RESEARCH  INTERESTS

PROMOTION OF HEALTHSPAN

Protection Against Chronic Diseases

We have recently suggested that the practice of dietary approaches to the prevention of chronic diseases like cancer beget more frugal medicine and can serve rich and poor alike. Dietary delivery of protective phytochemicals makes good sense and chemoprevention by whole foods, or simple extracts of whole foods, presents unprecedented opportunities to solve unmet global problems. They are intuitively the most logical, sustainable, ethical, and responsible way to deal with the epidemic of chronic and degenerative disease. They may also be among the most cost-efficient, certainly compared to treatment of frank disease. This is a frugal and realistic strategy that is economically sustainable in the U.S. and in the underserved and economically deprived populations that are increasingly stricken by chronic conditions such as diabetes and cardiovascular disease.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A very straightforward starting point for this paradigm shift is for physicians to prescribe preventive diets for their at-risk patients. The food system in the U.S. can readily facilitate the delivery of such diets, but our medical and graduate schools must do a far better job of teaching new physicians and biomedical scientists about human nutrition and the role of diet in disease prevention, and those newly trained professionals must in turn be proactive with their patients and counselees. They must make prevention as much the order of the day as cure. Food—chemopreventive diets—should be, and can be, the daily “multivitamin” of our immediate future.

The challenge for the next decade(s) and for new health professionals is how to convey the learnings directly to their patients and to the general public. Social scientists, the entire spectrum of stakeholders in the food industry (e.g., from farmers to retailers), medical, nursing, and public health schools, government (e.g., regulatory and research branches), and primary and secondary school educators will all need to become invested and involved. The new drivers of this revolution will be not the drug companies but the food and agricultural interests because they will stand to profit greatly from introduction of new foods, new plant cultivars, and the reintroduction of “old foods” into new markets. They should thus be expected to provide a larger share of the funding for chemoprevention research as well as for effective public outreach. The road to longer healthspan will of course be rocky, but we cannot afford to ignore a strategy of diet-based prevention without putting our health care system in even more severe jeopardy than it already is.

Excerpted from: Fahey JW and TW Kensler (2013) American Medical Association Virtual Mentor 15(4): 311-318.

I frequently discuss these concepts in my podcasts.

PHYTOCHEMISTRY

Evolving from the primordial soup about a half billion years ago, land plants first started the evolutionary process to develop biochemical detoxication mechanisms for their own protection. One of the beauties or symmetries of nature is that we inherited most of our biochemical detoxification mechanisms from the very plants upon which we depended for a food supply, and those phytochemicals are as effective as anything modern pharmacology has developed in assisting us in our own protection. Human beings have not just recently developed the need to detoxify air and water pollutants like pesticides, plasticizers, and volatile organic hydrocarbons. From the moment we (and our predecessor mammals) started eating, our survival depended upon our ability to detoxify toxins from fungal and bacterial food contaminants and from the plants and animals we ate. When Homo sapiens emerged from Neanderthal man and first tamed fire about 40,000 years ago, we started living in highly polluted microenvironments and charring our steaks to produce carcinogenic heterocyclic amines. As stated so eloquently by the populist writer Michael Pollan in The Botany of Desire, “While we animals were busy nailing down things like locomotion and consciousness, plants acquired an array of extraordinary and occasionally diabolical powers by discovering how to synthesize remarkably complicated molecules.” I am enamored with this process and the implications of it. To put it more in the vernacular of the here and now: EVOLUTION ROCKS!… and RULES!

BROCCOLI SPROUTS

In the mid-1990s, we discovered that broccoli sprouts are an exceptionally rich source of inducers of the enzymes that detoxify carcinogens, and we developed techniques to detect these inducers and assess their metabolism in humans.

 

More recently, we determined that one of these inducers (sulforaphane) has potent antibiotic activity against Helicobacter pylori, a causative agent of peptic ulcer disease and stomach cancer, and that sulforaphane inactivates urease (a major pathogenesis factor of this bacterium) by an apparently independent mechanism. Our work in the laboratory and with human subjects in the USA, and in China and Japan extends these observations on the cytoprotective pathways that are up-regulated by sulforaphane. We have participated in about dozens of collaborative clinical research studies in which standardized, well-characterized extracts of broccoli sprouts have been delivered to volunteers (research subjects) in order to provide critical insight into how they are metabolized, and how their phytochemical components may “boost” or up-regulate the cellular pathways which protect our bodies against cancers and other chronic diseases.

 

 

I co-founded a company to develop chemoprotective food products and to promote and produce broccoli sprouts (that we developed) as well as other related healthy, certified, fully analyzed, and scientifically-supported foods. As a founder who remains heavily engaged in his research at JHU, and become more and more involved over the years in clinical research to investigate and strengthen our scientific assertions of the disease preventive value of broccoli sprouts, I removed myself from any and all financial, managerial, and advisory roles at the company for reasons of conflict of interest. Since retiring from JHU I have resumed a role as a scientific advisor to the company.

MORINGA

Another of my professional passions is Moringa oleifera, which is a rapidly-growing tree (also known as the horseradish or drumstick tree), that is native to the sub-Himalayan tracts of India, Pakistan, Bangladesh and Afghanistan. This tree was utilized by the ancient Romans, Greeks and Egyptians; it is now widely cultivated and has become naturalized in many locations in the tropics. It is a perennial softwood tree with timber of low quality, but which for centuries has been advocated for traditional medicinal and industrial uses. It is already an important crop in India, Ethiopia, the Philippines and the Sudan, and is being grown in West, East and South Africa, tropical Asia, Latin America, the Caribbean, Florida and the Pacific islands.

All parts of the Moringa tree are edible and have long been consumed by humans, and it has been used for biomass production, animal forage, biogas, blue dye (wood), fencing (living trees), fertilizer, green manure (from leaves), gum (from tree trunks), honey- and sugar cane juice-clarifier (powdered seeds), honey (flower nectar), medicine (all plant parts), ornamental plantings, biopesticide, pulp (wood), rope (bark), tannin for tanning hides (bark and gum), water purification (powdered seeds). Moringa seed oil (accounting for 30-40% of the weight of the seeds), also known as Ben oil, is a sweet non-sticking, non-drying oil, that resists rancidity. It has been used in salads, for fine machine lubrication, and in the manufacture of perfume and hair care products. In the West, one of the best known uses for Moringa is the use of powdered seeds to flocculate contaminants and purify drinking water, but the seeds are also eaten green, roasted, powdered and steeped for tea or used in curries. This tree has in recent times been advocated as an outstanding indigenous source of highly digestible protein, Ca, Fe, Vitamin C, and carotenoids suitable for utilization in many of the so-called “developing” regions of the world where undernourishment is a major concern.

The nutritional properties of Moringa are now so well known that there is little doubt about the substantial health benefit to be realized by consumption of Moringa leaf powder in situations where starvation is imminent. In many cultures throughout the tropics, differentiation between food and medicinal uses of plants (e.g. bark, fruit, leaves, nuts, seeds, tubers, roots, flowers), is very difficult since plant uses span both categories and this is deeply ingrained in the traditions and the fabric of the community. Nonetheless, well-controlled and well-documented clinical studies are still by-and-large absent from the scientific literature and are greatly needed.

Link to:

UNDEREXPLOITED FOOD SOURCES

The diversity, and hence resilience, of the world’s food supply has been diminishing steadily over the past century.  This has in part been fueled by the steady expansion of the world’s premiere grain crops (wheat, originally from the Middle East; maize or corn, originally from Central America; and rice, originally from Asia). This expansion has invaded geographies to which better-adapted and more serviceable (e.g. nutritious) native grains were adapted, and which supported local food-plant populations since the emergence of anatomically modern humans. The inexorable expansion of the world’s premier crops has fostered increasing monoculture of both inedible fiber sources and edible crops, especially the cereals or grains.  This expansion, part of the much-vaunted Green Revolution, has been blamed for the destruction of traditional local knowledge, techniques and habits, and for disrupting the biological matrix between the natural environment and those traditional agricultural techniques (in other words, sustainability has gone out the window). There was an incredible abundance of locally adapted edible and nutritious plants all over the globe, but in many regions these plants, and the culture associated with their use (for both food and medicine) is being lost rapidly and cannot be re-created. Re-discovering, rescuing, cultivating, nourishing, and cherishing the genetic goldmine that has also been called “Lost Crops” should be a much higher priority for the nations of the world than it now is. Throughout my career, and when time and funding has allowed me to do so, I have attempted to be part of that reclamation effort.

HELICOBACTER PYLORI PROPHYLAXIS

Infections of the human gut with the bacterium Helicobacter pylori, and the fact that it can result in stomach cancer, have only been recognized since the organism’s discovery four decades ago.  Since then, clinical trials and basic research on the organism and its close relatives have so thoroughly validated its public health importance that it resulted in a Nobel Prize for the original researchers.  Helicobacter pylori is now recognized by the World Health Organization as a Class I human carcinogen.  Alongside a dramatically increased awareness of this infectious agent, there is a proliferation of strategies for cures, some real and many imagined, to eradicate H. pylori infection.

Stomach cancer, as well as gastritis, gastric ulcers, and duodenal ulcers (much of which are caused by H. pylori infection), are diseases of both the industrialized and the developing world. Although infection with H. pylori is rapidly declining in Western nations, the prevalence of infection is greater than 90% in much of the developing world and greater than 60% in Japan and S. Korea. Globally, gastric cancer is the second leading cause of cancer mortality, and it is still the leading cause of cancer death in many countries. About half a million new cases of gastric cancer yearly (about 55% of the total number of cases), are directly attributable to infection with H. pylori. Societal costs, not only of these cancers, but of gastric and duodenal ulcer, are enormous.

The development or identification of ways in which to lower the prevalence of H. pylori infection and the consequent risk of cancer is of compelling importance. There are currently no vaccines against this infection and none are expected in the near future. Because of the development of such antibiotics as metronidazole, omeprazole, clarithromycin, and the proton pump inhibitors, effective antibiotic therapies now exist for those who can afford them (e.g. residents of industrialized countries). However, antibiotic therapy of infected individuals in most of the developing world is impractical due to complex economic, social and logistic considerations. There are other problems with antibiotic treatment in that the development of antibiotic resistance is of considerable concern, and eradication rates in many studies is as low as 70%. This bodes ill for a strategy of treating entire populations with antibiotics.

Complete eradication of H. pylori in symptom-free people might not be prudent due to the intriguing, but not yet proven possibilities of adverse side-effects. Additionally, although over half of the world’s population is infected by H. pylori, the vast majority of infected individuals never develop gastric cancer. The concept that a diet-based treatment could reduce levels of H. pylori colonization or virulence, mitigate gastritis, inhibit progression of corpus atrophy, and perhaps eventually delay or prevent development of gastric cancer — without completely eradicating the organism in treated individuals, is attractive from a number of perspectives including those of cost, treatment tolerability, and cultural acceptability. A number of potential dietary treatments (e.g. Lactobacillus spp., broccoli sprouts, honey, cranberries and garlic) have been suggested in the scientific literature. Scores of other indigenous plants have been used for many centuries by native and traditional healers as cures for syndromes that are likely to involve H. pylori infection.

A question that underlies much of the dietary strategy to reduce the incidence of gastritis, ulcers, or stomach cancer, can be very simply stated as follows: Is it necessary to completely prevent or eradicate infection with H. pylori, or will reducing the level and/or virulence of colonization (of the gastric mucosae), result in a reduced risk of disease or reduced disease severity? Martin Blaser (of New York University) has provided a cogent analysis of this issue and he concludes: “Although further research may show that human beings are better off without their long-time companions H pylori, I maintain that we are at present too ignorant of the diversity of H. pylori strains and their interactions with human beings to advocate their total elimination.”

 

1. Blaser MJ. (1997) Not all Helicobacter pylori strains are created equal: Should all be eliminated? Lancet 349:1020-22. [Abstract]
2. Blaser MJ, Berg DE. (2001) Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest 107:767-73. [Abstract]
3. Blaser MJ. (2005) An endangered species in the stomach. Sci Amer February:38-45. [Abstract]

 

If we accept this statement, then we must identify suitable endpoints for interventions designed to reduce damage to the human stomach resulting from infection with H. pylori, without necessarily eradicating the bacterium. Several primary non-invasive endpoints for detecting eradication of infection have been used in recent years, however, the adaptability of such tests to the accurate measurement of a reduction of bacterial levels or bacterial virulence-related genotypes is problematic.

 

If by following a dietary regimen one can achieve a reduction in indicators of inflammation and of colonization, but not complete resolution of that infection (since complete resolution may be undesirable), then is this dietary strategy not worthy of further development, either by itself or in a combinative approach? I submit that a number of foods may each have a small but measurable effect on the severity of infection and/or the risk of gastritis, ulcers, or stomach cancer, and that it is therefore worthwhile to utilize the available biomarkers of H. pylori colonization in order to evaluate the efficacy of this incremental effect in vivo. This question of course must be considered in the context of rapid development of H. pylori strains resistant to synthetic antibiotics, oppressive poverty in many of the areas with very high prevalence of H. pylori infection, and the huge cost of any long-term pharmaceutical preventive strategy.

 

Compared with the use of synthetic pharmaceuticals, a dietary approach to prevention can be very inexpensive, and may be the only practical or affordable approach to take in areas underserved by healthcare. If indigenous plants and/or foods can be identified which are effective in preventing or reducing H. pylori infection, these could be introduced in such areas. For example, potent anti-inflammatory activity and rapid uptake by cells and organs has been demonstrated for certain phytochemicals (e.g. sulforaphane from broccoli sprouts). There is also considerable precedent for treating and ameliorating gastritis and digestive disorders with foods (e.g. garlic, honey, Lactobacillus spp.).

FOOD TECHNOLOGY

My comments on David H. Freedman’s “How Junk Food Can End Obesity” were printed in abbreviated form in The Atlantic in their October 2013 issue:

Working at the crossroads of public health, medicine, and nutrition, with a focus on dietary approaches to combat chronic disease, I took great interest in David Freedman’s recent article “How Junk Food Can End Obesity.” I think that his central thesis is quite reasonable. From a macro- and microeconomic perspective it (prodding “…Big Food to intensify and speed up its efforts to cut fat and problem carbs in its offerings….”) also appears to be a solution that makes good sense. That said, I think it is essential, and possible, for the approach espoused by Freedman to work in tandem with the approach of the Pollanites and Bittmanites. Although the latter vilify Big Food, I suspect that they would admit that there is not a one-size-fits-all approach to the public health problem we now face.

I was impressed with the fact that Freedman had the courage to articulate the politically unpopular reality that there is and will most likely always be a stratified society, and that eating habits are included in that stratification. Implicit in his thesis is the fact that corner stores in poor urban areas will still only have a few apples and bananas behind the Plexiglas shield at the cashier’s counter, but that the urban poor’s needs will be addressed by Corporate America and they will get a healthier tranche of food (or foodlike substances) when they step up to the fast food counter. In such a manner, Corporate America will continue to be part of the problem, but they will also be able to claim the high moral ground and convince their shareholders that they are part of the solution.

Indeed, any dietary adjustments “Big Food” is making are being done in a systematic way because their instincts are strong, their survival skills are powerful, and they (as Freedman noted) see the metaphorical dollar signs written on the wall. Although their motives revolve around survival and profit, there could actually be a health benefit for the great majority of the populace that does not shop at high-end grocery stores.

On balance, is it then better to have Corporate America incrementally improve the health of a large fraction of the population whilst the Pollan/Bittman approach simultaneously impacts an additional, but far smaller fraction of the population? Yes. The current obesity epidemic is too massive a threat to our nation to fight over which solution is better. The Pollan/Bittman approach to obesity is probably a heck of a lot of healthier, but for those who won’t or can’t adopt it, even a reduced fat fast food burger may be a step in the right direction.

I developed and taught a course entitled “Food, Technology, and Health” at the Johns Hopkins Bloomberg School of Public Health.

 

Recently, I’ve expressed a few strong opinions on the use of the term “superfood”:

A viewpoint on “superfoods” in the Johns Hopkins Health Review

A short feature on our Moringa work in the Johns Hopkins Magazine, that includes discussion of that word

A scientific publication on variations in protein and mineral content between species and cultivars of Moringa

GUT MICROBIOTA 

While I am not an expert on this subject, I find the fact that our gut microbiome (the collective DNA of all of the bacteria and other microbes in our gastrointestinal tract) or our gut microbiota (the microbes themselves) quantitatively overshadow our own DNA by orders of magnitude, immensely powerful in terms of their contribution to our overall health. We live more or less harmoniously with an entire microbial ecosystem within us that complements and augments the things that our body, our mammalian cells, can do. Many collaborative groups of scientists are currently studying this ecosystem from all angles. We have published very little on this subject, but it so clearly impacts the bioavailability of most if not all of the phytochemicals that we study. I also view our friend Helicobacter pylori as an organism which may ultimately be shown to be worthy of our attention as a partner to our gut ecosystem– something with which we can coexist peacefully, as most of the world’s population has done for almost all of human history. Dietary approaches to reducing the severity of chronic Helicobater pylori infection may suffice to reduce the risk of cancer, ulcers, and gastritis, associated with the inflammation that accompanies severe infection.

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