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Medication News & Update

Garlic has long been used by many people for various reasons. While there may be some beneficial health effects most are modest at best if at all. For an excellent article covering this topic please use the following link.

http://www.aafp.org/afp/20050701/103.html

Specific drug info on Garlic from Clinical Pharmacology

Garlic, Allium sativum
Centrum® Herbals Garlic | Garlicin® | GarliPure™ | Garlique™ | Kwai® | Kyolic™ | Oleomed™ Blood Pressure | One-A-Day® Garlic

Classification:
• Nutritional Supplements
    • Nutraceuticals
        • Phytomedicinals

Description, Mechanism of Action, Pharmacokinetics

NOTE: In the US, nutraceuticals are marketed under the Dietary Supplement and Health Education Act of 1994 (DSHEA). Consequently, scientific data supporting claimed benefit(s) are not always available for nutraceuticals as they are for traditional pharmaceuticals since nutraceuticals are not regulated as drugs. Consumers should also note that rigid quality control standards are not required for nutraceuticals and substantial variability can occur in both the potency and the purity of these products. Monographs on nutraceuticals are included in CP when reliable clinical data are available. The information presented below is condensed from the best clinical data we could find.

NOTE: All references to garlic powder in this monograph refer to garlic standardized to 1.3% alliin. Not all products available in the US meet these standards.

Description: Garlic is a dietary supplement derived from the bulb of Allium sativum, family Liliaceae. It can be regarded simultaneously as a food and a medicinal herb and has been used as such since the times of the Egyptian pharoahs and the earliest Chinese dynasties. Over 1000 papers have been published in the past 20 years on garlic and related alliums.[1797] Extensive clinical and scientific studies partially support the use of garlic for the treatment of hypercholesterolemia, infection, and the prevention of atherosclerosis. Garlic is composed of many natural sulfur compounds, including a sulfur-containing amino acid, alliin (S-allyl-L-cysteine sulfoxide). Alliin is pharmacologically inactive. When garlic is crushed, alliin mixes with the enzyme alliinase and is converted to allicin (diallyl thiosulfinate). Allicin is unstable and upon steam distillation or oil maceration yields various diallyl and dimethyl sulfides plus E-ajoene and Z-ajoene. In general, the total activity of garlic is in its ability to produce allicin, which then produces other active principles. This is referred to as the allicin yield.[1797] The allicin yield is decreased when garlic is exposed to heat or acidic environments. Garlic may also contain various amounts of vitamins and minerals. Garlic is listed in the USP and is Generally Recognized As Safe (GRAS) by the FDA.

Mechanism of Action: Garlic exhibits potentially beneficial clinical activity as an antihyperlipidemic, antimicrobial, antiplatelet, antioxidant, antidiabetic, and a vasoprotective agent. Allicin is commonly accepted as the pharmacologically active component in garlic.

•Antimicrobial Actions: Infectious microorganisms utilize alcohol dehydrogenase for nutrient digestion and cysteine proteinase for tissue invasion. Allicin has been shown to inhibit these enzymes through a reaction with their sulfhydryl groups. This may explain why garlic can prevent the development of dysentery due to Entamoeba histolytica in hamsters.

•Antihyperlipidemic Actions: Since sulfhydryl-containing compounds are involved in the synthesis of cholesterol, allicin's sulfhydryl binding ability may also explain the cholesterol-lowering action of garlic. The mechanism of action is believed to be through the formation of sulfide bridges by the disulfides found in garlic with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase or the reductase molecules found in lipids.

•Antiplatelet Actions: It is well documented that garlic inhibits platelet function, probably through inhibition of thromboxane synthesis. Methylallyltrisulfide (MATS) is the chemical substance found in garlic believed to be responsible for this effect.[2233] The ajoenes are also thought to possess potent antithrombotic actions.

•Antioxidant Actions: The blood levels of the antioxidant enzymes, catylase and glutathione peroxidase, are increased by the effects of allicin. Thus, garlic, through the effects of allicin, has antioxidant and free-radical scavenging potential.

•Hypoglycemic Actions: Limited animal data suggest that selected consituents in garlic might have some antidiabetic activity, resulting in increased serum insulin concentrations and increased glycogen storage in the liver.[5194] Patients with diabetes frequently purchase alternative remedies that have been purported to improve glycemic control, but there is no scientific or controlled evidence in humans of this action.[5195] Limited clinical evidence suggests that garlic does not affect blood glucose in those without diabetes.[5196]

•Vasoprotective Effects: Abnormal aortic function can result from any change in the structure of the arterial wall. Endothelium-derived relaxant factor (nitric oxide) and other substances can alter the elastic properties of the aortic wall through direct and indirect mechanisms. Increased nitric oxide synthetase activity was demonstrated when human tissues were treated with garlic extracts, which may facilitate endothelium-dependent smooth muscle relaxation. Thus, garlic may improve aortic elasticity through restoration of impaired endothelium.[2234] Other studies suggest garlic increases fibrinolytic activity, inhibits platelet aggregation and atherosclerotic plaque formation. The precise mechanism(s) remain to be defined.

Pharmacokinetics: Garlic is administered orally and topically. Potency of garlic products can vary substantially from manufacturer to manufacturer due to mode of preparation. An extract standardized to 1.3% alliin is recommended. Fresh garlic yields roughly 0.4% allicin, the desired active ingredient; garlic powder contains roughly 1.3% allicin; dried garlic contains no allicin, but does contain alliin (allicin precursor) and the enzyme (alliinase) necessary to convert alliin to allicin. However, this enzymatic process cannot occur in the acidic environment of the stomach. Dried garlic dosage forms must be enteric coated for protection from gastric fluid and allow enzymatic conversion to occur in the small intestine. Since allicin is unstable in oil, oil-based products should be avoided. A German study found that only 5 of 18 commonly sold garlic preparations contained acceptable amounts of allicin, garlic's major active ingredient. Urinary presence of sulfur compounds has been documented following oral administration of garlic in human subjects.[2235]

Description, Mechanism of Action, Pharmacokinetics last revised 4/27/2004 11:52:00 AM

Indications

† non-FDA-approved indication

Dosage

For the treatment of hypercholesterolemia†:
Oral dosage:
Adults: 300 mg tablets PO three times per day lowered total and LDL cholesterol by roughly 6% and 11%, respectively, after 12 weeks. Serum measurements of HDL, cholesterol and triglycerides did not change.[2236] Other studies utilized doses of 0.25—1 g of fresh garlic/kg/day, which is equivalent to 5—20 average-sized (4 g) garlic cloves/day for an 80 kg person. A German study showed that 800 mg of garlic powder reduced cholesterol and triglycerides by 12% and 17%, respectively. Based on this study, Tyler calculates that only 2.8 g of fresh garlic - less than one average-sized clove - is needed per day.[1797] Based on meta-analysis, one-half to one clove of fresh garlic per day was estimated as necessary to lower total serum cholesterol by roughly 9%.[2237] A recent double-blind, randomized, placebo-controlled, cross-over trial found 4000 mcg/day of steam-distilled garlic oil had no effect on serum lipoprotein levels of healthy patients with moderate hypercholesterolemia.[2238] The German Commission E recommends 4 g/day of fresh garlic for use as an adjunct to dietary measures for elevated blood lipid levels.
Children: 300 mg PO three times per day of an enteric coated garlic extract tablet, equivalent to 0.6 mg of allicin per tablet, demonstrated no significant effect on fasting total cholesterol in children with familial hyperlipidemia and a minimum fasting total cholesterol level greater than 185 mg/dL during an eight week randomized, double-blind, placebo-controlled clinical trial.[2239]

For the prevention of atherosclerosis† (arteriosclerosis†):
Oral dosage:
Adults: 300—900 mg/day PO of standardized garlic powder consumed on a regular basis for 2 years or more demonstrated lower pulse wave velocity (PWV) independent of age and SBP in healthy, non-smoking individuals between 50 and 80 years of age included in a cross-sectional, matched-pairs observational study.[2234] Arterial elasticity decreased in both groups with advancing age, but to a lesser extent for those who consumed garlic on a chronic basis. The German Commission E recommends 4 g/day of fresh garlic as a preventative measure for age-dependent vascular changes.

For the treatment of Microsporum canis†, sporotrichosis† and tinea pedis†:
NOTE: Both internal and external preparations have been used to treat topical infections. Even though raw garlic can be caustic to the skin resulting in dermatitis, external preparations are preferred.
Oral dosage:
Adults: 2—5 mg/day PO of allicin extract.
Topical dosage:
Adults: No well controlled studies exist, sliced fresh cloves or commercial garlic oil applied 2—3 times per day to affected areas for 1—2 weeks have been used.[2240] One case each of culture-confirmed Microsporum canis[2241] and sporotrichosis[2242] are reported to have healed with the topical use of garlic. Culture-confirmed tinea pedis in 34 soldiers was effectively treated with topical garlic extract (i.e., ajoene); no clinical signs of fungal infection were present and negative cultures were obtained after 1—2 weeks of therapy.[2243]

Maximum Dosage Limits:
No specific maximum dosage information is available.

Patients with hepatic impairment:
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with renal impairment:
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Intermittent hemodialysis:
Specific guidelines for dosage adjustments in HD are not available; it appears that no dosage adjustments are needed.

†non-FDA-approved indication

Indications...Dosage last revised 1/23/2003 3:28:00 PM

Administration Guidelines

Oral Administration
•Daily ingestion of a supplement containing at least 5000 mcg of allicin or chewing one garlic clove daily is suggested for therapeutic purposes. An extract standardized to 1.3% alliin is recommended.
•Garlic's active enzyme, alliinase, is destroyed by heat (cooking) and acid.
•Garlic is available in many different forms, but is best when consumed raw.
•Enteric coated, odor controlled garlic powder supplements may prevent body odor and inactivation of alliinase by gastric fluid. The activity of other garlic preparations is questionable.
•Treatment should be evaluated over a 3—6 month period to determine efficacy, except when used topically for skin infections.

Topical Administration:
•Commercially prepared garlic oil or slices of raw garlic are used topically for the treatment of fungal infections. Oral products have also been used.
•Even though raw garlic may be caustic to the skin and can cause contact dermatitis,
externally applied preparations are often preferred over internal consumption for the treatment of topical lesions.

†non-FDA approved

Administration last revised 7/1/2002

†non-FDA-approved indication

Contraindications/Precautions

NOTE: Garlic has not been evaluated by the Food and Drug Administration as a pharmaceutical. However, it is 'Generally Recognized As Safe' and appears on the FDA's GRAS list. Products containing garlic are not intended to diagnose, treat, cure, or prevent any disease. Consumers should also be informed that rigid quality control standards are not required for nutraceuticals and substantial variability can occur in both the potency and the purity of these products.

Elderly patients should consult a physician, pharmacist, nutritionist or other health-care professional prior to using a dietary supplement such as garlic.[2232] Beneficial effects of chronic garlic intake in healthy individuals 50 to 80 years of age have been demonstrated.[2234]

Garlic should be used cautiously in young children as safety has not been established. However, no significant absolute or relative effects on height, weight or blood pressure were noted during an 8 week randomized, double-blind placebo controlled clinical trial with 30 children who received 300 mg of garlic PO tid. There were statistically significant increases in laboratory parameters of albumin (avg. +2 g/L) and hemoglobin (avg. +5.2 g/L).[2239]

Garlic should be used cautiously during pregnancy as safety has not been established. However, there are no known contraindications to the use of garlic during pregnancy and lactation.[2244] One child reportedly refused breast-feeding after the mother had consumed garlic in excessive amounts, which was possibly transmitted through the breast milk.

Because components in garlic inhibit platelet aggregation and demonstrate antithrombotic activity, use caution when bleeding is a concern. This may include individuals who are receiving anticoagulant therapy or thrombolytic therapy.

Because garlic inhibits platelet function, patients should inform their health care professional that they take garlic prior to scheduling surgery.[5566] As with many other platelet inhibitors, discontinue garlic supplements at least 7 days prior to the surgical procedure. It may be wise to discontinue this herb 2—3 weeks prior to an elective procedure when possible.[5568]

Limited animal data suggest that selected consituents in garlic might have some antidiabetic activity.[5194] Patients with diabetes frequently purchase alternative remedies that have been purported to improve glycemic control, but there is no scientific or controlled evidence in humans of this action.[5195] Limited clinical evidence suggests that garlic does not affect blood glucose in those without diabetes.[5196] Until more data are available, individuals with diabetes mellitus should use caution in taking dietary supplements containing garlic, and follow their normally recommended strategies for blood glucose monitoring.

Garlic supplementation should be avoided by some patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). A serious drug interaction between garlic and a HIV protease inhibitor (i.e., saquinavir) has been reported; this interaction may compromise the effectiveness of anti-retroviral therapy and lead to increased rates of HIV drug-resistance (see Drug Interactions).

Contraindications last revised 4/27/2004 11:52:00 AM

Drug Interactions

Garlic, Allium sativum may produce clinically-significant antiplatelet effects [2233]; until more data are available, garlic should be used cautiously in patients receiving drugs with a potential risk for bleeding such as diflunisal, NSAIDs, anticoagulants, platelet inhibitors like aspirin, ASA, or thrombolytic agents. In regard to warfarin, no substantial clinical data are available to support or deny a potential for interaction; the data are limited to a random case report.[5200] A case of spontaneous spinal epidural hematoma, attributed to dysfunctional platelets from excessive garlic use in a patient not receiving concomitant anticoagulation, has been reported.[2245] Patients who choose to consume garlic supplements while receiving the listed medications should be observed clinically for evidence of adverse effects.

Limited animal data suggest that selected constituents in Garlic, Allium sativum might have some antidiabetic activity, resulting in increased serum insulin concentrations and increased glycogen storage in the liver.[5194] Patients with diabetes frequently purchase alternative remedies that have been purported to improve glycemic control, but there is no scientific or controlled evidence in humans of this action.[5195] Limited clinical evidence suggests that garlic does not affect blood glucose in those without diabetes.[5196] Until more data are available, individuals receiving antidiabetic agents should use caution in consuming dietary supplements containing garlic, and follow their normally recommended strategies for blood glucose monitoring.

Garlic, Allium sativum may produce clinically-significant antiplatelet effects [2233]. Garlic may theoretically interact with other herbs and dietary supplements that exhibit antiplatelet effects or anticoagulant activity, such as danshen; dong quai, Angelica sinensis, feverfew, Tanacetum parthenium; ginger, Zingiber officinale; ginkgo, Ginkgo biloba; ginseng, Panax ginseng; green tea, horse chestnut, Aesculus hippocastanum; willow bark; and others. NOTE: This list is not inclusive of all herbs or dietary supplements that might have antiplatelet effects or anticoagulant activity. Published clinical data describing dietary supplement interactions are not always available.

Garlic, Allium sativum supplementation may lead to a significant decline in plasma concentrations of the protease-inhibitor saquinavir, leading to saquinavir treatment failures and the potential development of viral resistance. In one study, mean saquinavir concentrations dropped by 51% in the presence of garlic supplementation equivalent to roughly 2 cloves/day (4.64 mg allicin and 11.2 mg allin per capsule given twice daily). HIV-infected patients who are taking saquinavir as the sole protease inhibitor in their HIV treatment regimen should avoid garlic supplements.[3400] [5730] No information is available regarding the use of garlic capsules with saquinavir that is enhanced or 'boosted' with ritonavir.[5730]

Interactions last revised 9/29/2004 7:12:00 AM

Adverse Reactions

Adverse effects from herbal products are not always reported. Garlic consumed in moderate amounts on a daily basis appears to have no adverse effects in normal individuals. Allergic reactions to garlic are rare.

The most common adverse effects associated with the use of garlic in therapeutic doses are related to gastrointestinal complaints. These include dyspepsia, flatulence, halitosis and pyrosis (heartburn). Eructation(belching) was reported in 1 of 20 patients utilizing garlic tablets.[2236]

Contact dermatitis may occur from exposure to garlic extract (juice) or bulbs. Patients should be advised to avoid direct contact with skin or to report cases of dermatitis if garlic is used as a topical antiinfective.

Headache and dyspepsia were the most common adverse effects reported by 15 pediatric patients during eight weeks of oral therapy with 900 mg/day of standardized garlic. Minor adverse effects were reported on the midpoint questionnaire by 36% of the placebo group compared to 31% in the garlic extract group; and on the endpoint questionnaire by 13% of the placebo group and 21% of the garlic extract group.[2239]

One case of spontaneous spinal epidural hematoma secondary to ingestion of excessive amounts of garlic has been reported.[2245] The authors associated the patient's platelet dysfunction with the use of large quantities of garlic.

Adverse Reactions last revised 7/1/2002

Product Information

More information about the following products is available:
• Centrum® Herbals Garlic
• Garlicin®
• GarliPure™
• Garlique™
• Kwai®
• Kyolic™
• Oleomed™ Blood Pressure
• One-A-Day® Garlic

References

1797. Robbers JE, Tyler VE. Tyler's Herbs of Choice: the Therapeutic Use of Phytomedicinals. Binghamton NY: Haworth Herbal Press, Inc.; 1999.

2232. Kurtzwell P. An FDA guide to dietary supplements. FDA Consumer 1998;Sept-Oct:1—5. Publication No. (FDA) 99-2323.

2233. Ariga T. Platelet aggregation inhibitor in garlic (letter). Lancet 1980;i:150.

2234. Breithaupt-Grogler K, Ling M, Boudoulas H, et al. Protective effect of chronic garlic intake on elastic properties of aorta in the elderly. Circulation 1997;96:2649—55.

2235. DeSmet P, Brouwers J. Pharmacokinetic evaluation of herbal remedies. Clin Pharmacokinet 1997;32:427—36.

2236. Jain AK, et al. Can garlic reduce levels of serum lipids? A controlled clinical study. Am J Med 1993;94:632.

2237. Warshafsky S, Kamer RS, Sivak SL. Effect of garlic on total serum cholesterol: a meta-analysis. Ann Intern Med 1993;119:599—605.

2238. Berthold HK, Sudhop T, von Bergmann K. Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism. JAMA 1998;279:1900—2.

2239. McCrindle B, Helden E, Conner W. Garlic extract therapy in children with hypercholesterolemia. Arch Pediatr Adolesc Med 1998;152:1089—94.

2240. Dietz V. Garlic for the treatment of topical infections: does it help? Alt Med Alert 1999;March:30.

2241. Rich GE. Garlic an antibiotic? Med J Aust 1982;1:60.

2242. Tutakne MA, et al. Sporotrichosis treated with garlic juice. A case report. Indian J Dermatol 1983;28:41—5.

2243. Ledezma E, et al. Efficacy of ajoene, an organosulphur derived from garlic, in the short-term therapy of tinea pedis. Mycoses 1996;39:393—5.

2244. Muller JL, Clauson KA. Pharmaceutical considerations of common herbal medicine. Am J Man Care 1997;3:1753—70.

2245. Rose KD, Croissant PD, Parliament CF, et al. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurg 1990;26:880—2.

3400. Piscitelli SC, Burstein AH, Weldon N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002;34:234—8.

5194. Sheela CG, Kumud K, Augusti KT. Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Planta Med 1995;61:356—7.

5195. Ryan EA, Pick ME, Marceau C. Use of alternative medicines in diabetes mellitus. Diabet Med 2001;18:242—5.

5196. Bordia A, Verma SK, Srivastava KC. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty Acids 1998;58:257—63.

5200. Vaes LP, Chyka PA. Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: nature of the evidence. Review. Ann Pharmacother 2000;34:1478—82.

5566. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001;286:208-16. Review.

5568. Leak JA. Herbal medicines: what do we need to know? ASA Newsletter 2000:64.

5730. Invirase® (saquinavir) package insert. Nutley, NJ: Roche Pharmaceuticals; 2005 Sep.