Garlic and Cardiovascular Disease Summary Points

1. In adults or children with or without dyslipidemia, does oral ingestion of garlic (fresh, cooked, or supplements) compared with no garlic, other oral supplements, or drugs lower plasma lipid levels?

Thirty-seven randomized trials, all but one in adults, consistently showed that compared with placebo, various garlic preparations led to small reductions in total cholesterol at 1 month (range of average pooled reductions 1.2 to 17.3 mg/dL) and 3 months (range of average pooled reductions 12.4 to 25.4 mg/dL). Eight placebo-controlled trials reported outcomes at 6 months; pooled analyses showed no significant reductions of total cholesterol with garlic compared with placebo. It is not clear whether statistically significant positive short-term effects, but negative longer term effects, are due to systematic differences in studies that have longer and shorter followup durations, fewer longer term studies, or time-dependent effects of garlic. Statistically significant reductions in LDL (range 0 to 13.5 mg/dL) and in triglycerides (range 7.6 to 34.0 mg/dL) also were found in pooled analyses at 3 months. No significant changes in HDL were seen in pooled analyses at 1 and 3 months. One multicenter trial involving 98 adults with hyperlipidemia found no differences in lipid outcomes at 3 months between persons given an antilipidemic agent and persons given a standardized dehydrated garlic preparation (Kwai^® ). Most trials had significant methodological flaws such as unclear randomization processes and no intention-to-treat analyses, which limited the ability to make firm conclusions.

2. In adults or children with or without hypertension, does oral ingestion of garlic compared with no garlic, other oral supplements, or drugs lower blood pressure?

Twenty-seven small, randomized trials, all but one in adults and of short duration, reported mixed, but never large, effects of garlic on blood pressure outcomes. Most studies did not find significant differences in persons randomized to garlic compared with those randomized to placebo. The one small trial (n=40) that directly compared a standardized dehydrated garlic preparation to an active antihypertensive agent found no differences in blood pressure between groups. Because of unclear randomization processes, lack of intention-to-treat analyses, missing data, and variability in blood pressure measurement techniques, no firm conclusions can be made from these trials.

3. In adults or children with or without diabetes, does oral ingestion of garlic compared with no garlic, other oral supplements, or drugs increase insulin sensitivity?

Two small, short trials, both in adults, reported no statistically significant effects of garlic compared with placebo on serum insulin or C peptide levels.

4. In adults or children with or without diabetes, does oral ingestion of garlic compared with no garlic, other oral supplements, or drugs lower plasma glucose levels or glycosylated hemoglobin?

Twelve small, randomized trials, all in adults and of short duration, suggested that garlic has no significant effect on glucose in persons with or without diabetes. Because of the small number of trials, the short followup, unclear randomization processes, no intention-to-treat analyses, and missing data, no firm conclusions can be made.

5. In adults or children with or without diabetes, does oral ingestion of garlic compared with no garlic, other oral supplements, or drugs increase antithrombotic activity?

Ten small, randomized trials, all but one in adults and of short duration, showed promising effects of garlic on platelet aggregation and mixed effects on plasma viscosity and fibrinolytic activity. Because of few participants in the trials, short followup durations, unclear randomization processes, no intention-to-treat analyses, missing data, and variability in techniques used to assess outcomes, no firm conclusions can be made.

6. In adults at average or high risk for cardiovascular disease, does oral ingestion of garlic compared with no garlic, other oral supplements, or drugs decrease cardiovascular morbidity or mortality?

There are insufficient data to confirm or refute effects of garlic on clinical outcomes such as myocardial infarction and claudication. One randomized trial with 492 participants found no statistically significant decreases in numbers of myocardial infarctions and deaths when placebo was compared with 6 to 10 g of garlic ether extract after 3 years. Numbers of participants who adhered to prescribed garlic regimens or who failed to complete the study followup were not described. This trial was not published in peer-review literature. Details confirming its randomization process and followup were not obtained despite requests to the author.

Two trials in patients with atherosclerotic lower extremity disease found that garlic increased pain-free walking distance at 12 to 16 weeks compared with placebo. In the first trial, 80 participants were randomized to standardized dehydrated garlic or placebo, but only 64 completed the trial. Among those, pain-free walking distance increased by approximately 40 meters with garlic compared with approximately 30 meters with placebo. In the second trial, 100 participants were randomized to placebo or a garlic oil macerate/soya lecithin/hawthorn oil/wheat germ oil combination. At 4 months, maximum walking distance increased significantly more in the garlic group (114 percent) than in the placebo group (17 percent) (p<0.05).

7. Do different preparations of garlic vary in effectiveness regarding any of the above outcomes?

RCTs do not establish whether garlic effectiveness varies across preparations or dosages. Limited data, not derived from head-to-head comparisons, suggest, but do not prove, that standardized dehydrated preparations may have greater short-term (1- to 3-month) lipid-lowering effects than other preparations.

Garlic and Cancer Summary Points

1. In adults without cancer risk factors, precancerous conditions, or malignancy, does garlic ingestion compared with no garlic, placebo, or other oral supplements reduce the risk of developing cancer?

Scant data, primarily from case-control studies, suggest, but do not prove, that dietary garlic consumption is associated with decreased odds of laryngeal, gastric, colorectal, and endometrial cancer, and adenomatous colorectal polyps. Single case-control studies suggest, but do not prove, that dietary garlic consumption is not associated with breast or prostate cancer. Data regarding esophageal cancer are conflicting. No conclusions regarding associations between the use of particular garlic supplements and precancerous lesions or cancer can be made. Preliminary 3-year evidence from a large cohort study suggests that consumption of "any" garlic supplement does not reduce the risk of breast, lung, colon, or gastric cancer. This study has not reported associations relevant to the consumption of fresh or raw garlic, and its data about supplements are limited because information is not available about different types and brands of garlic supplementations.

2. In adults with cancer risk factors, but no precancerous conditions or malignancy, does garlic ingestion compared with no garlic, placebo, or other oral supplements reduce the risk of developing cancer?

No controlled studies in humans specific to this question were found.

3. In adults, does garlic ingestion compared with no garlic, placebo, or other oral supplements reduce the risk of developing precancerous lesions?

There are very limited data regarding the associations of garlic with precancerous lesions. One small survey that was limited by low response rates showed no statistically significant associations between the consumption of raw garlic and precancerous gastric lesions. One large case-control study suggested that increased garlic consumption was associated with lower odds of colorectal polyps. There is an ongoing, but not yet reported, large trial in China that is evaluating the effects of two garlic preparations on gastric precancerous lesions.

4. In adults with cancer, does garlic ingestion compared with no garlic, placebo, or other oral supplements reduce morbidity or mortality of cancer?

No controlled studies in humans were found that inform this question.

5. Is garlic more effective against some types of risk factors, precancerous conditions, or cancer than others?

Evidence regarding different precancerous lesions and cancers is summarized under the first and third questions above. Associations with cancer have been studied using different definitions of garlic exposure, different study populations, and different study designs. These issues preclude sound judgments regarding whether garlic has greater protective associations with some cancers than with others.

Adverse Effects Summary Points

1. What are the symptomatic and serious adverse effects of different garlic preparations, and what is their frequency?

Adverse effects of oral ingestion of garlic are "smelly" breath and body odor. Other possible, but not proven, adverse effects include flatulence, esophageal and abdominal pain, small intestinal obstruction, contact dermatitis, rhinitis, asthma, bleeding and hematoma, and myocardial infarction. The frequency of adverse effects and whether they vary by particular preparations are not established. Adverse effects of inhaled garlic dust include allergic reactions such as asthma, rhinitis, urticaria, angioedema, and anaphylaxis. Adverse effects of topical exposure to raw garlic include contact dermatitis, skin blisters, and ulcero-necrotic lesions. Frequency of reactions to inhaled garlic dust or topical exposures of garlic is not established.

2. Are there interactions between garlic and commonly used medications for dyslipidemia, diabetes, or thrombogenic disease (e.g., statins, sulfonylureas, antithrombotic agents)?

We found no evidence in humans to inform this question except for reports of two patients taking warfarin who experienced increases in their International Normalized Ratio (INR) when taking garlic pearls or tablets.

Limitations

Many randomized trials that have evaluated effects of garlic on cardiovascular-related endpoints are limited by short durations, inadequate randomization and blinding procedures, lack of clear specification of contents of garlic preparations (including their constituents and dissolution properties), lack of intention-to-treat analyses, and incomplete reporting of data. The meta-analysis of lipid data that we performed is limited by some missing data at different time points and by the need to impute variability data from some trials.

Few studies assessed associations between garlic consumption and cancer, and some studies may have been missed because they addressed associations with multiple foods. Findings specific to garlic may not be analyzed or reported and, even if reported, may be presented only in an appendix or as a single line in the text. Studies that were found sometimes failed to distinguish the type of garlic exposure (raw, cooked, or specific supplement), used subject recall to assess different frequencies of use over varying time periods, and adjusted for various potential confounders in different ways. Although we believe we found most reported adverse-effect literature regarding garlic, adverse effects in general are frequently underreported or reported in manners that do not allow determination of causality and frequency.