Marian E. Swendseid

Immunocompetence and oxidant defense during ascorbate depletion of healthy men.

To determine nonscorbutic effects of moderate vitamin C deficiency we measured immune function and oxidative damage in eight healthy men (25-43 y) who consumed 5-250 mg/d of ascorbic acid over 92 d on a metabolic unit. During ascorbic acid intakes of 5, 10, or 20 mg/d, subjects attained a state of moderate ascorbic acid deficiency as ascorbic acid concentrations in plasma, leucocytes, semen, and buccal cells dropped to less than 50% of baseline with no scorbutic symptoms observed. No changes in cell proliferation, erythrocyte antioxidant enzymes, and DNA strand breaks were observed; however, blood levels of glutathione and NAD(P) decreased during ascorbic acid deficiency, as did delayed hypersensitivity responsiveness. Concentrations of the oxidatively modified DNA base, 8-hydroxydeoxyguanosine in sperm DNA and fecapentaenes, ubiquitous fecal mutagens, were increased during ascorbic acid depletion. Moderate vitamin C deficiency, in the absence of scurvy, results in alteration of antioxidant chemistries and may permit increased oxidative damage.

Vitamins C, E and A and Heme Oxygenase in Rats Fed Methyl/Folate-Deficient Diets

There is evidence that the development of hepatocarcinoma in rats fed a methyl-deficient diet is associated with oxidative stress. We investigated, therefore, whether the tissue concentrations of the antioxidant vitamins ascorbic acid (AA) and alpha- and gamma-tocopherol (T) are altered in methyl/folate deficiency. We also measured retinol concentrations in tissues and hepatic mRNA expression of heme oxygenase (HO1). A 6% gelatin, 6% casein diet, devoid of choline and folate (CFD) was selected based on the high rate of tumor development in rats fed this diet. Spectrophotometric measurement of AA and HPLC determination of tissue T and retinol showed decreased concentrations of AA in blood; alpha- and gamma-T in lung, heart and plasma, alpha-T and retinol in liver; retinol in lung; and increased expression of hepatic HO1 mRNA. Similar alterations in tissue vitamin concentrations were found when the CFD diet devoid of niacin (CFND) was fed. Reducing alpha-T in the CFND diet (CFNED) further decreased hepatic alpha-T concentrations. These results show that chronic methyl/folate deficiency is associated with a compromised antioxidant defense system.

Polyamine concentrations in red cells and urine of patients with chronic renal failure

Abstract Spermidine and spermine concentrations were measured in 6 healthy subjects, 18 patients with chronic renal failure and 6 patients undergoing maintenance hemodialysis. In nondialyzed patients with advanced renal failure (serum creatinine levels greater than 6 mg %), red cell spermidine concentrations were significantly higher than in normal subjects (54.8±14.5 vs. 24.8±63 SD nmoles/ml packed cells). However red cell spermine concentrations were unchanged as compared to normal subjects (18.7±7.3 vs. 12.4±3.4 nmoles/ml packed cells). In patients with serum creatinine levels below 6 mg%, neither red cell spermidine or spermine concentrations were significantly different from normal subjects. There was a significant correlation between red cell spermidine values and both serum urea and serum creatinine levels, but no correlations were observed for red cell spermine. Red cell spermidine values were also significantly higher in patients undergoing maintenance hemodialysis than in normal subjects. In each patient, red cell spermidine concentrations were no different after a hemodialysis treatment than immediately prior to dialysis. In urine, excretion rates of polyamines as well as the precursor diamine, putrescine, were lower in patients with chronic renal failure than in normal subjects. Hence in renal failure, one factor contributing to the accumulation of spermidine in red cells would appear to be a decrease in the urinary excretion of polyamines.

Limits of absorption of orally administered vitamin B12: effect of intrinsic factor sources.

Summary The results show the extreme limitation of vit. B12 absorption from the gastrointestinal tract of individuals with normal gastric function. Within the dose range used, an upper level of absorption appears to have been reached which averages 1.6 μg vit. B12. This level is not increased by giving the vitamin with a test meal or in conjunction with intrinsic factor sources. In patients with a total gastrectomy, a graded response to intrinsic factor is obtained using 0.5 μg vit. B12 but at a 5 μg level, increasing the amount of intrinsic factor does not increase B12 absorption beyond levels obtained in normal subjects.

Mechanisms involved in the development of vitamin B12 deficiency.

Summary The use of radioactive (cobalt 60 -labeled) vitamin B 12 constitutes a new method for studying intestinal absorption of vitamin B 12 . This tool has been useful in elucidating mechanisms involved in the development of vitamin B 12 deficiency. Four distinct mechanisms can be identified. These are: a) deficiency of intrinsic factor, b) bacterial or parasitic interference with normal absorption of vitamin B 12 , c) defective absorptive capacity of the intestinal mucosa, and d) inadequate dietary intake of vitamin B 12 The pathologic physiology involved in each of these categories is discussed, and illustrative cases are presented.

Excretion of Cobalt60-Labeled Vitamin B12 after Total Gastrectomy.

Summary Co60-labeled vit. B12 was administered orally in 0.5 γ doses to 4 patients who had had a total gastrectomy. Each patient excreted in the stools essentially all of the administered radioactivity. When gastric juice was given with the vitamin there was a decrease in Co60 excretion to levels similar to those found in control subjects.

Plasma carotenoid levels in anorexia nervosa and in obese patients

Publisher Summary In this chapter, the relationship between plasma carotenoid levels and body mass index (BMI) is examined over a wider range. BMI describes the degree of adiposity and the amount of other body compartments into which β -carotene can distribute. Increased body mass involves an increased amount of adipose tissue, increased blood volume, and increased extracellular fluid volume. The chapter provides evidence that supports the theory that body mass, and possibly tissue storage capacity, may play a role in the hypercarotenemia of anorexia nervosa. In the chapter, plasma levels of individual carotenoids are measured and carotenoid intake in patients with anorexia nervosa is assessed. These data are compared with data from normal subjects and from obese patients who had lost weight because of reduced-calorie diets of natural foods and exercise. Results from the study discussed in the chapter suggest that when similar types of diets and amounts of carotene-rich foods are consumed over a period, individuals with reduced body mass exhibit higher plasma β -carotene levels than those with greater body mass. This finding is corroborated by results from epidemiologic studies, which suggest that lower relative weight is associated with increased plasma β -carotene levels in the normal population.

Actinomycin D effect on amino acid absorption from rat jejunal loops.

The absorption of amino acids from jejunal loops was suppressed in anesthetized rats treated previously with 1.0 or 1.5 micrograms of actinomycin D per gram of body weight. The absorption of the acidic, neutral, and basic amino acids showed selective differences in response that were relative to the degree of inhibition and to the time interval required to demonstrate actinomycin sensitivity.

The Role of Folate, Choline, and Methionine in Carcinogenesis Induced by Methyl-Deficient Diets

In humans, deficiencies of choline and methionine are not likely to occur except for an occasional methyl deficiency as evidenced by low plasma choline levels and development of fatty livers in some patients given longterm parenteral nutrition (Burt et al. 1980, Tayek et al. 1990 and Buchman et al. 1991). However, folate deficiency is a problem in many population subgroups such as pregnant women, adolescents, elderly people (Sauberlich 1990 and Joosten et al. 1993), and alcoholics (Shaw et al. 1989). The participation of folate in methionine regeneration and other methyl transfers links folate metabolism closely to methyl metabolism (Krumdieck, 1991). In rats a deficiency of choline and methionine and its effect on hepatocellular carcinoma in the absence of carcinogens has been studied extensively. However study of possible involvement of folate deficency in carcinogenesis mediated through alterations in methyl metabolism has been somewhat neglected. Recent reports indicating an increased risk of cancer and precancerous lesions of various types in humans associated with low folate intakes or low red blood cell folate levels increase the relevance of such investigations (Giovannucci, E. et al. 1993, Butterworth, C.E. et al. 1992).

Metabolic and hormonal factors as predictors of nitrogen retention in obese men consuming very low calorie diets

The ability to conserve body protein during very low calorie diets in ten obese men was observed to correlate with plasma free amino acid concentrations, urinary N tau-methylhistidine: creatinine ratios, resting oxygen consumption, and serum triiodothyronine levels. A diet consisting of only protein, 1.3 g/kg ideal body weight/24 h, was given for 40 days. Cumulative nitrogen deficit ranged from -64 g to -227 g. Nitrogen balance on days 36 to 40 ranged from + 1.37 g/24 h to -3.30 g/24h. Nitrogen balance during this period had a significant direct correlation with pre-diet concentrations of branched-chain amino acids (r = 0.69 to 0.89), methionine (r = 0.85), histidine (r = 0.66), alanine (r = 0.73), arginine (r = 0.70), ornithine (r = 0.66), total essential (r = 0.87, and nonessential (r = 0.68) amino acids, with initial serum levels of triiodothyronine (r = 0.66) and with the fall in triiodothyronine over the 40 days (r = 0.79). Initial resting oxygen consumption was directly correlated (r = 0.78) with final nitrogen balance and inversely with total nitrogen loss (r = -0.81). On day 0, triiodothyronine levels also correlated positively (r ranging from 0.71 to 0.93) with plasma concentrations of several essential and nonessential amino acids. These correlations suggest that individuals who ultimately will or will not achieve nitrogen equilibrium during very low calorie diets can be identified prior to dieting. These data are consistent with the hypothesis that individuals with higher initial protein flux and triiodothyronine levels are better able to adjust the balance between synthesis and degradation to attain nitrogen equilibrium during hypocaloric dieting.