS. It is unclear if vitamin E can improve glycemic control, body weight, hormone levels, or symptoms of PCOS. Details: Meta-analyses of several small clinical studies in patients with PCOS show that taking vitamin E, alone or in combination with coenzyme Q10, fish oil, magnesium, or vitamin D, reduces total cholesterol by 9-18 mg/dL, low-density lipoprotein (LDL) cholesterol by 7-16 mg/dL, and triglycerides by 13-21 mg/dL when compared with placebo. However, vitamin E does not appear to increase high-density lipoprotein (HDL) cholesterol, reduce body weight, or improve hirsutism. The effects of vitamin E on glycemic indices and levels of testosterone, estradiol, and sex hormone binding globulin are unclear; individual meta-analyses show mixed results (112167,112168,112169). The validity of these findings is limited by a high degree of heterogeneity across the included studies, which varied in vitamin E dosing, treatment duration, and concomitant supplements used.
Premature rupture of membranes (PROM). Oral vitamin E does not seem to prevent PROM, although it's unclear if it might prevent premature delivery due to PROM. Details: Vitamin E has been evaluated for the prevention and management of PROM. A meta-analysis of clinical research shows that taking vitamin E with other ingredients throughout pregnancy does not affect the risk of developing PROM when compared with placebo (97075). However, a clinical study in patients with PROM shows that taking vitamin E (RRR-alpha-tocopherol acetate) 400 IU and vitamin C 1000 mg daily, starting within 1 hour of membrane rupture and continuing for an unspecified amount of time, seems to hold back premature delivery by about 5 days when compared with placebo. However, maternal or neonatal outcomes did not seem to be affected (90078). It is not clear if this effect is due to vitamin E, vitamin C, or the combination.
Radiation-induced sialadenitis. It is unclear if oral vitamin E is effective for the prevention or treatment of radiation-induced sialadenitis. Details: A small clinical study in patients undergoing radiation therapy for thyroid cancer shows that taking vitamin E 200 mg daily for 5 weeks, starting 1 week before radiotherapy, improves several measures of parotid and submandibular salivary gland function when compared to baseline, suggesting that vitamin E might prevent radiation-induced sialadenitis and its associated complications (112332). The validity of these findings is limited by a lack of control group.
Radiation dermatitis. It is unclear if topical vitamin E is effective for the prevention or treatment of radiation dermatitis. Details: A small clinical study in patients undergoing radiation therapy for breast cancer shows that applying a cream containing nanoparticles of vitamin E 2%, three times daily and after each radiation session until 2 weeks after radiation therapy is complete, does not reduce the severity of radiation dermatitis or improve quality of life when compared with a placebo cream. However, in patients that did not receive a boosted radiation dose, this vitamin E cream seems to slightly delay the onset of dermatitis when compared with placebo (112333).
Radiation fibrosis. It is unclear if topical vitamin E reduces radiation fibrosis symptoms. Details: Clinical research shows that taking vitamin E 1000 IU orally with pentoxifylline 800 mg daily seems to reverse radiation fibrosis (4672,4673). Regression of radiation fibrosis becomes significant after three months of treatment and continues to improve thereafter. After 12 months of treatment, mean surface area of fibrosis can decrease by 66% (4672). It is unclear if the benefit is due to vitamin E, pentoxifylline, or the combination. One very small study suggests that vitamin E alone does not seem to be effective when compared with placebo (10363).
Renal cell carcinoma. It is unclear if oral vitamin E reduces renal cell carcinoma risk. Details: In 2009, the US Food and Drug Administration (FDA) approved a qualified health claim regarding vitamin E and renal cell carcinoma risk. This qualified health claim was based on one weak and limited study. The FDA has determined that it is highly uncertain that vitamin E supplements reduce the risk of renal cell carcinoma (102332).
Restless legs syndrome (RLS). Oral vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in hemodialysis patients shows that taking vitamin E 596 IU, vitamin C 200 mg, or a combination of both daily for 8 weeks modestly reduces severity of restless legs syndrome when compared with placebo (90093).
Retinopathy of prematurity. It is unclear whether oral or parenteral vitamin E reduces the risk for retinopathy in prematurity (ROP). Details: A clinical study in very low birth weight infants with respiratory distress syndrome suggests that giving vitamin E 12.5 IU twice daily from 72 hours after birth through 28 days of age might reduce the incidence of stage 1 ROP when compared with placebo. However, the difference reached significance in the per-protocol analysis, but not in the intention-to-treat analysis (107864). Also, a meta-analysis that did not include this more recent study shows that administering oral, intravenous, or intramuscular vitamin E daily does not reduce the risk for ROP. Additionally, high levels of vitamin E and large intravenous doses of vitamin E have been associated with an increased risk for sepsis in premature infants (85062).
Rheumatoid arthritis (RA). It is unclear if oral vitamin E is beneficial in patients with RA. Details: A small clinical study in adults with RA shows that taking vitamin E 600 mg twice daily in conjunction with standard therapy for 12 weeks is superior to standard therapy alone for reducing pain, but not inflammation (4723). However, other studies show mixed results. A meta-analysis of 7 small clinical studies in patients with RA shows that taking vitamin E up to 1200 IU daily for up to 12 weeks does not reduce pain, tenderness, swelling, or morning stiffness when compared with control (112330).
Schizophrenia. Oral vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Taking vitamin E (RRR-alpha-tocopherol) 135.8 IU and a specific ascorbic acid supplement (CellaVie) 250 mg with or without ethyl eicosapentaenoate 500 mg daily for 16 weeks does not improve negative or positive symptoms of schizophrenia when compared with placebo (89234).
Sickle cell disease. Although there is interest in using oral vitamin E for sickle cell disease, there is insufficient reliable information about the clinical effects of vitamin E for this condition.
Stretch marks (striae gravidarum). Topical vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that using a moisturizer containing vitamin E, rosehip oil, hydroxyprolisilane C, and gotu kola triterpenes at least twice daily on affected areas does not decrease incidence of new stretch marks, but does decrease the severity of new stretch marks by about 30%, when compared with control cream in pregnant patients (90076). It is not clear if this effect is due to vitamin E, other ingredients, or the combination.
Stroke. It is unclear if oral vitamin E is beneficial for reducing stroke risk. Details: A trial-sequential meta-analysis of 12 clinical trials with 148,000 patients shows that vitamin E does not seem to reduce the risk of total stroke when compared with placebo. However, in a subgroup analysis, vitamin E was associated with an 8% lower risk of ischemic stroke and a trend to an increased risk of hemorrhagic stroke when compared with placebo. Based on subgroup analyses, there was no difference on risk based on vitamin E dosage, use of synthetic versus natural vitamin E, and whether prevention was primary or secondary (104408). This analysis was limited due to high heterogeneity, small study size, and insufficient power to detect differences between treatments. Older meta-analyses also found mixed results of using vitamin E 74.5-1192 IU daily alone or in combination for up to 10 years. However, there was a similar sub-group analysis finding that vitamin E might reduce the risk of ischemic stroke, but it might also increase the risk of hemorrhagic stroke (14621,85201). Some clinical research shows that taking all-rac-alpha-tocopherol (synthetic vitamin E) might reduce the risk of ischemic stroke in male smokers with hypertension and diabetes (3359).
Sunburn. Topical vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Oral vitamin E alone does not seem to prevent sunburn. Details: Two small, double-blind, placebo-controlled studies suggest that taking high dose oral RRR-alpha-tocopherol (natural vitamin E) up to 2 grams daily in combination with vitamin C 3 grams protects against skin inflammation after exposure to ultraviolet (UV) radiation. However, taking vitamin E alone does not seem to be beneficial when compared with control (4715,4716). This combination was also tried topically. In one study, topically applied vitamin E in combination with topical vitamin C and melatonin provided modest photoprotective effect when used prior to UV exposure, but had no effect when used during or after UV exposure (4713,4714).
Uveitis. Oral vitamin E has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking vitamin E 149 IU twice daily with vitamin C 500 mg daily for 8 weeks improves visual acuity in patients with acute anterior uveitis, but does not seem to decrease inflammation measured by laser flare, when compared with placebo (4730). It is not clear if this effect is due to vitamin E, vitamin C, or the combination.
Vaginal atrophy. It is unclear if a vitamin E suppository is beneficial in patients with vaginal atrophy. Details: A small clinical study in females with breast cancer and tamoxifen-induced vaginal atrophy shows that intravaginal administration of a vitamin E 1 mg suppository nightly before bed for 8 weeks improves self-reported symptoms of vaginal atrophy, decreases vaginal pH, and improves vaginal estrogenization, as measured by the Vaginal Maturation Index, when compared with placebo (99773). More evidence is needed to rate vitamin E for these uses.

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Safety view details

Below is general information about the safety of the known ingredients contained in the product Enhanced CoQsol-10. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COENZYME Q10 (Coenzyme Q-10)

LIKELY SAFE ...when used orally and appropriately. Coenzyme Q10 has been used safely in studies lasting up to 5 years (2134,6037,6038,6407,8163,8938,8939,8940,15395,17413,17716,96538)(109391). ...when used topically on the gums (2107,2108,8916,8917,8918).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Coenzyme Q10 in doses of 1-10 mg/kg/day has been used safely for up to 9 months under medical supervision (12199,13223,15256,44005,107449).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Coenzyme Q10 100 mg twice daily has been used with apparent safety during pregnancy, starting at 20 weeks gestation until term (17201).

LACTATION:
Insufficient reliable information available; avoid using.

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VITAMIN A

LIKELY SAFE ...when used orally or intramuscularly and appropriately. Vitamin A, as pre-formed vitamin A (retinol or retinyl ester), is safe in adults when taken in doses below the tolerable upper intake level (UL) of 10,000 IU (3000 mcg) per day (7135). Higher doses increase the risk of side effects. There is also growing concern that taking high doses of antioxidants such as vitamin A might do more harm than good. In an analysis of studies, taking vitamin A supplements alone or in combination with other antioxidants is associated with an increased risk of mortality from all causes (15305,90775). Keep in mind that vitamin A is available in two different forms: pre-formed vitamin A (retinol or retinyl ester) and provitamin A (carotenoids). The safety concerns associated with high vitamin A intake occur with pre-formed vitamin A only. Some supplements contain vitamin A in both pre-formed and provitamin A forms. For these supplements, the amount of pre-formed vitamin A should be used to determine if the amount of vitamin A is safe.

POSSIBLY SAFE ...when used topically and appropriately, short-term. Retinol 0.5% has been used on the skin daily for up to 12 weeks with apparent safety. No serious adverse effects have been reported in clinical trials (103671,103680).

POSSIBLY UNSAFE ...when used orally in high doses. Doses higher than the UL of 10,000 IU (3000 mcg) per day of pre-formed vitamin A (retinol or retinyl ester) might increase the risk of side effects (7135). While vitamin A 25,000 IU (as retinyl palmitate) daily for 6 months followed by 10,000 IU daily for 6 months has been used with apparent safety in one clinical trial (95052), prolonged use of excessive doses of vitamin A can cause significant side effects such as hypervitaminosis A. The risk for developing hypervitaminosis A is related to total cumulative dose of vitamin A rather than a specific daily dose (1467,1469). There is also concern that taking high doses of antioxidants such as vitamin A might do more harm than good. In an analysis of studies, taking vitamin A supplements alone or in combination with other antioxidants is associated with an increased risk of mortality from all causes (15305,90775). There is insufficient reliable information available about the safety of using sublingual formulations of vitamin A.

CHILDREN: LIKELY SAFE
when used orally or intramuscularly and appropriately. The amount of pre-formed vitamin A (retinol or retinyl ester) that is safe depends on age. For children up to 3 years of age, doses less than 2000 IU (600 mcg) per day seem to be safe. For children ages 4 to 8, doses less than 3000 IU (900 mcg) per day seem to be safe. For children ages 9 to 13, doses less than 5667 IU (1700 mcg) per day seem to be safe. For children 14 to 18, doses less than 9333 IU (2800 mcg) per day seem to be safe (7135). Keep in mind that vitamin A is available in two different forms: pre-formed vitamin A (retinol or retinyl ester) and provitamin A (carotenoids). The safety concerns associated with high vitamin A intake occur with pre-formed vitamin A only. Some supplements contain vitamin A in both pre-formed and provitamin A forms. For these supplements, the amount of pre-formed vitamin A should be used to determine if the amount of vitamin A is safe.

CHILDREN: POSSIBLY UNSAFE
when pre-formed vitamin A (retinol or retinyl ester) is used orally in excessive doses. For children up to 3 years of age, avoid doses greater than 2000 IU (600 mcg) per day. For children ages 4 to 8, avoid doses greater than 3000 IU (900 mcg) per day. For children ages 9 to 13, avoid doses greater than 5667 IU (1700 mcg) per day. For children ages 14 to 18, avoid doses greater than 9333 IU (2800 mcg) per day (7135). Higher doses of vitamin A supplementation have been associated with increased risk of side effects such as pneumonia, bone pain, and diarrhea (319,95051). Long-term supplementation with low to moderate doses on a regular basis can cause severe, but usually reversible, liver damage (11978).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally or intramuscularly and appropriately. Vitamin A, as pre-formed vitamin A (retinol or retinyl ester), is safe during pregnancy and lactation when used in doses less than 10,000 IU (3000 mcg) per day (7135,16823,107293). Keep in mind that vitamin A is available in two different forms: pre-formed vitamin A (retinol or retinyl ester) and provitamin A (carotenoids). The safety concerns associated with high vitamin A intake occur with pre-formed vitamin A only. Some supplements contain vitamin A in both pre-formed and provitamin A forms. For these supplements, the amount of pre-formed vitamin A should be used to determine if the amount of vitamin A is safe.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally or intramuscularly in excessive doses. Daily intake of greater than 10,000 IU (3000 mcg) can cause fetal malformations (3066,7135). Excessive dietary intake of vitamin A has also been associated with teratogenicity (11978). The first trimester of pregnancy seems to be the critical period for susceptibility to vitamin A-associated birth defects such as craniofacial abnormalities and abnormalities of the central nervous system (7135). Pregnant patients should monitor their intake of pre-formed vitamin A (retinol or retinyl ester). This form of vitamin A is found in several foods including animal products, some fortified breakfast cereals, and dietary supplements (3066).

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VITAMIN E

LIKELY SAFE ...when used orally or topically and appropriately. Vitamin E is generally considered safe, even at doses exceeding the recommended dietary allowance (RDA); however, adverse effects are more likely to occur with higher doses. The tolerable upper intake level (UL) in healthy people is 1000 mg daily, equivalent to 1100 IU of synthetic vitamin E (all-rac-alpha-tocopherol) or 1500 IU of natural vitamin E (RRR-alpha-tocopherol) (4668,4681,4713,4714,4844,89234,90067,90069,90072,19206)(63244,97075). Although there is some concern that taking vitamin E in doses of 400 IU (form unspecified) per day or higher might increase the risk of adverse outcomes and mortality from all causes (12212,13036,15305,16709,83339), most of this evidence comes from studies that included middle-aged or older patients with chronic diseases or patients from developing countries in which nutritional deficiencies are prevalent.

POSSIBLY UNSAFE ...when used orally in high doses. Repeated doses exceeding the tolerable upper intake level (UL) of 1000 mg daily are associated with significant side effects in otherwise healthy people (4844). ...when used intravenously in large doses. Large repeated intravenous doses of all-rac-alpha-tocopherol (synthetic vitamin E) were associated with decreased activity of clotting factors and bleeding in one report (3074). ...when inhaled. E-cigarette, or vaping, product-use associated lung injury (EVALI) has occurred among adults who use e-cigarette, or vaping, products, which often contain vitamin E acetate. In some cases, this has resulted in death. The majority of patients with EVALI reported using tetrahydrocannabinol (THC)-containing products in the 3 months prior to the development of symptoms. Vitamin E acetate has been detected in most bronchoalveolar lavage samples taken from patients with EVALI. Other ingredients, including THC or nicotine, were also commonly found in samples. However, priority toxicants including medium chain triglyceride (MCT) oil, plant oil, petroleum distillate, or terpenes, were undetectable in almost all samples. While this association shows a correlation between vitamin E acetate inhalation and lung injury, a causal link has not yet been determined, and it is not clear if other toxic compounds are also involved (101061,101062,102970).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Vitamin E has been safely used in children in amounts below the tolerable upper intake level (UL). The UL for healthy children is: 200 mg in children aged 1-3 years, 300 mg in children aged 4-8 years, 600 mg in children aged 9-13 years, and 800 mg in children aged 14-18 years. A UL has not been established for infants up to 12 months of age (23388).

CHILDREN: POSSIBLY UNSAFE
when used orally in doses above the UL due to increased risk of adverse effects (23388). ...when alpha-tocopherol is used intravenously in large doses in premature infants. Large intravenous doses of vitamin E are associated with an increased risk of necrotizing enterocolitis and sepsis in this population (85062,85083). ...when inhaled. E-cigarette, or vaping, product-use associated lung injury (EVALI) has occurred among adolescents and teenagers who use e-cigarette, or vaping, products. In some cases, this has resulted in death. The majority of patients with EVALI reported using tetrahydrocannabinol (THC)-containing products in the 3 months prior to the development of symptoms. Constituents in E-cigarette or vaping products with the potential to cause lung injury or impaired lung function include lipids, such as vitamin E acetate. Vitamin E acetate has been detected in all bronchoalveolar lavage samples taken from patients with EVALI. No other ingredient, including THC or nicotine, was found in all samples, and other ingredients, including medium chain triglyceride (MCT) oil, plant oil, petroleum distillate, or terpenes, were undetectable This shows that vitamin E acetate is at the primary site of lung injury. A causal link has not yet been described and it is not clear if other compounds are also involved (101061,101062).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. The tolerable upper intake level (UL) during pregnancy is 800 mg for those 14-18 years of age and 1000 mg for those 19 years and older. However, maternal supplementation is not generally recommended unless dietary vitamin E falls below the RDA (4260). No serious adverse effects were reported with oral intake of 400 IU per day starting at weeks 9-22 of pregnancy in healthy patients or those at high risk for pre-eclampsia (3236,97075), or with 600-900 IU daily during the last two months of pregnancy (4260). However, some preliminary evidence suggests that taking vitamin E supplements might be harmful when taken in early pregnancy. A case-control study found that taking a vitamin E supplement during the first 8 weeks of pregnancy is associated with a 1.7-9-fold increase in odds of congenital heart defects (16823). However, the exact amount of vitamin E consumed during pregnancy in this study is unclear. Until more is known, advise patients to avoid taking a vitamin E supplement in early pregnancy unless needed for an appropriate medical indication.

LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the tolerable upper intake level (UL). The UL during lactation is 800 mg for those 14-18 years of age and 1000 mg for those 19 years and older (4844).

LACTATION: POSSIBLY UNSAFE
when used orally in amounts that exceed the UL due to increased risk of adverse effects (4844).

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Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Enhanced CoQsol-10. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COENZYME Q10 (Coenzyme Q-10)

ALKYLATING AGENTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.

Details

Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy (5158,5159). The clinical importance of this interaction is unknown.

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.

Details

Some clinical research shows that coenzyme Q10 can significantly lower blood pressure (2122,3365,8907,9890,17702,17650,17651,44343,96541), although other studies have shown conflicting results (17651,44211,95607).

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.

Details

Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin (2128,6048,6199). Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported (2128,6048,11048). However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR (11905).

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VITAMIN A

HEPATOTOXIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = C

Theoretically, taking high doses of vitamin A in combination with other potentially hepatotoxic drugs might increase the risk of liver disease.

Details

The tolerable upper intake level (UL) is the highest level of intake that is likely to pose no risk of adverse effects. Doses of vitamin A above the UL can cause hepatotoxicity, ranging from elevated liver enzymes to liver failure (7135,82554).

RETINOIDS

Interaction Rating = Major Do not take this combination.

Severity = High • Occurrence = Probable • Level of Evidence = D

Concomitant use of retinoids with vitamin A supplements might produce supratherapeutic vitamin A levels.

Details

Retinoids, which are vitamin A derivatives, could have additive toxic effects when taken with vitamin A supplements (3046).

TETRACYCLINE ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, taking tetracycline antibiotics with high doses of vitamin A can increase the risk of pseudotumor cerebri.

Details

Benign intracranial hypertension (pseudotumor cerebri) can occur with tetracyclines and with acute or chronic vitamin A toxicity. Case reports suggest that taking tetracyclines and vitamin A concurrently can increase the risk of this condition (10545,10546,10547). Avoid high doses of vitamin A in people taking tetracyclines chronically.

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, high doses of vitamin A could increase the risk of bleeding with warfarin.

Details

Vitamin A toxicity is associated with hemorrhage and hypoprothrombinemia, possibly due to vitamin K antagonism (505). Advise patients taking warfarin to avoid doses of vitamin A above the tolerable upper intake level of 10,000 IU/day for adults.

(Read more about VITAMIN A)

VITAMIN E

ALKYLATING AGENTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of alkylating agents.

Details

There's concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding.

Details

Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors (4733,4844,11580,11582,11583,11584,11586,112162). These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily (11582,11585). Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol (10364). RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors (11999). Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.

ANTITUMOR ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of antitumor antibiotics.

Details

There's concern that antioxidants could reduce the activity of antitumor antibiotic drugs such as doxorubicin, which generate free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.

CYCLOSPORINE (Neoral, Sandimmune)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Unlikely • Level of Evidence = B

A specific form of vitamin E might increase absorption and levels of cyclosporine.

Details

There is some evidence that one specific formulation of vitamin E (D-alpha-tocopheryl-polyethylene glycol-1000 succinate, TPGS, tocophersolan, Liqui-E) might increase absorption of cyclosporine. This vitamin E formulation forms micelles which seems to increase absorption of cyclosporine by 40% to 72% in some patients (624,625,10368). However, this interaction is unlikely to occur with the usual forms of vitamin E.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.

Details

Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4 (13499,13500). Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.

NIACIN

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = A

Vitamin E might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.

Details

A combination of niacin and simvastatin (Zocor) effectively raises high-density lipoprotein (HDL) cholesterol levels in people with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% (7388,11537). Vitamin E alone combined with a statin does not seem to decrease HDL levels (11286,11287). It is not known whether the adverse effect on HDL is due to one of the other antioxidants or to the combination. It also is not known whether it will occur in other patient populations.

SELUMETINIB (Koselugo)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Taking selumetinib with vitamin E can result in a total daily dose of vitamin E that exceeds safe limits and therefore might increase the risk of bleeding.

Details

Selumetinib contains 48-54 IU vitamin E per capsule (102971). The increased risk of bleeding with vitamin E appears to be dose-dependent (11582,11585,34577). Be cautious when using selumetinib in combination with supplemental vitamin E, especially in patients at higher risk of bleed, such as those with chronic conditions and those taking antiplatelet drugs (102971).

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Using vitamin E with warfarin might increase the risk of bleeding.

Details

Due to interference with production of vitamin K-dependent clotting factors, use of more than 400 IU of vitamin E daily with warfarin might increase prothrombin time (PT), INR, and the risk of bleeding, (91,92,93). At a dose of 1000 IU per day, vitamin E can antagonize vitamin K-dependent clotting factors even in people not taking warfarin (11999). Limited clinical evidence suggests that doses up to 1200 IU daily may be used safely by patients taking warfarin, but this may not be applicable in all patient populations (90).

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Adverse Effects view details

Report an Adverse Reaction to Enhanced CoQsol-10

Below is general information about the adverse effects of the known ingredients contained in the product Enhanced CoQsol-10. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COENZYME Q10 (Coenzyme Q-10)

General ...Orally, coenzyme Q10 is generally well tolerated. In clinical studies, no serious adverse effects have been reported.
Most Common Adverse Effects:
Orally: Gastrointestinal side effects such as appetite suppression, diarrhea, epigastric discomfort, heartburn, nausea, and vomiting. These generally occur in less than 1% of patients. Some of these adverse effects can be minimized if daily doses above 100 mg are divided.

Cardiovascular ...Palpitations have been reported as being possibly associated with coenzyme Q10 treatment (89421). Death due to myocardial infarction occurred in one Parkinson disease patient taking coenzyme Q10; causality is unclear (15395).

Dermatologic ...Two of 143 participants in a case series reported skin itching after starting treatment with oral coenzyme Q10 (6047). Allergic rash has also been reported (6409,11872). An itching exanthema was seen in two heart failure patients treated with intravenous coenzyme Q10 (44284).

Gastrointestinal ...Gastrointestinal side effects of coenzyme Q10 have included nausea (3365,6409,8907,10152,43982,44172,44179,44330,89421,109392), vomiting (3365,10152,44330,89421), epigastric discomfort (3365,44179,44330,89421), constipation (109392), diarrhea (44179,92904,89421,109392), stomach upset (8940,12170,109387,109388,109392), loss of appetite (2121), heartburn (2121,44179,109392), and flatulence (43982), although this occurs in less than 1% of patients. In one clinical study, gastrointestinal bleeding in association with angiodysplasia has been reported to be possibly related to coenzyme Q10 treatment (89421).

Genitourinary ...An uncomplicated urinary infection was reported in a patient taking oral coenzyme Q10 (nanoQuinon, MSE Pharmazeutika) (44020).

Hematologic ...Thrombocytopenia was noted in one patient treated with oral coenzyme Q10 (44296); however, other factors (viral infection, other medications) may have been responsible for this adverse effect.

Musculoskeletal ...Increased plasma creatine kinase with high-intensity exercise has been reported in patients taking coenzyme Q10 (44303). Muscle pain has been reported rarely in one clinical trial (109392).

Neurologic/CNS ...Headache and dizziness have been reported in human research (3365,11872,43982,44330,109392). Insomnia has been reported as being possibly associated with coenzyme Q10 treatment (89421). Cognitive decline, depression, and sudden falls were reported rarely in a clinical trial of patients with Huntington disease (8940). Increased lethargy was reported for one patient treated with oral coenzyme Q10 (44042). Feeling of internal trembling has been reported in a clinical trial for one patient treated with coenzyme Q10 (44020).

Ocular/Otic ...Visual sensitivity to light has been reported for a patient treated with coenzyme Q10. However, the association of this effect with coenzyme Q10 treatment was not clear (6409).
A burning sensation has been reported for 10% of patients treated with a topical eye solution containing coenzyme Q10 and alpha-tocopheryl polyethylene glycol 1000 succinate following cataract surgery (44228).

Psychiatric ...Worsening depression has been reported as being possibly associated with oral coenzyme Q10 treatment (89421).

Pulmonary/Respiratory ...Drug-induced pneumonitis was diagnosed in a 61 year-old woman who had been taking coenzyme Q10 and perilla leaf extract for two months (43978). Symptoms improved after she stopped taking the supplements and began taking oral prednisone. Causation from coenzyme Q10 was unclear.

Other ...In a case report, a naval aviator using a supplement containing coenzyme Q10 and niacin had reduced G tolerance (44186). G tolerance was regained with cessation of the supplement.

(Read more about COENZYME Q10)

VITAMIN A

General ...Orally, vitamin A is generally well-tolerated at doses below the tolerable upper intake level (UL).
Serious Adverse Effects (Rare):
Orally: In very high doses, vitamin A can cause pseudotumor cerebri, pain, liver toxicity, coma, and even death.

Dermatologic ...Chronic oral use of large amounts of vitamin A causes symptoms of vitamin A toxicity including dry skin and lips; cracking, scaling, and itchy skin; skin redness and rash; hyperpigmentation; shiny skin, and massive skin peeling (7135,95051). Hypervitaminosis A can cause brittle nails, cheilitis, gingivitis, and hair loss (15,95051). Adverse effects from a single ingestion of a large dose of vitamin A is more common in young children than adults (15). In children, approximately 25,000 IU/kg can cause skin redness and generalized peeling of the skin a few days later and may last for several weeks (15).

Gastrointestinal ...There is some evidence that oral vitamin A supplementation might increase the risk of diarrhea in children. Although vitamin A can prevent diarrhea and reduce mortality in malnourished children, doses as low as 10,000 IU weekly for 40 weeks have been associated with diarrhea in well-nourished children (319). Diarrhea (82326,82389), nausea (7135,100329), abdominal pain (95051), abdominal fullness (100329), and vomiting (7135,82559,95051,95055,109755) have been reported following use of large doses of oral vitamin A. Adverse effects from a single ingestion of a large dose of vitamin A is more common in young children than adults (15). In children, approximately 25,000 IU/kg can cause vomiting and diarrhea (15). Chronic use of large amounts of vitamin A causes symptoms of vitamin A toxicity including anorexia, abdominal discomfort, and nausea and vomiting (7135).

Genitourinary ...Hypervitaminosis A can cause reduced menstrual flow (15). Intravaginally, all-trans retinoic acid can cause vaginal discharge, itching, irritation, and burning (9199).

Hematologic ...Hypervitaminosis A can cause spider angiomas, anemia, leukopenia, leukocytosis, and thrombocytopenia (15,95051).

Hepatic ...Since the liver is the main storage site for vitamin A, hypervitaminosis A can cause hepatotoxicity, with elevated liver enzymes such as alanine aminotransferase (ALT, formerly SGPT) and aspartate aminotransferase (AST, formerly SGOT), as well as fibrosis, cirrhosis, hepatomegaly, portal hypertension, and death (6377,7135,95051).

Musculoskeletal ...Vitamin A can increase the risk for osteoporosis and fractures. Observational research has found that chronic, high intake of vitamin A 10,000 IU or more per day is associated with an increased risk of osteoporosis and hip fracture in postmenopausal adults, as well as overall risk of fracture in middle-aged males (7712,7713,9190). A meta-analysis of these and other large observational studies shows that high dietary intake of vitamin A or retinol is associated with a 23% to 29% greater risk of hip fracture when compared with low dietary intake (107294). High serum levels of vitamin A as retinol also increase the risk of fracture in males. Males with high serum retinol levels are seven times more likely to fracture a hip than those with lower serum retinol levels (9190). Vitamin A damage to bone can occur subclinically, without signs or symptoms of hypervitaminosis A. Some researchers are concerned that consumption of vitamin A fortified foods such as margarine and low-fat dairy products in addition to vitamin A or multivitamin supplements might cause excessive serum retinol levels. Older people have higher levels of vitamin A and might be at increased risk for vitamin A-induced osteoporosis.
Vitamin A's effects on bone resorption could lead to hypercalcemia (95051).
Hypervitaminosis can cause slow growth, premature epiphyseal closure, painful hyperostosis of the long bones, general joint pain, osteosclerosis, muscle pain, and calcium loss from the bones (15,95051). One child experienced severe bone pain after taking vitamin A 600,000 IU daily for more than 3 months (95051). Vitamin A was discontinued and symptoms lessened over a period of 2 weeks. The patient made a full recovery 2 months later.

Neurologic/CNS ...Orally, adverse effects from a single large dose of vitamin A are more common in young children than adults (15). Headache, increased cerebrospinal fluid pressure, vertigo, and blurred vision have been reported following an acute oral dose of vitamin A 500,000 IU (7135). In children, approximately 25,000 IU/kg can cause headache, irritability, drowsiness, dizziness, delirium, and coma (15). Chronic use of large amounts of vitamin A causes symptoms of vitamin A toxicity including fatigue, malaise, lethargy, and irritability (7135).
There are reports of bulging of the anterior fontanelle associated with an acute high oral dose of vitamin A in infants (7135,90784,95053,95054). In children, approximately 25,000 IU/kg can cause increased intracranial pressure with bulging fontanelles in infants (15). Also, muscular incoordination has been reported following short-term high doses of vitamin A (7135).
A case of intracranial hypertension involving diffuse headaches and brief loss of vision has been reported secondary to topical use of vitamin A. The patient was using over-the-counter vitamin A preparations twice daily including Avotin 0.05% cream, Retin-A gel 0.01%, and Isotrexin gel containing isotretinoin 0.05% and erythromycin 2%, for treatment of facial acne. Upon exam, the patient was noted to have bilateral optic disc edema. The patient discontinued use of topical vitamin A products. Two months later, the patient reported decreased headaches and an improvement in bilateral optic disc edema was seen (95056).

Ocular/Otic ...In children, oral vitamin A approximately 25,000 IU/kg can cause swelling of the optic disk, bulging eyeballs, and visual disturbances (15). Adverse effects from a single ingestion of a large dose of vitamin A are more common in young children than adults (15).

Oncologic ...There is concern that high intake of vitamin A might increase some forms of cancer. Population research suggests high vitamin A intake might increase the risk of gastric carcinoma (9194).

Psychiatric ...Chronic oral use of large amounts of vitamin A causes symptoms of vitamin A toxicity, which can include symptoms that mimic severe depression or schizophrenic disorder (7135).

Pulmonary/Respiratory ...There is some evidence that oral vitamin A supplementation might increase the risk of pneumonia and diarrhea in children. Although vitamin A can prevent diarrhea and reduce mortality in malnourished children, doses as low as 10,000 IU weekly for 40 weeks have been associated with pneumonia and diarrhea in well-nourished children (319). In preschool children, high-dose vitamin A also increases the risk of respiratory infection (82288).

Other ...Chronic use of large amounts of vitamin A (>25,000 IU daily for more than 6 years or 100,000 IU daily for more than 6 months) can cause symptoms of vitamin A toxicity including mild fever and excessive sweating (7135). High intakes of vitamin A may result in a failure to gain weight normally in children and weight loss in adults (15).

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VITAMIN E

General ...Orally and topically, vitamin E is generally well-tolerated.
Serious Adverse Effects (Rare):
Orally: Bleeding, hemorrhagic stroke, cardiovascular complications.
Inhaled: Vitamin E acetate is thought to be responsible for e-cigarette, or vaping, product-use associated lung injury (EVALI).

Cardiovascular ...Some evidence suggests that taking vitamin E supplements, especially greater than or equal to 400 IU taken by mouth daily for over one year, might also increase the risk of mortality in non-healthy patients (12212,13036,15305,16709,83339). A population study shows that vitamin E use is associated with a significantly increased risk of mortality in people with a history of severe cardiovascular disease such as stroke or myocardial infarction (16709). In an analysis of clinical trials, patients who took either all-rac-alpha-tocopherol (synthetic vitamin E) or RRR-alpha-tocopherol (natural vitamin E) in doses of 400 IU/day or higher had an increased risk of mortality from all causes. The risk of mortality seems to increase when higher doses are used (12212). A large-scale study also suggests that patients with diabetes or cardiovascular disease who take RRR-alpha-tocopherol (natural vitamin E) 400 IU daily have an increased risk of heart failure and heart failure-related hospitalization (13036). However, in another large scale study, taking 600 IU vitamin E every other day for 10 years did not increase the risk of heart failure in healthy females over 45 years of age (90068). There is speculation that high-dose vitamin E might disrupt the normal antioxidant balance and result in pro-oxidant rather than antioxidant effects.
There is some evidence that vitamin E in combination with simvastatin (Zocor), niacin, selenium, vitamin C, and beta-carotene might lower high density lipoprotein-2 (HDL-2) by 15%. HDL-2 is considered to be the most cardioprotective component of HDL (7388). However, vitamin E and a statin alone don't seem to negatively affect HDL (11286,11287). In addition, vitamin E has been associated with increased triglycerides (85215). Although only certain isomers of vitamin E are included for determination of dietary requirements, all isomers are considered for determining safe intake levels. All the isomers are thought to potentially contribute to toxicity.

Dermatologic ...Topically, vitamin E has been associated with contact dermatitis, inflammatory reactions, and eczematous lesions (11998,85066,85285). Dermatitis, often associated with moisturizers containing vitamin E, has a scattered generalized distribution, is more common on the face than the hands, and is more common in females with a history of atopic dermatitis. In a retrospective analysis of results of patch tests for DL-alpha-tocopherol sensitivity, 0.9% of patients had a definite positive reaction, while over 50% had a weakly positive, non-vesicular erythematous reaction (107869).
Orally, vitamin E has been associated with pruritus in one clinical trial (34596).
Subcutaneously, vitamin E has been associated with reports of lipogranuloma (85188,112331). In one case, subcutaneous injection of a specific supplement (1Super Extenze), containing mineral oil and tocopherol acetate, into the penile tissue resulted in penile disfigurement due to sclerosing lipogranuloma (85188). In another case, a 50-year-old Iranian female presented with lipogranuloma of the face, characterized by severe facial erythema, edema, and tenderness, 3 months after receiving subcutaneous injections of vitamin E to the cheeks for "facial rejuvenation." The patient had noticed initial symptoms within 3 days, and her symptoms progressively worsened over time (112331).

Gastrointestinal ...Orally, vitamin E supplementation has been associated with abdominal pain, nausea, diarrhea, or flu-like symptoms (85040,85323). Intravenously, large doses of vitamin E in premature infants are associated with an increased risk of necrotizing enterocolitis and sepsis (85083,85231).

Genitourinary ...There is contradictory evidence about the effect of vitamin E on prostate cancer risk. One large-scale population study shows that males who take a multivitamin more than 7 times per week and who also take a separate vitamin E supplement have a significantly increased risk of developing prostate cancer (15607). In a large-scale clinical trial (The SELECT trial) in males over the age of 50 years, taking all-rac-alpha-tocopherol (synthetic vitamin E) 400 IU daily increased the risk of developing prostate cancer by 17% when compared with placebo. However, the difference in prostate cancer risk between vitamin E and placebo became significant only 3 years after patients stopped taking supplementation and were followed in an unblinded fashion. Interestingly, patients taking vitamin E plus selenium did not have a significantly increased risk of prostate cancer (17688).

Hematologic ...High doses of vitamin E might increase the risk of bleeding due to antagonism of vitamin K-dependent clotting factors and platelet aggregation. Patients with vitamin K deficiencies or taking anticoagulant or antiplatelet drugs are at a greater risk for bleeding (4098,4844,11999,34596,34538,34626,34594,112162).

Neurologic/CNS ...There is concern that vitamin E might increase the risk of hemorrhagic stroke (16708,34594,34596,108641). In one clinical study, there was a higher incidence of hemorrhagic stroke in male smokers taking all-rac-alpha-tocopherol (synthetic vitamin E) for 5-8 years compared to those not taking vitamin E (3949). Other studies lasting from 1.4-4.5 years and using either all-rac-alpha-tocopherol (synthetic vitamin E) or RRR-alpha-tocopherol (natural vitamin E) showed no significantly increased risk for stroke (2307,3896,3936). A meta-analysis of studies shows that vitamin E in doses of 300-800 IU daily, including both natural and synthetic forms, does not significantly affect total stroke risk. However, it significantly increases the risk of hemorrhagic stroke by 22%. This means that there will be one additional hemorrhagic stroke for every 1250 patients taking vitamin E. In contrast to this finding, the analysis also found that vitamin E significantly reduces the risk of ischemic stroke by 10%. This means that one ischemic stroke will be prevented for every 476 patients taking vitamin E (14621). In patients with moderately severe Alzheimer disease, taking vitamin E 2000 IU for 2 years has been associated with a modest, but significant, increase in falls and episodes of syncope when compared to placebo (4635).

Pulmonary/Respiratory ...When inhaled, vitamin E acetate is thought to play a role in the development of e-cigarette, or vaping, product-use associated lung injury (EVALI). Although a causal link has not yet been determined, in two case series, vitamin E acetate has been found in most bronchoalveolar lavage samples taken from the primary site of lung injury in patients with EVALI, whereas no vitamin E was found in healthy control samples. Other ingredients, including THC or nicotine, were also commonly found in samples. However, priority toxicants including medium chain triglyceride (MCT) oil, plant oil, petroleum distillate, or terpenes, were undetectable in almost all samples. EVALI has resulted in death in some patients (101062,102970).

Other ...In an analysis of 3 trials, taking vitamin E 400 IU with vitamin C 1000 mg daily for 14-22 weeks during gestation appears to increase the risk of gestational hypertension by 30% compared to placebo in patients at risk of pre-eclampsia. However, the risk of pre-eclampsia itself was not increased (83450).

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