______ Editorial See corresponding article on page 398. The stinking rose: organosulfur compounds and ‘2 David Heher In this issue of the AJC’N, Pinto et al ( 1) showed potentially leased, the allicin reacts rapidly with the amino acid cysteine important effects of aged garlic extract derivatives. S-allylcys- derived from protein in food consumed with the garlic. Much Downloaded from https://academic.oup.com/ajcn/article/66/2/425/4655750 by guest on 24 September 2021 teine and S-allylmencaptocysteine, on LNCaP prostate cancer work remains to be done on the metabolism of naturally de- cell glutathione and polyamine concentrations in vitro. This nived organosulfur compounds such as those found in garlic work adds additional support to the body of work in animals before we can be certain that the observations made in animals and cells showing potent effects of garlic in the inhibition of and in cell culture extend to humans. tumonigenesis. Some studies showed inhibition of carcinogen- Many different phytochemicals have potent activity on adduct formation as an important mechanism of action using carcinogenesis, risk factors for cardiovascular disease, and both garlic and selenium-enriched garlic (2-5). Another study aging in animals and humans. Why have plants evolved showed that the rise in polyamines seen after colonic irradia- substances that have potent effects in animal systems’? There tion could be inhibited by pretreatment with diallyl sulfide, an are at least two hypotheses. One hypothesis is that phyto- organosulfur compound found in garlic. However. the ultimate chemicals such as digoxin from the foxglove plant f’it the interest in garlic is as a dietary constituent or supplement. human candiotonic receptor through some accident of evo- S-Allylmercaptocysteine is only found in garlic bulbs that have lution in plants and humans. An alternative hypothesis is one been aged for at least a year. and it is not clear whether the in (if coevolution. Insects, birds, and other predators clearly vitro observations would translate into benefits for humans influenced the evolution of plants. and plants may have eating garlic. In fact, the epidemiologic studies examining influenced the evolution of mammals and humans. Plants garlic intake and cancer do not show a strong effect of garlic have been on this planet for one billion years compared with ingestion (6, 7). the relatively brief two million years that the human species Organosulfur compounds occur in a large number of differ- have been on this planet. On the basis of this chronology. it ent plants. including garlic, Chinese chive, Welsh onion, turfed may be that early humans were simply opportunists taking stone leek, and shallots. Garlic was consumed both as a food advantage of the rich bounty of phytochemicals in their and a medicine in the ancient Middle East and in the earliest environment. Early humans ingesting large amounts of cer- tam phytochemicals, such as ascorbic acid. lost the ability to Chinese dynasties. It has been extensively investigated both synthesize these substances as endogenous antioxidants. scientifically and clinically. Well over a thousand papers on These phytochemicals would then take on the role of essen- garlic and related alliums have been published in the past 20 y. tial nutrients on vitamins. This argument applies to some There is a clear rationale for garlic developing its distinctive extent to other phytochemicals such as the sulfur-containing smell as a defense against predators. The intact cells of garlic compounds found in garlic and other allium species. inhib- contain an odorless, sulfur-containing amino acid derivative. itors of cholesterol biosynthesis found in yeast and citrus alliin (S-allyl-L-cysteine sulfoxide). When the cells are crushed, fruits, and the isoflavones found in soybean protein isolate. it comes into contact with the enzyme alliinase located in The ancient environment of humans was rich in plant-derived neighboring cells. This enzyme converts alliin to allicin (diallyl phytochemicals. With the advent of agriculture 10 (XX) y ago, thiosulfinate). Allicin can be converted easily to many other humans began to influence the ecology of their food supply. This sulfurated compounds, including those found in aged garlic led to increased supplies of energy and nutrients, but in recent extract. The conversion to allicin occurs when garlic is chewed, times has led to a decrease in the biodiversity of food intake. It has resulting in odor production. which reduces the acceptability to been estimated that humans currently eat only l5()-2(X) of the some individuals of eating large amounts of garlic. Other side 50 (XX)-l(X)(XX) edible plant species on earth. Furthermore. only effects are gastrointestinal flatulence and frequent bowel move- 20% of Americans eat the five servings per day of fruits and ments. A 2.5% garlic powder diet found effective in some vegetables recommended by the National Cancer Institute. animal studies is equivalent to a 4.76-g/m2 dose in humans. This would be equivalent to a 70-kg man eating numerous average-sized cloves of garlic (4 g each). Because conversion From the Center for Human Nutrition. University of Califirmiia, Los of alliin to allicin does not proceed in the acid environment of Angeles. the stomach. entenic-coated capsules containing dried pow- 2 Reprints not available. Address correspondence to D Heber. Los An- dered garlic have been developed to deliver alliin and alliinase geles Rehabilitation Center, Division of Clinical Nutrition. Al-57. 1(88) to the alkaline environment of the small intestine. Once re- Veteramis Avenue. University of California. Los Angeles. CA 9(8)24. Am J Cliii Nuir 1997:66:425-fl. Printed in USA. U 1997 American Society for Clinical Nutrition 425 426 EDITORIAL Clearly, additional human studies of metabolism and efficacy are 2. Amagase H. Milner JA. Impact of dietary lipids on the ability of garlic needed using appropriate intermediate markers of the fate and to inhibit 7,12 dimethylbeiizanthracene (DMBA) binding to mammary effectiveness of garlic and its constituents. The other implication DNA. FASEB J 1993:7:A69 (abstr). of this new realization is that nutritional interventions for cancer 3. Amagase H, Milner JA. Impact of various sources of garlic and their prevention may need to include multiple phytochemicals and constituents on 7,12 dimethylbenzanthracene (DMBA) binding to mam- micronutrients. Although ongoing studies of the effects of fat, mary cell DNA. Carcinogenesis 1993:14:1627-31. 4. Baer AR. Wargovich MI. Role of ornithine decarboxylase in diallyl- energy, and individual micronutnients in cancer prevention trials sulfide inhibition of colonic radiation imijury in the mouse. Cancer Res are important, models of nutritional intervention that can incorpo- I 989:49:5073-6. rate some of the anticipated nutrient-nutrient interactions likely to 5. Ip C. Lisk Di. Mammary cancer prevention by regular garlic and occur are sorely needed. A selenium-enriched garlic. Nutr Cancer I 7:279-86. 6. Dorant E. VandenBrandt PA, Goldbohm RA. Allium vegetable con- REFERENCES sumption. garlic supplememit intake and female breast carcinoma mci- dence. Breast Cancer Res Treat 1995:33:163-70. Downloaded from https://academic.oup.com/ajcn/article/66/2/425/4655750 by guest on 24 September 2021 I . Pinto IT, Qiao C. Xing J. et al. Effects of garlic thioallyl derivatives 7. Dorant E, VandenBrandt PA, Goldbohm RA. A prospective cohort On growth, glutathioiie concentration, and polyamine formation of study on allium vegetable consumption. garlic supplementation and the human prostate carcinoma cells in culture. Am I Clin Nutr risk of lung carcinoma in the Netherlands. Cancer Res 1994:54: 1997:66:398-405. 6 148-53..