Used universally for flavoring and in traditional medicines and functional foods to enhance physical and mental health, garlic (Allium sativum
) is among the most popular condiments worldwide [1
]. Garlic contains organosulfur compounds (OSCs), which largely account for its protective effects [2
]. It has been suggested that garlic can prevent cardiovascular disease, cancer, and diseases associated with aging by in vitro and in vivo studies [3
]. In population-based studies, a number of beneficial effects have long been documented for garlic or its bioactive ingredients, especially the prevention of cancer and cardiovascular disease [4
]. Case–control studies also documented the protective effects of garlic consumption in gastric, colorectal, prostate, head and neck, and lung cancers in different populations [4
]. Evidence from randomized controlled trials indicated that garlic is beneficial in treating hypertension [9
]. However, the association between garlic supplement intake with gastric, colorectal, breast, or lung cancers in prospective cohort studies has not been found [10
]. Systematic reviews of randomized controlled trials have concluded that the inverse relationship between garlic supplementation and cardiovascular system disorders was only observed in special populations [11
]. There is also insufficient evidence to determine the difference in the reduction of cardiovascular morbidity risk and mortality risk between patients treated with garlic supplements or placebo [12
Reactive oxygen species (ROSs) accumulate in the aging process. The free radical theory has been proposed to explain the phenomenon of aging. Garlic (especially its OSCs) is known to exhibit antioxidant properties and is the most commonly used herbal supplement among community-dwelling elderly [13
]. However, there is a lack of epidemiologic evidence on the protective effects of garlic against morbidity or mortality in the elderly. In China, garlic is consumed mainly in its raw form, and its consumption is much higher than elsewhere in the world [4
]. Better biologic properties have been suggested for raw garlic than for cooked (processed or heated) garlic: heat seems to react with certain substances in garlic and change their chemical composition [15
]. As the largest exporter and producer of garlic [16
], the Chinese population would appear to be well suited for studying the association of garlic intake with mortality.
Uncertainties about the association between intake of either garlic or garlic supplements and health outcomes could be the result of confounding factors (e.g., tobacco smoking, alcohol drinking, tea drinking, or other dietary habits) or methodological issues (e.g., insufficient sample sizes). Therefore, to evaluate the association of dietary garlic consumption with all-cause mortality, we assessed information from 27,437 oldest-old individuals (≥80 years), adjusting for potential confounding factors, including demographic status, socioeconomic status, dietary habits, health practices, comorbidity, cognition status, and activities of daily living (ADL).
It was found that the habit of garlic consumption was inversely associated with mortality among 27,437 participants aged over 80 years in China. The oldest old who consumed garlic more than five times a week had a 11% decrease in the risk of mortality, compared with those who consumed it less than once a week. The association was consistent across different age groups (octogenarians, nonagenarians, centenarians), for different sex, and in different participant subgroups defined by various baseline characteristics.
This is the first study, to our knowledge, to examine the association between daily garlic consumption and mortality among the oldest old in a prospective cohort. A possible explanation for the results is reverse causality: participants with comorbidities (especially digestive system disease) might limit the consumption of garlic. However, the association remained after we excluded, in the sensitivity analyses, participants with comorbidities to eliminate a potential bias caused by a dietary change due to preexisting illness, affecting the exposure-outcome relation in this cohort study. Moreover, after excluding participants who died during the first year or further adjusting for the presence of digestive system diseases, we found that the association was robust.
The present result is in accordance with former studies revealing beneficial impacts of garlic consumption. Garlic contains a number of potentially active chemical constituents: OSCs, enzymes, amino acids and their glycosides, Se, and other trace minerals [28
]. Almost all studies have focused on OSCs as the active principles of garlic [3
], which in experimental or small-population studies have been demonstrated to be largely responsible for garlic therapeutic properties [29
]. However, other components may contribute to its overall beneficial effects [31
]. The biological activities of garlic (including anticarcinogenic, antioxidant, antibacterial, anti-inflammatory, antiprotozoal, antifungal, hypotensive, hypolipidemic, and antidiabetic actions) have been extensively investigated [3
]. Epidemiologically, the consumption of garlic was linked to a lower risk of colon, stomach, and oral cancers [4
]. Clinically, garlic supplements are used as hypotensives, cholesterol-lowering drugs, as well as glucose-lowering drugs [9
]. Although the effects of garlic’s bioactive ingredients on human health and the aging process require further investigation, some possible explanations have been proposed to explain the benefits of garlic consumption in the oldest old.
To explain the phenomenon of aging, many theories have been advanced, among which the free radical theory is widely accepted. It is generally acknowledged that with age, ROSs are generated, and oxidative damage to human cells accumulates; the damage is likely to contribute to degenerative diseases in the aging process [32
]. Almost all the above-mentioned chemical constituents of garlic, especially OSCs, have been shown to possess antioxidant properties both in vivo and in vitro [34
]. Thereby, these constituents possibly mediate the anti-aging effects of garlic. Accordingly, evidence from a few interventional studies in humans has documented the antioxidant properties of garlic. Plasma oxidized low-density lipoprotein (OxLDL) levels were found to fall sharply in subjects who received garlic supplementation compared with controls [35
]. Altogether, garlic and its OSCs have the potential to delay the onset and development of aging through suppressing the expression of NF-κB and lowering ROS concentration [36
Some other potential explanations for the protective effects of garlic consumption on survival have been advanced, as described below. (1) Garlic and cancer: A study by the US Food and Drug Administration and a Chinese double-blind intervention study have revealed the anti-carcinogenic potential of garlic [37
]. A garlic extract has been reported to inhibit the growth of several different cancer cells in vitro, as well as cancer growth in vivo, enhancing the activities of chemotherapeutics, and of MAPK and PI3K inhibitors [39
]. Besides, similar to other substances like olive oil, garlic may also have a chemopreventive action due to its phenolic compounds [40
]. (2) Garlic and cardiovascular disease (CVD): Garlic is able to enhance the production of hydrogen sulfide, reduce the bioavailability of nitric oxide, inhibit platelet aggregation, and lower hypercholesterolemia and hypertension, thereby potentially preventing CVD [41
]. (3) Antidotal effect of garlic: Both sulfur atoms and allyl groups in OSCs are vital to phase I and II transcription enzymes, which detoxify various endogenous and exogenous chemicals and accelerate metabolite excretion rate [41
]. (4) Anti-inflammatory function of garlic: Garlic has been used as an antibacterial and an immunity stimulant [44
]; its use is well reported in treating ear infections, toothaches, and upper respiratory infections [45
The present study found that garlic consumption, especially ≥5 times a week, was associated with lower mortality risk, possibly due to the bioaccessibility and bioavailability of garlic’s chemical components. This study found that the protective effect was modified by age. The physiological function of the digestive system declines with age; for centenarians, it is less easy to absorb the effective components (such as OSCs) of garlic, which leads to garlic’s weaker protective effect on survival in this age group. Dietary behavior and appetite are highly correlated with global cognitive function. Thus, it was unsurprising that garlic consumption was particularly associated with reduced mortality risk in people with normal cognition, who had a healthier dietary behavior and better health status [46
]. Further targeted investigations are warranted to explore the influence of potential interactions of garlic with other factors on all-cause mortality, especially tea drinking and gender.
Regarded as a safe food, garlic has been consumed for a long time. However, several health risks are reportedly associated with excessive consumption of garlic. It has been proposed that garlic may interact with some drugs and reduce their efficacy [48
]. Particularly, allergic reactions, gastrointestinal tract injury, and decrease in body weigh caused by garlic have attracted much attention [41
]. Accordingly, it would seem prudent for individuals with digestive system disease under medication to avoid garlic.
This study has some limitations. First, the quantity of garlic consumption was not assessed, preventing us from making definite conclusions about a dose–response relationship between the quantity of garlic consumed and the mortality rate; therefore, it not possible to provide more detailed advice on garlic consumption. Second, exposure of garlic to high temperatures was found to destroy OSCs and inhibit garlic anticancer activity [49
]. We did not obtain information about how garlic was consumed (raw, cooked, or processed); however, in China—unlike in other countries—garlic is mainly consumed raw [4
]. Third, the total energy intake was not adjusted for in our study, even though we adjusted for many other variables closely related to it, including age, sex, regular exercise, and BMI. Fourth, the overall dietary patterns were not adjusted for; garlic consumption in our study was closely correlated with other dietary habits, such as consumption of meat, fish, vegetables, and tea; garlic consumption may be an indicator of good appetite, which in turn has been closely associated with health status and risk of all-cause mortality [47
]. Although we carefully adjusted for some dietary habits and conducted a comprehensive sensitivity analysis obtaining robust findings, residual confounding factors, such as intake of minerals, hypercholesterolemia, medication use, can still be present. Fifth, cause-specific mortality was not documented for the participants, especially death of cancer or CVD. Further studies on the anti-cancer and CVD prevention effect of garlic consumption are recommended. Sixth, a recall bias in the collection of garlic consumption at the age of 60 may exist, even though the habit of garlic consumption was relative stable at baseline and at the age of 60 for this population. Seventh, due to the exclusion of 5019 participants lost-to-follow-up at the first follow-up survey, a selection bias may confound the findings, even though the differences between included and excluded subjects were very small.