Gastrointestinal cancer is one of the most commonly diagnosed cancer type worldwide, with millions of cases per year. The aim of this review was to investigate the relationship between garlic intake and the risk reduction of gastrointestinal cancer. We performed saturated data mining on various public domain databases, including PubMed (
Gastrointestinal cancer is a health issue with worldwide concern, of which gastric and colorectal cancers are the most common types (
Historically, garlic consumption has been associated with medicinal properties in ancient cultures of Indochina, the Mediterranean and Northern Africa (
Previous meta-analyses and reviews exploring the relationship between garlic consumption and the risk of gastric and colorectal cancers have come to inconsistent conclusion (
This systemic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The study was registered in PROSPERO (CRD42020179464). The authors completed the data search in September 2021. All relevant studies that related to garlic intake for gastric and colorectal cancers from 1980 to 2021 were identified by searching in the following databases: Pubmed (
During the database compilation, two investigators (YaW and DL) reviewed the full text of all the screened publications to determine whether the studies met the selection criteria. Further refinement of the database was completed by a third investigator (YuW). Studies were selected according to the following criteria: i) randomized controlled trials, case-control trials, or with cohort design; ii) studies that include the evaluation of the association between garlic intake and gastric or colorectal cancers over nearly 30 years; iii) studies that provide odds ratio (OR) or relative risk (RR) and with 95% confidence interval (CI) or providing sufficient information for OR/RR and 95% CI calculation; iv) studies published within the last 30 years. The exclusion criteria included: i) reviews or meta-analyses; ii) non-English literature; iii) studies that lacked OR or RR data, or without sufficient data estimation results; iv) studies for which animal, cell,
Data mining was performed by two investigators. Disagreements were resolved by consultation with a third investigator. The following information was extracted: author, year of publication, study period, study type, country, number of subjects, risk estimates and their 95% CI, description of garlic intake categories, and adjusted variables.
For randomized controlled trials (RCTs), we assessed the risk of bias using the Cochrane Risk of Bias assessment tool (
We first collected the OR of gastric cancer in various studies. Since the incidences of gastric cancer and colorectal cancer are relatively low, the approximate OR was obtained based on the RR. Then we explored the sources of heterogeneity and conducted a subgroup analysis by garlic intake level, geographic area, and the type of study.
The heterogeneity was assessed using the Cochrane's Q test and I2 statistic. P-values <0.1 and I2 values >50% suggested the existence of heterogeneity. If significant heterogeneity existed, a random effect model was selected; otherwise, the fixed-effects model was used. Meanwhile, I2 values of <30%, 30–60%, and >60% were considered to indicate low, moderate, and high heterogeneity, respectively. Results were assessed using forest plots. All data analysis was performed by STATA 12.0 (
Sensitivity analysis was performed to identify potential sources of heterogeneity according to garlic consumption level, research type and geographical area. Subgroup analysis was conducted to identify the cause of heterogeneity. Random effect model and fixed effect model were selected according to different degrees of heterogeneity.
Publication bias was assessed by conducting Begg's and Egger's funnel plot asymmetry tests, a P-value <0.1 suggested publication bias with statistical significance.
A total of 648 articles were initially identified, of which 226 articles were excluded as duplicate studies. Then we reviewed the titles and abstracts of each literature study according to inclusion and exclusion criteria. We excluded additional articles, among which 323 were irrelevant to this study, 54 were meta-analyses and review, and 14 were non-English literature. After a careful review of full texts in the remaining 31 articles, we finally included 20 articles after excluding 4 articles from the same study and 7 articles with insufficient data (
Of the 20 included articles (
We conducted an overall estimation by categories of garlic consumption (
In the subgroup analysis by geographic area (
We found that among those 11 included studies, 2 studies (
A total of 9 studies estimated the association between garlic intake and the risk of colorectal cancer (
Compared to the retrospective studies (OR=0.72, 95% CI=0.62-0.84, P<0.001), the results of the prospective study (OR=1.01, 95% CI=0.62-1.65, P<0.1) showed an insignificant effect of garlic intake on reducing the risk of colorectal cancer (
The random effect model suggested a strong heterogeneity with I2=69.8%, and P<0.1 in the studies of garlic and gastric cancer which were selected for the meta-analysis. Therefore, we conducted Galbraith test to further identify the source of heterogeneity. The result of Galbraith test showed that the studies of Gao
For the 9 studies of garlic and colorectal cancer, a significant heterogeneity was also suggested (I2=71.4%, P<0.001). According to the results of Galbraith test, three studies [Wu
A randomized controlled trial evaluated by the Cochrane risk assessment tool was rated as low risk, and the non-randomized controlled trials were scored using a NOS scale, as shown in
Potential publication bias was assessed using the Begg (
This meta-analysis combined the results of 20 studies regarding the association of garlic consumption with gastric cancer (11 studies) and colorectal cancer (9 studies). Our results indicated that garlic intake significantly reduces the risk of gastric cancer (OR=0.65, 95% CI=0.49-0.87, P<0.001) and colorectal cancer (OR=0.75, 95% CI=0.65-0.87, P<0.001), consistent with the epidemiological evidence supporting the correlation between garlic intake and a reduced risk of gastric and colorectal cancer. The results of the geographical subgroup analysis showed that a greater risk reduction occurs in the Asian region compared with other geographical regions. We suspect one of the possible reasons is that garlic consumption is higher in Asia, especially in China, where the habit of eating raw garlic leads to a higher consumption than other countries in the world (
A further review was conducted on the molecular mechanisms of the anticancer effects of garlic (
To summarize, DADS, DATS, SAMC, and allicin participate in tumor-related biological process through various mechanisms, eventually leading to apoptosis, cell cycle arrest, and migration inhibition in tumor cells. A medical compound containing active ingredients from garlics may exert potential tumor preventive or therapeutic effects through the above-mentioned mechanisms in the human body, representing a novel antitumor treatment alternative.
This meta-analysis has the following limitations. i) Only a small set of randomized controlled trials are included in the date, most of which are case-control and cohort studies. Compared with randomized controlled trials, case-control and cohort studies have more unaccounted parameters in blind control and follow-up, resulting in higher propensity of bias. ii) This meta-analysis included studies conducted in different countries since the 1990s. Not all studies were primarily based on onion vegetables, and there was inconsistent stratification among the studies. iii) Most of the included studies were conducted in China, where the incidence of gastric cancer is generally higher than the rest of the world. Moreover, garlic intake is relatively high in the diet of Chinese people. iv) Many studies did not control other diets, and the type of garlic consumption remains unstandardized. It is difficult to determine the minimum garlic intake for a tumor-protective effect. The minimum and maximum consumption levels varied greatly among the different studies.
The quantified I2 test showed that the included studies had significant heterogeneity, and Galbraith test suggested that some studies might be the sources. Therefore, we explored the possible cause for the heterogeneity. First, most of the included studies were retrospective studies with various confounding factors, and recall bias may have produced different results from the prospective studies. Second, most studies had collected data in the form of questionnaires instead of objective measurement. Third, studies conducted in Asia, especially in China, where garlic is a highly consumed food, may lead to certain bias on the results when pooled together with studies conducted in other places with much lower garlic consumption.
In summary, our meta-analysis provides strong evidence that garlic can reduce the risk of gastric and colorectal cancers. The conclusion was mainly based on case-control studies with many potential confounders, and further research is warranted to validate it.
Not applicable.
The study was registered in PROSPERO (CRD42020179464).
HJL designed the review and meta-analysis. YYW and HJL conceived and wrote the review. YFW and DRL acquired and analysed the data. MYJ and PH analyzed and confirmed the integrity of the data found in the literature. YSW was involved in drafting the manuscript. All authors contributed to the analysis, reviewed the results and read and approved the final manuscript.
Not applicable.
Not applicable.
ORCID: Huanjie Li, orcid.org/0000-0002-4997-0927; Yunshan Wang, orcid.org/0000-0003-3767-6728.
The authors declare that they have no competing interests.
Flow diagram of the included studies. A total of 648 articles were initially searched, of which 226 articles were excluded as duplicate studies. Then we reviewed the titles and abstracts of each literature according to inclusion and exclusion criteria. We excluded additional articles, among which 323 were irrelevant to this study, 54 were meta-analyses and reviews, and 14 were non-English literature. After a careful review of the full texts in the remaining 31 articles, we finally included 20 articles after excluding 4 articles from the same study and 7 articles with insufficient data. OR, odds ratio; RR, relative risk.
Associations between garlic intake and gastrointestinal cancer risk by garlic consumption. The (number/number) after each study in the figure indicates the (Cases/Controls). Vertical solid black line: invalid line; red dashed line: pooled effect size; horizontal black solid line: the width of the line represents the confidence interval (CI) of each study, the black diamond in the middle represents the OR of each study, and the gray square represents the weight of each study. Others: We have included some studies that differed from other classifications of garlic intake into this category. (A) Forest plots for the associations between garlic intake and gastric cancer risk by garlic consumption. The OR obtained by the pooled analysis was 0.65 (95% CI=0.49-0.87). (B) Forest plots for the associations between garlic intake and colorectal cancer risk by garlic consumption. The meta-analysis using the random-effects model showed a combined estimated OR of 0.75 (95% CI=0.65-0.87), suggesting that garlic intake could reduce the risk of colorectal cancer. OR, odds ratio; ES, effect size.
Positive and negative association studies between garlic intake and gastric cancer. The (number/number) after each study in the figure indicates the (Cases/Controls), Vertical solid black line: invalid line; red dashed line: pooled effect size; horizontal black solid line: the width of the line represents the confidence interval (CI) of each study, the black diamond in the middle represents the OR of each study, and the gray square represents the weight of each study. Among the 11 included studies, 2 studies showed that garlic intake had no association with the incidence of gastric cancer (OR=1.36, 95% CI=0.93-1.99), including 12,6976 subjects, and 9 studies showed that garlic intake could reduce the incidence of gastric cancer (OR=0.54, 95% CI=0.41-0.70), including 9,944 subjects. OR, odds ratio; ES, effect size.
Source of heterogeneity in the meta-analysis of garlic intake and gastrointestinal cancer risk. (A) The Galbraith test indicating the source of heterogeneity in the meta-analysis of garlic intake and gastric cancer risk. The studies of Gao
Sensitivity analysis of garlic and gastrointestinal cancer. (A) Sensitivity analysis of garlic and gastric cancer. No significant differences were found among the studies. (B) Sensitivity analysis of garlic intake and colorectal cancer. The results of the sensitivity analysis showed that no articles exceeded the limits and there were no significant differences among the studies.
Relationship between included studies and risk of gastrointestinal cancer by garlic intake. In all the included studies, the results of most studies indicated that garlic can reduce the risk of gastrointestinal cancers. OR, odds ratio.
Potential publication bias assessed by Begg's test. Funnel plot indicating the publication bias in the studies included in the meta-analysis of the garlic intake and gastrointestinal cancers. There was no significant evidence of publication bias for gastric and colorectal cancers. (A) Begg's funnel plot for garlic intake and gastric cancer. (B) Begg's funnel plot for garlic intake and colorectal cancer.
Potential molecular mechanisms of the anticancer effects of garlic. (A) DADS, DATS, SAMC and allicin can all promote the release of cytochrome
Details of all 20 studies included in this analysis.
Authors of the study (year) | Country | Study design | Study period | Cases/Controls | Garlic consumption types | Consumption | OR/RR (95% CI) | Adjustment | (Refs.) |
---|---|---|---|---|---|---|---|---|---|
You |
China | Population-based case-control study | 1984- 1986 | 564/1,131 | Garlic | 0 (kg/year) 0.1-1.5 (kg/year) >1.5 (kg/year) | 1.00 0.8 (0.5-1.2) 0.7 (0.4-1.0) | Age, sex, family income, and intake of other allium vegetables | ( |
Dorant |
The Netherlands | Cohort study | 1986-1990 | 152 (male 119, female 33)/3,340 (male 1,627, female 1,713) | Garlic supplement | No supplements Exclusively garlic | 1.00 1.27 (0.61-2.64) | Age, alcohol intake, vitamin C intake, and b-carotene as continuous variables and sex, smoking status, education, history of stomach di-orders, and family history of stomach cancer as categorical variables | ( |
Gao |
China | Population-based case-control study | 1995-1997 | 153 (male 140, female 53)/234 (male 154, female 80) | Garlic | <1 time/month 1–3 times/month ≥1 time/week | 1.00 0.4 (0.21-0.76) 0.31 (0.22-0.44) | Age, sex, income, smoking, drinking, tea consumption and intake of leftover gruel, pickled vegetables, meat, fruit, tomatoes, eggs and snap beans. | ( |
Muñoz |
Venezuela | Population- based case-control study | 1991-1997 | 292/485 | Garlic | Less than once/week Several times/week Every day | 1.00 0.7 (0.4-1.0) 0.5 (0.3-0.8) | Age, sex and SES | ( |
Takezaki |
China | Population-based case-control study | 1996-2000 | 187 (male 137, female 50)/333 (male 235,) female 98 | Garlic | <1 time/week 1–2 times/week 3–5 times/week Everyday | 1.00 1.00 (0.56-1.81) 0.72 (0.42-1.24) 0.66 (0.37-1.17) | Age, sex, smoking and drinking habits | ( |
De Stefani |
Uruguay | Hospital-based case-control study | 1997-2000 | 160 (male 114, female 46)/320 (male 225, female 95) | Garlic | 0.67 (0.38-1.18) | Age, sex, residence, urban/rural status, education, body mass index (BMI), and total energy intake, and total fruit intake | ( |
|
Setiawan |
China | Population-based case-control study | 1991-1993 | 750 (male 478, female 272)/750 (male 478, female 272) | Garlic | Never Occasional Often | 1.00 1.11 (0.87-1.41) 0.68 (0.37-1.26) | Matching variables (age, sex), education, BMI, pack-years of smoking, alcohol drinking, salt intake, and vegetable and fruit intake | ( |
Setiawan |
China | Population-based case-control study | 1991-1993 | 201 (male 143, female 58)/201 (male143, female 58) | Garlic | Never Occasional Often | 1.00 0.71 (0.27-1.88) 0.45 (0.15-1.30) | Matching variables (age, sex), education, BMI, pack-years of smoking, alcohol drinking, salt intake, and vegetable and fruit intake | ( |
Pourfarzi |
Iran | Population-based case-control study | 1999- 2005 | 217 (male 151, female 66)/394 (male 265, female 129) | Garlic | Never or infrequently 1–2 times/week >3 times/week | 1.00 0.48 (0.25-0.91) 0.35 (0.13-0.95) | Sex, age group, education, family history of GC, citrus fruits, garlic, onion, red meat, fish, dairy products, strength and warmth of tea, preference for salt intake and |
( |
Kim |
USA | Cohort study | 1984-2014 | 138/76,948 | Garlic | Never 0-<1 per week 1–4 per week 5 per week | 1.00 1.08 (0.67-1.73) 0.81 (0.50-1.31) 1.34 (0.72-2.47) | Age, Caucasian, BMI, physical activity, smoking status, alcohol consumption, current multivitamin use, current aspirin use, personal history of diabetes mellitus, and intakes of total calorie, red/processed meat, fruits, vegetables, and coffee | ( |
Kim |
USA | Cohort study | 1984-2014 | 154/46,244 | Garlic | Never 0-<1 per week 1–4 per week 5 per week | 1.00 1.13 (0.75-1.72) 1.15 (0.74-1.77) 1.45 (0.76-2.78) | Age, Caucasian, BMI, physical activity, smoking status, alcohol consumption, current multivitamin use, current aspirin use, personal history of diabetes mellitus, and intakes of total calorie, red/processed meat, fruits, vegetables, and coffee | ( |
Li |
China | Randomized controlled trial | 1995-2017 | 151/3,241 | Garlic supplementation | Twice a day | 0.81 (0.57-1.13) | Baseline histology, age, sex, history of ever using alcohol, and history of ever smoking | ( |
Yuan |
China | Hospital-based case-control study | 2014-2016 | 180/180 | Garlic | 0.35 (0.18-0.67) | Dietary/lifestyle habits, psychological factors, serum PG I level, serum PG II level, PG I/II ratio, serum G-17 level and |
( |
|
Steinmetz |
USA | Prospective cohort Study | 1986-1990 | 212/35004 | Garlic | L1 (0) L2 (0.5) L3 (1.0) | 1.00 1.07 (0.77-1.50) 0.68 (0.46-1.02) | Age and energy intake | ( |
Witte |
USA | Case control study | 1991-1993 | 488 (male 325, female 163)/488 (male 325, female 163) | Garlic | None 0.5 1.0-2.5 >-3.0 | 1.00 0.92 (0.64-1.34) 0.98 (0.61-1.56) 0.66 (0.43-1.01) | Race, BMI, physical activity, smoking, calories, and saturated fat using conditional logistic, regression dietary fiber, folate, β-carotene, and vitamin C | ( |
Dorant |
The Netherlands | Cohort study | 1986-1989 | 293 (male 150, female 143)/3,123 (male 1,525, female 1598) | Garlic supplement | No supplement Exclusively garlic | 1.00 1.36 (0.79-2.35) | Age, vitamin C and (J-carotene as continuous variables, and sex, smoking status, education, family history of intestinal cancer, previous history of chronic intestinal disease or chole cystectomy as categorical variables | ( |
Dorant |
The Netherlands | Cohort study | 1986-1989 | 150 (male 93, female 57)/3,123 (male 1,525, | Garlic supplement | No supplement Exclusively garlic | 1.00 1.28 (0.63-2.60) | Age, vitamin C and (J-carotene as continuous variables, and sex, smoking female 1,598) status, education, family history of intestinal cancer, previous history of chronic intestinal disease or cholecystectomy as categorical variables | ( |
Franceschi |
Italy | Case control study | 1991-1996 | 1,225/5,155 | Cooked garlic | 0.9 (0.8-1.0) | Age, sex, center, year of interview, education, physical activity, alcohol and energy intake | ( |
|
Franceschi |
Italy | Case control study | 1991-1996 | 728/5,155 | Cooked garlic | 0.9 (0.8-1.0) | Age, sex, center, year of interview, education, physical activity, alcohol and energy intake | ( |
|
Levi |
Switzerland | Case control study | 1992-1997 | 223 (male 142, female 81)/491 (male 211, female 280) | Garlic | Low Medium High | 1.00 0.51 (0.35-0.74) 0.32 (0.18-0.57) | Age, sex, education, smoking, alcohol, BMI, physical activity and total energy intake | ( |
Galeone |
Italy | Case control study | 1991-2004 | 2,280 (male 1,318, female 962)/4,765 (male 2,403, female 2,362) | Garlic | None or low Intermediate High | 1 0.88 (0.78, 0.98) 0.74 (0.63,0.86) | Age, sex, study center, education, BMI, energy intake, alcohol consumption, smoking habit, and physical activity | ( |
Annema |
Australia | Population-based case-control study | 2005-2007 | 834 (male 514, female 320)/939 (male 551, female 388) | Garlic | <0.02 (servings/day) 0.02-<0.14 (servings/day) 0.14-<0.28 (servings/day) 0.28+ (servings/day) | 1.00 0.92 (0.67-1.26) 0.84 (0.62-1.15) 0.86 (0.68-1.09) | Adjusted for sex, age, BMI at age 20 years, energy intake, multivitamin use, alcohol consumption, physical activity, smoking, diabetes and socioeconomic status | ( |
Wang |
China | Case control study | 2015-2016 | 317 (male 145, female 172)/317 (male 146, female 171) | Garlic | 0.499 (0.341-0.732) | ( |
||
Wu |
China | Hospital-based matched case-control study | 2009-2011 | 833/833 | Garlic | <0.60 (kg/year) 0.60-2.60 (kg/year) 2.60-3.65 (kg/year) >3.65 (kg/year) | 1.00 0.49 (0.35-0.66) 0.43 (0.30-0.59) 0.56 (0.39-0.79) | BMI, family history of CRC (first degree), education level, smoking, passive smoking, alcohol, the consumption of red meat, milk, other vegetables, fruit, total energy, fiber, calcium, fat, vitamin C, vitamin D, cholesterol, and folic acid | ( |