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PubMed1990

Dietary restriction alone and in combination with oral ethoxyquin/2-mercaptoethylamine in mice.

To investigate effects of dietary caloric restriction (DR) combined with antioxidant feeding, long-lived hybrid mice were divided into four dietary groups at weaning, and followed until natural death. Groups "C" and "R" received control (97 kcal/wk) and restricted (56 kcal/wk) diets respectively. Groups "C+ alpha ox" and "R+ alpha ox" received C or R diets supplemented with an antioxidant mixture (2-mercaptoethylamine plus ethoxyquin). R mice (mean life span 41 months) significantly outlived the other three groups (mean life span 30-34 months). Hepatic degeneration and increased hepatoma in the R+ alpha ox group suggested unusual hepatotoxicity of this regimen. Antioxidants had little effect on splenic cell mitogen response in similarly fed mice sacrificed at 12-15 months. Gompertz analysis suggests that the beneficial effect of DR may be due to reductions in initial vulnerability or rate-of-aging parameters, or both, and that the relative influence of each factor may vary with animal strain and DR protocol used.

Animals↗

PubMed2004

Antiangiogenic and proapoptotic effects of dietary restriction on experimental mouse and human brain tumors.

PURPOSE: The antiangiogenic and proapoptotic mechanisms of dietary caloric restriction (DR) are unknown. In this study, we evaluated the effects of moderate (40%) DR on the orthotopic growth of mouse and human brain tumors that differ in cell origin, angiogenicity, host environment, and biochemical composition. EXPERIMENTAL DESIGN: A malignant mouse astrocytoma (CT-2A) and a human glioma (U87-MG) were highly angiogenic and fast growing, whereas a mouse ependymoblastoma was less vascularized and slower growing. The tumors were evaluated for growth, cell proliferation, microvessel density, and apoptosis under DR and ad libitum feeding. Serum vascular endothelial growth factor and insulin-like growth factor I levels were examined as angiogenic biomarkers. RESULTS: DR significantly decreased vascularity (factor VIII) and increased apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling) in all tumors. These effects were associated with enhanced caspase-3 and poly(ADP-ribose) polymerase cleavage in the CT-2A and ependymoblastoma tumors, but not in the U87-MG tumor. DR also caused reductions of serum insulin-like growth factor I and glucose levels. CONCLUSIONS: DR had significant antiangiogenic and proapoptotic effects in the three distinct brain tumor models. DR, however, had differential effects on cell proliferation, biomarkers of angiogenesis, and apoptosis, suggesting multiple mechanisms of action. Because extensive angiogenesis and resistance to apoptosis are hallmarks of gliomas, this study provides new insight into the molecular basis of the DR-induced inhibition of brain tumor growth.

Animals↗

PubMed1988

Effect of diet restriction on glucose metabolism and insulin responsiveness in aging rats.

The effect of age and of prolonged caloric restriction on glucose tolerance and insulin responsiveness has been studied in male Fischer 344 rats. Beginning at 1 month of age dietary intake of an experimental group (R) was limited to 60% of that of the control group (AL) which was allowed to eat ad libitum. Studies were carried out at intervals up to 24 months of age. In AL rats the oral glucose tolerance curve showed progressively higher peak levels of plasma glucose with age, and a decrease in the plasma insulin concentration at the time of the glucose peak. The R group did not show the increase in peak value with age and the corresponding insulin concentration was lower than that of the AL group. These results are compatible with a delay in the first phase of insulin secretion in aging AL rats. Insulin-stimulated glucose disposal was assessed by the method of Reaven et al. [Diabetes, 32 (1983) 175], at ages 4, 12, 18 and 24 months; using infusions of 2 mU of insulin and 1 mg of glucose/min per kg, the steady-state plasma glucose level (SSPG) was slightly lower in R than in AL rats, while the steady-state plasma insulin level was reduced by 40-60%. In rats aged 18-24 months the hepatic glucose output, measured with [3-3H]glucose, was the same for AL and R rats in the basal state and was reduced to the same extent by insulin. In the presence of epinephrine and propranolol, infusion of glucose and insulin at various rates demonstrated that the plasma glucose clearance rate increased linearly with increasing SSPI, and at comparable SSPI levels was lower in R than in AL rats. The ability of insulin to stimulate glycogenesis from glucose was measured in primary hepatocyte cultures. Insulin increased glycogenesis 3-fold in cells from AL rats and 4-6-fold in cells from R rats. There was no effect of age. The increased insulin responsiveness of R rats was not due to an increase in insulin binding or to a decrease in insulin degradation (measured with intact cells or as cytosolic insulinase activity).(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1998

Canadian Bardet-Biedl syndrome family reduces the critical region of BBS3 (3p) and presents with a variable phenotype.

There are at least five distinct Bardet-Biedl syndrome (BBS) loci, four of which have been mapped: 11q (BBS1), 16q (BBS2), 3p (BBS3), and 15q (BBS4). A comparative study of the three Arab-Bedouin kindreds used to map the BBS2, BBS3, and BBS4 loci suggests that the variability in the number and severity of clinical manifestations, particularly the pattern of polydactyly, reflects chromosome-specific subtypes of BBS [Carmi et al., 1995a; Am J Med Genet 59:199-203]. We describe a Newfoundland kindred of northern European descent and confirm the initial finding of a BBS locus on chromosome 3. However, the "BBS3 phenotype," which includes polydactyly of all four limbs and a progression to morbid obesity, was not observed. Rather, four of the five BBS patients in this family had polydactyly restricted to their feet. The obesity in these patients was reversible with caloric restriction and/or exercise. Mental retardation has been considered a major symptom of BBS. However, formal IQ testing shows that these patients are of average intelligence. Haplotype analysis reduces the BBS3 critical region to a 6-cM interval between D3S1595-D3S1753.

Adult↗

PubMed1982

Effects of slimming and composition of diets on VO2 and thyroid hormones in healthy subjects.

Oxygen consumption and plasma thyroid hormone concentrations are modified by both low- and high-calorie diets. It has been suggested that the trigger may be changes in weight ("adipostatic" hypothesis involving the difference between the actual weight and the "set point") or changes in amount of carbohydrate in the diet ("carbohydrate" hypothesis). Two experiments were performed in order to test both hypotheses. Fourteen young healthy volunteers were studied: 1) at their spontaneous stable weight; 2) while losing weight rapidly on a calorically restricted diet; 3) and then at their stable new weight when consuming a refeeding diet. The calorie restricted diet resulted in decrease of VO2, and T3, and an increase of rT3; the refeeding diet resulted in values of VO2, T3, and rT3 intermediate between those of the spontaneous diet and those of the restricted diet. Another group of nine subjects were studied at their spontaneous caloric and proteic levels, comparing a diet containing only protein and carbohydrate with a diet containing only protein and fat. During the low carbohydrate diet rT3 increased and T3 decreased but they remained unchanged during the carbohydrate-rich diet. Thus neither the adipostatic hypothesis nor the carbohydrate hypothesis is sufficient alone to explain the observed changes in serum T3 and rT3.

Adolescent↗

PubMed2005

Neuronal protection by sirtuins in Alzheimer's disease.

Silent information regulator 2, a member of NAD+-dependent histone deacetylase in yeast, and its homologs in mice and humans, participate in numerous important cell functions, including cell protection and cell cycle regulation. The sirtuin family members are highly conserved evolutionarily, and are predicted to have a role in cell survival. The science of sirtuins is an emerging field and is expected to contribute significantly to the role of sirtuins in healthy aging in humans. The role of sirtuins in neuronal protection has been studied in lower organisms, such as yeast, worms, flies and rodents. Both yeast Sir2 and mammalian sirtuin proteins are up-regulated under calorie-restricted and resveratrol treatments. Increased sirtuin expression protects cells from various insults. Caloric restriction and antioxidant treatments have shown useful effects in mouse models of aging and Alzheimer's disease (AD) and in limited human AD clinical trials. The role sirtuins may play in modifying and protecting neurons in patients with neurodegenerative diseases is still unknown. However, a recent report of Huntington's disease revealed that Sirtuin protects neurons in a Huntington's disease mouse model, suggesting that sirtuins may protect neurons in patients with neurodegenerative diseases, such as AD. In this review, we discuss the possible mechanisms of sirtuins involved in neuronal protection and the potential therapeutic value of sirtuins in healthy aging and AD.

Aging↗

PubMed1984

Cardiac dysfunction in obese dieters: a potentially lethal complication of rapid, massive weight loss.

During 1977 and 1978, 17 obese but otherwise healthy adult Americans died suddenly of ventricular arrhythmias during or shortly after completing rapid, massive weight reduction induced by very low-calorie diets consisting largely of collagen hydrolysates for 2 to 8 months. A reexamination of the data on these victims has disclosed a significant positive correlation (r = 0.824) between their prediet body mass index and their duration of survival on the very low-calorie diets. Since body mass index reflects degree of fatness, this observation indicates that the ability to defer the lethal effects of severe caloric restriction was a function of the proportion of body fat before dieting. During caloric reduction, the ratio of nitrogen loss to weight loss is inversely related to body fat content; accordingly, we suggest that the fattest dieters survived the longest because they were better able to conserve body (and myocardial) protein. Also, obese people have an enlarged lean body mass which may afford additional protection.

Adult↗

PubMedDate not supplied

Dietary control of hyperlipoproteinemia.

A prospective study of the effect of dietary control of hyperlipoproteinemia (HLP) was carried out in 1,800 adult out-patients. The patients with type II A were treated with a diet low in saturated fat and cholesterol, with substitution of polyunsaturated fat. Additional carbohydrate and alcohol restriction was applied to patients with types II B, III and IV HLP. Caloric restriction was prescribed for overweighted patients. These diets were followed by sequences of stabilizing diets which were modified quarterly. After 7 years the best results were obtained for type IV (50%) followed by II B (22%). The nutritional HLP treatment, in keeping with the metabolic dependence, corrected HLP to one third of the initial sample, without improving the objective cardiovascular disturbances.

Adult↗

PubMed2001

Calorie restriction enhances the expression of key metabolic enzymes associated with protein renewal during aging.

Our studies show that dietary caloric restriction (CR) alters the expression of key metabolic enzymes in a manner consistent with an increased rate of extrahepatic protein turnover and renewal during aging. Of the key hepatic gluconeogenic enzyme genes affected by CR, glucose 6-phosphatase mRNA increased 1.7- and 2.3-fold in young and old CR mice. Phosphoenolpyruvate carboxykinase mRNA increased 2-fold in young mice, and its mRNA and activity increased 2.5- and 1.7-fold in old mice. These changes indicate that CR enhances the enzymatic capacity for gluconeogenesis. The carbon required for gluconeogenesis appears to be generated from peripheral protein turnover. Muscle glutamine synthetase mRNA increased 1.3- and 2.1-fold in young and old CR mice, suggesting increased disposal of nitrogen and carbon derived from protein catabolism for energy. mRNA for the key liver nitrogen disposal enzymes glutaminase, carbamyl phosphate synthase I, and tyrosine aminotransferase were increased by 2.4-, 1.8-, and 1.8-fold in CR mice. Consistent with increased hepatic nitrogen disposal, hepatic glutamine synthetase mRNA and activity were each decreased about 40% in CR mice. Together, these and our other published data suggest that CR enhances and maintains protein turnover, and thus protein renewal, into old age. These effects are likely to resist the well-documented decline in whole body protein renewal with age. Enhanced renewal may reduce the level of damaged and toxic proteins that accumulate during aging, contributing to the extension of life span by CR.

Aging↗

PubMed1993

Effect of meal pattern during food restriction on body weight loss and recovery after refeeding.

The present study was designed to assess whether the pattern of meal feeding and the degree of caloric restriction have an effect on the body weights and refeeding patterns of restricted 4-month-old Long-Evans rats, relative to ad lib-fed controls. Four experimental groups of rats (n = 6 each) were put on different paradigms of food restriction, and a fifth group fed ad lib throughout served as controls. Twelve rats were restricted to receiving 50% of their mean baseline food intake, and 12 rats received only 70% of their baseline food intake. Each experimental group was further subdivided with one subgroup receiving all of their calories in one meal/day and the other with caloric intake equally divided into two meals/day. There was no statistical difference in the final body weights of the restricted groups. Although there appeared to be identical patterns of weight regain, none of the restricted groups ever reached the mean body weight of the controls because of an asymptotic leveling off of rate of body weight regain. Rats that had received 50% of baseline calories as two meals/day had significantly more adipose mass than did any other group. The present findings suggest that in the rat, refeeding and, hence, regulation, occurs to normalize rate of weight gain rather than absolute body weight.

Animals↗

PubMed1992

Nutritional status seven years after Roux-en-Y gastric bypass surgery.

BACKGROUND: Nutritional deficiencies in patients after Roux-en-Y gastric bypass operations have been mainly attributed to dietary restriction. However, most of these studies have been performed during the period of greatest caloric restriction. METHODS: Two hundred patients who were morbidly obese were followed for 6 to 8 years (mean, 6.7 years) after Roux-en-Y gastric bypass surgery. Each underwent a thorough physical examination and behavioral and nutritional assessments, including hemoglobin, red blood cell indices, serum iron content, iron binding capacity, and serum vitamin B12 and folic acid concentrations. RESULTS: Data obtained from blood tests disclosed a significant gradual decrease of the mean serum hemoglobin (p less than or equal to 0.0000), mean corpuscular volume (p less than 0.001), and iron saturation (p less than or equal to 0.0000). Mean vitamin B12 concentration improved during the last 3 years of follow-up. The mean values of iron saturation and vitamin B12 were not correlated with the patients' weight loss. Meat intolerance was observed in 51%, 60.3%, 59.5%, and 55.1% of the patients during the 0 to 12 months, 13 to 24 months, 25 to 72 months, and 73 to 96 months after surgery, respectively. A significant correlation was found between the eating habits and the laboratory values. The mean serum iron saturation, vitamin B12, and folic acid were significantly higher in patients who eat meat than in patients who do not eat meat (piron less than 0.0046, pB12 less than 0.0052, folate less than 0.01). In addition, oral vitamin and mineral supplements significantly improved the nutritional status of the patients. The patients had no caloric malnutrition or protein deficiency. CONCLUSIONS: Roux-en-Y gastric bypass induces long-term changes in eating habits, independent of caloric intake. Iron continuously declines 6 to 8 years after surgery, depending (significantly) on the eating behavior, but not on the caloric intake.

Anastomosis, Roux-en-Y↗

PubMed1994

Recorded food intake of obese women with binge eating disorder before and after weight loss.

Because binge eating in obese individuals has been postulated to be a reaction to dietary restriction, we examined the recorded food intake of 17 obese women with and 16 obese women without binge eating disorder (BED) during 1-week periods before and 3 months after a very low calorie diet program in order to determine the effects of dietary restriction on binge eating frequency and severity. Before weight loss, rather than reporting severe caloric restriction, women with BED reported greater average energy intake than nonbinge eaters on both a total (2707 vs. 1869 k cal/day, p < .01) and weight-adjusted (25.1 vs. 18.1 kcal/kg, p < .01) basis, with both higher intake on nonbinge days and an increased frequency of binge days. After weight loss, there was no significant difference in energy intake, on either a total or weight-adjusted basis, between subjects with and without BED. Although average daily energy intake fell for both groups after weight loss, only subjects with BED reported significantly decreased energy intake when adjusted for change in body weight. This resulted from decreased intake on nonbinge days and a decreased frequency of binge days. Before weight loss, subjects with BED reported an average energy intake equivalent to 94% of their predicted energy expenditure. Whereas subjects without BED reported intake only 64% of predicted (p = .002). After weight loss, there was no significant difference between subjects with and without BED in the percentage of predicted energy expenditure reported as intake (64% vs. 58%). Restraint was similar in both groups before weight loss, but those with BED reported greater hunger and disinhibition. After weight loss treatment, restraint increased significantly, whereas disinhibition and hunger remained elevated in subjects with BED. Disinhibition, rather than restraint, appears to be a major contributor to the disordered eating of these individuals. Unlike normal-weight women with bulimia nervosa, dietary restriction does not appear to worsen symptoms of binge eating in obese women with BED. Over the short term, subjects with BED may respond to a standard weight loss treatment program with improvements in binge eating behaviors.

Adolescent↗

PubMed1995

Effect of diet on lung structure, connective tissue metabolism and gene expression.

Nutritional impairment can adversely affect the respiratory system. The structure of the lung is altered by severe calorie-protein restriction in rodents producing an emphysema-like lesion after several weeks of severe caloric restriction. Biochemical and morphological evidence suggests destruction of collagen and elastin in nutritional emphysema. Impaired lung growth may explain the biochemical changes in growing animals. Although the molecular basis of nutritional emphysema is not known, altered gene expression by nutrients affects several metabolic pathways, and examples of the effects of nutrients on gene expression are given. Nutritional emphysema in animals may be relevant to humans because malnutrition may accelerate the progression of the disease in patients with advanced emphysema.

Animals↗

PubMed1990

[Diet treatment of the diabetic patient: yesterday and today. What has changed? What can be learned from it?].

The initial treatment in the past of diabetes was one "of trial and error" as easily understandable. Carbohydrate restriction and their replacement by fats was followed, happily, last century already, by global caloric restriction. Around the fourties, after the introduction of insulin in 1922, the principle of the carbohydrate tolerance was introduced as an objective+ measure, followed by the proposal of "bread equivalencies" in the dietetic practice, assuring in this manner a figured evaluation. Around the seventies years the diet fiber came into its own and seemed very important for the evolution of the postprandial glycemia and insulinemia. Next to this, complex polysaccharides looked also of prime impact on this two biochemical parameters. The nature of this complex character is due to their liaison with other diet components (lectins, phytins, tannins etc.). So the concept of the glycemic index was born which explains why next to the presence of a given carbohydrate quantity the evolution of the glycemia is different from what is expected, just because the absorption is accelerated or retarded by the structure or the manipulation of these polysaccharides. This novel data are so much the more important because actually the hyperglycemia on the long run seems so important for the development of micro-angiopathy, at the base of the famous diabetic triad (nephropathy, retinopathy, neuropathy). The hyperlipemia is also beneficially influenced by the diet fiber and at the same level by the complex polysaccharides. All this statements are at the base of novel ways for the dietetic treatment of diabetes, as well on the quantitative as on the qualitative level and equally so for the diabetes of type I as of type II.

Blood Glucose↗

PubMed1990

[Lipid-lowering therapy in the prevention of coronary heart disease].

Reasons for the current emphasis on cholesterol as coronary risk factor are multiple. On one hand current studies have shown that primary as well as secondary prevention of ischemic heart disease is a realistic possibility with lipid lowering measures. On the other hand new drugs are actually available which permit a potent and adapted therapy of hyperlipidemias. According to new guidelines of the Swiss "lipid task force" screening for hypercholesterolemia is recommended. A cholesterol value greater than 6.5 mmol/l should be investigated and treated. Because a great proportion of adult Swiss fall into this category (approximately 1/3) it is essential that all those are efficiently treated that have markedly abnormal cholesterol values or present with other risk factors such as smoking and hypertension or have a personal or familiar history of ischemic heart disease. Because progression is likely in patients with or after manifest ischemic heart disease even when hypercholesterolemia is mild (over 5.2 mmol/l) all patients presenting with an infarct should be investigated for dyslipidemia. Cholesterol, triglycerides and HDL should be determined. Dietary measures are the basis of every attempt to reduce hyperlipidemia. Most importantly intake of saturated fats prevailing in animal products should be restricted. The next important step is reduction of dietary cholesterol and in obese patients also caloric restriction. Lipid lowering agents are recommended in patients at risk who do not respond to or comply with dietary regimens. According to type of dyslipidemia bile-acid-binding resins, fibrates, nicotinic acid or HMG-CoA reductase inhibitors are available.

Anticholesteremic Agents↗

PubMed1982

The medical syndrome of obesity.

Obesity is one of the most common medical disorders and perhaps the least responsive to usual medical therapeutic approaches. The syndrome is often defined as greater than 20 per cent above ideal body weight for height; however, vagaries in establishing this relationship result in significant differences in estimates of its incidence. The effects of obesity on health are broad indeed and include many disorders, hypertension being the most consistently associated and potentially most lethal. Despite this significance, the medical practitioner's ability to treat obesity is severely restricted by inadequate training in nutrition, the nearly complete failure of the usually prescribed caloric-restricted diet, and most importantly, the inappropriateness of the mode generally used in medical practice to address the complex interactions between diet, exercise, and behavior that are manifest in obesity. Failure on behalf of the medical community to address the problem has resulted in a commercial industry that consumes billions of dollars annually. Highly ethical, medically based alternatives to these commercial interests do not exist. Perhaps what is needed is the establishment of medical facilities that will provide practicing physicians, dietitians, nurses, and other health professionals with the capacity to bring to bear optimal dietetic intervention, exercise conditioning, and modifications of eating and exercise behavior as therapy for this complex medical disorder.

Adipose Tissue↗

PubMed2004

The impact of energy restriction and exercise in lactating women.

Exercise improves cardiovascular fitness, plasma lipids, and insulin response in lactating women. However, exercise alone, without caloric restriction, does not promote weight loss. Once lactation is established, over-weight women may restrict their energy intake by 500 kcal/day to promote a weight loss of 0.5 kg/week without affecting the growth of their infants. Moderate exercise does not affect maternal immune status or levels of sIgA, lactoferrin, and lysozyme in human milk. Further research is needed to determine the effect of exercise and energy restriction on maternal bone health and immune status and composition of human milk.

Adult↗

PubMed1996

Exercise and weight control in sedentary overweight men: effects on clinic and ambulatory blood pressure.

OBJECTIVE: To examine whether restriction of caloric intake and exercise of vigorous intensity can independently and additively influence clinic and ambulatory blood pressures in sedentary overweight men. DESIGN: Sixty subjects aged 20-50 years were randomly allocated either to continue their normal caloric intake or to restrict it by 4186-6279 kl/day, with 15% provided by protein, 30% by fat and 55% by carbohydrate, for 16 weeks. Within each of these groups subjects were further randomly allocated either to a control light intensity programme of exercise or to a vigorous intensity programme of exercise for 30 min three times a week. The light exercise group performed stationary cycling against no resistance, flexibility exercises and slow walking. The vigorous intensity group cycled on an ergometer at 60-70% of maximum their workload. RESULTS: Fifty-one subjects completed the study. Their maximal oxygen uptake was increased by approximately 24% with vigorous exercise but did not change with light exercise. Caloric intake restriction led to a significant loss of body mass of 9.5 kg (95% confidence interval 7.6-11.3), whereas vigorous exercise had no effect. Restriction of caloric intake reduced supine clinic systolic and diastolic blood pressures significantly by 5.6 (2.3-8.9) and 2.4 mmHg (0.4-4.2), respectively. Relative to the control light exercise group, exercise of vigorous intensity exercise had no significant effect on clinic blood pressure. In contrast, time series analysis revealed that both caloric intake restriction and vigorous exercise were associated with lower daytime ambulatory systolic blood pressure, the reduction in systolic blood pressure being sustained throughout the 24 h period when vigorous exercise and caloric intake restriction were combined. CONCLUSION: Compared with the effects of caloric intake restriction, the effects of a vigorous exercise programme on blood pressure are inconsistent, there being no influence on clinic blood pressure but a reduction in daytime ambulatory blood pressure. However, when combined with caloric intake restriction, regular vigorous exercise exhibits a synergistic effect in reducing ambulatory blood pressure throughout a 24 h period.

Adult↗