Garlic (Allium sativum)

Karen Pilkington, Edzard Ernst and the CAM Cancer Consortium | Published 14/11/2018

Abstract and key points
What is it?
Does it work?
Is it safe?
Evidence tables
References
Abstract and key points
  • Garlic (Allium sativum) is a food item and seasoning which has also been used for medicinal purposes.
  • Garlic is said to reduce the risk of certain cancers.
  • The evidence for this assumption is contradictory and not strong, being based mainly on observational studies.
  • Serious adverse-effects are not on record but interactions with a range of drugs including cancer drugs might be an issue and allergic reactions are possible.

Garlic (Allium sativum) is a bulbous plant from the onion family which is widely used as food seasoning.  It has also been used as a traditional medicine. Garlic is sometimes recommended for cancer-prevention based on observational population studies assessing garlic intake and risk of cancer and on studies indicating beneficial effects on processes such as activation of carcinogenic substances, cell proliferation and apoptosis (cell death). Reviews of the epidemiological evidence are contradictory due to differences in the methods used in the reviews, confounding factors and, possibly, to the nature and quality of the garlic consumed.  While some reviews conclude that, for some types of cancer including gastric cancer, regular garlic intake might reduce the risk, this is based on a mixture of study types and, often, a lack of quality assessment. Only very few clinical trials exist and their results are inconclusive. Serious adverse events are not to be expected at recommended doses or normal levels of dietary intake but herb-drug interactions might occur.

 

Citation

Karen Pilkington, Edzard Ernst, CAM Cancer Consortium. Garlic (Allium sativum) [online document], November 14, 2018.

Document history

Fully revised and updated in November 2018 by Karen Pilkington.
Revised and updated in August 2013 by Edzard Ernst.
Summary first published in September 2011, authored by Edzard Ernst.

What is it?

Description

Garlic is a bulbous plant of the Allium (onion) family, the bulb usually being composed of sections called cloves which produce a pungent odour, particularly when chopped or crushed, due to various sulfur compounds. Commonly used for culinary purposes, it is related to chives, leeks and onions and cultivated in most countries. For medicinal purposes, fresh or dried parts of the garlic bulb or the oil from the bulb are usually used.

Scientific / common name

Allium sativum L (Alliaceae/Liliaceae) is commonly referred to as garlic. Ajo is also sometimes used.

Ingredients

Alliin, diallyldisulfate, ajoen and others1. Allicin, considered to be one of the main active ingredients, and other sulfur-containing compounds are formed from alliin enzymatically when garlic is crushed or chopped1,2. It is considered that 1 mg alliin is equivalent to 0.45 mg allicin2,3. Commercial garlic preparations are often standardised on the content of sulfur-containing constituents, particularly to alliin, or on the allicin yield2.

Application and dosage

Garlic may be consumed in food as part of the normal diet usually as fresh garlic cloves added when cooking. It may also be taken as a medicinal preparation, for example, as capsules of the dried product. Doses vary widely depending on the product and indication. The following are some examples of dose ranges that have been reported:

Dried bulb: 2- 4g three times daily for upper respiratory tract infections4-6; 0.5-1.0 g daily for the prophylaxis of atherosclerosis7,8.
Fresh garlic: 4g daily1-3.
Oil: 0.03-0.12 ml three times daily2,9.
Juice of garlic (BPC 1949) 2-4 ml2,10.
Extract: 600-900mg of standardised extract (1.3% alliin content) daily in divided doses1.

The World Health Organization’s (WHO) 1999 guidelines on dose for adults are, unless otherwise prescribed, fresh garlic, 2–5 g; dried powder, 0.4–1.2 g; oil, 2–5 mg; extract, 300–1000 mg (as solid material)4.

For colorectal cancer, aged garlic extract 2.4 mL daily for 12 months as capsules has been used11,12,13, while for prostate cancer, a dose of 1 mg/kg of aqueous garlic extract for one month has been used14,15. In prevention of cancer, 200 mg synthetic allitridum/day has been used16,17 as has 400 mg aged garlic extract and 2 g garlic oil twice daily18.

History/providers

Garlic has been used medicinally in several ancient cultures. Prescribers today are mainly herbalists, naturopaths and doctors. Many consumers self-prescribe garlic supplements. Garlic is a common food and spice. It is offered as “over the counter “ (OTC) preparations (food supplements) in form of single-ingredient or multi-ingredients preparations by many providers11.

Claims of efficacy

The ESCOP Monograph (2003) recommends Allii sativi bulbus for the prophylaxis of atherosclerosis, for the treatment of elevated blood lipid levels insufficiently influenced by diet, for the improvement of the circulation in peripheral arterial vascular disease and for upper respiratory tract infections and catarrhal conditions3.

The WHO-Monograph states the that uses supported by clinical data are: as adjuvant to the dietetic management in the treatment of hyperlipidaemia, and in the prevention of atherosclerosis, age-dependent vascular changes and mild hypertension4.

In the context of cancer, it is claimed that garlic might reduce the cancer risk. Claims of efficacy in the prevention of cancer are based on in vitro and animal studies2 and the results of large-scale observational studies (see Does it work section?)

Mechanism of action

Garlic's mechanisms of action have been studied extensively. It has antibacterial, antiviral, antifungal, antihypertensive, blood glucose lowering, antithrombotic, antimutagentic and antiplatelet activities1.

Several pathways have been identified for each of which the evidence is substantial:

  • Modulation of carcinogen metabolism12
  • Inhibition of cell cycle progression19
  • Induction of apoptosis20-25
  • Histone modification12
  • Inhibition of angiogenesis12
  • Protection against DNA-damage26
  • Inhibition of cell proliferation27-30
  • Modulation of gene expression27,31
  • Inhibition of tumor cell motility32
  • Antioxidation33
  • Modification of drug metabolising enzymes especially the family of the hepatic cytochrome P450 (CYP) enzymes2
  • Immunomodulatory activity2,34

Many of the findings from animal studies support these postulated mechanisms23,28-30,33-36.

Prevalence of use

Garlic is widely used as a food and seasoning. Garlic supplements have become very popular in developed countries. Exact prevalence figures are not available. Garlic was reported to be used by approximately 10% of the Australian population in the past 12 months37. A similar prevalence was found in the USA38. Specific reasons for use were not recorded.

Legal issues

Garlic preparations are sold in most countries as food supplements, in the EU some preparation are medicinal herbal products.

Cost and expenditure

A one week supply of garlic supplements would cost between €5 and €10.

Does it work?

The literature on garlic (Allium sativum) as a means of reducing cancer risk is huge. Therefore, the following section is mainly based on systematic reviews and meta-analyses of the observational studies. The key characteristics of these are included in Table 1.

Systematic reviews, meta-analyses

Colorectal cancer

Four meta-analyses39-42, two ‘evidence-based’ reviews43,44 and one systematic review with meta-analysis45 assessed whether consumption of garlic was associated with risk of colorectal cancer. Four of these found no reduced risk of colorectal cancer with higher levels of garlic consumption, two found risk to be reduced and one reported that risk appeared to be increased by garlic supplements. The reason for the differences may be due to a range of factors such as the types and numbers of studies included, quality of the studies and how recently the search was conducted. In most cases, only one or two databases were searched and only four assessed quality of the studies.  The quality assessments also varied. An evidence-based overview graded studies according to design and concluded that there was evidence of a protective effect from animal studies but human studies were heterogeneous43. In the second evidence-based review, results of stronger studies were assessed separately from the weaker studies44. One of the meta-analyses included only cohort studies and carried out quality assessments judging the studies to be high quality40. The systematic review with meta-analysis included cohort and case control studies and quality of the included studies was judged to be moderate to high45. Three of the four reviews which assessed quality of the evidence found no association with garlic intake.

Gastric cancer

Four meta-analyses39,46,47,48 and the evidence-based review44 assessed whether garlic consumption was associated with gastric cancer. As above, there were differences in various aspects of the methods used in carrying out these reviews. The evidence-based review concluded that there was ‘no credible evidence’ of a link between intake and gastric cancer risk44. The four meta-analyses, all based on limited searches and no quality assessment, found a reduced risk linked to garlic (or in one case linked to total Allium) intake. One meta-analysis, which included a mixture of trials and observational studies, reported a link with high, low or even any intake of garlic versus no intake46. Two meta-analyses which included cohort and case-control studies also reported a link between garlic intake and reduced cancer risk (39,48) as did a meta-analysis of case-control studies47.

Other cancers

Two meta-analyses17,42 and the evidence-based review44 considered risk of other cancers.

The evidence-based review covered prostate cancer, breast cancer, lung cancer and various other cancers. No credible evidence of a reduction in risk was found for breast, lung, or endometrial cancer, very limited evidence (1 study each) was found for prostate, oesophageal, larynx, oral, ovary, or renal cell cancer.

A more recent meta-analysis that focused only on prostate cancer but included all Allium vegetables identified a total of 6 case-control and 3 cohort studies17. Subgroup analysis of the results for garlic intake from all the studies showed a significant association with garlic intake (OR = 0.77, 95% CI 0.64-0.91). However, while confounding variables were reported, there was no specific assessment of the effect of these or the quality of the individual studies.

Another meta-analysis focused on cancers of the oral cavity, pharynx, larynx, and oesophagus42. The risk ratio (RR) for squamous cell carcinoma indicated a reduction for highest versus lowest garlic consumption (0.74 95% CI 0.57–0.95).

There are a range of possible explanations for variations in addition to differences in the methods used in the original studies, possible confounding factors and the design of the secondary studies i.e. the meta-analyses and systematic reviews and overviews.  These may include factors such as differences in the nature and quality of the garlic consumed33.

Clinical trials

Few randomised controlled trials of garlic on prevention of cancer are available17,18,41,49,50,51. All but one are included in the systematic reviews and meta-analyses described above. Their key data are summarized in table 2. Collectively these studies fail to show conclusively that garlic-intake reduces the cancer risk and thus do not provide support for any positive results reported in the observational studies. One study examined a specific use for garlic: prevention of febrile neutropenia52. As with the other trials, the results were inconclusive.

Is it safe?

Adverse effects

Garlic (Allium sativum) is generally considered to be non-toxic (1,2,53,54. Adverse effects of unknown frequency that have been documented in humans include a burning sensation in the mouth and gastrointestinal tract, bloating, abdominal pain, fullness, anorexia2,53) and malodourous breath or body odour. Facial flushing, tachycardia, profuse sweating, bronchospasms, headache and dizziness have also been reported as has an increased risk of bleeding8 and with topical use, burn and contact dermatitis especially in children55.The allergenic potential of garlic is well recognized, and the allergens have been identified as diallyl disulfide, allylpropyl sulfide and allicin2,5. However, allergic reactions are rare3. Preclinical data on chronic toxicity are conflicting2,8. Genotoxicity studies using the micronucleus test have reported both positive and negative findings2. No evidence of mutagenicity has been reported when assessed using the Ames and Ree assay2. No conventional genotoxicity, carcinogenicity and reproduction toxicity studies are available.

Contraindications

Known allergy to Allium species. Garlic consumption should be avoided 7 days before surgery because of the post-operative bleeding risk2. Concomitant use with saquinavir  is contraindicated because of the risks of decrease in plasma concentration, loss of virological response and possible resistance to one or more components of the antiretroviral regime53.

Interactions

Garlic preparations should be used with caution in patients taking oral anticoagulation therapy and/or anti-platelet therapy because they may increase bleeding times. A potential interaction between garlic and warfarin has been documented2,56.  The results of two clinical trials suggest that dietary garlic consumption does not affect platelet function57,58. No relevant data are available regarding the potentiating effect of antiplatelet drugs (ASA, clopidogrel etc.) when co-administered with garlic.

In vitro, extracts of fresh garlic, garlic oil and freeze dried garlic exhibited an inhibitory effect on cytochrome P450 2C9*1, 2C19, 3A4, 3A5 and 3A7 mediated metabolism of a marker substrate59. The activity of 2D6 mediated-metabolism was generally unaffected by garlic. Extracts of the fresh garlic stimulated CYP2C9*2 metabolism of the marker substrate60,61,62. However, in patients carrying the CYP3A5*1A allele, garlic could affect the clearance of docetaxel, leading to higher toxicity61. In immortalised human hepatocytes (Fa2N-4 cells) exposure of hepatocytes to garlic extract (0-200 μg/ml) may reduce the expression and activity of CYP2C9 with no detectible effects on CYP3A463. Pharmacokinetics possibly affected are e.g. cyclophosphamide, diclofenac, haloperidol, ibuprofen, naproxen, paclitaxel, piroxicam, and tamoxifen)63. In observational studies slight changes were found in CYP1A2 levels (increase) and CYP2E1 activity (decrease) (pharmacokinetics possibly affected: e.g. ondansetron, etoposide)64.  

An increase has been noted in the expression of duodenal P-glycoprotein after the ingestion of garlic extracts65. This interaction is thought to be the most probable mechanism for the known impact that garlic supplements exert on the first-pass metabolism of HIV protease inhibitors53,54,66.

Finally, in observational studies alterations in the activity of the phase II biotransformation enzymes UDP glucuronosyltransferase and glutathion-S-transferase have been observed after the ingestion of garlic extracts64.

Quality issues

Garlic preparations should adhere to GAP (Good Agricultural Practices), GMP (Good Manufacturing Practices) and, in Europe, to the European guidelines “Quality of Herbal Medicinal products”.

Warning

Insufficient information exists for garlic use beyond amounts consumed as part of the daily diet during pregnancy and lactation. There are only few clinical studies during pregnancy and lactation. However, there are not experimental or clinical reports on adverse effects during pregnancy or lactation 2. There are only few clinical studies during pregnancy and lactation. However, there are not experimental or clinical reports on adverse effects during pregnancy or lactation2. In view of this, doses of garlic greatly exceeding amounts used in foods should not be taken during pregnancy and lactation2.

Other problems

Overdose may cause nausea and vomiting.

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