Coenzyme Q-10 50 mg With C [Discontinued] by Douglas Laboratories

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 (myoclonic epilepsy 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.
• 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)

EFFECTIVE

• Vitamin C deficiency. Oral or intramuscular vitamin C is effective for preventing or treating vitamin C deficiency. Details: Administering vitamin C orally or intramuscularly prevents and treats vitamin C deficiency, including scurvy. Vitamin C administration can reverse complications of scurvy within 2 days to 3 weeks (4844). In newborns with transient tyrosinemia due to vitamin C deficiency, oral or intramuscular vitamin C can correct this condition (15).

POSSIBLY EFFECTIVE

• Anemia of chronic disease. Oral vitamin C seems to improve markers of anemia in patients on hemodialysis. Details: Meta-analyses of clinical research in hemodialysis patients with anemia shows that treatment with vitamin C 200-300 mg three times weekly for 3-6 months increases hemoglobin levels by approximately 0.9 grams/dL, increases transferrin saturation by about 8%, and decreases the required recombinant human erythropoietin dose by 17 U/kg weekly when compared with standard care (83447,83475).
• Atrial fibrillation. Oral and intravenous vitamin C seems to help prevent atrial fibrillation after cardiac surgeries. Details: Meta-analyses of clinical research show that taking vitamin C prior to and after cardiac surgery reduces the risk of postoperative atrial fibrillation by 27% to 53%. Most studies administered vitamin C at doses of 1-2 grams orally daily for 1-3 days prior to cardiac surgery, followed by 1-2 grams in two divided doses daily for 4-5 days after cardiac surgery. Some studies provided vitamin C intravenously at similar doses, but oral vitamin C seems to be more effective (91233,96703,96705). Despite these findings, a meta-analysis of clinical research conducted only in the U.S. does not support the benefit of vitamin C for reducing postoperative atrial fibrillation (96703). These differences may be related to lifestyle factors such as nutrition, as well as differences in hospital treatments. Vitamin C has also been studied in combination with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with evidence of benefit (90701).
• Bowel preparation. Powdered vitamin C is approved for use as part of a polyethylene glycol-based bowel preparation for colonoscopy. Details: Clinical research shows that treatment with 2 liters of oral solution containing polyethylene glycol (PEG) plus vitamin C achieves a similar quality of bowel cleansing as treatment with 4 liters of PEG when administered on the evening prior to colonoscopy or when administered in a split-dose regimen. Patients given 2 liters of PEG plus vitamin C solution also have better adherence and experience fewer adverse events, such as nausea, vomiting, or abdominal bloating, compared to patients treated with 4 liters of PEG solution without vitamin C (90413,90415,90420,90424,90428). This treatment also appears to be effective and tolerable in elderly patients aged 60-79 years, including those with poor bowel habits and a high number of comorbidities (108085). Other clinical research in older adults undergoing bowel preparation for colonoscopy also shows that taking 1 liter of PEG plus vitamin C (CleanViewAL, Taejoon Pharm) results in similar quality of bowel cleansing overall and per segment with similar tolerability and adverse effects as sodium picosulfate 170 mL plus magnesium citrate or oral sulfate solution alone (111297,112476). The most common PEG plus vitamin C preparation used in clinical research is MoviPrep (Norgine BV), which contains macrogol 3350 100 grams, sodium sulfate 7.5 grams, sodium chloride 2.7 grams, potassium chloride 1 gram, vitamin C 4.7 grams, and sodium ascorbate 5.9 grams per liter of solution (90413,90415,90424). In the U.S., MoviPrep is approved by the Food and Drug Administration (FDA) for bowel preparation prior to a colonoscopy.
• Common cold. Oral high-dose vitamin C might modestly reduce cold symptoms; however, taking vitamin C prophylactically does not seem to prevent the development of a cold. Details: There is substantial controversy about the effectiveness of vitamin C for treating the common cold (1969,1989,7100,9835,9836). The majority of evidence shows that taking high doses of vitamin C orally might decrease the duration of cold symptoms by 1-1.5 days in some patients (1966,1967,1968,1987,6458,7102,9832,83487). However, other studies have found no effect with doses up to 3 grams daily (9833). A meta-analysis of clinical research suggests that vitamin C supplementation decreases the incidence of cold in individuals exposed to physical stress, but not in the general population (83487). Other research suggests vitamin C may be more effective for treating cold symptoms in children than in adults. Also, there may be a dose-dependent response; doses of at least 2 grams daily seem to work better than 1 gram doses (9834). Taking vitamin C supplements prophylactically does not decrease the risk of catching a cold (1966,1967,1968,1987,3042,6458,7101,9832). Dietary intake of vitamin C also does not seem to affect the risk of getting a cold (10780).
• Complex regional pain syndrome. Most research shows that taking oral vitamin C after a wrist or distal radius fracture or after orthopedic surgery seems to reduce the risk of developing complex regional pain. Details: Although some research has found no benefit in patients with distal radius (i.e. wrist) fractures (90411,96702), most clinical research shows that taking vitamin C 500 mg daily, and possibly doses of up to 1500 mg daily, for 45-50 days beginning immediately after fracture can reduce the risk of developing complex regional pain syndrome (2045,16302,96700,96706). Reasons for discrepancies are unclear but might relate to differences in diagnostic criteria for complex regional pain syndrome (96702). Research in patients undergoing orthopedic surgery has also shown benefit with the use of vitamin C for the prevention of complex regional pain syndrome (90422,108076,108087). One meta-analysis of clinical research in patients undergoing wrist, foot, or ankle surgery shows that taking vitamin C 500-1000 mg for 42-50 days following surgery reduces the rate of complex regional pain syndrome, and may improve pain following ankle or foot surgery, when compared with placebo (108076). The validity of these findings is limited by the high heterogeneity of included trials. Another meta-analysis of clinical research in patients undergoing orthopedic surgery (i.e. wrist, knee, ankle, foot, lumbar, rotator cuff) suggests that oral and intravenous vitamin C may have similar effectiveness; however, this evidence is low quality (108087).
• Exercise-induced respiratory infections. High-dose oral vitamin C seems to reduce the risk of respiratory infections associated with strenuous exercise. Details: Some preliminary clinical research suggests that prophylactic use of vitamin C in doses of 600 mg to 1 gram daily for 3-8 weeks before heavy physical exercise, such as a marathon, might prevent upper respiratory infections that sometimes follow heavy exercise (9831,83370). More recently, high doses of vitamin C have been studied. A large clinical study in army recruits undergoing basic military training shows that taking vitamin C 6 grams daily for one month reduces the odds of getting a cold by 20% when compared with placebo (102975).
• Hypercholesterolemia. Oral vitamin C seems to reduce lipid levels in patients with hypercholesterolemia. Details: A meta-analysis of clinical research in patients with hypercholesterolemia shows that taking vitamin C 500 mg daily for at least 4 weeks reduces low-density lipoprotein (LDL) cholesterol by about 8 mg/dL and reduces triglycerides by about 20 mg/dL when compared with control (83445).
• Hypertension. Oral vitamin C seems to modestly reduce blood pressure in patients with hypertension. Details: Vitamin C seems to modestly reduce systolic blood pressure, without meaningful effects on diastolic blood pressure (2044,9822,13162,83483,102974). A meta-analysis of 13 clinical trials in patients with hypertension, with or without other comorbidities, shows that taking a median dose of vitamin C 500 mg daily for 8 weeks reduces systolic, but not diastolic, blood pressure by about 5 mmHg. Some of the studies used vitamin C in combination with other supplements, such as vitamin E and magnesium. When studies assessing vitamin C alone were analyzed, the magnitude of reduction in systolic blood pressure decreased (83483). A newer meta-analysis of small clinical studies in patients with essential hypertension shows that taking vitamin C 200 mg or more daily reduces systolic blood pressure by about 4 mmHg and diastolic blood pressure by about 2 mmHg (102974). However, this newer analysis omitted numerous relevant studies and included studies with normotensive patients and those without an adequate control, limiting the validity of its findings.
• Laser skin resurfacing. Topical vitamin C seems to reduce erythema occurring after cosmetic laser skin resurfacing procedures intended to reduce scars and wrinkles. Details: There is some evidence that an aqueous formulation of topical vitamin C can decrease the degree and duration of erythema following cutaneous carbon dioxide laser resurfacing for scar and wrinkle removal (1959).
• Lead toxicity. Dietary vitamin C seems to lower concentrations of lead in the blood. Details: Observational research has found that consuming more vitamin C from dietary sources is associated with lower blood concentrations of lead. People who consumed at least 340 mg of vitamin C daily as part of the diet had lower blood lead levels than those who consumed less than 100 mg vitamin C daily (3097,3098,3099).
• Nitrate tolerance. Oral vitamin C might prevent nitrate tolerance in some patients. Details: Small clinical studies show that taking vitamin C orally seems to prevent the development of nitrate tolerance in patients taking sublingual nitroglycerin. There is some evidence that short-term vitamin C supplementation can prevent tolerance to the vasodilatory effects of nitrates (1441,1961).
• Postoperative pain. Oral or intravenous vitamin C might prevent acute postoperative pain following certain surgeries. It is unclear if vitamin C reduces chronic postoperative pain. Details: A meta-analysis of 7 small clinical studies in adults undergoing elective surgery shows that receiving perioperative vitamin C, either as 1 gram orally, 2-3 grams intravenously, or 50 mg/kg intravenously, modestly reduces acute pain and opioid requirements for up to 24 hours when compared with control (105457). Most surgeries were laparoscopic and included cholecystectomy, colectomy, hysterectomy; two non-laparoscopic surgeries included uvulopalatopharyngoplasty with tonsillectomy and major abdominal surgery (90418,99840,105457). A meta-analysis of clinical trials in adults undergoing noncardiac surgery (i.e., orthopedic, abdominal, gynecologic, kidney transplantation) shows that administering perioperative vitamin C, either orally or intravenously, reduces postoperative intravenous morphine requirements at 2, 24, and 48 hours after surgery and improves pain scores at 2, 6, and 24 hours after surgery when compared with placebo. The dose of vitamin C did not appear to impact outcomes. However, when only laparoscopic surgeries are included, perioperative vitamin C does not improve pain or morphine use when compared with placebo (108087). A moderate-sized clinical study in adults undergoing transurethral resection of a bladder tumor under general anesthesia shows that administering intravenous vitamin C 1 gram after induction of anesthesia reduces the incidence and severity of catheter-related bladder discomfort immediately after surgery and at 1 and 2 hours postoperatively, but not 6 hours, when compared with placebo. However, vitamin C does not reduce postoperative pain scores or analgesic requirements when compared with placebo (111645). Further research is needed to determine the effects of vitamin C for acute postoperative pain. Vitamin C has also been evaluated for reducing chronic pain after surgery. Clinical research in patients undergoing surgery for foot or ankle trauma shows that taking vitamin C 500 mg orally twice daily postoperatively for 6 weeks reduces pain scores when compared with placebo at 2 weeks and 6 weeks. The mean total amount of diclofenac used for pain relief over the 6-week period is also reduced, from 5.7 grams with placebo to 3.4 grams with vitamin C (102131).
• Wrinkled skin. Topical vitamin C might reduce the appearance of existing wrinkles. Details: Topical preparations containing vitamin C seem to improve the appearance of wrinkled skin. Some evidence shows that vitamin C 3% applied for 12 weeks might reduce facial wrinkles (14008). A small clinical study shows that applying a dissolving microneedle patch containing vitamin C 5.6% every 4 days for 12 weeks to crow's feet on one side of the face reduces wrinkles when compared to control treatment applied on the other side of the face (98780). Other clinical research in females aged 30-60 years shows that applying an oil-soluble cream containing the vitamin C derivative tetra-isopalmitoyl ascorbic acid 1%, 2%, or 3% to the periorbital area twice daily for 8 weeks reduces visual wrinkle grading when compared with placebo. A dose analysis shows greater improvements in wrinkle parameters, average wrinkle depth, and mean depth with the lower concentration, while greater improvements in maximum roughness and maximum depth are observed with the higher concentration (108072). This study only included individuals defined as having Fitzpatrick skin type III or IV; it effects on other skin types is unclear. Preparations containing vitamin C in combination with other ingredients have also been investigated. A small low-quality trial in females with moderately photodamaged and hyperpigmented facial skin shows that applying a moisturizer with vitamin C 30%, vitamin E, and coenzyme Q10 once daily in the morning, along with applying retinol 0.5% once daily or once every other day for 12 weeks, seems to improve skin tone, photodamage, and wrinkles when compared to baseline (99085). In another small trial, a topical preparation containing vitamin C 10% as L-ascorbic acid along with acetyl tyrosine, zinc sulfate, sodium hyaluronate, and bioflavonoids (Cellex-C High Potency Serum) applied to photo-aged facial skin for 3 months improves fine and coarse wrinkling, yellowing and sallowness, roughness, and skin tone when compared with placebo (6155). It is unclear if the beneficial effects of these products are due to vitamin C, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Acute bronchitis. Oral vitamin C doesn't seem to improve symptoms of acute bronchitis. Details: A clinical study in adults with acute bronchitis shows that taking vitamin C orally 500 mg on day 1, then 250 mg on days 2 through 5 (similar to an azithromycin regimen) doesn't seem to have any effect on quality of life or bronchitis duration when compared with azithromycin (9827).
• Asthma. Oral vitamin C doesn't seem to prevent asthma or improve lung function. Details: Although some observational research has found that some patients with asthma might have lower serum vitamin C levels (5873), other observational research found that increased dietary vitamin C intake is not associated with a reduced risk of asthma or improved lung function (15006,34567). In addition, clinical research shows that supplemental intake of vitamin C does not reduce asthma symptoms, improve lung function, or reduce the use of inhaled steroids in asthma patients (90409).
• Atherosclerosis. Oral vitamin C does not seem to reduce the progression of atherosclerosis. Details: A clinical study shows that taking a specific combination product containing slow-release vitamin C 250 mg and vitamin E 136 IU (CellaVie, Ferrosan A/S) twice daily modestly slows the 3-year progression of atherosclerosis of the carotid artery in males, but not females. This result persisted at a 6-year follow-up of this study (1918,10473). However, when this form of vitamin C is used alone, it does not slow the 3-year progression of atherosclerosis of the carotid artery (1918).
• Bladder cancer. Oral vitamin C does not reduce the risk of bladder cancer or mortality from bladder cancer. Details: Epidemiological research has found that supplemental vitamin C intake is not associated with mortality rate in patients with bladder cancer (9839). A secondary analysis of a large clinical trial, the Physicians' Health Study II, in healthy men aged at least 50 years also shows that taking vitamin C 500 mg daily alone or with vitamin E 400 IU daily for up to 10 years does not reduce the risk of developing bladder cancer or bladder cancer-related deaths when compared with placebo (90097).
• Cardiovascular disease (CVD). Oral vitamin C does not seem to be beneficial for either primary or secondary CVD prevention. Details: Vitamin C does not seem to be beneficial for primary prevention of CVD. Some population research has found that higher supplemental vitamin C or dietary vitamin C has been associated with a reduced risk of developing CVD (10358,14108,109779), while other observational research has found no benefit (34566,10358,14108). However, meta-analyses of clinical research in healthy patients show that vitamin C supplementation does not prevent CVD or coronary heart disease when compared with control (97308,104025). In 2004, the American Heart Association stated that current evidence does not justify use of antioxidants such as vitamin C for reducing the risk of CVD (12142). Evidence is also negative for secondary prevention in people with coronary heart disease. Population studies have found that higher serum vitamin C was associated with no effect or decreased CVD mortality from CVD (3910,5878). A meta-analysis of two large clinical trials shows that vitamin C supplementation does not reduce CVD events or CVD mortality when compared with control (97308).
• Colorectal cancer. Oral vitamin C does not seem to prevent colorectal cancer. Details: Population research has found that dietary vitamin C intake is not associated with a reduced risk of developing colon cancer. When total vitamin C intake from food and supplements is considered, there is a modest association (34600). However, most clinical trials show that supplemental vitamin C, alone or along with other antioxidants, does not reduce the risk of colorectal cancer development, colorectal cancer or adenoma recurrence, or colorectal cancer-related mortality (34580,34581,34594,90097,90089,92903).
• Coronavirus disease 2019 (COVID-19). Oral vitamin C, even at high doses, does not seem to speed recovery from COVID-19 in non-hospitalized patients. An analysis of clinical research suggests that oral or intravenous vitamin C might reduce mortality in patients hospitalized with COVID-19; however, given that nearly all individual studies are small and do not show benefit, larger and higher-quality studies are needed to confirm these findings. Details: A clinical study in adult outpatients with confirmed COVID-19 shows that taking oral vitamin C (ascorbic acid) 8000 mg in 2-3 divided doses daily, alone or with zinc gluconate 50 mg daily, for 10 days does not reduce symptom severity when compared with standard care (104450). The study was terminated prior to complete enrollment due to futility and apparent lack of effect from vitamin C and/or zinc supplementation. Limitations of this study include a lack of placebo control and blinding. Additionally, this study has been criticized for methodologic concerns (106624). Another small clinical trial in adult outpatients with confirmed COVID-19 shows that taking vitamin C 1000 mg daily for 14 days does not improve symptoms or quality of life when compared with placebo (109462). Vitamin C has also been evaluated in patients hospitalized with COVID-19. Individual prospective and retrospective studies in critically ill patients hospitalized with COVID-19 in various countries have found that administering vitamin C, either enterally as 500-1000 mg daily or intravenously as 8-24 grams daily or 50 mg/kg daily, does not significantly reduce in-hospital or short-term mortality, hospital length of stay, or end-organ failure when compared with control groups receiving standard care alone. Additionally, all but one study found no change in the need for mechanical ventilation (105458,105465,106937,106938,108075,108079,108081). One small study found a small improvement in survival rate when compared with standard care; however, the overall survival rate in this study was low (108075). Additionally, one clinical study in patients hospitalized in Turkey with COVID-19 shows that adding high-dose intravenous sodium ascorbate 50 mg/kg to a treatment regimen of hydroxychloroquine, azithromycin, and zinc may improve recovery time, with 57% and 39% of patients achieving total recovery at day 15 in the vitamin C and control groups, respectively (108071). However, the validity of this trial is limited due to unclear reporting. Additionally, these small studies were likely underpowered to detect differences between the vitamin C and control groups. A meta-analysis of 10 clinical trials and 9 observational studies in patients hospitalized with COVID-19 shows that receiving oral or intravenous vitamin C daily reduces the odds of in-hospital mortality by 41% when compared with control. When only clinical trials were considered, the odds of in-hospital mortality were decreased by 56%; however, this reduction was only identified in studies using vitamin C 10 grams daily or less. Conversely, supplementation with vitamin C increased the length of intensive care unit (ICU) stay by nearly 2 days and did not impact length of hospital stay or reduce the need for mechanical ventilation, liver injury, or cardiac injury (109955). Given that most individual studies in this analysis did not show improvements in mortality with vitamin C, larger and higher-quality prospective studies are needed to determine the role of vitamin C in hospitalized patients with COVID-19. Vitamin C has also been evaluated in patients with long COVID. Preliminary clinical research in adults with long COVID and persistent fatigue shows that taking a specific combination product containing vitamin C 500 mg and L-arginine 1.66 grams (Bioarginina C, Farmacetici Damor) for 28 days increases 6-minute walk test distance by 10% and reduces self-reported fatigue when compared with placebo (110390).
• Fetal and premature infant mortality. Oral vitamin C does not seem to prevent neonatal death. Details: Meta-analyses of clinical research show that taking vitamin C alone or with other supplements does not reduce the risk of neonatal death (83472,96707).
• Fractures. Oral vitamin C does not seem to improve fracture healing. Details: Clinical research shows that taking vitamin C 500 mg daily for 50 days following an acute distal radial fracture does not improve physical function, symptoms, or healing rates when compared with placebo (90411).
• Helicobacter pylori. Oral vitamin C does not seem to improve eradication of H. pylori. Details: Most clinical research shows that treatment with vitamin C, alone or in combination with vitamin E, does not improve the eradication rate of H. pylori when taken with a standard eradication regimen when compared with the eradication regimen alone (83476,90094).
• Hereditary motor and sensory neuropathy. Oral vitamin C does not seem to improve neuropathy in these patients. Details: In a meta-analysis of five studies in patients with Charcot-Marie-Tooth disease type 1A, taking vitamin C 1-4 grams orally daily for 1 year did not improve neuropathy when compared with placebo (99084). Continuing vitamin C 4 grams daily for 2 years also does not improve neuropathy in these patients (90419).
• Interferon-related retinopathy. Oral vitamin C does not seem to improve retinopathy associated with interferon therapy. Details: A small clinical study in patients with chronic hepatitis C receiving interferon therapy shows that taking vitamin C 600 daily orally does not seem to reduce the risk of retinopathy from interferon therapy when compared with control (10355).
• Leukemia. Oral vitamin C does not seem to reduce the risk of leukemia or mortality from leukemia. Details: A large clinical trial in men aged at least 50 years shows that taking vitamin C 500 mg daily, alone or along with vitamin E 400 IU daily, for up to 10 years does not reduce the risk of developing leukemia or leukemia-related deaths when compared with placebo (90097).
• Low birth weight. Oral vitamin C does not seem to reduce the risk of infants being born with a low birth weight. Details: Meta-analyses of clinical research show that maternal use of oral vitamin C alone or with other supplements does not reduce the risk of giving birth to infants with low birth weight when compared with control (83450,83472).
• Lung cancer. Oral vitamin C does not seem to reduce the risk of lung cancer. Details: Two meta-analyses of clinical research suggest that taking vitamin C, alone or in combination with vitamin E, does not reduce the incidence of lung cancer or lung cancer-related mortality (34528,34632). Also, a clinical study in females shows that taking supplemental vitamin C 500 mg daily, with or without vitamin E and beta carotene, is associated with an INCREASED risk of lung cancer when compared with placebo (34580).
• Melanoma. Oral vitamin C does not seem to reduce the risk of melanoma. Details: Clinical research shows that taking vitamin C 500 mg daily, alone or along with vitamin E 400 IU daily, for up to 10 years does not reduce the risk of developing melanoma or melanoma-related deaths when compared with placebo in men aged at least 50 years (90097).
• Miscarriage. Oral vitamin C does not seem to reduce the risk of miscarriage. Details: A meta-analysis of clinical research shows that taking vitamin C alone or with other supplements does not reduce the risk of miscarriage when compared with control (94820).
• Overall mortality. Oral vitamin C does not reduce overall mortality. Details: Although population research suggests that higher dietary intake and higher plasma vitamin C levels are associated with a reduced risk of mortality from all causes (3910,109779), vitamin C supplementation does not seem to affect overall mortality. Meta-analyses of clinical research show that taking vitamin C supplements does not reduce overall mortality when compared with control (34622,111641). Clinical studies of vitamin C used in combination with vitamin E, beta carotene, and/or selenium and zinc, also show no benefit for overall mortality (9817,14109).
• Pancreatic cancer. Oral vitamin C does not seem to prevent pancreatic cancer. Details: Observational research has found that increased dietary vitamin C intake is associated with up to a 30% reduced risk of pancreatic cancer (99083,99086). However, clinical research shows that supplemental vitamin C 500 mg daily does not reduce the risk of pancreatic cancer in females (34580). Also, taking vitamin C in combination with beta-carotene plus vitamin E does not reduce the risk of pancreatic cancer (12185,34581).
• Pre-eclampsia. Oral vitamin C does not seem to prevent pre-eclampsia. Details: Despite some early positive research in high-risk pregnancies, the majority of meta-analyses and clinical studies show that taking vitamin C alone or with vitamin E or other supplements does not reduce the risk of pre-eclampsia when compared with control. There is even some concern that vitamin C supplementation may increase the risk of gestational hypertension (3236,83450,83472,83474,96707).
• Preterm labor. Oral vitamin C does not seem to prevent preterm labor. Details: Meta-analyses of clinical research show that taking vitamin C alone or with other supplements does not reduce the risk of preterm labor when compared with control (83450,83472,96707).
• Prostate cancer. Oral vitamin C does not seem to prevent prostate cancer. Details: A large-scale clinical study (The SU.VI.MAX study) shows that a combination of vitamin C 120 mg, vitamin E (alpha-tocopherol) 30 mg, beta-carotene 6 mg, selenium 100 mcg, and zinc 20 mg, taken daily for an average of 8 years, does not reduce the risk of prostate cancer overall. However, it might reduce the risk of prostate cancer in those who have normal PSA levels. It does not seem to be beneficial for reducing the risk of prostate cancer in patients with PSA levels above 3 mcg/L (14135). Another large scale study (Physician's Health Study II) shows that taking vitamin C 500 mg daily for an average of 8 years does not significantly reduce the risk of prostate cancer when compared with placebo (16708). Similarly, results from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial seem to show that supplemental or dietary intake of vitamin C does not reduce the risk of prostate cancer when compared to individuals not taking vitamin C (14124).
• Radiation dermatitis. Topical vitamin C does not seem to prevent radiation dermatitis in cancer patients. Details: A small clinical study shows that applying a 10% vitamin C solution does not appear to protect from radiation dermatitis when applied to the scalps of patients treated with radiation for intracranial tumors (789).
• Small for gestational age (SGA). Oral vitamin C does not seem to reduce SGA. Details: Meta-analyses of clinical research show that taking vitamin C alone or with other supplements does not reduce the risk of small for gestational age birth when compared with control (83450,83472).
• Stillbirth. Oral vitamin C does not seem to prevent stillbirth. Details: Meta-analyses of clinical research show that maternal use of vitamin C alone or with other supplements does not reduce the risk of stillbirth when compared with control (83472,96707).

LIKELY INEFFECTIVE

• Sepsis. Intravenous vitamin C, alone or in combination with thiamine and/or hydrocortisone, does not prevent organ failure, reduce intensive care or hospital length of stay, or reduce mortality in sepsis or septic shock. Details: Observational research suggests that patients with septic shock are more likely to have low plasma levels of vitamin C (100317). However, two randomized clinical trials in patients with sepsis show no benefit with intravenous vitamin C, with or without thiamine, for improving organ function and preventing organ failure when compared with control treatment (102130,104027). A clinical study in patients with septic shock shows that administering an intravenous bolus of vitamin C 1000 mg followed by a continuous infusion of 250 mg/hour for 96 hours, starting within 24 hours of vasopressor initiation, does not improve 28-day or intensive care unit (ICU) mortality when compared with placebo. A subgroup analysis shows that the addition of corticosteroids does not affect outcomes in either group (108078). This study may have been inadequately powered to detect a difference between groups. Also, a larger clinical trial in adults with sepsis receiving vasopressor therapy in the ICU shows that intravenous administration of vitamin C 50 mg/kg every 6 hours for up to 4 days increases the risk of death or persistent organ dysfunction at day 28 by 14% to 21% when compared with placebo. There were no differences in mortality at 6 months (109459,111643). Vitamin C has also been frequently studied in patients with sepsis and septic shock in a specific combination regimen (HAT therapy) which includes intravenous vitamin C 1.5-2 grams with hydrocortisone 50 mg every 6 hours and thiamine 200 mg every 12 hours. While some retrospective research has found HAT therapy to be beneficial in sepsis (100315,102980), high quality, prospective clinical research has not confirmed these findings (105447,106620,109956). Several meta-analyses of randomized controlled trials and small clinical studies in patients with sepsis or septic shock show that intravenous vitamin C, either alone, as a component of HAT therapy, or in combination with thiamine, does not reduce short- or long-term mortality, ICU or hospital length of stay, kidney injury, or duration of mechanical ventilation, but modestly improves duration of vasopressor use and procalcitonin clearance, when compared with placebo or standard care. These analyses also show mixed results with respect to improvement in sequential organ failure assessment (SOFA) scores within 72 hours (105447,106620,106935,108073,109460,111298,111300,111301,111642,112479). Most studies included in the analyses administered HAT therapy for 2-10 days and compared it with normal saline control or with hydrocortisone alone (102129,102998,104027,104028,104032,105446). Although some subgroup analyses suggests that intravenous vitamin C alone in patients with sepsis may improve short-term mortality (106620,111298), other meta-analyses have not shown this benefit in subgroup analyses (111300). In addition, meta-analyses have identified significant publication bias (111298,111300). Long-term follow up from a study in patients with sepsis-induced respiratory and/or cardiovascular dysfunction shows that receiving HAT therapy does not improve cognitive, psychological, or functional status after 6 months and, for some domains, HAT therapy was worse when compared with placebo (111299). Studies evaluating intravenous vitamin C, either alone, as a component of HAT therapy, or in combination with thiamine, in mixed critically ill populations have also shown mixed findings. One such large meta-analysis of 27 randomized controlled trials and 21 observational studies shows that intravenous vitamin C reduces in-hospital mortality by 19% and ICU stay by about 1 day, but does not have a significant effect on hospital stay, mortality at 1 month, ICU mortality, or kidney injury, when compared with placebo or standard care. Also, effects on in-hospital mortality were no longer significant when data from randomized controlled trials were considered alone (106933). Other meta-analyses including 15-16 randomized controlled trials show that intravenous vitamin C, alone or as a component of HAT therapy, does not reduce overall, ICU, or in-hospital mortality when compared with control (106934,109957). A subgroup analysis in one of these analyses suggests that intravenous vitamin C as monotherapy, or in doses of at least 10 grams daily, may improve overall mortality (106934). Vitamin C also does not appear to benefit complications from sepsis, such as vasoplegic shock. A small clinical study in adults in the ICU with vasoplegic shock mostly secondary to sepsis and requiring moderate vasopressor support shows that administering intravenous vitamin C as sodium ascorbate 1.5 grams every 6 hours for 5 days or until cessation of vasoactive therapy does not reduce the duration of vasopressors, vasopressor dose, hospital or ICU length of stay, or mortality outcomes when compared with placebo (112475).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atrophic acne scars. It is unclear if applying topical vitamin C after microblading improves atrophic acne scars. Details: A clinical study in adults with mild to severe atrophic acne scarring shows that applying a serum containing vitamin C 17% to the face after a once-monthly home microblade treatment for 4 months improves the appearance of acne scars at month 5 when compared with baseline (108086). Although this study enrolled a control group that used topical insulin in place of vitamin C, no between-group statistical comparisons were conducted, limiting the validity of this study.
• Age-related macular degeneration (AMD). Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Most clinical research shows that taking the antioxidants vitamin C 500 mg, vitamin E 400 IU, and beta-carotene 15 mg daily, with or without elemental zinc 80 mg, reduces the risk of visual acuity loss by 23% to 27% and reduces the risk of progression to advanced AMD at 5 years by 25% to 32% in patients at high risk for developing advanced AMD (7303,7304,11326,90069). The antioxidant plus zinc combination seems to reduce the risk of progression to advanced AMD in these patients more than taking the antioxidants without zinc (7303,90069). There is not enough evidence to know if taking the antioxidants or antioxidants plus zinc prevents progression to advanced AMD in patients with early stage AMD (7303,7304). The effect of vitamin C intake on developing AMD is unclear. Some population studies have found no association between dietary or supplemental vitamin C intake on risk of developing AMD (14007,14257). In one population study, vitamin C intake was associated with increased odds of developing age-related maculopathy (9823); however, in another population study, intake of vitamin C along with other antioxidants and zinc was associated with a reduced risk of AMD (14257). More evidence is needed to determine what role, if any, vitamin C intake has on the risk of developing AMD.
• Aging skin. Topical vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in females aged 30-65 years shows that applying a specific liquid (Antioxidant and Collagen Booster Serum, Max Biocare Pty Ltd.) containing vitamin C 20%, red raspberry leaf cell culture extract 0.0005%, and vitamin E 1% 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).
• Albuminuria. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking vitamin C 1250 mg plus vitamin E 680 IU daily for 4 weeks can reduce the excretion of albumin by about 19% when compared with placebo in patients with type 2 diabetes (10434).
• Allergic rhinitis (hay fever). It is unclear if oral vitamin C is beneficial in patients with hay fever. Details: Epidemiological research has found that higher vitamin C plasma levels are not associated with a decreased risk of allergic rhinitis (15200). However, clinical research shows that some forms of vitamin C might help. In one small clinical study, intranasal vitamin C administered three times daily for 2 weeks reduces nasal secretions, nasal blockage, and edema in up to 74% of patients with perennial allergic rhinitis (15201). Another small clinical study in patients with seasonal allergic rhinitis shows that taking a single oral dose of vitamin C 2 grams reduces bronchial responsiveness to histamine at one hour after ingestion (15202). However, in another small study in patients with seasonal allergic rhinitis taking vitamin C orally in doses up to 4 grams daily for 3 days does not appear to suppress cutaneous or nasal response to histamine when compared to placebo (15203).
• Alzheimer disease. It is unclear if dietary vitamin C helps to prevent this condition. Details: Most epidemiological research has found that dietary intake of vitamin C is associated with a 17% reduced risk of developing Alzheimer disease (4636,9824,10131,13165,90082).
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if oral vitamin C helps to prevent ALS. Details: Observational research has found that increased dietary or supplemental intake of vitamin C is not associated with risk of developing ALS (90412).
• Anthracycline cardiotoxicity. Although there is interest in using oral vitamin C for anthracycline-induced cardiac toxicity, there is insufficient reliable information about the clinical effects of vitamin C for this condition.
• Aspirin-associated gastric damage. It is unclear if oral vitamin C helps to prevent gastric damage caused by aspirin. Details: Some clinical research shows that vitamin C 480 mg might prevent gastric damage associated with taking aspirin 400 mg by decreasing blood loss and preventing decreased gastric blood flow (10357). However, a small clinical study in healthy patients shows that taking vitamin C 500 mg as ascorbic acid with aspirin 600 mg actually increases gastrointestinal permeability to a greater extent than either ingredient taken alone (98781).
• Athletic performance. It is unclear if oral vitamin C improves athletic performance. Details: Although some small preliminary clinical studies suggest that vitamin C might improve certain biomarkers during exercise (82922), a meta-analysis of small clinical trials in older and younger adults shows that taking vitamin C 500-1000 mg daily, with or without vitamin E, does not improve endurance, lean mass, or muscle strength when compared with placebo (102973). A more recent, small clinical study in recreationally trained males shows that taking vitamin C 1000 mg and vitamin E (as alpha-tocopherol) 235 mg daily for 10 weeks while participating in a resistance training program does not improve measures of muscle strength when compared with placebo (109959).
• Atopic disease. It is unclear if dietary vitamin C helps to prevent atopic disease. Details: Population research has found that higher intake of vitamin C is not associated with a reduced risk of eczema, wheeze, IgE-mediated food allergy, or allergic sensitization (90098).
• Attention deficit-hyperactivity disorder (ADHD). Small clinical studies suggest that high-dose oral vitamin C may not improve symptoms in patients with ADHD. Details: Some research suggests that taking megadose vitamins, including vitamin C, does not improve ADHD symptoms (9957,9958,9959). However, other preliminary clinical research shows that taking 25 mg of vitamin C in combination with flaxseed oil providing alpha-linolenic acid 200 mg twice daily might improve measures of attention, impulsivity, restlessness, and self-control in children with ADHD when compared with baseline (14443). It is not clear if these effects are due to vitamin C, flaxseed oil, or the combination.
• Autism spectrum disorder. It is unclear if oral vitamin C is beneficial in patients with autism spectrum disorder. Details: One small clinical study shows that taking vitamin C 8 grams per 70 kg daily for 10 weeks modestly reduces autism symptom severity in school children when compared with placebo (83604).
• Bleeding. It is unclear if intravenous vitamin C can reduce bleeding after total abdominal hysterectomy. Details: A small clinical study in patients undergoing total abdominal hysterectomy shows that administration of intravenous vitamin C 1 gram the night before surgery and 1 gram during surgery reduces postoperative hemorrhage volume by around 40 mL when compared with placebo (109465).
• Brain tumor. It is unclear if oral vitamin C helps to prevent brain tumors. Details: Population research has found that vitamin C intake is associated with a 14% reduced risk of glioma. This risk reduction was more prevalent in America compared to other geographic locations (98782).
• Breast cancer. It is unclear if oral vitamin C helps to prevent breast cancer, its recurrence, or breast cancer-related mortality. Details: Some epidemiological research has found that dietary vitamin C is associated with a reduced risk of breast cancer (1444,10823,10824). However, other epidemiological research has found no association with dietary or supplemental vitamin C (10825,10826,108080). One cohort study found no association between breast cancer risk and total, dietary, or supplemental vitamin C, regardless of dose, treatment duration, or formulation (single ingredient or combination product). Additionally, hormone and menopausal status did not appear to impact risk. Vitamin C intake might be associated with a reduced risk in individuals with a family history of breast cancer in first-degree relatives (108080). In patients with breast cancer, supplemental or dietary intake of vitamin C might be associated with a reduced risk of mortality. A meta-analysis of results from population research shows that vitamin C supplementation following breast cancer diagnosis is associated with a 15% lower risk of breast cancer-related mortality when compared with no supplementation (90416). A large, observational study in patients with breast cancer undergoing radiation therapy has found that vitamin C supplementation does not reduce the risk of breast cancer recurrence over a period of 5 years when compared with no supplementation. Although the vitamin C group had notably less aggressive tumor types, recurrence-free survival was similar in both vitamin C and control groups (108082). The validity of these findings is limited due to unknown doses of vitamin C and the inclusion of various breast cancer subtypes.
• Burns. Small studies suggest that intravenous vitamin C may modestly improve symptoms in patients with severe burns. Details: A small clinical study in patients with severe burns shows that administering vitamin C intravenously (IV) 66 mg/kg hourly over 24 hours, as part of fluid resuscitation using lactated ringer solution, reduces wound edema and the volume of fluid needed when compared with fluid resuscitation alone (83145). A retrospective review of adults hospitalized with severe burns has found that those who receive a continuous IV infusion of at least 10 grams of vitamin C within 2 days of admission have an in-hospital mortality rate of 46%, compared with 58% for those who do not receive vitamin C (102128).
• Cancer. It is unclear if oral or intravenous vitamin C helps to prevent cancer or cancer-related mortality. Details: Some population research has found that DIETARY intake of vitamin C is linked with a lower risk of cancer and cancer-related mortality (3910,5878,10819,109779). However, clinical research shows that taking vitamin C SUPPLEMENTS does not reduce the risk for cancer (10819,14109,34580,90097). In people with cancer, although some clinical research has shown that taking high-dose vitamin C supplements can improve survival rates (9809,96704), other clinical research has not shown this benefit (4842,4843). In 2003, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that some scientific evidence suggests that antioxidant vitamins, such as vitamin C, may reduce the risk of certain forms of cancer. However, the FDA has determined that there is little scientific evidence supporting this claim (102334). Preliminary clinical research has also evaluated vitamin C supplements in patients with cancer. High-dose oral vitamin C, 10 grams daily, in patients with advanced cancer does not seem to improve survival or decrease disease progression (4842,4843,106617). However, preliminary clinical research suggests high doses of vitamin C, given intravenously, might have a beneficial effect on some outcomes, including survival rate in some patients with cancer (9809,96704,106617). However, there is no benefit to other patients studied in the case reports and this has not been tested in well-designed clinical trials (9809,96704).
• Carpal tunnel syndrome. Vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in adults with mild to moderate carpal tunnel syndrome shows that taking a combination product containing vitamins C, E, B1, B2, B6, and B12, alpha-lipoic acid, acetyl-L-carnitine, phosphatidylserine, and turmeric twice daily for 60 days reduces symptom severity and pain but does not improve measures of hand and wrist function when compared with control (111702). The validity of these effects is limited by a lack of blinding. The study may also be inadequately powered to detect a difference between groups. Additionally, it is unclear if the effects are due to vitamin C, other ingredients, or the combination.
• Cataracts. It is unclear if oral vitamin C helps to prevent cataracts. Details: Population research has found that people with the highest total intake of vitamin C have about a 19% reduced risk of developing cataracts when compared with those with the lowest total intake. The greatest benefit is observed for nuclear cataracts (96711). A separate study found that higher supplemental intake of vitamin C for 10 years is associated with a 60% reduction in the incidence of nuclear and cortical cataracts (4208). Other population research has found that the highest blood levels of vitamin C are associated with a 33% reduced odds of developing age-related cataract, but any benefit seems to be limited to Asian populations (90944). One prospective clinical study shows that taking vitamin C plus vitamin E and beta-carotene does not prevent the development or progression of age-related loss of vision due to cataracts in well-nourished people taking the supplement for an average of 6.3 years (7304).
• Cervical cancer. It is unclear if oral vitamin C helps to prevent cervical cancer. Details: Observational research has found that higher vitamin C intake is associated with a 33% to 42% reduced odds of cervical neoplasm. Increasing vitamin C intake by 50 mg daily is associated with an 8% reduced odds of cervical neoplasm (34609,98771).
• Chronic fatigue syndrome (CFS). Although there is interest in using oral vitamin C for CFS, there is insufficient reliable information about the clinical effects of vitamin C for this condition.
• Colistin-induced nephrotoxicity. It is unclear if intravenous vitamin C helps to prevent nephrotoxicity from colistin. Details: A small clinical study shows that intravenous administration of vitamin C 2 grams every 12 hours along with colistin for around 9-10 days does not prevent nephrotoxicity when compared with colistin therapy alone (99839). However, this study was limited by a lack of statistical power to detect differences between the study groups.
• Contrast induced nephropathy. It is unclear if oral vitamin C helps to prevent contrast-induced nephropathy (CIN). Details: Some clinical research shows that taking vitamin C before and after coronary angiography reduces the risk of developing CIN by 33% to 55% when compared with placebo in patients with renal dysfunction (12234,90421). However, other clinical evidence published since 2012 suggests that vitamin C given orally and/or intravenously before and after angiography does not reduce the risk of CIN compared with control in high-risk patients with chronic renal insufficiency or diabetes (91232,91236,90410,90425). Reasons for the discrepancies are not entirely clear. However, it is possible that the lack of significant benefit from vitamin C in the latter studies results from the fact that incidences of CIN have become less common than in the past due to avoidance of dehydration, use of smaller catheters, and use of contrast agents with reduced nephrotoxicity (90429).
• Coronary artery bypass graft (CABG) surgery. It is unclear if intravenous vitamin C helps to improve patient outcomes after CABG surgery. Details: A small clinical study shows that giving vitamin C 5 grams intravenously (IV) before anesthesia induction and 5 grams in the cardioplegia solution used during surgery shortens the length of stay in the intensive care unit (ICU) by about 8 hours (102127). However, some limited research suggests that IV vitamin C does not resolve cardiac surgery complications. A small clinical study in patients with vasoplegia after receiving CABG and other cardiac surgeries shows that receiving IV vitamin C 1.5 grams every 6 hours after being admitted to the ICU does not improve vasoplegia when compared with control (102981).
• Delirium. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in adults with septic shock has found that receiving intravenous thiamine 400 mg daily with vitamin C 6 grams daily, both in divided doses, is not associated with reduced delirium when compared with control (103001).
• Dental plaque. It is unclear if vitamin C in a chewing gum helps to reduce dental plaque formation. Details: A small clinical study in patients with calculus shows that chewing 10 pieces of gum, each containing 60 mg of vitamin C, daily for 3 months reduces the formation of dental calculus, visible plaque, and the number of bleeding sites when compared not chewing gum (83303). The validity of this finding is limited by a lack of placebo group.
• Depression. It is unclear if oral vitamin C is beneficial for the treatment or prevention of depression. Details: A small clinical study in children and adolescents shows that taking vitamin C 500 mg orally twice daily in combination with fluoxetine 10-20 mg daily for 6 months reduces most symptoms of major depressive disorder when compared with taking fluoxetine alone (90404). However, a small clinical study in adults shows that taking vitamin C up to 1000 mg daily for 2 months does not improve the response rate or decrease symptoms of depression in adults also taking citalopram when compared with citalopram alone (96708). Reasons for these conflicting results may relate to the age of the patients, study duration, or differences in antidepressant medication being taken. One clinical guideline also provisionally recommends against the use of oral vitamin C to treat patients with depression based on low-quality evidence (110318). Some research has also evaluated vitamin C intake for the prevention of depression. A secondary analysis of pre- and peri-menopausal adults enrolled in the Study of Women's Health Across the Nation (SWAN) program suggests that vitamin C intake is inversely associated with depressive symptoms. This association persisted regardless of age, race, physical activity, body mass index, antidepressant use or menopausal status (108083). The validity of these findings is limited due to the secondary nature of this study; additionally, follow-up time is unclear.
• Diabetes. It is unclear if oral vitamin C prevents diabetes. Some low-quality research suggests that vitamin C might improve glycemic control in patients with diabetes. Details: Population research has not found a link between dietary vitamin C and the risk of developing type 2 diabetes (14004). However, low certainty clinical research has found some benefit of taking vitamin C supplements for glycemic control. Two meta-analyses of several small, heterogeneous clinical studies in patients with type 2 diabetes show that taking vitamin C 200-3000 mg daily for 2-48 weeks reduces fasting blood glucose by approximately 11 mg/dL (112478) and glycated hemoglobin (HbA1c) by an average of 0.5% when compared with placebo, standard treatment, or no treatment (105461,112478). Subgroup analyses suggest that durations of supplementation longer than 12 weeks show greater glycemic benefit, and although one meta-analysis suggests there is no dose-response relationship (105461), another meta-analysis suggests that doses of vitamin C 1000 mg and higher are most beneficial for improving glycemic indices (112478). Some research has evaluated the effects of vitamin C supplementation on the lipid profile in patients with diabetes, with mixed findings. One meta-analysis of 17 small clinical studies shows that taking vitamin C 200-3000 mg daily for 2 to 48 weeks improves levels of triglycerides and total cholesterol, but not low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol. Subgroup analysis suggests that study durations of at least 12 weeks show greater benefit (106621). However, two other meta-analyses in patients with diabetes, one of 16 small heterogenous clinical studies and one of 11 small clinical studies, show no clinically important improvement in lipid levels after vitamin C supplementation (105461,105464).
• Dry mouth. Oral vitamin C has only been evaluated in combination with vitamin E; its effect when used alone is unclear. Details: A small clinical trial in patients receiving radiotherapy for head and neck cancer shows that taking vitamin E 100 IU and vitamin C 500 mg twice daily for an average of 3 months improves dry mouth when compared to baseline (99080). The validity of these results is limited by the lack of comparison with a control group.
• Endometrial cancer. Increased dietary vitamin C has been linked to reduced risk of endometrial cancer. Details: Population research has found that intake of vitamin C from dietary sources is associated with a slightly decreased risk of endometrial cancer when compared with control. However, this benefit is not observed when results from a prospective cohort study are assessed (34578).
• Endometriosis. Oral vitamin C has only been evaluated in combination with vitamin E; its effect when used alone is unclear. Details: A small clinical study in patients with endometriosis and pelvic pain shows that taking vitamin C 1000 mg and vitamin E 800 IU daily for 8 weeks improves dysmenorrhea, dyspareunia, and chronic pelvic pain scores when compared with placebo. Vitamin C and vitamin E supplementation also reduces some biochemical markers of oxidative stress when compared with placebo (106622).
• Endoscopy-associated adverse effects. It is unclear if a topical vitamin C spray reduces mucosal irritation in patients undergoing Lugol chromoendoscopy. Details: A small clinical trial in patients receiving a Lugol chromoendoscopy shows that spraying a vitamin C 2% solution after the application of the Lugol iodine 2% solution reduces the severity of mucosal irritation, heartburn, and pain when compared with using a normal saline spray after the Lugol iodine 2% solution (104030).
• Esophageal cancer. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Population research has found that higher dietary intake of vitamin C is associated with reduced odds of esophageal adenocarcinoma. A 50 gram increase in dietary vitamin C intake is associated with a 13% reduced odds of esophageal cancer (34551,98770). However, a meta-analysis of clinical research shows that taking a vitamin C supplement in combination with beta-carotene and vitamin E does not reduce the risk of esophageal cancer (34581).
• Exercise-induced asthma. Small clinical studies suggest that oral vitamin C may modestly improve symptoms in patients with exercise-induced asthma. Details: A meta-analysis of the available clinical research shows that vitamin C supplementation might reduce exercise-induced breathlessness when compared with placebo or control. However, the available research is of poor quality, and no clear conclusions can be drawn regarding its benefits for exercise-induced asthma (90409).
• Exercise-induced muscle damage. It is unclear if oral vitamin C is beneficial in exercise-induced muscle damage. Details: A small clinical study in healthy females shows that taking vitamin C 1000 mg before moderate intensity cycling does not prevent muscle damage when compared with placebo (99837). Another small clinical study in endurance-trained runners shows that taking vitamin C 1000 mg and vitamin E (as alpha-tocopherol) 235 mg 2 hours prior to an exercise protocol does not reduce delayed onset muscle soreness or improve other markers of exercise-induced muscle damage when compared with placebo (109961).
• Gallbladder disease. It is unclear if oral vitamin C reduces the risk of gallbladder disease. Details: Cross-sectional epidemiological evidence has found that vitamin C supplementation and increased vitamin C serum levels are associated with a decreased risk of developing gallbladder disease in females, but not males (5877).
• Gastric cancer. It is unclear if dietary or supplemental vitamin C reduces the risk of gastric cancer. Details: Most population research has not found an association between DIETARY intake of vitamin C and gastric cancer risk (9194,10822,10819,90083). Also, clinical research shows that taking vitamin C supplements in combination with other antioxidants does not reduce the risk of gastric cancer or precancerous gastric lesions (14447,34581,90085). However, some research suggests that it might be associated with a reduced risk for specific forms of gastric cancer (9838,90083). One clinical study shows that taking vitamin C orally 500 mg daily for 6 months after eradication of Helicobacter pylori infection decreases the incidence of precancerous changes in stomach tissue when compared with no treatment (10359). Also, other clinical research shows that taking vitamin C orally 1 gram daily helps promote the regression of precancerous gastric lesions in people at high risk for gastric cancer (2579). In 2009, the US Food and Drug Administration (FDA) determined that it would allow a qualified health claim stating that vitamin C supplements may reduce the risk of gastric cancer. However, the FDA has concluded that it is highly uncertain that vitamin C supplements actually reduce the risk of gastric cancer (102332).
• Gastritis. There is limited evidence on the oral use of vitamin C in omeprazole-induced corpus gastritis. Details: A small clinical study shows that taking vitamin C orally 1200 mg daily along with omeprazole decreases corpus gastritis associated with omeprazole therapy in patients with H. pylori infection (10360).
• Gout. It is unclear if oral vitamin C helps to prevent or manage gout. Details: Population research in men has found that taking vitamin C 500-1500 mg daily from the diet and/or supplements is associated with up to a 34% reduced risk of gout when compared with less than 250 mg daily (16755). Also, men who ingest over 500 mg of vitamin C daily from the diet and supplements have serum uric acid levels that are slightly lower than men who consume less than 90 mg daily (16820). However, taking supplemental vitamin C 500 mg daily for 8 weeks does not seem to lower serum uric acid levels in patients who already have gout (90423).
• Hearing loss. There is limited evidence on the intravenous use of vitamin C in idiopathic sudden sensorineural hearing loss. It is unclear if dietary vitamin C intake can affect the risk of hearing loss. Details: A small clinical study in patients with idiopathic sudden sensorineural hearing loss shows that receiving intravenous high-dose vitamin C 200 mg/kg daily in combination with steroid therapy for 10 days, followed by oral vitamin C 2000 mg daily for 30 days, increases recovery rate two-fold and modestly improves hearing threshold levels when compared with receiving steroid therapy only (90417). In addition, population research in females has found that high dietary intake of vitamin C is associated with a 22% increased risk of developing self-reported hearing loss over a 22-year period when compared with low intake (109807).
• Heart transplant complications. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that a combination of vitamin C 500 mg and vitamin E 400 IU, taken twice daily for 1 year starting within the first 2 years after cardiac transplant, reduced the progression of vasculopathy as measured by intravascular ultrasonography (IVUS) when compared with placebo. This suggests that the combination may help slow the progression of CAV (82826).
• Hepatitis C. It is unclear if oral vitamin C is beneficial in patients with hepatitis C. Details: A small clinical study in patients with confirmed hepatitis C shows that taking vitamin C 1000 mg daily with conventional therapy (sofosbuvir plus daclatasvir) for 4 weeks improves serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and albumin when compared with conventional therapy alone (109463).
• HIV/AIDS. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small, low-quality study in men with HIV shows that taking vitamin C 250 mg daily in combination with vitamin A, beta-carotene, vitamin E, selenium, and coenzyme Q10 does not improve viral load, although it seems to improve markers of oxidative stress when compared to baseline. However, a 1000 mg dose of vitamin C, as well as higher doses of the other antioxidants, do not seem to provide any additional effect (9830).
• HIV transmission. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in HIV-positive mothers shows that taking vitamin B, vitamin C, and vitamin E daily during pregnancy and while breast-feeding for 20 weeks seems to reduce child mortality and HIV transmission through breast milk when compared with taking vitamin A (9801).
• Hyperphosphatemia. Intravenous vitamin C might be beneficial for reducing phosphate levels in patients with end-stage renal disease. Details: A small clinical study in hemodialysis patients with elevated phosphorus levels suggests that administering vitamin C 500 mg intravenously three times weekly for 8 weeks reduces phosphorus levels about seven-fold when compared with placebo (90414).
• Idiopathic interstitial pneumonia. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with idiopathic pulmonary fibrosis, a form of idiopathic interstitial pneumonia, shows that taking a combination of vitamin C 250 mg every other day, vitamin D 50,000 IU daily, and vitamin E 200 IU daily for 12 weeks improves some, but not all, measures of lung function and reduces markers of inflammation and oxidative stress when compared to baseline (109464). The validity of these findings is limited by a lack of placebo control group.
• Infertility. It is unclear if oral vitamin C is beneficial in anovulatory females. Details: A very small clinical study suggests that taking vitamin C 400-1000 mg daily might improve fertility, resulting in ovulation and pregnancy in some anovulatory females, when compared with baseline (14018). The validity of these findings is limited by the small study size and lack of a comparator group.
• Male infertility. It is unclear if oral or intravenous vitamin C is beneficial in males with infertility. Details: A meta-analysis of three small, low-quality clinical trials in males with infertility shows that taking vitamin C up to 1000 mg daily for up to 12 weeks can improve sperm count, motility, and vitality, but does not seem to increase semen volume or sperm concentration, when compared with control (109461). It is unclear if vitamin C can increase pregnancy rates, as these studies did not assess this outcome. A retrospective study in males with or without varicocele-related infertility has found that taking a specific combination product containing vitamin C 90 mg, zinc 10 mg, L-carnitine fumarate 1725 mg, acetyl-L-carnitine 500 mg, coenzyme Q10 20 mg, folic acid 0.2 mg, selenium 0.05 mg, and vitamin B12 0.015 mg (Proxeed Plus, Sigma-Tau) orally twice daily for 6 months improves sperm count, sperm concentration, and sperm motility when compared with baseline. Improvement in semen parameters were greatest in subjects with more severe varicoceles. The validity of this study is limited by the lack of a comparator group (111296).
• Mastalgia. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with mastalgia shows that taking a combination of vitamin C 100 mg, vitamin B12, and gamma-linolenic acid daily for 12 weeks does not improve the proportion of patients with minimal or no pain when compared with placebo (111059).
• Melasma. It is unclear if topical vitamin C is beneficial in patients with melasma. Details: A small clinical study in patients with bilateral symmetrically distributed facial melasma shows that topical application of 0.5 mL of vitamin C (Cosmotech, Alpha Medical Cosmotech) following dermapen microneedling every 2 weeks for 6 weeks is similarly effective to tranexamic acid for improving melasma severity and pigmented, but not vascular, findings on dermoscopic examination (106939).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral vitamin C is beneficial in patients with NAFLD. Details: A clinical study in patients with NAFLD shows that taking vitamin C 250 mg, 1000 mg, or 2000 mg daily for 12 weeks improves some biochemical markers of liver health and glucose metabolism when compared with baseline. However, the improvement from baseline was similar between groups (106942).
• Nonalcoholic steatohepatitis (NASH). Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research suggests vitamin C in combination with vitamin E might improve hepatic fibrosis in patients with NASH. However, it does not seem to decrease liver inflammation (14005).
• Non-Hodgkin lymphoma. It is unclear if oral vitamin C reduces the risk of developing diffuse large B-cell lymphoma. Details: In one population study, higher dietary or supplemental intake of vitamin C was associated with a reduced risk of diffuse large B-cell lymphoma, a type of non-Hodgkin lymphoma, when compared with lower intake in postmenopausal adults (90945).
• Oral cancer. It is unclear if oral vitamin C reduces the risk of developing oral cancer. Details: Population research has found that higher dietary intake of vitamin C is associated with a reduced risk of oral cancer (10821). However, clinical research has not shown benefit with oral vitamin C supplements. A small clinical trial in Japanese adults with oral leukoplakia shows that taking vitamin C 500 mg and beta-carotene 10 mg daily for 12 months does not reduce the development of oral cancer over 5 years when compared with vitamin C 50 mg daily (91384).
• Oral leukoplakia. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in Japanese adults with oral leukoplakia shows that taking vitamin C 500 mg and beta-carotene 10 mg daily for 12 months does not improve leukoplakia symptoms or reduce the development of oral cancer over 5 years when compared with vitamin C 50 mg daily (91384).
• Osteoarthritis. It is unclear if dietary vitamin C reduces the risk of developing osteoarthritis. Details: Observational research has found that increased vitamin C from dietary sources is associated with a reduced risk of cartilage loss and disease progression in people with osteoarthritis (5881).
• Osteoporosis. It is unclear if dietary vitamin C improves bone density or reduces fracture risk in patients at risk for osteoporosis. Details: Some cross-sectional observational research in postmenopausal patients without a history of smoking or estrogen use has found that higher serum vitamin C levels are associated with lower bone mineral density (9828). However, other observational research in a larger population of adults at risk for osteoporosis has found that higher dietary vitamin C intake is not associated with fracture risk (104415).
• Ovarian cancer. Dietary vitamin C might not affect the risk of ovarian cancer. Details: Epidemiological research has found that dietary vitamin C intake is not linked with ovarian cancer risk (9193,102977).
• Pancreatitis. It is unclear if intravenous vitamin C is beneficial in patients with acute pancreatitis. Details: A small meta-analysis of clinical studies in patients with acute pancreatitis shows that intravenous vitamin C does not improve the odds of developing organ failure when compared with placebo or no intervention. Intravenous vitamin C seems to reduce hospital stay, but not in-hospital mortality (106941).
• Parkinson disease. Dietary vitamin C might not affect the risk of developing this condition. Details: Observational research has found that moderate or high dietary intake of vitamin C is not associated with a reduced risk of Parkinson disease (83316).
• Periodontitis. Oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. It is also unclear if dietary vitamin C reduces the risk of periodontitis. Details: A small clinical study in patients with moderate or advanced periodontitis shows that taking a supplement containing vitamin C 100 mg, alpha-lipoic acid, coenzyme Q10, cranberry extract, grapeseed extract, selenium, 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). It is unclear if these effects are due to vitamin C, other ingredients, or the combination. There is also interest in whether dietary vitamin C intake impacts the risk of periodontitis. Observational research in US adults has found that individuals with dietary intake of vitamin C in the third quartile, but not the second or fourth quartiles, have lower odds of periodontitis when compared with vitamin C intake in the lowest quartile. Furthermore, the investigators identified a non-linear relationship between vitamin C intake and periodontitis risk, suggesting that individuals with intakes either much lower or much higher than 158 mg daily are at increased risk of developing periodontitis (109958).
• Peripheral arterial disease (PAD). It is unclear if dietary vitamin C helps to reduce the risk of developing PAD. Details: In females, epidemiological evidence has found that dietary intake of vitamin C of 142 mg daily or greater is associated with a 36% reduced risk of PAD when compared with lower intake levels of less than 80 mg daily (10130).
• Physical performance. It is unclear if oral vitamin C helps to improve physical performance and muscle strength in older people. Details: Population research has found that higher intake of dietary vitamin C is associated with improved physical performance and muscle strength in elderly people (14006). In contrast, a small clinical study in elderly men undergoing strength training shows that taking vitamin C 1000 mg and vitamin E 258IU daily for 12 weeks does not increase strength, and might even attenuate increases in muscle mass, when compared with strength training alone (96701).
• Pneumonia. It is unclear if oral vitamin C helps to prevent pneumonia. Details: A meta-analysis of two small, low-quality clinical studies in children shows that vitamin C does not seem to reduce the occurrence of pneumonia when compared to control (104033).
• Postoperative recovery. It is unclear if oral or intravenous vitamin C improves postoperative recovery. Details: Meta-analyses of clinical research show that oral or intravenous vitamin C can shorten the duration of hospitalization after cardiac surgery when compared with control (91233,96703). However, other research shows no decrease in intensive care or hospital stay with vitamin C supplementation (96705). A meta-analysis of 37 clinical trials in adults undergoing low- to high-risk noncardiac surgery (i.e., orthopedic, abdominal, gynecologic, or kidney transplantation), shows that receiving perioperative vitamin C, either orally or intravenously, does not improve duration of hospitalization or overall mortality when compared with control (108087). There's also some limited evidence that vitamin C might reduce postoperative pulmonary complications such as lung infection, pleural effusion, and pneumothorax. A small clinical trial in low-risk cardiac surgery patients shows that receiving intravenous vitamin C 1 gram 10 minutes after anesthesia might slightly reduce the rate of postoperative pulmonary complications when compared with receiving a saline injection (104034).
• Premature rupture of membranes (PROM). Oral vitamin C seems to reduce the risk of PROM in some patients; however, the addition of oral vitamin E seems to negate any benefit. Details: A meta-analysis of clinical research shows that taking vitamin C alone decreases the risk of both term and preterm PROM by 45% and 34%, respectively, when compared with placebo or control (96707). Also, a more recent clinical study in patients with a history of PROM shows that taking vitamin C 100 mg daily, starting at 14 weeks' gestation, increases the gestational age at recurrent PROM by around 1 week and increases the gestational age at birth by around 1.3 weeks when compared with placebo (109960). Taking vitamin C in combination with vitamin E, however, does not seem to reduce the risk of term or preterm PROM; some research suggests that it might even increase the risk of non-preterm PROM (83472,96707). However, other research shows that taking vitamin C 1000 mg plus vitamin E 400 IU daily, beginning at 24 to 34 weeks gestation and continuing until delivery, may help increase the latency period until delivery by 5 days and increase gestational age at delivery by almost 1 week when compared with placebo in patients with preterm PROM (90078).
• Pressure ulcers. It is unclear if oral vitamin C, when used alone or in combination with other ingredients, can improve the healing of pressure ulcers. Details: A small clinical study in institutionalized patients with pressure ulcers shows that taking vitamin C 500 mg twice daily for 12 weeks does not improve wound closure or increase healing rates when compared with vitamin C 10 mg twice daily (83617). Oral vitamin C has also been evaluated in combination with other ingredients for the treatment of grade II-IV pressure ulcers. Two small clinical studies in hospitalized patients with pressure ulcers shows that administering an oral nutritional supplement enriched with vitamin C, L-arginine, and zinc improves ulcer healing when compared with a standard diet (31953,87173). Also, clinical research in patients living in long-term care facilities shows that taking an oral nutritional supplement enriched in protein, vitamin C, L-arginine, and zinc daily for 9 weeks reduces ulcer area and decreases oozing when compared to baseline (32045). The validity of this finding is limited by the lack of a comparator group.
• Radiation proctopathy. Oral vitamin C has only been evaluated in combination with vitamin E; its effect when used alone is unclear. Details: A small clinical study in patients with chronic radiation proctitis shows that vitamin C 500 mg plus vitamin E 400 IU three times daily might improve symptoms when compared with baseline (9825). The validity of these findings is limited by the lack of a comparator group.
• Renal cell carcinoma. It is unclear if increased dietary intake of vitamin C helps to reduce the risk of renal cell carcinoma. Details: Population research has found that increased dietary intake of vitamin C is associated with a 12% reduced risk of renal cell carcinoma (98779).
• Respiratory tract infections. It is unclear if oral vitamin C is beneficial for preventing respiratory tract infections or reducing the duration of these infections. Details: A meta-analysis of clinical research in children and adults shows that, when compared with placebo, oral vitamin C supplementation reduces the average number of symptomatic days per individual, but does not reduce the average symptom days per respiratory episode. Also, vitamin C intake does not reduce the incidence or severity of respiratory disease or improve recovery in hospitalized patients with respiratory tract infections (108077). The validity of this trial is limited by the high heterogeneity of included studies, which evaluated various vitamin C regimens, ranging from 100 mg to 8 grams daily, as preventive therapy or as an adjuvant to active treatment. A clinical study in children aged 3-10 years shows that taking vitamin C 50 mg in combination with a specific product (Lab4) containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium animalis subsp. lactis daily for 6 months reduces the incidence of cough and sore throat by 16% and 20%, respectively, when compared with placebo. However, it did not improve total symptoms, nasal congestion, nasal discharge, or sneezing. Also, aside from a 33% reduction in the average number of days with a sore throat, daily supplementation does not reduce the duration of individual symptoms or total symptoms (106943). It is unclear if these effects are due to vitamin C, the probiotics, or the combination.
• Restless legs syndrome (RLS). It is unclear if oral vitamin C helps to reduce symptoms of stress. Details: A small clinical study in hemodialysis patients with RLS shows that taking vitamin C 200 mg daily, alone or in combination with vitamin E 400 mg, for 8 weeks reduces the severity of RLS when compared with placebo (90093). More research is needed to determine if vitamin C is beneficial in treating RLS that is not associated with hemodialysis.
• Sunburn. Topical and oral vitamin C has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Taking vitamin C orally in combination with vitamin E seems to prevent ultraviolet (UV) radiation-induced erythema (sunburn) (4715,4716). Vitamin C in combination with high dose oral RRR-alpha-tocopherol (natural vitamin E) seems to protect against skin inflammation after exposure to UV radiation (4715). Also, applying topical vitamin C in combination with topical vitamin E and melatonin seems to provide modest photoprotective effects when used prior to UV exposure. However, it has no effect when used during or after UV exposure (4713,4714).
• Stress. It is unclear if oral vitamin C helps to reduce symptoms of stress. Details: A small clinical study in healthy adults shows that taking vitamin C 3000 mg daily for 14 days modestly reduces blood pressure and subjective stress response to psychological stress when compared with placebo (10353).
• Stroke. Observational research has found that although taking vitamin C supplements does not seem to be beneficial, eating more vitamin C-rich food is linked with reduced risk of stroke. Details: Lower plasma levels of vitamin C have been associated with increased stroke risk (90408). Additionally, population research has found that higher dietary intake of vitamin C is associated with a 8% to 19% reduction in stroke risk when compared to lower intake (90408,109779). This reduction appears to be dose-dependent, with each 100 mg/day increase in dietary vitamin C intake associated with about a 17% reduction (90408). However, taking vitamin C supplements has not been found to be associated with reduced stroke risk (1449,90408).
• Tetanus. It is unclear if intravenous vitamin C helps to reduce symptoms of tetanus. Details: A low quality clinical trial in children and young adults with tetanus shows that intravenous vitamin C 1 gram daily along with conventional treatment reduces fatality when compared to control (21539).
• Tooth extraction. It is unclear if oral vitamin C is beneficial for reducing pain or improving healing after tooth extraction. Details: A small clinical study in healthy patients aged 14-41 years who are undergoing bilateral premolar extraction shows that taking vitamin C 200 mg three times daily, beginning immediately after extraction and continued for 10 days, improves pain on days 1-3, and may reduce mesio-distal wound size between days 1 and 7, when compared with placebo, but not when compared with vitamin C 500 mg three times daily. A dose of 500 mg three times daily did not improve pain scores or extraction wound healing when compared with placebo (108084). The validity of this trial is limited by the short duration of treatment; additionally, this study did not report baseline vitamin C levels.
• Urinary tract infections (UTIs). Although there is interest in using oral vitamin C for UTIs, there is insufficient reliable information about the clinical effects of vitamin C for this condition.
• Vascular dementia. It is unclear if oral vitamin C reduces the risk of vascular dementia. Details: Population research has found that supplemental intake of vitamin C and vitamin E is associated with a reduced risk of vascular dementia in Japanese-American men (4636). However, when cases in which dementia was diagnosed prior to the study are excluded from data analysis, intake of vitamin C and vitamin E is not associated with a reduced risk of vascular dementia in these patients (9824).
• Wound healing. It is unclear if oral vitamin C improves the healing of chronic foot ulcers. It is also unclear if intravenous vitamin C improves healing of surgical wounds after total abdominal hysterectomy. Details: A very small clinical study in adults with chronic foot ulcers shows that taking slow-release vitamin C 500 mg daily for 8 weeks seems to result in a median of 100% ulcer healing, compared with a median of 14% ulcer healing in patients taking glucosamine 1000 mg daily (105456). This finding is limited due to the small and heterogeneous patient population, which included patients with diabetes, vascular disease, and/or vitamin C deficiency. Another small clinical study in patients undergoing total abdominal hysterectomy shows that administration of intravenous vitamin C 1 gram the night before surgery and 1 gram during surgery does not reduce the rate of surgical site infection or wound dehiscence when compared with placebo (109465). However, this study may not have been adequately powered to detect differences between groups. More evidence is needed to rate vitamin C for these uses.

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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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LIKELY SAFE ...when used orally, topically, intramuscularly, or intravenously and appropriately. Vitamin C is safe when taken orally in doses below the tolerable upper intake level (UL). Tell patients not to exceed the UL of 2000 mg daily (1959,4713,4714,4844). ...when used intravenously or intramuscularly and appropriately. Injectable vitamin C is an FDA-approved prescription product (15).

POSSIBLY UNSAFE ...when used orally in excessive doses. Doses greater than the tolerable upper intake level (UL) of 2000 mg daily can significantly increase the risk of adverse effects such as osmotic diarrhea and gastrointestinal upset (4844).

CHILDREN: LIKELY SAFE
when used orally and appropriately (4844,10352,14443).

CHILDREN: POSSIBLY UNSAFE
when used orally in excessive amounts. Tell patients not to use doses above the tolerable upper intake level (UL) of 400 mg daily for children ages 1 to 3 years, 650 mg daily for children 4 to 8 years, 1200 mg daily for children 9 to 13 years, and 1800 mg daily for adolescents 14 to 18 years. Higher doses can cause osmotic diarrhea and gastrointestinal upset (4844).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately (4844).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses. Tell patients over age 19 not to use doses exceeding the UL of 2000 mg daily when pregnant or breast-feeding and for those 14-18 years of age not to use doses exceeding 1800 mg daily when pregnant or breast-feeding. Higher doses can cause osmotic diarrhea and gastrointestinal upset. Large doses of vitamin C during pregnancy can also cause newborn scurvy (4844); avoid using.

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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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ACETAMINOPHEN (Tylenol, others) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Probable •  Level of Evidence = B High-dose vitamin C might slightly prolong the clearance of acetaminophen.  Details A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases (6451). This effect is not likely to be clinically significant.

ALKYLATING AGENTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.  Details The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

ALUMINUM Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.  Details Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption (10549,10550,10551,21556). In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely (10549). Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

ANTITUMOR ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.  Details The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

ASPIRIN Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Acidification of the urine by vitamin C might increase aspirin levels.  Details It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction is not clinically significant.

CHOLINE MAGNESIUM TRISALICYLATE (Trilisate) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.  Details It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046,4531). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Vitamin C might increase blood levels of estrogens.  Details Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products (129,130,11161). It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall (129,11161). When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements (11161). Monitor these patients for estrogen-related side effects.

FLUPHENAZINE (Prolixin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, vitamin C might decrease levels of fluphenazine.  Details In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started (11017). The mechanism is not known, and there is no further data to confirm this interaction.

INDINAVIR (Crixivan) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Vitamin C can modestly reduce indinavir levels.  Details One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown (11300,93578).

LEVOTHYROXINE (Synthroid, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Vitamin C can increase levothyroxine absorption.  Details Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH (102978).

NIACIN Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = A Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.  Details A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients 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% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

SALSALATE (Disalcid) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Acidification of the urine by vitamin C might increase salsalate levels.  Details It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D High-dose vitamin C might reduce the levels and effectiveness of warfarin.  Details Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption (11566). There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time (9804,9806). Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant (9805,9806,11566,11567). However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR) (90942). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

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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.

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General ...Orally, intravenously, and topically, vitamin C is well-tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, esophagitis, heartburn, headache, osmotic diarrhea, nausea, vomiting. Kidney stones have been reported in those prone to kidney stones. Adverse effects are more likely to occur at doses above the tolerable upper intake level of 2 grams daily.
Topically: Irritation and tingling.
Serious Adverse Effects (Rare):
Orally: There have been rare case reports of carotid inner wall thickening after large doses of vitamin C.
Intravenously: There have been case reports of hyperoxalosis and oxalate nephropathy following high-dose infusions of vitamin C.

Cardiovascular ...Evidence from population research has found that high doses of supplemental vitamin C might not be safe for some people. In postmenopausal adults with diabetes, supplemental vitamin C intake in doses greater than 300 mg per day is associated with increased risk of cardiovascular mortality. However, dietary intake of vitamin C is not associated with this risk. Also, vitamin C intake is not associated with an increased risk of cardiovascular mortality in patients without diabetes (12498).
Oral supplementation with vitamin C has also been associated with an increased rate of carotid inner wall thickening in men. There is preliminary evidence that supplemental intake of vitamin C 500 mg daily for 18 months can cause a 2.5-fold increased rate of carotid inner wall thickening in non-smoking men and a 5-fold increased rate in men who smoked. The men in this study were 40-60 years old (1355). This effect was not associated with vitamin C from dietary sources (1355).
There is also some concern that vitamin C may increase the risk of hypertension in some patients. A meta-analysis of clinical research suggests that, in pregnant patients at risk of pre-eclampsia, oral intake of vitamin C along with vitamin E increases the risk of gestational hypertension (83450). Other clinical research shows that oral intake of vitamin C along with grape seed polyphenols can increase both systolic and diastolic blood pressure in hypertensive patients (13162).

Dental ...Orally, vitamin C, particularly chewable tablets, has been associated with dental erosion (83484).

Dermatologic ...Topically, vitamin C might cause tingling or irritation at the site of application (6166). A liquid containing vitamin C 20%, red raspberry leaf cell culture extract 0.0005%, and vitamin E 1% (Antioxidant and Collagen Booster Serum, Max Biocare Pty Ltd.) has been reported to cause mild tingling and skin tightness (102355). It is unclear if these effects are due to vitamin C, the other ingredients, or the combination.

Gastrointestinal ...Orally, the adverse effects of vitamin C are dose-related and include nausea, vomiting, esophagitis, heartburn, abdominal cramps, gastrointestinal obstruction, and diarrhea. Doses greater than the tolerable upper intake level (UL) of 2000 mg per day can increase the risk of adverse effects such as osmotic diarrhea and severe gastrointestinal upset (3042,4844,96707,104450). Mineral forms of vitamin C, such as calcium ascorbate (Ester-C), seem to cause fewer gastrointestinal adverse effects than regular vitamin C (83358). In a case report, high dose intravenous vitamin C was associated with increased thirst (96709).

Genitourinary ...Orally, vitamin C may cause precipitation of urate, oxalate, or cysteine stones or drugs in the urinary tract (10356). Hyperoxaluria, hyperuricosuria, hematuria, and crystalluria have occurred in people taking 1 gram or more per day (3042,90943). Supplemental vitamin C over 250 mg daily has been associated with higher risk for kidney stones in males. There was no clear association found in females, but the analysis might not have been adequately powered to evaluate this outcome (104029). In people with a history of oxalate kidney stones, supplemental vitamin C 1 gram per day appears to increase kidney stone risk by 40% (12653). A case of hematuria, high urine oxalate excretion, and the presence of a ureteral stone has been reported for a 9-year-old male who had taken about 3 grams of vitamin C daily since 3 years of age. The condition resolved with cessation of vitamin C intake (90936).

Hematologic ...Prolonged use of large amounts of vitamin C can result in increased metabolism of vitamin C; subsequent reduction in vitamin C intake may precipitate the development of scurvy (15). In one case, a patient with septic shock and a large intraperitoneal hematoma developed moderate hemolysis and increased methemoglobin 12 hours after a high-dose vitamin C infusion. The patient received a blood transfusion and the hemolysis resolved spontaneously over 48 hours (112479).

Neurologic/CNS ...Orally, the adverse effects of vitamin C are dose-related and include fatigue, headache, insomnia, and sleepiness (3042,4844,83475,83476).

Renal ...Hyperoxalosis and oxalate nephropathy have been reported following high-dose infusions of vitamin C. Hyperoxalosis and acute kidney failure contributed to the death of a 76-year-old patient with metastatic adenocarcinoma of the lung who received 10 courses of intravenous infusions containing vitamins, including vitamin C and other supplements over a period of 1 month. Dosages of vitamin C were not specified but were presumed to be high-dose (106618). In another case, a 34-year-old patient with a history of kidney transplant and cerebral palsy was found unresponsive during outpatient treatment for a respiratory tract infection. The patient was intubated for acute hypoxemic respiratory failure, initiated on vasopressors, hydrocortisone, and antibacterial therapy, and received 16 doses of vitamin C 1.5 grams. Serum creatinine level peaked at greater than 3 times baseline and the patient required hemodialysis for oliguria and uncontrolled acidosis. Kidney biopsy revealed oxalate nephropathy with concomitant drug-induced interstitial nephritis (106625). In another case, a 41-year-old patient with a history of kidney transplant presented with fever, nausea, and decreased urine output 4 days after receiving intravenous vitamin C 7 grams for urothelial carcinoma. Serum creatinine levels increased from 1.7 mg/dL to 7.3 mg/dL over those 4 days, and hemodialysis was initiated 3 days after admission due to anuria. Renal biopsy confirmed the diagnosis of acute oxalate nephropathy (109962).

Other ...Intravenously, hypernatremia and falsely elevated ketone levels is reported in a patient with septic shock and chronic kidney disease after a high-dose vitamin C infusion. The hypernatremia resolved over 24 hours after cessation of the infusion (112479).

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