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PubMed2003

Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death.

Excitotoxic cell death is the fundamental process responsible for many human neurodegenerative disorders, yet the basic mechanisms involved are not fully understood. Here, we exploited the fact that the immature brain is remarkably resistant to seizure-induced excitotoxic cell death and examined the underlying protective mechanisms. We found that, unlike in the adult, seizures do not increase the formation of reactive oxygen species or result in mitochondrial dysfunction in neonatal brain, because of high levels of the mitochondrial uncoupling protein (UCP2). UCP2 expression and function were basally increased in neonatal brain by the fat-rich diet of maternal milk, and substituting a low-fat diet reduced UCP2, restored mitochondrial coupling, and permitted seizure-induced neuronal injury. Thus, modulation of UCP2 expression and function by dietary fat protects neonatal neurons from excitotoxicity by preventing mitochondrial dysfunction. This mechanism offers novel neuroprotective strategies for individuals, greater than 1% of the world's population, who are affected by seizures.

Age Factors↗

PubMed2001

Assessment of the effect of fat-modified foods on diet quality in adults, 19 to 50 years, using data from the Continuing Survey of Food Intake by Individuals.

Fat-reduction strategies and the role of fat-modified foods in the US diet were assessed using a nationally representative survey: the 1996 US Department of Agriculture Continuing Survey of Food Intakes by Individuals. A sample of 878 men and 853 women was included. The sample was divided into low fat and high fat based on the Dietary Guideline's cutoff poin of 30% or less of energy from total fat. The survey sample was further stratified in nonusers, low-users or high-users of fat-modified foods. Approximately 10% of 7,000 foods were classified as fat-modified. There was a 400 to 500 kcal difference in energy intake of individuals consuming low-fat compared with high-fat diets. Adults who were users of fat-modified foods consumed more nutrient-dense diets, with higher intakes of vitamin A, folate, and iron. Not all fat-reduction strategies were equally effective in reducing fat and maintaining nutrient intake. Nonusers of fat-modified foods who consumed a low-fat diet tended to do so by substituting carbohydrate, in part from carbonated beverages, for fat. Both men and women consuming a low-fat diet had lower average BMIs; this difference between individuals consuming low-fat vs high-fat diets was significant for women who were high-users of fat-modified foods. The data suggest that a low-fat diet with high use of fat-modified foods may be one strategy for achieving adequate nutrient intake while maintaining weight in the desirable BMI range of 19 to 25.

Adolescent↗

PubMed1998

Olestra Postmarketing Surveillance Study: design and baseline results from the sentinel site.

OBJECTIVE: To describe the design of the Olestra Postmarketing Surveillance Study (OPMSS) and to present baseline results from the sentinel site. The purpose of the OPMSS is to monitor consumption patterns of olestra-containing snacks and to determine whether consumption affects nutritional status. DESIGN: The OPMSS combines repeated cross-section, random-digit dial telephone surveys before and after the market release of olestra-containing foods as well as intensive dietary and clinical assessments on a subsample of survey participants. SUBJECTS: Data are from baseline telephone (n = 1,962) and clinical (n = 1,069) assessment of participants (aged 18 to 74 years) in the Marion County, Indiana, sentinel site. Mean age of participants in the telephone survey was 43.2 years; 19% of respondents were black and 29% had completed college. STATISTICAL ANALYSIS: Analyses examined associations among savory snack use, fruit and vegetable consumption, and demographic and health-related characteristics. Data from the telephone survey were adjusted to be representative of the Marion County population. RESULTS: Almost 96% of the population surveyed had eaten savory snacks in the month before the survey: 74% had eaten regular-fat, 26% fat-reduced, and 78% nonfat types. Total snack consumption did not differ by gender, education, or race. Residents younger than 35 years ate snacks 16 times a month compared with 12 times a month among older residents. Types of snacks consumed differed markedly by demographic characteristics. Male, younger, and less educated residents ate more regular-fat snacks; female, white, and college-educated residents ate more nonfat snacks. In general, residents practicing healthful behaviors, including not smoking, eating fruits and vegetables, and exercising, also ate fewer regular-fat and more nonfat snacks. Fat intake was also related linearly to use of snack foods, ranging from 33.2% of energy among those consuming 1 serving per month or less to 36.8% among those consuming 20 or more servings per month. APPLICATIONS/CONCLUSIONS: Procedures for recruitment and nutrition assessment appear adequate for evaluating the impact of olestra consumption on nutritional status. Nutritionists should be aware that there is potential for relatively high olestra consumption, given that almost 35% of Marion County residents eat snack foods at least 20 times a month. Consumers eating at least 20 servings of snacks per month derived more than 12% of their total energy and fat from snack foods, which suggests that substituting olestra snacks could substantially reduce intakes of fat and energy.

Adolescent↗

PubMedDate not supplied

Classification of obese patients and complications related to the distribution of surplus fat.

The relation between obesity and noninsulin-dependent diabetes mellitus is established. The weak association between obesity and cardiovascular disease or stroke might be attributable to a risk present only in a subgroup of obesity patients. Recent prospective studies have shown such a group to be characterized by abdominal localization of adipose tissue, reviving old empiric observations of such links. The sex-linked adipose tissue distribution is probably dependent on a balance between glucocorticoids and sex steroid hormones. The former are active mainly on intraabdominal adipose tissues through the high density of a specific receptor expressing lipoprotein lipase activity. This effect is counteracted by female sex steroid hormones, mainly progesterone, which promote fat deposition in the gluteal-femoral regions, utilized mainly during pregnancy and lactation. Testosterone stimulates lipid mobilization through transcriptional expression of beta-adrenergic receptors via a specific androgen receptor and also inhibits lipoprotein lipase activity. Intraabdominal adipose tissues, drained by the portal vein, have a very sensitive lipolytic system in men, based on an increased beta-adrenoceptor activity. This is probably a testosterone effect via the mechanisms mentioned. With testosterone deficiency, these mechanisms are less active, permitting accumulation of fat that can be reversed by testosterone substitution. Abdominal distribution of fat in men thus is probably a sign of relative testosterone deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1997

Association between Ala54Thr substitution of the fatty acid-binding protein 2 gene with insulin resistance and intra-abdominal fat thickness in Japanese men.

Alanine to threonine substitution at codon 54 of the fatty acid-binding protein 2 (FABP2) gene was recently shown to be associated with insulin resistance in Pima Indians. It has been hypothesized that the mutation may result in enhanced intestinal up-take of fatty acids, and thereby an impairment of insulin action. We analysed the association of the Ala54Thr substitution with insulin sensitivity and abdominal fat thickness in 395 Japanese men aged 50.5 +/- 8.8 years (mean +/- SD) with a body mass index of 24.4 +/- 3.0 kg/m2. The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly associated with diabetes or impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by homeostasis model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher beta-cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h insulin concentrations in individuals homozygous for the Thr54 allele when compared with heterozygotes or homozygotes for the Ala54 allele. No significant association was obtained between the polymorphism of the FABP2 gene and body mass index. However, ultrasound measurements of abdominal fat thickness revealed a greater accumulation of intra-abdominal fat in subjects homozygous for the Thr54 allele, whereas subcutaneous fat thickness was not associated with the polymorphism. These observations suggest that the Ala54Thr substitution in the FABP2 gene is associated with insulin resistance in Japanese men, and that visceral fat accumulation might be involved in the impaired insulin action associated with the substitution.

Abdomen↗

PubMed1995

Integration of the overall response to exercise.

Physical activity ellicits major perturbations in metabolism during the period of exertion and continues to influence metabolism afterwards as well. The overall effect of these intermittent and extended effects on the balance between energy expenditure and food intake regulation can best be judged by the impact of exercise on the fat mass. Expansion of the adipose tissue mass promotes fat oxidation more than glucose oxidation, but excessive fat accumulation is often necessary to reach the state where fat oxidation becomes commensurate with fat intake. Since the steady-state of weight maintenance is achieved with less body fat in physically active individuals, exercise is a substitute for an enlarged fat mass in bringing about rates of fat oxidation commensurate with fat intake. The increases in energy expenditure induced by expansion of the adipose tissue mass or by physical activity are quantitatively very different. The fact that they are substitutes for each other in relation to body weight maintenance indicates that the critical issue, under conditions where food availability is not a limiting factor, is not overall energy turnover. It appears therefore that it is the effect of exercise on the 24-h RQ that allows the organism to operate with an average RQ as low as the diet's FQ in the presence of less body fat. This also explains why the diet's carbohydrate-to-fat ratio can be an important parameter in shaping the interactions between physical activity and body weight maintenance.

Animals↗

PubMed1988

Trends in coronary heart disease mortality and food consumption in the United States between 1909 and 1980.

This study is an ecological comparison of coronary heart disease (CHD) mortality trends and trends in food consumption in the United States population between 1909 and 1980. CHD mortality data were obtained from published vital statistics. National food disappearance data, compiled regularly by the US Department of Agriculture (USDA), were the primary source of dietary information used. Food balance sheets and USDA household survey data were used for corroborative purposes. Dietary data were analyzed to observe trends in the per capita consumption of calories and fat; to determine the contribution of major food groups to both calories and fat; and to determine the effect of substitutions within those food groups on consumption of calories and fat. Dietary substitutions towards less-saturated fatty acids support the hypothesized relationship between dietary fat and CHD. These changes preceded CHD mortality changes by 10-20 y.

Coronary Disease↗

PubMed1997

Changes in food consumption in Brazil.

Changes in eating habits have occurred in the last decades in several countries associated to demographic, economic, social and epidemiologic factors. In Brazil, the available data about food consumption are the result of Family Budget Surveys undertaken by Getúlio Vargas Foundation and IBGE (Brazilian Institute of Geography and Statistics) in 1961/1963 and 1987/88, respectively, and the National Study of Family Expenditure (ENDEF), carried out by IBGE during 1974/75. They reveal as principal tendencies the decreasing consumption of staple foodstuffs (beans, rice, manioc flour), pork meat, lard and butter, the replacement of bovine meat for chicken, and the increase in the consumption of eggs, milk products and vegetable oils. Based on these surveys, the intake of macronutrients in urban areas showed a decrease of carbohydrate and an increase of fat contribution as sources of calories, an increase in the consumption of animal protein in detriment of vegetable protein, and substitution of animal fats for vegetable fats. It was also observed an increase in the use of industrialized foodstuffs, directly related to income, leading to a greater diversity of foodstuffs and lower consumption of staple foods. Recent studies with adult and elderly population from the city of São Paulo show a reduction in the consumption of fatty and fried foods and sugar, and an increase in the consumption of fruits and vegetables because of health concern. Studies that take into account the verified changes in eating habits and the new consumption tendencies, as well as their impact on nutritional and health conditions of the Brazilian urban population, are presently needed.

Brazil↗

PubMed1994

Effects of a tristearate-containing lipid and canola oil on plasma and tissue lipids in rats.

Male Sprague-Dawley rats were fed semipurified diets containing 12% fat and 0.4% cholesterol for 4 wk. The fats were palm oil, a high-stearate fat and canola oil; each of the latter two fat sources was substituted for palm oil in 4% (w/w) increments (i.e, 4, 8 and 12%) thus yielding 3 stearate-containing, 3 canola-containing, and a 12% palm oil diet. Stearate-fed animals exhibited significantly decreased food efficiency ratios, plasma total cholesterol, and liver cholesterol whereas the substitution of canola for palm oil did not consistently alter these parameters. Liver fatty acids generally reflected the composition of the dietary fat sources with the exception of significantly higher arachidonate observed in the stearate-fed rats.

Animals↗

PubMed1995

Secular trends in diet and risk factors for cardiovascular disease: the Framingham Study.

OBJECTIVE: In this study we examined changes in dietary intake and risk factors for cardiovascular disease that occurred over three decades in a US-population-based sample. DESIGN: Secular trends in dietary profiles and risk factors were studied in cross-sectional samples of subjects from the Framingham Study in 1957-1960, 1966-1969, and 1984-1988. RESULTS: Dietary levels of cholesterol appeared to have declined considerably, whereas macronutrient and fatty acid intakes appeared to change only slightly. Men appeared to increase their saturated fat intakes from 16.4% in 1966-1969 to 17.0% in 1984-1988 (P < .01). In spite of relatively stable mean total fat intake levels, 35% to 60% of Framingham Study men and women reported decreased consumption of higher-fat animal products over the 10-year period between 1974-1978 and 1984-1988. Framingham subjects who reported modifying their diets by substituting lower-fat foods for high-fat items between 1974-1978 and 1984-1988 were more likely to achieve the guidelines of the National Cholesterol Education Program and Healthy People 2000 for dietary fat and cholesterol intake and for serum total cholesterol level. Levels of systolic and diastolic blood pressure, total and low-density lipoprotein cholesterol, and cigarette smoking were also lower in 1984-1988 than in earlier times. Compared with 1957-1960, mean body mass index and prevalence rates of overweight and hypertension were higher in 1984-1988, despite higher levels of reported physical activity. CONCLUSIONS: The observed secular trends in diet and risk factor levels for cardiovascular disease in the Framingham population are important to guide the development and implementation of population-based strategies for promoting cardiovascular health, including nutrition interventions.

Adult↗

PubMed2006

Evaluation of pet food by-product as an alternative feedstuff in weanling pig diets.

Three experiments were conducted to evaluate pet food by-product (PFB) as a component of nursery starter diets and its effects on pig performance. The PFB used in these studies was a pelleted dog food that contained (as-fed basis) 21% CP, 1.25% total lysine, and 8.3% ether extract. In Exp. 1, 288 early-weaned pigs (5.2 kg at 14 d) were used to determine the effects of replacing animal protein and energy sources with PFB at 0, 10, 30, and 50% (as-fed basis) inclusion levels in phase I (d 0 to 7 after weaning) and phase II (d 7 to 21 after weaning) diets. Phase I diets contained 27.5% whey, 18.75% soybean meal, 1.50% lysine, 0.90% Ca, and 0.80% P, with PFB substituted for corn, fat, plasma protein, fish meal, limestone, and dicalcium phosphate. Phase II diets had a constant 10% whey, 1.35% lysine, and PFB was substituted for blood cells, a portion of the soybean meal, and other ingredients as in phase I diets. In phase I, growth performance by pigs fed PFB-containing diets was similar to that of the control diet. In phase II, ADG (linear; P < 0.05 and quadratic, P < 0.005), ADFI (linear and quadratic, P < 0.01), and G:F (quadratic, P < 0.01) were increased with increasing PFB inclusion. In Exp. 2, 80 weaned pigs (6.7 kg at 21 d) were fed a common phase I diet for 1 wk and used to further evaluate the effect of PFB in phase II diets (same as Exp 1; initial BW = 8.1 kg) on growth performance and apparent total tract nutrient digestibility. There were no differences in ADG, ADFI, or G:F across treatments. Dry matter and energy digestibility did not differ among diets; however, digestibilities of CP (P < 0.05) and the essential AA, arginine (P < 0.02), histidine (P < 0.01), lysine (P < 0.001), threonine (P < 0.01), and valine (P < 0.01), were greater as PFB was increased in the diet. In Exp. 3, the performance by pigs (n = 1 70; 5.5 kg; 21 d of age) fed diets with 0 or 30% PFB in both phases I and II was examined. Growth performance was similar in both diets. These studies demonstrate that pet food by-product can effectively be used as a partial replacement for animal protein sources and grain energy sources in the diets of young nursery pigs.

Animal Feed↗

PubMed2000

Ad libitum intake of low-fat diets rich in either starchy foods or sucrose: effects on blood lipids, factor VII coagulant activity, and fibrinogen.

People are advised to reduce their intake of saturated fat and replace it by carbohydrate to avoid coronary heart disease. It is unknown whether sucrose and starchy foods, two major sources of carbohydrates, have similar effects on cardiovascular risk markers if incorporated as a replacement for saturated fat into diets eaten ad libitum. We served 20 healthy, normal-weight women aged 21 to 52 years three strictly controlled diets ad libitum: FAT, high in total fat (46% of total energy [E%]) and saturated fat (21 E%); STARCH, high in total carbohydrates (59 E%) and low in sucrose (2.5 E%); and SUCROSE, high in total carbohydrates (59 E%) and sucrose (23.2 E%). The diets were eaten in randomized order for a period of 2 weeks. Blood lipids, factor VII coagulant activity (FVIIc), and fibrinogen concentrations were measured with subjects in the fasted state (9:45 AM) and the postabsorptive state (6:00 PM). STARCH was associated with lower total cholesterol (mean difference, 0.34 mmol/L; 95% confidence interval [CI], 0.18 to 0.50), low-density lipoprotein (LDL) cholesterol (0.25 mmol/L; 95% CI, 0.13 to 0.37), fasting triglycerides (0.15 mmol/L; 95% CI, 0.07 to 0.23), nonfasting triglycerides (0.44 mmol/L; 95% CI, 0.30 to 0.58), and nonfasting FVIIc (9.8%; 95% CI, 3.8 to 15.8) than SUCROSE. Compared with FAT, STARCH resulted in a desirable decrease of LDL cholesterol and nonfasting FVIIc. STARCH was also associated with a minor weight loss (0.7 kg) that was not found on the other 2 diets. We conclude that starchy foods with a natural content of dietary fiber can be recommended as substitutes for saturated fat in the dietary prevention of coronary heart disease. According to the present short-term findings in healthy females, substitution with sucrose is not advisable.

Adult↗

PubMedDate not supplied

[Duodenal obstruction due to chronic pancreatitis].

Chronic pancreatitis may cause a number of obstructive complications. Obstructions of the pancreatic and common bile duct are the most frequent, obstruction of the duodenum is rare and obstruction of the colon is very rare. Duodenal stenosis caused by chronic pancreatitis is usually moderate so that the surgical treatment is not necessary except if operation is necessary for other obstructive complications. The severe isolated duodenal stenosis for which surgery is mandatory is rare. We present a 46-year old male suffering from chronic alcoholic pancreatitis causing almost complete duodenal obstruction in whom surgical treatment was necessary. The truncal vagotomy and gastroenterostomy were performed. With abstinence of alcohol, low fat diet and substitute therapy more than 3 years after surgery the patient is symptom-free. He regained the previous weight and shows tendency to become fat.

Chronic Disease↗

PubMed2004

Dietary fat, insulin sensitivity and the metabolic syndrome.

Insulin resistance is the pathogenetic link underlying the different metabolic abnormalities clustering in the metabolic syndrome. It can be induced by different environmental factors, including dietary habits. Consumption of energy-dense/high fat diets is strongly and positively associated with overweight that, in turn, deteriorates insulin sensitivity, particularly when the excess of body fat is located in abdominal region. Nevertheless the link between fat intake and overweight is not limited to the high-energy content of fatty foods; the ability to oxidize dietary fat is impaired in some individuals genetically predisposed to obesity. Insulin sensitivity is also affected by the quality of dietary fat, independently of its effects on body weight. Epidemiological evidence and intervention studies clearly show that in humans saturated fat significantly worsen insulin-resistance, while monounsaturated and polyunsaturated fatty acids improve it through modifications in the composition of cell membranes which reflect at least in part dietary fat composition. A recent multicenter study (KANWU) has shown that shifting from a diet rich in saturated fatty acids to one rich in monounsaturated fat improves insulin sensitivity in healthy people while a moderate alpha-3 fatty acids supplementation does not affect insulin sensitivity. There are also other features of the metabolic syndrome that are influenced by different types of fat, particularly blood pressure and plasma lipid levels. Most studies show that alpha-3 fatty acids reduce blood pressure in hypertensive but not in normotensive subjects while shifting from saturated to monounsaturated fat intake reduces diastolic blood pressure. In relation to lipid abnormalities alpha-3 fatty acids reduce plasma triglyceride levels but in parallel, increase LDL cholesterol. Substitution of unsaturated fat for saturated fat not only reduces LDL cholesterol but contributes also to reduce plasma triglycerides in insulin resistant individuals. In conclusion, there is evidence available in humans indicating that dietary fat quality influences insulin sensitivity and associated metabolic abnormalities. Therefore, prevention of the metabolic syndrome has to be targeted: (1) to correct overweight by reducing the energy density of the habitual diet (i.e., fat intake) and (2) to improve insulin sensitivity and associated metabolic abnormalities through a reduction of dietary saturated fat, partially replaced, when appropriate, by monounsaturated and polyunsaturated fats.

Diet, Reducing↗

PubMed1975

Effects of carbohydrate-free diets on the insulin-carbohydrate relationships in rats.

Insulin-carbohydrate relationships were investigated in four groups of young rats fed low protein diets differing in carbohydrate and fat contents: (1) a diet in which the nonprotein energy was provided by fatty acids (FA); (2) a similar diet in which the fatty acids were substituted by neutral fat (NF); (3) FA diet supplemented with glycerol (FA-Glyc); and (4) a carbohydrate-rich diet (HC). Control rats were fed a stock diet. Rats fed the FA diet lost weight, were hypoglycemic and hypoinsulinemic in the fed state and normoglycemic and normoinsulinemic in the fasted state, and had an impaired glucose tolerance and hyperinsulinemia after a glucose load. Liver and muscle glycogen were low in fed rats. Fasting increased glycogen in liver and decreased glycogen in muscle. NF animals gained weight, were hypoglycemic in both fed and fasted states, and their plasma glucose level after an oral glucose load was almost normal. Plasma insulin/glucose ratio, both in fed and fasted states and after a glucose load indicated hyperinsulinism, which was accompanied by obesity. Muscle and liver glycogen were low in fed animals and did not change after a fast. Supplementation of the FA diet with glycerol (FA-Glyc) abolished weight loss and fasting hyperglycemia and normalized plasma glucose and insulin response to a glucose load. Rats fed the HC diet had an improved glucose tolerance and an increased sensitivity to insulin. Liver glycogen was high in the fed state and normal in the fasted state, whereas muscle glycogen was normal in both nutritional states.

Animals↗

PubMed1990

Effects of fat supplementation and immature alfalfa to concentrate ratio on lactation performance of cattle.

Forty-six multiparous Holstein cows were assigned 5 d postpartum to a completely randomized design employing a 2 x 3 factorial treatment arrangement. Factors were 0 or 5% added prilled fat (DM basis) substituted for shelled corn and alfalfa silage fed in forage-to-concentrate ratios of 45:55, 64:36, and 84:16 (DM basis). Interactions between fat and forage level were not observed for any of the parameters measured. Energy density, calculated using data from a digestibility trial, was similar between 45:55 and 64:36 diets (1.66 Mcal NE1/kg) and was lower with 84:16 diets (1.48 Mcal NE1/kg) for the 100 d trial. Fat supplementation increased energy density of the diets (1.67 vs. 1.53 Mcal NE1/kg). Dry matter digestibility, energy intake, and 4% FCM yields were similar for cows fed 45:55 and 64:36 diets and lower for those fed the 84:16 diets. Fat supplementation did not affect DM digestibility. Dry matter intake declined with increasing forage level and fat supplementation. Milk yield decreased as forage level increased. Fat supplementation did not affect yield of milk or FCM. Milk fat percentage was lower for cows fed 45:55 than 64:36 or 84:16 diets. Fat supplementation increased milk fat percentage. Milk protein yield decreased as forage level increased but was unaffected by fat supplementation. Results suggest higher levels of concentrate support higher milk yields, and prilled fat supplementation improves fat test when fed with immature forages. Prilled fat supplementation did not enhance lactation performance because of depressed DM intake in early lactation.

Animal Feed↗

PubMed1984

Studies with sucrose polyester.

Sucrose polyester (SPE) is a lipid synthesized from sucrose and fatty acid methyl esters. SPE has physical and organoleptic properties that closely resemble triglycerides, but it is not hydrolysed in the intestine and therefore not absorbed. By providing a persistent lipophilic phase in the intestine, SPE reduces the absorption of lipophilic substances such as cholesterol. SPE leaves the stomach more rapidly than triglyceride oils, presumably because of the absence of an effect on duodenal receptors. In studies with obese subjects, dietary SPE reduced total and LDL cholesterol by reducing the absorption of cholesterol from the intestine. In a study, in which SPE was covertly substituted for dietary fat, ten obese subjects in a weight-loss regimen did not increase dietary intake to compensate for the energy removed from the diet by SPE substitution. In a similar study with five naive, obese subjects, the investigators concluded that the mean energy intake decrease during SPE treatment [184 (769 kJ) kcal/d] was not significant. SPE continues to be studied as a means of reducing energy intake.

Cholesterol↗

PubMed1996

Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition.

OBJECTIVE: Studies with GH substitution in GH-deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End-points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day) versus placebo treatment for 12 months. DESIGN: Twenty-nine patients (mean age 45.5 +/- 2.0 years) with adult-onset GHD were studied in a double-blind, parallel design. Measurements of body composition by means of conventional anthropometry, bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and isometric muscle strength were performed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex-matched subjects was included. RESULTS: Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment. Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantly higher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral and subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P < 0.01) to levels no longer different from the control group. CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle: fat ratio (%) (placebo: 58:42 (baseline) vs 58:42 (12 months); GH: 66:34 (baseline) vs 72:28 (12 months) (P = 0.002); normal subjects: 67:33 (P < 0.05 when compared to 12 months placebo data)). Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over-hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7 +/- 9.8 (baseline) vs 51.6 +/- 8.2 (12 months); GH: 64.9 +/- 13.3 (baseline) vs 73.5 +/- 13.6 (12 months) (P < 0.05)). Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF-I levels (microgram/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270 +/- 31 (12 months GH) vs 156 +/- 8 (normal subjects (P < 0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months. CONCLUSIONS: (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained; (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo-controlled conditions; (3) uncontrolled data on muscle strength must be interpreted with caution; (4) a daily GH substitution dose of 2 IU/m2 seems too high in many adult patients.

Abdomen↗