When I think of garlic, I think of my late great-uncle Frank, the master gardener. Once, when he was in his late 80s, he showed me how he continued to plant garlic, even though his knees would no longer bend. We were standing indoors, so he moved in pantomime. Grasping an imaginary walking stick, he poked and twisted its pointed end into the "dirt" beside his foot until he had a satisfactory hole. Then he reached into his pocket and drew out an invisible clove, grasping it gently between thumb and forefinger. Taking a second to aim, he released the clove from waist height, then nudged the soil across to cover it with the outside of his shoe.
It was Uncle Frank who inspired me to plant garlic of my own. I bought several bulbs of the stuff at the supermarket, according to his instructions. (Uncle Frank was not one for fancy varieties, or for paying a lot for what could be had for a little.) Kneeling in the cold November earth, I could glance up and see the ancient, humpbacked ridges on either side of the valley as I pushed each fat clove down with my thumb, mounded the dark soil around it, covered it with straw. I planted two long rows, then went inside for the winter.
After the last snow had melted, I drew back the straw. Underneath, the twin green shoots of Allium sativum, still tender, lay flat against the ground. I let them grow through early spring, until they stood, sturdy and strong, then knocked them over with a rake handle. In a week, when the shoots were beginning to brown, I knelt to pull the first bulb. I shook and rubbed it free of dirt and, unfolding my pocketknife, cut away the shoots. I twisted the bulb in my hands until it broke, fingered a single clove, tipped it, and peeled it clean.
Who could then deny—slicing into that crisp, shining, milk-white crescent, releasing its juice, feeling its pungence chase instantly to a space deep behind my eyes—that this was some concentrated essence of life itself?
The Egyptians believed in garlic. The Codex Ebers, a medical text dating to 1,500 B.C., mentions garlic as a remedy for skin diseases, poisoning, heart problems, and tumors. Intact cloves of the stuff were found preserved in Tutankhamenís tomb. In the Old Testament, the desert-wandering Israelites sadly remember "the fish which we did eat in Egypt so freely, and the pumpkins and melons, and the leeks, onions, and garlic." Hippocrates prescribed garlic for protecting the skin, and Greek athletes ate it before competing in the first Olympic Games. In ancient China and Japan, garlic was thought to provide energy, lift depression, and improve male potency; in India it was used to treat arthritis and leprosy.
I learned all these things—and more—during the first session at "Recent Advances on the Nutritional Benefits Accompanying the Use of Garlic as a Supplement," a Penn State conference held in Newport Beach, California, last November. Medieval Europeans used "the stinking rose" to ward off plague as well as vampires. Henry IV of France was baptized in water laced with the stuff. "Could all these people have been wrong?" asked conference director John Milner, head of Penn Stateís nutrition program. Milner, the ebullient former president of the American Society for Nutritional Sciences and one of the early investigators of garlicís inhibitory effects on cancer, was well-suited as master of ceremonies for the three-day event. Its object, he said, was to move beyond belief to a better understanding of garlicís properties. To separate the medicine from the mystique.
The timing was certainly right. In the United States and elsewhere over the last ten years, consumption of garlic has boomed. As a foodstuff, garlic is suddenly everywhere; itís the hyphen in hyphen-American cuisine. North Americans seem determined to atone for being the last to recognize its charms. "The catsup of intellectuals," Milner called it.
Even more rapid has been the rise of garlic as a dietary supplement. According to industry figures, Americans spent $200 million on garlic supplements in 1997, an increase of 33 percent from 1995. That figure is projected to climb steeply as part of a larger trend toward herbal remedies and "biomedicinals," including gingko, green tea, echinacea, St. Johnís Wort, and a host of other plant-derived products, many adopted from traditional Oriental medicine.
One of the major sponsors of the conference was the Wakunaga Corporation of America, located in nearby Mission Viejo. Wakunaga of America is the U.S. arm of a Japanese pharmaceutical company that has been marketing an aged, odorless garlic extract known as Kyolic since the 1950s. Among the conference attendees were scattered upwards of 45 Wakunaga employees, including one reallive garlic evangelist—a remarkably fit and impeccably dressed older gentleman named Charlie Fox who offered a short version of the pep talks he said he frequently gives in health-food stores, and promised to mail me a sure-fire garlic remedy for sinus headaches.
It is big business all right, but garlic is indisputably serious science too. Another major sponsor of the gathering was the National Cancer Institute, which has recently funded a Garlic Information Center to provide accurate, up-to-date information on garlic to researchers, physicians, and the general public. (Thereís a garlic literature bank, a speakersí bureau, even a garlic hotline.) NCI also provided funding for some of the research that would be presented here at Newport Beach, as indeed did Wakunaga. On hand were oncologists, urologists, hematologists, pathologists, naturopaths, epidemiologists, pharmacologists—some 160 attendees, in all, from 12 countries. "We are here," Milner told the assembly during his introductory remarks, "to deal with the science. We are here to deal with the facts. We need to be critical."
The health benefits associated with the stinking rose in modern times make an impressive list: lowered blood cholesterol and blood pressure (and therefore decreased risk of hardening of the arteries and stroke), prevention and/or suppression of various cancers, enhanced immune function, and suppression of infectious disease, among others. The most intense research buzz, not surprisingly, has been for garlicís cardiovascular and anti-cancer effects.
What exactly are the "facts" on which these claims are based? They come from several sources. First are the epidemiologic studies that link garlic intake with lowered disease rates across populations. The strongest data in this regard come from a survey of two regions in northern China where dietary consumption of garlic in truly massive quantities—five to ten cloves per day!—has been connected with a markedly low incidence of stomach cancer. Similar studies involving lesser amounts of garlic have been undertaken in Sweden, Italy, and the Netherlands, with consistent,if less pronounced, results: lower rates of various gastrointestinal cancers.
Next are the studies of "model systems," using cell cultures and laboratory animals. Numerous studies of both types have shown garlic to inhibit the growth of cancerous tumors and malignant cells, to reduce cholesterol and artery-clogging sticky platelets in the blood of chickens, rabbits, and rats, and to boost at least the petridish effectiveness of various infection-fighting cells.
Lastly, there have been a handful of human clinical trials, most involving adding garlic supplements to the diets of men (less commonly, women) with slightly elevated levels of cholesterol and noticing reduction in those levels and in other cardiovascular risk factors like blood pressure.
Taken together, the available evidence is certainly tantalizing. "Itís pretty clear," Milner says, "that something is going on." The harder question, of course, is to determine just what that something is. As any good researcher will say, and several here did: Itís a big step from statistical comparisons and in vitro studies to definitive claims about human health. That step is even bigger when youíre dealing with a biomedicinal.
To begin with, a clove of garlic contains upwards of 200 known chemical compounds, roughly split between over 100 sulfur compounds—some of them water-soluble, others oily—and a balance of saponins,proteins, and carbohydrates. These compounds, moreover,are far from static: they under go "cascades" of chemical reactions when garlic is cooked, processed, consumed, and metabolized. These reactions, in turn, may or may not be altered by the host of possible interactions that must be accounted for—with compounds contained in other foods, in drugs or other medications . . . Suggesting a probable connection, under these conditions, is not hard. Producing definitive proof is a very different matter.
"There have been relatively few clinical trials undertaken," Milner acknowledged at the meetingís outset. "This is my biggest concern." Another worry among garlic researchers is inconsistent data. In the case of garlic and cardiovascular disease, for example, the first clinical trials, completed in the 1980s, uniformly showed that garlic lowers cholesterol levels and other cardiac risk factors by up to 20 percent. More recent, more tightly controlled studies, however, have reported distinctly checkered results. In particular, two widely publicized 1998 studies—conducted at the University of Bonn in Germany and the other at Yale—have found that subjects fed garlic supplements over a period of 12 weeks had no measurable decrease in blood cholesterol. ("When it comes to garlic, save your breath," ran one subsequent headline.) Earlier studies, it was suggested, had been poorly designed to account for other dietary factors.
The Bonn and Yale studies, predictably, were a topic of conversation on the first day at Newport Beach. Their results were quickly dismissed, however,and the reason given points up a shortcoming that garlic researchers are struggling to rectify: the absence of standardization. The Yale study, it turns out, employed a preparation of garlic powder; the reseachers at Bonn had used garlic oil. In many other studies, usingpowder, oil,raw garlic,and the aged, deodorized version, Milner asserted, the data "overwhelmingly" point to garlic having an effect. "We need to look at all the information thatís out there."
All garlic is not alike. Forget for a moment that there are over 150 varieties of Allium sativum, from purple-striped Russian Skuri to red-tipped Persian Star. Nutritionally speaking, a raw clove and a cooked one pulled from the same old bulb of Oswego White are worlds apart. Kun Song, a Ph.D. student in Milnerís lab at Penn State, presented a poster in Newport Beach depicting a study that he and Milner had recently completed. It showed that the application of heat negates the anti-cancer properties activated by enzymes released when fresh garlic is chopped or crushed. Let that same chopped garlic sit for 10 minutes before you cook it, however, and it retains its cancer-fighting ability.
Geography is another variable. Garlic harvested from the northern Japanese is land of Hokkaido may have different qualities from that grown in northern California or Russian Georgia. Even two bulbs drawn from different ends of the same field can have distinct chemical properties.
The differences between commercially available garlic preparations—garlic supplements—are even more pronounced. Each type of supplement, it seems, distills a different fraction of the garlicky whole. Aged garlic extract is produced by slicing fresh garlic and placing it in an alcohol bath for up to 20 months, which leaves the odorless water-soluble sulfur compounds. Garlic oil supplements, on the other hand, contain mostly the fat-soluble compounds that are associated with odor. And capsules of garlic powder may vary in content depending on how the garlic is dried, how it is milled, and how much it is extended with inert "carriers." "Thereís a whole variety of processing methods for each type," Milner said, "any of which might have significant impact." No wonder, then, that the results obtained in research can vary, even be contradictory.
All this variety makes it that much harder to figure out just what is going on. "I submit that it is not one component in garlic, but many, that are involved in the health benefits we associate with it," Milner told the group. "Which leads to a question. How do we standardize a product that contains multiple compounds of potential benefit?" The answer, he went on, is to identify one or more "biomarkers" of garlic effects: readily measured changes in the body that could be used to compare benefits across various preparations.
Agreeing on a suitable biomarker requires getting down to specifics: pinpointing the compounds in garlic that are bioactive,and their precise biological effects; noting the specific circumstances in which those effects might be enhanced, or blocked; even identifying specific populations that might or might not be affected. The first step in all this is a fuller understanding of what happens to garlic when it enters your body.
Two speakers addressed the subject of garlic metabolism in Newport Beach. Biochemist Chung Yang of Rutgers University described the basics, outlining a series of "phase-one" and "phase-two" reactions, with squadrons of different enzymes activated and metabolites produced by each phase. "It is a very complex, very variable metabolism," he concluded. "It will be very difficult to set biomarkers."Food chemist Robert Rosen, also of Rutgers, detailed the technique he has used to measure the volatile components that result in the much-dreaded garlic breath. He had garlic-chewing subjects blow into absorbent lined Tevlar bags, then desorbed the bags into a gas chromatograph and ran them through a mass spectrometer. Me thylallylsulfide, the compound he identified as the main culprit, is a product of glutathione, formed in the blood. It can be released into the breath for up to six hours.
The first researchers to attempt extricating garlicís "active ingredients" focused on allicin, another volatile sulfur compound and the one that gives garlic its powerful odor. Allicin, which is not present in the intact clove, exists only fleetingly after garlic is bruised or crushed. Then it breaks down into something else. Discovered in 1944, allicin was soon noticed to have anti-fungal and antimicrobial properties—and later, to kill normal cells along with infection.
Some supplement makers continue to tout allicin as the healthy ingredient in garlic. But according to Haru Amagase, Wakunagaís director of research and development, recent studies show that allicin is destroyed by the acidity of the stomach. Nor can its presence be detected in the bloodstream. In short, Amagase said, the only way for allicin to be absorbed into the body is if it is delivered directly to the intestines. Special "enterically coated" garlic pills can accomplish this—they donít dissolve until they get past the stomach—but laboratory studies show that allicinís harshness can irritate and inflame the intestinal walls.
There seem to be no shortage of other compounds better suited to be garlicís key ingredients. Among the sulfur compounds, Shoji Fukushima, a pathologist at the Osaka City University in Japan, has isolated two, Smethyl cysteine and cysteine, that inhibit carcinogenesis in the large intestines and livers of rats. (Interestingly, another of the sulfur compounds Fukushima tested, known as diallyl sulfide, or DAS, actually promoted carcinogenesis in the large intestine.) Richard Rivlin of Memorial Sloan Kettering Cancer Center has shown that the compounds Sallylcysteine (SAC) and Sallylmercaptocysteine (SAMC) slow the growth of prostate and breast cancer cells. Penn State professor of nutrition Yu-Yan Yeh has identified at least three sulfur compounds that inhibit cholesterol synthesis.
Saponins, the other major class of compounds in garlicís make-up, look like a reasonably good bet for bioactivity too. Hiromichi Matsuura of the University of Illinois College of Pharmacy has shown that some saponins bind with cholesterol, and suggests that these may be responsible for garlicís cholesterol-lowering effect. And thereís always selenium, a compound well-known (thanks to the work of Milner and others in the late 1980s) as a powerful anti-carcinogen. Selenium is present in garlic, although probably not in high concentrations. Still, Milner says, there is evidence to show that taking garlic and selenium together provides stronger anti-tumor protection than taking either one alone.
Others among the researchers who presented work at Newport Beach took an opposite approach, concerning themselves not with isolating compounds but with better pinpointing some of garlicís health effects. Benjamin Lau, professor of micro-biology, immunology, and surgeryat Loma Linda Medical School, reported that garlicís benefit with regard to cholesterol has to do with its preventing the oxidation of LDL, or "bad," cholesterol. ("We think of LDL as the bad guy," Lau noted, "but the real culprit is oxidized LDL.") Donald Lamm, a urological surgeon at West Virginia University, showed that garlic can boost the immune system following surgery for bladder cancer, effectively reducing the recurrence of tumors. Gowsala Sivam, a cancer researcher at Bastyr University in Bothell, Washington, has demonstrated that moderate amounts of raw garlic can kill Helicobacter pylori, a common bacterium whose presence in the stomach has been linked to both ulcers and stomach cancer. The finding is especially significant, she suggested, because of very high (and growing) rates of resistance by this bacterium to standard antibiotics.
Some of the most intriguing work presented in Newport Beach goes beyond the effects of garlic on risk factors to look at its effects on actual disease. After all, "The fact that garlic lowers cholesterol does not necessarily mean that it has been effective on atherosclerosis," argued vascularcell biologist Julie Campbell, of the University of Queensland in Australia. "The proof of the pudding is in the eating." Campbell, in fact, found virtually no effect on bloodcholesterol levels when she gave aged garlic extract to rabbits fed on a diet high in fat. Yet her slides of these rabbitsí aortas needed little explanation: those of the garlic poppers looked pink and healthy, while the non-garlicked were streaked with the whitish fatty deposits that are the first sign of arterial hardening.
Nobuyoshi Nishiyama, professor of pharmacology at the University of Tokyo, presented similarly vivid results in a very different area. Nishiyama used genetically engineered mice to test garlicís antiaging properties. So-called "senescenceprone" mice, he explained, are liable to learning and memory problems, brain atrophy, and early death—an accelerated process of aging, in other words. In the course of a ten-month study, Nishiyama reported, among a group of senescence-prone mice who sediet was not supplemented with aged garlic extract, almost 50 percent died. Of those given aged garlic extract, however, all survived—along with all the normal mice used as controls. Aged garlic extract also significantly improved performance on a pain-avoidance test and a water maze test designed to stir spatial memory, and it significantly lessened shrinkage of the brainís frontal lobe.
Nishiyamaís results were pretty impressive, but the question-and-answer period that followed again demonstrated the complex of interactions that have to be nailed down before research into the effects of biomedicinals can be considered conclusive. "Is the laboratory meal fed to your mice soy-based, or casein-based?" asked Mary Frances Picciano, professor of nutrition at Penn State. "Because soy could have a synergistic effect on anti-aging results." Nishiyama acknowledged that he didnít know.
It will likely be a while, most of these garlic researchers seemed to agree, before they can definitively isolate compounds and dosages, cause and effect, to the point where they can decide on a suitable biomarker (or two) for garlic. Even longer until garlic—or some of its constituents—might actually be prescribed as a drug. Indeed, that may never happen, and if it did, it would entail a level of regulatory control that many consumers, and producers, would not welcome. ("In this country talking about garlic as a drug causes heart palpitations," Milner said, with characteristic candor. "I donít want to see it changed from a supplement.")
"Maybe in 20 or 30 years, weíll come up with a magic bullet," one attendee ventured. In the meantime, Robert Rosen, the food chemist who analyzed the compounds in garlic breath, concluded, "We canít look at garlic as a pharmaceutical. We canít look for active ingredients. We must look at it as a beneficial ënutraceuticalí—a food whose total content has been effective."
Most of the beneficial effects being reported so far, it should probably be stressed, are associated with what are clearly megadoses of garlic. "Itís like stopping a freight train with a freight train," according to Michael Wargovich, director of the South Carolina Cancer Center. Even so, when Wargovich and a panel of fellow cancer researchers were asked point-blank whether they would recommend that the average consumer increase his or her garlic intake, all but one said yes. (The lone hold-out said, "It looks promising, but we need more research.")
In his summation at the close of the conference, Milner acknowledged that the science of garlic is still in its infancy. "Weíve raised important issues," he said. "I hope you all will walk away a little more of a believer."
Well, I guess I did that. I resolved at least to take home the sample box of garlic extract that had been supplied to me. And to keep garlic as a staple of my diet. In the end, however, I walked away feeling some-what disappointed, a little out of balance. After three days of strict reductionism, there was definitely something missing.
Garlic, for one thing. I had hoped, perhaps unreasonably, for some Szechuan garlic pork, or some nice tangy Middle Eastern hummus. On the airplane heading west, my mind had roamed to basil pesto and 20-clove garlic chicken. Instead, the conferenceís catered meals had been all but garlic-free. Business-meeting bland. Tasteful, but hardly taste-full.
Garlic was missing—and maybe that was understandable. But there was something more. Nobody but me seemed to miss it. The place was awash in respect for garlic; cold-eyed clinical respect; esteem for what garlic could do,for what it might be worth. This was a gathering that took garlic seriously, all right. Maybe too seriously. . . . At some point it began to seem a remarkable oversight that there was no one here to sing of garlic, to declaim the joy of garlic.
I felt something for those poor Israelites, stuck in that garlic-less desert.
A resolution of sorts came on that last afternoon. There was an impromptu press conference at the hotel, with Milner holding forth before a small knot of Japanese reporters and camera people. (The Japanese media were considerably more numerous at these proceedings than were their western counterparts.) After some polite back and forth, and some queries on the data, one of these reporters raised a general, philosophical question: In light of what was happening here, and where the science of garlic was going, he asked, did the professor think that there would someday be a standard world cuisine, a universal diet tailored to promote optimum human health?
Milner, his face drawn in thought, took a second to process the question.
"I certainly hope not," he boomed out at last. "My goodness! Wouldnít that be boring?"
I lowered my pen then, and cut loose with a small sigh of relief. Maybe there were some garlic lovers here after all.
John A. Milner, Ph.D., is professor and head of the department of nutrition in the College of Health and Human Development, 126 South Henderson Building, University Park, PA 16802; 814-865-0108, or email@example.com. Yu-Yan Yeh, Ph.D., is professor of nutrition, 129 South Henderson, 863-2920, or firstname.lastname@example.org. Kun Song is a Ph.D. student in nutrition. "Recent Advances on the Nutritional Benefits Accompanying the Use of Garlic as a Supplement," an international conference, was held November 14-17, 1998 at the Newport Beach Marriott Hotel in Newport Beach, California. The conference was sponsored by the National Cancer Institute and Penn State, and supported by Rexall-Sundown, Inc. and Wakunaga of America Co., Ltd.