Garlic & Parsley by Douglas Laboratories

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Chemotherapy-related infection. It is unclear if oral fermented wheat germ extract is effective for the prevention of febrile neutropenia in children receiving chemotherapy. Details: A small, open-label clinical study in children undergoing chemotherapy shows that a specific fermented wheat germ extract (Avemar) 6 grams/m2 dissolved in water and taken by mouth twice daily along with standard chemotherapy for an average of 10-11 chemotherapy cycles (approximately 29 months) reduces the frequency of febrile neutropenia when compared with chemotherapy alone. Thirty episodes of febrile neutropenia were reported for children receiving fermented wheat germ extract, compared to 46 episodes reported for children receiving chemotherapy alone (27702).
• Colorectal cancer. It is unclear if oral fermented wheat germ extract is beneficial in patients with colorectal cancer. Details: Small non-randomized, open-label clinical studies in patients with colorectal cancer show that taking a specific fermented wheat germ extract (Avemar) 9 grams once or twice daily for at least 6 months in addition to chemotherapy reduces colon cancer progression, the frequency of new metastases, and the risk of mortality when compared with chemotherapy alone (27703,27704). The validity of these findings is limited by a lack of randomization and blinding.
• Melanoma. It is unclear if oral fermented wheat germ extract is beneficial in patients with melanoma. Details: A small clinical study in patients with melanoma shows that a specific fermented wheat germ extract (Avemar) 8.5 grams mixed in a drink and taken once daily in addition to dacarbazine (DTIC)-based chemotherapy for 12 months increases overall survival after 7 years of follow-up by around 22 months and progression-free survival by around 26 months when compared with dacarbazine (DTIC)-based chemotherapy alone (27707).
• Prostate cancer. It is unclear if oral fermented wheat germ extract is beneficial in patients with prostate cancer. Details: A small clinical study in patients with castration-resistant prostate cancer shows that a specific fermented wheat germ extract (Avemar) 8.5 grams mixed in a drink and taken once or twice daily in addition to a gonadotropin releasing hormone analog for at least 4 months increases the doubling time for prostate specific antigen levels in most patients, but does not seem to improve quality of life, when compared to baseline (109632). The validity of these findings is limited by a lack of control group.
• Rheumatoid arthritis (RA). It is unclear if oral fermented wheat germ extract is beneficial in patients with RA. Details: A small, uncontrolled clinical study in females with RA shows that taking a specific fermented wheat germ extract (Avemar) 8.5 grams by mouth in a drink twice daily in addition to disease-modifying anti-rheumatic drug (DMARD) and steroid therapies for 12 months reduces morning stiffness and the dose of steroid drug needed when compared to baseline (27706). The validity of these findings is limited by a lack of control group.
• Systemic lupus erythematosus (SLE). Although there has been interest in using oral fermented wheat germ extract for SLE, there is insufficient reliable information about the clinical effects of fermented wheat germ extract for this purpose. More evidence is needed to rate fermented wheat germ extract for these uses.

(Read more about FERMENTED WHEAT GERM EXTRACT)

POSSIBLY EFFECTIVE

• Atherosclerosis. When used alone or in combination with other ingredients, oral garlic seems to slow the progression of atherosclerosis. Details: Taking low doses of garlic powder (Kwai, Lichtwer Pharma) 300 mg, administered as a single dose or three times daily for up to 4 years, seems to lessen age-related decreases in aortic elasticity (4797,51595). Additionally, taking a specific time-released garlic powder supplement (Allicor, INAT-Farma) 150 mg twice daily for 24 months seems to reduce the rate of atherosclerosis progression, as measured by carotid intima-media thickness, when compared with placebo in males with early evidence of carotid atherosclerosis (88394). Higher doses of 900 mg daily seem to slow development of atherosclerosis in both aortic and femoral arteries when used over a four-year period in females, but not in males (3315,4798). In patients with evidence of coronary artery calcium and a Framingham risk score of greater than 10%, taking aged garlic extract (Kyolic Reserve, Wakunaga) 1200 mg twice daily for 12 months reduces coronary artery calcium progression by 29% when compared with placebo (102670). A meta-analysis also found that garlic powder tablets and aged garlic extract may reduce coronary artery calcium scores when compared with placebo (110721). Some clinical research has investigated the use of garlic in combination with other ingredients. Taking a specific supplement (Kyolic, Total Heart Health, Formula 108, Wakunaga) containing aged garlic extract 250 mg plus vitamin B12 100 mcg, folic acid 300 mcg, vitamin B6 12.5 mg, and L-arginine 100 mg daily for 12 months significantly reduces coronary artery calcium progression and improves vascular function in patients with a Framingham risk score of 10% to 20% without coronary artery disease (88385). In addition, taking a combination product containing aged garlic extract 1200 mg and coenzyme Q10 120 mg daily for one year significantly improves vascular elasticity endothelial function in firefighters facing high degrees of occupational stress (44225).
• Diabetes. Most clinical research suggests that oral garlic, taken alone or in combination with metformin for at least 12 weeks, modestly reduces fasting blood glucose levels in patients with diabetes. It is unclear if garlic improves postprandial glucose levels or glycated hemoglobin (HbA1c). Details: A meta-analysis of results from seven clinical studies in adults with type 2 diabetes shows that taking garlic powder 600-1500 mg daily, garlic oil 8.2 mg daily, or aged garlic extract 1000 mg daily reduces fasting blood glucose levels by about 2 mg/dL when compared with control. The greatest benefit is seen for patients with hyperglycemia at baseline, for interventions lasting at least 12 weeks, and for formulations consisting of garlic powder (96004). Specific garlic formulations used in the reviewed studies have included garlic powder 300 mg 2-3 times daily as tablets (Kwai, Lichtwer Pharmaceuticals) or time-released tablets (Allicor, INAT-Farma) for 4-24 weeks, sometimes in combination with metformin or a sulfonylurea (51396,51463,96004). In one study, when used in combination with metformin, garlic reduced fasting blood glucose levels 70% more than when metformin was used alone (51463). The findings from these studies are in contrast with the results from older meta-analyses, which showed that garlic does not improve glycemic indices or lipid levels in patients with diabetes. Reasons for these discrepancies may relate to the fact that the older analyses included lower quality research (6465,6897). There is insufficient reliable information available to determine if garlic significantly improves postprandial glucose levels or HbA1c (96004). A small clinical trial shows that taking aged garlic extract (Kyolic, Wakunaga) 2400 mg daily for 12 months does not reduce left ventricular myocardial mass, a marker of poor cardiac outcomes, in patients with diabetes. However, this study may have been inadequately powered to detect a difference between groups (102671).
• Endometriosis. Oral garlic seems to improve pain in people with endometriosis. Details: A clinical study in patients with endometriosis shows that taking a tablet containing garlic powder 400 mg, providing allicin 1.1 mg, daily for 3 months along with standard care reduces overall pain scores from baseline by 72%, compared with an increase of 4% from baseline in patients receiving placebo along with standard care (106615).
• Hyperlipidemia. Most research shows that taking oral garlic for at least 8 weeks seems to modestly reduce total and low-density lipoprotein (LDL) cholesterol levels in patients with hyperlipidemia. However, evidence is conflicting on whether garlic improves high-density lipoprotein (HDL) cholesterol or triglyceride levels. Details: A robust meta-analysis on this topic suggests that, on average, garlic preparations reduce total cholesterol by 15 mg/dL and LDL cholesterol by 6 mg/dL when compared with placebo in patients with hyperlipidemia. These improvements appear to be more pronounced when garlic is taken for more than 8 weeks and in patients with total and LDL cholesterol levels that are at least borderline high before treatment. This same analysis shows no reduction in triglycerides and only a slight increase in HDL of 1.5 mg/dL with garlic treatment (88399). A more recent meta-analysis supports prior findings that taking garlic improves HDL, LDL, and apolipoprotein-A levels while having no impact on triglycerides level. The meta-analysis found that while garlic does not appear to reduce cholesterol in the general population, it may reduce total cholesterol when taken by patients with cardiovascular risk factors (110721). Another partially conflicting meta-analysis found that garlic powder reduces total cholesterol, LDL, and triglyceride levels, but has no impact on HDL levels (110720). The majority of available research supports these findings, but conflicting results exist (279,731,732,1873,1875,4782,4783,4784,4785,4786)(4787,4788,4789,4792,4793,4794,4795,4807,6457,6897)(51343,15295,15296,51422,51429,51469,51590,88399,107238)(107352,110721). Whether garlic is beneficial for treating hyperlipidemia may also depend on the specific formulation or product taken. Mixed results have been reported for a variety of specific garlic products, including garlic powder tablets (Kwai, Lichtwer Pharma) 600-900 mg daily in two or more divided doses for 6-16 weeks (279,731,4782,4783,4784,4785,4787,4789,4792,4793)(4795,4807), aged garlic extract (Kyolic, Wakunaga) 1000-7200 mg daily in divided doses for 4-6 months (1873,1875,15295), a garlic powder product (Garlex, Bosch Pharmaceuticals) 300 mg twice daily for 12 weeks (51343), aged back garlic extract (ABG+; PharmActive Biotech Products) 250 mg daily for 6 weeks (108607), and others (732,15295). Subgroup analyses from the most robust meta-analysis to date suggest that products containing aged garlic extract may be more effective for lowering total cholesterol than garlic powder preparations. If garlic powder preparations are used, total cholesterol levels seem to be lowered to a greater degree in patients taking enteric-coated garlic powder tablets. The opposite trend may be true for reducing LDL cholesterol. Garlic powder tablets seem to reduce LDL cholesterol levels while aged garlic extract does not. However, the few studies that did evaluate the effect of aged garlic extract on LDL cholesterol did so in patients with low baseline LDL cholesterol levels. There is limited evidence on the use of raw garlic or garlic oil products for treating hyperlipidemia (88399). Taking garlic 1200 mg with fish oil 3 grams daily for 4 weeks or garlic oil 500 mg with fish oil 700 mg daily for 60 days also appears to improve lipid parameters in some patients (4789,4790,51669). Garlic alone may be more effective than garlic plus fish oil for improving LDL cholesterol levels, but the combination may be useful in patients with elevated levels of total cholesterol, LDL cholesterol, and triglycerides (4789).
• Hypertension. Some clinical research suggests that oral garlic seems to modestly reduce blood pressure in hypertensive and normotensive patients. Details: One meta-analysis of clinical studies show that taking garlic can reduce systolic and diastolic blood pressure by about 5 mmHg and 3 mmHg, respectively, in patients with or without hypertension (16605,51414,96007). However, another meta-analysis found that taking garlic may not impact systolic or diastolic blood pressure in patients with coronary artery disease when compared with placebo (110721). When only patients with hypertension are considered, taking garlic can decrease systolic blood pressure by about 7-9 mmHg and diastolic blood pressure by about 4-6 mmHg. These results are limited by the fact that many of the included studies were of low to moderate quality and short duration (96007,96008,96014). Most clinical research appears to support these findings (278,279,1873,51442,88398). However, conflicting results exist (107238,110721). Some garlic formulations evaluated for hypertension have included a specific garlic powder formulation (Kwai, Lichtwer Pharma) 2400 mg as a single dose or 600 mg daily for 12 weeks and a specific aged garlic extract (Garlic High Potency Everyday Formula 112, Wakunaga/Wagner) 960 mg to 7.2 grams daily in up to three divided doses for up to 6 months (278,279,1873,51442,88398). Other doses used in the available research have included garlic tablets 300-1500 mg in divided doses daily for 24 weeks (88386) and garlic oil 500 mg plus fish oil 600 mg daily for 60 days (51669). Hypotensive effects of garlic have also been examined in population research. A large population study found that eating raw garlic at least twice daily is associated with a reduced likelihood of having prehypertension when compared with eating raw garlic three or fewer times per week. However, any significant relationship was eliminated after adjusting for dietary salt, making conclusions difficult (102677).
• Nonalcoholic fatty liver disease (NAFLD). Oral garlic seems to reduce the severity of hepatic steatosis in patients with NAFLD. Details: A meta-analysis including 4 studies with 186 patients with NAFLD found that taking 800-1600 mg of garlic powder daily may reduce aspartate aminotransferase (AST) and alanine transaminase (ALT) and lower the probability of hepatic steatosis by 2.75 times when compared with placebo (110720). Clinical research in patients with NAFLD shows that taking garlic powder reduces the severity of steatosis in 51% to 62% of patients, compared to 16% to 26% of those taking placebo (102681,103470). Doses of garlic included a specific powder (Amin Pharmaceutical Company) 800 mg twice daily for 12 weeks or an enteric-coated powder 400 mg twice daily for 15 weeks (102681,103479). There was also an improvement in most liver enzymes, other than alkaline phosphatase, and the level of low-density lipoprotein (LDL) cholesterol when compared with placebo (102681). In addition, population research shows a 7% reduction in odds of developing NAFLD with each 1 gram of raw garlic per 1000 kcal consumed. However, this association was not observed in females (102673). NAFLD is strongly and independently associated with an increased risk for prehypertension and hypertension. A clinical study in adults with NAFLD and stable diet- or antihypertensive-controlled blood pressure shows that taking an enteric-coated tablet containing garlic powder 400 mg (Amin Pharmaceuticals), providing allicin 1.5 mg, twice daily for 15 weeks reduces systolic blood pressure, diastolic blood pressure, and mean arterial pressure by 8, 3, and 6 mmHg, respectively, when compared with placebo. High-sensitivity C-reactive protein is also reduced by 16% when compared with placebo (106614).
• Periodontitis. Oral aged garlic extract seems to improve some measures of gum health in people with mild to moderate periodontitis. Details: Clinical research in otherwise healthy patients with mild to moderate periodontitis shows that taking a specific aged garlic extract (Kyolic, Wakunaga) orally 1200 mg twice daily for 18 months improves probing pocket depth, but not gingival recession, when compared with placebo (105760). The validity of these findings is limited by the lack of an intention to treat analysis.

POSSIBLY INEFFECTIVE

• Gastric cancer. Oral garlic does not seem to prevent gastric cancer. Details: Clinical research evaluating the effects of taking aged garlic extract for 7 years failed to show a reduced risk of developing gastric cancer up to 22 years later (14447,51470,102016), although there was a reduction in mortality associated with gastric cancer in subjects followed for 12-22 years (5-15 years after stopping the garlic extract) (102016). Also, a prospective, case-control study of 123,484 adults over a 30-year review period suggests that garlic intake, whether obtained from the diet or via supplementation, is not associated with a reduction in the rate of gastric cancer occurrence (97034). However, some research disagrees. One prospective population study suggests that a 1 kg/year increased increment in garlic intake is associated with a 17% reduced risk in gastric cancer incidence over 22 years. Also, consuming at least 3.25 kg yearly is associated with at least a 12% reduced risk when compared with consuming less than 2 kg each year. A sub-analysis suggests that this potential benefit is associated with garlic stalks, rather than garlic bulbs (111764). Meta-analyses of population research, as well as small population studies, have suggested 23% to 51% lower odds of developing gastric cancer with increased dietary garlic intake when compared with never eating garlic (3320,4775,4776,51209,51460,96005,108604). However, these studies have limited external validity.
• Helicobacter pylori. Oral garlic does not seem to be beneficial for Helicobacter pylori eradication. Details: Despite some promising initial laboratory research suggesting activity against Helicobacter pylori, garlic cloves, powder, or oil does not seem to have any beneficial effect when used to treat patients infected with Helicobacter pylori (3322,4761,4762,4763,4765,4774,97034).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral garlic for allergic rhinitis (hay fever), there is insufficient reliable information about the clinical effects of garlic for this condition.
• Alopecia areata. Topical garlic may increase hair growth by a small amount. Details: Preliminary clinical research in adults with alopecia areata shows that applying garlic 5% gel four times daily for 3 months, in addition to topical corticosteroid use, increases hair growth by 18% when compared with placebo plus topical corticosteroid (51386).
• Asthma. Although there has been interest in using oral garlic for asthma, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Athletic performance. It is unclear if oral garlic is beneficial for athletic performance. Details: Preliminary clinical research shows that taking a single dose of garlic 900 mg prior to exercise increases endurance when compared with placebo in young athletes (51623). A small preliminary clinical trial shows that taking garlic extract 1000 mg daily for 4 weeks does not reduce the time to cycle 40 km when compared to placebo (111765).
• Benign prostatic hyperplasia (BPH). It is unclear if oral garlic is beneficial for BPH. Details: In patients with BPH, preliminary clinical research shows that taking aqueous garlic extract 1 mg/kg daily for one month decreases prostate mass and urinary frequency and improves symptom scores and urinary flow rates when compared to baseline (10374). The validity of these findings is limited by the lack of a comparator group.
• Bladder cancer. Although there has been interest in using oral garlic for bladder cancer, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Breast cancer. It is unclear if oral garlic prevents breast cancer. Details: The relationship between garlic intake and risk of breast cancer is unclear. Overall, population research suggests that taking garlic does not seem to decrease the risk of breast cancer. However, when garlic and onions are examined together, there is some evidence of an association with a decreased risk of breast cancer (4779,102674). More research is needed.
• Bronchitis. Although there has been interest in using oral garlic for bronchitis, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Cardiovascular disease (CVD). It is unclear if oral garlic is beneficial for reducing CVD risk factors in adults with hypercholesterolemia. Details: A clinical crossover study in adults with moderate hypercholesterolemia shows that taking a specific product (ABG+; PharmActive Biotech Products) containing aged black garlic extract 250 mg, standardized to provide S-allyl-L-cysteine 1.25 mg, daily for 6 weeks does not improve blood pressure, glucose or cholesterol levels, or anthropometric measures when compared with placebo. A subgroup analysis in males with elevated diastolic blood pressure at baseline shows that taking this product reduces diastolic blood pressure by 5-mmHg when compared with placebo (108607). It is unclear if garlic is beneficial in patients with existing CVD.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral garlic for CFS, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Colorectal cancer. It is unclear if oral garlic prevents colorectal cancer. Details: Several individual population studies have found that higher dietary intake of garlic is associated with a reduced risk of colorectal cancer (3320,4770,4771,4772). However, results from meta-analyses of population research are mixed (96003,102669). Reasons for the discrepancy seem to relate to the type of population study conducted. A meta-analysis of case-control studies supports a preventative effect of garlic. However, this is not supported when cohort studies are analyzed separately (102669). Case-control studies are prone to recall and selection bias, and some do not account for confounding factors associated with colorectal cancer (96003). Two separate meta-analyses of observational research conducted in various countries have found that consumption of garlic and other allium-containing vegetables (onions, leeks, chives and scallions) is associated with a reduced risk of colorectal cancer; however, subgroup analyses suggest improvement is greatest in studies conducted in Asian countries, modest in those conducted in North America, and absent in those conducted in Europe (108604,108605). The reasons for these differing findings are unclear but may be related to regional differences in dietary habits, such as the use of raw or cooked garlic. Few studies have examined the effects of garlic supplements. While a single preliminary clinical study in patients with confirmed colorectal adenomas shows that taking high-dose aged garlic extract 2.4 mL daily for 12 months reduces the risk of developing new adenomas by 29% when compared with a lower dose of 0.16 mL daily (51320), other studies do not support the use of garlic supplements for this purpose (4773,96003).
• Common cold. Oral garlic might reduce the frequency of the common cold when used prophylactically. Details: Preliminary clinical research shows that taking one capsule of garlic daily for 12 weeks during the winter months reduces the number of self-reported colds by approximately 63% when compared with placebo. The duration of symptoms was also reduced by approximately one day (10787). Also, a small clinical trial in older patients living in residential care shows that 12% of those taking one capsule daily of a combination of garlic and onion powder (Aliocare, Domca Sau, Spain) for 36 weeks had one or more common cold episodes compared with 45% of those taking placebo. Each capsule provided 14 mg garlic powder (111768).
• Corns. It is unclear if topical garlic is beneficial for corns. Details: Preliminary clinical research in a small number of patients with corns shows that applying a lipid soluble garlic extract topically to corns on the feet twice daily for 10-20 days results in improvement in most patients when compared with baseline (15030). The validity of this finding is limited by the lack of a comparator group.
• Coronary heart disease (CHD). It is unclear if oral garlic is beneficial for CHD. Details: A meta-analysis of preliminary clinical research in adults with CHD shows that taking garlic orally 800-2000 mg daily for 2-48 weeks reduces total cholesterol levels by an average of 16 mg/dL when compared with placebo. Taking garlic did not affect other cholesterol levels; however, the study may have been inadequately powered to detect a difference between groups. The validity of this study is limited by inclusion of patients with and without dyslipidemia at baseline (107238).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral garlic is beneficial for COVID-19. Details: Clinical research in non-critically ill patients hospitalized with COVID-19 shows that taking garlic extract (Gallecina, Samisaz Pharmaceutical Company, Iran) 90 mg every 8 hours for 5 days or until discharge modestly reduces the proportion of patients requiring supplemental oxygen for at least 1 day when compared with placebo. However, there was no overall effect on clinical status, intensive care admission, or discharge prior to day 6. All patients also took remdesivir (111766). A small preliminary clinical study in patients hospitalized with mild to moderate symptoms of COVID-19 shows that taking garlic essential oil orally 50 mg twice daily before breakfast and dinner for 10 days, in addition to standard COVID-19 treatment, reduces the median duration of fever from 5 to 4 days, cough from 7 to 5 days, and weakness from 9 to 7 days when compared with standard treatment alone. The median time to a negative COVID-19 test decreased from 8 to 7 days (109530). The validity of this study is limited by incomplete randomization, the lack of a placebo comparator, and the exclusion of people with severe symptoms.
• Cystic fibrosis. It is unclear if oral garlic is beneficial for cystic fibrosis. Details: Preliminary clinical research shows that taking garlic oil macerate 625 mg daily for 8 weeks does not improve pulmonary function, symptom scores, or the need for antibiotic therapy when compared with placebo in children with cystic fibrosis and chronic pulmonary infection (51438).
• Dental hypersensitivity. Although there has been interest in using oral garlic for dental hypersensitivity, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Denture stomatitis. It is unclear if topical garlic as a mouthwash is beneficial for denture stomatitis. Details: Preliminary clinical research in patients with oral denture stomatitis shows that using a garlic mouthwash 40 mg/mL three times daily for 4 weeks improves redness when compared to baseline. When compared with nystatin, garlic has a lesser degree of recovery, but better patient satisfaction (51466).
• Diabetic retinopathy. It is unclear if oral garlic is beneficial for diabetic retinopathy. Details: Preliminary research in patients with diabetic retinopathy and macular edema, treated with intravitreal bevacizumab and laser photocoagulation, shows that taking garlic powder 1 gram orally daily for 4 weeks improves the best-corrected visual acuity by 0.18 logMAR (logarithm of the minimum angle of resolution), compared with 0.06 for placebo. It also decreases intraocular pressure by 1 mmHg, compared with 0.3 mmHg for placebo (109529).
• Diarrhea. Although there has been interest in using oral garlic for various types of diarrhea, including travelers' diarrhea and dysentery, there is insufficient reliable information about the clinical effects of garlic for these conditions.
• Dysmenorrhea. Although there has been interest in using oral garlic for dysmenorrhea, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Esophageal cancer. It is unclear if oral garlic prevents esophageal cancer. Details: Observational research regarding the use of garlic in preventing esophageal cancer is conflicting. Some evidence suggests that raw garlic consumption does not prevent the development of esophageal cancer (51508). However, other population research suggests that weekly garlic consumption decreases the risk of developing esophageal cancer (51209).
• Exercise-induced muscle soreness. It is unclear if oral garlic is beneficial for exercise-induced muscle soreness. Details: Preliminary clinical research shows that taking allicin, a constituent of garlic, 80 mg daily for 14 days can reduce subjective assessments of exercise-induced muscle soreness in athletes when compared with placebo (51404).
• Fatigue. Although there has been interest in using oral garlic for fatigue, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Familial hypercholesterolemia. Oral garlic does not seem to improve blood lipid levels in children with familial hypercholesterolemia. Details: In children with familial hypercholesterolemia, a small clinical trial shows that taking garlic powdered extract, standardized based on alliin content, does not improve levels of total cholesterol, low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol, triglycerides, lipoprotein (a), apolipoprotein B-100, homocysteine, fibrinogen, or blood pressure (4796).
• Fibrocystic breast disease. Oral garlic has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product (Karinat, INAT-Farma), containing garlic powder 150 mg, beta-carotene 2.5 mg, alpha-tocopherol 5 mg, and ascorbic acid 30 mg twice daily for 6 months reduces the severity of breast pain, premenstrual syndrome, and menstruation pain, and can cause regression of palpable symptoms of breast fibromatosis (51317). It is unclear if these effects are due to garlic, other ingredients, or the combination.
• Gastritis. Oral garlic has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with gastritis shows that taking a specific combination product (Karinat, INAT-Farma), containing garlic 150 mg, beta-carotene 2.5 mg, alpha-tocopherol 5 mg, and ascorbic acid 30 mg twice daily for 6 months improves digestion, inhibits H. pylori infection, and reduces the risk of precancerous lesion formation when compared with placebo (51308). It is unclear if these effects are due to garlic, other ingredients, or the combination.
• Gout. Although there has been interest in using oral garlic for gout, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Hepatitis. It is unclear if oral garlic is beneficial for hepatitis. Details: Preliminary clinical research shows that taking 3-6 capsules of a product containing garlic oil 50 mg and diphenyl-dimethyl-dicarboxylate 25 mg per capsule daily for 6 weeks improves liver function enzyme levels when compared with placebo in patients with chronic hepatitis (51478). The effects of garlic alone have not been determined.
• Hepatopulmonary syndrome. It is unclear if oral garlic is beneficial for hepatopulmonary syndrome. Details: Preliminary clinical research shows that garlic oil (Garlic Pearls, Ranbaxy, India) 1-2 grams/m² daily in two divided doses for 9-18 months may improve oxygen levels and remission rates when compared with placebo in patients with hepatopulmonary syndrome (51439).
• Influenza. Oral garlic has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in older patients living in residential care shows that 12% of those taking one capsule daily of a combination of garlic and onion powder (Aliocare, Domca Sau, Spain) for 36 weeks had one or more influenza-like episodes compared with 36% of those taking placebo. Each capsule provided 14 mg garlic powder (111768).
• Lead toxicity. It is unclear if oral garlic is beneficial for lead toxicity. Details: Preliminary clinical research shows that taking garlic powder 400 mg three times daily for 4 weeks reduces blood lead concentration when compared with baseline, but not when compared to treatment with D-penicillamine, in patients with mild to moderate lead poisoning (51467).
• Lung cancer. It is unclear if oral garlic prevents lung cancer. Details: Some population research suggests that eating raw garlic is associated with a reduced odds of developing lung cancer. However, other research suggests that eating garlic or taking garlic supplements is not associated with a reduced risk of lung cancer (4778,103482). Reasons for the discrepancy possibly relate to the type of garlic consumed.
• Metabolic syndrome. Small studies suggest that oral garlic may improve some metabolic parameters in patients with metabolic syndrome. Details: A clinical study in adults with metabolic syndrome shows that taking four tablets of garlic powder (Amin Pharmaceuticals), providing a total of 1600 mg garlic and 6 mg allicin, daily for 3 months improves waist circumference by 1.3 cm, blood pressure by 7-8 mmHg, HDL cholesterol levels by 4.5 mg/dL, and triglycerides levels by 40 mg/dL from baseline, compared with no improvement or worsening in patients taking placebo (106616). Similarly, preliminary clinical research in adults with metabolic syndrome shows that taking raw, crushed garlic 100 mg/kg twice daily for 4 weeks increases high-density lipoprotein (HDL) cholesterol and decreases waist circumference, blood pressure, triglycerides, and fasting blood glucose when compared to baseline (98812). The validity of these findings is limited by the lack of a control group. Another clinical study in adults with metabolic syndrome suggests that taking 1600 mg of garlic powder daily for 3 months may improve intestinal transit time, lipid accumulation product, cardiometabolic index, atherogenic index of plasma, and atherogenic indices including Castelli risk indices I and II (110722).
• Mosquito repellent. It is unclear if oral garlic is beneficial as a mosquito repellent. Details: Preliminary clinical research shows that taking a single dose of garlic orally does not seem to effectively repel mosquitos (51322). The effect of long-term garlic administration is unclear.
• Multiple myeloma. It is unclear if oral garlic prevents multiple myeloma. Details: A case-control study comparing a small population of adults with and without multiple myeloma has found that increased intake of garlic in the diet may be associated with a decreased risk of developing multiple myeloma (51476).
• Muscle strength. It is unclear if oral garlic is beneficial for muscle strength. Details: Population research has found that increased consumption of raw garlic is associated with increased hand grip strength in healthy adults. Females consuming raw garlic 2-3 times per week were 23% less likely to have low handgrip strength, defined as being below the 20th percentile, when compared to those who almost never eat garlic. In males, the odds of having low handgrip strength were 34% lower. Eating any raw garlic, even less than once per week, was associated with an increased likelihood for having high grip strength (102678).
• Obesity. It is unclear if oral garlic is beneficial for obesity. Details: Clinical research shows that taking garlic powder (Amin Pharmaceutical Company) 1600 mg daily for 12 weeks does not reduce body weight or body mass index when compared with placebo in overweight or obese patients with nonalcoholic fatty liver disease (NAFLD), although there is a small effect on waist circumference (102681). One small clinical study evaluating garlic in combination with multiple other ingredients shows that the combination (Prograde Metabolism) modestly improves body weight, fat mass, and waist and hip circumference when compared with placebo. The other ingredients include raspberry ketone, caffeine, capsicum extract, ginger root extract, bitter orange fruit, L-theanine, and black pepper fruit (40802). However, it is unclear if this benefit is due to garlic, other ingredients, or the combination.
• Onychomycosis. Although there has been interest in using topical garlic for onychomycosis, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Oropharyngeal candidiasis. It is unclear if oral garlic is beneficial for oropharyngeal candidiasis. Details: Preliminary clinical research in patients with oral candidiasis shows that applying a topical garlic paste four times daily for 14 days to affected areas can increase the rate of complete eradication of oral lesions by 23% when compared with clotrimazole solution (51330).
• Osteoarthritis. It is unclear if oral garlic is beneficial for osteoarthritis. Details: Preliminary clinical research in overweight and obese females with knee osteoarthritis shows that taking garlic tablets (Nature Made) 500 mg twice daily for 12 weeks modestly reduces pain scores by an additional 15% when compared with placebo (98813).
• Otitis media. Although there has been interest in using topical garlic for otitis media, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Peripheral arterial disease (PAD). Oral garlic seems to improve pain-free walking distance by a small amount in patients with PAD. However, it does not seem to improve blood pressure. Details: In patients with stage II peripheral arterial occlusive disease, a small clinical trial shows that taking garlic (Kwai) 400 mg twice daily for 12 weeks improves pain-free walking distance by about 15 meters. There was no effect on blood pressure or ankle or brachial pressures (4801).
• Polycystic ovary syndrome (PCOS). It is unclear if oral garlic is beneficial for PCOS. Details: Preliminary clinical research in adults with PCOS shows that taking garlic orally 800 mg daily for 8 weeks reduces low-density lipoprotein (LDL) cholesterol levels by approximately 8% when compared with placebo. Taking garlic did not affect other cholesterol levels; however, the study may have been inadequately powered to detect a difference between groups. Garlic supplementation also modestly reduces body mass index (BMI) and waist circumference in this population. However, there was no change in hip circumference (107238,111763).
• Pre-eclampsia. It is unclear if oral garlic prevents pre-eclampsia during the third trimester. Details: Preliminary clinical research shows that taking a specific garlic extract (Garlet, Cosar Pharmaceutical Company) 800 mg daily during the third trimester of pregnancy does not reduce the risk of developing pre-eclampsia in high-risk patients with first-time pregnancies (9201,51626).
• Premenstrual syndrome (PMS). It is unclear if oral garlic is beneficial for PMS. Details: Preliminary clinical research in adult students with moderate to severe PMS shows that taking a specific garlic supplement (Allium-S, Dineh Pharmaceutical Company) orally 400 mg daily, standardized to contain 1.1 mg allicin, for 3 menstrual cycles improves PMS symptom scores 1.4 times more than placebo. After taking garlic for 3 cycles, 91% of students improved to mild PMS, compared with only 36% in the placebo group (107239).
• Prostate cancer. Observational research on the relationship between garlic intake and prostate cancer risk is conflicting. It is unclear if garlic supplements are beneficial in patients with prostate cancer. Details: Observational research in Chinese males shows that those who eat garlic 2.14 grams/day (about one clove) seem to have a 50% lower risk of developing prostate cancer (9876). Also, a pooled analysis of epidemiological research suggests that garlic consumption may be associated with a 23% decreased odds of developing prostate cancer (88410). A case-control study has also found that garlic, consumed at least twice weekly, may reduce the risk for prostate cancer when compared with lower consumption (4777). However, other population research suggests that garlic consumption has no effect on prostate cancer risk in Iranian males (51454). One very small clinical study in patients with prostate cancer shows that taking garlic extract 1 mg/kg daily for one month might improve prostate specific antigen (PSA) levels, urinary flow, and urinary frequency when compared with baseline (10374). The validity of these findings is limited by the small study size and lack of a comparator group.
• Rheumatoid arthritis (RA). Oral garlic seems to reduce pain by a small amount in patients with RA. Details: Clinical research in females with RA shows that taking dried garlic (Garcin; Goldaru Co.) 500 mg twice daily, providing allicin 5 mg, for 8 weeks reduces pain after activity and improves functional ability by a small amount when compared with placebo. Fatigue and pain were reduced by approximately 13% and tender joint count was reduced by 47% (102680,103481). The long-term effect of garlic supplementation is unclear.
• Scleroderma. It is unclear if oral garlic is beneficial for scleroderma. Details: Clinical research shows that taking garlic 900 mg daily for 7 days does not have an effect on vasomotor function when compared with placebo in females with scleroderma (51374).
• Stress. Although there has been interest in using oral garlic for stress, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Tick repellent. It is unclear if oral garlic is beneficial as a tick repellent. Details: Preliminary clinical research shows that taking garlic 1200 mg daily for 8 weeks reduces the number of tick bites when compared with placebo (3318). However, the effect of garlic when compared with commercially available tick repellents is unknown (8027).
• Tinea capitis. Although there has been interest in using topical garlic for tinea capitis, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Tinea corporis. It is unclear if topical garlic is beneficial for tinea corporis. Details: Applying a gel containing 0.6% ajoene, a constituent of garlic, twice daily for one week seems to be as effective as terbinafine 1% cream for tinea corporis (4767).
• Tinea cruris. It is unclear if topical garlic is beneficial for tinea cruris. Details: Applying a gel containing 0.6% ajoene, a constituent of garlic, twice daily for one week seems to be as effective as terbinafine 1% cream for tinea cruris (4767).
• Tinea pedis. It is unclear if topical garlic is beneficial for tinea pedis. Details: Applying a gel containing 1% ajoene, a constituent of garlic, twice daily seems to be more effective than 0.6% ajoene gel, and seems to be as effective as 1% terbinafine (Lamisil) for tinea pedis infections. Sixty days after completing one week of treatment, mycological cure occurred in 100% of patients using 1% ajoene, 72% of patients using 0.6% ajoene , and 94% of those using 1% terbinafine (8019). Additional research suggests that 0.4% ajoene gel twice daily has a 7-day cure rate of around 80% (4766).
• Trichomoniasis. Although there has been interest in using oral garlic for trichomoniasis, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Tuberculosis. Although there has been interest in using oral garlic for tuberculosis, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Unstable angina. It is unclear if intravenous garlic is beneficial for unstable angina. Details: Preliminary clinical research in patients with unstable angina shows that giving garlicin, 60 mg by intravenous infusion daily for 10 days improves symptoms by 7% when compared with intravenous nitroglycerin (51244).
• Urinary tract infections (UTIs). Although there has been interest in using oral garlic for UTIs, there is insufficient reliable information about the clinical effects of garlic for this condition.
• Vaginal candidiasis. It is unclear if oral or topical garlic is beneficial for vaginal candidiasis. Details: One small clinical study in asymptomatic patients with culture-positive candida infections shows that taking garlic (Garlicin, Nature's Way) 1050 mg (3 tablets) twice daily for 14 days does not improve vaginal symptoms, candida colony counts, or cases of vaginal candidiasis when compared with placebo (88405). Another small clinical study shows that application of a vaginal cream containing garlic and thyme nightly for 7 nights is as effective as clotrimazole vaginal cream for treating vaginal candidiasis (88387). However, it is unclear if this effect is due to garlic, thyme, or the combination.
• Warts. It is unclear if topical garlic is beneficial for warts. Details: Preliminary clinical research shows that applying a specific lipid-soluble garlic extract topically to warts on the hands twice daily results in wart resolution within 1-2 weeks. An aqueous garlic extract applied twice daily also seems to provide modest improvement, but only after 30-40 days of treatment (15030). The validity of these findings is limited by the lack of a comparator group.
• Wound healing. It is unclear if topical garlic is beneficial for wound healing. Details: Based on patient and physician evaluations, preliminary clinical research shows that applying an ointment containing fresh garlic in petroleum jelly twice daily for 2 weeks results in 80% of surgical wounds healing at a faster rate than those treated with petroleum jelly. Most patients also indicated that the wound treated with garlic experienced less discomfort (102676). More evidence is needed to rate garlic for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Melasma. Preliminary clinical research in adults with melasma shows that applying a brewed parsley water to the face with a cotton ball on 6 days of each week for 8 weeks is as effective as hydroquinone 4% cream for improving dark spots (96828). More evidence is needed to rate parsley for this use.

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POSSIBLY SAFE ...when used orally and appropriately. A specific fermented wheat germ extract (Avemar) has been used safely in clinical research at doses of 8.5-9 grams once or twice daily for up to 12 months (27703,27704,27706,27708,109632). There is insufficient reliable information available regarding the safety of fermented wheat germ extract when applied topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. A specific fermented wheat germ extract (Avemar) has been used safely in clinical research at a dose of 6 grams/m2 twice daily for approximately 29 months (27702).

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

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LIKELY SAFE ...when used orally and appropriately. Garlic has been used safely in clinical studies lasting up to 7 years without reports of significant toxicity (1873,4782,4783,4784,4785,4786,4787,4789,4790,4797)(4798,6457,6897,14447,96008,96009,96014,102016,102670,103479)(107238,107239,107352,108607,110722,111763).

POSSIBLY SAFE ...when used topically. Garlic-containing gels, lipid-soluble garlic extracts, garlic pastes, and garlic mouthwashes have been safely used in clinical research for up to 3 months (4766,4767,8019,15030,51330,51386). ...when used intravaginally. A vaginal cream containing garlic and thyme has been safely used nightly for 7 nights (88387).

POSSIBLY UNSAFE ...when raw garlic is used topically (585). Raw garlic might cause severe skin irritation when applied topically.

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Garlic is reported to have abortifacient activity (11020). One study also suggests that garlic constituents are distributed to the amniotic fluid after a single dose of garlic (4828). However, there are no published reports of garlic adversely affecting pregnancy. In clinical research, garlic 800 mg daily was used during the third trimester of pregnancy with no reported adverse outcomes (9201,51626). There is insufficient reliable information available about the safety of topical garlic during pregnancy.

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).

LACTATION: POSSIBLY UNSAFE
when used orally in amounts greater than those found in foods. Several small studies suggest that garlic constituents are secreted in breast milk, and that nursing infants of mothers consuming garlic are prone to extended nursing (3319,4829,4830). There is insufficient reliable information available about the safety of topical garlic during lactation.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 8 weeks. Garlic extract 300 mg three times daily has been used with apparent safety for up 8 weeks in children ages 8-18 years (4796). There is insufficient reliable information available about the safety of garlic when used over longer durations or in higher doses.

CHILDREN: POSSIBLY UNSAFE
when raw garlic is used topically. Raw garlic might cause severe skin irritation when applied topically (585,51210).

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

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term (12,13173).

LIKELY UNSAFE ...when used orally in very large doses e., 200 grams). Parsley oil contains significant amounts of the potentially toxic constituents, apiole and myristicin (11). Apiole can cause blood dyscrasias, kidney toxicity, and liver toxicity; myristicin can cause giddiness and hallucinations (4). ...when parsley seed oil is used topically. Applying parsley seed oil to the skin can cause photodermatitis upon sun exposure (4). There is insufficient reliable information available about the safety of the topical use of parsley leaf and root.

PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts. Parsley has been used orally as an abortifacient and to stimulate menstrual flow (4,12,515,19104,92873). Population evidence suggests that maternal intake of An-Tai-Yin, an herbal combination product containing parsley and dong quai, during the first trimester increases the risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).

LACTATION:
Insufficient reliable information available; avoid using.

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IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, fermented wheat germ extract might decrease the effects of immunosuppressants.  Details Animal research suggests that fermented wheat germ extract can stimulate immune function (27709,27712,27713,27714,27727).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time (586,616,1874,3234,4366,4802,4803,51397,96013).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research suggests that garlic and garlic extract lower blood glucose levels in healthy and diabetic individuals (51463,96004).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.  Details In human research, both garlic and garlic extracts have blood pressure-lowering effects (277,278,279,1873,4787,6897,16605,51414,51442,51669)(88386,88398,96007).

ATAZANAVIR (Reyataz) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, garlic might decrease levels and effects of atazanavir.  Details In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4) (88388). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Garlic might increase levels of drugs metabolized by CYP2E1.  Details Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39% (10847). Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.  Details Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa (7027,93578). Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels (17221). Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days (96010). Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).

ISONIAZID Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, garlic might decrease levels of isoniazid.  Details Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa (15031); however, the exact mechanism of this potential interaction is not known.

PROTEASE INHIBITORS (PIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, garlic products containing allicin might decrease levels of PIs.  Details Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa (7027,93578). Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).

SAQUINAVIR (Fortovase, Invirase) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, garlic containing allicin might decrease levels of saquinavir.  Details Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa (7027,93578). Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506). Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.

SOFOSBUVIR (Sovaldi) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.  Details Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic (109524).

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, garlic might increase levels of tacrolimus.  Details In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus (96010).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, garlic might increase the risk of bleeding with warfarin.  Details Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time (586,616,1874,3234,4366,4802,4803,51397). In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use (51228,51631). However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk (15032,16416). More evidence is needed to determine the safety of using garlic with warfarin.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that parsley has antiplatelet effects (68209). Theoretically, concomitant use of parsley with other anticoagulant/antiplatelet drugs might reduce platelet aggregation and increase the risk of bleeding.  Details Some anticoagulant/antiplatelet drugs include aspirin, clopidogrel (Plavix), ticagrelor (Brilinta) diclofenac (Voltaren, Cataflam), ibuprofen (Advil, Motrin), naproxen (Anaprox, Naprosyn), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Laboratory research suggests that parsley can inhibit cytochrome P450 1A2 (CYP1A2) (68176). Theoretically concomitant use may increase the levels of CYP1A2 substrates.  Details Some drugs metabolized by CYP1A2 include amitriptyline (Elavil), haloperidol (Haldol), ondansetron (Zofran), propranolol (Inderal), theophylline (Theo-Dur, others), verapamil (Calan, Isoptin, others), and others.

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that parsley seed extract increases urine elimination (68119). Theoretically, parsley leaf and root might interfere with diuretic therapy due to aquaretic effects (512).  Details Some diuretic drugs include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), hydrochlorothiazide (HCTZ, HydroDiuril, Microzide), spironolactone (Aldactone), triamterene (Dyrenium), and others.

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General ...Orally, fermented wheat germ extract seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, nausea.

Gastrointestinal ...Orally, fermented wheat germ extract may cause diarrhea, nausea, flatulence, satiation, soft stools, and constipation. In one clinical study, diarrhea and nausea with or without vomiting were reported in 6% and 3% of patients, respectively (27703).

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General ...Orally, garlic is generally well tolerated. Topically, garlic seems to be well tolerated. Intravenously, there is insufficient reliable information available about adverse effects.
Most Common Adverse Effects:
Orally: Abdominal pain, body odor, flatulence, malodorous breath, and nausea. Allergic reactions in sensitive individuals.
Topically: Burns and dermatitis with fresh garlic.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with garlic.

Dermatologic ...Orally, garlic may cause pruritus (51316,51474,107239), flushing, and acne (107239). Oral intake of a specific garlic product containing allicin (Allimax) has been associated with a case of pruritic rash (51474). Enteric-coated garlic tablets standardized to 1.5% allicin have also been associated with a case of pruritus (51316). Garlic has also been associated with a case of superficial pemphigus in a 49-year-old male with type 2 diabetes (51564). Garlic-induced oral ulcers have also been reported (51467).
Topically, garlic may cause contact dermatitis and urticaria (4833,5004,12635,51258,51265,51375,51403,51412,51459,51483)(51511,51512,51530,51616,51617,51618,111769), as well as contact cheilitis (51384). Fresh garlic may be more likely to elicit a reaction than garlic extract. Most reactions have resolved following withdrawal of garlic therapy. In one case report, applying crushed garlic on the neck to help ease a sore throat resulted in an itchy, burning, erythematous lesion in a young female patient. The lesion healed after one week of treatment with topical antibiotics, steroids, and antihistamine ointments (88390). Cases of occupational eczema or dermatitis have been reported in cooks (51303,51210), food handlers (51292), and caterers (51304). According to one case report, dermatitis appeared in chefs exposed to garlic (15033). Treatment with acitretin 25 mg daily or topical psoralen-ultraviolet A (PUVA) for 12 weeks proved effective in mitigating the symptoms. A 34-year-old female with a history of hand dermatitis and paronychia had a worsening of these conditions after peeling raw garlic. She had a positive skin patch test to fresh, raw garlic but not to any other tested allergens, and the conditions resolved when she avoided contact with garlic (105528). Topically, garlic may also cause chemical burns, usually within 12 hours of application. Second- and third-degree chemical burns have been reported in adults, children, and infants exposed to topical garlic, often as an unintended consequence of using garlic medicinally on the skin (585,4832,51226,51230,51252,51281,51377,51418,51468,51495,51536)(51558,51576,51577,88409,96006). A case of painful blisters on the soles of the feet of a 23-year-old Chinese female has been attributed to chemical burns caused by applying crushed raw garlic for 3 hours (51440). Topically, garlic may also cause hyperpigmentation, ulcers, necrotic lesions, facial flushing, and local irritation (4832,15030,51268,51269,108606). In one case report, applying crushed raw garlic to the palatal mucosa for several minutes to relieve mouth pain resulted in a chemical burn that produced a 3 cm necrotic ulcer in an adult female with trigeminal neuralgia (108606).

Gastrointestinal ...Orally, dehydrated garlic preparations or raw garlic may cause malodorous breath (51438,51444), body odor (732,1873,4784,4793,4795,4798,9201,10787,42692,49769)(51269,51316,51467,51602), abdominal pain or fullness, anorexia, diarrhea, constipation, flatulence, belching, heartburn, nausea, unpleasant taste, reflux, and bowel obstruction (1884,6457,6897,9201,49769,51269,51343,51380,51438,51442)(51450,51457,51466,51471,51474,51520,51593,51602,51623,88398)(88405,111766).
Large quantities of garlic may damage the gastrointestinal tract. In one case report, a patient taking garlic for hypertension reported odynophagia and retrosternal pain after taking garlic without any water the previous day. An esophageal lesion 3 cm in length was detected upon endoscopy. The symptoms resolved 3 days after starting a liquid diet and taking lansoprazole 30 mg twice daily and sucralfate four times daily (88389). One case of bowel obstruction was reported in a 66-year-old male who ingested an entire garlic bulb (51525). Esophageal perforation has been reported in at least 17 individuals who consumed entire garlic cloves. In one case the perforation led to mediastinitis and death (102672).
Garlic has also been associated with eosinophilic infiltration of the gastrointestinal tract. In one case report a 42-year-old female presented with symptoms of eosinophilic gastroenteritis, which included pollinosis, asthma, diarrhea, heart burn, peripheral eosinophilia, and urticaria. After stopping use of garlic and sesame, the patient improved (51441). In a case report of eosinophilic esophagitis, garlic was determined to be the causative agent in a patient with long-standing gastrointestinal symptoms. The patient had attempted to treat upper gastrointestinal symptoms as gastrointestinal reflux disease without success for many years. Skin prick testing showed a positive reaction to garlic, of which the patient noted frequent consumption. Marked symptom improvement was noted within 3 weeks of garlic avoidance (88393).
Intravenously, garlic 1 mg/kg of body weight daily diluted into 500 mL saline and administered over 4 hours has been reported to cause abdominal discomfort, vomiting, diarrhea, nausea, anorexia, flatulence, weight loss, and garlicky body odor (51462).
Clinical research suggests that patients with metabolic syndrome taking 1600 mg of powdered garlic by mouth daily for 3 months may experience improved intestinal transit time when compared with placebo, suggesting that garlic powder may reduce symptoms of constipation (110722).

Genitourinary ...Orally, garlic might cause dysuria or polyuria (51438,51450,51467).

Hematologic ...Oral use of dietary garlic or supplements containing garlic has caused platelet dysfunction, increased fibrinolytic activity, prolonged bleeding time, retrobulbar hemorrhage (bleeding behind the eye) postoperative bleeding, and spinal epidural hematoma (586,587,4801,4802,11325,51397,51473,51491,51532,51534)(51570,51584,51593,51594). Also, a case of kidney hematoma following extracorporeal shock-wave lithotripsy (SWL) has been reported in a patient with nephrolithiasis who took aged garlic (51630). A case of increased bleeding time that complicated epistaxis management has been reported in a patient taking garlic, aspirin, and milk thistle (51426).
Intravenously, garlic has been associated with the development of thrombophlebitis at the injection site (51462).

Immunologic ...There is a case report of an immediate sensitivity reaction to oral raw garlic, resulting in wheals, in a 31-year-old female. The patient did not react to cooked garlic, and skin prick tests showed allergy only to raw garlic (96015). Researchers note that at least some allergens in raw garlic are heat labile (88392,96012,96015). This suggests that consuming cooked rather than raw garlic may help avoid this reaction in patients allergic to raw garlic. However, different people react to different allergens in garlic. At least some of these allergens are heat stable (96012). While rare, garlic-induced anaphylaxis has been reported (88392,96012).
Topically, allergic contact dermatitis has been reported in case reports (51406,51498,51510,51519,51560).

Musculoskeletal ...Orally, garlic has been associated with individual cases of gout and low back pain (51474,51467), but it is not clear if these adverse events can be attributed to garlic.

Neurologic/CNS ...Orally, dizziness, insomnia, headaches, diaphoresis, fever, chills, somnolence, increased appetite, euphoria, and weight loss have been reported with garlic (15032,42692,51316,51467,51471,51520). In one case, the smell of garlic was identified as a trigger for migraines in a 32-year-old female. The subject reported fortification spectra along with visual spots for a few seconds followed by instantaneous biparietal, crushing level (10/10) headaches upon exposure to the scent of garlic or onion (88404).

Pulmonary/Respiratory ...Garlic exposure, most notably in occupational settings, may cause asthma and other symptoms such as sneezing, nasal obstruction, rhinorrhea, and sinusitis (40661,51218). A case of minor hemoptysis has been reported for one patient with cystic fibrosis following intake of garlic capsules orally once daily for 8 weeks (51438). A 77-year-old female developed pneumonia related to the intake of one whole black garlic clove daily. The cloves were prepared by heating a whole garlic bulb in a pot for one month. Symptoms included dyspnea and coughing, and test results were positive for lymphocyte-induced stimulation by black garlic and raw garlic. The patient required treatment with oral steroids and was told to avoid garlic (96011).

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General ...Orally, parsley seems to be well tolerated when used low to moderate doses. In rare cases, allergy to parsley has been reported (92869,92870). In large doses (i.e., 200 grams) parsley oil may cause significant adverse effects due to its potentially toxic constituents, apiole and myristicin (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hemolytic anemia, thrombocytopenia purpura, nephrosis, hepatic dysfunction, and kidney irritation (4). Adverse effects specifically associated with the constituent myristicin include giddiness, deafness, hallucinations, hypotension, bradycardia, paralysis, and fatty degeneration of the liver and kidneys (4). Parsley oil can also cause contact photodermatitis with sun exposure (4).
Topically, parsley can cause contact photodermatitis (4).

Cardiovascular ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with myristicin include hypotension and bradycardia (4).

Dermatologic ...Orally, parsley oil can cause contact photodermatitis with sun exposure (4).
Topically, parsley can cause contact photodermatitis (4).

Hematologic ...Parsley contains the potentially toxic constituent apiole, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hemolytic anemia and thrombocytopenia purpura (4).

Hepatic ...Parsley contains the potentially toxic constituents, apiole and myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include hepatic dysfunction (4). Adverse effects specifically associated with the constituent myristicin include fatty degeneration of the liver (4).

Immunologic ...A case of anaphylaxis involving severe angioedema leading to unconsciousness has been reported in a woman who consumed parsley 45 minutes prior to symptoms. The patient responded to epinephrine, antihistamines, intravenous fluids, oxygen therapy, and 1 mg/kg methylprednisolone. The woman had consumed one cup of chopped parsley nearly every day for several years, but upon skin testing, the patient tested positive to parsley (92869). There is also a report of lip angioedema after consumption of raw parsley. The patient had anaphylaxis to raw arugula, and reported itchy red lesions after contact with the leaves of either raw parsley or arugula. The patient had positive skin prick tests to both plants. The reaction may have been due to oral allergy syndrome, as the patient could tolerate cooked arugula and parsley, but not raw (92870).

Ocular/Otic ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). An adverse effect specifically associated with the constituent myristicin includes deafness (4).

Psychiatric ...Parsley contains the potentially toxic constituent, myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with the constituent myristicin include giddiness and hallucinations (4).

Renal ...Parsley contains the potentially toxic constituents, apiole and myristicin, which can cause significant adverse effects at high doses (11). Adverse effects specifically associated with more than 10 grams of the constituent apiole include nephrosis and kidney irritation (4). Adverse effects specifically associated with the constituent myristicin include fatty degeneration of the kidneys (4).

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