Description
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).
Efficacy
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. Only very few clinical trials exist and their results are inconclusive.
Prevention of cancer
Colorectal cancer: The evidence from 6 systematic reviews/meta-analyses on prevention of colorectal cancer is conflicting so that no clear conclusions can be reached.
Gastric cancer: Evidence assessed in 5 systematic reviews/meta-analyses suggests a reduced risk but this has not been confirmed in rigorous clinical trials
Other cancers: Evidence from 5 systematic reviews/meta-analyses on prevention of other cancers including breast and prostate cancer is not convincing being either not assessed for quality, poor quality or highly heterogenous.
Supportive care
Prevention of neutropenia: a single randomized clinical trial (n=95) produced inconclusive results.
Safety
Garlic is generally considered to be non-toxic. Garlic preparations should be used with caution in patients taking oral anticoagulation therapy
Citation
Karen Pilkington, CAM Cancer Collaboration. Garlic (Allium sativum) [online document], [March 6 2024].
Document history
Updated in December 2023 and November 2018 by Karen Pilkington, and August 2013 by Edzard Ernst. Summary first published in September 2011, authored by Edzard Ernst. Next update due in March 2027.
Description
Allium sativum L (Alliaceae/Liliaceae) is commonly referred to as garlic. Ajo is also sometimes used.
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.
Background
Garlic has been used medicinally in several ancient cultures. For medicinal purposes, fresh or dried parts of the garlic bulb or the oil from the bulb are usually used. It is offered as “over the counter” (OTC) preparations (food supplements) in form of single-ingredient or multi-ingredients preparations by many providers (Barnes 2002). Prescribers today are mainly herbalists, naturopaths and doctors. Many consumers self-prescribe garlic supplements.
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 months Zhang 2008. A similar prevalence was found in the USA (Barnes 2008). Specific reasons for use were not recorded.
Ingredients and quality issues
Alliin, diallyldisulfate, ajoen and others (Ernst 2006). 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 chopped (Ernst 2006, Barnes 2007). It is considered that 1 mg alliin is equivalent to 0.45 mg allicin (Barnes 2007, ESCOP 2019). Commercial garlic preparations are often standardised on the content of sulfur-containing constituents, particularly to alliin, or on the allicin yield (Barnes 2007).
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”.
Alleged indications
The ESCOP Monograph (2019) recommends Allii sativi bulbus for the’prophylaxis of atherosclerosis; treatment of elevated blood lipid levels if insufficiently controlled by diet; supportive treatment of hypertension; reducing severity of upper respiratory tract infections and catarrhal conditions.’
The 1999 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 hypertension (WHO 1999).
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 studies (Barnes 2007) and the results of large-scale observational studies (see Does it work section)
Application and dosage
Garlic's mechanisms of action have been studied extensively. It has antibacterial, antiviral, antifungal, antihypertensive, blood glucose lowering, antithrombotic, antimutagenic, and antiplatelet activities (Ernst 2006).
Several pathways have been identified for each of which the evidence is substantial:
- Modulation of carcinogen metabolism (Antony 2011)
- Inhibition of cell cycle progression (Viry 2011)
- Induction of apoptosis (Kim 2011, Lee JE 2011, Lee Y 2011, Li 2012, Yu 2012, Zhang 2010).
- Histone modification (Barnes 2002)
- Inhibition of angiogenesis (Barnes 2002)
- Protection against DNA damage (Chang 2012)
- Inhibition of cell proliferation (Huang 2011, Kaneko 2012, Liang 2011, Wu 2011).
- Modulation of gene expression (Huang 2011, Lai 2012).
- Inhibition of tumor cell motility (Park 2011)
- Antioxidation (Shirzad 2011).
- Modification of drug metabolising enzymes especially the family of the hepatic cytochrome P450 (CYP) enzymes (Barnes 2007)
- Immunomodulatory activity (Barnes 2007, Wang 2012)
Many of the findings from animal studies support these postulated mechanisms (Li 2012, Kaneko 2012, Liang 2011, Wu 2011, Shirzad 2011, Wang 2012, Bianchi 2001, Appel 2011) .
Legal issues
Garlic preparations are sold in most countries as food supplements. In the EU, some preparations are categorised as medicinal herbal products.
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 (cohort and case-control studies) published since 2010. The key characteristics of these are included in table 1.
Few randomised controlled trials of garlic on prevention of cancer are available (Zhou 2013, You 2006, Turati 2014, Tanaka 2004, Zhu 2014, Ma 2012). 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.
Cancer prevention
Colorectal cancer
Three meta-analyses (Hu 2014; Turati 2014; Zhu 2014) and three systematic reviews with meta-analysis (Chiavarini 2015; Zhou 2020; Wang 2022) assessed whether consumption of garlic was associated with risk of colorectal cancer. Three 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 three reviews, searches were limited and only four reviews assessed quality of the studies. The quality assessments also varied. One of the systematic reviews assessed cohort and case-control studies separately (Chiavarini 2015).
One of the meta-analyses included only cohort studies and carried out quality assessments judging the studies to be high quality (Hu 2014). The two remaining systematic reviews with meta-analyses included cohort and case control studies and quality of the included studies was judged to be adequate (Wang 2022) or high quality (Zhou 2020). Three of the four reviews which assessed quality of the evidence found no association with garlic intake. The two most recent reviews found an association but results were highly heterogeneous.
Gastric cancer
Three meta-analyses (Kodali 2015; Turati 2015; Zhou 2011) and two systematic reviews with meta-analysis (Li 2018; Wang 2022) 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 reviews and meta-analyses all found a reduced risk linked to garlic intake. The two systematic reviews which included quality appraisal found the studies to be adequate (Wang 2022) or poor (Li 2018).
Other cancers
Two meta-analyses (Guercio 2016; Zhou 2013), and three systematic reviews (two including meta-analysis) (Lee 2021; Zhang 2021; Zhang 2022) considered risk of other cancers.
A meta-analysis that focused only on prostate cancer but included all Allium vegetables identified a total of 6 case-control and 3 cohort studies (Zhou 2013). 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 oesophagus Guercio 2016). 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). No quality assessment was reported.
Two systematic reviews included a range of cancers and found no effect (Lee 2021; Zhang 2021). Studies were assessed as low or moderate quality.
A systematic review focused on breast cancer did find a reduction in risk but studies were of mixed quality and results heterogeneous (Zhang 2022).
There are a range of possible explanations for variations in results 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 consumed (Shirzad 2011).
Randomized and controlled trials
Collectively these studies (table 2) 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 RCT which has involved a prolonged period of follow-up of over 20 years reported a reduced risk of cancer although no such reduction was noted at the previous 15-year follow-up and a p trend value was reported and not a p value (Su 2023). One RCT of 95 patients with hematological malignancies examined a specific use for garlic: prevention of febrile neutropenia (Gatt 2015). As with the RCT other trials, the results were inconclusive.
Adverse effects
Garlic (Allium sativum) is generally considered to be non-toxic (Ernst 2006, Barnes 2007, Piscitelli 2002, Berginc 2010). 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, anorexia Barnes 2007, Piscitelli 2002) 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 bleeding (NatMed 2023) and with topical use, burn and contact dermatitis especially in children (Shamseer, 2006). The allergenic potential of garlic is well recognized, and the allergens have been identified as diallyl disulfide, allylpropyl sulfide and allicin (Barnes 2002, Papageorgiou 1983).
However, allergic reactions are rare (ESCOP 2019). Preclinical data on chronic toxicity are conflicting (Barnes 2007). Genotoxicity studies using the micronucleus test have reported both positive and negative findings (Barnes 2007). No evidence of mutagenicity has been reported when assessed using the Ames and Ree assay (Barnes 2007). A recent investigation using the AMES test found no evidence of genotoxicity (Lin 2022). 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 risk (Barnes 2007). 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 regime (Piscitelli 2002).
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 documented (Barnes 2007, Ishikawa 2006). The results of two clinical trials suggest that dietary garlic consumption does not affect platelet function (Beckert 2007, Scharbert 2007). 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 substrate (Ho 2010). The activity of 2D6 mediated-metabolism was generally unaffected by garlic. Extracts of the fresh garlic stimulated CYP2C9*2 metabolism of the marker substrate (Foster 2001, Cox 2006, Greenblatt 2006).
However, in patients carrying the CYP3A5*1A allele, garlic could affect the clearance of docetaxel, leading to higher toxicity (Cox 2006). 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 CYP3A4(Ho 2010). Pharmacokinetics possibly affected are e.g. cyclophosphamide, diclofenac, haloperidol, ibuprofen, naproxen, paclitaxel, piroxicam, and tamoxifen) (Ho 2010). In observational studies slight changes were found in CYP1A2 levels (increase) and CYP2E1 activity (decrease) (pharmacokinetics possibly affected: e.g. ondansetron, etoposide) (Le Bon 2003).
An increase has been noted in the expression of duodenal P-glycoprotein after the ingestion of garlic extracts (Hajda 2010). 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 inhibitors (Piscitelli 2002, Berginc 2010a, Berginc 2010b).
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 extracts(Le Bon 2003).
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 (Barnes 2007). In view of this, doses of garlic greatly exceeding amounts used in foods should not be taken during pregnancy and lactation (Barnes 2007).
Other problems
Overdose may cause nausea and vomiting.
Evidence tables
Table 1: Systematic reviews of garlic (Allium sativum) for cancer prevention
Table 2: RCTs of garlic (Allium sativum) for cancer prevention
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