Grace A. Goldsmith

Human requirements for vitamin C and its use in clinical medicine.

Human requirements for vitamin C have been investigated extensively. The minimal quantity that will prevent the development of scurvy has been established with reasonable certainty, but the desirable intake for the maintenance of health remains unknown and is a subject of considerable controversy. The amount of ascorbic acid that has been found to prevent scurvy is approximately 10 mg. a day or somewhat less. The first information in this regard stems from the observations of Lind in 1753 who showed that scurvy could be prevented by a daily allowance of 25 to 30 ml. of lemon juice. According to present knowledge, this quantity of lemon juice should furnish 10 to 15 mg. of ascorbic acid. Early experiences indicated that the substitution of lime juice for lemon juice was not an effective preventive measure.’ Lime juice contains about one-fourth as much vitamin C as does lemon juice. Infantile scurvy is a disease of modem times that was noted with increasing frequency as formulas of cow’s milk replaced breast feeding. In infants who received raw diluted cow’s milk, mild symptoms of scurvy were not rare. In these instances, it was estimated by UhP that the infant received 3 to 6 mg. of ascorbic acid daily; hence the minimum requirement must be greater than his. Van EekelenO reported that infants who received raw cow’s milk containing 2 mg. of ascorbic acid per 100 ml. or boiled cow’s milk containing 1.5 mg./100 ml., or a total intake of about 7 mg. of ascorbic acid daily, do not get scurvy. Vitamin C deficiency is extremely rare in infants who are breast-fed. The quantity of ascorbic acid in human milk fluctuates according to the maternal diet. In a study in the Netherlands: it was found that mother’s milk contained between 0.8 and 3.5 mg./100 ml. (average 1.8 mg./100 ml.) during the season when least ascorbic acid was eaten, whereas the content ranged between 4.1 and 6.8 mg./100 ml. when more ascorbic acid was available. It is generally stated that if the mother’s diet is reasonably good the milk will contain 4 to 8 mg./100 ml. In such instances, breast-fed infants receive a daily allowance of a t least 20 mg. of ascorbic acid and often as much as 40 to 50 mg. daily. Such infants do not develop scurvy. Hamil and his associates4 in a study of 427 infants found that 10 mg. of vitamin C daily would protect from scurvy. During the course of their study, 21 infants developed mild evidence of the disease according to the criteria of Park el dM Fourteen of these 21 infants received an average of 9 mg. of ascorbic acid daily; 7 received less than this amount. Ingalls6 showed progressive exhaustion of vitamin C reserves with increasing age in premature infants who died before 4 months of age and who had received only pasteurized mother’s milk. Histologic changes were present in the bones and costochondral junctions although no signs of scurvy were apparent during lie. Plasma ascorbic acid levels in healthy breast-fed infants have been reported

The effect of neomycin on cholesterol metabolism

Oral neomycin lowers serum cholesterol in man, whereas intramuscular doses are ineffective. Probably it exerts its effect in the gastrointestinal tract. It has been suggested that neomycin specifically involves alteration of the intestinal flora. An increased excretion of bile acids and the failure of the conversion of cholic acid to deoxycholic acid has been demonstrated, which supports this hypothesis. It has also been suggested that the decrease in serum cholesterol is related to a malabsorption syndrome. Although large doses of neomycin do cause a malabsorption syndrome there is no agreement as to the occurrence or severity of a malabsorption syndrome related to therapeutic doses of neomycin.

Human studies of biologic availability of niacin in coffee.

Summary Coffee contains a significant amount of niacin which is biologically available for man. This beverage can furnish an appreciable share of daily requirement of niacin and should be considered in estimating the niacin content of the human diet.

Evaluation of Nicotinic Acid Nutrition by Studies of Urinary Excretion

The adequacy of nicotinic acid nutrition in man is determined at the present time solely on the basis of clinical findings. Several investigators 1 , 2 , 3 have reported that there is little difference in the quantity of nicotinic acid and its derivatives excreted in the urine in a 24 hr period by normal persons and by patients with dietary deficiency. Perlzweig, Sarett and Margolis 2 have recently suggested that the urinary excretion following the administration of 500 mg of nicotinamide may serve as a test of nicotinic acid deficiency. This report deals with observations made on 6 normal persons, 18 hospital patients without signs of deficiency disease and 10 patients with clinical findings indicating deficiency of one or more members of the B group of vitamins. Of this last group 7 had lesions of pellagra, 5, evidence of ariboflavinosis and one, thiamin deficiency. The quantity of nicotinic acid and its derivatives excreted in the urine in a 24 hr period was determined by the method of Perlzweig, Levy and Sarett 4 with minor modifications. 5 Nicotinic acid is excreted in a number of forms, a small percentage as nicotinamide, coenzyme and nicotinuric acid (acid hydrolyzable derivatives) and a large percentage as trigonelline, which must be determined separately. The method is very satisfactory for the determination of acid hydrolyzable derivatives and is the best available for the estimation of trigonelline, although in our experience only 40 to 50% of this compound added to urine can be recovered. Since trigonelline is the main excretion product of nicotinic acid and since it is present in many foods, it is essential in studying nicotinic acid metabolism to place subjects on a diet low in trigonelline, which was done in this investigation.

Therapy of hypercholesterolemia

animals suggest that atherosclerosis may be reversed to some extent. Patients with high levels of serum cholesterol, and probably also those with elevated serum triglycerides, are in a high-risk group relative to the development of atherosclerotic heart disease and myocardial infarction. Accordingly, it would seem wise to try to reduce these high concentrations of serum lipids with the aim of influencing the atherosclerotic process. Therapy of hyperlipidemia should be combined with active measures to control all other factors that may be related to atherogenesis, such as hypertension, obesity, physical inactivity, etc. REDUCTION OF SERUM LIPIDS Serum lipid levels can be influenced by diet, hormones, and a number of pharmacologic agents. Reduction of serum lipids can be accomplished by several mechanisms. The dietary supply of lipids can be reduced, absorption can be diminished, or tissue synthesis of specific lipids can be inhibited. Degradation and excretion of lipids can be stimulated. A redistribution of lipids can occur, with an increase in lipids in tissues at the expense of those in the circulating blood. The concentration of cholesterol in serum is tile resultant of the amount ingested and absorbed plus the amount synthesized, as related to the amount degraded to bile acids and excreted in the bile as such, or as cholesterol, and the amount utilized or stored in the tissues. Some of the bile acids and

Hematologic Effects of Pteroylglutamic Acid (Folic Acid) in Man.

Conclusion The administration of pteroylglutamic acid was followed by definite improvement in 17 of 23 cases of human macrocytic anemia. The hematologic effects of pteroylglutamic acid closely resembled those of liver extract but differed in that oral administration was equally or more effective than parenteral and that restoration of the blood picture to normal was often incomplete.

Excretion of N1-methylnicotinamide and the 6-pyridone of N1-methylnicotinamide in urine of human subjects.

Summary Essentially normal subjects maintained for short periods on diets low in nicotinamide and tryptophan excrete approximately 3 mg of N1-Me and 5 mg of pyridone per day. Following an oral 50 mg test dose of nicotinamide; the average increase in excretion of N1-Me is 5.5 mg and that of pyridone, 23.4 mg. The excretion of N1-Me following the test dose rises rapidly during the first 4 hours and decreases to basal levels within 24 hours; pyridone is excreted more slowly the first few hours but appears in large amounts later in the day. After graded doses of nicotinamide, the excretion of pyridone increases more rapidly than does that of N1-Me. In subjects with pellagra, the excretion of these metabolites is lower both on standard diets and following administration of small doses of nicotinamide. These data suggest procedures that may be of use in evaluating niacin nutrition.

Determination of Vitamin C Nutrition by Means of a Skin Test. A Critical Evaluation

Conclusion In 100 tests there was no correlation between the amount of ascorbic acid in the blood during fasting and the time of decolorization of an intradermal injection of 2–6-dichlorphenol-indo-phenol. This skin test is not a satisfactory method for the determination of the state of vitamin C nutrition.