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We measured the effects of iopanoic acid on thyroid hormone metabolism in obese men during severe calorie restriction to study the nutrition regulation of thyroid hormone metabolism. Eight morbidly obese men received a weight-maintenance diet followed by 6 wk of 600 kcal/d. During underfeeding, patients received iopanoic acid or placebo for 2-wk periods in a double-blind crossover fashion. Underfeeding alone (UF) produced a 28.3% decline in the serum triiodothyronine (T3) concentration, and iopanoic acid plus underfeeding (IOP) produced a 49.5% decline in T3 concentration from baseline. Serum reverse T3 concentrations increased 289% during IOP compared with UF alone (p less than 0.001). Serum TSH concentration was unchanged by underfeeding but increased twofold during IOP treatment. Thyroid hormone kinetics demonstrated a decrease in T3 production during IOP compared with UF. These findings suggest that calorie restriction regulates T3 production by modulating only type I 5'-deiodinase activity.

This study examined changes in body fat distribution in 68 women who lost an average of 12.3 kg from an initial weight of 103.6 kg. Weight reduction was accompanied by a small but statistically significant reduction of 1.2% in the waist-to-hip ratio, suggestive of a reduction in upper-body obesity. Subjects with greater upper-body obesity tended to achieve greater reductions in the waist-to-hip ratio. Changes in five circumference measures were highly correlated with losses of fat and showed that subjects with lower-body obesity tended to lose large amounts of fat from both their upper and lower fat depots while subjects with upper-body obesity lost fat primarily from their upper depots. Women with lower-body obesity tended to lose more total body fat than did women with upper body obesity (r = -0.26, p less than 0.04).

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.

The background information is reviewed regarding the American Society for Clinical Nutrition task force consensus statement on calories. Prevention or treatment of obesity necessarily involves manipulation of energy intake and output. The most important public health disorders to which obesity contributes are cardiovascular disease, diabetes mellitus, gallbladder disease, psychosocial disability, and musculoskeletal disorders. Other conditions associated with obesity include renal disease, liver disorders, ventilatory defects, venous stasis and thromboembolisms, gout, cerebrovascular disease, and (in women) endometrial and possible breast cancer. Obese persons are open to greater risk from surgery, anesthesia, and accidents, and they have a high rate of employee absenteeism. Statistics regarding relative body weight and longevity are examined.

It has been suggested that sufficient fiber in the diet will tend to prevent excessive food intake and depot fat accumulation by decreasing the caloric density of the diet, stowing rate of food ingestion, increasing the effort involved in eating, promoting intestinal satiety, and interfering slightly with efficiency of energy absorption. The increase in the prevalence of obesity in Western countries since 1900 has taken place concurrently with marked changes in the nature of the diet. Per capita intake of dietary fiber associated with starchy foods has greatly decreased, but intake of fiber associated with fruits and green vegetables has increased. Thus, although the type of fiber in the diet has changed, the total quantity may not have diminished considerably. Studies of the effect of caloric dilution with cellulose and other metabolically inert bulking agents have disclosed little or no inhibitory effect on the spontaneous energy intake of nonobese laboratory animals and human subjects. Nevertheless, there is evidence that obese rats and humans may defend their excess weight against nutritive dilution with less tenacity than their nonobese counterparts. The hypothesis that dietary fiber can protect against obesity therefore deserves further testing since an increase in the fiber content of the diet may tend to prevent overeating and excessive weight gain even if it does not reduce spontaneous energy intake in nonobese organisms.

Five different procedures were used to estimate composition of weight loss by six obese individuals maintained on low-calorie regimens: 1) energy-nitrogen (E-N) balance; 2) total body water-nitrogen balance (TBW-N); 3) total body water (TBW); 4) total body potassium (TBK); and 5) an anthropometric method. Quantity of weight lost by obese subjects during comparison periods lasting 25–40 days ranged from 7.9 to 17.1 kg. Expressed as percent of aggregate weight loss, collective fat loss was 47.6 by E-N balance; 46.3 by TBW-N balance; 51.7 by TBK; 50.9 by anthrometry; and 33 by TBW. The E-N balance method yielded a tight cluster of individual means, whereas the other procedures gave a wide scatter of means. For short-term studies, the E-N balance procedure, although tedious and difficult, should yield results less variable than those generated by any of the other methods examined.

The effects of starvation, an 800-kcal mixed diet and an 800-kcal ketogenic (low carbohydrate-high fat) diet on the composition of weight lost were determined in each of six obese subjects during three 10-day periods. The energy-nitrogen balance method was used to quantify the three measurable components of weight loss; protein, fat, and water. On the 800-kcal ketogenic diet, subjects lost (mean +/- SE) 466.6 +/-51.3 g/day; on the isocaloric mixed diet, which provided carbohydrate and fat in conventional proportions, they lost 277.9+/- 32.1 g/day. Composition of weight lost (percentage) during the ketogenic diet was water 61.2, fat 35.0, protein 3.8. During the mixed diet, composition of loss was water 37.1, fat 59.5, protein 3.4...

The study was designed to determine whether overfeeding rats with a diet containing medium-chain triglyceride (MCT) as the major fat source (45% of calories) would impede the expected gain in weight and body fat as compared to rats overfed with isocaloric amounts of diet containing long-chain triglyceride (LCT). For 6 wk rats were fed either MCT diet or LCT diet twice daily via a gastrostomy tube. MCT-fed rats gained 20% less weight (P less than 0.001) and possessed fat depots weighing 23% less (p less than 0.001) than LCT)-fed rats. Mean adipocyte size was smaller (p less than 0.005) in MCT- than in LCT-fed rats. Weights of carcass protein and water were similar for both groups as were concentrations of serum insulin and levels of physical activity. The decreased deposition of fat in the MCT-fed rats may have resulted from obligatory oxidation of MCT-derived fatty acids in the liver after being transported there via the portal vein, leaving almost no MCT derivatives for incorporation into body fat. MCT may have potential for dietary prevention of human obesity.

Although the association between body weight and blood pressure is irrefutable, body fat mass and blood pressure level may not necessarily be directly related. To clarify the relative contribution of fat mass to blood pressure level, we analyzed data on 399 adults consecutively entering a weight control program. Although most subjects were notably overweight (mean ideal body weight 177%), the population represented a wide spectrum of body weights and blood pressure levels. Study parameters included body fat mass (by total body water, 40K, and Steinkamp formula), lean body mass, body build (chest to height ratio), fat cell number and size from bilateral buttock biopsy specimens, upper fat pattern by arm to thigh circumference ratio, and central fat pattern by subscapular to triceps skinfold ratio. Our results concurred with previously noted correlations between obesity and blood pressure (as mean arterial pressure): weight (r = 0.44), percentage of body fat (r = 0.19), and absolute fat mass (r = 0.38; all p less than 0.01); however, lean body mass, age, and body build correlated highly with both fat mass and mean arterial pressure, thereby confounding this relationship. Multivariate analysis was performed to evaluate the relative contribution of fat mass to mean arterial pressure in the presence of these and other potentially confounding variables. Lean body mass, age, body build, and an upper body fat pattern were found to contribute significantly to the variation in mean arterial pressure (p less than 0.01). In their presence, percentage of body fat, absolute fat mass, central fat pattern, fat cell characteristics, and age of onset of obesity did not significantly improve the predictability of mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose tissue, the logical target component in weight reduction regimens, was measured in five obese subjects during weight reduction, and in four normal weight controls. The two compartment model of Ljunggren, consisting of adipose tissue (AT) and adipose tissue-free mass (AFM), was further developed by finding experimental values for total water, extracellular water (ECW), lipid, and cell solids in 16 biopsied subjects. The AFM was estimated from body potassium content (40K counting) by use of an age/sex specific constant for the K content in the fat free body. Five obese subjects maintained for 46 days on regimens averaging 800 kcal/day had initial AT from 48% to 60% of body weight compared with AT 27% to 46% in four normal controls. Weight reductions averaged 17.4 kg (12% of initial weight), with approximately equal reductions in adipose tissue, adipose-free mass, and water. Initial fluid compartment ratios in the obese were unusually high (ECW:ICW in AFM was 0.74 +/- 0.23 [S.D.] compared with 0.42 +/- 0.05 in normals); these values returned toward normal (to 0.59 +/- 0.06) with weight reduction. The fact that it was possible to disclose a hitherto unappreciated abnormality of hydration in the adipose-free mass of obese subjects and its change toward normal with weight reduction, suggests that the adipose:adipose-free model may have a special utility when body composition measurements are used to monitor the effects of weight reduction regimens on various body constituents.

Fat patterning was studied in a sample of 76 obese women before and after weight reduction by principal components analysis. Circumferences were selected as variables rather than skinfolds because circumferences correlated more highly with body composition determined either by total body water or total body potassium. A separate sample of 136 males and females, measured once, was employed to validate the results. The validation sample yielded similar findings. Two significant components were found, the first contrasting upper and lower fatness and the second trunk and extremity fatness. Waist circumference was the best predictor of upper-body fat patterning. For the lower body, thigh circumference loaded more highly than did the iliac crest circumference. Arm circumference did not contribute significantly to upper-lower fat patterning.

The spontaneous food intake of six normal-weight male volunteers was measured for 24 days while the subjects were inpatients on a metabolic unit. They were fed a palatable diet of conventional foods and were kept unaware that their food intake was being measured. On days 7-18 the caloric content of their diet was covertly reduced by 25% by substituting aspartame-sweetened analogues for all menu items containing sucrose. Subjects did not alter their food intake for 3 days. Then between days 4-6 on the aspartame diet, they increased their intake to compensate for 40% of the missing calories. Food intake stabilized at 85% of baseline and remained the same for the rest of the 12-day dilution period. Subjects did not show a shift in either sweetened or unsweetened food choices while their diet was being diluted. In adjusting for the missing calories, they simply ate more of their customary diet. The replacement of sucrose by aspartame tended to curb the weight gain observed on the baseline diet.

SummaryAdministration of glucagon intravenously to 7 normal subjects resulted in prompt abolition of gastric hunger contractions on each of 16 occasions. This was associated with decrease in the experience of hunger and coincided with a rise in blood glucose levels and an increased peripheral capillary-venous glucose difference. Fall in blood glucose levels with decreasing capillary-venous differences was associated with a return of hunger contractions and intensification of the experience of hunger in 14 of the 16 occasions. Such a pattern may be a component of the normal satiety mechanism.

NUTRITION in clinical medicine has come to have several different connotations depending on whether one is thinking of diagnosis and specific treatment or of patient management. Under the first hea...

The ingestion of a diet higher in caloric content than is required for energy needs leads to energy storage; this is accomplished by the deposition of triglycerides in adipose tissue. There is no clear evidence that the metabolic burden of excess calories is in any way hazardous to health except insofar as it leads to weight gain and eventually to obesity. Some studies show that a high caloric intake coupled with physical exertion that is sufficiently increased to maintain energy balance may be more beneficial to health than is a lower caloric intake balanced by a reduction in physical activity. Caloric intake and physical activity are so interrelated that it is impossible to gauge the effects of one independently of the other.

O delineate the role of nutrition in the regulation of blood pressure and the pathogenesis of hypertension, the National Heart, Lung, and Blood Institute in conjunction with the National Institute on Aging and the National Institutes of Health Nutrition Coordinating Committee, sponsored a Workshop on Nutrition and Hypertension in Bethesda, Maryland, on March 12 to 14, 1984. The purpose of the workshop was to identify the research needed to strengthen the understanding of the relationships between nutrition, blood pressure regulation, and hypertension. This research is important for two reasons: first, there is still an enormous amount of knowledge to be gained about the pathogenesis of hypertension, and any insights that can be derived about nutritional influences are highly desirable. Second, because the majority of patients with elevated blood pressure fall in the borderline and mild hypertensive categories, there is a need to support research on nonpharmacological strategies for management of these patients, in particular, nutritional interventions. The format of the workshop consisted of two major activities: position papers on selected dietary nutrients that may influence blood pressure and working group sessions devoted to the specification of research objectives. In addition to touching on an overview of hypertension and nutrition research methods, the position papers expounded on the roles of sodium and other electrolytes; caloric intake and obesity; dietary proteins, amino acids, carbohydrates, alcohol, and trace metals; and dietary fats and prostaglandins. Nutritional considerations of special populations, including the young and the elderly

Six morbidly obese subjects were maintained in a metabolic ward for 64 days on liquid diets providing 600 to 800 kcal/day. Three received protein at a level of 1.5 g/kg desirable weight per day. The other three were given an identical diet in which half the protein was replaced by carbohydrate. Because there were no significant differences in either mean protein or mean fat losses between the two groups, the data on all six subjects were combined. Over the 64 days, the mean weight loss (±SEM) ofthe subjects per 1000 kcal deficit was 174.3 ± 25.5 g. The composition of this weight loss was 36.0% water, 58.9% fat, and 5.1% protein. Although the rate of fat loss was relatively constant throughout the study, wide interindividual variations in cumulative protein (nitrogen)deficit were observed. Total nitrogen losses per subject ranged from 90.5 to 278.7 g. Cumulative nitrogen loss during the first 16 days tended to correlate negatively with initial mean fat cell size and positively with initial lean body mass. Most notable was the strong negative correlation between the size of the decrease in serum triiodothyronine over the 64-day study and the magnitude of the concurrent cumulative N deficit. During severe caloric restriction, one's ability to decrease circulating serum triiodothyronine levels may be critical to achievement of an adaptational decrease in body protein loss. Am J C/in Nuir l984;40:6l1-622.

Compression of the animal stomach gives rise to vagal discharges that could signal satiety. To test a noninvasive method of inducing compression of the human stomach, we first employed extra-abdominal pressure levels of 0, 10, and 20 Torr, counterbalanced for sequence, in six lean and obese subjects. A large blood pressure cuff was wrapped around the abdomen of the subject with the air bladder over the epigastrium. The bladder was inflated before ingestion of a liquid meal by the subject until satiated. Relative to 0 Torr, pressures of 10 and 20 Torr significantly reduced spontaneous food intake (P less than 0.03) without producing discomfort. In a second study, extra-abdominal pressure of 20 Torr also raised intragastric pressure by a mean of 5.5 Torr (P less than 0.03). In a third study, extra-abdominal pressure of 20 Torr did not alter gastric emptying rate during meal ingestion but ultimately enhanced emptying rate when this pressure was maintained for greater than 100 min after meal completion (P less than 0.01).

In comparison with lean marathon runners whose fat content was 15%, obese subjects with a fat content of 55% showed a 36% reduction in intracellular potassium. It is hypothesized that as much as 60% of this decrease may have been due to the lower proportion of muscle (which has the highest intracellular potassium of any tissue) in the fat free mass of very obese subjects. The remainder of the decrease seems to have been a measurement artefact owing to self-absorption of gamma rays by adipose tissue, most of which is distributed over potassium rich lean tissue. The low intracellular potassium values found in obesity should not be interpreted as necessarily signifying potassium deficiency.

The effect of a medium chain triglyceride (MCT) preparation on blood ketones was determined in fourteen normal subjects and six patients with diabetes mellitus of the maturity-onset type. Ingestion of 100 gm. of the MCT (containing 86 per cent C8 and 14 per cent C10 fatty acids) was followed by a small but statistically significant rise in blood ketones in each of the groups. The rise in ketones was slightly but significantly higher in the diabetic patients than in the normal subjects. In all subjects, ketone rises were negligible after ingestion of 100 gm. of corn oil. The ketogenic effect of MCT may result in part from its rapid absorption from the gut, with a high proportion of the component fatty acids traveling in the portal vein directly to the liver in the free acid form. In the liver, these fatty acids appear to be rapidly degraded and converted in part to ketones. The predictable mild hyperketonemia induced by MCT makes this glyceride a useful tool in the study of ketogenesis.

SummaryRats with depot fat enriched with undecanoate maintain significantly higher concentrations of liver glycogen and plasma glucose during prolonged starvation than do conventionally fed controls. When food motivated behavior was tested by means of a progressive ratio schedule of reinforcement, the undecanoate-enriched rats exhibited a significantly lower drive for food after 48 hr of starvation than did their nonenriched controls.We thank K. Porikos for critical comments on the manuscript and C. Wang and K. Ellis for technical assistance.

ONE of the most frustrating features of primary biliary cirrhosis is pruritus, often so intense and unrelenting that the victim seriously contemplates suicide.1 Such patients suffer from chronic insomnia and irritability, and their bodies become covered with excoriations from uncontrollable scratching. Attempts to control the intolerable itching with sedatives, analgesics, glucocorticoids and methyltestosterone have met with little success. Recently, norethandrolone has been reported fairly effective in relieving the pruritus; however, its administration is associated with deepening jaundice and other side effects.2 3 4 Bile acids accumulate in the blood of patients with primary biliary cirrhosis, and it has been proposed that the . . .

Serum Lipids and Atherogenesis With this necessarily sketchy discussion of lipid physiology as a background, it is appropriate to consider what the relation of the serum lipids and atherosclerosis ...