Organo Sulfur Compounds

Allium and cruciferous vegetables are an excellent addition to any strategy to promote joint, muscle, bone, and tendon health. Allium and cruciferous vegetables are a rich source of organo sulfur compounds. Organo sulfur compounds are a subclass of organic substances that contain sulfur and  have been utilized for thousands of years to remedy human disease and more recently as life-saving antibiotics, such as penicillin and cephalosporins .

As sulfur is essential for life, nature is teeming with organo sulfur compounds.These compounds are found in a wide variety of locations, including interstellar space, deep within the ocean, and inside hot volcanoes. They can be found in the bodies of all living things in the form of some amino acids,  coenzymes, hormones, and vitamins.

 

Musculoskeletal health benefits of organo sulfur compounds

Chronic disease of bone, muscle, tendon, and joint, at least in part, share a common destructive pathway governed by excessive inflammation and oxidative stress. While the exact manner in which organosulfur substances promote musculoskeletal well being is unknown the likely mechanism is its reduction of chronic oxidative stress and inflammation.

Antioxidant

Organo sulfur compounds possess impressive antioxidant attributes. Scientific data indicates that organosulfur compounds display a variety of antioxidant properties:

  • Direct quenching of high energy, destructive free radicals
  • Boost the potency of glutathione and glutathione disulfide reductase. Glutathione is the body's bulwark against oxygen free radicals, oxidized fat, and heavy metal toxins.
  • Enhance superoxide dismutase activity, the body’s best defense against super dangerous oxygen molecules called superoxide anions.

Anti-inflammatory

Organo sulfur derivatives provide multi pronged defense against chronic inflammation. Reserarch has demonstrated that organo sulfur compounds:

  • Thwart Nuclear Factor-kB(NF-kB) pathway activation. NF-kB directs the activation of sequences of DNA that magnify inflammation
  • Suppress the activity of  Tumor Necrosis Factor Alpha and IL-1B, two master signaling molecules that orchestrate chronic inflammation 
  • Decrease the synthesis of COX-2 enzyme. COX-2 enzymes produce substances called prostaglandins that cause pain and swelling
  • Reduce production of matrix metalloproteinases, substances that breakdown healthy tissue

Selected Evidence

1. Organo sulfur Compounds Support Joint Health

Population twin studies from England identified a potential protective effect of allium vegetables against osteoarthritis.  When examining pairs of twins with near identical genetics, the twin that consumed allium vegetables on a regular basis had a significantly less likelihood of developing osteoarthritis. (Skinner et al. BMC Musculoskelet Disord. 2010 Dec 8;11:280)

2. Organo sulfur Compounds Support Bone Health

Researchers in China exposed mouse bone resorbing cells called osteoclasts to a garlic extract high in allium. The investigators concluded that the extract reduced the production of bone resorbing cells by reducing the cells exposure to free radicals and oxidative stress. Excessive bone resorption is the cardinal cause of osteoporosis. (Chen et al. Alliin Attenuated RANKL-Induced Osteoclastogenesis by Scavenging Reactive Oxygen Species through Inhibiting Nox1.Int J Mol Sci. 2016 Sep 20;17(9). pii: E1516.)

3. Organo sulfur Compound Supports Muscle Health

Chinese investigators administered sulforaphane to mice and assessed its effect on muscle inflammation. The researchers found that sulforphane reduced muscle inflammation by reducing the influx of immune cells into muscle tissue and decreasing the production of inflammation promoting cytokines. (Cheng-Cao Sun et al. Sulforaphane Attenuates Muscle Inflammation in Dystrophin-deficient mdx Mice via NF-E2-related Factor 2 (Nrf2)-mediated Inhibition of NF-κB Signaling Pathway. J Biol Chem. 2015 Jul 17; 290(29): 17784–17795.)

Other Health benefits of organo sulfur compounds

According to research, eating cruciferous vegetables and garlic is linked with several health benefits:

  • Reduces risk of colorectal and stomach cancers 
  • Gives strength and resiliency to hair
  • Supports healthy blood sugar
  • Promotoes heart and blood vessel health

How to properly prepare these vegetables in order to preserve their compounds

Broccoli

For broccoli, the best way is to steam. Study found that steaming gives the sulforaphane 3 times more bioavailable than heavy cooking.

Onions and garlic

The best way to eat these allyl sulfur compounds is to eat them raw. So chopping up some onion and garlic and mixing them into your salad will give you most of the benefits of these compounds.

Cabbage

Research has shown that you can get more bioavailable organosulfur compounds from your cabbage if you lightly steam them. Cooking in high heat in the microwave destroys many of these beneficial compounds. Chop it up to your desired consistency and then let sit for a few minutes. Steam for four to five minutes. If you want to use the microwave, use the low or medium setting.

Cauliflower

Cut into small florets and then let sit for ten minutes; it’ll allow the myrosinase enzyme to do its job and make glucosinates more available. Now, steam or bake them. One delicious recipe: Bake a few small florets of cauliflower and mix them with curry powder, turmeric, cayenne, salt and olive oil.

Brussels sprouts

Best way to prepare Brussels sprouts is to quarter and stem them for 5 minutes. Remove them from the steamer and toss with olive oil or butter.

Best natural sources of foods high in sulfur

Cruciferous Vegetables

Cruciferous vegetables including broccoli, cabbage, cauliflower, Brussels sprouts, kale, bok choy, turnips, and kohlrabi, are packed with glucosinolates, which give them a pungent aroma and slightly bitter taste.

Allium Vegetables

Onions, garlic, leeks and chives, contain organosulfur compounds.

 

Precautions

Organo sulfur compounds from natural foods is generally well tolerated. 

High intake may cause mild gastrointestinal symptoms, breath and body odor. High dose supplementation may enhance anti-coagulation effects of blood thinners and decrease the bioavailability of HIV protease inhibitors. 

Any consideration a supplementation should be discussed with a qualified health professional familiar with your unique medical history.

References

1.  Guercio V, Galeone C, Turati F, La Vecchia C. Gastric cancer and allium vegetable intake: a critical review of the experimental and epidemiologic evidence. Nutr Cancer. 2014;66(5):757-773.  (PubMed)

2.  Block E. The chemistry of garlic and onions. Sci Am. 1985;252(3):114-119. 

3.  Blumenthal M. Herb Sales Down 7.4 Percent in Mainstream Market. HerbalGram: American Botanical Council; 2005:63.

4.  Trio PZ, You S, He X, He J, Sakao K, Hou DX. Chemopreventive functions and molecular mechanisms of garlic organosulfur compounds. Food Funct. 2014;5(5):833-844.  (PubMed)

5.  Lawson LD. Garlic: a review of its medicinal effects and indicated active compounds. In: Lawson LD, Bauer R, eds. Phytomedicines of Europe: Chemistry and Biological Activity. Washington, D. C.: American Chemical Society; 1998:177-209.

6.  Amagase H. Clarifying the real bioactive constituents of garlic. J Nutr. 2006;136(3 Suppl):716S-725S.  (PubMed)

7.  Lawson LD, Wang ZJ. Allicin and allicin-derived garlic compounds increase breath acetone through allyl methyl sulfide: use in measuring allicin bioavailability. J Agric Food Chem. 2005;53(6):1974-1983.  (PubMed)

8.  Lawson LD, Hughes BG. Characterization of the formation of allicin and other thiosulfinates from garlic. Planta Med. 1992;58(4):345-350.  (PubMed)

9.  Minami T, Boku T, Inada K, Morita M, Okasaki Y. Odor components of human breath after the ingestion of grated raw garlic. J Food Sci. 1989;54:763-765. 

10.  Rosen RT, Hiserodt RD, Fukuda EK, et al. Determination of allicin, S-allylcysteine and volatile metabolites of garlic in breath, plasma or simulated gastric fluids. J Nutr. 2001;131(3s):968S-971S.  (PubMed)

11.  Suarez F, Springfield J, Furne J, Levitt M. Differentiation of mouth versus gut as site of origin of odoriferous breath gases after garlic ingestion. Am J Physiol. 1999;276(2 Pt 1):G425-430.  (PubMed)

12.  de Rooij BM, Boogaard PJ, Rijksen DA, Commandeur JN, Vermeulen NP. Urinary excretion of N-acetyl-S-allyl-L-cysteine upon garlic consumption by human volunteers. Arch Toxicol. 1996;70(10):635-639.  (PubMed)

13.  Jandke J, Spiteller G. Unusual conjugates in biological profiles originating from consumption of onions and garlic. J Chromatogr. 1987;421(1):1-8.  (PubMed)

14.  Kodera Y, Suzuki A, Imada O, et al. Physical, chemical, and biological properties of s-allylcysteine, an amino acid derived from garlic. J Agric Food Chem. 2002;50(3):622-632.  (PubMed)

15.  Percival SS. Aged Garlic Extract Modifies Human Immunity. J Nutr. 2016;146(2):433S-436S.  (PubMed)

16.  Steiner M, Khan AH, Holbert D, Lin RI. A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. Am J Clin Nutr. 1996;64(6):866-870.  (PubMed)

17.  Nagae S, Ushijima M, Hatono S, et al. Pharmacokinetics of the garlic compound S-allylcysteine. Planta Med. 1994;60(3):214-217.  (PubMed)

18.  Budoff MJ, Takasu J, Flores FR, et al. Inhibiting progression of coronary calcification using Aged Garlic Extract in patients receiving statin therapy: a preliminary study. Prev Med. 2004;39(5):985-991.  (PubMed)

19.  Horev-Azaria L, Eliav S, Izigov N, et al. Allicin up-regulates cellular glutathione level in vascular endothelial cells. Eur J Nutr. 2009;48(2):67-74.  (PubMed)

20.  Liu C, Cao F, Tang QZ, et al. Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways. J Nutr Biochem. 2010;21(12):1238-1250.  (PubMed)

21.  Chen C, Kong AN. Dietary chemopreventive compounds and ARE/EpRE signaling. Free Radic Biol Med. 2004;36(12):1505-1516.  (PubMed)

22.  Zeng T, Zhang CL, Song FY, et al. The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress. Biochim Biophys Acta. 2013;1830(10):4848-4859.  (PubMed)

23.  Tsai CY, Wang CC, Lai TY, et al. Antioxidant effects of diallyl trisulfide on high glucose-induced apoptosis are mediated by the PI3K/Akt-dependent activation of Nrf2 in cardiomyocytes. Int J Cardiol. 2013;168(2):1286-1297.  (PubMed)

24.  Hiramatsu K, Tsuneyoshi T, Ogawa T, Morihara N. Aged garlic extract enhances heme oxygenase-1 and glutamate-cysteine ligase modifier subunit expression via the nuclear factor erythroid 2-related factor 2-antioxidant response element signaling pathway in human endothelial cells. Nutr Res. 2016;36(2):143-149.  (PubMed)

25.  Gomez-Sierra T, Molina-Jijon E, Tapia E, et al. S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. J Pharm Pharmacol. 2014;66(9):1271-1281.  (PubMed)

26.  Shi H, Jing X, Wei X, et al. S-allyl cysteine activates the Nrf2-dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo. J Neurochem. 2015;133(2):298-308.  (PubMed)

27.  Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411-418.  (PubMed)

28.  Lundblad C, Grande PO, Bentzer P. Hemodynamic and histological effects of traumatic brain injury in eNOS-deficient mice. J Neurotrauma. 2009;26(11):1953-1962.  (PubMed)

29.  Bhattacharyya M, Girish GV, Karmohapatra SK, Samad SA, Sinha AK. Systemic production of IFN-α by garlic (Allium sativum) in humans. J Interferon Cytokine Res. 2007;27(5):377-382.  (PubMed)

30.  Lei YP, Liu CT, Sheen LY, Chen HW, Lii CK. Diallyl disulfide and diallyl trisulfide protect endothelial nitric oxide synthase against damage by oxidized low-density lipoprotein. Mol Nutr Food Res. 2010;54 Suppl 1:S42-52.  (PubMed)

31.  Chen W, Qi J, Feng F, et al. Neuroprotective effect of allicin against traumatic brain injury via Akt/endothelial nitric oxide synthase pathway-mediated anti-inflammatory and anti-oxidative activities. Neurochem Int. 2014;68:28-37.  (PubMed)

32.  Shouk R, Abdou A, Shetty K, Sarkar D, Eid AH. Mechanisms underlying the antihypertensive effects of garlic bioactives. Nutr Res. 2014;34(2):106-115.  (PubMed)

33.  Yang J, Wang T, Yang J, et al. S-allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats. Andrology. 2013;1(3):487-494.  (PubMed)

34.  Ho SC, Su MS. Evaluating the anti-neuroinflammatory capacity of raw and steamed garlic as well as five organosulfur compounds. Molecules. 2014;19(11):17697-17714.  (PubMed)

35.  Liu KL, Chen HW, Wang RY, Lei YP, Sheen LY, Lii CK. DATS reduces LPS-induced iNOS expression, NO production, oxidative stress, and NF-κB activation in RAW 264.7 macrophages. J Agric Food Chem. 2006;54(9):3472-3478.  (PubMed)

36.  You S, Nakanishi E, Kuwata H, et al. Inhibitory effects and molecular mechanisms of garlic organosulfur compounds on the production of inflammatory mediators. Mol Nutr Food Res. 2013;57(11):2049-2060.  (PubMed)

37.  Lee HH, Han MH, Hwang HJ, et al. Diallyl trisulfide exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophages by suppressing the Toll-like receptor 4/nuclear factor-κB pathway. Int J Mol Med. 2015;35(2):487-495.  (PubMed)

38.  Gebhardt R, Beck H. Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures. Lipids. 1996;31(12):1269-1276.  (PubMed)

39.  Ferri N, Yokoyama K, Sadilek M, et al. Ajoene, a garlic compound, inhibits protein prenylation and arterial smooth muscle cell proliferation. Br J Pharmacol. 2003;138(5):811-818.  (PubMed)

40.  Liu L, Yeh YY. S-alk(en)yl cysteines of garlic inhibit cholesterol synthesis by deactivating HMG-CoA reductase in cultured rat hepatocytes. J Nutr. 2002;132(6):1129-1134.  (PubMed)

41.  Singh DK, Porter TD. Inhibition of sterol 4α-methyl oxidase is the principal mechanism by which garlic decreases cholesterol synthesis. J Nutr. 2006;136(3 Suppl):759S-764S.  (PubMed)

42.  Allison GL, Lowe GM, Rahman K. Aged garlic extract may inhibit aggregation in human platelets by suppressing calcium mobilization. J Nutr. 2006;136(3 Suppl):789S-792S.  (PubMed)

43.  Chan KC, Hsu CC, Yin MC. Protective effect of three diallyl sulphides against glucose-induced erythrocyte and platelet oxidation, and ADP-induced platelet aggregation. Thromb Res. 2002;108(5-6):317-322.  (PubMed)

44.  Lawson LD, Ransom DK, Hughes BG. Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products. Thromb Res. 1992;65(2):141-156.  (PubMed)

45.  Allison GL, Lowe GM, Rahman K. Aged garlic extract inhibits platelet activation by increasing intracellular cAMP and reducing the interaction of GPIIb/IIIa receptor with fibrinogen. Life Sci. 2012;91(25-26):1275-1280.  (PubMed)

46.  Rahman K, Lowe GM, Smith S. Aged garlic extract inhibits human platelet aggregation by altering intracellular signaling and platelet shape change. J Nutr. 2016;146(2):410S-415S.  (PubMed)

47.  Hedin U, Roy J, Tran PK. Control of smooth muscle cell proliferation in vascular disease. Curr Opin Lipidol. 2004;15(5):559-565.  (PubMed)

48.  Campbell JH, Efendy JL, Smith NJ, Campbell GR. Molecular basis by which garlic suppresses atherosclerosis. J Nutr. 2001;131(3s):1006S-1009S.  (PubMed)

49.  Golovchenko I, Yang CH, Goalstone ML, Draznin B. Garlic extract methylallyl thiosulfinate blocks insulin potentiation of platelet-derived growth factor-stimulated migration of vascular smooth muscle cells. Metabolism. 2003;52(2):254-259.  (PubMed)

50.  Lei YP, Chen HW, Sheen LY, Lii CK. Diallyl disulfide and diallyl trisulfide suppress oxidized LDL-induced vascular cell adhesion molecule and E-selectin expression through protein kinase A- and B-dependent signaling pathways. J Nutr. 2008;138(6):996-1003.  (PubMed)

51.  Pryor WA, Houk KN, Foote CS, et al. Free radical biology and medicine: it's a gas, man! Am J Physiol Regul Integr Comp Physiol. 2006;291(3):R491-511.  (PubMed)

52.  Lefer DJ. A new gaseous signaling molecule emerges: cardioprotective role of hydrogen sulfide. Proc Natl Acad Sci U S A. 2007;104(46):17907-17908.  (PubMed)

53.  Ried K, Fakler P. Potential of garlic (Allium sativum) in lowering high blood pressure: mechanisms of action and clinical relevance. Integr Blood Press Control. 2014;7:71-82.  (PubMed)

54.  Benavides GA, Squadrito GL, Mills RW, et al. Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci U S A. 2007;104(46):17977-17982.  (PubMed)

55.  Yang CS, Chhabra SK, Hong JY, Smith TJ. Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic. J Nutr. 2001;131(3s):1041S-1045S.  (PubMed)

56.  Brady JF, Ishizaki H, Fukuto JM, et al. Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem Res Toxicol. 1991;4(6):642-647.  (PubMed)

57.  Taubert D, Glockner R, Muller D, Schomig E. The garlic ingredient diallyl sulfide inhibits cytochrome P450 2E1 dependent bioactivation of acrylamide to glycidamide. Toxicol Lett. 2006;164(1):1-5.  (PubMed)

58.  Jeong HG, Lee YW. Protective effects of diallyl sulfide on N-nitrosodimethylamine-induced immunosuppression in mice. Cancer Lett. 1998;134(1):73-79.  (PubMed)

59.  Park KA, Kweon S, Choi H. Anticarcinogenic effect and modification of cytochrome P450 2E1 by dietary garlic powder in diethylnitrosamine-initiated rat hepatocarcinogenesis. J Biochem Mol Biol. 2002;35(6):615-622.  (PubMed)

60.  Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther. 2002;72(3):276-287.  (PubMed)

61.  Gurley BJ, Gardner SF, Hubbard MA, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005;22(6):525-539.  (PubMed)

62.  Loizou GD, Cocker J. The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone. Hum Exp Toxicol. 2001;20(7):321-327.  (PubMed)

63.  Munday R, Munday CM. Induction of phase II enzymes by aliphatic sulfides derived from garlic and onions: an overview. Methods Enzymol. 2004;382:449-456.  (PubMed)

64.  Andorfer JH, Tchaikovskaya T, Listowsky I. Selective expression of glutathione S-transferase genes in the murine gastrointestinal tract in response to dietary organosulfur compounds. Carcinogenesis. 2004;25(3):359-367.  (PubMed)

65.  Hatono S, Jimenez A, Wargovich MJ. Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase. Carcinogenesis. 1996;17(5):1041-1044.  (PubMed)

66.  Munday R, Munday CM. Relative activities of organosulfur compounds derived from onions and garlic in increasing tissue activities of quinone reductase and glutathione transferase in rat tissues. Nutr Cancer. 2001;40(2):205-210.  (PubMed)

67.  Lee IC, Kim SH, Baek HS, et al. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. Food Chem Toxicol. 2014;63:174-185.  (PubMed)

68.  Lee IC, Kim SH, Baek HS, et al. Protective effects of diallyl disulfide on carbon tetrachloride-induced hepatotoxicity through activation of Nrf2. Environ Toxicol. 2015;30(5):538-548.  (PubMed)

69.  Stewart ZA, Westfall MD, Pietenpol JA. Cell-cycle dysregulation and anticancer therapy. Trends Pharmacol Sci. 2003;24(3):139-145.  (PubMed)

70.  Powolny AA, Singh SV. Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds. Cancer Lett. 2008;269(2):305-314.  (PubMed)

71.  Singh SV, Powolny AA, Stan SD, et al. Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice. Cancer Res. 2008;68(22):9503-9511.  (PubMed)

72.  Jikihara H, Qi G, Nozoe K, et al. Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation. Oncol Rep. 2015;33(3):1131-1140.  (PubMed)

73.  Wu X, Kassie F, Mersch-Sundermann V. Induction of apoptosis in tumor cells by naturally occurring sulfur-containing compounds. Mutat Res. 2005;589(2):81-102.  (PubMed)

74.  Balasenthil S, Rao KS, Nagini S. Apoptosis induction by S-allylcysteine, a garlic constituent, during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Cell Biochem Funct. 2002;20(3):263-268.  (PubMed)

75.  Balasenthil S, Rao KS, Nagini S. Garlic induces apoptosis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Oral Oncol. 2002;38(5):431-436.  (PubMed)

76.  Zhang CL, Zeng T, Zhao XL, Yu LH, Zhu ZP, Xie KQ. Protective effects of garlic oil on hepatocarcinoma induced by N-nitrosodiethylamine in rats. Int J Biol Sci. 2012;8(3):363-374.  (PubMed)

77.  Bauer D, Redmon N, Mazzio E, et al. Diallyl disulfide inhibits TNFα induced CCL2 release through MAPK/ERK and NF-Kappa-B signaling. Cytokine. 2015;75(1):117-126.  (PubMed)

78.  Matsuura N, Miyamae Y, Yamane K, et al. Aged garlic extract inhibits angiogenesis and proliferation of colorectal carcinoma cells. J Nutr. 2006;136(3 Suppl):842S-846S.  (PubMed)

79.  Fenwick GR, Hanley AB. The genus Allium--Part 3. Crit Rev Food Sci Nutr. 1985;23(1):1-73.  (PubMed)

80.  Harris JC, Cottrell SL, Plummer S, Lloyd D. Antimicrobial properties of Allium sativum (garlic). Appl Microbiol Biotechnol. 2001;57(3):282-286.  (PubMed)

81.  Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic. Microbes Infect. 1999;1(2):125-129.  (PubMed)

82.  Cavallito CJ, Bailey JH. Allicin, the antibacterial principle of Allium sativum. I. Isolation, physical properties and antibacterial action J Am Chem Soc. 1944;66(11):1950-1951. 

83.  Martin KW, Ernst E. Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials. J Antimicrob Chemother. 2003;51(2):241-246.  (PubMed)

84.  Gail MH, Pfeiffer RM, Brown LM, et al. Garlic, vitamin, and antibiotic treatment for Helicobacter pylori: a randomized factorial controlled trial. Helicobacter. 2007;12(5):575-578.  (PubMed)

85.  You WC, Brown LM, Zhang L, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006;98(14):974-983.  (PubMed)

86.  Ledezma E, DeSousa L, Jorquera A, et al. Efficacy of ajoene, an organosulphur derived from garlic, in the short-term therapy of tinea pedis. Mycoses. 1996;39(9-10):393-395.  (PubMed)

87.  Nantz MP, Rowe CA, Muller CE, Creasy RA, Stanilka JM, Percival SS. Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention. Clin Nutr. 2012;31(3):337-344.  (PubMed)

88.  Keys A. Wine, garlic, and CHD in seven countries. Lancet. 1980;1(8160):145-146.  (PubMed)

89.  Wirth J, di Giuseppe R, Boeing H, Weikert C. A Mediterranean-style diet, its components and the risk of heart failure: a prospective population-based study in a non-Mediterranean country. Eur J Clin Nutr. 2016;70(9):1015-1021.  (PubMed)

90.  Ackermann RT, Mulrow CD, Ramirez G, Gardner CD, Morbidoni L, Lawrence VA. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med. 2001;161(6):813-824.  (PubMed)

91.  Wojcikowski K, Myers S, Brooks L. Effects of garlic oil on platelet aggregation: a double-blind placebo-controlled crossover study. Platelets. 2007;18(1):29-34.  (PubMed)

92.  Zeng T, Zhang CL, Zhao XL, Xie KQ. The roles of garlic on the lipid parameters: a systematic review of the literature. Crit Rev Food Sci Nutr. 2013;53(3):215-230.  (PubMed)

93.  Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. 2013;71(5):282-299.  (PubMed)

94.  Koscielny J, Klussendorf D, Latza R, et al. The antiatherosclerotic effect of Allium sativum. Atherosclerosis. 1999;144(1):237-249.  (PubMed)

95.  Siegel G, Klussendorf D. The anti-atheroslerotic effect of Allium sativum: statistics re-evaluated. Atherosclerosis. 2000;150(2):437-438.  (PubMed)

96.  Almoudi M, Sun Z. Coronary artery calcium score: Re-evaluation of its predictive value for coronary artery disease. World J Cardiol. 2012;4(10):284-287.  (PubMed)

97.  Kwon SW, Kim YJ, Shim J, et al. Coronary artery calcium scoring does not add prognostic value to standard 64-section CT angiography protocol in low-risk patients suspected of having coronary artery disease. Radiology. 2011;259(1):92-99.  (PubMed)

98.  Matsumoto S, Nakanishi R, Li D, et al. Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study. J Nutr. 2016;146(2):427S-432S.  (PubMed)

99.  Hadamitzky M, Distler R, Meyer T, et al. Prognostic value of coronary computed tomographic angiography in comparison with calcium scoring and clinical risk scores. Circ Cardiovasc Imaging. 2011;4(1):16-23.  (PubMed)

100.   Nakanishi K, Fukuda S, Shimada K, et al. Non-obstructive low attenuation coronary plaque predicts three-year acute coronary syndrome events in patients with hypertension: multidetector computed tomographic study. J Cardiol. 2012;59(2):167-175.  (PubMed)

101.   Reinhart KM, Coleman CI, Teevan C, Vachhani P, White CM. Effects of garlic on blood pressure in patients with and without systolic hypertension: a meta-analysis. Ann Pharmacother. 2008;42(12):1766-1771.  (PubMed)

102.   Ried K. Garlic lowers blood pressure in hypertensive individuals, regulates serum cholesterol, and stimulates immunity: an updated meta-analysis and review. J Nutr. 2016;146(2):389S-396S.  (PubMed)

103.   Ried K, Frank OR, Stocks NP, Fakler P, Sullivan T. Effect of garlic on blood pressure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2008;8:13.  (PubMed)

104.   Silagy CA, Neil HA. A meta-analysis of the effect of garlic on blood pressure. J Hypertens. 1994;12(4):463-468.  (PubMed)

105.   Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17(3):223-231.  (PubMed)

106.   Xiong XJ, Wang PQ, Li SJ, Li XK, Zhang YQ, Wang J. Garlic for hypertension: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine. 2015;22(3):352-361.  (PubMed)

107.   Rohner A, Ried K, Sobenin IA, Bucher HC, Nordmann AJ. A systematic review and metaanalysis on the effects of garlic preparations on blood pressure in individuals with hypertension. Am J Hypertens. 2015;28(3):414-423.  (PubMed)

108.   Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.  (PubMed)

109.   Stabler SN, Tejani AM, Huynh F, Fowkes C. Garlic for the prevention of cardiovascular morbidity and mortality in hypertensive patients. Cochrane Database Syst Rev. 2012(8):CD007653.  (PubMed)

110.   Ried K, Travica N, Sali A. The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: the AGE at Heart trial. Integr Blood Press Control. 2016;9:9-21.  (PubMed)

111.   Kodali RT, Eslick GD. Meta-analysis: Does garlic intake reduce risk of gastric cancer? Nutr Cancer. 2015;67(1):1-11.  (PubMed)

112.   Kim JY, Kwon O. Garlic intake and cancer risk: an analysis using the Food and Drug Administration's evidence-based review system for the scientific evaluation of health claims. Am J Clin Nutr. 2009;89(1):257-264.  (PubMed)

113.   US Food and Drug Administration. Guidance for industry: evidence-based review system for the scientific evaluation of health claims - final. In: US Department of Health and Human Services, ed; 2009. Available at: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/LabelingNutrition/ucm073332.htm. Accessed 1/6/17.

114.   Hansson LE, Nyren O, Bergstrom R, et al. Diet and risk of gastric cancer. A population-based case-control study in Sweden. Int J Cancer. 1993;55(2):181-189.  (PubMed)

115.   Kim HJ, Chang WK, Kim MK, Lee SS, Choi BY. Dietary factors and gastric cancer in Korea: a case-control study. Int J Cancer. 2002;97(4):531-535.  (PubMed)

116.   Dorant E, van den Brandt PA, Goldbohm RA. A prospective cohort study on the relationship between onion and leek consumption, garlic supplement use and the risk of colorectal carcinoma in The Netherlands. Carcinogenesis. 1996;17(3):477-484.  (PubMed)

117.   Ma JL, Zhang L, Brown LM, et al. Fifteen-year