GinkgoPlus for Memory by Aboca S.p.a.

Alzheimer disease. It is unclear if oral bacopa is beneficial in patients with Alzheimer disease. Details: A small clinical study in patients with Alzheimer disease or mild cognitive impairment shows that taking bacopa 300 mg daily for 12 months does not improve measures of cognitive function or memory when compared with donepezil or baseline measures (109623).
Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral bacopa is beneficial in children with ADHD. Details: A small clinical study in boys 6-14 years of age with symptoms consistent with ADHD but without an official diagnosis shows that taking a specific bacopa supplement (KeenMind - CDRI 08, Flordis) for 14 weeks does not improve symptoms of ADHD but improves some cognitive outcomes including error-making, cognitive flexibility, executive functioning, and sleep when compared with placebo. Bacopa 160 mg was given once daily in those weighing 20-35 kg and twice daily in those over 35 kg (109625). However, another small, open-label study in children aged 6-12 years with ADHD shows that taking a different bacopa supplement (BacoMind, Natural Remedies), 225 mg daily for 6 months, improves symptoms such as restlessness, impulsivity, learning problems, and attention deficit when compared to baseline (97603). The validity of these findings is limited by the lack of blinding or comparator group.
Back pain. Although there is interest in using oral bacopa for back pain, there is insufficient reliable information about the clinical effects of bacopa for this condition.
Cognitive function. Bacopa seems to improve some measures of cognitive function, but data are conflicting. Details: A meta-analysis of 9 small clinical studies, along with more recent clinical research, shows that taking bacopa 300-600 mg daily for at least 12 weeks is not associated with improved measures of cognition including working memory, learning rate, recognition of pictures and words, reaction time, or attention when compared with placebo. However, subgroup analysis of this meta-analysis and another small clinical study show some evidence of improved reaction times, verbal learning, total recall, retention, memory, and information processing in healthy adults when compared with placebo (10058,17946,33287,97605,109624,111520). In children aged 6-8 years old, a very small clinical study shows that taking a syrup containing bacopa extract 350 mg three times daily for 3 months improves visual motor function and immediate memory when compared to baseline (33304). The validity of this finding is limited by the lack of a statistical comparison to the placebo group. Bacopa has also been studied in combination with other ingredients. A study in healthy adults aged 18-60 years shows that taking a single dose of a combination of bacopa 300 mg, American ginseng 100 mg, and coffee fruit extract 100 mg (Bacognize) improves some measures of working memory and attention by a small amount at 45 minutes when compared with placebo (103375). It is unclear if these effects are due to bacopa, other ingredients, or the combination. In contrast, a moderate-sized study in healthy, middle-aged adults shows that taking a combination product containing whole plant bacopa 7.5 grams, gingko biloba, and group B vitamins for 12 weeks does not improve measures of memory, attention, cognition, mood, or stress reactivity when compared with placebo. Subgroup analysis shows a possible benefit of bacopa supplementation on measures of attention in those with an optimal diet at baseline (111334).
Cognitive impairment. It is unclear if oral bacopa is beneficial in patients with cognitive impairment. Details: A small clinical study in patients with mild cognitive impairment or Alzheimer disease shows that taking bacopa 300 mg daily for 12 months does not improve measures of cognitive function or memory when compared with donepezil or baseline (109623).
Congestive heart failure (CHF). Although there is interest in using oral bacopa for CHF, there is insufficient reliable information about the clinical effects of bacopa for this condition.
Depression. It is unclear if oral bacopa is beneficial in patients with depression. Details: Preliminary clinical research in adults with depression who have not responded to citalopram 40 mg daily shows that adding bacopa extract 300 mg twice daily for 4 weeks improves scores on depression rating scales when compared with citalopram alone (103378).
Hypertension. Although there is interest in using oral bacopa for hypertension, there is insufficient reliable information about the clinical effects of bacopa for this condition.
Insomnia. Although there is interest in using oral bacopa for insomnia, there is insufficient reliable information about the clinical effects of bacopa for this condition.
Irritable bowel syndrome (IBS). Bacopa has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with diarrhea-predominant IBS shows that taking a combination of bacopa and bael (Aegel marmalos) reduces symptoms in 65% of patients, compared with 78% of patients taking clidinium bromide, chlordiazepoxide, and blond psyllium, and 33% taking placebo. Neither treatment is more effective than placebo for preventing relapses (10059).
Parkinson disease. It is unclear if oral bacopa is beneficial in patients with Parkinson disease. Details: A very small study in older adults with Parkinson disease taking levodopa shows that taking a specific bacopa extract (Cognitus, Herbarium) 225 mg or 450 mg daily for 90 days does not improve Parkinsonian or systemic symptoms, motor activity, emotional function, or social outcomes when compared with placebo (111523). The validity of these findings is limited by a small sample size and lack of randomization.
Rheumatoid arthritis (RA). Although there is interest in using oral bacopa for RA, there is insufficient reliable information about the clinical effects of bacopa for this condition.
Sexual dysfunction. Although there is interest in using oral bacopa for sexual dysfunction, there is insufficient reliable information about the clinical effects of bacopa for this condition.
Smoking cessation. Oral bacopa has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults in India with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing bacopa 100 mg, ashwagandha, clove, ginger, cowhage, turmeric, and other herbal extracts (Smotect , Smotect India) twice daily for 3 months reduces the number of cigarettes smoked daily and alveolar carbon monoxide and carboxyhemoglobin levels but does not improve lung capacity when compared with placebo (112115). It is unclear if these effects are due to bacopa, other ingredients, or the combination. More evidence is needed to rate bacopa for these uses.

POSSIBLY EFFECTIVE

Irritable bowel syndrome (IBS). A specific strain of oral brewer's yeast seems to be beneficial for some IBS symptoms. Details: A meta-analysis of results from two clinical studies shows that taking the specific brewer's yeast strain CNCM I-3856 500 mg or 1000 mg daily, standardized to 8 billion colony-forming units (CFUs) per gram, for up to 12 weeks might reduce abdominal pain and discomfort and improve stool consistency in patients with constipation-predominant IBS. It seems to take at least one month for any benefits to occur (95611). Another small clinical study shows that taking the same product as 2 billion CFUs twice daily in addition to standard treatment for 8 weeks modestly improves abdominal pain and stool consistency when compared with standard treatment alone. Benefits were evident within 4 weeks and were found in patients with diarrhea-predominant, constipation-predominant, and mixed-type IBS (105170). Additionally, a large clinical trial in patients with constipation-predominant IBS shows that taking the same brewer's yeast product 8 billion CFUs daily for 8 weeks increases the likelihood of abdominal pain response, defined as a 30% or greater reduction in average daily abdominal pain scores, by 33% and improves quality of life scores when compared with placebo. However, no improvements in bloating, flatulence, stool frequency, or stool consistency were reported (111108).

Acne. Although there has been interest in using oral or topical brewer's yeast for acne, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
Allergic rhinitis (hay fever). It is unclear if oral dried, inactive brewer's yeast is beneficial for allergic rhinitis. Details: Preliminary clinical research in adults with seasonal allergies shows that taking a specific dried, inactive brewer's yeast preparation (EpiCor, Embria Health Sciences) 500 mg once daily for 12 weeks reduces the median severity of nasal congestion by 14%, the median severity of rhinorrhea by 19%, and the median number of days with nasal congestion by 12.5 days during weeks of highest pollen counts when compared with placebo. However, taking this brewer's yeast preparation does not appear to reduce ocular symptoms or sneezing. Also, it does not appear to improve nasal or ocular symptoms during weeks in which pollen counts are lower (92821).
Clostridioides difficile infection. Although there has been interest in using oral brewer's yeast for C. difficile infection, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
Diarrhea. Although there has been interest in using oral brewer's yeast for diarrhea, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
Furuncles (boils). Although there has been interest in using oral brewer's yeast for furuncles, there is insufficient reliable information about the clinical effects of brewer's yeast for this condition.
Hypercholesterolemia. It is unclear if oral brewer's yeast is beneficial for hypercholesterolemia. Details: Preliminary clinical research shows that taking brewer's yeast 20 grams, containing chromium 48 mcg, daily for 8 weeks decreases levels of total cholesterol by 24-26 mg/dL and increases levels of high-density lipoprotein (HDL) cholesterol by 5-6 mg/dL when compared to baseline in normocholesterolemic and hypercholesterolemic patients (37178).
Influenza. It is unclear if oral dried, inactive brewer's yeast is beneficial for influenza. Details: Preliminary clinical research shows that taking a specific dried, inactive brewer's yeast preparation (EpiCor, Embria Health Sciences) 500 mg daily for 12 weeks reduces the incidence of common cold or flu-like symptoms by 10% to 20% when compared with placebo in adults with no history of influenza vaccination. Taking this preparation does not appear to reduce the duration or severity of cold or flu-like symptoms that do occur in these patients (92822). However, in patients recently vaccinated for influenza, clinical research shows that taking this same preparation 500 mg daily for 12 weeks reduces the risk of developing symptoms of the common cold or flu by about 11% and reduces the duration of symptoms that develop by 0.85 days when compared with placebo (16117).
Premenstrual syndrome (PMS). Oral brewer's yeast has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking a specific combination product (Sillix Donna, Giuliani) containing folic acid, vitamin B6, vitamin E, various minerals, and brewer's yeast might help reduce scores on the Menstrual Distress Questionnaire (MDS) when compared to baseline (7845). It is unclear if this benefit is due to brewer's yeast or the vitamins and minerals also contained in the preparation. More evidence is needed to rate brewer's yeast for these uses.

POSSIBLY EFFECTIVE

Genital herpes. Oral eleuthero root extract might help to prevent and reduce the severity of genital herpes outbreaks. Details: One clinical study in patients with recurrent genital herpes infections shows that taking a specific eleuthero root extract (Elagen) 400 mg, standardized to contain eleutheroside 0.3%, daily for at least 3 months reduces the frequency, severity, and duration of outbreaks when compared with placebo (730).

Athletic performance. Small clinical studies suggest that oral eleuthero root is not beneficial for improving athletic performance. Details: One study in trained distance runners shows that a specific eleuthero root liquid extract, standardized to eleutherosides B and E content, taken as 3.4 mL daily for 6 weeks, does not affect endurance, performance, or psychological, cardiac, or respiratory parameters when compared with placebo (7522). Small studies in trained athletes or healthy adults show that taking eleuthero 800-1200 mg daily (Endurox) for 1-6 weeks does not seem to have any effect on cycling performance time, respiration, lactate production, or heart rate recovery during cycling, stair-stepping exercise, treadmill, or cycle ergometry when compared with placebo (2335,7600,7601,8994). However, there has been some speculation that a longer duration of supplementation is needed for benefit. One study in recreationally trained athletes shows that taking a specific powdered eleuthero root product 400 mg twice daily for 8 weeks increased cycling endurance time by 23% and maximal oxygen consumption by 12% when compared with placebo. This product was standardized to contain eleutheroside B 0.11% and eleutheroside E 0.12% (17186).
Bipolar disorder. It is unclear if oral eleuthero root is beneficial for bipolar disorder. Details: A small clinical study in Chinese adolescents aged 12-17 years with bipolar disorder shows that taking eleuthero root 750 mg orally three times daily, in conjunction with lithium for 6 weeks, induces similar response rates and remission rates when compared with lithium plus fluoxetine 20 mg (75028). It is not clear how this response rate compares to the use of lithium alone.
Cardiovascular disease (CVD). It is unclear if oral eleuthero fruit is beneficial for preventing the development of CVD. Details: One small clinical study in healthy adults with at least two cardiovascular risk factors shows that taking an aqueous extract of eleuthero fruit 500 mg daily for 12 weeks seems to modestly reduce systolic blood pressure and arterial stiffness, as measured by brachial-ankle pulse wave velocity, when compared with placebo. It did not affect diastolic blood pressure, flow-mediated dilation, or carotid intima-media thickness. Also, taking a higher 1000 mg dose of the same eleuthero extract daily did not have significant effects on any measured parameters (105025).
Chronic fatigue syndrome (CFS). It is unclear if oral eleuthero root is beneficial for CFS. Details: One clinical study in adults with CFS shows that taking eleuthero root extract 2 grams daily for 2 months improves fatigue severity and duration when compared to baseline, but not when compared with placebo (11099).
Cognitive function. It is unclear if oral eleuthero is beneficial for cognitive function. Details: A very small clinical study in middle-aged people shows that taking eleuthero 325 mg twice daily might improve selective memory when compared with placebo (2574). Another very small study in healthy adults shows that taking a combination product containing extracts of eleuthero leaf 203 mg and Drynaria fortunei 20 mg daily for 12 weeks improves figure recall, but not immediate memory or attention, when compared with placebo (102316). It is unclear if this effect is due to eleuthero, Drynaria fortunei, or the combination.
Common cold. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking capsules of a specific combination product containing eleuthero plus andrographis (Kan Jang, Swedish Herbal Institute) orally improves symptoms of the common cold when started within 72 hours of symptom onset. Some symptoms can improve after 2 days of treatment; however, it typically takes 4-5 days of treatment for maximal symptom relief (5784,10795,12380). Some research shows the combination of eleuthero and andrographis relieves cold symptoms better than echinacea or placebo in children (12381). It is unclear if this effect is due to eleuthero, andrographis, or the combination.
Coronavirus disease 2019 (COVID-19). Oral eleuthero extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with a history of COVID-19 infection and current symptoms of long COVID-19 shows that taking a specific combination product containing eleuthero extract 78 mg, rhodiola extract 90 mg, and schisandra extract 300 mg (ADAPT-232/Chisan, Swedish Herbal Institute) twice daily for 2 weeks increases exercise capacity by about 13 minutes but does not reduce the duration of cough, fatigue, headache, pain, or other respiratory problems when compared with placebo (109635). It is unclear if these findings are due to eleuthero, other ingredients, or the combination.
Diabetes. It is unclear if oral eleuthero is beneficial for improving glycemic control in type 2 diabetes. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, decreases fasting glucose by a mean of 36 mg/dL, postprandial blood glucose by a mean of 35 mg/dL, glycated hemoglobin (HbA1c) by a mean of 0.8%, triglycerides by a mean of 106 mg/dL, and total cholesterol by a mean of 21 mg/dL when compared with placebo (91509).
Diabetic neuropathy. It is unclear if oral eleuthero is beneficial for diabetic neuropathy. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, modestly improves subjective symptoms of diabetic neuropathy when compared with placebo (91509).
Dry eye. Oral eleuthero root has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults with dry eye disease shows that taking a specific combination product containing eleuthero root 50 mg, zinc 10 mg, L-carnitine 50 mg, elderberry fruit extract 300 mg, and currant 100 mg (Meramirt CM) once daily improves dry eye symptom scores when compared with no intervention. Contrast sensitivity scores also improved when compared to baseline in the treated group, but not in the control group (111295). It is unclear if these effects are due to eleuthero, other ingredients, or the combination.
Familial Mediterranean fever. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children ages 3-15 years with familial Mediterranean fever shows that taking a specific combination product (ImmunoGuard, Inspired Nutritionals) containing eleuthero, andrographis, schisandra, and licorice for one month reduces the duration, frequency, and severity of disease recurrence when compared with placebo (12382). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
Fibromyalgia. Although there is interest in using oral eleuthero for fibromyalgia, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
Hangover. It is unclear if oral eleuthero root is beneficial for hangovers. Details: One small clinical study in healthy males shows that consuming one bottle of a powdered polysaccharide-rich extract of eleuthero root before and after consuming alcohol modestly reduces the severity of hangover as measured by the Acute Hangover Scale questionnaire score when compared with placebo (91508). However, the validity of these findings is brought into question due to the incomplete study information provided.
Influenza. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with influenza shows that taking a specific combination product containing eleuthero 20-30 mg plus andrographis 178-266 mg (Kan Jang, Swedish Herbal Institute) three times daily for 3-5 days relieves symptoms more quickly than amantadine. This combination product also reduced the risk of post-influenza complications, such as sinusitis or bronchitis, when compared with amantadine (10441). It is unclear if these effects are due to eleuthero, andrographis, or the combination.
Osteoarthritis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules each containing 400 mg of a combination of eleuthero, Panax pseudoginseng, and rehmannia daily for 6 weeks improves physical function in individuals with knee osteoarthritis when compared with placebo. However, the combination does not seem to reduce pain or stiffness when compared with placebo (74950). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
Osteoporosis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in postmenopausal patients shows that taking low-dose calcium and vitamin D3 in combination with a 250 mg blend of rehmannia root and eleuthero stem bark extracts twice daily for 12 months attenuates the loss of spine and femur bone mineral density when compared with placebo or high-dose calcium and vitamin D (75036). It is unclear if this effect is due to eleuthero, rehmannia, or the combination.
Pneumonia. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute, nonspecific pneumonia shows that taking a specific combination product (ADAPT-232), containing eleuthero, rhodiola, and schisandra, as 20 mL twice daily for 10-15 days in conjunction with conventional treatment, reduces the duration of antibiotic treatment and improves quality of life when compared with conventional treatment alone (71152).
Quality of life. It is unclear if oral eleuthero root improves quality of life in older healthy adults. Details: A small clinical study in elderly volunteers shows that taking eleuthero 300 mg daily improves social functioning and mental well-being after 4 weeks of treatment when compared with placebo. However, this improvement was not maintained after 8 weeks of treatment (15586).
Rheumatoid arthritis (RA). Although there is interest in using oral eleuthero for RA, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
Stress. It is unclear if oral eleuthero root is beneficial for stress. Details: One clinical study in adults 30-50 years of age with symptoms of stress shows that taking a specific eleuthero root extract (WS 1070) 120 mg daily for 8 weeks does not improve fatigue, exhaustion, cognitive alertness, or measures of stress when taken alone or in conjunction with stress management training (91510). However, another small clinical study in healthy females 20-68 years of age who have experienced stress for a prolonged period of time shows that taking 270 mg of a combination agent (ADAPT-232) containing eleuthero, rhodiola, and schisandra improves attention and cognitive speed and accuracy when compared with placebo (19289). It is unclear if these effects are due to eleuthero, other ingredients, or the combination.
Upper respiratory tract infection (URTI). Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with an uncomplicated URTI shows that taking 30 mL of a combination product (Kan Jang, Swedish Herbal Institute) containing extracts of eleuthero root (eleutherosides B and E 0.03 mg/mL), echinacea root, and malabar nut leaf daily does not reduce the severity or frequency of cough by a clinically meaningful amount after 3-4 days of treatment when compared with bromhexine hydrochloride or placebo (95648). However, a non-blinded clinical study shows that taking 30 mL of this same product three times daily for 6 days improves the severity and frequency of coughing and the degree of nasal congestion when compared with bromhexine. Additionally, patients taking the combination product recovered two days sooner, on average, than those taking bromhexine (48569). The reason for these conflicting findings is unclear but may be due to an inadequate duration of treatment in the first study and/or lack of blinding in the second study. Also, it is unclear if any benefit is due to eleuthero, other ingredients, or the combination. Other research has evaluated a capsule formulation of Kan Jang (Swedish Herbal Institute), with each capsule containing eleuthero root 11.4 mg and andrographis 195 mg. One small clinical study in patients with an uncomplicated URTI shows that taking this product as two capsules three times daily for 5 days reduces the median number of sick leave days to 2 days, compared with 3 days in the placebo group. It also increases the total number of recovered patients on day 3 to 75%, compared with 55% of those taking placebo (107471). More evidence is needed to rate eleuthero for these uses.

GELATIN

POSSIBLY INEFFECTIVE

Diarrhea. Oral gelatin tannate does not seem to be beneficial for diarrhea treatment in infants and young children. Details: A pooled analysis of three clinical trials shows that taking gelatin tannate 250-500 mg four times daily for 5 days does not reduce the duration of diarrhea or stool frequency in infants and young children with acute diarrhea and gastroenteritis when compared with placebo (103296).

Aging skin. Although there has been interest in using oral gelatin for aging skin, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Beta-thalassemia. It is unclear if oral gelatin is beneficial for beta-thalassemia. Details: Preliminary clinical research in pregnant adults with minor or intermediate beta-thalassemia and mild iron-deficiency anemia shows that taking a specific form of gelatin made from donkey hide, colla corii asini, 15 grams daily for 4 weeks, increases hemoglobin by 11%, compared with a 5% reduction in those receiving no treatment (97634).
Brittle nails. Although there has been interest in using oral gelatin for brittle nails, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Exercise-induced muscle soreness. Although there has been interest in using oral gelatin for exercise-induced muscle soreness and damage, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Joint pain. Although there has been interest in using oral gelatin for general joint pain, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Obesity. Although there has been interest in using oral gelatin for weight loss, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Osteoarthritis. Although there has been interest in using oral gelatin for osteoarthritis, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Osteoporosis. Although there has been interest in using oral gelatin for osteoporosis, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Rheumatoid arthritis (RA). Although there has been interest in using oral gelatin for RA, there is insufficient reliable information about the clinical effects of gelatin for this purpose.
Ulcerative colitis. Rectal gelatin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults admitted to the hospital in China with mild to moderate ulcerative colitis lesions shows that administering a 1-gram suppository containing a specific form of gelatin made from donkey hide, colla corii asini, and multiple other ingredients rectally for 3 months improves diarrhea and bloody stool symptom scores when compared with an 0.8-gram suppository containing the same ingredients. Recurrence at 12 months occurred in approximately 10% of the patients who received the higher-dose combination product compared with 47% of patients who received the lower dose. Patients in each group received 2 suppositories twice daily for the first month, 1 suppository twice daily for the second month, and 1 suppository once daily for the third month (109673). The interpretation of these results is limited by the lack of comparison to placebo or active control with known effectiveness for ulcerative colitis.
Uterine fibroids. Oral gelatin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Meta-analyses of a small number of preliminary clinical trials show that taking traditional Chinese medicines containing multiple ingredients including ejiao, a gelatin made from donkey hide, modestly reduces the volume of uterine fibroids and fibroid-related symptoms more effectively than mifepristone. When used in combination with mifepristone, benefits exceed those of mifepristone alone (106850). It is unclear whether any benefits are related to gelatin, one or more of the other ingredients, or their combination.
Wrinkled skin. Although there has been interest in using oral gelatin for wrinkled skin, there is insufficient reliable information about the clinical effects of gelatin for this purpose. More evidence is needed to rate gelatin for these uses.

ZINC

EFFECTIVE

Zinc deficiency. Orally or intravenously, zinc is effective for treating and preventing zinc deficiency. Details: Taking zinc orally or intravenously prevents and treats zinc deficiency (2619). However, routine zinc supplementation is not recommended (403). Zinc deficiency requiring supplementation may occur in patients with severe diarrhea, malabsorption syndromes, liver cirrhosis, and alcoholism; after major surgery, renal failure, and dialysis; or during long-term administration of total parenteral nutrition (3900,24321). Zinc supplementation (136 mg of elemental zinc per day) in patients with cirrhosis and zinc deficiency seems to improve liver function and glucose tolerance, possibly by increasing insulin-like growth factor (8624,87520).

LIKELY EFFECTIVE

Diarrhea. Oral zinc reduces duration and severity of acute diarrhea in malnourished children. Doses of 5-20 mg seem to be effective, while 5-10 mg daily is less likely to cause vomiting. Details: Most research, including meta-analyses and over 30 clinical trials, show that taking zinc orally reduces the duration and severity of acute and persistent diarrhea in malnourished or zinc-deficient children, but not in well-nourished children (87236,96074). Most studies have been conducted in Bangladesh and India, so it is unclear if these findings are generalizable to other geographic locations. The most comprehensive meta-analysis of clinical studies in children older than 6 months shows that zinc supplementation reduces the duration of acute diarrhea by about 11 hours and the duration of persistent diarrhea by about 16 hours when compared with placebo. However, zinc does not seem to reduce the duration of acute diarrhea in children younger than 6 months. Zinc supplementation seems to have the greatest benefit in children with clear malnutrition and diarrhea. In these children, zinc reduces diarrhea duration by about 26 hours and reduces the risk of diarrhea persisting through days 3, 5, and 7 by 18% to 24% when compared with placebo. There was no clear benefit of using zinc in a specific dose or salt form. The most common dose of zinc was 20 mg daily and salt forms included zinc sulfate, gluconate, and acetate (96074). Also, a large clinical trial in children with acute diarrhea shows that taking zinc 5 or 10 mg daily for 14 days is non-inferior to taking 20 mg. Furthermore, zinc 5 or 10 mg results in a respective 29% and 19% lower risk of vomiting within the first 30 minutes when compared with zinc 20 mg (104045). It's unclear whether zinc supplementation reduces mortality in children with diarrhea. A meta-analysis of clinical research in children under the age of five years shows that supplementation with zinc reduces the risk of mortality from diarrhea by 15% when compared with either placebo, other vitamin and/or mineral supplementation, or no supplementation (106239). However, many studies were conducted in hospitals where rates of mortality are low and were not adequately powered to determine whether zinc has an effect on mortality in children with acute diarrhea (87210,96074,106239).
Wilson disease. Taking zinc orally improves symptoms of this condition. Details: Zinc acetate (Galzin) is an FDA-approved orphan drug for treating this condition. Zinc blocks copper absorption and increases copper elimination in the stool of people with Wilson disease (2692,2693,87327). Small clinical studies suggest that taking zinc after 8 weeks of treatment with tetrathiomolybdate alone can improve Kayser-Fleischer rings, urine copper levels, and neurological symptoms for up to 6 years post-treatment (63588,87491).

POSSIBLY EFFECTIVE

Acne. Orally, zinc might help to reduce symptoms of acne. However, it's unclear how oral zinc compares to conventional acne treatments. Topical zinc doesn't seem to be beneficial if used alone. Details: Observational research has found that people with acne seem to have lower zinc levels in the serum and skin (104056). A meta-analysis of small, low quality clinical trials suggests that taking zinc sulfate or zinc gluconate 137-300 mg 2-3 times daily by mouth can modestly improve acne when compared with placebo (104056). However, not all individual trials show benefit (87002,104056). So far, it is not clear how oral zinc compares to other treatments. Trials comparing zinc sulfate with various tetracyclines have yielded conflicting results (6505,6506,86946,106233). One large open-label clinical trial shows that taking zinc sulfate 200 mg twice daily for 12 weeks is at least as effective as lymecycline 300 mg daily for reducing acne severity. Quality of life related to acne was modestly improved in the patients using zinc sulfate (106233). However, in another clinical trial, a 3-month treatment of oral zinc gluconate 30 mg daily reduced the number of acne lesions from baseline, but was not as effective as minocycline (86946). When applied topically, clinical research shows that zinc does not help treat acne when compared with placebo (87297,104056). However, when used in combination with erythromycin, topical zinc seems to result in improvement (819,820,2687,2688).
Acrodermatitis enteropathica. Oral zinc seems to improve symptoms of this rare genetic disorder. Details: Multiple case reports have found that taking oral zinc seems to help improve symptoms of acrodermatitis enteropathica, a rare disorder (821,2689,2690,2691). One case report in a female with necrolytic acral erythema and hepatitis C suggests that adding oral zinc sulfate 225 mg twice daily to interferon alfa-2b for 6 months contributed to resolving all lesions. Necrolytic acral erythema is categorized in the family of necrolytic erythemas that includes acrodermatitis enteropathica (6192).
Age-related macular degeneration (AMD). Oral zinc, especially in combination with antioxidant vitamins, seems to slow the progression of AMD. Details: Clinical research shows that taking elemental zinc 80 mg plus vitamin C 500 mg, vitamin E 400 IU, and beta-carotene 15 mg daily reduces the odds of progression to advanced AMD by 28%. In patients with more severe AMD, this combination reduced the odds of progression to advanced AMD by 34%. This combination also reduced the odds of visual acuity loss by 27% in patients with severe AMD (7303,11326). However, there is contradictory evidence about the effects of zinc plus antioxidants on visual acuity loss or the progression to advanced AMD in low-risk patients with AMD (6583,6584,7303). Some clinical evidence shows that, when taken without antioxidant vitamins, zinc supplementation does not slow the progression of existing AMD (6580,90069). However, a subgroup analysis of results from a large clinical trial that included patients with intermediate or advanced AMD suggests that the effect of zinc on AMD progression might vary depending on a patient's genetic predisposition. Complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) are two genes for which specific variations (i.e., risk alleles) have been associated with an increased risk of AMD. Results from the retrospective subgroup analysis suggest that zinc supplementation may DECREASE the progression of AMD in patients with ARMS2 risk alleles and INCREASE the progression of AMD in patients with CFH risk alleles (90193). However, some experts question the results from this analysis due to the retrospective nature of the study (93045). Another retrospective analysis of similar data found that only zinc plus antioxidants, but not zinc alone, was beneficial for slowing the progression of AMD, regardless of the patient's genotype (93046). Consequently, the American Academy of Ophthalmology does not currently recommend routine genetic screening to determine which patients would benefit from zinc, antioxidants, or the combination. Instead, patients with intermediate or advanced AMD are recommended to take an antioxidant and zinc supplement similar to those used in the Age-Related Eye Disease Study (AREDS) and the Age-Related Eye Disease Study 2 (AREDS2) (93047). Large scale population studies suggest that increasing dietary intake of zinc might reduce the risk of developing AMD (6579,14257).
Child growth. Oral zinc seems to increase growth when taken by children and improve infant growth in the first year of life when taken by pregnant adults. Details: A meta-analysis of 8 clinical studies in healthy children over 2 years old shows that taking supplemental zinc 5-15 mg daily for 6-56 weeks modestly increases height and weight when compared with placebo. This analysis also shows that taking zinc may improve height for age, but not weight for age when compared with placebo (112474). Most of these studies were conducted in developing countries; results may not apply elsewhere. Another clinical study in pregnant adults in Peru shows that taking zinc 15 mg daily in addition to iron and folic acid, starting during the first or second trimester and continuing up to one month after delivery, modestly improves growth measures of infants at one year when compared with taking iron and folic acid alone. Improved growth measures include body weight, calf and chest circumference, and calf muscle area (87130).
Common cold. Oral zinc seems to help treat cold symptoms in adults. However, it is unclear if zinc is beneficial for common cold prevention. Details: Using zinc oral lozenges seems to be beneficial in helping TREAT the common cold in adults. The majority of clinical trials and analyses of clinical research show a significant decrease in the duration of symptoms of the common cold when adults take zinc gluconate or zinc acetate lozenges providing 9-24 mg of elemental zinc per dose. It is recommended that lozenges be taken every 2 hours while awake, starting within 48 hours of symptom onset for a total daily dose of at least 75 mg in order to attain a mean cold duration reduction of 3 days (333,334,335,337,6703,6705,87501,92212,106902). However, not all studies have been positive (333,338,339,6522,6700,87512). The reasons for these different findings are not clear, but might be due to differences in zinc formulations and doses and study methodologies. In some cases, flavoring agents such as citric acid, mannitol, and sorbitol might chelate zinc and decrease zinc ionization. Since ionization is thought to be necessary for zinc activity, a decrease in zinc ionization could decrease effectiveness (300,340,6522). Some of the positive studies have also been criticized for inadequately blinding the unpleasant, distinctive taste of zinc (6522,6706). Allergy and smoking status do not appear to impact the efficacy of zinc acetate lozenges (92212). Overall, zinc products may be beneficial for modestly reducing the duration of symptoms of the common cold in adults, but adverse effects such as bad taste and nausea may limit their usefulness (18216). There is conflicting evidence for the use of oral zinc products to PREVENT colds. Some clinical research suggests that taking zinc prophylactically does not prevent the common cold in adults (10780,10784) or children (341). However, other clinical research suggests that administering zinc gluconate lozenges can reduce the incidence of colds in children and adolescents (10803,86972). In a meta-analysis of 28 randomized controlled trials with a total of 5446 participants, oral zinc prevented 5 viral upper respiratory tract infections per 100 person months of zinc use when compared with placebo, with a number needed to treat (NNT) of 20 (106902). Intranasal zinc is not recommended for the prevention or treatment of the common cold due to the risk for anosmia. See the Adverse Effects section for more information. Some research shows that zinc nasal spray (as a sulfate, gluconate emulsion, or gluconium gel) reduces the severity and duration of cold symptoms; however, other research has found no effect (6471,8628,8629,10247,87035). Zinc nasal spray does not seem to prevent experimentally-induced colds (8628).
Coronavirus disease 2019 (COVID-19). While oral zinc does not seem to speed recovery from COVID-19 in non-hospitalized patients, an analysis of a small number of studies suggests that oral or intravenous zinc might reduce the risk of death in hospitalized patients with COVID-19. Details: A small observational study in patients with COVID-19 has found that lower serum zinc levels are associated with worse clinical outcomes, such as admission to the intensive care unit (ICU) and death, when compared with higher zinc levels (105681). Another small observational study has found that 96% of patients with confirmed COVID-19 were zinc-deficient based on plasma levels of zinc, and that these patients had lower plasma zinc levels than a group of individuals without COVID-19. However, plasma zinc concentrations were only weakly correlated with length of hospital stay and there was no correlation with morbidity or mortality (106236). One clinical study in adult outpatients with COVID-19 shows that taking zinc gluconate 50 mg daily at bedtime, alone or with vitamin C (ascorbic acid) 8000 mg daily, for 10 days does not reduce symptom severity when compared with standard care (104450). This study was terminated prior to complete enrollment due to a lack of effect with zinc and/or vitamin C supplementation. Limitations of this study include a lack of placebo control and blinding. Zinc supplementation also does not appear to enhance the clinical efficacy of hydroxychloroquine in patients with confirmed COVID-19 infection. Taking zinc sulfate 220 mg twice daily during a 6-day course of hydroxychloroquine does not improve the clinical recovery rate, reduce the mortality rate, or reduce the need for mechanical ventilation when compared with hydroxychloroquine alone (104818). Other research has evaluated zinc in hospitalized patients. Multiple meta-analyses of small and low-quality clinical studies, including randomized controlled trials and retrospective studies, involving hospitalized patients with COVID-19 shows that supplementation with oral or intravenous zinc is associated with a 29% to 43% reduction in the odds of in-hospital mortality when compared with control (109451,110631). However, in one meta-analysis, the odds of 30-day mortality were not different between groups (110631). These meta-analyses did not elevate the most effective form, dose, frequency, or duration of zinc supplementation (109451,110631). Additionally, a retrospective study in adults admitted to the ICU with COVID-19 has found that those who received oral zinc sulfate, 220 mg daily for a median of 11 days, had a lower 30-day mortality rate when compared with those who did not receive zinc. However, there was no difference in hospital length of stay or in-hospital mortality (106903).
Depression. Oral zinc seems to be beneficial when used in combination with antidepressant treatments. Details: Population research has found that higher zinc levels and higher dietary intake of zinc are associated with a 28% lower incidence of depression (90227,97139,104057). Oral zinc seems to be beneficial as an adjunct therapy in depression. A meta-analysis of small, low-quality studies in patients with major depression shows that taking zinc in addition to antidepressant therapy is associated with modestly improved depression symptoms when compared with antidepressant therapy alone (104044). Clinical studies used zinc doses of 7-25 mg daily for up to 12 weeks (86985,90221,104044). One small clinical study also shows that adding zinc to imipramine therapy might improve depression that was previously resistant to antidepressant treatment (87158). One clinical guideline also provisionally recommends use of zinc 25 mg elemental orally daily to treat patients with depression based on low-quality evidence. This guideline recommends use of chelated or picolinate zinc products over other forms of zinc (110318).
Diabetes. Oral zinc might modestly improve glycemic control in some patients. Details: A meta-analysis of 12 clinical studies in patients with diabetes shows that taking zinc supplements reduces fasting blood glucose by up to 20 mg/dL and glycated hemoglobin (HbA1c) by 0.35% when compared with control. However, when only high quality studies were included, the reduction in fasting blood glucose dropped to 12 mg/dL. Zinc seems to only have glycemic benefit in patients living in the Eastern hemisphere, and not the Western hemisphere. Also, glucose reduction seems to be higher with inorganic zinc formulations at doses of at least 30 mg daily taken for at least one month (104080). Zinc has also been evaluated for improving lipid parameters in patients with diabetes. A meta-analysis of nine studies in patients with diabetes shows that taking zinc reduces triglycerides by 17 mg/dL, but does not seem to affect low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol levels, when compared with placebo (104041). The findings from these meta-analyses are limited by the high heterogeneity and small size of the included studies. Zinc has also been studied for gestational diabetes. Some clinical research in patients with gestational diabetes shows that taking zinc gluconate for 6 weeks, starting at 24-28 weeks' gestation, reduces fasting plasma glucose levels by about 10% and improves insulin resistance by 14% when compared to baseline (96072). However, taking zinc gluconate does not reduce the need for caesarean section or insulin therapy, or improve infant outcomes, such as size or health at birth, in these patients (96073).
Diaper rash. Topical and oral zinc seem to reduce the incidence and severity of diaper rash in infants. Details: Clinical research shows that administering oral zinc gluconate 10 mg daily for 4 months can reduce the incidence of diaper rash in infants when compared with placebo (87281). Other clinical research shows that applying 47% zinc oxide paste to affected areas for 5 days can improve the healing of diaper rash. However, the effect of zinc oxide paste is inferior to eosin 2% solution (86918).
Gingivitis. Topical zinc seems to reduce the development of gingivitis. Details: While some clinical research shows that zinc, in combination with triclosan, does not prevent plaque and gingivitis (24093,87020), most clinical research shows that using zinc toothpaste or mouthwash, alone or in combination with triclosan, can prevent plaque accumulation, gingivitis, or the formation of calculus (6523,6524,6525,6526,6527,6528,6529,87418,87507). However, most studies used zinc citrate in combination with triclosan, which is not available in the US (6523). For treating existing plaque, calculus, and gingivitis, some clinical research suggests that using zinc citrate 0.5% toothpaste three times daily for 3 months reduces calculus scores by 14% when compared with placebo (87205). However, other evidence suggests that stannous fluoride 0.454% toothpaste is more effective than zinc citrate 0.75% toothpaste for reducing plaque levels (87136).
Halitosis. Oral zinc seems to reduce halitosis when taken as a gum, mouth rinse, or candy. Details: Clinical research shows that chewing zinc-containing gum reduces volatile sulfur compounds and related odor levels when compared with placebo gum in patients with moderate to severe halitosis (87538). Clinical research also shows that using one of two mouth rinses (Halita, which contains 0.05% chlorhexidine and 0.14% zinc lactate, or Meridol, which contains 0.025% fluoride plus 0.2% zinc lactate) improves breath odor and volatile sulfur compounds by approximately two-fold when compared with mouth rinse containing only 0.05% fluoride or chlorhexidine 0.12% (90206). Additional clinical research shows that sucking a candy containing abrasive substances and zinc gluconate 0.5% or candy containing abrasive substances plus zinc 0.25% and propolis 1% improves breath malodor two- to three-fold when compared with sucking placebo candy (90196).
Herpes labialis (cold sores). Topical zinc seems to reduce the severity and duration of cold sores. Details: Applying zinc topically seems to help treat herpes simplex infection (6538,6539,8623,11051). Zinc sulfate seems to reduce the severity and duration of symptoms in both orolabial and genital herpes (6538,6539). Zinc oxide (0.3%) in combination with glycine cream applied topically every 2 hours to facial and circumoral herpes seems to reduce symptoms such as blistering, soreness, itching, and tingling. It can also reduce the duration of lesions from 6.5 days to 5 days when treatment is begun within 24 hours of onset of symptoms (8623). A specific combination product containing zinc oxide and L-lysine plus 14 other ingredients (Super Lysine Plus +) also seems to help decrease symptoms and duration of herpes lesions when applied topically every 2 hours (11051). However, zinc may not be effective for recurrent herpes simplex infections. In one clinical study, applying zinc sulfate 0.0025% or 0.05% solution to affected areas did not reduce the frequency, severity, or duration of herpes episodes when compared with a placebo solution in patients experiencing more than five episodes per year (87330).
Hypogeusia. Oral zinc might improve taste disturbance and taste acuity in people with hypogeusia of various etiologies. Details: A meta-analysis of low-quality studies in patients with taste disorders that are idiopathic or due to zinc deficiency shows that taking oral zinc modestly improves taste acuity when compared with placebo (104055). Studies tested zinc gluconate, zinc sulfate, zinc acetate, and zinc-carnosine as Polaprezinc (Promac, Zeria Pharmaceutical Co., Ltd.), containing 17-68 mg elemental zinc, daily for up to 12 weeks (104055). Zinc also might improve hypogeusia conditions unrelated to zinc deficiency, such as gustin/carbonic anhydrase VI deficiency, captopril-induced taste disturbances, hypogeusia due to chronic renal failure, and post-traumatic olfactory disorder (6543,6544,104055). It also seems be beneficial in radiation-induced dysgeusia. A meta-analysis of three small clinical trials shows that oral zinc reduces the risk of radiation-induced dysgeusia by 28%, but does not improve taste acuity when compared with placebo (104043). However, patients with hypogeusia from other causes may not benefit. Zinc supplementation does not seem to improve taste perception when compared with placebo in patients with acetazolamide-induced taste dysfunction or chemotherapy-induced taste dysfunction (87388,90214).
Leishmania lesions. Oral zinc and intralesional injections of zinc might improve healing of these lesions. Details: Clinical research shows that taking zinc sulfate 2.5-10 mg/kg orally in three divided doses daily, improves the cure rate of cutaneous leishmania lesions after 45 days when compared with no treatment (86935). Other clinical research shows that intralesional injections of zinc sulfate 2% solution for 6 weeks improves cure rates of cutaneous leishmania lesions when compared with no treatment (6587). However, intralesional injections with zinc sulfate solution does not appear to be more effective than intralesional injections of meglumine antimoniate (Glucantime), hypertonic saline, or sodium stibogluconate (6587,86996,87008).
Leprosy. Oral zinc seems to be beneficial when used in combination with anti-leprosy drugs. Details: Zinc levels appear to be reduced in people with leprosy. Early clinical research suggests that the addition of zinc improves tolerance of the anti-leprosy drug regimen and might allow for lowering or eliminating steroid doses in erythema nodosum leprosum, a severe form of leprosy (6534,6535,6536,6537).
Low birth weight. Oral zinc supplementation seems to improve growth in low birth weight infants. Whether oral zinc can improve other outcomes, including mortality, is unclear. Taking oral zinc during pregnancy does not seem to reduce the risk of having a low birth weight infant. Details: While there is some mixed evidence regarding the effects of zinc supplementation on weight gain and length in infants born with low birth weight (87172,87452,90229), a meta-analysis of 14 clinical trials in preterm or low birth weight infants receiving breastmilk shows that zinc supplementation, typically 5-7 mg daily started at birth and continued for up to 12 months with or without other micronutrients, increases weight by around 380 grams, length by around 3 cm, and head circumference by around 0.6 cm when compared with control (109455). There is also mixed evidence regarding the effect of zinc supplementation on other outcomes in low birth weight infants. A large clinical trial in full-term, underweight infants aged 1-6 months in developing countries shows that adding zinc to nutritional supplementation reduces the risk of mortality by about 68% when compared with nutritional supplementation not containing zinc (8920). A small clinical trial in very low birth weight preterm infants born in an industrialized country shows that adding zinc to multivitamin supplementation appears to reduce the occurrence of necrotizing enterocolitis and mortality. However, adding zinc does not appear to prevent late-onset sepsis, bronchopulmonary dysplasia, or retinopathy of prematurity (90229). A meta-analysis of these trials and two other studies in low birth weight infants shows that supplementation with zinc reduces the risk of all-cause mortality by 52% when compared with either placebo, other vitamin and/or mineral supplementation, or no supplementation (106239). Another small clinical study in low birth weight and preterm infants born in a developing country shows that zinc supplementation seems to improve alertness and attention when compared with placebo (97140). However, a meta-analysis of 14 clinical trials in preterm or low birth weight infants receiving breastmilk shows that zinc supplementation, typically 5-7 mg daily started at birth and continued for up to 12 months with or without other micronutrients, does not improve mental or psychomotor development or reduce the risk of mortality, hospitalization, acute respiratory infection, or sepsis when compared with control (109455). Some of these discrepant findings may be due to differences in patient populations (hospitalized, non-hospitalized), milk sources (breastfed, formula-fed, or both), and duration of follow-up. The effect of zinc intake or supplementation during pregnancy has also been evaluated. Population research has found that low dietary intake of zinc during pregnancy is associated with low birth weight in infants; similarly, zinc supplementation is associated with increased infant weight at birth (87471,105678). However, a meta-analysis and a large clinical study show that zinc supplementation during pregnancy does not reduce the risk of having a low birth weight infant (97142,105679). Reasons for the discrepancies may be due to differing zinc status prior to supplementation. Also, numerous factors contribute to the risk of low birth weight, which may confound research on the use of zinc supplementation alone.
Peptic ulcers. Oral zinc seems to treat and prevent peptic ulcers. Details: Taking zinc orally seems to help treat and prevent peptic ulcers (6588,6589,6591). Some clinical research shows that zinc acexamate improves peptic ulcers when compared with placebo (6589,87285), and seems to be as effective as H2-receptor antagonist drugs (6589,87533). It is not known if other zinc salts are effective.
Pneumonia. Oral zinc might reduce the risk for pneumonia in children, but it doesn't seem to improve symptoms in children that already have pneumonia. Details: A meta-analysis of four clinical studies shows that giving zinc supplements to children, ages 3 months to 5 years living in developing countries, some of whom were undernourished, reduces the risk of pneumonia incidence by 21% when compared with placebo (104047). Another meta-analysis of clinical research in children under the age of five years shows that supplementation with zinc reduces the risk of pneumonia mortality by 21% when compared with either placebo, other vitamin and/or mineral supplementation, or no supplementation (106239). The research on TREATING existing pneumonia in children is inconsistent. Most meta-analyses and clinical studies in children ages 2 months to 5 years with severe pneumonia show that taking elemental zinc in addition to antibiotic therapy does not improve symptom resolution or the time to recovery when compared with antibiotic therapy alone. Zinc also does not seem to reduce mortality in these patients (87248,90197,96080,98131,104042). However, two clinical studies in children in the same age group with pneumonia suggest that adding zinc to standard antibiotic therapy improves symptom resolution and decreases hospital stay when compared with placebo (11052,87242). Reasons for these discrepancies are not clear, but may be related to zinc status prior to treatment.
Prematurity. Analyses of clinical studies suggest that oral zinc improves growth in premature infants. Whether zinc improves development or reduces the risk of mortality in these patients is unclear. Details: A meta-analysis of small clinical trials in hospitalized infants born prematurely suggests that receiving enteral zinc supplementation at a dose of up to 10 mg daily reduces mortality and might improve short-term weight gain when compared with placebo (105687). Another meta-analysis of small clinical studies in preterm infants shows that adding zinc to formula or to a multivitamin seems to modestly increase infant weight and height and improve motor development when compared with control (105676). A larger meta-analysis of 14 clinical trials in preterm or low birth weight infants receiving breastmilk shows that zinc supplementation, typically 5-7 mg daily started at birth and continued for up to 12 months with or without other micronutrients, increases weight by around 380 grams, length by around 3 cm, and head circumference by around 0.6 cm when compared with control. However, zinc supplementation did not improve mental or psychomotor development or reduce the risk of mortality, hospitalization, acute respiratory infection, or sepsis when compared with control (109455). These analyses are limited by imprecision as well as a high risk of bias in some of the included studies. Some of the discrepant findings may be due to differences in patient populations (hospitalized, non-hospitalized), milk sources (breastfed, formula-fed, or both), and duration of follow-up.
Pressure ulcers. Topical zinc paste seems to work as a skin barrier and improve pressure ulcer healing. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that applying zinc oxide paste to pressure ulcers daily for 8 weeks reduces necrotic tissue and decreases the surface area of skin pressure ulcers similarly to using a topical streptokinase-streptodornase product (Varidase) (87331). Other small clinical studies show that applying zinc oxide paste to pressure ulcers daily for 8-12 weeks improves healing similarly to a hydrocolloid dressing (Duoderm) (87181) or a specific barrier film product (Cavilon No Sting Barrier Film) (87017). Oral zinc has been evaluated in combination with other ingredients for the treatment of grade II-IV pressure ulcers. Two small clinical studies in hospitalized patients shows that administering an oral nutritional supplement enriched with zinc, L-arginine, and vitamin C 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, zinc, L-arginine, and vitamin C 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.
Sickle cell disease. Oral zinc seems to improve symptoms of sickle cell disease in patients with zinc deficiency. Details: Taking zinc orally seems to help reduce symptoms of sickle cell disease in people with zinc deficiency (6594,6595,6596,8626,87343). Taking zinc supplements also seems to decrease the occurrence rate of sickle-cell crises and infections (6594,6596,90228). Additionally, zinc might reduce the number of hospitalizations for sickle cell crises, although the severity of the crises that do develop is not necessarily decreased by taking zinc supplements (6594,6596). In prepubertal children and adolescents with homozygous sickle cell disease, taking zinc seems to improve growth, height, and weight gain (8626,87403).
Warts. Oral and topical zinc seem to improve the cure rate of cutaneous warts. Details: A small clinical study suggests that applying zinc sulfate 10% solution three times daily for 4 weeks improves plane warts, but not common warts, when compared with distilled water (87094). Another small clinical study suggests that applying topical zinc oxide 20% ointment twice daily for up to 3 months seems to have a similar cure rate as ointment containing salicylic acid 15% with lactic acid 15% (87082). Taking zinc orally may also be effective in treating warts (87227). A meta-analysis of low quality clinical studies shows that taking zinc sulfate orally improves the odds of curing cutaneous warts nearly 17-fold when compared with respective controls (87227). Preliminary clinical research in adults treated with cryotherapy for anogenital warts shows that taking zinc gluconate 30 mg orally three times daily for 2 months does not reduce the number of warts when compared with placebo (111445).

POSSIBLY INEFFECTIVE

Alopecia areata. Oral zinc does not seem to improve symptoms of this condition. Details: Although there is preliminary evidence that suggests zinc in combination with biotin might be helpful for alopecia areata (6932), most studies indicate that zinc is not effective for alopecia areata, alopecia totalis, or alopecia universalis (6931,6932).
Cystic fibrosis. Oral zinc does not improve cystic fibrosis symptoms or progression. Details: Clinical research shows that taking supplements providing 30-90 mg of elemental zinc for 6 weeks to one year does not improve lung function when compared with placebo in children and adolescents with cystic fibrosis (87066,87113,96079). One clinical study also shows that taking elemental zinc for one year does not reduce the number of days requiring oral or intravenous antibiotics for pulmonary infections (96079). However, one study shows that taking zinc can reduce the number of days of oral antibiotic use when compared with placebo (87113).
HIV/AIDS. Oral zinc does not seem to improve outcomes in patients with HIV. Details: Clinical research in adult HIV patients with normal or low zinc levels shows that taking elemental zinc 12-15 mg daily orally for 18 months along with antiretroviral therapy does not improve viral load, CD4/8 counts, or mortality when compared with placebo (87036,87216,105686). In children with HIV-1, clinical research shows that administering zinc sulfate, providing 10 mg elemental zinc, daily for 6 months does not improve mortality, viral load, or CD4 counts when compared with placebo (82377).
HIV/AIDS-related pregnancy complications. Oral zinc does not prevent pregnancy complications related to HIV infection. Details: Adding zinc 25 mg orally during pregnancy does not seem to reduce parent-to-child vertical transmission of HIV, infant mortality, birth weight, or gestational period in HIV-infected females with low zinc levels (11054,87034). Also, one clinical study in HIV-1-infected pregnant patients suggests that supplemental zinc can increase the risk of wasting, as assessed by weight and mid-upper arm circumference, by 170% when compared with placebo (87034).
HIV/AIDS-related wasting. Oral zinc does not seem to improve HIV-related wasting syndrome. Details: A clinical study in patients with HIV-related wasting syndrome shows that taking zinc orally in combination with vitamins and albendazole does not seem to improve diarrhea or mortality when compared with taking albendazole alone (6564).
Infant development. Oral zinc does not seem to improve infant mental and psychomotor development. Details: Clinical research, including a meta-analysis of eight studies, shows that giving zinc to infants or children at high risk for zinc deficiency does not improve mental and psychomotor development when compared with placebo (87013,90209). In another meta-analysis of studies in children whose baseline zinc status was not specified, there was no beneficial effect of zinc supplementation on mental or psychomotor development at 6 or 12 months of age (104817).
Inflammatory bowel disease (IBD). Oral zinc does not improve symptoms of IBD. Details: Some clinical research shows that taking zinc orally does not seem to help treat IBD (6913,6915,6916).
Influenza. Oral zinc does not seem to reduce the risk for influenza. Details: Supplemental zinc seems to improve cell-mediated immune response in elderly people (824), but it does not seem to have a significant effect on antibody response and incidence of influenza infection after the vaccine (6553,6563). Additionally, zinc supplementation in patients on hemodialysis, who have a high risk of zinc deficiency, does not seem to improve response to influenza vaccine (10809). Taking zinc supplements orally is unlikely to improve immune function in people without risk factors for zinc deficiency (10789). However, there is preliminary evidence that suggests zinc along with selenium might reduce the incidence of infections in institutionalized older patients (8921).
Otitis media. Oral zinc does not prevent otitis media in children. Details: A meta-analysis of clinical research shows that taking elemental zinc 3-70 mg daily for up to 24 months does not prevent the occurrence of ear infections in children from low- or middle-income countries (87258).
Pre-eclampsia. Oral zinc taken prenatally does not seem to be beneficial for pre-eclampsia prevention. Details: A meta-analysis and a large clinical study show that zinc supplementation during pregnancy does not reduce the risk of pre-eclampsia when compared with placebo (97142,105679).
Prostate cancer. Oral zinc does not reduce the risk for prostate cancer or prostate cancer-related mortality. Details: Some epidemiological research has found an inverse relationship between dietary zinc intake and prostate cancer (96075). Also some clinical research shows that taking zinc 20 mg in combination with vitamin C 120 mg, vitamin E (alpha-tocopherol) 30 mg, beta-carotene 6 mg, and selenium 100 mcg daily for an average of 8 years might reduce the risk of prostate cancer in men with normal PSA levels; however, it does not seem to be beneficial for reducing the risk of prostate cancer in patients with PSA levels above 3 mcg/L (14135). However, some evidence raises concern that zinc might actually INCREASE the risk of prostate cancer. A large-scale population study found that taking more than 100 mg of supplemental zinc daily or taking supplemental zinc for 10 or more years doubles the risk of developing prostate cancer (10306). Another large-scale population study shows that men who take a multivitamin more than seven times per week and who also take a separate zinc supplement have a significantly increased risk of prostate cancer-related mortality (15607). Despite these studies suggesting the potential for adverse effects of zinc, a meta-analysis of mainly population research has found that there is no association between zinc intake and the risk of prostate cancer (96075).
Psoriasis. Oral zinc does not reduce the severity of psoriasis symptoms. Details: Zinc epidermal levels are reportedly lower in people with psoriasis (6509). However, taking zinc orally does not seem to help treat psoriasis (6513,6514,6912,87363). Zinc supplementation has no effect on the psoriasis area and severity index (6513,6514).
Rheumatoid arthritis (RA). Oral zinc does not treat symptoms of RA. Details: Multiple clinical studies in patients with RA show that taking zinc orally does not improve function or symptoms when compared with baseline or control (6517,6518,6519,87406).
Sexual dysfunction. Oral zinc does not improve sexual function in males with chronic kidney disease (CKD). Details: Clinical research shows that zinc supplementation does not improve sexual activity or libido when compared with placebo in males with sexual dysfunction secondary to CKD (6708,6568,87220,87386,87416). In fact, one clinical study shows that taking zinc can decrease the frequency of intercourse by 76% when compared with placebo in patients with CKD-related sexual dysfunction (87220).
Tinnitus. Oral zinc does not improve severity of tinnitus or reduce tinnitus-related disability. Details: A meta-analysis of three small clinical trials in adults with tinnitus shows that taking elemental zinc 50 mg daily for up to 16 weeks does not improve tinnitus severity, or disability from tinnitus when compared with placebo (104051).

LIKELY INEFFECTIVE

Malaria. Oral zinc does not prevent or treat malaria in undernourished children or pregnant adults in developing countries. Details: A meta-analysis of clinical research in children or pregnant adults shows that taking zinc orally, alone or in combination with other supplements, for does not reduce the risk of malaria parasitemia (111444). A large multi-country study in zinc-deficient preschool children with acute malaria shows that taking zinc supplements does not affect fever, parasitemia, or hemoglobin when compared with placebo (10246). An even larger clinical study of over 40,000 children with malaria aged 1-36 months shows that taking zinc 5-10 mg daily orally for approximately 17 months does not reduce mortality when compared with placebo (87078). Zinc supplements also do not appear to protect against infection by Plasmodium falciparum (8638,87235,86937). However, one small study in children with low and high levels of parasitemia shows that taking zinc 10 mg daily for 46 weeks may lower the incidence of fever episodes by 38% and 69%, respectively, when compared with placebo (86937).

Age-related cognitive decline. It is unclear if oral zinc is beneficial in patients with age-related cognitive decline. Details: An epidemiological study based on elderly adults enrolled in the National Health and Nutrition Examination Survey (NHANES) has found that taking zinc may improve cognition in a non-linear manner. Daily doses below 9 mg and 8 mg in males and females, respectively, showed a positive association with cognitive function, but doses above that level showed no association. Additionally, high intake of both zinc and selenium was associated with improved cognition in females, but not in males (108446). Dietary intake was collected from two patient-reported 24-hour recalls and cognition was only measured once, limiting the validity of these findings.
Alcohol-related liver disease. It is unclear if oral zinc is beneficial in patients with alcoholic-related liver cirrhosis. Details: A small clinical study in patients with alcoholic liver cirrhosis shows that taking zinc sulfate 600 mg daily for 6 weeks improves liver function, based on increased alkaline phosphatase activity and reduced serum bilirubin, when compared to baseline (87325).
Anorexia nervosa. Oral zinc seems to improve weight gain in people with anorexia nervosa. Details: Anorexia nervosa might be linked with zinc deficiency. Small clinical trials in adolescents and adults with anorexia nervosa show that oral zinc supplements might help increase weight gain and improve depressive symptoms when compared with placebo (6905,6906).
Arsenic poisoning. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study shows that taking zinc 4 mg in combination with spirulina extract 500 mg daily for 16 weeks can decrease skin manifestations and reduce arsenic levels in the urine and in hair of patients with chronic arsenic poisoning (18301).
Asthenopia (eye strain). Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults without dry eye disease shows that taking a specific combination product containing zinc 10 mg, L-carnitine 50 mg, elderberry fruit extract 300 mg, currant 100 mg, and Eleutherococcus root 50 mg (Meramirt CM) orally once daily for 1 month improves measures of eye strain and contrast sensitivity when compared to baseline. Improvements in these measures were lacking in the control group (111295). Statistical comparison between the two groups was not reported. It is unclear if these effects are due to zinc, other ingredients, or the combination.
Athletic performance. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in sleep-deprived recreational athletes shows that taking a combination of zinc 90 mg, magnesium 1350 mg, and vitamin B6 31.5 mg orally for 3 nights at bedtime does not improve grip strength, squat, or bench press performance when compared with placebo (113655).
Atopic dermatitis (eczema). It is unclear if oral zinc is beneficial for alleviating eczema in children. Details: A small clinical study in children with eczema shows that taking zinc sulfate 185.4 mg orally daily for 8 weeks does not appear to improve the surface area affected and degree of erythema, symptom scores of itch and sleep disturbance, or topical steroid use when compared with placebo. Also, plasma zinc levels appear to be normal in children with eczema (6911).
Attention deficit-hyperactivity disorder (ADHD). Oral zinc might improve certain symptoms in children with ADHD. Details: Observational research has found that lower serum zinc levels are both more prevalent in children with ADHD and are linked to worsened response to stimulant therapy (9965,9966,9967). Based on this evidence, there is some interest in using zinc to improve symptoms in children with ADHD. A meta-analysis of six small clinical trials shows that although taking zinc modestly improves overall symptoms of ADHD when compared with placebo, there is no effect on hyperactivity or inattention when these outcomes are examined separately. The sub-analyses conducted for these two separate outcomes included only 3 studies. Most, but not all, of the included studies were conducted in children also receiving methylphenidate treatment (106240). Elemental zinc, usually as sulfate, was typically used in doses of 10-40 mg daily for 6-12 weeks (11350,12060,106240). There is some evidence that zinc could be most helpful in children with a high body mass index (BMI), low zinc levels, and low free fatty acid levels (11350). It is unclear if zinc is beneficial in children who are not already taking stimulant medications. One clinical guideline also provisionally recommends against use of oral zinc to treat patient with ADHD based on low-quality evidence (110318).
Autism spectrum disorder. It is unclear if oral zinc is beneficial in children with autism spectrum disorder. Details: One small clinical study conducted in children with autism spectrum disorder shows that taking zinc 15-30 mg orally, alone or as add-on therapy to amphetamine, does not improve attention deficit hyperactivity disorder (ADHD) symptoms when compared with placebo (98711). However, the optimal mg/kg dose of amphetamine was shown to be 37% lower for those children also taking zinc 15 mg twice daily when compared with those taking placebo (98711).
Autoimmune thyroiditis. It is unclear if oral zinc is beneficial in children with autoimmune thyroiditis. Details: A small clinical study in children aged 3-18 years with autoimmune thyroiditis shows that taking zinc acetate 25 mg daily in addition to standard therapy for 12 weeks does not change thyroid auto-antibody levels, thyroid function tests, or oxidative stress markers when compared with standard therapy alone. However, subjects taking zinc did not require escalation in levothyroxine doses when compared with the control group control group, which did require levothyroxine dose escalation (113661).
Behcet disease. It is unclear if oral zinc is beneficial in patients with Behcet disease. Details: A small clinical trial in patients with Behcet disease shows that taking zinc gluconate 30 mg daily for 12 weeks does not improve disease activity scores, quality of life, or measures of inflammation when compared with placebo (109453).
Benign prostatic hyperplasia (BPH). Although there is interest in using oral zinc for BPH, there is insufficient reliable information about the clinical effects of zinc for this condition.
Beta-thalassemia. It is unclear if oral zinc is beneficial in patients with beta-thalassemia major. Details: A small clinical study in children recently diagnosed with beta-thalassemia major shows that initiating zinc sulfate in addition to standard blood transfusions increases linear growth rate when compared with transfusions alone (87329). Another small clinical study in adult and pediatric patients with thalassemia major and low bone mass shows that taking zinc 25 mg daily (as zinc sulfate) for 18 months improves whole-body bone mineral content, as well as hip and spine bone mineral density, by small amounts when compared with placebo (90208).
Brain tumor. It is unclear if dietary zinc is beneficial for reducing the risk for brain cancer. Details: Population research has found that zinc intake is not associated with a reduced risk of developing brain cancer (87098).
Breast cancer. It is unclear if increased dietary zinc intake is beneficial for reducing the risk for breast cancer. Details: Population research has found that neither zinc intake nor blood levels of zinc are associated with a reduced risk of breast cancer (106229).
Bronchiolitis. It is unclear if oral zinc is beneficial for viral bronchiolitis in infants and children. Details: A small clinical study in children 2 years or younger with acute viral bronchiolitis shows that taking elemental zinc 10-20 mg as zinc sulfate for 5 days improves clinical recovery and reduces the duration of hospital stay by almost one day when compared with placebo. After 72 hours, 98% of infants and children taking zinc were considered fully recovered, compared to only 52% of infants taking placebo (96076).
Burning mouth syndrome. Topical zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with burning mouth syndrome shows that taking zinc 15 mg and vitamin C 35 mg once daily, along with a vitamin B complex twice daily, for 30 days modestly decreases pain and burning when compared to baseline (105195). The validity of this finding is limited by the lack of a comparator group. Furthermore, it is unclear if the benefit is due to zinc, other vitamins, or the combination.
Burns. Intravenous zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. The effects of oral zinc for burn healing are unclear. Details: Administering zinc intravenously in combination with other minerals seems to improve the outcomes of burn patients. Supplementation with zinc, copper, and selenium appears to improve wound healing, reduce pulmonary infections, and shorten intensive care unit stay in patients with serious burns (6520,87085). The effect of supplementation with zinc alone is unclear.
Canker sores. It is unclear if oral zinc is beneficial in patients with canker sores. Details: Evidence for the use of zinc in canker sores is conflicting. A small clinical crossover study in patients with recurrent canker sores shows that taking zinc sulfate 660 mg daily for 3 months does not improve the size or frequency of canker sore ulcers when compared with control (6592). However, another clinical study in patients with recurrent sores and low or normal zinc levels shows that taking zinc sulfate 220 mg daily for 1 month reduces recurrence of sores when compared with placebo (86964). Reasons for conflicting results are unclear. Zinc might be beneficial when used in a muco-adhesive formulation. A small clinical study in patients with canker sores shows that taking a muco-adhesive zinc sulfate 5 mg tablet three times daily for 7 days reduces pain and speeds up healing when compared with placebo (104048).
Cataracts. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Taking zinc orally in combination with antioxidant vitamins does not seem to help treat or prevent cataracts. Taking elemental zinc 80 mg plus vitamin C 500 mg, vitamin E 400 IU, and beta-carotene 15 mg daily does not seem to have any effect on the development or progression of age-related lens opacities (cataracts) or the need for cataract surgery in well-nourished people 55-80 years of age. However, it is unknown whether earlier intervention and/or a longer period of treatment with supplements would have any effect on cataracts (7304).
Chemotherapy-induced acral erythema. It is unclear if oral zinc reduces the severity of acral erythema induced in patients treated with the vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) treatment regorafenib. Details: A small study in patients with metastatic colorectal cancer undergoing treatment with regorafenib shows that taking zinc gluconate 78 mg twice daily reduces the proportion of patients with more severe acral erythema when compared with control. Though there is no association in the zinc treatment group, lower serum zinc levels seem to correlate with more severe acral erythema in the control group, suggesting a possible role of zinc deficiency in the pathogenesis of acral erythema (112472). The validity of this study is limited by the lack of blinding.
Chemotherapy-related fatigue. It is unclear if oral zinc improves symptoms in patients with fatigue due to chemotherapy. Details: A small clinical study in patients undergoing 4 or more cycles of chemotherapy for colorectal cancer shows that taking zinc 70 mg daily for 16 weeks does not improve fatigue or quality of life when compared with placebo (97141).
Chronic fatigue syndrome (CFS). Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in females with CFS shows that taking zinc 10 mg as zinc sulfate plus melatonin 1 mg daily for 16 weeks modestly reduces self-reported symptoms of physical fatigue when compared with placebo. However, there was no effect on cognitive or psychological symptoms, sleep, or symptoms of anxiety or depression (106241). This study may not have been adequately powered to detect differences between groups.
Cirrhosis. It is unclear if zinc is beneficial for reducing cirrhosis-related mortality. Details: A meta-analysis of four small clinical trials shows that zinc supplementation does not seem to reduce mortality in patients with cirrhosis when compared with control (104054). This finding is limited due to the heterogeneity and small size of the available studies.
Cognitive function. It is unclear if zinc is beneficial for cognitive function. Details: A very small clinical study in adults with overweight and obesity shows that taking supplemental zinc 30 mg daily for 12 weeks improves some measures of cognitive function and executive processing but does not improve verbal fluency when compared with placebo (112471). Zinc has also been evaluated in combination with other ingredients. A small clinical trial in healthy adults shows that taking a specific product containing a combination of zinc 9 mg, Lactobacillus helveticus, Lactiplantibacillus plantarum, Bifidobacterium longum, and other ingredients (Puraflor, GSK Consumer Healthcare, Milano, Italy) orally daily for 4 weeks does not affect cognitive performance during acute stress when compared with placebo (110923).
Colorectal adenoma. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study shows that taking a combination supplement containing zinc 30 mg, selenium 200 mcg (as l-selenomethionine), vitamin A 2 mg (as retinol), vitamin C 180 mg, and vitamin E 30 mg (as D-a-tocopherol acetate) by mouth daily for 5 years or until the recurrence of an adenoma reduces the risk of recurrent large-bowel adenomas by approximately 40% when compared with placebo (92903). It is not clear if the benefit is due to zinc, other supplements, or the combination.
Colorectal cancer. It is unclear if oral zinc is beneficial for reducing colorectal cancer risk. Details: Population research has found that increased intake of zinc is associated with a 17% to 20% reduced risk of colorectal cancer (90213,90220).
Congenital heart disease. It is unclear if oral zinc is beneficial for reducing the risk of congenital heart defects. Details: An observational study in pregnant adults has found that consuming the recommended nutritional intake of zinc may be associated with a lower risk of total congenital heart defects in infants, including atrial and ventricular septal defects, when compared with low zinc intake. This association appears to persist despite copper or selenium intake (108445).
Critical illness (trauma). It is unclear if oral zinc is beneficial for critically ill patients. Details: A meta-analysis of two small randomized clinical trials in adults with head trauma shows that supplementing zinc, given as 120 mg elemental zinc orally daily or 12 mg elemental zinc intravenously daily for 15 days to 3 months, regardless of serum zinc levels, does not improve the risk of 30-day mortality when compared with control (111290). However, the study may have been inadequately powered to detect a difference between groups.
Dementia. Although there is interest in using oral zinc for dementia, there is insufficient reliable information about the clinical effects of zinc for this condition.
Diabetic foot ulcers. Although there is interest in using oral zinc for diabetic foot ulcers, there is insufficient reliable information about the clinical effects of zinc for this condition.
Diabetic neuropathy. It is unclear if oral zinc is beneficial in patients with diabetic neuropathy. Details: A small clinical study in patients with poorly-controlled diabetic neuropathy shows that taking zinc sulfate 660 mg daily for 6 weeks improves motor nerve conduction velocity and reduces fasting and postprandial blood sugar when compared to baseline (86933). The validity of this finding is limited by the lack of statistical comparison to the control group.
Down syndrome. It is unclear if oral zinc is beneficial for improving immune function in people with this condition. Details: A very small clinical study in Down syndrome patients with zinc deficiency shows that taking zinc sulfate 1 mg/kg daily for 2 months seems to improve immune function and reduce recurrent infections when compared with baseline (87289). The validity of this finding is limited by the lack of a control group. Another small clinical study in children with Down syndrome shows that zinc 25-50 mg daily for 6 months does not improve immune function when compared with placebo (87278). Reasons for the discrepancies may be related to the dose of zinc or zinc status at baseline.
Dysmenorrhea. It is unclear if oral zinc is beneficial in patients with dysmenorrhea. Details: Preliminary clinical research in females aged 13 to 21 years with primary dysmenorrhea shows that taking zinc sulfate 40 mg orally daily for the first 3 days of menstruation for three cycles reduces mean pain scores by 51% when compared with placebo (111446).
Epilepsy. There is limited evidence on the oral use of zinc in children with intractable seizures. Details: A small clinical study in children with intractable epilepsy shows that taking elemental zinc 1 mg/kg daily as zinc sulfate heptahydrate for 6 months reduces seizures when compared with placebo. About 31% of children taking zinc experienced a 50% decrease in seizure frequency, compared to only 5% of children taking placebo (96078).
Erectile dysfunction (ED). It is unclear if oral zinc is beneficial in patients with erectile dysfunction. Details: A moderate-sized, open-label clinical study in adults with mild-to-moderate ED shows that taking a specific combination supplement (Icarifil, Anvest Health S.p.A) containing zinc 15 mg, L-carnitine, L-citrulline, tribulus, and other ingredients daily for 3 months improves patient-reported erectile function when compared to baseline. Additionally, taking the supplement with tadalafil improves some, but not all, patient-reported assessments of erectile function when compared with taking tadalafil alone (114989). It is unclear if this effect is due to zinc, other ingredients, or the combination. Additionally, the interpretation of these results is limited by poor methodology, including the use of per-protocol analysis and lack of a placebo group.
Esophageal cancer. It is unclear if oral zinc is beneficial for esophageal cancer prevention. Details: Population research in Chinese and Iranian patients has found that low intake of zinc is associated with an increased risk of esophageal squamous cell cancer (17205,87059). However, other population research in patients from America, Europe, or Asia has found that dietary zinc intake is not associated with esophageal cancer risk (90213).
Fatigue. It is unclear if oral zinc is beneficial for reducing fatigue in older individuals. Details: A clinical study in adults 50 years and older, some with below-normal levels of zinc at baseline, shows that taking zinc 30 mg daily for 70 days improves subjective fatigue when compared with no intervention (105675). The validity of this finding is limited due to a lack of placebo control and potential performance bias. Additionally, it is unclear whether baseline zinc status alters the benefits of zinc supplementation.
Fecal incontinence. Topical zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with fecal incontinence shows that topically applying an ointment containing zinc sulfate 1% and aluminum sulfate 5% to the anal canal mucosa three times daily for 4 weeks improves symptoms approximately twice as much as a placebo ointment. Quality of life related to the incontinence also improved (90219).
Gastric cancer. It is unclear if dietary zinc is beneficial for gastric cancer prevention. Details: Population research has found that increased dietary zinc intake is not associated with a decreased risk of gastric cancer (90213).
Head and neck cancer. It is unclear if oral zinc improves survival in patients with head and neck cancers. Details: Preliminary clinical research in patients with head and neck cancers shows that zinc supplementation does not improve disease-free or metastasis-free survival rates after 3 years when compared with placebo (87103).
Hepatic encephalopathy. It is unclear if oral zinc is beneficial for reducing the severity of hepatic encephalopathy or preventing recurrence. Details: A meta-analysis of small clinical studies, as well as some individual clinical studies, show that short-term zinc supplementation improves cognitive function and possibly quality of life in patients with hepatic encephalopathy. These findings are based on results from the number connection test and other tests (87377,90202,106227). One study in patients with minimal hepatic encephalopathy used zinc bisglycinate 75 mg three times daily, providing elemental zinc 45 mg daily for 12 weeks (106227). However, other preliminary clinical research shows that short-term zinc supplementation does not improve hepatic encephalopathy severity when compared with placebo when assessed using Conn's index, which includes evaluation of mental state, asterixis (flapping tremor), number connection test, electroencephalogram (EEG) record, and plasma ammonia (87144). Also, a meta-analysis of clinical research shows that zinc sulfate supplementation does not reduce encephalopathy recurrence (90202). Based on these results, zinc supplementation may marginally improve cognitive function in hepatic encephalopathy patients, but it does not appear to improve disease severity or reduce the risk of recurrence.
HIV/AIDS-related diarrhea. It is unclear if oral zinc is beneficial for preventing diarrhea in adult HIV patients. Details: Short-term zinc supplementation does not appear to TREAT diarrhea in adult HIV patients with persistent diarrhea. Clinical research shows that taking zinc 50 mg twice daily for 7 days does not reduce the duration of HIV-related diarrhea when compared with placebo (87055). However, zinc supplementation may help PREVENT HIV-related diarrhea when administered long-term. Clinical research shows that taking elemental zinc 12-15 mg daily for 18 months reduces the rate of diarrhea by about half when compared with placebo in adult HIV patients with zinc deficiency (87216). In HIV-infected children, clinical research shows that taking elemental zinc 10 mg daily for 6 months can reduce the occurrence of diarrhea by 49% when compared with placebo (82377). However, administering zinc in combination with vitamin A until 2 years of age does not reduce the occurrence of diarrhea when compared with vitamin A alone in HIV-infected children (82417).
HIV/AIDS-related opportunistic infections. It is unclear if oral zinc is beneficial in opportunistic infections in patients with HIV/AIDs. Details: A small clinical study in patients with AIDS shows that taking zinc supplements orally in combination with zidovudine (AZT, Retrovir) might reduce opportunistic infections of Pneumocystis carinii and Candida when compared with taking zidovudine without zinc (6566).
Human papillomavirus (HPV). It is unclear if oral zinc is beneficial for preventing relapse in patients with vulvar warts or for treating HPV infections and cervical lesions in patients with abnormal cervical cytology. Details: One small clinical study in patients with vulvar warts shows that taking zinc sulfate 400 mg daily for 8 weeks in addition to topical treatments including podophyllin 20%, imiquimod 5%, or cryotherapy, does not affect the duration of response, but does reduce the relapse rate by approximately 66% after 6 months, when compared with topical treatments alone (90190). Additionally, a small, open-label study in zinc-sufficient females with HPV shows that taking zinc sulfate 220 mg twice daily for 3 months reduces the odds of persistent HPV infection by 87% and improves the resolution of pre-existing cervical lesions when compared with no treatment (109456).
Hypertension. It is unclear if oral zinc reduces blood pressure in normotensive or hypertensive patients. Details: A meta-analysis of small clinical trials shows that taking zinc reduces systolic blood pressure by about 1.5 mmHg, but does not reduce diastolic blood pressure, when compared with placebo. Response did not differ with the dosage of zinc or duration of supplementation. Only one study evaluated patients with hypertension; other patient populations included those with type 2 diabetes, diabetic retinopathy, pre-diabetes, obesity, polycystic ovary syndrome (PCOS), and patients on dialysis (104052). More research in patients with hypertension is needed to determine if zinc is beneficial in this population.
Impaired glucose tolerance (prediabetes). While some conflicting evidence exists, several small clinical studies suggest that oral zinc may improve glycemic control in patients with prediabetes. Details: A meta-analysis of three low-quality studies in patients with prediabetes suggests that taking zinc sulfate 20-30 mg, alone or in combination with lysine and vitamin C, for 6-12 months reduces fasting blood glucose and postprandial glucose when compared with control (105682). Furthermore, a small clinical study in patients with prediabetes shows that taking zinc gluconate 30 mg daily for 90 days improves glycemic parameters when compared with placebo. All study participants were also instructed to increase physical activity and start a calorie-restricted diet (105391). However, another small clinical study in patients with prediabetes shows that taking zinc gluconate 30 mg daily for 12 months does not improve glycemic parameters when compared with placebo (109454). The available research has been conducted in Sri Lanka, Bangladesh, Iran, and Australia; it is unclear if these findings are generalizable to other geographic locations.
Intestinal parasite infection. It is unclear if oral zinc is beneficial in patients with intestinal parasitic infections. Details: Zinc supplementation may help TREAT infection from Schistosoma mansoniin, but not other parasites, in children in developing countries. Results from one clinical study show that taking oral zinc sulfate 30-50 mg for 12 months reduces the intensity of Schistosoma mansoniin infection in children, as measured by number of eggs per gram in feces, when compared with placebo (87495). However, supplementation with zinc does not appear to reduce the intensity of Ascaris lumbricoides, Trichiuris trichura, nor Giardia lamblia infection in children (6586). Furthermore, preliminary clinical research suggests that supplementation with zinc may increase the duration of Entamoeba histolytica infection in children (87099). There are also inconsistent results regarding the effects of zinc in PREVENTING intestinal parasite infections. Some clinical research shows that taking zinc in combination with vitamin A reduces the incidence of Giardia lamblia infections when compared with placebo (87099). However, zinc supplementation does not appear to prevent intestinal infections by Ascaris lumbricoides, Schistosoma haematobium, nor Schistosoma mansoniin (87099,87495).
Kidney failure. It is unclear if oral zinc is beneficial for patients on hemodialysis who have resistance to erythropoiesis-stimulating agents (ESAs). Details: Zinc deficiency is thought to play a role in ESA-resistant anemia in patients with kidney failure. A small clinical trial in patients on hemodialysis with low zinc levels shows that taking zinc acetate hydrate, usually 25mg or 50 mg daily, for 12 months increases plasma levels of zinc and modestly reduces the required weekly dose of ESAs when compared with placebo. However, there was no effect on hemoglobin levels (109781).
Leukemia. It is unclear if oral zinc is beneficial for improving weight maintenance in children and adolescents with leukemia. Details: A small clinical study in children and adolescents with acute leukemia shows that taking zinc 2 mg/kg (as an amino acid salt) in two divided doses daily for 60 days doubles weight gain and reduces infection rate by approximately 60% when compared with placebo. However, zinc supplementation does not appear to improve nutritional status (90204).
Liver cancer. It is unclear if oral zinc is beneficial for preventing hepatocellular carcinoma (HCC). Details: In patients treated for hepatitis C, the presence of hepatic fibrosis increases the risk for development of HCC, and is also associated with low plasma zinc levels. In a retrospective analysis of patients with a sustained virological response to hepatitis C therapy, those taking oral zinc supplements for at least 6 months had approximately half the risk of developing HCC when compared with those not taking zinc. Maintaining a serum zinc level above 90 mcg/dL seems to reduce the risk for HCC (106904).
Lung cancer. It is unclear if increased dietary zinc intake is beneficial for reducing the risk of lung cancer. Details: Population research suggests that the highest dietary intake of zinc is associated with a 32% reduced risk of lung cancer when compared with the lowest intake (106235). Additionally, another large epidemiological cancer screening trial with a mean follow-up of 12.2 years suggests that dietary intake of zinc is protective against lung cancer, with the highest quartile of dietary intake showing the greatest benefit. However, this protective effect was not found for supplemental intake of zinc (112096).
Male infertility. It is unclear if oral zinc is beneficial for infertility in males. Details: Some preliminary clinical research shows that taking zinc sulfate 66 mg daily increases sperm count, testosterone levels, and the incidence of pregnancy in idiopathic infertile men with low testosterone levels (9334,87430). Another clinical study shows that taking zinc sulfate 66 mg daily can improve sperm morphology by approximately 33% when compared to baseline in men with a grade III varicocele (90194). However, not all research agrees. One clinical study shows that taking elemental zinc 30 mg with folic acid 5 mg daily for 6 months does not improve sperm morphology or pregnancy rates when compared with placebo in infertile men (102085). It is possible the lower dose used in this study was insufficient to produce the beneficial effects observed in earlier research. Zinc supplementation has also been studied as part of combination therapy. A retrospective study in males with or without varicocele-related infertility has found that taking a specific combination product containing zinc 10 mg, L-carnitine fumarate 1725 mg, acetyl-L-carnitine 500 mg, vitamin C 90 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. Improvements 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). There is also interest in using zinc to improve results of in vitro fertilization (IVF). A small clinical study in couples undergoing IVF suggests that infertile male partners who take a specific combination product (Menevit) containing zinc and other antioxidants seem to have an increased rate of viable pregnancies when compared with placebo (87087). However, it's unclear if the benefit can be attributed to zinc, other antioxidants, or the combination.
Melasma. It is unclear if topical zinc reduces melasma severity. Details: A small clinical study shows that applying a topical solution containing zinc sulfate 10% once daily for 2 months is less effective at reducing melasma severity when compared with hydroquinone 4% (90232).
Menopausal symptoms. It is unclear if oral zinc improves sexual function after menopause. Details: A single clinical trial shows that taking zinc sulfate 110 mg daily for 6 weeks modestly improves testosterone levels and sexual function, including desire, arousal, satisfaction, and pain, after menopause when compared with placebo (106228).
Migraine headache. It is unclear if oral zinc is beneficial in patients with migraine. Details: Two small clinical studies in patients with migraine show that taking zinc sulfate 200 mg or zinc gluconate 15 mg daily for 8-12 weeks modestly reduces migraine severity and frequency when compared with placebo (104040,105684). Both studies were conducted in Iran; it is unclear if these findings are generalizable to other geographic locations.
Nasopharyngeal cancer. It is unclear if oral zinc is beneficial in patients with this type of cancer. Details: A small clinical study in patients with locally advanced nasopharyngeal cancer shows that zinc supplementation 75 mg daily for 2 months may improve disease-free survival rates after 5 years when compared with placebo (87163).
Neonatal jaundice. It is unclear if oral zinc is beneficial for neonatal jaundice. Details: There is contradictory evidence about the effects of oral zinc in infants with hyperbilirubinemia. Two small clinical studies in infants with idiopathic neonatal hyperbilirubinemia show that receiving oral zinc sulfate 5 mg twice daily for 5-7 days does not affect levels of total bilirubin, the required duration of phototherapy, or the duration of hospitalization, when compared with placebo (90212,104814). However, a larger clinical trial in preterm infants receiving phototherapy and zinc 1.2 mg/kg daily as zinc sulfate heptahydrate, via either orogastric or nasogastric tube for 10 days, serum bilirubin levels were modestly decreased only on days 8-10 when compared with phototherapy alone (106242). Additionally, a second larger clinical trial in infants with idiopathic hyperbilirubinemia shows that receiving oral zinc sulfate (Zinc sulfate, Ramofarmin Company) 1 mg/kg daily for 3 days reduces total bilirubin levels and duration of phototherapy when compared with placebo; additionally length of hospitalization is reduced by less than 1 day (115631). The reason for these discrepant findings is unclear but may be attributed to variations in baseline characteristics, treatment duration, and dose.
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral zinc is beneficial in patients with NAFLD. Details: A small clinical study in patients with NAFLD shows that following a calorie-restricted diet and taking zinc 30 mg daily for 12 weeks reduces certain liver enzymes, but does not improve steatosis or reduce weight, when compared with taking placebo and following a calorie-restricted diet (104046).
Non-Hodgkin lymphoma. It is unclear if oral zinc is beneficial for non-Hodgkin lymphoma prevention. Details: Population research has found that higher dietary intake of zinc is associated with a 42% decreased odds of developing non-Hodgkin lymphoma (87048).
Obesity. Small studies suggest that oral zinc does not reduce weight or calorie intake in people with overweight or obesity. Details: A very small clinical study in adults with overweight or obesity shows that taking supplemental zinc 30 mg daily for 12 weeks does not reduce body weight, body mass index (BMI), calorie intake, or macronutrient intake when compared with placebo (112471). Additionally, clinical research in adults with overweight or obesity shows that taking zinc gluconate 25 mg and L-selenomethionine 200 mcg once daily for 8 weeks does not improve BMI, total body fat, or fat free mass when compared with placebo (111448).
Obsessive-compulsive disorder (OCD). It is unclear if oral zinc reduces symptoms in patients with OCD. Details: A small clinical study in patients with OCD shows that taking zinc sulfate 200 mg twice daily with fluoxetine 20 mg daily for 8 weeks modestly reduces the severity of OCD symptoms when compared with taking placebo with fluoxetine (90223).
Oral mucositis. It is unclear if oral or topical zinc prevents oral mucositis due to chemotherapy. Some small clinical studies suggest that oral zinc might prevent mucositis due to radiotherapy. Details: Two small clinical studies in adults with leukemia and other cancers shows that taking zinc sulfate 220 mg three times daily for 14 days or until the end of chemotherapy treatment reduces oral mucositis and pain intensity when compared with placebo (90191,98132). However, smaller doses have not shown benefit. A small clinical study in children and adolescents with leukemia shows that taking zinc 2 mg/kg daily (up to 60 mg daily) in two divided doses does not affect chemotherapy-induced mucositis when compared with placebo (90204). An unblinded clinical study in children and adolescents aged 8-16 years with recently diagnosed leukemia shows that taking zinc gluconate 50 mg (7 mg elemental zinc) daily does not significantly reduce the incidence or duration of oral mucositis when compared with a control group not receiving zinc (104816). Zinc also doesn't seem to be beneficial with high-dose chemotherapy. A small clinical study in adolescents and adults receiving high-dose chemotherapy prior to undergoing hematopoietic stem cell transplantation (HSCT) suggests that taking zinc sulfate 220 mg (50 mg elemental zinc) twice daily, beginning one day prior to the chemotherapy regimen and continuing for 3 weeks, does not affect the severity, duration, or onset of mucositis when compared with placebo (90215). Other preliminary clinical research in children aged 3-18 years receiving chemotherapy for leukemia or other cancer also shows that taking zinc 1 mg/kg orally daily for 14 days, beginning on the first day of chemotherapy, does not reduce the incidence or severity of mucositis when compared with placebo (111447). Topical zinc has also been investigated for radiation-induced or chemotherapy-induced oral mucositis. In two clinical studies, using 7.5 mL of a mouthwash containing zinc chloride 0.2% twice for 2 minutes every 8 hours for 3 weeks modestly reduces the incidence and severity of oral mucositis, and improves quality of life, when compared with a placebo mouthwash (106232,109690). In one study, the average patient weight was higher in the group using the mouthwash containing zinc (106232). Other preliminary clinical research in adults with head and neck cancer undergoing radiotherapy treatment, consisting of at least 30 Gy radiation exposure shows that using zinc sulfate 1% mouthwash, 5 mL three times daily for 6 weeks, beginning on the first day of radiation therapy, moderately improves oral mucositis severity and pain scores when compared with chlorhexidine 0.2% or placebo mouthwash (111291). Taking zinc orally might be beneficial in radiation-induced oral mucositis. A small clinical study in patients with head and neck tumors shows that taking zinc sulfate, providing 150 mg elemental zinc, daily starting at the first day of radiation therapy and ending at 6 weeks, reduces the severity of mucositis and prolongs the onset of mucositis when compared with placebo (86981). Another clinical study in patients with head and neck cancer shows that taking zinc sulfate 150 mg daily during and after chemoradiotherapy treatment, consisting of a total 69.5 Gy radiation exposure and cisplatin 40 mg/m2 weekly, is associated with less severe mucositis when compared with placebo (105677).
Osteoporosis. It is unclear if oral zinc improves bone density in patients with osteoporosis. Details: Population research has found that reduced zinc intake and lower zinc serum levels seem to be associated with lower bone mineral density (BMD) (6920,14410). In elderly patients with at least marginal zinc deficiency who are taking standard therapy for osteoporosis, preliminary clinical research shows that taking zinc acetate dihydrate (Nobelzin, Nobelpharma) providing elemental zinc 25 mg twice daily for 12 months increases BMD when compared with baseline. Increases in serum zinc were associated with improvements in BMD. However, it is unclear if increases in BMD were significant when compared with placebo (106230). It is also unclear if zinc improves BMD in patients without zinc deficiency. A small clinical study in healthy postmenopausal adults suggests that taking zinc in combination with copper, manganese, and calcium might slow bone loss when compared with placebo (1994). It is not clear if this effect is due to zinc, other ingredients, or the combination.
Overall mortality. It is unclear if oral zinc reduces overall mortality in young children. Details: A meta-analysis of clinical research in children under the age of five years shows that supplementation with zinc in daily doses of at least 10 mg reduces the risk of all-cause mortality by 16% when compared with either placebo, other vitamin and/or mineral supplementation, or no supplementation. The risk of mortality was reduced by 54% when children took zinc for up to one year, but overall mortality was not reduced in studies lasting at least one year (106239).
Periodontitis. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate or advanced periodontitis shows that taking a combination supplement containing zinc 3.75 mg, alpha-lipoic acid, coenzyme Q10, cranberry extract, grapeseed extract, selenium, vitamin C, and vitamin E twice daily for 8 weeks in addition to standard nonsurgical therapy does not reduce periodontal indices including bleeding on probing, gingival recession, plaque index, or inflammation when compared with placebo (111708).
Polycystic ovary syndrome (PCOS). It is unclear if oral zinc is beneficial in patients with PCOS. Details: A small clinical study in adults taking metformin for PCOS shows that also taking zinc sulfate 220 mg (50 mg elemental zinc) daily for 8 weeks improves hair loss and facial growth, but not acne, when compared with placebo (96071).
Postoperative sore throat. It is unclear if oral zinc is beneficial for postoperative sore throat. Details: Clinical research shows that dissolving a lozenge containing zinc 40 mg as zinc sulfate in the mouth in the 30 minutes before surgery involving endotracheal intubation reduces the incidence of postoperative sore throat by 58% when compared with placebo lozenges. It also seems to reduce the severity of postoperative sore throat that does occur (97138). Other clinical research in adults undergoing a procedure that required endotracheal intubation shows that using a preoperative 30-mL gargle containing zinc 40 mg does not affect sore throat scores when compared with magnesium sulphate 250 mg or budesonide 200 mcg gargles (114763).
Postpartum depression. It is unclear if oral zinc prevents postpartum depression after a Cesarean section (C-section). Details: A small observational study in pregnant patients with anemia who underwent C-section has found that taking zinc sulfate 100 mg daily for 4 days after surgery is associated with a 75% reduction in the odds of developing postpartum depression when compared with no supplementation (109452).
Premenstrual syndrome (PMS). It is unclear if oral zinc improves symptoms in patients with PMS. Details: A small clinical study in female college students shows that taking elemental zinc 30 mg daily for 3 months improves quality of life, but not quality of sleep, when compared with placebo (104049).
Preterm labor. It is unclear if oral zinc reduces the risk of preterm labor. Details: Observational research has found that low dietary intake of zinc during pregnancy is associated with an increased likelihood of preterm deliveries (87471). Also, most meta-analyses of clinical research show that taking zinc supplements during pregnancy modestly reduces the risk of preterm birth (106231). However, one large meta-analysis of 22 clinical studies shows that zinc supplementation during pregnancy seems to have little or no benefit for reducing the risk of preterm birth when compared with control (105679). Zinc supplementation also does not seem to reduce the risk of stillbirth, neonatal death, spontaneous abortion, or premature rupture of membranes (97142,105679,106231).
Prostatitis. It is unclear if oral zinc improves symptoms in men with chronic prostatitis. Details: A clinical study in men with chronic prostatitis shows that taking zinc sulfate 220 mg daily along with prazosin 2 mg daily for 12 weeks does not improve difficulty urinating or quality of life, but does seem to improve pain, when compared with prazosin alone (90210). The validity of this study was limited by a significant dropout rate.
Pruritus. There is limited evidence on the oral use of zinc for reducing pruritis in hemodialysis patients. Details: A small clinical study in end-stage renal disease patients with hemodialysis-associated pruritus shows that taking zinc sulfate 220 mg twice daily for 2 months reduces pruritus severity when compared with placebo (90218).
Psoriatic arthritis. It is unclear if oral zinc improves psoriatic arthritis symptoms. Details: Two small clinical trials in patients with psoriatic arthritis show that taking zinc orally, alone or in combination with nonsteroidal anti-inflammatory drugs (NSAIDs), does not seem to reduce pain or improve function when compared with control (6514,6515).
Respiratory tract infections. It is unclear if oral zinc reduces respiratory tract infections in children. Details: An open-label study in children aged 6 months to 5 years with zinc deficiency shows that taking zinc sulfate 20 mg orally once daily for 2 weeks reduces the number of episodes and the mean duration of upper and lower respiratory tract infections over 6 months of follow-up when compared with the 6 months prior to zinc supplementation (104815). The validity of this finding is limited by the lack of a comparator group.
Rosacea. It is unclear of oral zinc improves symptoms of rosacea or quality of life. Details: A small clinical trial shows that taking zinc sulfate 440 mg in two divided doses daily for 90 days does not improve quality of life or symptoms associated with rosacea when compared with placebo (90195).
Seizures. It is unclear if oral zinc reduces recurrent febrile seizures in children. Details: Although some individual preliminary clinical research disagrees (96069), a meta-analysis of generally low-quality research in children under 5 years of age with a previous febrile seizure shows that taking zinc sulfate 1-2 mg/kg or 20 mg daily for 6-12 months does not reduce febrile seizure recurrence when compared with placebo (106237). Also, a small clinical study shows that taking zinc does not increase the time to first febrile seizure recurrence (96069).
Sepsis. It is unclear if oral zinc is beneficial in pediatric or adult patients with sepsis. Details: A meta-analysis of clinical research in children under the age of five years shows that supplementation with zinc reduces the risk of sepsis mortality by 57% when compared with either placebo, other vitamin and/or mineral supplementation, or no supplementation (106239). Also, a small clinical study in newborns with sepsis shows that giving zinc sulfate monohydrate 3 mg/kg twice daily for 10 days along with antibiotics reduces the likelihood of neurological abnormalities, such as those related to posture, behavior, and reflexes, by 70% when compared with antibiotics alone. Mortality and length of hospital stay were not improved, but the study may have been inadequately powered to detect a difference in these parameters (96077). Another study in preterm infants with late-onset sepsis (developing at least 72 hours after birth), shows that giving 1.4 mg/kg elemental zinc daily orally for 10 days in addition to antibiotics reduces the number of infants with unresolved sepsis at 10 days, and reduces C-reactive protein and procalcitonin levels, when compared with giving antibiotics alone (104819). A meta-analysis of small clinical studies in infants less than 4 months old shows that administering zinc 1-3 mg/kg daily for 1-18 weeks may reduce the rate of infant mortality and treatment failure when compared with placebo or control, but does not seem to prevent sepsis or improve sepsis-related mortality (108444). Additionally, zinc has been evaluated in adults. A single-center observational study in adults with sepsis found that administering zinc orally or enterally in various doses, ranging from less than 15 mg to greater than 50 mg daily, does not improve survival rates or reduce the length of stay in the intensive care unit (115630).
Shigellosis. It is unclear if oral zinc is beneficial in patients with acute shigellosis from food poisoning. Details: A small clinical study in malnourished children with acute shigellosis (food poisoning) shows that administering a multivitamin syrup containing elemental zinc 20 mg daily for 2 weeks, in addition to standard treatment, can improve recovery time and reduce the number of diarrhea episodes when compared with multivitamin syrup without elemental zinc (87088).
Sleep deprivation. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in sleep-deprived recreational athletes shows that taking a combination of zinc 90 mg, magnesium 1350 mg, and vitamin B6 31.5 mg orally for 3 nights at bedtime does not change sleep quality, subjective sleepiness, mood, or fatigue when compared with placebo (113655).
Substance use disorder. It is unclear if oral zinc is beneficial for substance use disorder. Details: Preliminary clinical research in adults with opioid use disorder that were being treated with methadone shows that taking zinc sulfate, containing 12 mg zinc, orally daily for 3 months moderately improves relapse prevention scores, including drug use and drug craving scores, when compared with control. Taking zinc also modestly improved stress and anxiety scores (111293).
Tonsillopharyngitis. It is unclear if oral zinc is beneficial in patients with tonsillopharyngitis. Details: A moderate-sized, open-label clinical study in pediatric patients aged 3 to 10 years with acute tonsillopharyngitis shows that taking a specific combination solution (PediaFlù, Pediatrica S.r.l.) containing zinc (age dependent doses ranging from 2 to 4 mg), honey, propolis, and pelargonium sidoides daily for 6 days along with standard of care reduces tonsilitis severity scores when compared with standard care alone; however, this improvement is not clinically significant. (115632). It is not clear if these effects are due to zinc, other ingredients, or the combination.
Traumatic brain injury (TBI). There is limited evidence on the parenteral use of zinc for closed head injury. Details: A small clinical study shows that administering zinc parenterally immediately following severe closed head injury seems to improve the rate of neurological recovery when compared with standard therapy (2696).
Tuberculosis. It is unclear if oral zinc can improve outcomes in patients receiving tuberculosis treatment. Details: Low levels of zinc are common in patients with tuberculosis. In patients newly diagnosed with tuberculosis and using anti-tuberculosis treatment, some clinical research shows that taking zinc 50 mg daily as zinc sulfate for 6 months increases the number of patients with negative sputum smears by 50% to 80% within the first 6 weeks of treatment when compared with placebo. However, there were no differences in the number of patients with negative smears after this time point. There were also improvements in some liver function enzyme levels after 2 months, but not 6 months, when compared with placebo (106238). However, other clinical research shows that taking zinc 15-90 mg daily for 2-6 months does not improve cure rates or sputum smear conversions when compared with placebo. However, when combined with vitamin A, serum levels of vitamin A, zinc, and hemoglobin were modestly improved and there was a modest increase in sputum smear conversions (109754).
Urinary tract infections (UTIs). It is unclear if oral zinc is beneficial in children with UTI. Details: A low-quality, clinical study in children aged 3-12 years hospitalized for a UTI and receiving intravenous antibiotic treatment shows that taking zinc 1 mg/kg daily for 14 days reduces the duration of dysuria, urinary frequency, and urgency when compared with intravenous antibiotics alone. Zinc does not improve fever or the time to negative urine culture (96081). However, this study did not demonstrate that treatment groups were equal at baseline.
Venous leg ulcers. It is unclear if oral or topical zinc is beneficial for leg ulcer healing. Details: Two small studies in elderly patients with leg ulcers suggest that using a zinc saline solution on a wound dressing or applying zinc oxide to a dressing might improve healing of leg ulcers (2694,6901). However, oral zinc supplementation does not seem to be beneficial. A meta-analysis of four small clinical trials in patients with venous leg ulcers shows that taking zinc orally does not improve healing when compared with placebo (104079).
Vertigo. Oral zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with benign paroxysmal positional vertigo with serum 25-hydroxyvitamin D levels less than 20 ng/mL shows that taking a specific combination product containing zinc 7.5 mg, alpha-lipoic acid 600 mg, L-carnosine 165 mg, curcumin 100 mg, piperine 1 mg, cholecalciferol 800 units, vitamin B2 0.8 mg, and vitamin B6 1 mg (Vertistop D, Difass) orally daily for 6 months moderately reduces the number of vertigo relapse episodes when compared with control. However, in patients with serum 25-hydroxyvitamin D levels greater than 20 ng/mL that took a specific combination product containing zinc 7.5 mg, alanine 600 mg, L-carnosine 165 mg, curcumin 100 mg and piperine 1 mg (Vertistop L, Difass) orally daily for 6 months there was no difference in relapse episodes when compared with control (111294). It is unclear if this effect is due to zinc, other ingredients, or the combination.
Water warts. It is unclear if oral zinc is beneficial for the treatment of water warts in children. Details: In children with water warts, preliminary clinical research shows that taking zinc sulfate heptahydrate (as Zinco syrup) for 2 months results in lesion resolution in 70% of patients when compared with baseline. Lesion resolution occurred in an additional 13% of patients in the month after treatment completion, with no recurrence in any of these children over the next 9 months. Zinc 3 mg daily was used in children up to 3 years of age, and 5 mg daily was used in older children (106234). Due to the lack of a comparator group, it is unclear if these outcomes are due to zinc or the natural resolution of the condition.
Wound healing. Topical zinc might be beneficial for the healing of uncomplicated wounds. Details: A small clinical study shows that applying zinc chloride solution, standardized to contain zinc 20 mcg/mL, twice daily improves wound healing when compared with saline solution in patients with uncomplicated, skin wounds. However, when zinc is administered as a component of an insulin product (Humulin, Eli Lilly and Company), it seems to be more effective than zinc chloride alone (90192).
Wrinkled skin. Topical zinc has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A topical preparation containing 10% vitamin C as L-ascorbic acid and acetyl tyrosine, zinc sulfate, sodium hyaluronate, and bioflavonoids (Cellex-C High Potency Serum) applied to photo-aged facial skin for 3 months seems to improve fine and coarse wrinkling, yellowing and sallowness, roughness, and skin tone when compared with placebo (6155). More evidence is needed to rate zinc for these uses.

Safety view details

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

BACOPA

POSSIBLY SAFE ...when used orally and appropriately, short-term. Bacopa has been used safely in clinical trials at a dose of up to 600 mg daily for up to 12 weeks (10058,10059,17946,97605).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Clinical research suggests bacopa extract might be safe to use at a dose of 225 mg daily for up to 6 months or 320 mg daily for up to 14 weeks in children aged 6-14 years (33304,97603,109625).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

POSSIBLY SAFE ...when used orally and appropriately, short-term (7845,16117). A specific dried, inactive brewer's yeast preparation (EpiCor, Embria Health Sciences) has been used with apparent safety at a dose of 500 mg once daily for 12 weeks (92821,92822). A specific living brewer's yeast strain CNCM I-3856 has been used with apparent safety at a dose of 500-1000 mg daily (standardized to 8 billion colony-forming units per gram) for up to 12 weeks (95611,105170,111108). There is insufficient reliable information available about the safety of the long-term use of brewer's yeast or about the safety of using brewer's yeast topically.

CHILDREN:
There is insufficient reliable information available about the safety of brewer's yeast as a probiotic or postbiotic in children of any age. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

LIKELY SAFE ...when used orally and appropriately, short-term. Eleuthero root extract 300-2000 mg has been used safely in clinical trials lasting up to 3 months (730,1427,2574,7522,11099,15586,91509). There is insufficient reliable information available about the safety of eleuthero when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally in adolescents aged 12-17 years, short-term. Eleuthero 750 mg three times daily was used for 6 weeks with apparent safety in one clinical trial (75028). There is insufficient reliable information available about the safety of eleuthero in children or adolescents when used long-term.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

GELATIN

LIKELY SAFE ...when used orally in amounts commonly found in foods. Gelatin has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term . A specific type of gelatin from donkey hide, called colla corii asini, has been safely used in doses of 6-10 grams orally daily for 6-8 weeks. Higher doses of 15 grams daily have been associated with an increased risk of inflammatory adverse effects, including sore throat, swollen gums, local eczema, and oral ulcers (97634,107011). Since gelatin is often derived from bovine bones and skin, there is some concern about contamination with diseased animal parts (1825). So far, there are no reports of disease transmission to humans due to use of contaminated gelatin preparations.

CHILDREN: POSSIBLY SAFE
when gelatin tannate is used orally and appropriately in medicinal amounts, short-term. In children under 15 kg or under 3 years of age, gelatin tannate has been used with apparent safety at doses up to 250 mg four times daily for up to 5 days. In children over 15 kg or over 3 years of age, it has been used with apparent safety at doses up to 500 mg four times daily for up to 5 days (103296). There is insufficient reliable information available about the safety of other forms of gelatin in children.

PREGNANCY: LIKELY SAFE
when used orally in the amounts commonly found in foods.

PREGNANCY: POSSIBLY SAFE
when a specific type of gelatin from donkey hide, called colla corii asini, is used orally in doses of 10 grams daily for 6 weeks. Higher doses of 15 grams daily have been associated with an increased risk of inflammatory adverse effects, including sore throat, swollen gums, local eczema, and ulcers in the oral cavity (97634). There is insufficient reliable information available about the safety of other types of gelatin when used during pregnancy in medicinal amounts.

LACTATION: LIKELY SAFE
when used orally in the amounts commonly found in foods. There is insufficient reliable information available about the safety of using larger amounts of gelatin during lactation; avoid using.

ZINC

LIKELY SAFE ...when used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 40 mg daily (7135). ...when used topically and appropriately (2688,6538,6539,7135,8623,11051,111291).

POSSIBLY SAFE ...when used orally and appropriately in doses higher than the tolerable upper intake level (UL). Because the UL of zinc is based on regular daily intake, short-term excursions above 40 mg daily are not likely to be harmful. In fact, there is some evidence that doses of elemental zinc as high as 80 mg daily in combination with copper 2 mg can be used safely for approximately 6 years without significant adverse effects (7303,8622,92212). However, there is some concern that doses higher than the UL of 40 mg daily might decrease copper absorption and result in anemia (7135).

POSSIBLY UNSAFE ...when used intranasally. Case reports and animal research suggest that intranasal zinc might cause permanent anosmia or loss of sense of smell (11155,11156,11703,11704,11705,11706,11707,16800,16801,17083). Several hundred reports of anosmia have been submitted to the US Food and Drug Administration (FDA) and the manufacturer of some intranasal zinc products (Zicam) (16800,16801). Advise patients not to use intranasal zinc products.

LIKELY UNSAFE ...when taken orally in excessive amounts. Ingestion of 10-30 grams of zinc sulfate can be lethal in adults (7135). Chronic intake of 450-1600 mg daily can cause multiple forms of anemia, copper deficiency, and myeloneuropathies (7135,17092,17093,112473). This has been reported with use of zinc-containing denture adhesives in amounts exceeding the labeled directions, such as several times a day for several years (17092,17093). Advise patients to follow the label directions on denture adhesives that contain zinc.

CHILDREN: LIKELY SAFE
when used orally and appropriately (7135). Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL). The UL for children is based on age: 4 mg daily for 0-6 months, 5 mg daily for 7-12 months, 7 mg daily for 1-3 years, 12 mg daily for 4-8 years, 23 mg daily for 9-13 years, and 34 mg daily for 14-18 years (7135,97140).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Taking amounts greater than the UL can cause sideroblastic anemia and copper deficiency (7135). ...when used topically on damaged skin. An infant treated with 10% zinc oxide ointment for severe diaper rash with perianal erosions developed hyperzincemia. Absorption seemed to occur mainly via the erosions; plasma levels dropped after the erosions healed despite continued use of the ointment (106905).

PREGNANCY: LIKELY SAFE
when used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during pregnancy in those 14-18 years of age and 40 mg daily in those 19-50 years of age (7135).

PREGNANCY: LIKELY UNSAFE
when used orally in doses exceeding the UL (7135).

LACTATION: LIKELY SAFE
when used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during lactation in those 14-18 years of age, and 40 mg daily for those 19-50 years of age (7135).

LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL. Higher doses can cause zinc-induced copper deficiency in nursing infants (7135).

Interactions with Drugs view details

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

BACOPA

ANTICHOLINERGIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concurrent use might decrease the effectiveness of both agents.

Details

Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs (17946). Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.

CEVIMELINE (Evoxac)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, bacopa might increase the effects and adverse effects of cevimeline.

Details

In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes (109627). However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.

CHOLINERGIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.

Details

Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels (17946). Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.

Details

Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.

Details

In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes (97606). It is not known whether this is clinically significant.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.

Details

Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.

Details

Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant (97269,97606).

THYROID HORMONE

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, bacopa might have additive effects when used with thyroid hormone.

Details

Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40% (33286).

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Taking brewer's yeast with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Clinical research shows that taking chromium-containing brewer's yeast can decrease levels of blood glucose in diabetic patients being treated with antidiabetes drugs (37157).

ANTIFUNGALS

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, taking antifungals with some brewer's yeast products might decrease the effectiveness of brewer's yeast.

Details

Some brewer's yeast products contain live yeast. Therefore, simultaneously taking antifungals might kill a significant number of the organisms (4363).

LITHIUM

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, taking brewer's yeast with lithium might cause additive effects and side effects.

Details

Some brewer's yeast products contains lithium (37179).

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Interaction Rating = Major Do not take this combination.

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

Theoretically, taking brewer's yeast with MAOIs might increase the risk of hypertension.

Details

Brewer's yeast contains tyramine. Taking brewer's yeast with MAOIs might increase the risk for hypertensive crisis (2).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation (7592,74976). Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. This effect has not been reported in humans.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.

Details

Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals (7591,73535,74932,74956,74988,74990). A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels (91509). However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo (12536). These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.

Details

In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.

Details

In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.

Details

In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism (7532,10400).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.

Details

In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism (7532,10400).

DIGOXIN (Lanoxin)

Interaction Rating = Moderate Be cautious with this combination.

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

Eleuthero might increase serum digoxin levels and increase the risk of side effects.

Details

In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal (543). It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay (15585). Although the product was found to be free of digoxin and digitoxin (543), it was not tested for other contaminants (797).

IMMUNOSUPPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.

Details

Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity (74887,74915).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

Interaction Rating = Minor Be watchful with this combination.

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

Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.

Details

In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1 (35450). Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.

Details

In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein (22639,91509). However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

GELATIN

None known.

ZINC

AMILORIDE (Midamor)

Interaction Rating = Minor Be watchful with this combination.

Severity = Insignificant • Occurrence = Probable • Level of Evidence = B

Amiloride can modestly reduce zinc excretion and increase zinc levels.

Details

Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses (830,11626,11627,11634). The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

ATAZANAVIR (Reyataz)

Interaction Rating = Minor Be watchful with this combination.

Severity = Insignificant • Occurrence = Probable • Level of Evidence = B

Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.

Details

Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption (93578). Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication (90216).

CEPHALEXIN (Keflex)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.

Details

A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose (94163). To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

CISPLATIN (Platinol-AQ)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, zinc might interfere with the therapeutic effects of cisplatin.

Details

Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin (11624,11625). It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

INTEGRASE INHIBITORS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.

Details

Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation (93578,93579).

PENICILLAMINE (Cuprimine, Depen)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Zinc might reduce the levels and clinical effects of penicillamine.

Details

By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated (2678,4534,11605). Advise patients to take zinc and penicillamine at least 2 hours apart.

QUINOLONE ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Zinc can decrease the levels and clinical effects of quinolones antibiotics.

Details

Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time (828,2682,3046,11600). Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

RITONAVIR (Norvir)

Interaction Rating = Moderate Be cautious with this combination.

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

Zinc modestly reduces levels of ritonavir.

Details

Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption (93578). In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16% (90216). However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

TETRACYCLINE ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Zinc might reduce levels of tetracycline antibiotics.

Details

Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time (3046,4945). Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40% (11615). Demeclocycline and minocycline cause a similar interaction (4945). However, doxycycline does not seem to interact significantly with zinc (11615). Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

Report an Adverse Reaction to GinkgoPlus for Memory

Adverse Effects view details

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

BACOPA

General ...Orally, bacopa is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, dry mouth, headache, nausea.

Cardiovascular ...Orally, bacopa has been reported to cause palpitations (10058).

Gastrointestinal ...Orally, bacopa has been reported to cause abdominal cramps, abdominal pain, bloating, decreased appetite, diarrhea, dry mouth, excessive thirst, flatulence, indigestion, nausea, and increased stool frequency. Rates of adverse gastrointestinal events have ranged from 12% to 30% (10058,17946,33295,97605,109623,111520).

Musculoskeletal ...Orally, bacopa has been reported to cause arthralgia, muscle fatigue, and myopathy (10058,109623,111522). In one case, a 21-year-old male experienced progressive proximal weakness, muscle atrophy, weight loss, dark urine, and elevated serum markers of myopathy, with muscle biopsy showing immune-mediated necrotizing myopathy, after taking a supplement containing bacopa for 5 years (111522).

Neurologic/CNS ...Orally, bacopa has been reported to cause drowsiness, headache, insomnia, and vivid dreams (10058,10059,17946,109623).

Other ...Orally, bacopa has been reported to cause flu like symptoms and fatigue (10058,97605,111520).

General ...Orally, brewer's yeast seems to be well tolerated in most patients when used short-term.
Most Common Adverse Effects:
Orally: Flatulence, migraine.
Serious Adverse Effects (Rare):
Orally: There is concern that brewer's yeast may cause fungemia in some people. It may also cause anaphylaxis in sensitive individuals.

Gastrointestinal ...Orally, brewer's yeast can cause intestinal discomfort and flatulence in hypersensitive individuals (2). Anal irritation and abdominal pain have been reported rarely (105170).

Immunologic ...Allergic reactions to brewer's yeast can occur in hypersensitive individuals. Symptoms include itching, urticaria, local or general exanthemas, and Quincke's edema (2). Rarely, anaphylaxis may occur. In one case, a 33-year-old male experienced dyspnea, chest tightness, and throat tightness shortly after ingesting a few sips of craft beer brewed using brewer's yeast. The patient took diphenhydramine, and symptoms improved prior to his arrival in the emergency department. While the patient had no history of hypersensitivity to other beers from the same brewery, a positive skin test and oral challenge suggested that he was sensitive to the specific strain of brewer's yeast uniquely used only in the offending beer (111107).

Neurologic/CNS ...Orally, brewer's yeast can cause migraine-like headaches in sensitive individuals (2).

General ...Orally, eleuthero root is generally well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastrointestinal upset, headache, nausea, and urticaria.

Cardiovascular ...Orally, increased blood pressure has been reported in children with hypotension taking eleuthero in one clinical study (74980). Eleuthero has been reported to cause tachycardia, hypertension, and pericardial pain in patients with rheumatic heart disease or atherosclerosis. It is unclear if these effects were caused by eleuthero, or by the cardioglycoside-containing herb, silk vine (Periploca sepium), which is a common adulterant found in eleuthero products (12,797,6500).

Dermatologic ...Orally, eleuthero has been reported to cause rash in some clinical studies (75013,75028).

Gastrointestinal ...Orally, eleuthero has been reported to cause dyspepsia, nausea, diarrhea, and gastrointestinal upset in some patients (74938,75028,91510).

Genitourinary ...Orally, mastalgia and uterine bleeding were reported in 7. 3% of females taking eleuthero 2 grams daily in one clinical study (6500,11099). These adverse effects seem to be more likely with higher doses.

Neurologic/CNS ...Orally, headaches have been reported in 9. 8% of people taking eleuthero in one clinical study (11099).
In one case report, a 53-year-old female developed spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero (70419). It is unclear if this event was related to the use of eleuthero, the other ingredients, the combination, or another cause entirely.

Psychiatric ...Orally, nervousness has been reported in 7. 3% of people taking eleuthero in one clinical study (11099). Eleuthero has also been reported to cause slight anxiety, irritability, and melancholy in some patients (6500,11099). These adverse effects seem to be more likely to occur with higher doses.

GELATIN

General ...Orally, gelatin seems to be well tolerated.
Most Common Adverse Effects:
Oral: Belching, bloating, and dyspepsia.
Serious Adverse Effects (Rare):
Injection: IgE-mediated allergic reactions, Kounis syndrome.

Gastrointestinal ...Orally, gelatin can cause unpleasant taste, sensation of heaviness in the stomach, bloating, dyspepsia, and belching (7704).

Immunologic ...Gelatin can cause allergic reactions. Gelatin in foods can cause initial sensitization (7703). Gelatin-containing medicines including oral medications, suppositories, vaccines, and injectable products can cause IgE-mediated allergic reactions, including urticaria, angioedema, wheezing, hypotension, and anaphylaxis (7708,7709,7710,97633,111345). In the US, gelatin is used as a stabilizer in some vaccines such as measles, mumps, and rubella (MMR), and diphtheria, pertussis, tetanus (DPT) (7711). In one case report, a 73-year-old male experienced anaphylactic symptoms within 10 minutes of receiving gelatin lysate as a plasma expander during a routine surgery. The patient proceeded to develop heart, respiratory, and kidney failure and died 76 days after receiving the gelatin infusion (97633). At least 12 case reports describe life-threatening anaphylaxis after administration of gelatin-containing hemostatic agents during surgery. In these cases, hypotension, tachycardia, and increased airway pressure occurred shortly after injection of the agent into the pedicle tract (111345).
There are at least two cases of Kounis syndrome, an acute coronary syndrome related to a massive mast cell activation, after the use of a gelatin infusion during general anesthesia. In one case, immediate symptoms included bradycardia and hypotension, followed by myocardial ischemia and coronary vasospasm (97631).

Other ...Since gelatin is sometimes produced from bovine bones and skin, there is some concern about the potential risk of contamination with diseased animals and transmission of bovine spongiform encephalopathy (BSE, mad cow disease) and other diseases (1825). So far, there are no reports of BSE or other disease transmission to humans from gelatin products.

ZINC

General ...Orally, zinc is well tolerated in doses below the tolerable upper intake level (UL), which is 40 mg daily for adults. Topically, zinc is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, metallic taste, nausea and vomiting (dose-related).
Topically: Burning, discoloration, itching, stinging, and tingling when applied to irritated tissue.
Intranasally: Bad taste, dry mouth, headache, irritation, reduced sense of smell.
Serious Adverse Effects (Rare):
Orally: There have been cases of acute renal tubular necrosis, interstitial nephritis, neurological complications, severe vomiting, and sideroblastic anemia after zinc overdose.
Intranasally: There have been cases where intranasal zinc caused permanent loss of smell (anosmia).

Dermatologic ...Topically, zinc can cause burning, stinging, itching, and tingling when applied to inflamed tissue (6911,8623,87297). Zinc oxide can be deposited in the submucosal tissue and cause dark discoloration of the skin. This can occur with prolonged topical application to intact skin, application to eroded or ulcerated skin, or penetrating traumatic exposure, and also parenteral administration (8618).
In rare cases, oral zinc has resulted in worsened acne (104056), skin sensitivity (6592), a leishmanial reaction with a macular rash that occurred on exposed parts of the body (86935), eczema (104055), systemic contact dermatitis (109457), and the development of severe seborrheic dermatitis (86946).

Gastrointestinal ...Orally, zinc can cause nausea (338,2663,2681,6592,6700,18216,106230,106233,106227,113661), vomiting (2663,2681,6519,6592,96069,96074), a metallic or objectionable taste in the mouth (336,338,6700,11350,18216,106902,113661), abdominal cramping (6592,96069), indigestion (87227), heartburn (96069), dry mouth (87533), and mouth irritation (336,2619). When used orally in amounts above the tolerable upper intake level, zinc may cause irritation and corrosion of the gastrointestinal tract (331,86982,87315,106902), watery diarrhea (1352), epigastric pain (2663,2681), and severe vomiting (2663,2681).
Intranasally, zinc can cause bad taste, dry mouth, and burning and irritation of the throat (8628,8629).
When used topically as a mouth rinse, zinc may cause tooth staining (90206).

Hematologic ...There is concern that high daily doses of zinc, above the tolerable upper intake level (UL) of 40 mg per day, might increase the risk of copper deficiency, potentially leading to anemia and leukopenia (7135,112473). To prevent copper deficiency, some clinicians give a small dose of copper when zinc is used in high doses, long-term (7303).

Hepatic ...There are two cases of liver deterioration in patients with Wilson disease following initiation of treatment with zinc 50-200 mg three times daily. The mechanism of action is not understood, and the event is extremely uncommon (86927,87470).

Immunologic ...Daily doses of 300 mg of supplemental zinc for 6 weeks appear to impair immune response (7135). A case of erythematosus-like syndrome, including symptoms such as fever, leg ulcers, and rash, has been reported following intake of effervescent tablets (Solvezink) containing zinc 45 mg (87506). In another case, severe neutropenia was reported after taking supplemental zinc 900 mg daily for an unknown duration (112473).

Musculoskeletal ...Orally, zinc may cause body aches in children (113661).

Neurologic/CNS ...Zinc-containing denture adhesives can cause toxicity if used more frequently than recommended for several years. Case reports describe hyperzincemia, low copper levels, blood dyscrasias, and neurological problems, including sensory disturbances, numbness, tingling, limb weakness, and difficulty walking in patients applying denture adhesive multiple times daily for several years (17092,17093,90205,90233). Due to reports of zinc toxicity associated with use of excessive amounts of zinc-containing denture adhesives for several years, GlaxoSmithKline has reformulated Polygrip products to remove their zinc content (17092,17093).
Intranasally (8628) and orally (87534), zinc can cause headache. When used orally in amounts above the tolerable upper intake level (UL), zinc may cause central nervous system (CNS) symptoms including lethargy, fatigue, neuropathy, dizziness, and paresthesia (2663,2681,87369,87470,87533,87534,112473).

Oncologic ...There is concern that zinc might worsen prostate disease. For example, some preliminary evidence suggests that higher dietary zinc intake increases the risk for benign prostatic hyperplasia (6908). Epidemiological evidence suggests that taking more than 100 mg of supplemental zinc daily or taking supplemental zinc for 10 or more years doubles the risk of developing prostate cancer (10306). Another large-scale population study also suggests that men who take a multivitamin more than 7 times per week and who also take a separate zinc supplement have a significantly increased risk of prostate cancer-related mortality (15607). However, a large analysis of population research suggests that there is no association between zinc intake and the risk of prostate cancer (96075).

Pulmonary/Respiratory ...There are several hundred reports of complete loss of sense of smell (anosmia) that may be permanent with use of zinc gluconate nasal gel, such as Zicam (11306,11155,11707,16800,16801,17083,86999,87535). Loss of sense of smell is thought to be dose related but has also been reported following a single application (11306,11155,11707,16800). Patients often report having sniffed deeply when applying the gel, then experiencing an immediate burning sensation, and noticing anosmia within 48 hours (17083). On June 16, 2009, the US Food and Drug Administration (FDA) advised patients not to use a specific line of commercial zinc nasal products (Zicam) after receiving 130 reports of loss of smell (16800). The manufacturer of these products had also received several hundred reports of loss of smell related to its intranasal zinc products (16801). Zinc sulfate nasal spray was used unsuccessfully for polio prophylaxis before the polio vaccine was developed. It caused loss of smell and/or taste, which was sometimes permanent (11713). Animal studies suggest that zinc sulfate negatively affects smell, possibly by damaging the olfactory epithelium and neurons (11156,11703,11704,11705,11706). Zinc gluconate nasal spray has not been tested for safety in animals or humans. The clinical studies of intranasal zinc have not described anosmia as an adverse effect, but testing was not done to see if zinc use adversely affected sense of smell (6471,8628,8629,10247). Also, these clinical studies reported tingling or burning sensation in the nostril, dry nose, nose pain, and nosebleeds.
When used in amounts above the tolerable upper intake level (UL), zinc may cause flu-like symptoms including coughing (2663).

Renal ...In overdose, zinc can cause acute renal tubular necrosis and interstitial nephritis (331,1352,87338).

Other ...Occupational inhalation of zinc oxide fumes can cause metal fume fever with symptoms including fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, and salivation (331).

Report an Adverse Reaction to GinkgoPlus for Memory