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Individual assessment of a patient's particular vitamin C needs is important before dosage advice is given. The biochemical and physiological effects of Vitamin C need to be carefully analyzed under controlled experimentation before its value as a pharmacologic agent in preventive medicine can be fully understood.

Although megavitamin therapy can be ineffective and possibly even dangerous, legitimate uses for mega doses of certain vitamins have been found. The author reviews the risks and benefits of megavitamin therapy.

The effects of vitamin A deficiency on the absorption, retention and distribution of 59Fe were studied in Sprague-Dawley rats. By means of whole-body counting, organ counting (liver and spleen) and measurement of fecal radioactivity, data were collected daily for periods of 6 or more days following 90 days of vitamin A depletion. No significant difference in 59Fe absorption was observed between group 1, control (6,500 IU vitamin A/kg diet), and group 2, vitamin A-deficient rats fed ad libitum. Group 3, pair-fed control rats, whose food intake was restricted to that of the deficient group, absorbed and retained less 59Fe than either group 1 or group 2. In a second experiment, iron turnover and red cell incorporation of 59Fe were investigated in young adult rats following 125 days of vitamin A depletion or supplementation. Changes in plasma and blood volumes and tissue distribution of the isotope were determined. The values were obtained after intravenous administration of 10 μCi of 59Fe/100 g body weight. At the end of the experiment the animals were killed and the isotope concentration in different tissues was determined. There were no differences between the vitamin A supplemented and deficient rats with respect to the initial estimates for iron turnover and rate of 59Fe clearance from plasma. Red cell incorporation of 59Fe, however, was significantly reduced in the deficient animals (40 to 50% of control values). There also was a significant reduction in plasma and blood volumes of vitamin A-deficient rats. Moreover, there was a significantly greater isotope accumulation in the liver and spleen of the vitamin A-deficient rats.

Anemia associated with vitamin A deficiency and increased liver iron has implicated vitamin A in the regulation of iron release from the liver. To study this relationship further, groups of weanling rats were fed diets as follows: low iron/low vitamin A, low iron/high vitamin A, normal iron/normal vitamin A, high iron/low vitamin A and high iron/high vitamin A. After 6 weeks the animals were killed, and blood and liver samples were taken for analyses of hemoglobin, hematocrit, red blood cell count, serum and liver vitamin A, serum and liver iron and total iron-binding capacity. Low dietary iron, but not low vitamin A intake, affected hemoglobin, hematocrit and red blood cell counts but not serum vitamin A levels. Mean serum vitamin A levels were not significantly lower in groups fed high dietary iron. High dietary iron was also associated with lower mean liver vitamin A levels; these differences were statistically significant only for the low vitamin A diet group. A high vitamin A intake was associated with a significantly lower mean hepatic iron level for the high dietary iron intake group. These data support the hypothesis that vitamin A is involved in the regulation of iron release from the liver.

MYXEDEMA is a clinical disease entity resulting from failure of the thyroid gland to maintain a daily output of thyroid hormone consistent with health. Since the publication of the report of the committee appointed by the Clinical Society of London to investigate the subject in 1888,1 myxedema has been a well recognized disease and numerous reviews and investigations have been published. Despite increasing knowledge of the physiology of the thyroid gland and the continuous development of better means of investigating thyroid function, myxedema has frequently remained undiagnosed. This probably is the result of the wide variety of presenting symptoms, some of which have been considered rather vague or nonspecific. It is particularly so in old people, as myxedema develops so slowly that its manifestations are often mistaken for those of aging. The tendency to look for the "classic" symptoms and signs of a full-blown case of myxedema is probably

Changes in the American diet over the last seventy years have been analyzed with particular emphasis on the sources of fats and carbohydrates in the light of the increasing incidence of coronary heart disease. The main changes have been (1) a considerable decrease in the consumption of total carbohydrates with a greater progressive decline in the intake of complex carbohydrate from flours, cereals, and potatoes, and a concurrent dramatic increase of simple sugars, especially in the first part of this century; and (2) a slight increase in total fat consumption contributed mainly by the increase of unsaturated fatty acids. The increase in polyunsaturated fatty acids has surpassed the increase in the saturated ones and consequently the ratio has increased about 37 per cent since 1909. Obviously these data do not fit the hypothesis that low ratios of polyunsaturated to saturated fatty acids in the food supply contribute to the increased incidence of coronary heart disease in the United States. The changes which have occurred in the type of dietary carbohydrates, however, may be a factor.

A study of the metabolism of ascorbic-l-14C acid in experimental human scurvy was conducted with the following results:1) Labeling the body ascorbic acid pool during the depletion phase resulted in no detectable urinary excretion of 14C-labeled reduced ascorbic acid or dehydroascorbic acid.2) Urinary excretion of 14C by all subjects occurred as a first order process during the depletion phase. The urinary 14C excretion curves of the four subjects did not differ from the average man by more than ± 3%, despite marked differences in body weight and age.3) First symptoms of mild scurvy appeared in the subjects when their body ascorbic acid pool had been reduced to approximately 300 mg.4) Once the body pool of ascorbic acid was repleted to a level of 1.5 g, urinary loss of reduced ascorbic acid occurred.5) The rate of repletion of ascorbic acid was found to be a zero-order process and proportional to the level of daily ascorbic acid intake.6) When the subjects were fed a high intake of ascorbic acid, only a limited quantity of the ingested vitamin was equilibrated with the 14C-labeled ascorbate pool.7) All of the radioactivity excreted during the depletion phase was in the form of stable organic material that did not behave as ascorbic acid. This organic material was separated into four unknown compounds.8) The daily intake of 6.5 mg/day of ascorbic acid was sufficient to alleviate and cure the clinical signs of scurvy in one man.

Despite the recorded rarity of ocular vascular lesions in human scurvy, conjunctival lesions appeared during deprivation of ascorbic acid in five of nine volunteers who participated in two studies of experimental scurvy in man, three of four men in the first study and two of five men in the second. The ocular lesions often appeared early in the development of clinical scurvy and were first noted after deprivation of ascorbic acid for 74–95 days.These lesions varied from minute bulbar conjunctival hemorrhages and varicosities to a large subconjunctival hemorrhage accompanied by palpebral petechial hemorrhages, and conjunctival congestion.

Six apparently healthy men from the Iowa State Penitentiary volunteered for metabolic studies of human scurvy. They were hospitalized on the metabolic ward and given a diet totally devoid of vitamin C but adequate in all other essential nutrients. Although two of the prisoners escaped, the remaining four developed clinical signs of scurvy; follicular hyperkeratosis of the thighs, buttocks, calves, and the posterior aspects of the arms; swollen bleeding gums; perifollicular hemorrhages and congested follicles; and conjunctival hemorrhages. Biochemically there was virtually complete disappearance of ascorbic acid from the blood and urine, although an interfering substance gave erratic results once deficiency occurred.Carbon-14 labeled l-ascorbic acid was used to estimate the pool size in these subjects and to measure the rate of catabolism of this vitamin. These results are reported elsewhere (6)Blood counts, numerous biochemical measurements, the rate of wound healing, and physiologic tests including electrocardiograms, electroencephalograms, basal-metabolism rates, and blood coagulation studies, showed no abnormalities as a result of induced scurvy.It is estimated that clinical symptoms began to appear when the total body pool had decreased to approximately 300 mg and when the rate of catabolism of vitamin C had fallen to less than 2.5 mg daily.The present studies do not provide sufficient evidence to estimate the optimal daily allowance of ascorbic acid, nor do they answer the question of what enzymatic roles are supplied by ascorbic acid, but they are in close accord with the British Sheffield study (4) in which a supplement of 10 mg ascorbic acid daily was found to cure and to prevent clinical scurvy.

Both patients of normal weight and those with significant obesity were studied under the controlled circumstances of the Clinical Research Center on diets rigidly restricted in carbohydrate content and containing varying levels of protein and fat. The men of normal weight, when receiving a low-carbohydrate diet at a caloric level sufficient to maintain weight, exhibited significant elevations of blood lipid levels, particularly of cholesterol, and also developed moderate elevations of the blood urea nitrogen. Under circumstances of an adequate caloric intake, no significant elevations of uric acid or ketone bodies were noted.

Recent information which attempts to relate a high intake of sugar in the diet to a high incidence of ischemic heart disease has been reviewed. Data collected by the Interdepartmental Committee on Nutrition for National Development (ICNND) have been evaluated for sixteen countries. In these countries the average intake of fat was associated in a significantly positive fashion with the intake of sugar. Similarly, there was a negative association between the average concentration of cholesterol in the blood and the average intake of complex carbohydrates as represented by cereals, vegetables and the like. It is of interest to note that this idea was published more than one hundred and fifty years ago by Young, who quoted Dr. Stark as saying, “does not an excess in sweets give a greater shock to the system than an excess in fats.”

It is evident that we are still a long ways from having nutritional surveys which provide completely accurate and reliable information regarding the nutritional status of human subjects. Nevertheless, many guidelines have been developed which offer a great deal of help in determining segments of populations that are poorly fed and malnourished to a variable degree. Additional biochemical methodologies must be developed which will provide more specific information relative to nutrient function at the cellular level. These methodologies must be simple enough so that they may be adapted and used in large nutrition surveys. By perfecting methodologies and doing a better job of evaluating individuals within a group, we should come closer to the ideal objective of achieving correlation between dietary intake, biochemical nutrient levels and clinical findings. Unquestionably, more effort needs to be expended on evaluating the nutritional status of populations with an abundant food supply, such as those of the United States, and on gaining more information about the late effects of early nutrition.

The publications which have been reviewed support the concept that hypercholesterolemia and atherosclerosis, as they relate to diet, are influenced by the type of carbohydrates as well as by fats and cholesterol.Experiments in man suggest that the concentration of cholesterol and lipids in the blood can be altered by interchanging complex carbohydrates and sugar in the diet.The experiments reported here were designed to compare the effects of feeding diets equal in caloric value and containing the same percentage of proteins, carbohydrates and fats but in which the source of carbohydrates was changed from sugar to complex carbohydrates. The following observations were made: (1) Replacement of sugar by complex carbohydrates was followed by a decrease in the concentrations of cholesterol and glycerides in the blood of man. (2) Subjects complained of hunger when fed the sugar diet but often felt “stuffed” when they ate the complex carbohydrate diet. (3) The distribution of meals was an important factor in the lipid metabolism of these subjects. Feeding three equal meals daily rather than the customary pattern of unequal meals resulted in lower levels of cholesterol and glycerides in the blood.

The findings in the first year of a five year nutrition survey among teenagers in Iowa are reported. This survey involved 2,045 students who underwent a brief physical examination including measurements of their height and weight. Approximately one third of these underwent a detailed examination and contributed samples of blood and urine for biochemical tests. Half of these individuals also gave a detailed dietary history.In a group of 252 students data on all variables of this examination were complete, thus allowing detailed statistical evaluations. Although the average teenager is healthy and well nourished, a significant minority of these students have physical lesions and biochemically abnormal test results.The dietary questionnaire indicates that a substantial minority of students omit breakfast and eat diets which cannot be considered as well balanced. The consumption of dairy products is very high and the consumption of sugar, as contained in candy, soft drinks, etc., is also high.Particular attention has been paid to lipid metabolism as it may relate to body characteristics and to dietary history. Supporting data indicate that a high intake of dairy fat is associated with higher concentrations of triglycerides in the blood. Although a substantial number of students had high concentrations of cholesterol in their blood, statistically significant dietary correlations were lacking.Subsequent examinations of many of these students included in the first year of this survey may lead to more firm conclusions regarding the role of diet in growth rate, general health and, more specifically, in lipid metabolism.

MYXEDEMA in women is usually associated with altered menstrual function, infertility, or repeated abortion.1 Parkin and Greene2 described the occurrence of pregnancy in one patient with cretinism, in two with juvenile myxedema, and in three with adult myxedema. Their review of the world's literature revealed 10 previously recorded cases of pregnancy in true hypothyroidism, making a total of 16 cases.3 Their methods of diagnosis included determinations of the basal metabolic rate and the serum cholesterol, the clinical appearance, and the response of the patient to thyroid extract. Myxedema cannot always be diagnosed unequivocally by clinical findings plus these laboratory aids. In the past, many, varied disorders of the female reproductive function unfortunately have been attributed to hypothyroidism on the basis of a single basal metabolic rate determination. We agree that the 16 previously reported cases represented true myxedema. One might expect that the increased accuracy of diagnosis

The benefits of self-treatment of coronary heart disease with vitamin E are being promoted to the lay public. The bases for the claims, however, are quite tenuous and not based on controlled investigations carried out in a scientific manner.