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Fasting-refeeding stimulates the development of mammary tumors induced by 7,12-dimethylbenz[a]anthracene.

The effect of fasting-refeeding during the promotion phase of dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis has been investigated. Female Sprague-Dawley rats were given 130 mg/kg of DMBA and divided into four groups: Group 1 was fed ad libitum; Group 2 was fed ad libitum and, in addition, received daily subcutaneous injections of beta-estradiol and haloperidol for eight days, beginning two weeks after DMBA administration; Group 3 was exposed to three days of fasting one week after carcinogen injection, then fed ad libitum until the end of the experiment; Group 4 was treated as Group 2, except the animals were fasted for three days beginning one week after DMBA administration. Treatment with beta-estradiol and haloperidol enhanced the development of DMBA-induced mammary tumors. Rats fasted after DMBA administration showed increased genesis and growth and reduced latency of mammary tumors. Fasting before beta-estradiol and haloperidol injection resulted in a more pronounced effect on tumor yield and latency than hormones or fasting alone. The data indicate that, in rats fasted during the promotion phase, tumor growth is enhanced and the permissive effects of hormones on mammary carcinogenesis are potentiated.

9,10-Dimethyl-1,2-benzanthracene↗

Neuropsychological impairment in anorexia nervosa: before and after refeeding.

Neuropsychological measures were administered to 18 patients with anorexia nervosa shortly after admission to hospital and again after substantial weight gain. These patients were compared with a group of 18 normal weight controls, also tested on two occasions, who were matched for age, sex, and estimated premorbid IQ. At low weight, impairment was evident on tests of attentional-perceptual-motor functions and on tests of visuospatial construction and problem-solving. Learning was less affected. Refeeding resulted in significant improvements in performance.

Adult↗

Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations in children with kwashiorkor in the acute stage and during refeeding.

Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations were measured in 22 children with kwashiorkor on admission to hospital and on days 5, 10 and 30 of refeeding. Twenty similarly aged, healthy, well nourished children served as controls. The mean (SEM) zinc, copper and selenium concentrations of 7.5 (0.93), 10.8 (0.64) and 0.29 (0.02) mumol/l, respectively, in the children with kwashiorkor on admission were all significantly lower than the values of 13.7 (0.66), 25.6 (1.72) and 0.72 (0.04) mumol/l in the controls. In contrast, the erythrocyte manganese level of 1.67 (0.09) micrograms/gHb and the median ferritin concentration of 293 micrograms/dl were significantly higher than in the controls. After 30 days there was full clinical recovery with significant weight gain and a return of the plasma albumin, caeruloplasmin, copper and ferritin to normal. However, manganese remained elevated and zinc and selenium concentrations remained significantly low. Our results suggest that nutritional rehabilitation of children with kwashiorkor is incomplete by 30 days and cannot be judged purely by a return of the plasma proteins to normal. Addition of selected trace elements to the diet may hasten full recovery.

Acute Disease↗

Pilot study of growth hormone administration during the refeeding of malnourished anorexia nervosa patients.

OBJECTIVE: In anorexia nervosa (AN), medical stabilization and nutritional repletion are pivotal steps toward physical and psychological recovery. Nutritional stabilization is often difficult in this patient group. Recombinant human growth hormone (rhGH) has been safely used as adjuvant therapy in other groups of malnourished patients. We hypothesize that rhGH treatment will hasten medical stabilization in AN patients. STUDY DESIGN: Fifteen patients admitted for inpatient treatment for AN, ages 12-18 years, were enrolled in a 28-day randomized, double-blind, placebo-controlled study. Patients received rhGH (0.05 mg/kg subcutaneously) or an equivalent volume of placebo daily. Outcome measures included time to reach medical/cardiovascular stability, rate of weight gain, and duration of hospitalization. All patients received a standard refeeding protocol. RESULTS: Mean admission body mass index was 14.5 kg/m2. The rhGH and placebo groups did not differ significantly in admission weight, BMI or daily caloric intake. Patients treated with rhGH reached medical/cardiovascular stability more rapidly than those treated with placebo (median 17 vs. 37 days, p = 0.02). Numerical but not statistically significant improvements were seen in weight gain and length of hospitalization in the rhGH group. CONCLUSION: Patients treated with rhGH achieved medical/cardiovascular stability more rapidly than those treated with placebo, and this, in turn, decreased the length of stay.

Adolescent↗

Protein turnover in malnourished elderly subjects: the effects of refeeding.

A primed constant-rate infusion of L-(l-14C)-leucine was used to assess protein flux, synthesis, and breakdown in a group of malnourished elderly subjects (n = 9) and a group of age-matched healthy elderly control subjects (n = 9). No significant differences between the two groups were observed in measures of protein metabolism. Four out of six malnourished subjects, restudied after a period of dietary replenishment, showed non-significant increases in protein synthesis and breakdown. Plasma insulin concentrations were significantly suppressed (p less than 0.05) and plasma growth hormone and cortisol concentrations significantly elevated (p less than 0.05) in the malnourished subjects before and after refeeding compared with the healthy elderly controls.

Age Factors↗

Refeeding syndrome.

CASE REPORT: An elderly woman with poor nutritional intake developed profound hypophosphataemia and hypokalaemia following the institution of nasogastric feeding. DISCUSSION: Refeeding syndrome is well recognized in certain undernourished groups of patients, but may not be so well known to physicians looking after elderly patients, whose nutritional status may be more deficient than is originally apparent.

Aged↗

Diet and cerebral malaria: the effect of famine and refeeding.

In an outbreak of Plasmodium falciparum malaria following refeeding after famine cerebral malaria was restricted to children eating grain. Nomad children consuming a predominantly milk diet were free of this complication despite an equivalent incidence of uncomplicated malaria. Freedom of nomads from cerebral complications may be due to inhibition by the milk diet of rapid division of the parasite combined with delayed recovery after famine of T cell function.

Animals↗

Hepatic response to a very-low-energy diet and refeeding in rats.

Hepatic effects of very-low-energy diets (VLEDs) and refeeding were studied in dietary obese rats. Rats weighing 490-530 g (ages 72-119 d) were randomly assigned to control (C) and VLED groups. Control animals consumed a complete diet ad libitum whereas VLED animals consumed 20% of the energy intake of C animals for 7, 14, or 21 d, and some VLED animals were refed the C diet for 7 d. Hepatic weights, lipid, DNA, and total protein decreased in VLED animals. Observed hepatocytic lipid was high in C and progressively decreased in VLED rats. Hepatocytes from VLED rats lost cytoplasmic organelles, contained myelin figures, and became smaller. Decreased protein-DNA ratios and lipids in these same animals is consistent with atrophy. Other biochemical findings included reductions in blood urea nitrogen, albumin, triglycerides, total protein, and glucose, all of which are synthesized or metabolized by the liver. These observations suggest that attenuation of hepatic function is likely.

Adipose Tissue↗

Effects of cycles of food restriction followed by ad libitum refeeding on body composition and energy expenditure in obese rats.

Male Wistar rats rendered obese by a cafeteria diet were subjected to three successive cycles alternating food restriction with ad libitum cafeteria-diet feeding (WC rats). Body composition, energy intake, energy required for maintenance, and oxygen consumption were studied. Results were compared with those for rats fed a standard stock diet (CON rats) or a cafeteria diet (CAF rats). The rate of weight loss or regain was independent of the number of cycles. WC rats were fatter than CON rats and as fat as CAF rats after the third cycle. Cost of maintenance of WC rats decreased; their oxygen consumption decreased in the lean state, increased again in the fat state, but remained lower than that of CON and CAF rats. We conclude that the practice of successive restriction and refeeding did not result in resistance to weight loss, but rather in a defect in the utilization of energy intake, facilitating the development of obesity.

Animals↗

Effect of hypoenergetic feeding and refeeding on muscle and mononuclear cell activities of mitochondrial complexes I--IV in enterally fed rats.

BACKGROUND: Previous studies suggested that cell energetics are altered by malnutrition. OBJECTIVE: We hypothesized that nutritional manipulations influence mitochondrial enzyme activities of the electron transport chain in both skeletal muscle and blood mononuclear cells. DESIGN: After a gastrostomy tube was inserted, 44 rats were randomly assigned to 1 of 4 experimental groups: control fed (CF; 364 kJ/d for 7 d), hypoenergetic fed (HF; 92 kJ/d for 7 d), hypoenergetic protein refed (HPR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d), and hypoenergetic glucose refed (HGR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d). The protein and glucose contents of the liquid formulas were different for the HPR and HGR groups. After mitochondria were isolated from the soleus muscle, the activities of complexes I--IV were measured spectrophotometrically. Because of the lack of available tissue, only the activity of complex I was measured in the mononuclear cell extract. RESULTS: The recovery of complex activities in the CF and HF groups was not significantly different in the mitochondrial fraction of the soleus muscle. Compared with that in the CF group, the activities of complexes I--III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly lower in the HF group. The activities of complexes I--III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly higher in the HPR than in the HF group. The activity of complex IV was generally not affected by nutritional manipulations. CONCLUSION: Malnutrition decreases activities of mitochondrial complexes, which are restored by protein but not glucose refeeding.

Adenosine Triphosphate↗

Effects of fasting and refeeding on blood pressure are determined by nutritional state, not by body weight change.

It is commonly assumed that caloric restriction is effective in lowering blood pressure because of the accompanying weight loss and reversal of obesity. However, clinical trials of caloric restriction reporting the greatest falls in blood pressure were those that produced the most rapid weight loss on diets allowing the fewest calories, but the amount of weight loss was unrelated to antihypertensive effect. In obese rats undergoing a supplemented fast, blood pressure fell almost immediately but then stabilized despite continuing weight loss. The depressor effect of fasting was reversed within 2 days of refeeding. Body weight change was no longer correlated with blood pressure change after nutritional state was controlled for. Nutritional state (fed, fasted, refed), but not body weight, has important effects on blood pressure.

Animals↗

Effect of starvation and refeeding a high-protein or high-carbohydrate diet on lipid composition and glycogen content of rat livers in relation to age.

Rats of two different ages (72 and 490 days) were subjected to a 3-day fast and then refed for the same period a high-protein (89%) or high-carbohydrate (99%) diet. This experimental model served to study whether alterations occur in the content of the main lipid components, triacylglycerol, phospholipids and cholesterol in liver. It also examined whether the aging process itself has any effect on the lipid pattern. With the high-protein diet the content of all lipids returned to or nearly to the control level regardless of age. Refeeding the 72-day-old rats the high-carbohydrate diet led to a 2.4-fold overshoot in the triacylglycerol content, while the phospholipids and the cholesterol remained far below their control levels. In the 490-day-old rats the total lipids, phospholipids and cholesterol remained at the starvation level. With aging, the total cholesterol content showed a marked increase of about four-fold when corrected for growth.

Aging↗

Effects of estrogen on the responses of male and female rats to starvation-refeeding.

The effects of sex, castration and estrogen treatment of castrated rats subjected to starvation-refeeding were studied. Food intakes, liver lipid levels and the activities of glucose 6-phosphate dehydrogenase and malic enzyme in ad libitum-fed, starved and starved-refed rats were determined. Sex differences observed in the intact ad libitum-fed rats could be explained in part by the differences in estrogen levels. Sex differences were obliterated in the starved-refed intact rats but were observed when castrated female starved-refed rats were compared to castrated male starved-refed rats. The differences could not be erased with the administration of estrogen. Estrogen significantly reduced food intake of castrated rats. Results of this study suggest that the characteristically higher liver lipid level and enzyme activity in the female, compared to the male, may reflect the female's tendency to undereat when circulating estrogen levels are high and to compensate (by overeating) for this undereating when estrogen levels are low.

Alcohol Oxidoreductases↗

Effects of bone fracture and starvation-refeeding on lipogenesis in rats.

The effects of trauma and/or starvation-refeeding on lipogenesis in rats was studied. Male Sprague-Dawley rats were subjected to fracture of the right femur and either ad libitum fed or starved for 48 hours and refed a 65% glucose diet for 48 hours. Lipogenesis was assessed in terms of glucose-6-phosphate dehydrogenase activity or the incorporation of 3HOH into lipids by liver and adipose tissue. Traumatized rats differed little from control rats in their lipogenic activity, whereas starved-refed and starved-refed-traumatized rats had greatly increased lipogenic activities. These results suggest that the fatty liver that frequently develops as a consequence of trauma in humans may be due to their decreased food intake rather than to the trauma itself.

Animals↗

Hepatic responses to edible gums during refeeding of starved rats.

The ability of edible gums to depress total liver lipids and activities of two hepatic enzymes (glucose-6-phosphate dehydrogenase and NADP-linked malic enzyme) was examined during the refeeding of 2 d starved rats. Gums were fed as 4% of dry ingredients, occasionally with added water, in otherwise identical high glucose, nutritionally adequate diets. Feeding of xantham gum for 1 or 2 d decreased the rise in two enzyme activities and in total liver lipids, but after 4 or 7 d only total liver lipids were affected. Agar, which is insoluble at room temperature, was effective only when incorporated in the diet as a stiff gel. Guar, carrageenan, karaya and pectin reduced the change in at least one hepatic parameter, but acacia and gum ghatti, which impart little viscosity to water, were without effect. The ability of seven gums to form semisolid gels at low concentrations was measured and appeared to be associated with the variable effectiveness of those gums in influencing lipid contents and enzyme activities of the liver.

Animals↗

Serum insulin-like growth factor (IGF)-I concentrations are reduced by short-term dietary restriction and restored by refeeding in domestic cats (Felis catus).

Nutritional modulation of insulin-like growth factors (IGF) and their binding proteins (IGFBP) is well established. The effect of nutritional restriction on the serum IGF/IGFBP system of adult cats was investigated to evaluate serum IGF-I as a biochemical marker of nutritional status. Assays for measuring feline serum IGF and IGFBP were validated and normal ranges established in a study population of 46 healthy nonobese adult cats. Serum concentrations of IGF-I and IGF-II correlated significantly with body weight (r = 0.75, P < 0. 0001 and r = 0.34, P < 0.03, respectively). Serum IGFBP profiles were similar to other species, including humans, dogs and guinea pigs. IGFBP-3 was the predominant binding protein reflecting IGF-I concentrations and body size. Serum IGFBP-2 concentrations were high relative to the normal human serum pool (NHS) control. Food withdrawal for 18 h followed by refeeding did not alter circulating IGF or IGFBP concentrations, including IGFBP-1, in nine cats. Short-term dietary restriction of nine adult cats to supply initially 56% (56%M) and then 42.5% (42.5%M) of calculated maintenance energy requirements for 14 d resulted in a significant weight loss (P < 0.01). However, serum IGF-I concentrations fell significantly (-51%, P < 0.01) only with 42.5%M restriction. Serum IGF-II, IGFBP, insulin and albumin concentrations were not altered during the study. We conclude that nutrition does modulate the adult feline IGF/IGFBP system, but to a lesser extent than in other species. Further evaluation is required before serum IGF-I can be used for the assessment of nutritional status in adult cats.

Animals↗

Guidelines for refeeding the marasmic patient.

Nutritional support of the malnourished patient can be lifesaving. However, the efficacy of total parenteral nutrition in this setting depends on: a) careful estimation of energy requirements, using the Harris-Benedict equation or indirect calorimetry; b) minimizing the fluid retention which invariably complicates refeeding in marasmus; c) adequate repletion of P, K, and Mg on a daily basis; and d) accurate assessment of the rate of weight regain.

Basal Metabolism↗

The effects of maternal deprivation and of refeeding on the blood pressure of infant rats.

Blood pressure regulation was explored in infant rats 12-14 days of age during the 30-40% changes in cardiac rate that accompany nutrient (maternal) deprivation and refeeding at this age. Using specially modified tail cuff and intraarterial cannulation techniques, blood pressure was found to be maintained at stable levels (65-75 mm Hg) throughout these marked changes in pumping rate. The results suggest that adrenergic vasoconstrictor tone is controlled reciprocally with heart rate during a complex cardiovascular response to changes in nutrient levels at this early age. The possible role of such a mechanism in the development of "spontaneous" hypertension is discussed.

Animals↗