Weight loss, dietary carbohydrate modifications, and high intensity, physical performance.

Well trained subjects (N = 12) were studied before and after losing approximately 6% of body weight to determine whether physical performance could be maintained while consuming a hypocaloric, high percentage carbohydrate diet. During a 4-d period of weight loss, subjects were randomly assigned to a high carbohydrate (HC) or low carbohydrate (LC) diet. A crossover design was used; subjects were measured before (PRE) and after (POST) weight loss on both diets for a 6-min bout of high intensity arm cranking, weight, skinfold thickness, and profile of mood states (POMS). Hemoglobin, hematocrit, and glycerol concentrations were analyzed for resting blood samples, while lactate, pH, and base excess were analyzed for blood samples drawn at rest and 1, 3, and 5 min after arm cranking. A three-way ANOVA of sprint work revealed a weight loss effect, a diet by weight loss interaction, and an order by diet by weight loss interaction (P less than 0.05). Total sprint work (mean +/- SE) PRE and POST HC was 37.7 +/- 2.1 kJ and 37.4 +/- 2.2 kJ, respectively. Sprint work was higher for PRE LC vs POST LC, with mean values of 37.4 +/- 2.1 kJ and 34.4 +/- 2.2 kJ, respectively. Post-arm cranking lactate was significantly higher PRE compared to POST for both HC and LC. Post-exercise blood pH was lower (P less than 0.05) at PRE vs POST, with no diet effect. Regardless of the diet, POMS variables tension, depression, anger, fatigue, and confusion were significantly elevated from PRE to POST; vigor was significantly lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional factors in cataract.

Age-related cataract is a condition characterized by multiple mechanisms and multiple risk factors. The mechanisms that bring about a loss in transparency include oxidation, osmotic stress, and chemical adduct formation. Risk factors for cataract include diabetes, radiation (ultraviolet B, x-ray), certain pharmaceutical substances, certain nutritional states, and possibly acute episodes of dehydration. Interaction occurs between and among mechanistic factors and risk factors. Thus nutrition must be considered as one part of a tapestry of intertwined events and responses. Certain experimental models for nutritional cataract have been useful for study of the cataractogenic process but are probably not important factors in the human disease. Little current evidence supports significant roles in human senile cataract for imbalances of tryptophan or other amino acids, deficiencies of calcium or selenium, or excessive intake of selenium. Overconsumption of galactose is likely to be hazardous only in subjects with genetic inability to metabolize this sugar. Vitamins with antioxidant potential (riboflavin, vitamin E, vitamin C, carotenoids) deserve further research scrutiny to ascertain their significance in cataract etiology. Excessive caloric intake needs to receive added emphasis as a factor contributing to cataract. Diabetes increases the likelihood of cataract three- to four-fold. Obesity, defined as more than 20% overweight, is considered a major risk factor for non-insulin-dependent, or type II, diabetes (69, 73). Weight control can be recommended as a prudent, safe, economic, and effective means of lowering risk probability for diabetes and the associated complication of cataract.

Adaptation of the exocrine pancreas to diet.

Pancreatic adaptation represents dietary regulation of gene expression; dietary substrates alter the synthesis and mRNA levels of their respective digestive enzymes. The mechanisms whereby mRNA levels change are not understood, but they must be elucidated. Although the changes in synthesis of proteases, amylase, and lipase parallel the changes in their mRNA levels in response to respective substrates, the concomitant changes in the synthesis of the other enzymes can be discordant with mRNA levels. The evidence supports a pretranslational mechanism of the adaptation of proteases, amylase, and lipase to their respective substrates and suggests potential translational mechanisms of other enzymes in these adaptations. Changes in synthesis occur within hours after a dietary change, but whether mRNA levels also change so early is unknown. Rapid, adaptive changes may occur by a different mechanism from later adaptation, possibly by translational control or nuclear transport. The differential effects of acute and chronic caerulein administration support the possibility of multiple mechanisms of regulation by a single effector. The mediators of pancreatic adaptations have not yet been identified, except for adaptation to dietary protein. CCK appears to mediate protease adaptation through the feedback regulation of its release by dietary protein. Available evidence supports a role of insulin and glucose in the adaptation to carbohydrate and a role of secretin and ketones in the adaptation to dietary fat. Elucidation of the mediators of pancreatic adaptation to carbohydrate and fat and their mechanisms is needed.

Protein and carbohydrate selection respond to changes in dietary saturated fatty acids but not to changes in essential fatty acids.

We previously reported differences in protein and carbohydrate selection patterns in post-weanling rats fed beef tallow or soybean oil-based diets. Two experiments were designed to determine the characteristic of the dietary fat which mediates the selection behavior. For each experiment, dietary fat was 20% (w/w) of diets and fatty acid profiles were obtained by blending fat sources. Rats were randomly assigned to diets (24% protein, 40% carbohydrate) which varied only in fatty acid composition. After 2 weeks, rats selected from 2 diets with the fat composition previously fed, but varying in their protein and carbohydrate composition (55% protein, 4% carbohydrate and 5% protein, 61% carbohydrate). Experiment 1 was designed to test the effect of relative (omega 6: omega 3 ratios of 1 and 20) and absolute (15% or 4% omega 6, 0.7% or 0.2% omega 3) differences in essential fatty acids on macronutrient selection patterns. Differences in dietary essential fatty acids had no effect on energy intake or the proportion of energy consumed as protein and carbohydrate. Experiment 2 examined the effect of differences in the level of saturated fat (3-10% diet (w/w] on protein and carbohydrate selection. Animals selecting from diets with higher levels of saturated fat consumed more energy as protein and less as carbohydrate than rats selecting from diets with lower levels of saturated fat (p less than 0.0001). Regression analysis was used to examine the relationship between percent protein or carbohydrate energy and classes of dietary fat. The strongest relationship existed between percent dietary saturated fat and percent protein or carbohydrate energy (p less than 0.0001). Polyunsaturated:saturated fat ratio was also weakly associated with percent protein and carbohydrate energy (p less than 0.05). Polyunsaturated, monounsaturated, omega 6 and omega 3 fatty acids were not significantly related to percent protein or carbohydrate energy. These results indicated that protein and carbohydrate selection patterns are altered in response to qualitatively different dietary fatty acids, and that the amount of saturated fat in the diet is the important characteristic of dietary fat mediating the behavioral alteration.

Dietary treatment of familial hypercholesterolemia.

The principal goal of dietary treatment of familial hypercholesterolemia (FH) is the reduction of the plasma low density lipoprotein (LDL) cholesterol. This is best accomplished by enhancing the number of LDL receptors and, at the same time, depressing liver synthesis of cholesterol. Both cholesterol and saturated fat down-regulate the LDL receptor and inhibit the removal of LDL from the plasma by the liver. Saturated fat down-regulates the LDL receptor, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is also important. The greater the flux of chylomicron remnants into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect LDL synthesis could be important. These include excessive calories (obesity) that enhance very low density lipoprotein (VLDL) and, hence, LDL synthesis, and weight loss and omega-3 fatty acids, which depress synthesis of VLDL and LDL. The optimal diet for treatment of children and adults has the following characteristics: cholesterol (100 mg/day), total fat (20% of kcalories, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% kcalories, two thirds from starch), and protein (15% kcalories). This low-fat high-carbohydrate diet can lower the plasma cholesterol 18% to 21%. It is also an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Dietary therapy is the mainstay of treatment of FH to which various drug therapies can be added.

Transcriptional and posttranscriptional regulation of malic enzyme synthesis by insulin and triiodothyronine.

To investigate the transcriptional and posttranscriptional regulation of malate dehydrogenase (EC 1.1.1.40) induction by insulin, the transcriptional rate, mRNA concentration and enzyme induction of malic enzyme were compared in livers of normal and diabetic rats fed a high-carbohydrate diet. When rats were fed the diet for 4 days, the enzyme induction and mRNA concentration in livers of diabetic rats were only about 10% and 39%, respectively, of the values of normal rats, and the transcriptional rate was about 64%. Insulin treatment restored the transcriptional rate and mRNA concentration in 8 h and the enzyme induction in 4 days. Thus, it is suggested that insulin is involved in malic enzyme transcription of the gene and also possibly in the translation of the cytoplasm. On the other hand, by giving triiodothyronine treatment, the transcriptional rate and mRNA concentration were increased about twice and the enzyme induction, about 10-times in the diabetic animals. Triiodothyronine appears to stimulate malic enzyme transcription and possibly post-transcriptional steps even at a very low insulin level.

Behavioral and metabolic effects of sucrose-supplemented feeding in hyperactive rats.

Two hyperactive rat strains [spontaneously hypertensive rats (SHR) and SHR-Wistar-Kyoto cross (WK-HA)] and their nonhyperactive genetic control strain (Wistar-Kyoto) were fed ad libitum sucrose-supplemented rat chow, or chow alone in controls, to determine the effects of dietary sugar on behavior. The diets were given either overnight (acute sugar) or for 14-18 days (chronic sugar), and testing was carried out on the morning after each of the dietary schedules. The metabolic studies revealed significant strain, sex, and age differences in appetite for sucrose, caloric intake, postprandial plasma levels of glucose and insulin, and weight gain after sucrose feeding. The findings indicate that sugar feeding led to increased plasma glucose and insulin levels; however, total caloric intake was decreased, and less weight gain was observed than in chow-fed controls, particularly among the hyperactive strains. In behavioral tests, sugar feeding did not alter spontaneous activity levels in any of the strains after either acute or chronic diets. There were also no significant effects of sucrose consumption on spatial learning and memory in a plus-shaped maze as determined by use of a shock-avoidance paradigm. The only significant behavioral effects of sucrose observed were an impairment in habituation and distractibility among the WK-HA females, the most hyperactive group among these strains.

Comparison of different dietary sugars as inducers of intestinal sugar transporters.

Intestinal sugar transport increases with dietary carbohydrate levels, but the specific regulatory signals involved have been little studied. Hence we compared rations containing one of five sugars [D-glucose, D-galactose, 3-O-methyl-D-glucose (3-O-MG), D-fructose, and maltose] in their effects on brush-border uptake of five transported solutes (D-glucose, D-galactose, 3-O-MG, D-fructose, and L-proline) by everted sleeves of mouse small intestine. As confirmed by transepithelial potential difference (PD) measurements, there is a distinct fructose transporter that does not evoke a PD, along with one or more aldohexose transporters that do evoke a PD. Galactose and 3-O-MG rations cause a twofold increase in feeding rates, mucosal hyperplasia, and hence nonspecific increases in uptake per unit length of intestine for all transported solutes. Dietary fructose is by far the best specific inducer of the fructose transporter. The five dietary sugars are of fairly similar potency as specific inducers of aldohexose transport, but dietary galactose and fructose may be slightly more potent than glucose. Regulatory signals need not be transported substrates, or vice versa, and need not be metabolizable. Variation in uptake ratios of pairs of aldohexoses with ration and intestinal position suggest multiple aldohexose transporters of overlapping specificity, with different relative activities at different positions and with different susceptibilities to induction by different dietary sugars.

Effect of thyroid hormones and high carbohydrate feeding on gene expression in rat epididymal adipose tissue.

We have determined the messenger RNA activity profiles of epididymal fat in euthyroid, hypothyroid, and hyperthyroid rats as well as in animals fed a high carbohydrate fat-free (lipogenic) diet. Radioautographs of two-dimensional gels of the in vitro translational products of RNA were quantitated by computer-assisted videodensitometry and analyzed by multivariate statistics. Of the 250 spots observed, each presumably representing the translational product of a separate messenger RNA, 21 were responsive to changes in hormonal state. Eighteen increased and two decreased at some stage in the transition from the hypothyroid to the hyperthyroid state. One spot changed in a biphasic manner. Eight products responded to the lipogenic diet, six increasing and two decreasing. Six of these eight spots responded in a similar fashion to thyroid hormone administration. As previously shown for liver, there appears to be a substantial overlap between the genomic response to carbohydrate and thyroid hormone administration. Whereas the carbohydrate-generated changes are largely included in the thyroid-hormone induced alterations, the majority of thyroid hormone responsive changes are not duplicated by the diet. Multivariate analysis showed a clear separation of each state from the others and revealed that it was necessary to monitor only nine spots to achieve an effective separation of the states analyzed.

Tissue-specific control of rat malic enzyme activity and messenger RNA levels by a high carbohydrate diet.

In euthyroid rats fed a high carbohydrate fat-free diet for 10 days, the mass of cellular malic enzyme mRNA in liver is increased 7- to 8-fold above the basal level. Malic enzyme activity is stimulated to the same extent. This effect does not result from an increase either in the transcriptional activity of the malic enzyme gene, as determined by nuclear run-off transcription assay, or in the content of intranuclear malic enzyme RNA sequences. Mathematical modeling shows that this increase in cytoplasmic mRNA is compatible with retarded degradation of cytoplasmic mRNA. Regulation of malic enzyme by carbohydrates is liver-specific, since no response is observed in the following nonhepatic tissues: brain, heart, spleen, kidney, testis, and lung. Furthermore, the amplitude of the response in liver depends on the thyroid state of the animals, being lower (by a factor of approximately 4) in hypothyroidism and higher (12- to 15-fold) when normal animals are injected simultaneously with a daily dose of 15 micrograms of triiodothyronine per 100 g of body weight for 10 days. Since thyroid hormones regulate liver malic enzyme synthesis predominantly at the nuclear level and carbohydrates at the cytoplasmic level, the additive effect of triiodothyronine and a high carbohydrate diet on the activity of malic enzyme is readily explicable.

Diet, nutrition, and cancer.

Evidence pertaining to the role of dietary factors in carcinogenesis comes from both epidemiological studies and laboratory experiments. In 1982, the Committee on Diet, Nutrition, and Cancer of the National Research Council conducted a comprehensive evaluation of this evidence. That assessment as well as recent epidemiological and laboratory investigations suggest that a high fat diet is associated with increased susceptibility to cancer of different sites, particularly the breast and colon, and to a lesser extent, the prostate. Current data permit no definitive conclusions about other dietary macroconstituents including cholesterol, total caloric intake, protein, carbohydrates and total dietary fiber. Specific components of fiber, however, may have a protective effect against colon cancer. In epidemiological studies, frequent consumption of certain fruits and vegetables, especially citrus fruits and carotene-rich and cruciferous vegetables, is associated with a lower incidence of cancers at various sites. The specific components responsible for these effects are not clearly identified, although the epidemiological evidence appears to be most consistent for a protective effect of carotene on lung cancer and less so for vitamins A and C and various cancer sites. The laboratory evidence is most consistent for vitamin A deficiency and enhanced tumorigenesis, and for the ability of various nonnutritive components in cruciferous vegetables to block in-vivo carcinogenesis. The data for minerals and carcinogenesis are extremely limited, although preliminary evidence from both epidemiological and laboratory studies suggests that selenium may protect against overall cancer risk. Frequent consumption of cured, pickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer, however, the specific causative agents in these foods are not clearly identified. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, larynx, and respiratory tract. The mechanisms of action of dietary factors on carcinogenesis are poorly understood. The NRC committee, and more recently, the National Cancer Institute and the American Cancer Society have proposed interim dietary guidelines to lower the risk of cancer. These guidelines are consistent with general dietary recommendations proposed by U.S. government agencies for maintenance of good health.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of diets deficient in glucose and glucose precursors on the growth of the Walker carcinosarcoma 256 in rats.

The effects of carbohydrate-deficient diets on the growth of the Walker carcinosarcoma 256 in rats and on the carcinostatic action of the glucose analogue 2-deoxyglucose were studied. All diets contained 13.0% casein with glucose levels as indicated and the balance of calories present as corn oil free fatty acids. The growth of the tumor was directly related to the glucose level in such diets; after 16 days rats fed 0.0, 1.5 and 4.5% glucose had tumors weighing 7.0, 11.1 and 13.3 g, respectively. The decrease in tumor weight was related to dietary glucose level rather than the anorexia produced by the diets low in glucose, as shown by the fact that tumors in rats fed 4.5% glucose were larger than rats fed 1.5% glucose even when the rats fed 4.5% glucose were pair-fed to the levels consumed by those fed 1.5% glucose. 2-Deoxyglucose (0.2%) also caused a reduction in tumor growth in a manner independent from the anorexia produced by its presence in the diet. This carcinostatic effect was potentiated by low glucose levels in the diets in the rats fed 4.5% glucose plus 0.2% 2-deoxyglucose had proportionally greater reductions in tumor weights due to the glucose analogue than did rats fed 20% glucose plus 0.2% 2-deoxyglucose.

Regulation of amylase messenger RNA concentration in rat pancreas by food content.

Regulation of the expression of pancreatic amylase genes was studied by comparing groups of rats fed diets with high (75%), intermediate (20%) and low (11%) carbohydrate content. Animals on the high carbohydrate diet had nine times as much amylase mRNA as those on low carbohydrate diet, and twice as much as the intermediate group, as determined by filter hybridization of equal amounts of total pancreatic RNA to an excess of a cloned rat amylase cDNA probe. Parallel results were obtained when levels of translatable amylase RNA were compared by means of an RNA-dependent rabbit reticulocyte cell-free system. Amylase mRNA-directed synthesis represented 35% of the total in the high carbohydrate group, 4% in the low group and 14% in the intermediate group. Relative rates of amylase synthesis, determined 30 min after [3H]phenylalanine injection, followed the same pattern. While 37% of total was incorporated into amylase in the high carbohydrate group, only 8% was incorporated in the low carbohydrate group, as compared with 22% in the intermediate group. These data indicate that modifications of diet composition alter the expression of pancreatic amylase genes as a consequence of changing the level of their transcript, and that pancreatic amylase production is mostly regulated at the pre-translational level.

Effects of food deprivation on intake of solid and liquid sugars in the rat.

In free-feeding rats, glucose at 0.025 M or 2 M evokes a vigorous bout of drinking. Powdered sucrose evokes more feeding than would occur without it, but powdered glucose does not. Food deprivation has little effect on intake of 2 M glucose, but it markedly augments intake of the powders, which rises to caloric-intake values higher than that of the 2 M solution. This occurs even if the powders are offered only after solution intake has come to an end and at a time when it would remain inhibited. We conclude: 1. Some sweet-tasting commodities will evoke ingestive behavior in free-feeding rats, but others, some of them even sweeter, will not. 2. Solid carbohydrates follow different laws from concentrated carbohydrate solutions, in that the former, but not the latter, rise with deprivation. Intake of powders must therefore be limited or satiated by different and more permissive mechanisms from the ones that limit solution intake.

Reduction in oocyte number following prenatal exposure to a diet high in galactose.

When pregnant rats were fed a 50 percent galactose diet there was a striking reduction in oocyte number in the offspring. The most prominent effects were noted after exposure to galactose during the premeiotic stages of oogenesis. Prenatal exposure to galactose or its metabolites may contribute to the premature ovarian failure characteristic of human galactosemia.

Interrelationships between environmental temperature and nutritional status of chicks.

The interrelationship between nutritional status and resistance to acute heat stress has been studied in chicks. Fasting up to 72 hours progressively increases survival time. Chicks that had been consuming a diet in which all nonprotein calories were supplied as triglycerides as compared to glucose survive longer in both nonfasted and 48-hour fasted states. Phosphorus deficiency reduces survival time of 24- or 48-hour fasted chicks but not nonfasted chicks. A calcium deficiency enhances survival time of 24-hour fasted chicks subjected to heat stress but a calcium excess progressively reduces survival time. The chick may serve as a model to study the relationship of nutritional status to acute heat stress.