Opioid peptides, adrenocorticotrophic hormone, and idiopathic (orthostatic) edema.

The effect of dextroamphetamine sulfate (Dexedrine) on plasma opioid peptides, hormones, and other metabolites was studied in eight female subjects with idiopathic (orthostatic) edema and five healthy females. All subjects were given 20 mg of dextroamphetamine sulfate, a drug widely used in the treatment of this disorder, and blood samples were collected before and 30, 60, and 90 minutes after treatment. Patients with idiopathic (orthostatic) edema had significantly lower plasma sodium levels but higher blood urea nitrogen, aldosterone, and renin levels. D-amphetamine decreased aldosterone and renin levels in both groups. Plasma adrenocorticotropin levels were lower whereas met-enkephalin levels were higher in idiopathic (orthostatic) edema subjects compared to control subjects. D-amphetamine had no significant effect on plasma beta-endorphin, adrenocorticotrophic hormone, or enkephalins. Our data indicate that opioid peptides, especially enkephalins, and adrenocorticotrophic hormone may be involved in the pathogenesis of idiopathic (orthostatic) edema syndrome, but they seem uninvolved in the aldosterone- and renin-lowering action of amphetamine. It is possible that amphetamine is acting further down the chain, either directly on the adrenal and kidney or the microvasculature, rather than at hypothalamus-pituitary axis.

Seven-day validation of doubly labeled water method using indirect room calorimetry.

Carbon dioxide production, water production, and energy expenditure (EE) determined with 2H2(18)O were validated using a room calorimeter. Nine human subjects (5 males, 4 females) resided in the calorimeter for five to seven consecutive 23.5-h days. Daily carbon dioxide and water production and EE were averaged from calorimeter data and compared with 2H2(18)O results for the same period and for the following week. Isotope concentrations were measured by isotope ratio mass spectroscopy (18O) and infrared spectrophotometry (2H). Isotope clearance rates and pool sizes were determined by two multipoint methods and the two-point method. No significant differences were measured between calorimetry and 2H2(18)O results for the period within the chamber [multipoint A.M. urine 1.55% +/- 2.57 (SD) %, multipoint A.M. + P.M. urine 0.98% +/- 8.19%, two-point 1.59% +/- 4.50%]. Free-living EE was 13% +/- 7% greater. The results indicate that the 2H2(18)O method as applied is a valid technique for measuring EE, that multipoint calculation methods can be as precise as the two-point method, and that EE was greater in free-living than in calorimeter-confined conditions.

Supplemental-chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets.

The effects of low-chromium diets containing chromium in the lowest quartile of normal intake on glucose tolerance and related variables in 11 females and 6 male subjects were evaluated. Subjects with glucose concentration greater than 5.56 mmol/L but less than 11.1 mmol/L 90 min after an oral-glucose challenge were designated as the hyperglycemic group and the remainder, the control group. Glucose tolerance and circulating insulin and glucagon of the hyperglycemic group all improved during chromium supplementation (200 micrograms/d) whereas those of the control group were unchanged. Glucose and insulin concentrations 60 min after the oral-glucose challenge and the sum of the 0-90 min and 0-240 min glucose values were all significantly lower after chromium supplementation in the hyperglycemic group. These data demonstrate that consumption of diets in the lowest 25% of normal chromium intake lead to detrimental effects on glucose tolerance, insulin, and glucagon in subjects with mildly impaired glucose tolerance.

Influence of genetic obesity, dietary carbohydrate and age on parameters of glucose tolerance and kidney and adrenal gland histology in female SHR/N-corpulent rats.

Young female obese (cp/cp) and lean littermates (?/+) of the recently developed congenic strain, SHR/NIH-corpulent (SHR/N-cp), were fed for 6.5 months isocaloric diets containing 54 percent carbohydrate as either sucrose or starch. Glycemic, lipidemic and renal parameters were determined after 1, 3 and 6 months. Systolic blood pressure and plasma corticosterone levels were determined after 3 months. After 6.5 months rats were killed for histological examination. Obese rats were hyperglycemic following an oral glucose challenge (1 hour response greater than 11.1 mmol/l) (200 mg/dl), hyperinsulinemic, hypertriglyceridemic, and developed proteinuria and mild hypertension. Feeding sucrose, as compared to starch, further increased serum glucose, insulin and triglyceride levels and urinary protein excretion in obese rats and serum triglyceride levels in lean rats. An amelioration of glucose intolerance was observed in sucrose-fed obese rats by 6 months. In contrast to serum insulin levels, serum triglyceride levels increased with age in obese rats. Obese rats exhibited hypertrophy of the kidney and adrenal cortex with abnormal histology. The study demonstrates that obese female SHR/N-cp rats exhibit some of the metabolic and histopathological changes associated with NIDDM in humans and that feeding sucrose, as the source of dietary carbohydrate, further magnifies the expression of diabetes in this model.

Day-long glucose, insulin, and fructose responses of hyperinsulinemic and nonhyperinsulinemic men adapted to diets containing either fructose or high-amylose cornstarch.

Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed a typical American diet containing 20% of calories either as fructose or as high-amylose cornstarch for 5 wk in a crossover design to determine their effects on indices of glucose tolerance. Blood glucose, insulin, and fructose were determined before and 30, 60, 90, 120 and 180 min after breakfast, lunch, and dinner. Glucose responses were significantly lower 60 and 120 min and the insulin response lower 60 min after the meals containing fructose. Hyperinsulinemic men showed a tendency toward decreased insulin sensitivity after consuming fructose on the basis of an increased insulin-to-glucose ratio and decreased insulin binding to erythrocytes. These results generally show a beneficial effect of fructose on glucose tolerance; however, recommendations for including large amounts of fructose in the diet should also be based on a complete evaluation of the effect on other metabolic risk factors.

Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch.

Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed for 5 wk each in a cross-over design a diet, similar to one currently consumed in the United States, with 20% of the kilocalories from either fructose or high-amylose cornstarch to determine the effects of the two diets on various blood metabolites considered to be risk factors associated with heart disease. In the hyperinsulinemic men the intake of fructose as compared with cornstarch significantly increased total triglycerides and their lipoprotein distribution; total and very-low-density lipoprotein cholesterol; apoproteins B-100, C-II, C-III; and uric acid. In the nonhyperinsulinemic men total triglycerides, total and low-density lipoprotein cholesterol and uric acid were significantly greater after the consumption of fructose than after cornstarch. The results indicate that in a diet high in saturated fatty acids and cholesterol, fructose increases the levels of risk factors associated with heart disease, especially in hyperinsulinemic men.

Mineral balances of men fed a diet containing fiber in fruits and vegetables and oxalic acid in spinach for six weeks.

In an investigation of the effects of fiber and oxalic acid on weekly mineral balances, 12 men consumed two diets consisting of natural foods for 6 wk each in a crossover design. One diet contained about 25 g neutral detergent fiber (NDF) in fruits and vegetables and included 100 g spinach, which is high in oxalic acid, every other day. The second diet was a low fiber diet that contained about 5 g NDF and the same amount of spinach as the first diet. On the basis of mean values for 6 wk, balances for calcium, magnesium, iron, zinc or manganese were not significantly different due to diet. Copper balances were significantly lower when the low fiber diet was consumed than when the diet containing fiber in fruits and vegetables and consequently a higher level of copper was consumed. Mineral balances were significantly different due to week. When results of both diets were considered together, mean mineral balances decreased at some time after wk 1 and returned to the wk 1 level during wk 6. Balances for wk 1 and 6 were not significantly different for any of the six minerals. These results demonstrate the importance of determining weekly balances for several weeks when conducting a human metabolic study.

Impact of variation in carbohydrate intake on mineral utilization by vegetarians.

Dietary intakes of two groups of vegetarians (of Asian Indian and of American origin) residing in the United States were compared with intakes of a group of nonvegetarians. Mineral intakes and balances were determined for all three groups for a 7-d period. The vegetarians had a significantly higher percent of energy intake from carbohydrate and significantly higher intakes of crude fiber (CF) and neutral detergent fiber (NDF) than did the nonvegetarians. The American vegetarians had significantly higher intakes of magnesium, iron, and copper than did the other groups. Manganese intakes were significantly higher for the two vegetarian groups than for the nonvegetarians. Calcium, iron, zinc, and copper balances were not significantly different among the groups. Magnesium and manganese balances were significantly more negative for the American vegetarians than for the other two groups. In general, the higher percent of carbohydrate intake or the higher level of fiber intake did not appear to affect mineral utilization by the vegetarians.

Vitamin E and relationships among tocopherols in human plasma, platelets, lymphocytes, and red blood cells.

Plasma, RBC, platelets, and lymphocytes from human subjects on graded intakes of vitamin E were analyzed for tocopherols to determine which humoral compartment most closely followed changes in the dietary intake. Relative merits of the various blood elements to reflect changes in vitamin E intake were calculated by the sensitivity concept of Mandel and Stiehler (ie, rate of change of tocopherol levels with dose divided by the standard deviation). Sensitivities of alpha-tocopherol levels of the various blood components to vitamin E intake decreased in the order platelets greater than RBC greater than plasma lipids greater than plasma greater than lymphocytes. Changes in tocopherol levels in platelets most closely followed changing dietary intakes of vitamin E when compared with data from RBC, lymphocytes, and plasma. Furthermore, for studying the effects of diets on vitamin E status, tocopherol levels of platelets appear to be a better measure than tocopherol levels of either RBC, lymphocytes, or plasma lipids.

Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia.

To determine if chromium (Cr) is involved in hypoglycemia, eight female patients with symptoms of hypoglycemia were supplemented with 200 micrograms of Cr as chromic chloride for three months in a double-blind crossover experimental design study. Chromium supplementation alleviated the hypoglycemic symptoms and significantly raised the minimum serum glucose values observed two to four hours following a glucose load. Insulin binding to red blood cells and insulin receptor number also improved significantly during Cr supplementation. These data suggest that impaired Cr nutrition and/or metabolism may be a factor in the etiology of hypoglycemia.

An insulinogenic effect of oral fructose in humans during postprandial hyperglycemia.

This study proposed to determine whether the stimulation of insulin secretion observed in humans infused with fructose when glucose levels were elevated could be observed when fructose was consumed during postprandial hyperglycemia. At 2-wk intervals, healthy volunteers consumed drinks containing glucose, starch, glucose followed 20 min later by fructose, starch followed 20 min later by fructose, and water followed 20 min later by fructose. Fructose consumption following glucose or starch drinks produced significantly higher levels of plasma insulin, but not plasma glucose, as compared to corresponding drinks consumed without fructose. Ten subjects whose blood glucose response levels were above 155 mg% after a glucose-containing drink appeared to be particularly responsive to the effects of fructose with increases in insulin levels of 60-288%. Results indicate that oral fructose can be insulinogenic in humans when blood glucose levels are elevated.

Long-term consumption of beef extended with soy protein by men, women and children: II. Effects on iron status.

The iron status of men, women and children consuming beef extended with soy protein was evaluated by measuring serum ferritin and clinical parameters of iron status during a six-month study. Fifty-two families (245 participants) were randomly assigned to consume, for 180 days, 1 of 7 beef products: all beef, beef extended with either soy isolate, soy concentrate or soy flour (20% reconstituted soy product, 80% beef), or beef extended with each of the three soy products fortified with 60 mg Fe and 25 mg Zn/100 g protein. The beef product was consumed by the subjects as their principal source of protein for 1 meal a day (children 1-18 yr) or 1-2 meals a day (11 per week; adult men and women). A control group consumed their usual self-selected diets. No evidence was found that consumption of beef extended with soy protein deleteriously affected the iron status of men, women or children. Consumption of beef extended with soy protein, at the levels used in this study, by military men and women and by school lunch participants would not appear to impose a risk in these population groups.

Long-term consumption of beef extended with soy protein by men, women and children: I. Study design, nutrient intakes, and serum zinc levels.

The effect of long-term consumption, under practical conditions, of beef extended with soy protein on serum zinc levels of men, women and children was studied. Fifty-two families were randomly assigned to consume for 180 days 1 of 7 beef products: all beef, beef extended with either soy isolate, soy concentrate or soy flour (20% reconstituted soy product, 80% beef), or beef extended with each of the 3 soy products fortified with 60 mg Fe and 25 mg Zn/100 g protein. The beef product was consumed by the subjects as their principal source of protein for 1 meal a day (children 1-8 yrs) or 1-2 meals a day (11 per week) for adult men and women. A control group consumed their usual self-selected diet. Diet records (4-day) of all foods and beverages consumed by the subjects were obtained pre-study and 63 +/- 7 and 126 +/- 7 days for calculation of nutrient intakes. No deleterious effects were found on the serum zinc levels when subjects consumed beef extended with soy protein for 180 days.

Long-term consumption of beef extended with soy protein by children, women and men: III. Iron absorption by adult men.

Forty-nine ostensibly healthy men consumed either patties of all-beef or beef extended with soy-isolate, -concentrate or -flour as the principal protein source in 1 to 2 meals daily for 180 days. Iron status was monitored by absorption of radioiron from a reference dose of ferrous ascorbate and by serum ferritin concentration. In addition, nonheme iron absorption from a test meal of the respective beef pattie consumed for the 180 days was estimated by the extrinsic tag procedure. There was no detrimental effect on iron stores as indexed by reference ferrous ascorbate absorption or serum ferritin concentration. Absorption of nonheme iron from the test meals was low except for individuals having indices of low iron stores. When adjusted for the effect of level of iron stores the relative absorption of nonheme iron from soy-isolate and -flour containing meals was greater than from the all-beef meal, indicating marked differences in the effect on iron absorption by different soy products. Consumption of soy-extended beef should have no detrimental effect on iron status of adult men if consumed in mixed diets at the level used in this study.

Effects of low fat diets varying in P/S ratio on nutrient intakes, fecal excretion, blood chemistry profiles, and fatty acids of adult men.

Twenty-three apparently healthy volunteers aged 35 to 60 years consumed closely monitored self-selected (SS) diets for five weeks followed by two low fat controlled diets (25% energy) for two six-week periods followed by another five-week SS diet. The two low fat diets, fed in a crossover design to one-half of the subjects per controlled diet period, had a polyunsaturated/saturated (P/S) fat ratio of either 0.3 or 1.0. Results are reported for bi-weekly measurements of energy and nutrients; blood profiles and plasma fatty acids; and for end-of-period values for stool characteristics. Blood chemistry profiles differed in the two groups. The low P/S diet produced significant increases not only in cholesterol, but in 16:0, 16:1, and percent saturated fatty acids and decreases in 18:2 and omega 6 fatty acids. The reverse was seen with the high P/S diet. The essential fatty acid (EFA) linoleic acid returned in the poststudy period to prestudy levels (all subjects), but arachidonic acid did not. The explanation for negative correlation between magnesium intake or excretion and percent plasma linoleic acid must await further research.

Self-selected vs. controlled diet as a baseline for human studies: effects of nutrient intakes on blood pressure and on constituents of blood and urine.

This study demonstrates that a three-week stabilization period, in which all subjects eat an identical diet, produced a more uniform but different baseline of metabolic parameters than the subject's self-selected or "habitual" diets. Subjects required more food energy to maintain initial body weights during the stabilization period than when they ate their reported self-selected diets; average intakes of almost all nutrients were higher from the stabilization than from the self-selected diet. The switch to the stabilization diet produced small but significant reductions in blood pressure, in some serum enzymes, urine volume, and sodium; and statistically significant increases in serum LDL cholesterol, potassium, aldosterone, protein, albumin, phosphorus, BUN, and in urine potassium. The findings indicate that results must be interpreted with caution from studies in which the baseline for measuring metabolic variables is established by feeding subjects a standardized diet that differed markedly from their regular, self-selected diets.

Effects of sugars on indices of glucose tolerance in humans.

Ten men and nine women were studied to determine whether replacement of utilizable complex carbohydrate by sugars (mono- and disaccharides) in a high-fiber, low-saturated fat diet would affect indices of glucose tolerance. Diets differed in that the 50% of calories derived from carbohydrate was either 35% complex and 15% sugars (low-sugar) on 15% complex and 35% sugars (high-sugar). Summation of glucose responses 30-180 min following an oral glucose tolerance test was significantly higher in men, but not women, after they consumed the high-sugar diet. Corresponding insulin responses were significantly higher in men consuming the high-sugar compared to the low-sugar diet. Insulin binding was significantly lower during the base line period and after the high-sugar diet compared to the low-sugar diet. Results indicate that sugars adversely affect indices of glucose tolerance when they replace complex carbohydrates even in a high-fiber, low-saturated fat diet.

Modification of the United States' diet to effect changes in blood lipids and lipoprotein distribution.

Twenty men, 19 premenopausal and 14 postmenopausal women consumed a diet for 13 weeks that supplied 35% of the calories from fat, 50% from carbohydrate, and 15% from protein. The diet was low in cholesterol, saturated fat, and salt, and high in complex carbohydrate and fiber. The 7-day menu was composed of common well-accepted foods prepared in a simple attractive manner. Plasma total cholesterol, LDL cholesterol, and VLDL cholesterol were reduced, but triglyceride levels were not different than after self-selected diets. When 20% of the complex carbohydrate was replaced by simple carbohydrate and other diet components remained optimal, triglyceride and VLDL cholesterol levels increased in men and premenopausal women and total cholesterol increased in premenopausal women. These results suggest that beneficial effects on the blood lipids and lipoprotein distribution of men and women may be obtained by minimal modification of a typical U.S. diet.