February 2020 Issue
CPE Monthly: The Disease-Protective Properties of Garlic
By Elizabeth Streit, MS, RDN, LD
Vol. 22, No. 2, P. 46
Suggested CDR Learning Codes: 8.1.2, 8.3.1, 8.4.1
Suggested CDR Performance Indicators: 2010, 2020, 4040
CPE Level 2
Garlic as a flavoring as well as a form of medicine has been well known throughout history. It’s been prized for its healing powers by physicians and healers in countries all over the world, including ancient China, Egypt, India, and Greece. The bulb, for example, was regarded as a powerful antibiotic, a remedy for snakebites, a way to cure constipation and stomachache, and even a relief for colic.1 Emerging research provides considerable evidence for the remedial properties of garlic touted in ancient times and suggests that garlic may offer protective benefits for the heart, brain, and immune system and improve hypertension, fasting blood sugar, and serum lipid levels. However, most of these benefits have been associated in research with garlic supplements rather than dietary garlic.
Due to the complexity of garlic’s chemical composition, the exact mechanisms through which garlic protects against diseases aren’t well understood.2 Processing methods appear to influence the concentration of certain compounds and the overall benefits of garlic preparations. Recent studies have identified a variety of forms of garlic and compounds in them that may have beneficial effects.
This continuing education course assesses current research findings on garlic’s health benefits, summarizes the mechanisms of action of the various compounds found in garlic, and evaluates the safest and most effective way to reap the benefits of this bulb.
Several compounds found in garlic may produce health benefits, but the abundance and efficacy of these compounds depend on the preparation technique. The most common garlic preparations include raw or cooked garlic, powder from dried garlic, oil, and aged extract formed by soaking crushed garlic in aqueous solutions. Raw, intact garlic possesses sulfur-containing compounds such as alliin that contribute to its characteristic flavor and smell. Crushing or cutting garlic converts these sulfur compounds into active and volatile forms called thiosulfinates, the most well known of which is allicin. Although many individuals believe that allicin is the main compound that contributes to the health benefits of garlic, research shows that this thiosulfinate is unstable in the human body. In the conditions of the body, allicin decomposes into other sulfur-containing compounds and, therefore, isn’t likely a main health-promoting compound of garlic.2 Instead, the variety of compounds that develop from allicin are more likely to be responsible for the health benefits of garlic.
However, some studies continue to explore the benefits of allicin. Researchers who have isolated allicin in the laboratory have found that it acts as an antioxidant and can trap free radicals. In addition, findings from research on rats suggest that allicin may prevent hypertension by fighting oxidative stress and inhibiting the processes that lead to high blood pressure. The implication of these findings for humans is undermined by allicin’s lack of bioavailability in the human body, due to its volatility and rapid decomposition when ingested.3
During the preparation of garlic oil or oil-soluble garlic extracts, more organosulfur compounds than those that exist in raw garlic are created. Many of these compounds may demonstrate health benefits, although research on individual compounds is limited. Garlic oils largely are composed of diallyl sulfide and diallyl trisulfide, compounds that are the focus of several studies.2 Research focusing on the specific health benefits of garlic oil suggests possible implications for the prevention of osteoporosis4,5 and protection against certain types of cancer.6,7 For example, one study on rats found that garlic oil extract promotes the transfer of calcium in the intestines, which may prevent the reduced bone density that can lead to osteoporosis.5 Another study showed that rats treated with garlic oil developed a significantly lower number of tumors on their livers when exposed to a compound that causes liver cancer.6
Aqueous solutions, another common liquid preparation of garlic, lead to the development of water-soluble organosulfur compounds such as S-allyl-cysteine (SAC). SAC is most commonly found in aged garlic extract (AGE), the type of garlic used in several research studies. Researchers suspect the aging process transforms the volatile compounds found in raw garlic into more stable substances, such as SAC, which may have antioxidant activity and protect against heart disease and cancer.2,8,9 Unlike allicin and the organosulfur volatiles found in oil-soluble garlic preparations, SAC has been found to be one of the most bioavailable and active compounds in garlic.2
Understanding the complexity of garlic’s chemistry is key to assessing past and emerging research about its health benefits. While several factors, including study designs, may contribute to the differing conclusions about garlic’s potential, the variety of forms of garlic used in studies is one of the factors that most influences results. In addition, several studies were performed on rats, used varying doses of garlic, and occurred over a short timeline.
This article analyzes the conclusions of recent literature while considering the form of garlic used to inform best practice for the use of garlic to protect against disease. More clinical and animal studies, especially those that explore the bioavailability and safety of certain garlic compounds alone and together, are needed.
Mechanisms of Action and Health Benefits
The following sections summarize the current literature on the health effects of garlic and the possible reasons behind these benefits.
Researchers who have investigated the hypotensive effects of garlic mostly have focused on AGE. As previously mentioned, AGE contains a high concentration of SAC, one of the most bioavailable and least volatile compounds in garlic. SAC may be able to lower blood pressure, as it can act as an antioxidant and trap reactive oxygen species. SAC also may inhibit the increased expression of a transcription factor that contributes to hypertension and enhance the production of nitric oxide, a vasodilator.3
Ried and colleagues designed studies that test the impact of AGE capsules with varying doses of SAC on hypertension.8,10-12 In a double-blinded randomized controlled trial with 50 patients with treated yet uncontrolled hypertension, the researchers gave the treatment group 960 mg AGE with 2.4 mg SAC daily for 12 weeks and gave the control group placebos. Every patient in the trial was taking one or more blood pressure medications at the time of the study. The results showed that in conjunction with these medications, AGE contributed to a significant decrease in systolic blood pressure (10.2 ± 4.3 mm Hg, p=0.03) compared with the placebo. Furthermore, participants tolerated AGE well, and the researchers reported a 92% acceptability of the treatment.10 In a similar study, Ried and colleagues found that individuals with uncontrolled blood pressure who received 480 mg AGE experienced a significant reduction in their mean systolic blood pressure (11.8 ± 5.4 mm Hg, p=0.006) at the 12-week mark compared with their own blood pressures at baseline.11
Subsequently, Ried and colleagues assessed the effect of an even higher dose of AGE on blood pressure. In this trial, 88 patients with uncontrolled hypertension received either 1.2 g AGE with 1.2 mg SAC or a placebo for 12 weeks. Each patient also took conventional blood pressure medications, but the differences in medication types weren’t significant among participants at baseline. The results of this trial were consistent with Ried’s previous studies. The group that received AGE had a significantly lower mean systolic blood pressure (5 ± 2.1 mm Hg, p=0.016) at 12 weeks compared with the start of the trial.12 These findings suggest that garlic, especially AGE, may be a safe and effective adjunct treatment for uncontrolled high blood pressure.
Garlic powder and AGE may provide lipid-lowering benefits through at least two suspected mechanisms. Research suggests that the organosulfur compounds in garlic, especially SAC, may inhibit enzymes involved in cholesterol synthesis in the liver.13 Certain compounds in garlic also may stop LDL oxidation.14
Meta-analyses of the existing literature on the beneficial effects of garlic on lipid levels suggest that garlic preparations can significantly reduce total cholesterol levels.15,16 Garlic’s efficacy in reducing total cholesterol appears to depend on the length and type of supplementation. Trials that lasted longer than eight weeks and those that used AGE show a more pronounced cholesterol-lowering effect of garlic.15 Results of studies assessing the efficacy of garlic in reducing LDL or triglyceride levels and increasing HDL levels offer less clear conclusions.
Sobenin and colleagues analyzed the effects of time-released 600 mg garlic powder tablets on the lipid levels of 42 men who were aged 35 to 70 and had slightly high cholesterol levels. The participants were randomized into two groups that received either the garlic tablets or a placebo. The results of the study suggest that, along with a heart-healthy diet, garlic powder tablets may provide cholesterol-lowering effects. The total cholesterol and LDL cholesterol levels of the treatment group decreased by 11.5% and 13.8%, respectively, compared with those in the placebo group after 12 weeks.17
A study by Seo and colleagues assessed the efficacy of AGE extract on lipid levels in 30 women in their 50s. It showed a significant decrease in LDL levels in women who consumed 80 mg AGE, those who exercised and took AGE, or those who just exercised and took a placebo, compared with those in the group who didn’t exercise and took a placebo.18
These results suggest a possible protective effect of certain garlic supplements against elevated lipid levels that may put individuals at risk of heart disease. However, more clinical studies are needed to assess the most effective duration, type, and dose of garlic preparations.
In some studies, researchers have demonstrated that garlic supplements can lower blood sugar levels in individuals with type 2 diabetes. Ashraf and colleagues recruited 60 patients with fasting blood sugar between 100 and 130 mg/dL and divided them into two groups. Each group received 500 mg of metformin two times per day and either 900 mg of garlic tablets or a placebo. After analyzing fasting blood sugar levels at 24 weeks, the authors concluded that garlic tablets contributed to a significant 3.12% reduction in these levels for those in the experimental group compared with the control group participants. The garlic tablets generally were well tolerated, and only one participant reported stomach discomfort. The researchers acknowledge that the mechanism through which garlic tablets can lower blood sugar isn’t well known, but that garlic appears to promote the secretion of insulin.19
Another study by Ashraf and colleagues analyzed the effect of garlic tablets in doses of 300, 600, 900, 1,200, and 1,500 mg per day on both fasting blood sugar and hemoglobin A1c (HbA1c) in 210 individuals with type 2 diabetes. The researchers divided the participants into seven groups; five received one of the doses of garlic, another group received metformin, and a final group took a placebo. Compared with the placebo group, every group that received a dose of garlic had significantly lower fasting blood sugar and HbA1c after 24 weeks.20 The garlic tablets, especially at doses greater than or equal to 900 mg, were comparable to metformin in reducing blood sugar and HbA1c. These studies offer very promising support for the use of garlic in diabetes management.
Due to the antioxidant effects of garlic compounds, especially SAC, it appears that garlic also may protect against cancer. Dong and colleagues investigated a mechanism through which aged black garlic extract may thwart cancer cell production by performing a study on in vitro colon cancer cells. Their results suggest a promising anticancer mechanism, indicating that aged black garlic extract induces cell death in cancer cells by blocking a specific pathway that signals cancer cell growth.9
Additional research on the effects of garlic on cancer has analyzed the impact of garlic oil preparations. Specifically, garlic oil appears to protect against liver cancer that develops from exposure to the environmental carcinogen N-nitrosodiethylamine, found in cheese, processed meats, some alcohol, and agricultural chemicals. Researchers gave rats doses of the carcinogen over 20 weeks to induce nodules on their livers. At the same time, they gave a continuous administration of garlic oil to one group of rats and equal doses of corn oil to the other group. The rats in the garlic oil group had a significantly lower number of nodules on their livers compared with their counterparts.6 This cancer-protective effect of garlic oil may be due to the induction of phase II liver enzymes that block the development of cancerous nodules.21
Finally, even raw garlic may protect against cancer by upregulating genes that promote cell death. Charron and colleagues found that just a single meal with 5 g (the equivalent of one clove) of raw, crushed garlic activated genes related to apoptosis and destruction of cancer cells.22 The different types and doses used in studies that analyze the protective effects of garlic make it difficult to assess the most beneficial garlic preparations related to cancer prevention. However, the promising results of studies that used AGE, garlic oil, and raw garlic suggest benefits from consuming garlic in any form.
Garlic also may have immunomodulatory effects and anti-inflammatory activities, such as the inhibition of the proliferation of proinflammatory cytokines and stimulation of immune cells.7 Specifically, garlic oil may prevent the activity of Th1 lymphocytes that regulate the proinflammatory response and enhance the ability of Th2 lymphocytes to produce an anti-inflammatory process. Liu and colleagues analyzed the effects of garlic oil on Th1 and Th2 lymphocytes in rats and suggested that the response was dose-dependent; larger doses of garlic oil were more effective at inducing an anti-inflammatory response from Th2 cells over a two-week period. Interestingly, smaller doses of the oil had the opposite effect and stimulated Th1 cell responses.23
Other studies clarify the role of garlic in immune response. For example, a study designed by Nantz and colleagues analyzed the ability of AGE to influence immune cell proliferation. They recruited 120 participants and divided them into two groups, one that received 2.56 g AGE per day and one that received placebos. After 45 days, they analyzed blood samples and found that those who took AGE had significantly more proliferation of two specific immune cells compared with those who didn’t. The researchers hypothesized that AGE may improve the capability of certain immune cells to become activated, leading to a stronger immune reponse.24
Strengthening the immune system, especially in those susceptible to infection or illness, is a possible benefit of garlic preparations. Madineh and colleagues performed a short trial with 94 patients admitted to the ICU to analyze the effect of taking a 400 mg garlic tablet daily for six days on inflammatory blood markers and the occurrence of infections. In comparison with those who took a placebo, patients who received the garlic supplements had a significantly lower body temperature.25 However, there were no other significant differences between the groups, suggesting the need for additional studies, perhaps with larger sample sizes and longer durations.
Garlic preparations, due to their antioxidant and anti-inflammatory potential, also may have neuroprotective effects. Specifically, AGE may provide protection against the inflammatory process thought to be related to the development of Alzheimer’s disease. AGE may have this effect due to SAC’s ability to trap reactive oxygen species, as mentioned previously. Based on their work examining neuronal cells of mice that were treated with reactive oxygen species, Ray and colleagues found that AGE protected cells from oxidative damage.26 Furthermore, since diabetes and cardiovascular risk factors may play a role in the development of Alzheimer’s, and since garlic appears to protect against those issues as well, AGE could play a significant role in the fight against Alzheimer’s.
AGE also may protect the brain after cerebral ischemia. By inducing ischemia for one hour and then administering 1.2 mL AGE/kg of weight in rats, Colín-González and colleagues examined the impact of garlic in reducing ischemia-related inflammation. Their results suggested AGE protected against the damage caused by ischemia and diminished the amount of inflammatory markers in the blood after the event. The levels of inflammatory markers in rats that received the AGE were more than 75% lower after the induced ischemia than in the rats that didn’t receive the garlic extract.27
Certain garlic preparations appear to provide protection against the development of osteoporosis in women after menopause. The prevalence of osteoporosis in postmenopausal women may be due to estrogen deficiency and often is treated with estrogen replacement therapy. In rats whose ovaries had been removed, garlic oil was found to be as effective as conventional therapies in preventing bone loss.4 The possible mechanism through which garlic prevents bone mineral loss caused by hormone deficiencies involves the increased transfer of calcium through the intestines.5
A study of 44 women with osteoporosis offered different results. Mozaffari-Khosravi and colleagues examined the effect of raw garlic tablets on the presence of proinflammatory cytokines that have been linked to postmenopausal bone loss due to their influence on bone resorption. The study included two groups, one whose members took approximately 800 mg garlic per day and another whose members took a placebo. After one month of intervention, the blood levels of one inflammatory cytokine were significantly reduced by an average of 47% in the garlic group compared with their baseline levels. However, no significant differences in the cytokine levels of the garlic and placebo groups at the end of the study were observed.28 These studies suggest the possibility that garlic supplements may prevent bone loss, but more research is needed.
Dosage and Type
The majority of research on garlic suggests several promising benefits of this widely used bulb. The variety of dosages and types of garlic preparations appears to contribute significantly to the different and sometimes inconsistent observed effects of garlic. Thus, it remains difficult to recommend tangible applications of the reviewed research to dietetics practice. More research, especially on the most effective, safe, and tolerable types of garlic, is needed.
The accompanying table lists the main forms of commercially available garlic supplements, the dosages at which they have been used in clinical trials or studies using lab rats, and the demonstrated effects.
It appears that AGE may be the most well-tolerated form of garlic preparation, in addition to being superior in efficacy and bioavailability. The extraction procedure seems to increase the potency of garlic and eliminate the odor and irritating components of raw garlic that can cause heartburn, burning sensations when handling, and related symptoms.2 AGE is suspected to be safer and less toxic than raw or powdered garlic versions.2,10 A study by Hoshino and colleagues about the effects of garlic preparations on the mucosa of the gastrointestinal (GI) tract of dogs found that AGE didn’t cause any negative effects.29 This is supported by Ried and colleagues’ research, which reported a 92% acceptance rate of AGE from human participants who took it.10
Researchers also point to the more stable nature of SAC in AGE when compared with volatile compounds, such as allicin.2,10 Whereas allicin may quickly disappear from the blood once digested, SAC doesn’t; it’s thought to be one of the most active components of garlic.2 The stability of SAC makes AGE a supplement that can easily be standardized. The minimal side effects associated with AGE make it an appealing alternative to current medications that can cause more serious side effects, such as statins and antihypertensive drugs.
Other forms of garlic, such as dehydrated raw garlic powder and even enteric-coated capsules of garlic powder, may damage GI mucosa and cause stomach irritation. Hoshino and colleagues found that dehydrated raw garlic powder caused erosion and severe damage in the GI tracts of dogs. Enteric capsules caused reddening and, when taken orally, produced damage in the dogs’ ileums.29
Furthermore, long-term use of any supplement raises concerns for toxicity. While garlic preparations such as AGE appear to have no adverse effects when consumed in varying doses, more research on the impact of garlic supplements over long periods of time is necessary. Without a strong base of research to support the suspected minimal side effects of garlic supplements, it’s difficult to make recommendations for a standardized type or dose. Another important consideration is that the FDA doesn’t regulate supplements, which can lead to differences in content and purity among supplements that claim to have a specific amount and/or type of a substance. The actual dose and the one listed on the label may not always correspond. Supplements that have been tested by a third party may have a more accurate stated dosage.
A serious concern surrounding the use of garlic supplementation is the possible contraindications for people taking certain medications. Individuals taking antihypertensive medications and/or warfarin (Coumadin) often are told to use garlic supplements with caution to prevent bleeding, since garlic also may prevent blood clotting.2,30 However, a 2006 study by Macan and colleagues including 66 patients taking warfarin found that those who also took 5 mL AGE per day for 12 weeks didn’t have an increased risk of hemorrhages compared with those who took a placebo.31
Note on Culinary Garlic
Most studies focus on the possible health benefits of garlic supplements, oils, and extracts, and rarely provide information on raw or cooked garlic as it would appear in everyday recipes to participants.
However, eating garlic and adding it to food is associated with health benefits in observational studies. Most of the studies that assess the relationship between dietary garlic intake and disease risk are focused on cancer. An epidemiologic study by Jin and colleagues included close to 6,000 Chinese adults and found that people who ate raw garlic two times or more per week over seven years had a 44% lower risk of developing lung cancer.32
Epidemiologic studies on the possible link between garlic intake and the prevention of other diseases are limited, and more research is needed. Nevertheless, culinary garlic has been used to help with ailments for centuries.1
Dietitians can instruct patients to increase their use of garlic in the kitchen by recommending recipes with garlic and teaching them how to crush or chop raw garlic cloves.
Implications for Dietitians
As the nutrition experts for clients, patients, and the general public, RDs should be aware of the current evidence for the health benefits of garlic. Studies have demonstrated that garlic may improve hypertension, lower cholesterol, protect against cancer, prevent bone loss, lower fasting blood sugar, and strengthen the immune system. While raw and cooked garlic has been used for its medicinal properties for thousands of years, emerging research points to the potential of supplemental forms of garlic, especially AGE. However, concerns about the safety and efficacy of garlic supplements remain, and recommendations for a standardized dose and type don’t exist. Until more research is available, dietitians and other health professionals should be cautious about recommending garlic supplements for health promotion and disease prevention.30
As garlic continues to gain recognition as a functional food and possible alternative or adjunctive therapy to modern medications, the development of a standardized supplement tested for safety may not be far off. In the meantime, dietitians should continue to recommend a predominantly plant-based diet rich in vegetables, fruits, herbs, spices, and traditional flavorings such as garlic.
— Elizabeth Streit, MS, RDN, LD, is founder of the food blog and business It’s a Veg World After All, a contributing writer for Healthline: Authority Nutrition, and an instructor at Northwestern Health Sciences University.
After completing this continuing education course, nutrition professionals should be better able to:
1. Evaluate garlic’s mechanism of action and the impact of different processing and preparation methods on garlic’s efficacy.
2. Distinguish the effects of garlic from food vs supplement form.
3. Discuss the potential benefits of garlic, including immune-modulating, hypotensive, cholesterol-lowering, neuroprotective, anticancer, and antiosteoporotic effects.
4. Analyze at least two reasons why research on the health benefits of garlic shows contradictory results.
CPE Monthly Examination
1. Which of the following compounds in garlic is the least bioavailable?
a. Diallyl sulfide
b. Diallyl trisulfide
2. Aged garlic extract (AGE) can lower blood pressure due to which of the following mechanisms of action?
a. It acts as an antioxidant.
b. It lowers heart rate.
c. It increases blood flow.
d. It heals damaged arteries.
3. Which of the following two lipid measurements have been shown to improve after treatment with garlic preparations?
a. HDL cholesterol and LDL cholesterol
b. Triglycerides and total cholesterol
c. Total cholesterol and HDL cholesterol
d. Total cholesterol and LDL cholesterol
4. What is the suspected mechanism by which garlic supplements lower blood sugar?
a. Increasing insulin secretion
b. Decreasing glucose production by the liver
c. Contributing to weight loss
d. Decreasing appetite
5. According to research, AGE, garlic oil, and raw garlic all may protect against the development of which disease?
d. Cystic fibrosis
6. In rats with induced ischemia, Colín-González and colleagues found that AGE did which of the following?
a. Decreased inflammatory markers by 50%
b. Increased inflammatory markers by 50%
c. Decreased inflammatory markers by 75%
d. Increased inflammatory markers by 75%
7. What type of garlic preparation appears to be the most effective, safe, and bioavailable?
a. Garlic oil
b. Garlic powder
c. Raw garlic
8. When examining the effect of different garlic preparations on gastrointestinal mucosa in dogs, what type of preparation did Hoshino and colleagues find to cause erosion and severe damage?
a. Raw garlic
b. Garlic essence
c. Garlic oil
d. Dehydrated raw garlic powder
9. In their epidemiologic study, Jin and colleagues found that those who ate raw garlic two or more times per week had a 44% lower risk of developing which of the following conditions?
a. Breast cancer
b. Lung cancer
c. Prostate cancer
d. Skin cancer
10. In one of their clinical trials, Ried and colleagues found that 480 mg AGE per day for 12 weeks led to a significant reduction in what measurement related to heart health?
a. Systolic blood pressure
b. Diastolic blood pressure
c. HDL cholesterol
d. LDL cholesterol
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18. Seo DY, Lee SR, Kim HK, et al. Independent beneficial effects of aged garlic extract intake with regular exercise on cardiovascular risk in postmenopausal women. Nutr Res Pract. 2012;6(3):226-231.
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