Diet and nutrition research goes on in almost every medical school, university, and pharmaceutical laboratory throughout the world. Thus, the knowledge of how to prevent illness and maintain health through nutrition grows every year. However, for such areas as reversing the effects of chronic disease through dietary or nutritional intervention or determining levels of nutrients required to achieve optimal metabolic or immune system functioning, there often is no critical mass of researchers or funds to follow up promising initial experimental results.
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In fact, the history of nutrition research is marked by examples where, for one reason or another, preliminary reports of a positive therapeutic effect of a certain vitamin, mineral, or nutritional manipulation appear but are often not followed up by the overwhelming majority of the medical community. In cases where such therapies eventually are proven to be safe ~and effective, it is sometimes not until years or even decades after the initial reports. The result is that many individuals may die or suffer needlessly, while effective interventions are available but not yet validated.
For example, in the 1930s, Australian psychiatrist John Cade began a series of crude experiments on guinea pigs in which he injected them with the urine of psychiatric patients to test his hypothesis that mania--a mood disorder characterized by, among other things, periods of euphoria--might represent a state of intoxication resulting from an excess of some commonly occurring metabolite. Depression, on the other hand, might represent the effects of abnormally low levels of the same metabolite (Johnson, 1984). Although all the urine samples proved toxic to the guinea pigs--Cade traced the toxicity to the urea component of the urine--the urine from the manic patients was far more toxic than urine from the schizophrenic or depressive patients.
In his attempts to find out what was increasing the toxicity of the urea in the manic patients' urine, Cade happened upon the compound lithium citrate, which he eventually began ~injecting by itself into the guinea pigs to judge its effect. To his amazement, the guinea pigs became lethargic and unresponsive for several hours after receiving lithium, before fully recovering. In 1949, Cade published the results of a crude clinical trial, stating that lithium salts given to 10 manic patients resulted in a dramatic improvement in each one's condition (Cade, 1949). Unfortunately for Cade, just as his results were reaching the United States, a number of table salt substitutes containing lithium chloride had just been recalled by the Food and Drug Administration (FDA) due to toxic side effects and, in some cases, death with heavy use. So much publicity was given to the toxicity associated with these salt substitutes--which were marketed for use by people on salt-restricted diets--that for 5 years after Cade's original report, relatively little work with lithium was undertaken (Georgotas and Gershon, 1981).
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According to medical historian Frederick Johnson (1984), "Cade's report of lithium treatment of mania might well have succumbed to the same fate as that suffered by many proposed therapeutic techniques before and after that time ... had lithium salts been at all expensive or hard to come by...." Instead, because canisters of lithium salts were to be ~found in most hospitals and pharmacies at the time, many psychiatrists in the mid-1950s, for lack of adequate treatments for manic disorders, simply started experimenting with lithium on their own. By the mid-1960s, a spate of reports appeared in the medical literature reporting on the effectiveness of lithium in the treatment of manic and other psychiatric disorders (Gershon and Yuwiler, 1960; Schlagenhauf et al., 1966). Today lithium, in some patients with bipolar disorders (i.e., mood swings), is the most successful therapeutic drug of the five major types of drugs currently used in psychiatry (Horrobin, 1990), often producing normalization in acute mania patients in 1 to 3 weeks.
A situation analogous to the lithium story occurred in the late 1980s in the United States. Just as reports were emerging that suggested the effectiveness of the amino acid L-tryptophan in treating mild depression (Boman, 1988), chronic insomnia (Demisch et al., 1987), and mood disorders (Maurizi, 1988), there was a severe outbreak of a sometimes deadly inflammatory disorder called eosinophilia myalgia syndrome (EMS). The cause of the EMS outbreak was linked by epidemiologists to the over-the-counter use of tryptophan (Varga et al., 1993). Although all cases of this disorder were eventually found to be caused by contaminants in ~batches of tryptophan produced by a single manufacturer in Japan (Barnhart et al., 1990) and not by the effects of tryptophan itself, this nutritional supplement was taken off the market by the FDA and is no longer available over the counter. Just as with lithium, the publicity about toxicities associated with tryptophan may have hindered rational scientific discourse about the effectiveness of this nutritional therapy for some time to come. In fact, FDA uses the tryptophan example to justify its efforts to regulate as drugs most dietary and nutritional supplements whose manufacturers make any health claims (U.S. Food and Drug Administration, 1992).
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There have been numerous other instances in recent decades when individuals or groups of individuals have advocated nutritional interventions or alternative dietary lifestyles as a means of preventing or even treating disease and have met not only indifference but often hostility. This was especially true for those advocating vegetarianism or an extremely low-fat diet as a means of preventing or treating illnesses such as heart disease (see below). As was the case with John Cade and lithium, it took many decades for the facts to win out over misconceptions and biases.~The rest of this chapter discusses a number of areas of diet and nutrition research in which there is at least preliminary scientific evidence indicating the need for more in-depth studies, but for which there often is no critical mass of researchers or funds to follow up promising initial experimental results. However, it should be noted that only an overview of the field is presented, and it is by no means comprehensive. This field of research is so complex and diverse that no more than a few examples can be offered for each subsection.
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