Nutrition: at the crossroads
Brian Leibovitz, Ph.D. The future is what we make it, and is molded by today&Mac226;s thoughts and tomorrow's actions. As I see it, nutrition is at a crucial junction from which there are two possible directions: 1) one in which nutrients are extensively used to prevent and treat human diseases, and 2) one in which the therapeutic applications of nutritional supplements continue to be ignored. I started this article with the intention of discussing all the players, concepts, and events. There is simply too much to cover, however, and some of the topics will have to wait for future issues. NO VESTED INTERESTS Although often stated, it always bears repeating that I do not profit from product sales. Although I am the Scientific and Nutritional Consultant for Twin Laboratories, Inc., I am not, and have never been, financially rewarded from the sale of any nutrient or product. I receive no bonuses, no stock, no percentages, no perks of any kind. Equally important, I am not required (nor have I ever been asked) to write or speak about any nutrient or product which, in my opinion, lacks sufficient documentation. Consequently, I have no vested interests whatsoever, which allows me to maintain objectivity. Those who are familiar with the health food industry know how very rare this relationship really is. My only goal is to help speed the day when nutritional supplements are used to the fullest extent possible to reduce the morbidity and mortality of human diseases and to improve the quality of life. CRISIS IN THE HEALTH CARE SYSTEM There is little doubt that the health care system is in serious trouble, and both public and private sectors have been hurt by escalating medical costs that far exceed the rate of inflation. Expensive, high-tech equipment, unnecessary operations, and superfluous diagnostic tests all contribute to the problem. Yet as bad off as the health care system is financially, things are even worse in the area of therapeutic efficacy. LOST IN THE FOREST "If it isn't broken, don't fix it", states the age-old adage. Conversely, if the system is obviously broken, it's time for repairs. The medically- approved drugs used for treating a number of diseases are often so ill-conceived, and present such great health hazards, as to warrant a major overhaul of the system. This is particularly true for drugs used in treating chronic, age- associated disorders; the majority are either ineffective or toxic; many drugs are both. Sidney Harris eloquently expressed this in a cartoon in which a patient told his doctor that "he had stopped taking the drug, as he preferred the original disease to the side effects". One need only look at The New England Journal of Medicine (NEJM), The Journal of the American Medical Association (JAMA) or any other medical journal to discover this awful truth. And you don&Mac226;t need to look for very long. HEARTLESS MEDICINES Drugs used for treating cardiovascular diseases are, by-and-large, essentially worthless (albeit these drugs are an effective means of population control). A classic example was published in the Nov. 21, 1991 issue of NEJM. This article was about a double-blind, randomized, multicenter trial of milrinone (a drug which inhibits phosphodiesterase ) in 1,088 patients with severe chronic heart failure (1). Compared to placebo, milrinone therapy resulted in a 28 percent increase in mortality from all causes (P = 0.038) and a 34 percent increase in cardiovascular mortality (P = 0.016). Furthermore, milrinone significantly increased the number of serious adverse cardiovascular reactions and also hospitalizations as compared with the placebo group (1). Nice drug! An increase in mortality after treatment with cardiac drugs is the rule, not the exception. Consider the drug clofibrate, a lipid-lowering drug prescribed for millions of men world-wide. In a six-year, World Health Organization (WHO) study of 5,000 patients with known coronary heart disease, clofibrate-treatment resulted in a 44% higher mortality rate as compared to placebo (2). Side Effects. In addition to higher mortality rates, most cardiac drugs produce a plethora of harmful side-effects. Consider the drug Plendil (felodipine), a calcium channel blocker. In the latest issue of NEJM, an advertisement for Plendil lists over 15 adverse reactions at a dose of 5 mg (in percent of patients), including: peripheral edema (22%); headache (19%), flushing (6%), dizziness (6%), upper respiratory infection (6%), and palpitation (2%). Moreover, the toxicity of Plendil is dose-dependent: at a 20 mg dose, the incidence of peripheral edema is 36%, palpitation 12%, headache 28%, and flushing 20%. The advertisement also stated that Plendil's "safety in patients with heart failure has not been established". Imagine the FDA's reaction to a nutrient that produced such an array of untoward side-effects! The FDA would undoubtedly deem it toxic and ban its sale. Recall that guar gum (a soluble fiber) was banned from weight-loss products by the FDA because a few individuals didn't dilute it properly and choked (the FDA never said how many people, nor did they mention the outcome). It's no joke that the average drug advertisement has one sentence of indications followed by a full page (sometimes more) of contraindications, warnings, precautions, adverse reactions, and toxic effects. Leaving drugs for a moment, other treatment modalities of modern cardiovascular medicine are even more deranged. Artificial hearts, for example, are even further removed from the ultimate management of cardiovascular diseases. In a recent review of the artificial heart program, a blue-ribbon panel from the Institute of Medicine concluded "the projected costs would be greater, and the benefits lower, than for any medical procedure now in use, but that research should go on anyway" (3). THE CURIOUS CASE OF CANCER CHEMOTHERAPY One of the most puzzling, unfathomable aspects of modern medicine is in the area of cancer chemotherapy, specifically, the justification behind the drugs currently prescribed. Virtually all anticancer drugs are carcinogens in their own right, a feature I've never been able to figure out. These drugs, by-and-large, are the worst chemicals on the shelf; they work by damaging the DNA of fast-growing cells, thereby inhibiting growth potential. That&Mac226;s fine for tumor cells, but the indiscriminate toxicity of these anti-metabolites also obliterates cells in the gastrointestinal tract, bone marrow, mucous epithelium, hair, and the immune system (particularly those involved in anticancer and antimicrobial immunity). The non-specific nature of chemotherapy results in severe gastrointestinal damage, malnutrition, anemia, loss of hair, and immune dysfunction. Naturally, death from bacterial or other infections is common in cancer patients given chemotherapy; estimates of infection as the proximate cause of death in cancer patients range from 50% (in those with solid tumors) to 75% (in leukemia patients) (4). In a recently-published review of the book "Cancer Risk After Medical Treatment", the Dr. Penn (the reviewer) observed that: "It is one of the great paradoxes of medicine that the treatment of cancer may be complicated by the development of a second type of cancer induced by radiotherapy, chemotherapy, or both treatments. There is an increased risk of acute non- lymphocytic leukemia after treatment with a variety of alkylating agents and an increased risk of carcinoma of the bladder after treatment with cyclophosphamide" (5). In another article published recently in NEJM, continuous combination chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) was compared to no treatment in 250 women with metastatic breast cancer (6). The results: chemotherapy did not improve survival, but it did significantly decrease the quality of life (as evidenced by an increased frequency of vomiting, nausea, mucositis, and other "side- effects" of these noxious poisons). Another class of chemotherapy agents is based on adriamycin (aka doxorubicin). Adriamycin works by redox cycling, thereby generating copious quantities of free radicals which overwhelm defense systems of cancer cells as well as cells in the heart. Not surprisingly, adriamycin is very cardiotoxic, and approximately 10-15% of cancer patients given this drug die from cardiomyopathy (7). In fact, adriamycin is so effective (meaning cardiotoxic), it&Mac226;s become a favorite model system for many laboratories studying oxidative damage and antioxidants. The bottom line is that the twenty-year, $22 billion dollar war on cancer has failed to produce any real benefits. As discussed in a recent issue of Science , "Overall death rates from many common cancers remain stubbornly unchanged -- or even higher than when the war began" (8). Dr. Samuel Epstein and 60 physicians and scientists -- at a press conference in Washington D.C. -- charged that the cancer establishment repeatedly and grossly exaggerated its&Mac226; ability to treat and cure cancer : "The cancer establishment confuses the public with repeated claims that we are winning the war...Our ability to treat and cure most cancers has not materially improved"(9). THE BITTER TRUTH The question which must be honestly addressed, and which has not heretofore even been asked, is: If the medications presently used to treat the major diseases were truly efficacious, then why are cardiovascular diseases, cancer, and lung diseases still the leading causes of death? The cold, cruel fact is that -- despite the highly-proclaimed advancements in medicine -- many hundreds of thousands of Americans die each year because they are given the wrong medicines. Aside from emergency medicine, diagnostics, orthopedics, and certain other specialties, modern medicine has simply missed the forest for the trees. I would be remiss in not mentioning The National Cancer Institute (NCI)-- a remarkable exception. NCI is currently supporting some 40 studies on the anticancer effects of a variety of nutrient supplements (vitamin A, beta-carotene, vitamin C, vitamin E, selenium, folic acid, and others). Most other branches of medicine, however, have been slow to recognize the value of supplementation. This is particularly true of the heart disease establishment, which is trapped in the dogma about polyunsaturated fatty acids (PUFAs) of the omega-6 series being of benefit in treating coronary heart disease. That fantasy, plus the idea that cholesterol per se is the cause of coronary artery disease, has been promulgated for so long, and with such fanaticism, that a retraction at this stage would involve a serious loss of credibility. SCENARIO #1. NUTRITION AS THE FOUNDATION OF MEDICINE In this scenario, there will be an ever-increasing incorporation of nutritional supplements in the prevention and treatment of human diseases. Many, if not most, diseases will probably be successfully managed with dietary supplements of vitamins, minerals, and non-vitamin nutrients (eg., coenzyme Q10, L-carnitine, anthocyanins and other flavonoids, d-limonene and other terpenes, and carotenoids). In addition, macronutrient composition and quantity will be used for therapeutic benefit (eg., the inhibition of platelet aggregation by fish oil supplements or the improvement in blood lipid profiles by supplementary fiber). This prediction is based on several factors, the most important being the thousands of studies (published in respectable, peer-reviewed journals) which I've accumulated over the past 18 years. The volume of literature is incredibly large at present, and it's growing by leaps and bounds. I xerox 10-30 articles on supplements each week at the U.C. Davis Health Sciences Library. My collection of articles on nutrition and disease now fills 38 metal file cabinets (two 5-stack, six 4-stack, and two 2-stack file cabinets -- the 25"-deep kind). I believe that nutrients -- especially micronutrients - - will be recognized as the medicines of choice, and that, ultimately, nutrients will supplant most drugs used in clinical medicine. The handwriting is clearly on the wall. Most people think of nutritional supplements for the prevention of disease, which is fine as substantial data have accumulated in support of this concept. In real life, however, most people wait for the lumps, bumps, aches, and pains: it is a rare individual who actually has the foresight to use supplements prophylactically. Nutritional supplementation as a therapeutic modality is at least as important as it&Mac226;s preventive roles. This topic has begun to be studied in earnest, and results document the benefits of increasing dietary intakes of nutrients in the treatment as well as prevention of numerous human diseases. Non-Vitamin Nutrients: The Gray Area. This interface between vitamins and natural products includes coenzyme Q10, bioflavonoids, carotenoids, carnitine, and terpenes -- compounds which belong to a group I call "non-vitamin nutrients". These naturally-occurring compounds are not considered vitamins (except for some pro-vitamin A carotenoids); nonetheless, numerous beneficial effects are elicited by dietary supplementation with these remarkable molecules. The volume of the data is really quite astounding: articles about carnitine fill an entire file cabinet, as do the bioflavonoids; coenzyme Q10 and carotenoids fill yet another. Bioflavonoids are probably the hottest class of non-vitamin nutrients, and their medical applications span almost every pathology and organ. Silybin, a flavonolignin complex isolated from Milk Thistle, was chosen as the cover molecule for this inaugural issue. In Europe, silybin is marketed as a drug for the treatment of cirrhosis. Like most bioflavonoids, it has potent antioxidant and metal-chelating properties; in addition, silybin raises liver glutathione levels. SUPPLEMENTS: A "RADICAL" CONCEPT? The idea that optimal nutrition requires super-physiological amounts of the micronutrients is by no means a new concept. In 1938, Drs. Stepp, Kuhnau, and Schroeder published a book entitled Vitamins And Their Clinical Applications in which they stated the following (10) : "The conception that the investigation of the pure vitamin might possibly disclose new and so far unknown effects has proven especially productive with vitamin C. It appears that this vitamin given in pure form may influence disease conditions, which (so much may be said today) have nothing to do with states of avitaminoses or hypovitaminoses. Thus, the vitamins, beyond the service they render as accessory substances, possess the properties of curative stuffs [emphasis added]. " This is a good description of JON's focus, namely, that dietary supplements of macronutrients and micronutrients are beneficial in the prevention and/or treatment of disease as well as in the maintenance of optimal health. So JON's unique focus is really based on ideas conceived over half a century ago. This is both a tribute to the early nutrition investigators and a reason for humility about the novelty of our conceptions. The interest and excitement in this field is blossoming as never before, as reflected by the present number of nutrition journals (>35), books (>50/yr), and conferences (>40/yr is a conservative estimate). The recent New York Academy of Sciences Conference entitled "Beyond Deficiency: New Views On The Function And Health Benefits Of Vitamins" (chaired by Drs. Machlin and Sauberlich) is further confirmation of the growing interest in nutritional supplementation. TIME FOR A CHANGE Time Magazine recently published a lead article entitled "The New Scoop On Vitamins" (11); this cover story had a huge impact, and it is still being widely discussed. It was six pages in length, and -- considering it was written for the general public -- rather well done. The article covered free radicals/antioxidants and cancer, heart disease, aging, cataracts, birth defects, infectious diseases, and a host of other diseases. In addition, folic acid supplementation as a means of preventing neural tube defects in children was discussed, as was folate&Mac226;s capacity to reverse precancerous lesions of the cervix .The increased requirement for vitamins and other nutrients with advancing age was also pointed out, as was the increased requirements for nutrients in persons taking various medications. The author hit the nail on the head in the summary statement: "They [vitamins] may be much more important than doctors thought in warding off cancer, heart disease, and the ravages of aging -- and no, you may not be getting enough of these crucial nutrients in your diet." The fact that Time Magazine went out on a limb with this provocative cover story indicates their lawyers felt the documentation was sufficient to protect against lawsuit. The NY Times also joined in with it's article entitled "Vitamins Win Support As Potent Agents Of Health" (NY Times, March 10, 1992). These were soon followed by an article in USA Today entitled "Megadose Vitamin C Linked To Longer Life" (USA Today, May 8-10, 1992). The latter report (published in Epidemiology) was based on a study of 11,348 U.S. adults, and revealed that men with the highest vitamin C intakes had a 35% lower mortality rate and a 42% lower death rate from heart disease and stroke (women had a 10% lower mortality rate and a 25% lower death rate from heart disease and stroke. In fact, it seems everyone in the U.S. knows that nutritional supplements can be of benefit in disease prevention and/or treatment. Even the conservative dietitian at CNN (Carolyn O'Neil) brought up this concept when she reported that calcium intakes above the RDA could benefit those with high blood pressure. Yes, most Americans are aware of nutrients' potential health benefits -- a concept whose time has indeed arrived. Most, that is, except those at the FDA who are entrusted with regulating the supplement industry. SCENARIO #2: A DISMAL FUTURE In this doleful scenario, nutritional supplements would remain the unwanted stepchild of medicine. More importantly, medical policies would continue to be decided by financial or political considerations rather than scientific facts. In this future, many nutrients would be banned, others available only by prescription and in limited quantities. It goes without saying that costs would skyrocket, perhaps as much as 10 fold over today&Mac226;s prices. Moreover, there would continue to be the hundreds of thousands of needless deaths resulting from use of the wrong medicines (and to the lack of availability of nutrient supplements). There are many forces working to make scenario #2 a reality. The remainder of this article details some of these forces and how they work. THE FDA RUN AMOK The FDA has, for all intents and purposes, been running amok, and it&Mac226;s already claimed two victims: America's public health and the integrity of science. The ban on L-tryptophan, the upcoming Dietary Supplement Task Force report by Associate Commissioner Dykstra (in which all amino acids are to be banned from over-the-counter sale), the switch from RDA to the worthless "RDI", the institution of a bogus measurement of protein quality (the so-called "PDCAAS", see below) to sell a type of protein, and swat-team style arrests of physicians working in their clinics are just a few examples. IF IT WORKS, IT'S A DRUG There is a legal "catch 22" in the supplement industry resulting from current regulations. If a nutrient or food factor is well documented to be therapeutically effective, the FDA will probably label it a drug and ban its OTC sale. If it is effective, but the data are not unequivocal, the FDA can nail you for marketing an approved "drug" without following proper procedure (eg., a New Drug Application). Conversely, they could also cite you for marketing an unapproved food substance for the treatment of disease. It's a case of where you just can't win for trying. Even stranger is that ineffective OTC supplements never seem to get noticed or hassled, such as diosgenin, gamma-oryzanol, Smilax, and other plant sterols which are marketed as anabolic agents. These ideas gave rise to the following principle: The stronger the data supporting the efficacy of a nutritional supplement, the sooner it will be banned from over-the-counter sales. Corollary: The drug derivative, however, will soon be widely acclaimed for its therapeutic value. THE B-VITAMIN BUST: DID FDA WRONG WRIGHT? On May 6, a raiding party of six FDA agents attacked the clinic of Jonithan Wright, M.D. in Kent, Washington. With guns drawn and wearing flak jackets, they broke down the door and --swat team style -- stormed the clinic. And just in case (in case of what I still can't figure out), the FDA had a backup of 10 local police. They pointed their guns at both staff and patients in an obvious (and probably successful) attempt to harass and intimidate. This lasted for some time, after which FDA agents removed many office items (eg., supplements, records, files, and medical equipment). Apparently, FDA also raided a nearby pharmacy and medical laboratory at the same time. The increased number, and ferocity, of FDA raids might well be a prelude to further restrictions on the OTC availability of nutritional supplements. Indeed, the FDA recently hired approximately 100 agents, presumably for such purposes. If the incident in Kent, Washington is any indication, we won&Mac226;t have long to wait. What was the heinous crime that led to this raid? Did Dr. Wright commit rape, child abuse, or murder? Was he selling crack or cheating on his income tax? Nope. Dr. Wright's crime was simply the possession of vitamins, specifically, an injectible mixture of B complex. If this is difficult to fathom, or evokes feelings of anger and frustration, relax. You're in good company. Intelligent people throughout the U.S. were, and continue to be, baffled by these unexplainable, objectionable, and possibly unlawful actions of the FDA. What If... Imagine being arrested for possession of L-carnitine? Or six months hard labor for N-acetylcysteine, or L-arginine. Because its&Mac226; benefits are so well-documented, possession of coenzyme Q10 would probably get you two to four years in the Federal Penitentiary, assuming that was your first offense. Where would it stop? We'd have to purchase our nutrients from shady characters on dark street corners. Of course, a black market would develop, with drug czars and all. Crime usually follows lucrative, illicit enterprises, so the number of murders and muggings would be bound to rise. The "vitamin pushers" -- once arrested -- would further overcrowd our already-overflowing jails. On Wall Street, the market would certainly suffer from the loss of U.S. dollars to foreign "vitamin kingpins". More police would have to be hired to assist the overburdened "supplement police", and the army would likely get diverted from the war on drugs to the war on vitamins. Naturally, taxes would have to be raised to pay for all this. And so on. This all sounds pretty silly until you realize that the FDA is well on its' way to implementing such a plan. The "Great Vitamin War". The arrest of Dr. Wright did produce one unexpected benefit: it shocked us into doing something. Suddenly, people realized that action must be taken, and soon, to protect our rights to the unrestricted availability of nutrients and food factors, and to prevent FDA's strangulation of the supplement industry. The "Great Vitamin War", as it's been called, is on. In a way, after so many years of "cold war", the recent declaration is almost a relief. TRYPTOPHAN, EMS, AND THE FDA The FDA has already removed one nutrient from the OTC market. In late 1989, the FDA recalled virtually all L-tryptophan-containing products following the deaths of several dozen people from EMS. EMS is a rare disorder which is characterized by abnormally high blood eosinophil counts, influenza like symptoms, and by muscular pain. The first breakthrough in understanding EMS came in July of 1990, when EMS was firmly linked to L-tryptophan from a single manufacturer (Showa Denko--a large Japanese chemical and pharmaceutical company) (12). Later studies revealed that suspect batches of L-tryptophan from Showa Denko contained an impurity which might be the cause of EMS. This impurity was isolated by high-performance liquid chromatography as "peak E", and was suggested to be the dl-tryptophan aminal of acetaldehyde (DTAA) (13). More recently, however, chemical and spectral studies have demonstrated that "peak E" is a tryptophan derivative called 1,1'-ethylidenebis[tryptophan] (14). The presence of this toxic impurity has been linked to the use of a new, genetically-recombined strain of bacteria (Bacillus amyloliquefaciens, Strain V) in Showa Denko's lots produced between October 1988 and June 1989 (15). In addition, the toxic contaminant has been attributed to several changes in the purification procedures which were instituted during the time period in question. This former point raises serious concerns about the use of recombinant bacteria in fermentation technology. The FDA apparently did not learn the lesson of EMS, namely, that recombinant genetic techniques can produce novel toxins in our nutrient (or food) supply. If EMS was caused by consumption of gram quantities of genetically-recombined material (L-tryptophan supplements), what may happen when kg quantities of recombinant vegetables are eaten? Be that as it may, the bottom line is that L-tryptophan per se is not the cause of EMS; this disease is due to the presence of a contaminant which resulted from inappropriate production and inadequate purification procedures (16). Clearly, production and purity standards need to be defined and implemented so that this kind of industrial mistake never happens again. With proper quality control protocols, there is no reason not to lift the ban. To retain the ban on L-tryptophan supplements, however, is absurd in light of the fact that L-tryptophan is used every day in every U.S. hospital in total parenteral nutrition (TPN) solutions. TPN is given intravenously, and hence purity is even more critical than for oral supplements. If L- tryptophan is allowed for use in TPN solutions (where it is used as the free amino acid), then it would most certainly be safe given by the oral route. And a final comment: L-tryptophan occurs in many foods, particularly protein-rich foods like steak and milk; humans consume 1-2 grams per day in the average diet. Should the FDA consider banning steak, milk, cheese or other foods rich in L-tryptophan? This argument is a reductio ad absurdum, but it does serve to illustrate the inherent fallacy in the FDA&Mac226;s indictment of L-tryptophan. The crucial point is that an amino acid (or other nutrient) which is essential for life in a given, nutritional quantity cannot, by definition, be toxic when consumed in such amounts. DON'T CONFUSE THEM WITH FACTS What really boggles the mind is that the FDA, Victor Herbert, and a few others in the nutrition community actually deny the existence of any convincing data on the use of therapeutic applications of nutritional supplements. Such a stance flies in the face of overwhelming evidence to the contrary, and is as hard to comprehend as the denial of the holocaust. What I'd really like to know is: how do they avoid seeing any of the thousands of articles published in the scientific literature? It must be a very special talent: only the FDA, Victor Herbert, Stephen Barrett, Frederick Stare, Richard Wurtman, and a handful of others believe that nutrient supplements are worthless except for treating nutritional deficiency diseases. It is very doubtful that one could spend 10 minutes in any Health Sciences Library periodicals room and not find at least one article about nutritional supplements benefiting some disease or condition. In summer of 1991 while Editor-in-Chief of the Journal of Applied Nutrition, I wrote to Dr. Kessler, Gary Dykstra, and Dr. Vanderveen (Head of Nutrition at FDA) about joining my Editorial Board. By Autumn, I'd sent two letters and made dozens of follow-up calls to each of these FDA officials. In addition, I offered to send complimentary copies of all the nutrition articles I find in my weekly sojourns to the library. Not a bad offer, considering the large number of articles I always end up with. Only Mr. Dykstra had the courtesy to respond to the Editorial Board invitation (he declined, of course). And none responded to my offer of free copies of the latest nutritional literature. Evidently, these top FDA officials aren't interested in learning about what they are regulating. My experiences only confirm what is most Americans already know: The FDA is apparently not interested in an honest evaluation of the overwhelming amount of documentation regarding medical applications of nutritional supplements. THE RDI: FROM BAD TO WORTHLESS The FDA has proposed a new food labeling standard for vitamins and minerals called the "Reference Daily Intake" (RDI). The RDI is intended to replace the existing U.S. RDA, and is a part of the broader National Labeling and Education Act (NLEA). RDIs will go into effect without the approval of any other branch of government or scientific body on Nov. 8, 1992. If you think the RDAs are bad, wait till you see the RDIs !! First off, there is only one RDI value for any nutrient, regardless of age, sex, or pregnancy/lactation. Worse, the RDIs are significantly lower than the RDAs (by 10-40 percent) for 16 nutrients. Biotin is down 40%, calcium by 25%, magnesium by 25%, vitamin A by 12%, thiamin by 20%, vitamin B-6 by 25%, and so on. A comparison of RDA and RDI values for selected nutrients is provided in TABLE 1. Switching from RDAs (already low) to RDIs is analogous to reducing the definition of poverty to annual incomes of less than $1,000. The poor would cease to exist on paper, but in reality nothing would change. With the RDIs, dietary deficiencies may cease to exist simply because of how they are defined. More information on the RDI may be found in the article by Jeffrey Blumberg. CONFUSION AS A WEAPON: THE RDI, DRV, AND PDV One tactic of the FDA is to confuse and befuddle. If enough three- letter acronyms are introduced, the general public gets confused and quits trying to understand nutrient intakes. This is, in my opinion, one reason for the FDA&Mac226;s introduction of the RDI. And more recently, the FDA revealed another three-letter acronym: the Daily Reference Value (DRV) (17). This is the only place I&Mac226;ve seen the DRV mentioned, and in this article DRV was not even defined! The article only referred to DRV once, and stated that: "The proposed FDA collective term for RDI and DRV is "Percent of Daily Value"." Like the DRV, the "Percent of Daily Value" was not defined. It's almost laughable, like a Charlie Chaplin movie; we&Mac226;ve got, in addition to the RDA, the RDI, DRV, and PDV ("Percent of Daily Value", whatever that nonsensical term might be). In the midst of all these acronyms, I'd like to add one more: Generally Regarded As True (GRAT). The FDA needs to learn that, despite the RDA, RDI, DRV, PDV, GRAS or PDBCAA (see below), the therapeutic benefits of supplementary nutrients are GRAT. However humorous this may seem, their strategy works. Make no mistake about it: the public, confused and bewildered by all these acronyms, simply gives up trying to understand nutrition. SCIENCE BY PROCLAMATION: THE PDCAAS The FDA has really hit a new low with the PDCAAS -- the "Protein Digestibility Chemical Amino Acid Score". The PDCAAS was described in the same recent article as was the DRV and PDV (17). Basically, FDA plans to redefine how protein quality is measured. They argue that the PER (Protein Efficiency Ratio), being done in rats, is not a good measure; yet the Protein Digestibility (PD) part of PDCAAS is determined using a rat assay! It gets worse. FDA plans to set soy protein at a PDCAAS of 1.0 -- the top of the PDCAAS rating scale. More importantly, they state that: "If a food has a PDCAAS above 1.0, then it shall be set at 1.0" (17). In other words, all higher-quality proteins (eg., lactalbumin, egg albumin, fish, or casein) will, by the FDA's definition, be equal to soy protein. The only exception is in infant foods, where the PER will be retained and required for labeling purposes. The FDA must have realized that they'd have a lot of dead babies on their hands if they allowed the PDCAAS to replace the PER in infant formulas, since infants need higher- quality protein than soy can supply. Incidentally, the article was written by Dr. E.C. Henley, Director of Nutritional Science at Protein Technologies International, Checkerboard Square, St. Louis. And the FDA&Mac226;s decision to change the determination of protein quality was in response to a "citizen petition submitted by Protein Technologies International, Inc., (Docket No. 90P-0052)" (17). Could Ralston-Purina be looking to sell some soy protein? Soy is a good protein, to be sure, but it will never be as high-quality as lactalbumin -- no matter what it's PDCAAS rating. If the FDA is ever allowed to change science to sell product -- the ultimate prostitution of science -- we are all in deep trouble. NUTRACEUTICALS, NUTRITIONISTS, AND NATURE There are several key concepts that need to be mentioned, but because of space considerations, the discussions will be brief. NUTRIENTS AS DRUGS: THE "USE PATENT" GAME Why does it seem like nutrient supplements are dismissed as worthless by both the orthodox medical community as well as some nutritionists. And why has the acceptance of the clinical value of nutritional supplements been so agonizingly slow, despite the enormous volume of scientific documentation? If truth be told, it is money. The fact is nutrients are non-patentable; without such protection, the pharmaceutical industry has very little incentive to investigate nutrients. In contrast, therapeutic applications of nutritional supplements can -- and are -- patentable (so-called "use patents"). Several nutritional entrepreneurs hold a number of these, but the King of use patents has to be Dr. Richard Wurtman -- a professor at the Massachusetts Institute of Technology. A recent search of U.S. patents revealed that Dr. Wurtman owns over 20 use patents on various medical applications of supplementary amino acids. Some examples include: L-tyrosine for increasing blood pressure (US Patent # 4,745,130), choline for neurological diseases and aging (US Patent # 4,737,489) or for enhancing muscular performance (US Patent #4,626,527), and L-tryptophan for increasing brain serotonin levels (US Patent # 4,687,763) or for reducing depression (US Patent #4,377,595). This is the ultimate in hypocrisy. Wurtman states that all amino acids are toxic and should be taken off the OTC market; all the while he is secretly accumulating use patents so that when amino acids are removed (as appears imminent), he is ready to roll. The problem with use patents, from the patent-holder's point of view, is that they are only salable if the nutrient in question cannot be purchased OTC. This is the rub, and probably explains Wurtman&Mac226;s testimony before a House Subcommittee Hearing last year where he implored the Congress to ban OTC sales of amino acids. I particularly enjoyed his statement to the effect that "L-tryptophan has nothing to do with nutrition"; this comment is rather inane, considering the essentiality of this amino acid. Unfortunately, Wurtman is not alone in his greed, and there seems to be a trend towards profiteering at the expense of the nation&Mac226;s health. Dr. Stephen De Felice, for example, has long been trying to get carnitine removed from the OTC market, as his use patents can't be sold to drug companies (eg., Sigma Tau, which already markets a "drug" form of carnitine called Carnitor -- actually nothing more than L-carnitine at many fold the OTC price) until this is accomplished. I met De Felice in 1983 just prior to publication of my book on carnitine; I still remember him telling me what a great drug carnitine could be. De Felice's latest thing is "nutraceuticals" -- nutrients turned into pharmaceuticals. A recent paper describes De Felice&Mac226;s so-called "White Paper" -- his "Nutraceutical Initiative: A Proposal For Economic And Regulatory Reform": "A nutraceutical can be defined as any substance that may be considered a food or part of a food and provides medical or health benefits, including the prevention and treatment of disease. Nutraceuticals may range from isolated nutrients, dietary supplements, and diets to genetically engineered "designer" foods, herbal products, and processed products, such as cereals, soups, and beverages." (18). Apparently, De Felice won't be satisfied with just getting carnitine classed as a drug; he wants it all -- vitamins, minerals, non-vitamin nutrients, herbs, foods, etc. I believe that De Felice has similar goals, namely, the use of nutrients for preventing and treating diseases; the only difference is that he wants to make his fortune selling us the nutrients at many fold their OTC price. There are, of course, a number of easier ways to make a nutrient into a drug. You can oxidize it (retinoids), add a chlorine or two (4",6- dichloroflavan), methyoxylate it (glutathione monomethylester), dimerize it (sodium cromolyn) or acetylate it (acetyl-L-carnitine). You can even link it to another vitamin -- as in Juvela-Nicotinate (dl-alpha tocopheryl nicotinate) -- or non-vitamin nutrient, as in Hexopal (inositol nicotinate). COMPLICITY IN THE NUTRITION COMMUNITY This is perhaps the most difficult aspect to comprehend -- why those at the very top levels of nutrition tacitly, and sometimes not so tacitly, accept the dogma about supplements being worthless. Dr. Victor Herbert, a professor of medicine at Mount Sinai School of Medicine, is the best example of how nutritionists assist the FDA and others in suppressing the use of nutritional supplements. This is exemplified in an article by Victor Herbert appearing in the March/April issue of Nutrition Today (not peer-reviewed, despite Victor's criticism of such journals) (19). Victor Herbert has really outdone himself in this article which, in my opinion, is not even a reasonable facsimile of science. It certainly ranks among his worst, and that's saying quite a bit as Victor has penned some real dillies. Remember the fable about vitamin C destroying vitamin B12 in foods? That was one of Victor's contributions to nutrition. [NOTE: some textbooks, even today, still use B12 destruction as a "toxic effect" of vitamin C, even though it's been unequivocally disproved. The error, as it turned out, was that Victor used the wrong assay for vitamin B12]. Victor's "Medicolegal" Case Against OTC Amino's. There are so many errors that we&Mac226;ll only be able to mention a few of the more important ones. Victor stated that "The potential toxicity of large doses of single amino acids led the FDA to remove these from the GRAS list in 1974." But where is the evidence of individual amino acid toxicity when given as oral supplements? Aside from EMS (a disease which was due to a contaminant in L-tryptophan supplements), his one reference to a peer- reviewed journal was a 1958 study by Fahey in which intravenous amino acids raised blood ammonia. His only other "reference" to amino acid toxicity is a book by none other than Richard Wurtman. If amino acid toxicity was as well known as Victor implied, there must be some references in the literature. Why aren't more references cited by Herbert regarding amino acid toxicity? It's simple: there's virtually nothing to cite. Amino acids are not toxic despite proclamations by Victor Herbert, Richard Wurtman, or the FDA. Although a number of false "toxic effects" were mentioned (like the unreferenced accusation that "large doses of L-tryptophan will block gluconeogenesis"), Victor missed the only real undesirable side-effect of aminos (diarrhea at very high intakes, as occurs with consumption of large amounts of any substance). Victor has consistently criticized the supplement industry for unsubstantiated claims; well, where is his proof? In his summary, Victor states that: "Not only is there no need for free tryptophan in the diet, but free tryptophan is not recognized as safe by the Food and Drug Administration. It is a drug whose only use is as a drug or food additive (in infant formulas, medical foods, and as an additive to tryptophan-poor protein of plant origin)"(19). Without getting into the specifics of this moronic statement, I&Mac226;d just like to know why, if free tryptophan is not recognized as safe by the FDA, it is being fed to babies and given to people as a drug? Stonewalling In Academia. I have observed an incredible resistance to JON at the very top of the academic community. Both the American Journal of Clinical Nutrition and the Journal of Nutrition refused to run my Ñcall for papersâ notice (a paid advertisement). This is in spite of the fact that they had run the exact same ad for three and six months, respectively, the previous year (when I was Editor-in-Chief of The Journal of Applied Nutrition). [In truth, the ads were slightly different: The Journal of Applied Nutrition was changed to The Journal of Optimal Nutrition]. Neither AJCN nor JN responded in writing to my written requests, nor were any reasons given for their rejections. Even more lamentable was that I was not told how to change the ad to make it acceptable. All I got from JN was the proverbial run-around, and all I was told was that "someone had said they didn't like it". I tried, in vein, to find out more about how they had arrived at their decision by contacting Dr. Willard Visek (the Editor-in-Chief of JN). The irony was that I had been elected to the American Institute of Nutrition (JN's parent organization) the same week as the rejection occurred. Nice welcome! The story at AJCN was much the same: Dr. Stephen Schiaffino (the Managing Editor of AJCN) said that he&Mac226;d asked four individuals about this ad, and they all disapproved. When asked how many he had to choose from, his response was 500, but on further questioning he was unwilling to get any other opinions. In essence, I was told that 0.8% of the total reviewing board was sufficient to reject the JON Ñcall for papersâ ad. Further discussions with Dr. Norman Kretchmer (Editor-in-Chief of AJCN) were equally revealing. He told me that AJCN didn&Mac226;t have to say why the ad was rejected, or let me know how it could be changed to make it acceptable, or even respond in writing! One take-home lesson is that there is something amiss with the decision-making process at the very highest echelons of academic nutrition -- at levels I'd previously thought immune to petty politics and common corruption. The Bottom Line: Fear. I also brought this up to illustrate the depth of resistance to any one or any group focusing on the science of nutritional supplements. I definitely got the impression that there was no way either JN or AJCN would carry the ad, not because of me personally, but because of what JON represents. But of greater import is the fear that gets registered every time the terms "science" and "supplements" are used in the same sentence. Nutritionists are terrified of even appearing to be supplement- oriented, fearing (probably rightfully so) that their grants would be cut and their reputations ruined. At several free radical/antioxidant meetings, I have proposed that we (the leaders in antioxidant research) make some recommendations to the general public, as we have the knowledge (and responsibility) to do so. No recommendations ever emerged, however; the fear was simply too great. Moreover, several members of JON's Editorial Board have related instances where they have been warned not to publish positive results on supplemental nutrients, for by doing so their careers would suffer. By Claudio Capozza MBBS (Italy), Naturopathic Doctor (Australia)
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