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Incorporation of fasting therapy in an integrative medicine ward: evaluation of outcome, safety, and effects on lifestyle adherence in a large prospective cohort study.

OBJECTIVES: The aim of this study was to implement fasting therapy in an inpatient integrative medicine ward and to evaluate safety, acceptance, and effects on health-related outcomes and lifestyle adherence. DESIGN: This was a prospective observational study with consecutive inpatients over 3 [corrected] years. Inclusion and exclusion criteria for fasting therapy were checked by treating physicians and recommendations given. After receiving full information patients decided whether they would participate in fasting. Outcomes were assessed on admission, at discharge, and 3 and 6 months after discharge. SETTING: The study took place in an integrative medicine department of an academic teaching hospital. SUBJECTS: Subjects were newly admitted inpatients with chronic internal diseases and chronic pain syndromes, with lengths of hospital stay of >3 days. INTERVENTIONS: All patients received intensive integrative treatments including Mind/Body Medicine, acupuncture, nutritional/lifestyle education, and hydrotherapy. Fasting patients participated in a 7-day juice fast (intake <350 kcal/day) with accompanying bowel cleansing, 2 prefasting relief days, and 3 days with stepwise reintroduction of food. OUTCOME MEASURES: Outcomes were assessed based on rate of participation in fasting, severity of main complaint, quality of life (QOL, MOS 36-Item Short-Form Health Survey), safety, lifestyle adherence to recommendations given (relaxation, diet, exercise). RESULTS: Of 2121 patients with complete discharge questionnaires, 952 patients participated in fasting, 873 had a normocaloric vegetarian diet, and 296 patients had other diets and were excluded. Response rates were 71% and 56% at 3- and 6-month follow-up. The main disease-related complaint at discharge was significantly greater improved in fasters versus nonfasters (p < 0.01). Patient QOL increased significantly and comparably from baseline to discharge in both groups. Fasting was well tolerated and no serious fasting-related adverse effects were reported. In all, 743 (78%) of fasting patients reported improvement of their health through fasting. Descriptors of lifestyle adherence showed higher levels of related activities in the 3 and 6 months of follow-up. CONCLUSIONS: Fasting can safely and successfully be implemented in an inpatient integrative medicine concept and is perceived as a health-promoting method by the majority of patients. Potential effects on disease-related complaints and lifestyle adherence should be further evaluated in randomized trials.

Adolescent↗

Preprocedural fasting state and adverse events in children receiving nitrous oxide for procedural sedation and analgesia.

STUDY OBJECTIVE: Established fasting guidelines for analgesia and sedation are difficult to follow in the emergency department (ED), and the association between preprocedural fasting and adverse events has been questioned. We characterize the fasting status of patients receiving procedural sedation and analgesia with nitrous oxide (N2O) in a pediatric ED and assess the relationship between fasting status and adverse events. METHODS: A prospective case series was conducted in a children's hospital ED over an 8-month period. Patients receiving N2O for procedural sedation and analgesia were enrolled and followed up by telephone call. Preprocedural fasting state and adverse events, as well as N2O concentration, adjunctive drugs, and deepest level of sedation, were recorded. Adverse events were analyzed in relation to fasting status. RESULTS: Two hundred twenty children who underwent procedural sedation and analgesia with N2O were enrolled. Fasting status was obtained in 218 patients (99.1%). Of these, 155 (71.1%; 95% confidence interval [CI], 64.5%-77.0%) did not meet fasting guidelines for solids There were no serious adverse events and no episodes of aspiration (1-sided 97.5% CI, 0%-1.7%). While in the ED, 46 minor adverse events occurred in 37 patients (16.8%; 95% CI, 12.1%-22.4%). Emesis occurred in 15 patients (7%), including 4 (6.3%; 95% CI, 1.8%-15.5%) of 63 patients who met and in 11 (7.1%; 95% CI, 3.6%-12.3%) of 155 patients who did not meet fasting guidelines for solids. There was no significant difference in median fasting duration between patients with and without emesis. CONCLUSION: Seventy-one percent of patients undergoing ED procedural sedation and analgesia with N2O did not meet established fasting guidelines. In this series, there was no association between preprocedural fasting and emesis. There were no serious adverse events.

Administration, Inhalation↗

Temperature-dependent changes in the viscoelasticity of intact resting mammalian (rat) fast- and slow-twitch muscle fibres.

1. The tension and sarcomere length responses induced by ramp stretches (at amplitudes of 1-3 % fibre length (Lo) and speeds of 0.01-12 Lo s-1) were examined at different temperatures (range, 10-35 degrees C) in resting intact muscle fibre bundles isolated from the soleus (a slow-twitch muscle) and extensor digitorum longus (a fast-twitch muscle) of the rat. Some observations are also presented on the effects of chemical skinning on passive viscoelasticity at 10 degrees C. 2. As previously reported, the tension response to a ramp stretch, in different preparations and under various conditions, could be resolved into a viscous (P1), a viscoelastic (P2) and an elastic (P3) component and showed characteristic differences between slow and fast muscle fibres. 3. Chemical skinning of the muscle fibres led to a decrease in the amplitude of all three tension components. However, the fast-slow fibre differences remained after skinning. For example, the viscosity coefficient derived from P1 tension data decreased from 0.84 +/- 0.06 before skinning to 0.44 +/- 0.06 kN s m-2 after skinning in fast fibres; the corresponding values in slow fibres were 2.1 +/- 0.08 and 0.87 +/- 0.09 kN s m-2, respectively. 4. Increasing the experimental temperature from 10 to 35 degrees C led to a decrease in all the tension components in both fast and slow muscle fibre bundles. The decrease of P1 (viscous) tension was such that the viscosity coefficient calculated using P1 data was reduced from 0.84 +/- 0.1 to 0.43 +/- 0.05 kN s m-2 in fast fibres and from 2.0 +/- 0.1 to 1.0 +/- 0.1 kN s m-2 in slow fibres (Q10 of approximately 1.3 in both). 5. In both fast and slow muscle fibre preparations, the plateau tension of the viscoelastic component (P2) decreased by 60-80 % as the temperature was increased from 10 to 35 degrees C giving P2 tension a Q10 of approximately 1.4 in slow fibres and approximately 1.7 in the fast fibres. Additionally, the relaxation time of the viscoelasticity decreased from 11.9 +/- 1 ms (fast) and 43.1 +/- 1 ms (slow) at 10 degrees C to 3 +/- 0.5 ms (fast) at 25 C degrees and 8. 7 +/- 0.6 ms (slow) at 35 degrees C (Q10 of approximately 2.0 in slow and approximately 2.5 in fast fibres). 6. The fast-slow fibre differences in passive viscoelasticity remained at the high physiological temperatures. The physiological significance of such fibre-type differences and their possible underlying mechanisms are discussed.

Animals↗

Attenuated responses of muscle protein synthesis to fasting and insulin in adult female rats.

One-year-old adult female rats were fasted for 12 or 36 h followed by a 30-min infusion of insulin. The responses of the fractional rate of protein synthesis (Ks) in the individual muscles (measured in vivo) to fasting were small and mostly nonsignificant. After 12 h of fasting, only the epitrochlearis muscle (ET) showed a significant decrease in Ks, and, even after 36 h of fasting, a significant decrease in Ks was seen in only ET, extensor digitorum longus, and tensor fasciae latae (TFL). After the 36-h fast, infusion of insulin restored the fed Ks in all muscles except TFL. The fiber-type composition of the individual muscles appeared to influence the muscles' responsiveness to the fasting, since the highly glycolytic TFL was the most sensitive (particularly after 36 h of fasting), whereas the highly oxidative adductor longus and soleus muscles were unaffected by either fasting or insulin. In a second experiment, refeeding of fasted adult rats also had little effect on Ks, consistent with the low sensitivity to fasting shown by the first experiment. The parallel results in the two experiments confirmed that the low responsiveness to fasting and insulin infusion in these adult rats was not a result of failure to absorb in "fed" animals or insufficient levels of insulin during insulin infusions. In contrast, a third experiment showed that muscle protein synthesis in the gastrocnemius muscle from young adult (5-mo-old) female rats was significantly reduced after only 12 h of fasting.

Aging↗

Prolonged fasting significantly changes nutrient oxidation and glucose tolerance after a normal mixed meal.

The aim of this study was to establish the experimental paradigm of fasting, followed by refeeding, to investigate individual differences in nutrient partitioning. Eight nonobese men were fed a normal meal (25% of daily energy requirements) on two occasions, after an overnight (13-h) fast and after a prolonged (72-h) fast. During the entire fasting period, subjects were resident in a whole room indirect calorimeter, and blood samples were drawn periodically. Because no other food was consumed over the 12 h after either meal, negative energy balance was observed after the overnight and prolonged fast. Postprandial carbohydrate oxidation was significantly reduced after the 72- vs. 13-h fast (P < 0.0001), whereas fat oxidation was significantly increased (P < 0.0001). Interestingly, carbohydrate balance was positive after the prolonged fast but negative after the overnight fast (24 +/- 17 vs. -57 +/- 16 g/12 h, respectively; P < 0.001), whereas fat balance was negative under both conditions (-78 +/- 7 vs. -47 +/- 8 g/12 h, respectively; P < 0.002). With 72 h of fasting, the glucose and insulin excursions in response to the mixed meal were significantly greater compared with the 13-h fast (P < 0.001). In conclusion, prolonged fasting resulted in a significant decrease in carbohydrate oxidation and an increase in fat oxidation, after a normal mixed meal, in healthy men. This was associated with a significant decrease in glucose tolerance. Because circulating free fatty acids were greatly elevated at all times after the prolonged fast, these may be mediating some of the changes in postprandial metabolism.

Adult↗

Impaired fasting glucose, blood pressure and cardiovascular disease mortality.

Impaired fasting glucose (fasting plasma glucose 6.1 to 6.9 mmol/L [110 to 125 mg/dL]) is a common glycemic disorder which usually progress to diabetes mellitus. The relationships between impaired fasting glucose, other risk factors including blood pressure, and mortality have never been clearly investigated. We studied 63 443 consecutive men (ages 21 to 60 years), each of whom had a routine health examination with a fasting plasma glucose measurement. Men with known ischemic cardiac disease and treatment for diabetes or hypertension were excluded. Impaired fasting glucose was found in 10 773 (17.0%) of these men. Mean body mass index, serum triglyceride and cholesterol levels, and systolic, diastolic, and pulse blood pressure were significantly higher for men with impaired fasting glucose compared with those men with normal fasting glucose (fasting plasma glucose 3.9 to 6.0 mmol/L). When adjusted for confounding variables, relative risk of 8-year cardiovascular mortality associated with impaired fasting glucose was dependent on systolic blood pressure level (1.02 [95% CI: 0.62 to 1.70] when <140 mm Hg and 2.10 [95% CI: 1.16 to 3.80] between 140 and 160 mm Hg). Inversely, relative risk of 8-year cardiovascular mortality associated with moderate systolic hypertension (140 to 159 mm Hg) compared with normal systolic blood pressure (<140 mm Hg) was highly dependent on the glycemic status (2.97 [95% CI: 1.58 to 5.55] for men with impaired fasting glucose compared with 1.35 [95% CI: 0.84 to 2.18] in those with normal fasting glucose). Similar results were found concerning overall mortality. In conclusion, the presence of moderate systolic hypertension can identify subjects with impaired fasting glucose who are at risk of cardiovascular and overall mortality, and vice versa, probably through the metabolic syndrome.

Adult↗

Effects of fasting on insulin binding, glucose transport, and glucose oxidation in isolated rat adipocytes: relationships between insulin receptors and insulin action.

UNLABELLED: Insulin binding, glucose transport, and glucose oxidation were studied in isolated adipocytes obtained from fasting rats. Fasting led to an increase in the overall binding affinity for insulin, while the number of receptor sites per cell remained constant. Glucose oxidation was markedly attenuated during fasting. Basal rates of oxidation decreased by about 50%, while insulin-stimulated rates decreased 6 to 10-fold. Glucose transport was assessed by measuring initial uptake rate of 2-deoxy-glucose. Fasting led to a 40-50% decrease in the apparent maximal transport capacity (Vmax) of 2-deoxy-glucose uptake with no change in apparent Km. A progressive decrease in basal and insulin-stimulated rates of 2-deoxy-glucose uptake was seen from 24-72 h of starvation and a significant correlation (r=0.85, P less than 0.001) existed between basal and maximal insulin-stimulated uptake rates in individual animals. When 2-deoxy-glucose uptake was plotted as a function of insulin bound, due to the decrease in maximal uptake capacity, cells from fasting animals took up less hexose for any amount of insulin bound. When the insulin bound was plotted as a function of the percent insulin effect on uptake, control cells and cells from 24-h-fasted rats gave comparable results, while cells from 48- and 72-h-fasted animals still took up less hexose for any amount of bound insulin. The effects of fasting on 3-O-methyl glucose uptake were comparable to the 2-deoxy-glucose data. IN CONCLUSION: (a) insulin binding is increased during fasting due to an increased overall binding affinity with no change in receptor number; (b) glucose oxidation is severely impaired during fasting; (c) 2-deoxy-glucose uptake decreases with fasting due to a decrease in maximal transport capacity (Vmax) with no change in Km; (d) the decrease in glucose oxidation is much greater than the decrease in glucose transport, indicating impaired intracellular oxidative metabolism; and (e) coupling between insulin receptors and the glucose transport system is normal after 24 h of fasting but is impaired at 48 and 72 h.

Adipose Tissue↗

Sympathoadrenal activity in fasting pregnant rats. Dissociation of adrenal medullary and sympathetic nervous system responses.

The pattern of urinary catecholamine excretion in fasting differs in pregnant and nonpregnant rats, which suggests that the sympathoadrenal response to fasting is altered by pregnancy. In fasting nonpregnant animals, urinary norepinephrine (NE) excretion decreases and epinephrine (E) excretion remains unchanged, whereas the excretion of both catecholamines rises significantly with refeeding. In contrast, fasting third-trimester pregnant rats exhibit a 420% increase in urinary E and a 345% increase in urinary NE, elevations which fall with refeeding. Specific evaluation of sympathoadrenal activity in fasting pregnant rats reveals stimulation of the adrenal medulla and suppression of sympathetic nerves. In fasting third-trimester rats the adrenal content of E is 37% lower in innervated adrenals as compared with contralateral denervated glands, which indicates the presence of neurally-mediated adrenal medullary activation. Adrenalectomy completely abolishes the fasting-induced rise in urinary E and NE in pregnant rats. Studies with 2-deoxy-D-glucose suggest that stimulation of the adrenal medulla results from hypoglycemia, which is present after 3 d of fasting in pregnant rats (plasma glucose 36.7 mg/dl). Sympathetic nervous system activity, as measured by [(3)H]NE turnover in the heart, decreases in fasting pregnant rats despite hypoglycemia, a response similar to that seen in fasting nonpregnant animals where plasma glucose is maintained above 50 mg/dl. The calculated NE turnover rate is 44% lower in 2-d fasted pregnant rats than in fed pregnant animals (17.6 +/- 1.3 vs. 31.3 +/- 1.8 ng NE/heart per h, respectively). Thus adrenal medullary and sympathetic nervous system responses in fasting pregnant rats appear to be dissociated, which suggests that diet-induced changes in sympathetic activity and stimulation of the adrenal medulla by hypoglycemia may be independently regulated.

Adrenal Medulla↗

Influence of a 60-hour fast on insulin-mediated splanchnic and peripheral glucose metabolism in humans.

A brief period of starvation (2-3) depletes the hepatic glycogen stores but results in only a limited reduction of the muscle glycogen depots. In this situation insulin resistance contributes to the glucose intolerance, but it is not known which tissue or tissues are responsible for the decreased insulin sensitivity. The present study was therefore undertaken to examine the influence of a 60-h fast on insulin sensitivity in splanchnic and peripheral tissues in normal humans. Euglycemic (95 mg/dl) 1-mU insulin and hyperglycemic (215-225 mg/dl) glucose clamp studies were conducted for 2 h in overnight (12 h) and prolonged (60 h) fasted nonobese subjects. Splanchnic exchange of glucose and gluconeogenic precursors was measured using the hepatic vein catheter technique. During the euglycemic clamp, insulin infusion resulted in similar steady state insulin levels in 60-h and 12-h fasted subjects (73 +/- 7 vs. 74 +/- 5 microU/ml). Total glucose disposal was reduced by 45% after 60 h of fasting (4.0 +/- 0.3 vs. 7.6 +/- 1.1 mg/kg per min, P less than 0.05) and the splanchnic glucose balance reverted from a net release in the basal state (12 h fast, -1.7 +/- 0.2, and 60-h fast, -0.9 +/- 0.1 mg/kg per min, P less than 0.01) to a net uptake during the clamps that was similar after 60 h and 12 h of fasting (0.6 +/- 0.1 vs. 0.6 +/- 0.2 mg/kg per min). During the hyperglycemic clamp, insulin levels rose rapidly in all subjects. In the 12-h fasted group this rise was followed by a further gradual one, reaching significantly higher values than in 60-h fasted subjects during the second hour (67 +/- 15 vs. 25 +/- 2 microU/ml, P less than 0.05). Total glucose disposal was lower, though not significantly so, after the 60-h fast (2.6 +/- 0.4 vs. 5.4 +/- 1.3 mg/kg per min, 0.05 less than P less than 0.10), and as with the euglycemic clamp, the splanchnic glucose balance was altered from a basal net release to a net uptake during the clamp (1.3 +/- 0.2 vs. 1.1 +/- 0.2 mg/kg per min). After an overnight fast, splanchnic lactate uptake fell and the arterial lactate concentration rose in response to both hyperglycemia and hyperinsulinemia, whereas these variables were unchanged in the 60-h fasted subjects during both types of clamp studies.

Adult↗

Pulsatile secretion of thyrotropin during fasting: a decrease of thyrotropin pulse amplitude.

The effect of fasting on circadian and pulsatile TSH secretion was investigated in eight healthy subjects (four men and four women in the follicular phase). Each subject was studied twice, once during 24 h with normal food intake and once during the last 24 h of a 60-h fast. Blood was sampled every 10 min during 24 h for measurement of TSH by a sensitive immunoradiometric assay. Fasting induced a decrease in plasma T3 [1.73 +/- 0.06 vs. 1.36 +/- 0.04 nmol/L; P less than 0.01 (mean +/- SE), control period vs. fasting] and thyroglobulin (52 +/- 8 vs. 35 +/- 7 pmol/L; P less than 0.001) and an increase in plasma rT3 (0.30 +/- 0.06 vs. 0.44 +/- 0.09 nmol/L; P less than 0.02). Plasma T4, thyroid hormone binding index, and free T4 were not statistically different in both periods. The mean plasma 24-h TSH concentration was lower during fasting than in the control period (2.0 +/- 0.3 vs. 1.0 +/- 0.2 mU/L; P less than 0.005). This was associated with a decrease in mean TSH pulse amplitude during fasting (Desade program: 0.6 +/- 0.1 vs. 0.3 +/- 0.1 mU/L; P less than 0.01; Cluster program: 0.5 +/- 0.1 vs. 0.2 +/- 0.1 mU/L; P less than 0.05), whereas TSH pulse frequency during fasting was unchanged (Desade program: 8.4 +/- 0.9 vs. 9.8 +/- 0.8 pulses/24 h; Cluster program: 9.5 +/- 0.5 vs. 7.9 +/- 0.9 pulses/24 h). There was a highly significant correlation between the mean 24-h TSH concentration and the mean TSH pulse amplitude during both the control period and fasting. Although the decrease in TSH concentration during fasting was evident over 24 h, fasting especially decreased the absolute (1.3 +/- 0.3 vs. 0.4 +/- 0.1 mU/L, P less than 0.02) and the relative (101 +/- 18% vs. 40 +/- 14%; P less than 0.02) nocturnal TSH surge (mean TSH 0000-0400 h vs. mean TSH 1500-1900 h). The decreased nocturnal TSH surge during fasting was associated with a significantly decreased TSH pulse amplitude, but with an unaltered number of TSH pulses between 2000-0400 h. In conclusion, fasting decreases 24-h TSH secretion and the nocturnal TSH surge in the absence of a change in plasma T4 concentration. This is associated with a decreased TSH pulse amplitude, whereas TSH pulse frequency remains unchanged.

Adult↗

Short-term fasting is a mechanism for the development of euglycemic ketoacidosis during periods of insulin deficiency.

To determine the etiology of euglycemic ketoacidosis, the effect of a 32-h fast on the rate of metabolic deterioration was examined in a group of 10 healthy subjects with type I diabetes mellitus. Patients were studied during 5 h of insulin withdrawal after 8 h (postprandial) and 32 h (fasted) of food deprivation. Study parameters included substrate levels, electrolytes, counterregulatory hormone levels, and rates of glucose and glycerol turnover. In the fasted state, mean peak plasma glucose concentrations were significantly lower than those in the 8-h postprandial state (13.3 +/- 1.6 vs. 17.4 +/- 1.4 mmol/L, respectively; P < 0.05), and mean rates of glucose production were also significantly lower at all time points in the fasting state. The rate of development of ketosis was significantly more rapid during insulin deficiency after a fast (8.82 +/- 0.63 vs. 6.23 +/- 0.30 micro/L.min; P < 0.05), while plasma nonesterified fatty acids and glycerol turnover showed a biphasic response to insulin withdrawal, which was also more robust after a fast. Metabolic acidosis, as reflected in the rate of decrease in serum bicarbonate concentration, was more severe after 32 h of fasting than in the postprandial state (mean nadir, 15.4 +/- 0.9 vs. 18.6 +/- 0.5 mmol/L; P < 0.001). In contrast to values in the postprandial state, serum glucagon levels rose during insulin withdrawal in the fasting state, and plasma norepinephrine levels also correlated positively with the ongoing metabolic decompensation. Other counterregulatory hormones did not differ significantly in the fasted vs. postprandial states in these short term metabolic studies. We conclude that a fast of moderate duration, such as might be expected to occur during the development of diabetic ketoacidosis, predisposes patients with type I diabetes to euglycemic ketoacidosis during periods of insulin deficiency. Furthermore, decreased rates of hepatic glucose production are responsible for the lower plasma glucose values observed during a fast. The development of ketosis continued progressively in both conditions, but the rate of rise of plasma ketones was increased in the fasted state. This accelerated development of ketosis may be attributable to the effects of elevated levels of glucagon and/or catecholamines on lipolysis.

Adult↗

Pulsatile growth hormone secretion in older persons is enhanced by fasting without relationship to sleep stages.

Spontaneous secretion of GH decreases with aging. To investigate whether fasting increases pulsatile GH secretion in older as it does in younger subjects, we studied six subjects (four postmenopausal women and two men, aged 55-81 yr; body mass indexes, 22-24 kg/ m2). Blood was obtained every 5 min for 24 h on a control (fed) day and on the second day of a fast. Serum GH concentrations, measured by an immunoradiometric assay, were analyzed with a multiple parameter deconvolution method to stimultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 4-fold increase in the 24-h GH production rate (38 +/- 25 vs. 166 +/- 42 micrograms/L distribution volume; P = 0.003) and a 2-fold increase in the amount of GH secreted per pulse (2.4 +/- 1.4 vs. 5.5 +/- 1.2 micrograms/L distribution volume; P = 0.02). The latter was a result of increased secretory burst amplitudes with unchanged secretory burst durations. The number of detectable GH secretory bursts per 24 h was also increased by fasting (13 +/- 1.4 vs. 30 +/- 1.1; P = 0.0004); the GH pulse frequency may have been underestimated in the fed state, as 33 +/- 4.9% of the samples had undetectable ( < 0.2 microgram/L) serum GH concentrations compared to 5.2 +/- 2.6% of the samples on the fasting day (P = 0.004). The t1/2 of endogenous GH was not significantly altered by fasting. The fold increase in GH secretion with fasting was similar to that previously observed in young men, although absolute levels of GH secretion were approximately 50% lower in both fed and fasted conditions. Fasting decreased the proportion of sleep time spent in rapid eye movement sleep (4.7 +/- 1.3 vs. 15 +/- 2.1%; P = 0.005), but did not significantly increase slow wave (stages 3 and 4) sleep. In both fed and fasted conditions, mean GH secretion rates were similar during daytime wakefulness, nocturnal wakefulness, rapid eye movement sleep, and stages 1, 2, and 3 of sleep. We conclude that hyposomatotropism associated with aging is partially reversed by fasting, and the enhancement of GH secretion by fasting is not related to changes in slow wave sleep. These data indicate that GH secretion in older persons can be enhanced by physiological interventions.

Aged↗

Effects of fasting on neuroendocrine function and follicle development in lean women.

A 72-h fast in normal weight women during the follicular phase results in transient alterations in neuroendocrine function, but follicle development and follicular phase length remain unaltered. In this study we evaluated neuroendocrine and ovulatory function in lean women (body fat, < or = 20%) undergoing a similar 72-h fast. Compared to fed controls, fasted lean women experienced significant weight loss, blunting of the diurnal variation of cortisol, suppression of the nocturnal TSH rise, and a decrease in T3 levels after a 72-h fast. In contrast to similarly fasted, normal weight women, lean women have significantly higher evening cortisol levels and do not exhibit a normal nocturnal TSH rise after the fast. Lean fasted women exhibited a 19% decrease in the number of LH pulses over 24 h compared to fed women (12.9 +/- 1.3 vs. 16.0 +/- 1.9; P < 0.05). Fasting did not result in significant differences in mean LH, LH amplitude, LH area under the curve, and mean FSH levels in these lean women. Of the seven fasted cycles, two were anovulatory. In the five women studied in fed and fasted cycles, one had interrupted lead follicle development with anovulation, and four had significant lengthening of the follicular phase compared to those during their fed cycles (14.4 +/- 1.2 vs. 13.2 +/- 1.0 days; P = 0.01). The clinical observations made in this small sample of lean women showing more profound changes in neuroendocrine function, anovulation, and lengthened follicular phase after fasting suggest that lean women may be more vulnerable to fasting stress than normal weight women.

Absorptiometry, Photon↗

Rats socially-reared and full fed learned an autoshaping task, showing less levels of fear-like behaviour than fasted or singly-reared rats.

During the learning of instrumental tasks, rats are usually fasted to increase reinforced learning. However, fasting produces several undesirable side effects. The aim of this study was to test the hypothesis that control rats, i.e. full-fed and group-reared rats, will learn an autoshaping task to the same level as fasted or singly-reared rats. The interaction between fasting and single-rearing of rats was also tested. Results showed that control rats and fasted rats acquired the autoshaping task similarly, independently of rearing condition or gender. However, fasted or singly-reared rats produced fear-like behaviour, since male rats group-reared and fasted (85% body/wt, P <0.05), male rats singly-reared (full fed, P <0.05; 12 h fasted, P <0.05; 85% body/wt, P <0.05), female rats group-reared (12 h fasted, P <0.05; 85% body/wt, P <0.05) and female rats singly reared (full fed, P <0.05; 12 h fasted, P <0.05; 85% body/wt, P <0.05) displayed reduced amounts of time exploring the open arms of the elevated plus-maze. In conclusion, control rats learned the autoshaping task to the same level as fasted or singly-reared rats. However, fasting or single-rearing produced fear-like behaviour. Thus, the training of control rats in autoshaping tasks may be an option that improves animal welfare.

Analysis of Variance↗

The influence of plasma concentrations of tri-iodothyronine on the acute increases in insulin and muscle protein synthesis in the refed fasted rat.

To examine whether the low plasma levels of triiodothyronine (T3) in fasted rats might limit the recovery of muscle protein synthesis on refeeding, rats were fasted for either 3 or 4 days and refed with or without pretreatment with thyroid hormones. Fasting suppressed T3 levels, plasma insulin and the rate of the translational phase of muscle protein synthesis (KRNA; the rate per unit RNA), especially after the 4-day fast. On refeeding, plasma T3 levels remained low for more than 3 h after the 3-day fast and for more than 8 h after the 4-day fast. Insulin concentrations increased within the first hour of refeeding, eventually achieving supranormal concentrations after the 3-day fast. The KRNA increased within the first hour of refeeding, achieving well-fed control values by 3 h after the 3-day fast or 24 h after the 4-day fast. The increases in KRNA were significantly correlated with the increases in insulin at low insulin concentrations, achieving a plateau value at 150 pmol/l, so that further increases in insulin were not associated with any further increases in protein synthesis. Pretreatment with thyroid hormone induced increased T3 levels which were maintained for up to 8 h of refeeding. This had no effect on the responses of either insulin or protein synthesis to refeeding after the 3-day fast, but did result in an acceleration of the recovery in the KRNA and plasma insulin levels in the rats fasted for 4 days. Analysis of the insulin-KRNA relationship showed no evidence for any increase in the insulin sensitivity of muscle protein synthesis with thyroid pretreatment, the initial stimulation of protein synthesis on refeeding the rats fasted for 4 days reflecting increased insulin secretion. Since in the untreated animals, insulin secretion on refeeding was also correlated with T3 levels, these results are consistent with the previously reported thyroidal dependence of insulin secretion.

Animals↗

Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat.

Fasting results in a reciprocal shift in hypothalamic neuropeptide Y (NPY) and GH-releasing hormone (GHRH) expression in the adult male rat. It is hypothesized that the fasting-induced rise in NPY is responsible for the GHRH decline and subsequent attenuation of pulsatile GH release. Fasting also leads to a decrease in circulating IGF-I, attributed to both reduced GH release and peripheral GH resistance. Although pituitary GH output is suppressed in the fasted rat, we report herein that pituitary GHRH receptor (GHRH-R) and GH secretagogue receptor (GHS-R) mRNA levels are increased, while pituitary expression of the somatostatin receptor subtype 2 (sst2) and 5 (sst5) is decreased, as determined by real-time reverse transcription (RT)-PCR. A shift in the expression of pituitary receptor subtypes to favor GH synthesis and release may be due, at least in part, to a decline in GH/IGF-I negative feedback. In order to test this hypothesis, we compared hypothalamic and pituitary response to fasting (72 h) in normal male rats and rats with isolated GH deficiency (spontaneous dwarf rats (SDR)). Circulating GH levels were undetectable in SDR, and IGF-I levels were less than 10% of normal controls. Fasting stimulated NPY mRNA levels in SDR; however, the rise in NPY mRNA levels was not accompanied by a fall in GHRH mRNA, as observed in fasted normal rats. In fact, GHRH mRNA levels paradoxically rose in the fasted SDR to 135% of fed controls. At the pituitary level, fasting did not alter sst2 and sst5 mRNA levels in SDR but did stimulate the expression of GHRH-R and GHS-R to 165% and 149% of fed controls, respectively. These results demonstrate that the fasting-induced changes in pituitary expression of sst2 and sst5, but not GHRH-R and GHS-R, are GH/IGF-I dependent. In addition, these results argue against the theory that the negative association of NPY and GHRH expression observed following fasting represents a simple cause-and-effect relationship and suggest that GH, either directly or indirectly, mediates the effects of fasting on hypothalamic GHRH expression.

Actins↗

Effect of a short-term fast on intestinal disaccharidase activity and villus morphology of piglets suckling insulin-like growth factor-I transgenic sows.

The objectives of this study were to use transgenic sows that overexpress IGF-I in milk to investigate the effect of a short-term fast on piglet intestinal morphology and disaccharidase activity and to determine how milk-borne IGF-I influences the response to fasting. After farrowing, litters were normalized to 10 piglets. On d 6, piglets (n = 30) suckling IGF-I transgenic (TG) sows and piglets (n = 30) suckling nontransgenic sows (control) were assigned randomly to three treatments: fed piglets (0 h), which remained with the sow until euthanized on d 7, or fasted piglets, which were removed from the sow at either 6 or 12 h before euthanasia on d 7. Serum IGF-I and IGFBP, intestinal weight and length, jejunal protein and DNA content, disaccharidase activity, and villus morphology were measured. Fasting for 12 h resulted in a negative weight change between d 6 and 7 (quadratic response to fasting; P < 0.001). Piglets suckling TG sows tended to have greater intestinal length (P = 0.068), but no effect of IGF-I overexpression was noted for intestinal weight. Fasting, however, resulted in linear (P < 0.001) and quadratic (P = 0.002) decreases in intestinal weight. Serum IGF-I did not differ between control and TG sows, but decreased linearly (P = 0.003) with fasting. Serum IGFBP-4 decreased (linear and quadratic; P < or = 0.02) with fasting, whereas IGFBP-1 increased quadratically (P < 0.001) with fasting. Jejunal villus height, width, and crypt depth were all increased with fasting (linear and quadratic; P < 0.04). Disaccharidase activity was not affected by fed state; however, piglets suckling TG sows had greater jejunal lactase-phlorhizin hydrolase (P < 0.01) and sucrase-isomaltase (P = 0.02) activities than control piglets. In summary, intestinal weight, villus morphology, serum IGF-I, serum IGFBP-1 and -4, and piglet BW change were altered (P < or = 0.02) in response to fasting. Thus, the duration of food deprivation before euthanization should be considered when designing experiments to assess intestinal development or the IGF axis, as the magnitude of differences between the fed and fasted state may exceed those expected as a result of experimental treatment.

Animals↗

Hypercholesterolaemia of prolonged fasting and cholesterol lowering of re-feeding in lean human subjects.

Serum cholesterol and triglycerides were determined in 36 lean, healthy adults (mean body mass index = 24.3 +/- 0.4 kg m-2) during a period of fasting of 7-21 days. Fasting for 1 week resulted in significant elevation of serum cholesterol (mean increase 25%, range 0-68) and triglycerides (mean increase 24%). No correlation was observed between pre-fast cholesterol level and fasting-induced hypercholesterolaemia. Continued fasting for up to 21 days resulted in lowering of both cholesterol and triglycerides to pre-fast levels. One week of hypocaloric re-feeding resulted in significantly lower than pre-fast cholesterol (mean decrease 13%) and significantly higher than prefast triglycerides (mean increase 86%). The net change in serum cholesterol observed as a result of fasting and re-feeding correlated with prefast cholesterol (r = -0.6901, p = 0.0001). No significant change in the ratio of unesterified cholesterol to total cholesterol was observed during fasting. Fasting for 3 weeks followed by 1 week of hypocaloric re-feeding, however, resulted in a significant (p = 0.05) increase in this ratio from 0.27 +/- 0.0057 to 0.34 +/- 0.01. Fasting for 1 or 2 weeks followed by re-feeding also resulted in a similar increase in the ratio of unesterified cholesterol to total cholesterol. Cholesterol in the HDL fraction remained within normal range throughout the fasting and re-feeding period, with no significant changes between time points.

Adult↗