The need for human data: the role of clinical trials and postmarketing surveillance in the safety assessment of macronutrient substitutes.

It seems self-evident to me that macronutrient substitutes are important additions to the medical, dietetic, and individual armamentarium for maintenance and/or improvement of overall health status. This is particularly true given the enormous amount of obesity in our population. Regarding clinical trials and postmarketing surveillance, there are two basic principles that stand out to me: 1. Clinical trials are absolutely necessary for marketing, but the extent of such trials is a function of the specific food or ingredient under consideration. 2. Postmarketing surveillance may or may not be necessary or desirable, depending on the possibility of adverse effects after prolonged consumption.

Generally recognized as safe (GRAS) evaluation of 4-hexylresorcinol for use as a processing aid for prevention of melanosis in shrimp.

4-Hexylresorcinol (C12H18O2) is proposed for use as a processing aid for prevention of melanosis ("black spot") in shrimp and as an alternative to the currently approved sulfites. A safety evaluation was conducted to affirm, based upon scientific procedures, the generally recognized as safe ("GRAS") status of 4-hexylresorcinol for proposed use. The GRAS safety evaluation compiled, reviewed, and analyzed data on the following areas: chemical identity, analytical methodology, historical and proposed uses, functionality, and safety. The publicly available safety data on 4-hexylresorcinol cover a broad range of potential toxicity concerns including acute and subacute toxicity, subchronic toxicity, carcinogenicity, mutagenicity, and allergenicity. These studies, along with the aforementioned data, demonstrate that 4-hexylresorcinol presents no risk of toxicity at the levels proposed for treatment of shrimp, and the use of 4-hexylresorcinol as a processing aid to prevent melanosis in shrimp is GRAS.

Comparison of in vitro, animal, and clinical determinations of iron bioavailability: International Nutritional Anemia Consultative Group Task Force report on iron bioavailability.

Relative bioavailability of two iron fortificants, electrolytic Fe and ferric orthophosphate, was related to that of the reference ferrous sulfate with in vitro and rat model depletion-repletion methods in four laboratories to compare values directly with those obtained in a parallel human study. In vitro testing was performed on Fe compounds with both solubility and dialysis in a simulated in vitro gastrointestinal digestion system. Two depletion-repletion techniques, hemoglobin-regeneration efficiency (HRE) and an official method of the Association of Official Analytical Chemists (AOAC), were examined. AOAC relative biological values (RBV) of electrolytic Fe were 0.66 and 0.78 and of FePO4 were 0.25 and 0.34. HRE values were 0.78 and 0.58 for electrolytic Fe and FePO4, respectively. When compared with FeSO4 in a radiolabeled farina-based meal fed to humans, the RBV of FePO4 was 0.25 and electrolytic Fe 0.75. Results obtained with the AOAC method serve as the most reliable prediction of Fe bioavailability in the human although in vitro dialysis is a promising screening technique.

National Nutrition Monitoring System: implications for public health policy at FDA.

The National Nutrition Monitoring System (NNMS) plays an essential role in major nutrition activities of the Food and Drug Administration (FDA). In relation to the current sodium initiatives, it permits the measurement over time of changes in the sodium content of the food supply and in typical diets; in sodium labeling in the marketplace; in public awareness, concerns, and practices; and in the prevalence of hypertension and related factors, such as obesity. The FDA is responsible for U.S. fortification policy and its regulation. Currently, fortification policies and practices are being reexamined, largely on the basis of analysis and interpretation of data from the 1976-1980 second National Health and Nutrition Examination Survey, which is a core component of the NNMS. FDA studies that are components of the NNMS, such as a recent survey of dietary supplement consumption, provide comprehensive data in specialized areas. Department-wide nutrition programs are also heavily dependent upon the NNMS for monitoring capabilities. Two current activities that will rely on NNMS data are the monitoring of progress in the Nutrition Objectives for the Nation for the 1990s and the development of departmental policy regarding diet, nutrition, and degenerative diseases.

Nutrition in adverse environments, 3. The metabolic effects of a restricted food intake on men working in a tropical environment.

As part of a research programme concerned with the need to lighten the load carried by soldiers engaged in long foot patrols, a field experiment was undertaken in West Malaysia. For 12 d a group of 15 men consumed 7.4 MJ/d (1770 kcal/d) whilst a control group of 14 men ate 12.9 MJ/d (3080 kcal/d); both groups expended on average about 15.8 MJ/d (3770 kcal/d). The low-energy group incurred an energy deficit of 98 MJ (23 410 kcal) with a weight loss of 3.9 kg, whereas corresponding figures for the control group were 37 MJ (8840 kcal) and 2.4 kg. Before, during and after the energy deprivation phase, assessment was made of work capacity (estimated VO2 max), vigilance and military skills but no difference was found between the groups.

RDA and related tracking systems concerned with sodium.

The U.S. Food and Drug Administration (FDA) and the Department of Health and Human Services have developed a five-point set of sodium initiatives aimed at moderation of sodium consumption, improved sodium-related information for consumers and health professionals, and improved consumer choice in the marketplace. Implimentation is fundamentally based on a voluntary premise, and indications to date are that the program is working. FDA has established a series of tracking systems to measure change over time, particularly relative to changes in the sodium content of the food supply, in the sodium content of American diets, in sodium labeling -- both quantitative and qualitative, in consumer understanding of the sodium-and-hypertension problem, and in consumer food purchasing practices. Some of these efforts are conducted in cooperation with other Federal agencies such as the National Heart, Lung, and Blood Institute and the Department of Agriculture. The epidemiological approach to measurement of the prevalence of hypertensive disease as provided by the periodic National Health and Nutrition Examination Surveys is at the center of all other tracking systems to measure effectiveness of the national effort to reduce sodium intakes and thereby hopefully moderate the magnitude and severity of hypertensive disease as a major public health problem in the United States.

Perspective of Food and Drug Administration on Dietary sodium.

The sodium and potassium content of typical American diets of infants, toddlers, and adults was determined, both for total content and for content at the commodity group level, by chemical analysis of representative diets from 1977 through 1980. In recent years the scientific community has reached a consensus that high sodium intake is positively associated with hypertension. Various professional groups urge the American public to reduce their sodium intake. Several monitoring initiatives of the Food and Drug Administration relative to sodium in the national food supply are discussed.

Sudden death associated with very low calorie weight reduction regimens.

We studied the cases of 17 individuals who died suddenly of ventricular arrhythmia after prolonged use (median 5 months) of very low calorie weight reduction regimens consisting entirely or largely of protein. The deaths appeared to be independent of type of medical supervision received during the diet, daily dosage of potassium supplementation, and biological quality of the protein product used. Factors common to all cases were marked obesity at the onset of dieting, prolonged use of extremely low calorie diets (approximately 300 to 400 kcal daily), and significant and rapid weight loss. Our review of available electrocardiograms and pathological specimens revealed a pattern of cardiac changes previously described in starvation. We conclude that use of very low calorie weight reduction regimens should be curtailed until further studies determine what modifications, if any, can insure their safety.

Calcium, phosphorus, iron, iodine, and zinc in the "total diet".

Advances in food technology have changed the nutrient composition of foods, raising questions as to whether mineral intakes in the U.S. are now adequate or excessive. When the FDA assayed "market basket" samples collected at the retail level in twenty urban areas of the U.S. during 1974 and 1975, the following minerals and the daily intake as percentages of the U.S. RDAs were found: (a) For adults (based on a 2,800 kcal intake)--calcium, 114; phosphorus, 171; iron, 98; iodine, 428; and zinc, 89; (b) for six-month-old infants--calcium, 163; phosphorus, 173; iron, 47; iodine, 878; and zinc, 112; and (c) for two-year-olds--calcium, 114; phosphorus, 130; iron, 112; iodine, 526; and zinc, 106.

Protein in the U.S. diet.

Nationwide studies carried out between 1965 and 1975 have been reviewed to determine: (a) The adequacy of dietary protein nutrition in the United States, (b) the level of protein available from the national food supply, and (c) the effects of excessive amounts of protein in the diet. On the basis of the studies reviewed, it can be concluded that the diets of most Americans are adequate in quantity and quality of protein.