A computerized eating monitor which weighed the amount and rate that food was eaten by groups of normal and obese children. The results were:

a) The normal weight children ate 293 +/- 108 grams of food during 9.6 +/- 3.5 minutes and the obese children ate 339 +/- 339 grams of food during 8.5 +/- 3.2 minutes. These differences are not considered statistically significant due to the size of the study. However, the obese consumed about 15% more.

b) The Obese children ate faster, 42 +/- grams per minute compared with the normal weight children who ate 33+/- 14 grams per minute.

c) The Obese did not decelerate during the second half of the meal, whereas normal weight children did decelerate with mean Im value of 0.15 +/- 0.13, where Im is calculated as the intake of food in the first half of the meal minus the intake in the second half, divided by the total intake. This difference was considered statistically significant.

d) Many other items were studied with little else considered significant.

Sichieri, Rosely, et al, "Relative Weight Classifications in the Assessment of Underweight and Overweight in the U.S.", International Journal of Obesity (1992) 16, 303-312

9-17% of U.S. population is considered Underweight, 25-45% were categorized as overweight, with Black and Mexican-American women leading with 38%-58.6%. Recommended BMIs provided from various sources.

Schlundt, David G., et al, "Identification of High-Risk Situations in a Behavioral Weight Loss program: Application of the Relapse Prevention Model", International Journal of Obesity (1989( 13, 223-234

Review of 36 studies concerning behavioral weight loss programs and including at least one year follow-up. They reported an average of 15 pounds weight loss decreasing to 12 pounds at one year follow-up. The trouble is that most participants are much more than 10-15 pounds overweight. Individuals seem to be unable to maintain the kinds of lifestyle changes necessary for long-term weight loss. These studies note an inability to adhere to caloric restriction for more than the average 12 week behavioral program, where usually, individuals were able to make rapid and substantial changes in nutrient intake over a nine week meeting. Three basic categories of high-risk situations emerge: Positive social interactions, negative emotions, and physiological craving.

Tokunaga, Katsuto, et al, "Ideal Body Weight Estimated from the Body Mass Index with the Lowest Morbidity", International Journal of Obesity (1991), 15, 1-5

A study of 4565 Japanese men and women aged 30-59 years. Ten medical problems served as indices of morbidity: lung disease, heart disease, upper GI disease, hyperlipidemia, hyperuricemia, diabetes mellitus, and anemia. From this study, they propose that the ideal BMI is 22 kg/m², for the age group studied.

Fricker, J., et al, "Circadian Rhythm of Energy Intake and Corpulance Status in Adults", International Journal of Obesity (1990), 14, 387-393

The dietary history method of questioning participants provides little difference in the consumption habits between obese and non-obese subjects. Minor increase in consumption at lunch was noted.

Burns, Catherine M., et al, "Nutrition Knowledge in the Obese and Overweight", International Journal of Obesity (1987) 11, 485-492.

In this study, the Obese and Overweight scored better than other groups on a 20-question multiple choice questionnaire on nutrition knowledge. Therefore, health education as a form of treatment for overweight is questioned.

Gaul, Donna J., et al, "Relationship Between Eating Rates and Obesity", Journal of Consulting and Clinical Psychology (1975), 43-2, 123-125

A comparison was made in eating behaviors of obese and nonobese subjects in a naturalistic setting. It was found that obese subjects took more bites, performed fewer chews per bite, and spent less time chewing than did nonobese subjects.

Lappalainen, Raimo, "Hunger/Craving Responses and Reactivity to Food Stimuli during Fasting and Dieting", International Journal of Obesity (1990), 14, 689-688

Groups of dieting and fasting obese patients were instructed to report their feelings of hunger and craving continuously during a three-week treatment period. Hunger responses show a decrease during fasting but not during dieting. This confirms the prior result of LeGoff, et al, that a consistent pattern of dietary restraint (as in anorexics) is related to less hunger, as measured by salivary response to food odors, and that a sporadic pattern of dietary restraint (as in bulimics) is related to more hunger.

Wadden TA, Sternberg JA, Letizia KA, Stunkard AJ, Foster GD. "Treatment of obesity by very low calorie diet, behavior therapy, and their combination: a five year prospective", Int J Obesity 1989.

Wadden el al has shown that if no other treatment is given, less than 5% of individuals maintain weight loss for five years after completion of a comprehensive weight reduction program.

Woo R, " The effect of increasing physical activity on voluntary food intake and energy balance.", Int J Obes 1985;9 Suppl 2:155-60

Energy homeostasis with increased physical activity is dependent upon compensatory changes in intake. Results from metabolic balance studies in obese women indicate a dissociation of energy intake from that expended as exercise. Voluntary intake remained fixed at a sedentary level whether activity was added to or subtracted from total daily expenditure. The importance of physiological factors such as excess energy stores or psychological factors such as habit or sensory perceptions in obesity needs consideration.

Friedman MI, " An energy sensor for control of energy intake", Proc Nutr Soc 1997 Mar;56(1A):41-50

Control of energy intake, either in response to changes in the energy content of food or in energy expenditures and storage, is based on the detection of a feedback signal generated in the processing of metabolic fuels for energy. Evidence from studies of the fructose analogue, 2,5-AM, indicates a sensor in liver responds to changes in intracellular ATP or some closely associated event and communicates this information to the brain via vagal afferent neurons. Such a mechanism could serve as the energy sensor which controls energy intake.

Preparation and Use of Food-based Dietary Guidelines, Report of a Joint FAO/WHO Consultation, Technical Report Series, No. 880, 1998, vi + 108 pages, ISBN 92 4 120880 5

This report provides an expert practical guide to the formulation and implementation of national dietary guidelines based on recommended foods and food groups rather than nutrients. Addressed to policy-makers and the nutritionists who advise them, the report aims to facilitate the use of food-based dietary guidelines as a sensible new way to help consumers make healthy food choices. Throughout the report, recommendations – whether concerning the importance of food variety or the percent of dietary protein that should be of animal origin – draw on the latest biochemical and physiological knowledge about human nutritional requirements in health and disease. Health problems related to both dietary insufficiency and excess are considered in this comprehensive report.

The book opens with an explanation of the many reasons why dietary recommendations based on foods are more effective as an instrument of public health nutrition than are guidelines based on nutrients. Readers are also reminded of the need to formulate dietary guidelines in response to specific diet-related health problems important in a country, and to ensure that recommendations are based on sound scientific evidence.

Against this background, the first main section establishes the scientific rationale for the development of food-based dietary guidelines, drawing on current knowledge in four main areas: nutrition science; food science and technology; educational, behavioral, and social sciences; and agricultural and environmental sciences. The section also compares different methods for assessing the nutritional quality of diets and explains each of the steps to follow when reorienting dietary recommendations from nutrients to foods. Methods of monitoring food and nutrient intake are presented and compared in the next section, which includes advice on how data from a range of sources can be used when setting dietary goals and formulating recommendations.

Section three provides detailed, step-by-step guidance on how to develop food-based dietary guidelines and ensure that populations understand them and follow their advice. The remaining sections explain how to transform guidelines into message and slogans and monitor their effectiveness in improving dietary practices.

In a key achievement, the second part of the report provides an expert state-of-the-art review of scientific knowledge, from animal, clinical, and epidemiological studies, about the relationship between diet, nutrition and health. Throughout this review, a special effort is made to identify areas where scientific data support firm dietary recommendations based on individual foods, food groups, and food combinations. Information ranges from advice on the use of nutrient densities in the development and evaluation of dietary guidelines, through data on the role of vitamins as chemopreventive agents, to a discussion of non-nutrient components found in fruit that may explain their capacity to prevent cardiovascular diseases and gastrointestinal cancers. The report concludes with examples of the ways in which foods and food groups have been incorporated into dietary guidelines in selected countries.

Medicine & Science in Sports and Exercise, (from 11/30/1998 Union Tribune)

Study focussed on the effects of gentle cycling on college women with high levels of anxiety. The women reported feeling less anxious after just 20 minutes of pedaling on a stationary bike at 40% of their maximum capacity. Previous research had indicated that higher exercise intensity was needed to reduce anxiety.

Fletch· er· ism (Flech´b riz´b m), n. the practice of chewing food until it is reduced to a finely divided, liquefied mass: advanced by Horace Fletcher, 1849-1919, U.S. Nutritionist [1905-1910, Amer.] --Fletch· er· ize´, v.t., -ized, -iz· ing. Webster's College Dictionary, Random House, 1996.

Weyer C, Linkeschowa R, Heise T, Giesen HT, Spraul M " Implications of the traditional and the new ACSM physical activity recommendations on weight reduction in dietary treated obese subjects", Int J Obes Relat Metab Disord 1998 Nov;22(11):1071-8

Ewbank PP, Darga LL, Lucas CP, " Physical activity as a predictor of weight maintenance in previously obese subjects", Obes Res 1995 May;3(3):257-63

We examined the association between exercise and weight loss maintenance in a group of 45 previously obese subjects 2 years post very-low-calorie diet (VLCD) to suggest exercise goals for this population. At baseline, subjects weighed a mean 100 kg and had a mean total cholesterol (TC) of 5.8 mmol/L. With VLCD they lost an average 28 kg and decreased their TC by 1.6 mmol/L. Two years post-VLCD their weight and lipids were measured and they completed a physical activity survey (Paffenbarger). Subjects were grouped into tertiles by reported exercise levels: low active (< 850 kcals per week), moderate active (850-1575 kcals per week) and high active (> 1575 kcals per week). Walking accounted for the greatest calorie expenditure (65%). Analysis of variance showed that baseline characteristics and weight and blood lipid changes during the VLCD did not differ (P > 0.05) among groups. At follow-up, high active patients maintained significantly greater weight loss, had a lower percent regain and a significantly greater decrease in total cholesterol (P < 0.05) than less active patients. Multiple regression analysis indicated that total exercise calories independently predicted overall weight loss and percent regain (r = 0.66 and r = 0.62, respectively). Exercise calories also predicted total cholesterol change (r = -0.37). The high active group walked more miles (16.2 per week) than the low and moderate active groups (4.8 and 9.1 per week, respectively) and exercised more days per week (5.3 vs. 1.9 and 3.7).

van Dale D, Schoffelen PF, ten Hoor F, Saris WH, " Effects of addition of exercise to energy restriction on 24-hour energy expenditure, sleeping metabolic rate and daily physical activity.", Eur J Clin Nutr 1989 Jul;43(7):441-51

Body composition, sleeping metabolic rate (SMR), 24-h energy expenditure (24-EE) and daily physical activity were determined in 12 obese women during and after 12 weeks of exercise (4 h per week on 55 per cent of VO2 max) and/or energy restriction (2.9-3.5 MJ/d). Diet(D) and diet-exercise (DE) groups were formed by matching the subjects on their body mass index (BMI, kg/m2; mean 30.3). After 12 weeks no significant differences were shown in loss of weight (D 12.2 and DE 13.2 kg) and loss of fat mass (D 9.4 and DE 10.9 kg). Both groups reduced their SMR (D 29.9 per cent and DE 21.7 per cent) and their metabolic rate during the entire night measured by indirect calorimetry (12-EE) (D 36.4 per cent and DE 28.6 per cent; P less than 0.05). Energy expenditure over 24 h, estimated by means of heart-rate monitoring, was reduced by 22.1 per cent for D and by 19.6 per cent for DE (n.s.). Daily physical activity, which was determined during 5 d using an actometer, was increased after 12 weeks for DE (27 per cent; P less than 0.05) and D (10 per cent; n.s.). The suggestion that a reduction in normal activities of daily life in a diet-exercise group is the explanation for the absence of significant differences in weight and fat loss between a diet-exercise and a diet group is not confirmed in this study. Daily physical activity showed a significantly higher increase for the diet-exercise group than for the diet group, while the decline of SMR and 24-EE tended to be smaller.

Huttunen NP, Knip M, Paavilainen T, " Physical activity and fitness in obese children.", Int J Obes 1986;10(6):519-25

Daily physical activity and physical fitness were studied in 31 obese and 31 normal-weight children matched for age and sex. The ages of the children ranged from 5.7 to 16.1 years. The history of their physical activity was examined using a questionnaire completed by the child and the parents. Physical fitness was measured using a two-stage exercise test on a bicycle ergometer. There were no significant differences in daily activities between the obese and the non-obese children, while the sports grades at school were lower and participation in the training teams of sports clubs was less frequent among obese than normal-weight subjects. The obese children were physically less fit than the normal-weight subjects as judged from the pedalling time in exercise test (P less than 0.05) and from the maximum oxygen consumption (VO2 max) related to lean body mass (LBM) (P less than 0.001). Twenty-seven children participated for 1 year in a weight-reduction programme which comprised individual nutrition counselling, guidance on physical activities and supportive therapy. The reduction in weight was successful in 25 out of 27 children and VO2 max increased on average from 44.2 to 47.1 ml/min/kg of LBM (P less than 0.025). There was no change in the time used for physical activities during the weight reduction period although the children's participation in the training teams of sports clubs increased. It was concluded that obese children are less fit than their non-obese counterparts. Weight reduction results, however, in an improvement of the maximum oxygen consumption towards normal.

Kempen KP, Saris WH, Westerterp KR, " Energy balance during an 8-wk energy-restricted diet with and without exercise in obese women.", Am J Clin Nutr 1995 Oct;62(4):722-9

The effects of severe energy restriction alone (2.0 MJ/d for 4 wk and subsequently 3.5 MJ/d for 4 wk) or energy restriction plus moderate exercise on energy balance were studied in 20 healthy obese women. Subjects aged 25-50 y were matched on the basis of body mass index and percentage body fat and randomly assigned to diet alone (D) or diet and exercise (DE) for 8 wk. DE resulted in a significantly increased loss of fat mass compared with D (7.8 +/- 0.8 compared with 5.5 +/- 0.8 kg; P < 0.05). The average daily metabolic rate measured with doubly labeled water decreased with both treatments, with no differences between the treatments. Energy balance data show that the DE treatment resulted in a significantly greater energy deficit than the D treatment. The relative contribution of fat to energy expenditure during exercise was significantly enhanced by DE treatment whereas it did not change after D. The energy expended on physical activity was not changed at the end of both treatments, with no differences between the two groups. The unchanged energy expended on physical activity indicates that DE might be accompanied by partial compensation of daily physical activities outside the training for the energy expended during the training. The energy deficit due to energy restriction alone was not compensated by a decrease in free-living daily physical activities. Addition of moderate exercise to an energy-restriction program in obese women has advantages with respect to changes in body composition, energy expenditure, and substrate utilization.

Bertram SR, Venter I, Stewart RI , " Weight loss in obese women--exercise v. dietary education.", S Afr Med J 1990 Jul 7;78(1):15-8

It was postulated that a nutrition-education programme was as effective an adjunct to a diet-based weight-loss programme as an exercise regimen. Forty-five obese female volunteers were placed on the same 5,000 kJ diet and were then assigned to each of three therapy groups: (i) an exercise group, involving three 1-hour exercise sessions per week (15 women); (ii) a lecture group involving a weekly 1-hour group lecture session (15); and (iii) a control group (15) who received only the diet and no activity. Weight loss, body fat loss (%) and daily energy intake reductions were equally reduced in the subjects in all three groups who completed the programme. There was, however, a significantly higher dropout rate in the control group. Taking this into account, the weight loss in the two test groups was similar and greater than that of the control group. We conclude that, in the short term, dietary education was as effective as exercise in promoting dietary compliance and weight loss.

Miller WC, Koceja DM, Hamilton EJ, " A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention.", Int J Obes Relat Metab Disord 1997 Oct;21(10):941-7

OBJECTIVE: The therapeutic effectiveness of diet, exercise, and diet plus exercise for weight loss in obesity was determined.

DATA SOURCES: All human research reported in English, published in peer-reviewed scientific journals within the past 25 y was reviewed.

STUDY SELECTION: Acceptance criteria (n = 493 from > 700 studies) were that a therapeutic intervention of diet, exercise or diet plus exercise was employed, specifically for weight reduction in obese adult humans and that weight change was reported numerically. Only aerobic exercise studies were included, while drug, hormone and surgical treatments were excluded.

DATA EXTRACTION: All data were extracted by the same investigator from the original research report. Except for gender and program type, all extracted data were numerical.

DATA SYNTHESIS: ANOVA, with a Newman-Keuls post hoc test, was used to determine differences among programs (P < 0.05). One analysis was performed on the group mean data and one based on effect sizes. Analyses were repeated using initial body weight, initial percent body fat and program length, as covariates.

RESULTS: Primarily, subjects aged 40 y have been studied (39.5 +/- 0.4 y, mean +/- s.e.m.) who are only moderately obese (92.7 +/- 0.9 kg, 33.2 +/- 0.5 body mass index (BMI), 33.4 +/- 0.7% body fat); for short durations (15.6 +/- 0.6 weeks). Exercise studies were of a shorter duration, used younger subjects who weighed less, had lower BMI and percentage body fat values, than diet or diet plus exercise studies. Despite these differences, weight lost through diet, exercise and diet plus exercise was 10.7 +/- 0.5, 2.9 +/- 0.4* and 11.0 +/- 0.6 kg, respectively. However, at one-year follow-up, diet plus exercise tended to be the superior program. Effect size and covariate analyses revealed similar program differences.

CONCLUSION: Weight loss research over the past 25 y has been very narrowly focused on a middle age population that is only moderately obese, while the interventions lasted for only short periods of time. The data shows, however, that a 15-week diet or diet plus exercise program, produces a weight loss of about 11 kg, with a 6.6 +/- 0.5 and 8.6 +/- 0.8 kg maintained loss after one year, respectively.

Racette SB, Schoeller DA, Kushner RF, Neil KM, Herling-Iaffaldano K , " Effects of aerobic exercise and dietary carbohydrate on energy expenditure and body composition during weight reduction in obese women.", Am J Clin Nutr 1995 Mar;61(3):486-94

To test the benefits of aerobic exercise and dietary carbohydrate during reduced-energy feeding, 23 obese women (44 +/- 4% fat) were randomly assigned to either aerobic exercise (Ex) or no exercise (Nx), and to a low-fat (LF) or low-carbohydrate (LC) reducing diet (5.00 +/- 0.56 MJ/d) for 12 wk. Changes in body composition, postabsorptive resting metabolic rate (RMR), thermic effect of a meal (TEM), and total daily energy expenditure (TDEE) were measured by respiratory gas exchange and doubly labeled water. Significant effects of Ex included a greater loss of fat mass (Ex: -8.8 +/- 2.1 vs Nx: -6.1 +/- 2.3 kg, P = 0.008) and maintenance of TDEE (Ex: +0.07 +/- 1.23 vs Nx: -1.46 +/- 1.04 MJ/d, P = 0.004), due to a difference in physical activity (Ex: +0.75 +/- 1.06 vs Nx: -0.61+/- 1.03 MJ/d, P = 0.006), which was not attributable solely to the Ex sessions. RMR in both groups decreased comparably (-0.54 MJ/d), and TEM (% of meal) did not change. Diet composition did not significantly influence body composition or energy expenditure changes, but a greater weight loss was observed after the LC than after the LF (-10.6 +/- 2.0 vs -8.1 +/- 3.0 kg, P = 0.037) diet. The addition of aerobic exercise to a low-energy diet was beneficial in the treatment of moderate obesity because of its favorable effects on body composition, physical activity, and TDEE.

Wadden TA, Foster GD, Letizia KA, Mullen JL, " Long-term effects of dieting on resting metabolic rate in obese outpatients.", JAMA 1990 Aug 8;264(6):707-11

There is growing concern that dieting may adversely affect the metabolic rate and exacerbate efforts to control weight. In this study we measured the resting metabolic rate nine times over 48 weeks in 18 obese women (108.0 +/- 3.1 kg) who were randomly assigned to one of two dietary conditions. Nine patients consumed approximately 5021 kJ/d (1200 kcal/d) throughout the 48 weeks, while the other nine consumed a 1757-kJ/d (420-kcal/d) diet for 16 of the first 17 weeks and a conventional reducing diet for the remainder of treatment. All patients increased their physical activity, primarily by walking. During the first 5 weeks, the fall in metabolic rate was more than double the relative reduction in weight. By contrast, at week 48, the metabolic rate of patients in the two conditions was reduced by 9.4% +/- 4.0% and 8.3% +/- 2.2%, respectively, while weight was reduced by 16.6% +/- 2.7% and 19.5% +/- 2.7%, respectively. Thus, neither dietary regimen, combined with modest physical activity, was associated with long-term reductions in resting metabolic rate that exceeded decreases anticipated with the achievement of a lower body weight.

Velthuis-te Wierik EJ, Westerterp KR, van den Berg H , " Impact of a moderately energy-restricted diet on energy metabolism and body composition in non-obese men.", Int J Obes Relat Metab Disord 1995 May;19(5):318-24

OBJECTIVE: Since little information is available on the capacity of the non-obese to adapt to a moderate decrease in energy intake, the effect of a 10-week moderately energy-restricted diet (ER) on energy expenditure and body composition was studied.

DESIGN: A controlled intervention study. After a weight-maintaining run-in period of 2 weeks, the ER group received a diet that contained 9.2 MJ/day on average, i.e. 80% of the energy of their habitual diet (estimated by means of a 7-day dietary record) for the next ten weeks while the control group received the weight-maintaining diet.

SETTING: Subjects continued daily life habits and came to the Institute every evening to have dinner and to receive food for the next 24 h.

SUBJECTS: 24 healthy non-obese, middle-aged men participated. Subjects were matched for age and body mass index and randomly assigned to a control group (n = 8) or an ER group (n = 16).

RESULTS: Average daily metabolic rate (ADMR, i.e. total energy expenditure), measured with doubly labeled water in eight subjects of the ER group, appeared to be 82.5% of reported energy intake resulting in an actual level of energy restriction in these eight subjects of 33% on average (range 18-42%), rather than 20%. Subjects in the ER group lost 7.4 +/- 1.7 kg; 83% of this weight loss was fat mass, 17% was fat-free mass. Subjects in the control group lost some weight too (2.1 +/- 1.5 kg). Resting metabolic rate (RMR) (MJ/day) decreased in the ER group (P < 0.001). In this group the thyroid hormone triiodothyronine (T3) decreased (P < 0.001), while reverse T3 (rT3) increased (P < 0.05). ADMR decreased significantly.

CONCLUSION: Under conditions of a controlled moderately energy-restricted diet in daily life a significant weight loss can be induced, similar to that observed after a balanced dietary deficit, providing 5 MJ/day. In addition, moderate energy restriction induces a decrease in fat-free mass and a fall in RMR.

van Dale D, Saris WH, ten Hoor F, " Weight maintenance and resting metabolic rate 18-40 months after a diet/exercise treatment ", Int J Obes 1990 Apr;14(4):347-59

In the present study 44 participants (32 females and 12 males) of the studies on the effects of a diet (D) diet-exercise (DE) treatment on body composition and sleeping metabolic rate (SMR), were followed over a period of 18, 36 or 42 months post-treatment.

Mean weight loss after treatment (12-14 weeks) was 12.0 and 16.5 kg for D and DE respectively (P less than 0.05; D. v. DE) and fat loss (9.5 kg and 13.5 kg for D and DE respectively, D v. DE P less than 0.05). Nine subjects dropped out during the follow-up phase. After 18, 36 or 42 months follow-up the diet group regained 90% of their initial weight loss compared to 60% of the diet-exercise group (P less than 0.05). Seven subjects out of the original diet-exercise group kept up their exercise activities, while two subjects from the diet group started exercising. These subjects (EX) gained only 23 per cent of their weight loss, but their body weight at the start of the study tended to be lower compared to the diet and the diet-exercise group (86.5 (EX) v. 91.4 and 95.2 for D and DE respectively).

During the last follow-up measurement SMR of 18 subjects was determined and revealed a persistent lower SMR for nine non-exercising subjects (18.6 per cent lower than before treatment), whereas for subjects who kept on exercising, SMR was 9.8 per cent lower than baseline values. Per kg FFM SMR was almost restored to baseline values for the EX group, whereas the non-exercising subjects still showed depressed values (EX 3.7 per cent and D + DE 15.8 per cent lower than before treatment; P less than 0.05).

It was concluded that exercise is one of the factors which contributes to the restoration of SMR and long term weight maintenance.

Finer N, Swan PC, Mitchell FT, " Metabolic rate after massive weight loss in human obesity ", Clin Sci 1986 Apr;70(4):395-8

Resting metabolic rate, measured by the ventilated hood technique in 11 obese subjects before weight loss was 6.5 +/- 0.3 kJ/min, not significantly different from the value predicted by regression equations relating metabolic rate to body weight (established from measurements in 106 subjects). After 34.5 kg mean weight loss, and during continued dieting, resting metabolic rate fell an average of 25% to 5.0 +/- 0.18 kJ/min, significantly below that predicted for the new slimmed weight. The fall in metabolic rate, over and above that expected from weight loss alone, suggests that the slimmed obese are hypometabolic compared with subjects of the same weight who have not lost weight. The failure of the slimmed obese to maintain their weight loss is unlikely to be due solely to this excessive fall in resting metabolic rate, since they still had quantitatively higher energy expenditure than lean subjects.

Heymsfield SB, Casper K, Hearn J, Guy D, " Rate of weight loss during underfeeding: relation to level of physical activity", Metabolism 1989 Mar;38(3):215-23

The kinetics and bioenergetic-metabolic determinants of weight loss were examined in obese women ingesting 900 kcal/d for 5 weeks. The patients were assigned either to a sedentary group (n = 5) or to an exercise group (n = 6) in which the participants expended an additional (X +/- SD) 346 +/- 61 kcal/d in aerobic physical activity. The percentage weight loss and the fractional rates (K1 = fast component; K2 = slow component) of weight loss were almost identical between the two groups. The failure of added exercise to increase the velocity of weight loss could not be explained by differences between the groups in any of the following: gastrointestinal energy and nitrogen (N) absorption; fractional rates of urinary urea N and total N loss; or the thermic effect of the formula diet. The cumulative and fractional rates of protein (ie N) loss were also similar between the groups. The exercise group lost more fat (5.3 +/- 1.0 kg) than the non-exercise group (4.4 +/- 1.6 kg, P less than .001) as measured by underwater weighing. The maximum between-group difference in the rate of fat loss, as determined by energy-N balance, occurred during early underfeeding. With continuation of the 900 kcal/d diet, the between-group differences in the rate of fat loss diminished. The exercise subjects significantly lowered their resting heat losses relative to the non-exercise subjects (P less than .025). This in turn reduced the degree of negative energy balance in the more energy-deficient exercise group.

Poehlman ET, Melby CL, Goran MI, " The impact of exercise and diet restriction on daily energy expenditure ", Sports Med 1991 Feb;11(2):78-101

In addition to the direct energy cost of physical activity, exercise may influence resting energy expenditure in 3 ways: (a) a prolonged increase in postexercise metabolic rate from an acute exercise challenge; (b) a chronic increase in resting metabolic rate associated with exercise training; and (c) a possible increase in energy expenditure during nonexercising time. It seems apparent that the greater the exercise perturbation, the greater the magnitude of the increase in postexercise metabolic rate. An exercise prescription for the general population that consists of exercise of low (less than 50% VO2max) or moderate intensity (50 to 75% VO2max) does not appear to produce a prolonged elevation of postexercise metabolic rate that would influence body-weight. Inconsistent results have been found with respect to the effects of exercise training and the trained state on resting metabolic rate. Whereas some investigators have found a higher resting metabolic rate in trained than untrained individuals and in individuals after an exercise training programme, other investigators have found no chronic exercise effect on resting metabolic rate. Differences in experimental design, genetic variation and alterations in energy balance may contribute to the discrepant findings among investigators. A relatively unexplored area concerns the influence of exercise training on energy expenditure during nonexercising time. It is presently unclear whether exercise training increases or decreases the energy expenditure associated with spontaneous or nonpurposeful physical activity which includes fidgeting, muscular activity, etc. The doubly labelled water technique represents a methodological advance in this area and permits the determination of total daily energy expenditure. Concomitant with the determination of the other components of daily energy expenditure (resting metabolic rate and thermic effect of a meal), it will now be possible to examine the adaptive changes in energy expenditure during nonexercising time. A plethora of studies have examined the combined effects of diet and exercise on body composition and resting metabolic rate. The hypothesis is that combining diet and exercise will accelerate fat loss, preserve fat-free weight and prevent or decelerate the decline in resting metabolic rate more effectively than with diet restriction alone. The optimal combination of diet and exercise, however, remains elusive. It appears that the combination of a large quantity of aerobic exercise with a very low calorie diet resulting in substantial loss of bodyweight may actually accelerate the decline in resting metabolic rate. These findings may cause us to re-examine the quantity of exercise and diet needed to achieve optimal fat loss and preservation of resting metabolic rate.

Donnelly JE, Jacobsen DJ, Jakicic JM, Whatley JE, " Very low calorie diet with concurrent versus delayed and sequential exercise ", Int J Obes Relat Metab Disord 1994 Jul;18(7):469-75

Obese females undergoing very-low-calorie diet (VLCD) were studied for 12 weeks to determine the effects of concurrent vs delayed and sequential exercise. Subjects were assigned to one of six groups: control (C) n = 28; endurance exercise (EE) n = 18; weight training (WT) n = 26; endurance exercise plus weight training (EEWT) n = 21; control for 4 weeks with subsequent EE (C4EE) n = 10; WT for 4 weeks with sequential EE (WT4EE) n = 12. EE was performed 3 days a week using five weight lifting exercises. Loss in body weight did not differ between groups. Expressed as a ratio of fat-free mass (FFM) to weight loss WT4EE showed a 8.1%, 9.7%, and 11.4% difference compared to EE, C4EE, and C, respectively (P < 0.05). WT4EE also showed significant increases from baseline of 8.2% in aerobic capacity (L/min) and 12.5% in the strength index (SI/kg FFM). WT4EE showed the smallest decrease of all groups in resting metabolic rate of 6.1% of the baseline value; however, this decrease was significant. Although WT4EE showed some favorable changes from baseline, the magnitude of the changes between groups was small. There were no significant differences found between C4EE and the other study groups. Thus, the delay or sequential use of exercise during VLCD provided only small differences for WT4EE compared to the other groups and any clinical significance for the individual is presently unknown.

Racette SB, Schoeller DA, Kushner RF, Neil KM," Exercise enhances dietary compliance during moderate energy restriction in obese women ", Am J Clin Nutr 1995 Aug;62(2):345-9

The effect of aerobic exercise on dietary compliance was assessed in 13 obese women (44 +/- 3% fat) during a 12-wk weight-reduction program (EX group). Seventeen obese women (45 +/- 5% fat) not engaged in aerobic exercise (NX group) served as control subjects. The reducing diets were designed to promote a weight loss of 1 kg/wk, with energy intakes individually prescribed (mean +/- SD: 4.9 +/- 0.6 MJ/d) to approximate 75% of each subject's measured basal metabolic rate. The EX group completed of three 45-min sessions/wk of supervised aerobic exercise at 65% of maximal oxygen consumption (VO2max). Daily energy intakes were calculated by summing changes in body stores, measured by total body water isotope dilution, and total daily energy expenditure, measured by doubly labeled water (DLW). Dietary compliance was assessed by comparing calculated intakes with prescribed intakes. Both the EX and NX groups reported consuming close to their prescribed daily intakes, with differences of -0.08 +/- 0.28 (EX group) and +0.03 +/- 0.57 (NX group) MJ/d, respectively. However, expenditure/balance data determined by the DLW method indicated that the EX subjects exhibited better dietary compliance than the NX subjects, with intakes exceeding those prescribed by only 0.7 +/- 1.5 compared with 2.3 +/- 1.6 MJ/d for the NX subjects (P = 0.01). Therefore, an additional benefit of aerobic exercise during energy restriction is enhanced dietary compliance, which has important implications for the treatment of moderate obesity.

Bingham SA, Goldberg GR, Coward WA, Prentice AM, Cummings JH, " The effect of exercise and improved physical fitness on basal metabolic rate ", Br J Nutr 1989 Mar;61(2):155-73

1. The suggestion that there is a sustained enhancement in metabolic rate after exercise was investigated during the course of a study in which six normal-weight volunteers (three men, three women) took part in a 9-week training programme. Baseline values were assessed in a 3-5 week control period of minimal activity before training. At the end of the study the subjects were capable of running for 1 h/d, 5 d/week.

2. Throughout the entire study the subjects were maintained on a constant diet. Measurement of energy expenditure by the doubly-labelled water (2H2(18)O) method showed that the subjects had an energy imbalance of +3% in the control and -20% at the end of the training period. The subjects were in positive (1.1 (SE 0.2) g) nitrogen balance in the second week of the control, and in negative (-0.6 (SE 0.3) g) N balance in the last week of the exercise period.

3. Over the course of the study maximum oxygen consumption (VO2max) and high-density-lipoprotein-cholesterol levels increased by 30%. Heart rate at rest and when performing a standard step test fell significantly.

4. Body composition was assessed weekly by 40K counting and skinfold thickness measurements, in addition to 2H2 dilution at the beginning and end of the study. Fat-free mass was apparently gained in the early phases of the study, but there was lack of agreement between the different methods of assessing body composition. Changes in body-weight were not significant.

5. Basal metabolic rate (BMR), overnight metabolic rate (OMR) and sleeping metabolic rate (SMR) were measured on three occasions: in the control period, and the beginning and end of the training periods. Average BMR in the control period was 5.91 (SE 0.39) MJ/24 h and was not changed with activity. There were no changes in OMR (5.71 (SE 0.27) MJ/24 h in the control) nor in SMR (5.18 (SE 0.27) MJ/24 h in the control), nor in BMR, OMR or SMR when expressed per kg body-weight, or per kg fat-free mass.

6. These results do not support the suggestions that there is a sustained increase in BMR following exercise that can usefully assist in weight-loss programmes.

Odber J, Cawood EH, Bancroft J, " Salivary cortisol in women with and without perimenstrual mood changes.", J Psychosom Res 1998 Dec;45(6):557-68

An increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA axis) is frequently associated with major depression. During the premenstrual phase of their reproductive cycle some women experience depressive mood changes that are proposed to be of similar intensity to that experienced during periods of major depression. This study examined the secretion of cortisol, the end-product in the HPA axis, at different stages of the menstrual cycle in women with and without premenstrual depression. Women who experienced only mild physical and emotional changes in the premenstrual phase of their cycle had a significantly higher cortisol secretion on a premenstrual day (measured hourly) compared to a postmenstrual day. Those who were significantly more depressed premenstrually showed the opposite pattern of cortisol secretion with significantly lower levels on the premenstrual day compared with the postmenstrual day. Across the menstrual cycle, women who were significantly more depressed premenstrually also had lower evening cortisol levels in their premenstrual phase. The results of this study indicate that, unlike major depression where the underlying neurological changes are manifest as overactivity of the HPA axis, premenstrual depressive changes are associated with reduced HPA axis activity. Premenstrual depression may, therefore, be similar neurologically to seasonal affective disorder, which is associated with underactivity of the HPA axis.

Choi PY, Salmon P, " Stress responsivity in exercisers and non-exercisers during different phases of the menstrual cycle ", Soc Sci Med 1995 Sep;41(6):769-77

It has been suggested that, premenstrually, women are more vulnerable to the effects of stress. It has also been proposed that the fitter the individual is, the less the body responds to, and the more quickly it recovers from, a stressful experience. The present study investigated whether premenstrual sensitivity to a stressful laboratory task would be attenuated in women who exercised. Responses to the task across the menstrual cycle were studied in 20 women who exercised regularly and 20 women who were sedentary. Heart rate and blood pressure as well as subjective mood responses were measured in each of three phases: premenstrual, menstrual and postmenstrual. Exercising and sedentary women differed in sensitivity to stress: heart rate responsivity to stress was less in exercisers, but mood fluctuation was greater. Menstrual cycle phase, by contrast, influenced general levels of heart-rate and mood, but did not affect responsivity to stress or performance. These findings suggest that the menstrual cycle and physical exercise have independent effects on cardiovascular and emotional state.

Stokes PE," The potential role of excessive cortisol induced by HPA hyperfunction in the pathogenesis of depression ", Eur Neuropsychopharmacol 1995;5 Suppl:77-82

Prolonged hypothalamic-pituitary-adrenocortical (HPA) axis overactivity occurs at all levels of this axis during stress in normals and some depressed patients. This can induce enlargement of the pituitary and adrenals. Various reports showed that cortisol can affect mood and behavior, and disrupt memory and recall. The integrity of the hippocampus is essential for memory function and, via the high density of its cortisol receptors, cortisol induced inhibitory feedback to the HPA axis. Animal data suggest that over time aging and stress can permanently downregulate hippocampal cell receptors, produce chronic hippocampal inflammation (astroglial), and kill cells. Cushing's syndrome patients (high cortisol) show diminished hippocampal size and verbal recall inversely related to cortisol levels. All the above is consistent with the 'cascade hypothesis' of cortisol induced hippocampal damage with resultant diminished inhibition to HPA hyperactivity in a circular manner. High cortisol is associated with altered neurotransmitter function, e.g., diminished brain serotonin synthesis, low CSF 5HIAA, and increased noradrenergic activity.

Halbreich U, Asnis GM, Zumoff B, Nathan RS, Shindledecker R, " Effect of age and sex on cortisol secretion in depressives and normals.", Psychiatry Res 1984 Nov;13(3):221-9

The mean 24-hour plasma level of cortisol with plasma sampling every 20-30 minutes was determined in 32 normal women aged 12-73, 40 normal men aged 10-55, 21 depressed women aged 20-61, and 11 depressed men aged 22-66. The mean levels of cortisol were higher in the group of depressives compared with the controls. Cortisol levels showed a significant linear correlation with age in normal women but not in normal men. Both depressed women and men had a significant linear increase of cortisol levels with age. The finding that age substantially contributes to increased levels of cortisol calls for cautious interpretation of any data concerning that hormone when the variable of age is not adequately controlled. Furthermore, aging and depression may have some underlying mechanisms whose elucidation may contribute to the understanding of the pathophysiology of vulnerability to affective disorders.

Kalin NH, Dawson G, Tariot P, Shelton S, Barksdale C, Weiler S, Thienemann M, " Function of the adrenal cortex in patients with major depression ", Psychiatry Res 1987 Oct;22(2):117-25

Failure to suppress cortisol secretion after administration of dexamethasone occurs in up to 50% of depressed patients. To test whether this hypothalamic-pituitary-adrenal (HPA) overactivity is associated with adrenocortical hyperresponsiveness, we performed dexamethasone suppression tests (DSTs) and adrenocorticotropic hormone (ACTH) stimulation tests in depressed subjects and subjects with other psychiatric disorders. Three groups were defined: depressed nonsuppressors, depressed suppressors, and other suppressors. While predexamethasone and postdexamethasone cortisol concentrations were greater in the depressed nonsuppressor group, ACTH concentrations did not differ among groups. After receiving alpha-ACTH[1-24] (4.2 micrograms/kg), depressed nonsuppressors had greater increases in stimulated cortisol secretion than the other groups. These results demonstrate that in a subgroup of depressed patients, HPA overactivity is associated with adrenocortical hyperresponsiveness.

Chapotot F, Gronfier C, Jouny C, Muzet A, Brandenberger G, " Cortisol secretion is related to electroencephalographic alertness in human subjects during daytime wakefulness ", J Clin Endocrinol Metab 1998 Dec;83(12):4263-8

To determine whether human hypothalamo-pituitary-adrenal axis activity is related to the alertness level during wakefulness, 10 healthy young men were studied under resting conditions in the daytime (0900-1800 h) after an 8-h nighttime sleep (2300-0700 h). A serial 70-sec gaze fixation task was required every 10 min throughout the daytime experimental session. The corresponding waking electroencephalographic (EEG) segments were submitted to quantitative spectral analysis, from which EEG beta activity (absolute power density in the 13-35 Hz frequency band), an index of central alertness, was computed. Blood was collected continuously through an indwelling venous catheter and sampled at 10-min intervals. Plasma cortisol concentrations were measured by RIA, and the corresponding secretory rates were determined by a deconvolution procedure. Analysis of individual profiles demonstrated a declining tendency for EEG beta activity and cortisol secretory rate, with an overall temporal relationship indicated by positive and significant cross-correlation coefficients between the two variables in all subjects (average r=0.565, P < 0.001). Changes in cortisol secretion lagged behind fluctuations in EEG beta activity, with an average delay of 10 min for all the subjects. On the average, 4.6+/-0.4 cortisol secretory pulses and 4.9+/-0.5 peaks in EEG beta activity were identified by a detection algorithm. A significant, although not systematic, association between the episodes in the two variables was found: 44% of the peaks in EEG beta activity (relative amplitude, near 125%; P < 0.001) occurred during an ascending phase of cortisol secretion, cortisol secretory rates increasing by 40% (P < 0.01) 10-min after peaks in EEG beta activity. However, no significant change in EEG beta activity was observed during the period from 50 min before to 50 min after pulses in cortisol secretion. In conclusion, the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEG beta activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.

Luecken LJ, " Childhood attachment and loss experiences affect adult cardiovascular and cortisol function ", Psychosom Med 1998 Nov-Dec;60(6):765-72

OBJECTIVE: This study proposes to test the hypothesis that early loss of a parent, coupled with poor quality family relationships, would result in long-term increased cardiovascular and cortisol reactivity to stress. METHODS: Subjects included 30 university students who lost one parent before age 16, and 31 control subjects. Blood pressure (BP) was measured continuously during 5-minute baseline and recovery periods, and during each of 2 tasks--viewing a 7-minute video clip depicting the death of a parent, and giving a 3-minute impromptu speech (1-hour rest between tasks). Salivary cortisol samples were collected immediately before each task, and at 5 and 20 minutes posttask. Quality of family relationships (FR) was measured using the Moos Family Environment Scale. RESULTS: Repeated-measures analysis of covariance revealed significant main effects on BP of both parental loss and FR for both tasks (all p values < .05) such that subjects who lost a parent or reported poor quality FR showed higher BP across all periods. The loss by FR by period interaction was not significant. An FR by period interaction was found for cortisol during the movie, in which poor quality FR subjects showed increased cortisol, whereas all others showed decreases. A loss by period interaction was found for cortisol during the speech, in which cortisol increased in loss subjects and decreased in non-loss subjects. CONCLUSIONS: These findings indicate that both childhood loss of a parent and poor quality of caretaking are associated with long-term increases in BP and altered neurohormonal responses to stress.

Larson MC, White BP, Cochran A, Donzella B, Gunnar M, "Dampening of the cortisol response to handling at 3 months in human infants and its relation to sleep, circadian cortisol activity, and behavioral distress", Dev Psychobiol 1998 Dec;33(4):327-37

The decrease in responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) system is marked over the first months of life. Seventy-eight healthy infants (44 girls), 7 to 15 weeks old, were given a laboratory mock physical examination. Salivary cortisol samples were collected pre- and postexamination and at home. Behavioral state during the examination and home sleep/wake activity were measured. Subjects younger than 11 weeks showed an increase in pre- to postexamination cortisol, while older subjects did not. Further, there was no decrease in behavioral distress to the examination with age. Infants who showed an early- morning peak (EMP) in home cortisol levels were significantly older and were likely to be those who slept through the night. However, the presence of an EMP was not associated with a lack of cortisol response to the examination. The decrease in cortisol responsiveness witnessed around the age of 3 months is presumably due to other processes associated with age, and not with the expression of the day-night rhythm in basal cortisol.

Armanini D, Spinella P, Simoncini M, Basso A, Zovato S, Pozzan GB, De Palo CB, Bucciante G, Karbowiak I, "Regulation of corticosteroid receptors in patients with anorexia nervosa and Cushing's syndrome ", J Endocrinol 1998 Sep;158(3):435-9

We have studied 16 patients with anorexia nervosa (11 with a stabilised weight loss and 5 in the weight-losing phase), 11 healthy controls, and 10 patients with Cushing's syndrome, by measuring plasma cortisol (by enzyme-immunoassay), ACTH (by RIA), corticosteroid (Type I-mineralocorticoid and Type II-glucocorticoid) receptors in mononuclear leukocytes (by radio-receptor assay), and lymphocyte subpopulations (by cytofluorimetry). In anorexic patients with a stabilised weight loss and in Cushing's syndrome the mean value of both Type I and Type II corticosteroid receptors in mononuclear leukocytes was significantly lower than in controls. The correlation between Type II receptors and plasma cortisol was inverse in stabilised anorexia nervosa and in Cushing's syndrome, and direct in healthy controls. Anorexic patients in the weight-losing phase showed a significant increase in plasma cortisol levels and a normal number of Type II receptors. From these results we hypothesise that in anorexia nervosa there is a progression from an increase in plasma cortisol in the weight-losing phase, to a concomitant decrease in Type II receptors when the disease is stabilised.

Tout K, de Haan M, Campbell EK, Gunnar MR, "Social behavior correlates of cortisol activity in child care: gender differences and time-of-day effects", Child Dev 1998 Oct;69(5):1247-62

The relations between social behavior and daily patterns of a stress-sensitive hormone production were examined in preschool children (N = 75) attending center-based child care. Three behavioral dimensions, shy/anxious/internalizing, angry/aggressive/externalizing, and social competence, were assessed by teacher report and classroom observation, and their relations with 2 measures of cortisol activity, median (or typical) levels and reactivity (quartile range score between second and third quartile values) were explored. Cortisol-behavior relations differed by gender: significant associations were found for boys but not for girls. Specifically, for boys externalizing behavior was positively associated with cortisol reactivity, while internalizing behavior was negatively associated with median cortisol. Time of day of cortisol measurement affected the results. Surprisingly, median cortisol levels rose from morning to afternoon, a pattern opposite to that of the typical circadian rhythm of cortisol. This rise in cortisol over the day was positively correlated with internalizing behavior for boys. The methodological and theoretical implications of these findings for the study of the development of hormone-behavior relations are discussed.

Field T, Schanberg S, Kuhn C, Field T, Fierro K, Henteleff T, Mueller C, Yando R, Shaw S, Burman I, "Bulimic adolescents benefit from massage therapy", Adolescence 1998 Fall;33(131):555-63

Twenty-four female adolescent bulimic inpatients were randomly assigned to a massage therapy or a standard treatment (control) group. Results indicated that the massaged patients showed immediate reductions (both self-report and behavior observation) in anxiety and depression. In addition, by the last day of the therapy, they had lower depression scores, lower cortisol (stress) levels, higher dopamine levels, and showed improvement on several other psychological and behavioral measures. These findings suggest that massage therapy is effective as an adjunct treatment for bulimia.

Metabolism 1998 Nov;47(11):1376-8

Treatment with growth hormone suppresses cortisol production in man.

Vierhapper H, Nowotny P, Waldhausl W

The effect of biosynthetic human growth hormone (GH) on the cortisol production rate was determined in healthy men (N=8) using the stable isotope dilution technique and mass spectrometry. 1alpha,2alpha-D-Cortisol was infused at a dose of 110+/-9 microg/h for 10 hours (8 AM to 6 PM). Blood samples obtained at 20-minute intervals from 2 PM to 6 PM were pooled during two 2-hour periods. Subsequently, each subject received a daily dose of biosynthetic human GH (4 IU/d subcutaneously [SC]) for 7 days. This resulted in an increase of plasma somatomedin C from a basal level of 0.65+/-0.13 U/mL to 1.18+/-1.2 U/mL on day 7 (P < .0001). Plasma concentrations of corticotropin (ACTH) and cortisol-binding globulin (CBG) were similar before and after administration of GH. Determination of the cortisol production rate was repeated on day 7 of treatment with GH. Due to its physiological diurnal rhythmicity, endogenous production of cortisol during basal conditions was higher (P < .05) between 2 and 4 PM (0.70+/-0.30 mg/h) versus 4 to 6 PM (0.55+/-0.28 mg/h). Following treatment with GH, the values were 0.40+/-0.11 mg/h (2 to 4 PM, P < .01 v day 1) and 0.31+/-0.11 mg/h (4 to 6 PM, P < .01 v day 1). Thus, in healthy men, treatment with SC, GH induces a decrease in endogenous cortisol production rates.

Med Hypotheses 1998 Oct;51(4):289-91

Cortisol's purpose.

Weber C

It is proposed that cortisol's primary purpose is to mobilize the body's defenses against water-losing intestinal diseases and corticosterone's against serum diseases. They do this by inversely controlling those immune cells, enzymes, and hormones, etc. that affect survival during infection. These glucocorticosteroids affect fight-or-flight mobilization as an adjunct made possible because most processes that enhance immunity have a reverse effect on fight-or-flight.

Med Hypotheses 1991 Mar;34(3):198-208

Cortisol and immunity.

Jefferies WM

The relationship between adrenocortical function and immunity is a complex one. In addition to the well-known detrimental effects of large, pharmacologic dosages of glucocorticoids upon the immune process, there is impressive evidence that physiologic amounts of cortisol, the chief glucocorticoid normally produced by the human adrenal cortex, is necessary for the development and maintenance of normal immunity. This evidence is reviewed, and the importance of differentiating between physiologic and pharmacologic dosages and effects is discussed. The popular use of synthetic derivatives of cortisol, which differ greatly from the natural hormone in strength, and the dynamic nature of the normal adrenocortical response, which varies with the degree of stress being experienced, have contributed to the confusion. Further studies of the nature of the beneficial effect of cortisol, and possibly of other normal adrenocortical hormones, upon immunity in humans are needed, especially in view of recent evidence of a feedback relationship between the immune system and the hypothalamic-pituitary-adrenal axis, and with the increasing awareness not only that the immune process provides protection against infection, but also that its impairment seems to be involved in the development of autoimmune disorders, malignancies and the acquired immunodeficiency syndrome (AIDS).

Acta Physiol Scand 1994 Jul;151(3):413-6

Lowering cortisol enhances growth hormone response to growth hormone releasing hormone in healthy subjects.

Dinan TG, Thakore J, O'Keane V

Cortisol is known to influence growth hormone release probably by modulating somatostatin tone. We examined the effect of metyrapone (the 11 beta-hydroxylase inhibitor) treatment on growth hormone response to growth hormone releasing hormone (1 microgram kg-1 body wt). Six healthy male subjects were tested on two occasions 1 wk apart. On one occasion they received metyrapone followed by growth hormone releasing hormone and on the other placebo followed by growth hormone releasing hormone. In all subjects metyrapone produced a significant drop in cortisol levels. Together with this drop there was a significant enhancement of growth hormone response to growth hormone releasing hormone. The GH response was negatively correlated with the cortisol level. Growth hormone release in response to growth hormone releasing hormone challenge is thus seen to be heavily influenced by cortisol levels.

Clin Exp Pharmacol Physiol Suppl 1998 Nov;25:S51-6

Cortisol and hypertension.

Kelly JJ, Mangos G, Williamson PM, Whitworth JA

1. In humans, the hypertensive effects of adrenocorticotropic hormone (ACTH) infusion are reproduced by intravenous or oral cortisol. Oral cortisol increases blood pressure in a dose-dependent fashion. At a dose of 80-200 mg/day, the peak increases in systolic pressure are of the order of 15 mmHg. Increases in blood pressure are apparent within 24 h. 2. Cortisol-induced hypertension is accompanied by a significant sodium retention and volume expansion. Co-administration of the type I (mineralocorticoid) receptor antagonist spironolactone does not prevent the onset of cortisol-induced hypertension. Thus, sodium retention is not the primary mechanism of cortisol-induced hypertension. 3. Direct and indirect measures of sympathetic activity are unchanged or suppressed during cortisol administration, suggesting that cortisol-induced hypertension is not mediated by increased sympathetic tone. 4. Preliminary evidence in humans suggests that suppression of the nitric oxide system may play a role in cortisol-induced hypertension. 5. These potential mechanisms of cortisol action may be relevant in a number of clinical contexts, including Cushing's syndrome, apparent mineralocorticoid excess, the hypertension of liquorice abuse and chronic renal failure. There is also preliminary evidence suggesting a role for cortisol in essential hypertension.

Biofeedback Self Regul 1996 Sep;21(3):217-28

Evaluation of stress induced by flight activity by measuring the hormonal response.

Farrace S, Biselli R, Urbani L, Ferlini C, De Angelis C

The aim of the present study was to quantitatively investigate the different levels of adaptation to flight and to evaluate the hormonal response to flight activity as a possible reliable tool to quantify the level of stress induced by flight. The hormonal response of growth hormone (GH), cortisol, and prolactin (PRL) to flight activity was evaluated in a group of student pilots (n = 11; all male; age 20 +/- 2 years) and flight instructors (n = 11; all male; age 27 +/- 2 years) of an Italian Air Force flight school. Blood samples were obtained immediately before and after a training flight session. Hormonal determination by RIA technique after flight showed a significant increase of plasma hormonal levels of GH, PRL, and cortisol in the students. Conversely, in the instructors only GH showed a significant increase versus preflight values, whereas PRL and cortisol did not show significant differences. Moreover, preflight hormonal levels of GH and PRL were significantly higher for student pilots compared to the same values for flight instructors. The data lead to establishing a close correlation between the hormonal response to flight activity and the level of tolerance and adaptation to flight-induced stress.

Med Hypotheses 1981 Mar;7(3):315-31

An adventitious role of cortisol in degenerative processes due to decreased opposition by insulin: implications for aging.

Sorenson D

Cortisol can be implicated as contributing to a number of degenerative processes including arteriosclerosis, atherosclerosis, diabetes, and deterioration of muscle and the immune system. These effects of cortisol are amplified in diabetes due to a diminished opposition by insulin. In addition, this phenomena may not be restricted to diabetes. There is evidence that tissue sensitivity to insulin generally decreases with age, although insulin levels and metabolism may remain constant; this is not generally true for cortisol. This results in an increased cortisol activity with some pathological consequences which are most evident in vascular connective tissue and the immune system. The decrease in tissue responsiveness to insulin with respect to cortisol may reflect relative aging differences in the corresponding receptor-effector systems.

Comp Biochem Physiol A 1986;83(4):727-30

Evaluation of oral administration of cortisol and metyrapone: the effects on serum cortisol in rainbow trout (Salmo gairdneri).

Bennett RO, Rhodes RC 3d

The effect of manipulating dietary levels of cortisol and metyrapone on peripheral concentrations of serum cortisol was examined in rainbow trout, Salmo gairdneri. Fish were fed 0, 10, 20, 30, 40 or 50 mg/kg body weight/day of metyrapone or cortisol for 7 days. All levels of cortisol tested increased peripheral levels of serum cortisol. Feeding a level of 30-40 mg/kg body weight/day of metyrapone depressed serum cortisol. We describe, herein, a noninvasive technique for suppression or stimulation of serum cortisol in rainbow trout.

Med Hypotheses 1984 Jan;13(1):31-44

Stress, cortisol, interferon and "stress" diseases. I. Cortisol as the cause of "stress" diseases.

Sapse AT

An attempt is made to define a biochemical formula for stress, as an overproduction of cortisol +/- impaired interferon response. The behavior Type A individual under stress, would exhibit elevated levels of cortisol with normal interferon response, whereas the Type C individual, would exhibit elevated levels of cortisol and impaired interferon responses. Evidence is presented that elevated levels of cortisol manufactured chronically under the affect of stress, and regardless of the type of individual affected, are a cause or the cause of chronic diseases, and not the result of same. This evidence would show that: Elevated levels of cortisol precede certain diseases, and do not follow them, when cortisol is checked out for this purpose in pre-disease conditions. When elevations of cortisol levels are induced through long-term corticosteroids therapy, in patients suffering of diseases requiring this type of treatment, conditions mimicking chronic diseases, would appear. When corticosteroids therapy would be discontinued, the "chronic diseases" mentioned above would disappear. When pharmaceuticals with potential cortisol antagonistic capabilities, were used in diseases totally unrelated, but having in common, elevated levels of cortisol, alleviation of symptoms and/or diseases would occur.

Med Sci Sports Exerc 1998 Nov;30(11):1603-7

Elevated serum antioxidant capacity and plasma malondialdehyde concentration in response to a simulated half-marathon run.

Child RB, Wilkinson DM, Fallowfield JL, Donnelly AE

PURPOSE AND METHODS: Indices of antioxidant status, membrane permeability, and lipid peroxidation were investigated in venous blood immediately before and after a simulated half-marathon run. In serum, these included the ability to scavenge free radicals (total antioxidant capacity, TAC), the concentration of uric acid (UA), and the activities of creatine kinase (CK) and beta-glucuronidase (beta G). The plasma concentration of malondialdehyde (MDA) was used as a marker of lipid peroxidation. Data were analyzed with paired t-tests. After a standardized warm-up, 17 trained male runners (mean +/- SD, age 31 +/- 4 yr, peak VO2 63.2 +/- 4.8 mL.kg-1.min-1) each completed a self-paced half-marathon run, on a motorized treadmill. Average exercise intensity was 77.1 +/- 1.0% peak VO2, with a performance time of 87.1 +/- 7.0 min. RESULTS: After exercise, elevations were observed in MDA from 1.48 +/- 0.39 mmol.L-1 to 1.65 +/- 0.32 mmol.L-1 (P < 0.05), TAC from 475 +/- 84 to 564 +/- 113 mmol Trolox Eq.L-1 (P < 0.0001), UA from 268 +/- 45 to 312 +/- 51 mmol.L-1 (P < 0.001), serum cortisol concentration from 339 +/- 95 to 557 +/- 157 nmol.L-1 (P < 0.01), CK from 98 +/- 67 to 133 +/- 89 IU.L-1 (P < 0.0001), and beta G from 15.39 +/- 5.34 to 17.05 +/- 5.7 Sigma Units.mL-1 (P < 0.001). CONCLUSIONS: The rise in TAC did not prevent exercise-induced lipid peroxidation and muscle damage as both MDA and CK were elevated after exercise. This may indicate inadequacies in the antioxidant defense system during the half-marathon run.

Altern Ther Health Med 1998 Nov;4(6):38-43

Integrated medicine and the prevention and reversal of memory loss.

Khalsa DS

This article, based on scientific research and clinical observations, suggests that memory loss is not an inevitable consequence of aging and that Alzheimer's disease can be prevented and reversed using an integrated medical approach. Three new associations with memory loss other than age, heredity, and genetics are described. They include a high-fat diet, chronic unbalanced stress with its attendant risk in the adrenal hormone cortisol, and the presence of cardiovascular disease. A 4-pillar integrative medical program on brain longevity is presented. The program includes a diet consisting of 15% fat and supplementation with brain-specific nutrients such as vitamin B complex, vitamin E, ubiquinone, ginkgo biloba, and phosphatidylserine. In addition, stress-relieving meditation, mind-body and cognitive exercise, antiaging drugs like L-deprenyl citrate, as well as hormones such as dehydroepiandrosterone and pregnenolone complete the program. Patient benefits such as greater wisdom and spiritual happiness are also explored.

Eur J Appl Physiol 1998 Oct;78(5):466-71

Effects of amount of training on the saliva concentrations of cortisol, dehydroepiandrosterone and on the dehydroepiandrosterone: cortisol concentration ratio in women over 16 weeks of training.

Filaire E, Duche P, Lac G

Unite de Formation et de Recherche en Sciences et Techniques deo Activites Physiques et Sportives, Universite Blaise Pascal, Clermont-Ferrand II, Aubiere,

France.

This study was designed to investigate in the saliva the influence in female athletes of handball or volleyball training on concentrations of cortisol [C], dehydroepiandrosterone [DHEA], and on the [DHEA]:[C] ratio over 16 weeks of training. Data were compared to those of sedentary women. Saliva samples were collected upon waking after an overnight fast during the 1st week (W1) of the training programme and in the 16th week (W16). The training programme increased the resting concentrations of saliva [DHEA] in all the sportswomen. In contrast, a decrease of [DHEA] was noted in the sedentary group (W16 < W1; P < 0.05). In none of the women did the [C] at rest change significantly during the study. Between W1 and W16, the [DHEA]:[C] ratio increased by more than 30% in all the sportswomen. In addition, the athletes with the highest performance levels and greatest amount of training had the lowest [DHEA]:[C] ratio. Negative linear relationships between the amount of training and the [DHEA]:[C] ratio were found both at W1 (r = -0.53 P < 0.001), and W16 (r = -0.73 P < 0.001), suggesting that the latter could be used as an indicator of the training status of sportswomen.

Clin Exp Pharmacol Physiol 1998 Nov;25(11):945-6

The nitric oxide system and cortisol-induced hypertension in humans.

Kelly JJ, Tam SH, Williamson PM, Lawson J, Whitworth JA

1. The aim of the present study was to assess the role of the nitric oxide (NO) system in cortisol-induced hypertension in humans.

2. Plasma and urinary nitrate/nitrite concentrations and plasma concentrations of arginine and symmetric (SDMA) and asymmetric (ADMA) dimethyl arginine were measured in six subjects on a restricted nitrate diet who were treated with 80 mg/day cortisol and in subjects on an unrestricted nitrate diet who were treated with cortisol (80 mg/day, n = 6, or 200 mg/day, n = 10) for 5 days.

3. Cortisol significantly increased systolic and mean arterial pressure. Significant reductions in plasma nitrate/nitrite concentrations were observed in subjects on a restricted nitrate diet on days 3, 4 and 5 of cortisol treatment (to 11 +/- 1, 10 +/- 1, 11 +/- 1 pmol/L, respectively) compared with pretreatment (16 +/- 1 pmol/L; P < 0.01). There were no significant changes in plasma arginine, ADMA or SDMA concentrations.

4. Cortisol treatment significantly increased blood pressure and reduced plasma nitrate/nitrite concentrations. Reductions in plasma nitrate concentrations are not explained by changes in substrate availability or in endogenous nitric oxide synthase inhibitors. These data support a role for the NO system in cortisol-induced hypertension in humans.

Can J Physiol Pharmacol 1998 Apr;76(4):373-80

Immune function in aged women is improved by ingestion of vitamins C and E.

la Fuente MD, Ferrandez MD, Burgos MS, Soler A, Prieto A, Miquel J

We have investigated the effects of supplementation of the diet with the antioxidant vitamins C and E on several functions of the immune response of aged women. Ten healthy women and 20 women (72 +/- 6 years old) suffering two diseases often associated with age (10 with major depression disorders, MDD, and 10 with coronary heart disease, CHD) were administered 1 g of vitamin C and 200 mg of vitamin E daily for 16 weeks. Blood samples were collected before and after treatment for measurement of several immunological functions, namely proliferative response of lymphocytes to the mitogen phytohemagglutinin (20 mg/L) and phagocytic functions of polymorphonuclear (PMN) neutrophils, i.e., adherence to vascular endothelium, chemotaxis, phagocytosis of latex beads, and superoxide anion production. In addition, we also determined the levels of serum cortisol and lipid peroxides. Intake of vitamins resulted in a significant increase in the lymphoproliferative capacity and in the phagocytic functions of PMN neutrophils as well as in a significant decrease of serum levels of lipid peroxides and cortisol, both in the healthy aged women and in the aged women with MDD or CHD. These findings suggest an important role of antioxidant supplementation in the improvement of immune function in aged females as well as in the prevention and treatment of specific diseases associated with age that are quite prevalent in the developed countries.

Health Psychol 1998 Sep;17(5):436-44

Effects of video-relayed social support on hemodynamic reactivity and salivary cortisol during laboratory-based behavioral challenge.

Thorsteinsson EB, James JE, Gregg ME

The authors tested the effects of a laboratory analogue of social support on reactivity to laboratory-based behavioral challenge. Video-relayed supportive commentary was provided by a same-sex confederate while participants (40 healthy men and women assigned to support and no-support groups) performed a demanding computer task, and their heart rate, systolic and diastolic blood pressure, and salivary cortisol were measured. The authors found that heart rate and cortisol level (but not blood pressure) were attenuated in the support condition for both genders. Objective performance on the task was similar in both groups, but the social support group reported higher levels of perceived support and rated the task as easier than did participants in the no-support condition. Video presentation offers new opportunities for systematically examining social support and its effects.

Int J Sports Med 1998 Aug;19(6):432-7

Differential white cell count after two bouts of downhill running.

Smith LL, Bond JA, Holbert D, Houmard JA, Israel RG, McCammon MR, Smith SS

The purpose of this study was to compare blood markers associated with eccentrically biased exercise and muscle damage, after two bouts of downhill running. Nine active, untrained males performed 2 x 45 min bouts of downhill running (-0.16 radians), at a speed that would elicit 70% of each subjects VO2max, on a level grade; runs were spaced 14d apart (RUN1, RUN2). Blood samples were obtained before, after, and every hour for 12 h after exercise, as well as every 24 h for 5 d, to assess numbers of circulating neutrophils, monocytes, and lymphocytes, serum cortisol, creatine kinase (CK); subjective sensations of delayed onset muscle soreness (DOMS) were monitored. To control for diurnal variation, two weeks prior to the RUN1, subjects had blood draws performed at the same time as would occur after exercise, but did no exercise (CONTROL). During the 5 d after exercise, DOMS and CK were significantly greater (p < 0.05) after RUN1 compared to RUN2 and CONTROL. During the 12 h after RUN1 and RUN2, neutrophils showed similar responses compared to CONTROL. However, neutrophils were significantly elevated at 96 h after RUN1 and 24 h after RUN2. Monocytes were significantly elevated during 5-11 h after RUN1 and RUN2, compared to CONTROL. Cortisol showed a similar significant diurnal decrease for all three conditions during the 12 h following exercise. The significantly lower levels of CK and DOMS seen after RUN2, compared with the initial run is consistent with the literature. The similar changes in neutrophils and monocytes during the 12 h following RUN1 and RUN2, followed by disparate responses over the subsequent 5 d, requires further investigation.

J Clin Endocrinol Metab 1998 Oct;83(10):3487-92

A prospective study on cortisol, dehydroepiandrosterone sulfate, and cognitive function in the elderly.

Kalmijn S, Launer LJ, Stolk RP, de Jong FH, Pols HA, Hofman A, Breteler MM, Lamberts SW

The objective of this study was to investigate the relation between the peripheral concentrations of the adrenal steroid hormones cortisol and dehydroepiandrosterone sulfate (DHEAS) and cognitive impairment and decline. A prospective study design was used. The setting was a suburb of Rotterdam, The Netherlands. The study population consisted of a sample of 189 healthy participants from the population-based Rotterdam Study, aged 55-80 yr, who were invited for an additional examination. Follow-up examinations took place 1.9 yr after baseline, on the average. We determined fasting blood levels of DHEAS before dexamethasone administration and of cortisol and corticosteroid-binding globulin before and after the administration of 1 mg dexamethasone overnight. The 30-point Mini-Mental State Examination (MMSE) was used to assess cognition. The associations with cognitive impairment (MMSE score of <26; 6% of the sample) and cognitive decline (drop in MMSE score of >1 point/yr; 24%) were estimated using logistic regression, with adjustment for age, sex, education, and depressive symptoms. An increase of 1 SD in the estimate of free cortisol (SD = 30.3) was associated with cognitive impairment, although not significantly [odds ratio (OR) = 1.5; 95% confidence interval (CI), 0.9-2.4]. A 1 SD increase in the natural logarithm of cortisol after the administration of 1 mg dexamethasone (SD = 0.68) was associated with an OR for cognitive decline of 1.5 (95% CI, 1.0-2.3). A 1 SD increase in DHEAS (SD = 2.10 micromol/L) was inversely, but nonsignificantly, related to cognitive impairment (OR = 0.5; 95% CI, 0.2-1.1) and cognitive decline (OR = 0.6; 95% CI, 0.4-1.1). The ratio of free cortisol over DHEAS was significantly related to cognitive impairment (OR = 1.8; 95% CI, 1.0-3.2). This prospective study among healthy elderly subjects suggested that basal free cortisol levels were positively related to cognitive impairment, and cortisol levels after dexamethasone treatment were related to cognitive decline. There was an inverse, but nonsignificant, association between DHEAS and cognitive impairment and decline.

J Appl Physiol 1998 Oct;85(4):1544-55

Hormonal responses to consecutive days of heavy-resistance exercise with or without nutritional supplementation.

Kraemer WJ, Volek JS, Bush JA, Putukian M, Sebastianelli WJ

Nine resistance-trained men consumed either a protein-carbohydrate supplement or placebo for 1 wk in a crossover design separated by 7 days. The last 3 days of each treatment, subjects performed resistance exercise. The supplement was consumed 2 h before and immediately after the workout, and blood was obtained before and after exercise (0, 15, 30, 45, and 60 min postexercise). Lactate, growth hormone, and testosterone were significantly (P </= 0.05) elevated immediately postexercise. The lactate response was significantly lower during supplementation on days 2 and 3. Growth hormone and prolactin responses on day 1 were significantly higher during supplementation. After exercise, testosterone declined below resting values during supplementation. Cortisol decreased immediately postexercise on day 1; the response was diminished on days 2 and 3. Glucose and insulin were significantly elevated by 30 min during supplementation and remained stable during placebo. Insulin-like growth factor-I was higher during supplementation on days 2 and 3. These data indicate that protein-carbohydrate supplementation before and after training can alter the metabolic and hormonal responses to consecutive days of heavy-resistance exercise.

Int J Clin Pharmacol Ther 1998 Sep;36(9):501-5

Effect of fat distribution on the pharmacokinetics of cortisol in obesity.

Lottenberg SA, Giannella-Neto D, Derendorf H, Rocha M, Bosco A, Carvalho SV, Moretti AE, Lerario AC, Wajchenberg BL

OBJECTIVE: Patients with predominantly upper body obesity are at greater risk for developing diabetes mellitus, hyperlipidemia, hypertension, and cardiovascular disease. Little is known about the mechanisms involved in the regulation of regional body distribution. It has been accepted that the accumulation of fat into adipose tissue depends on regional metabolic regulation of adipocytes and that glucocorticoids play a role in this mechanism. The aim of the present study is to investigate how the pharmacokinetics of cortisol correlate to intraabdominal and subcutaneous fat distribution in obese patients. METHODS: A group of 24 obese patients (13 males and 11 females) were submitted to a CT scan for intraabdominal and subcutaneous fat area evaluation. A 30-min cortisol infusion (0.25 mg/kg) was administered and plasma cortisol was measured over 6 hours. RESULTS: Patients with larger intraabdominal fat areas were found to have a higher cortisol clearance than those with lower intraabdominal fat areas. Cortisol clearance (both, absolute and body-weight corrected) showed a statistically significant correlation with intraabdominal fat area, either expressed by waist-hip ratio or obtained by computerized tomography. CONCLUSIONS: These findings indicate a more effective clearance capability for cortisol in patients with central obesity resulting in lowered cortisol plasma levels despite an increased cortisol secretion observed in this patient group.

Issues Compr Pediatr Nurs 1998 Jul-Sep;20(3):183-90

Salivary cortisol testing in children.

Schmidt NA

Biological markers can identify links between human biology and human behavior. Cortisol, a marker of hypothalamic-pituitary-adrenocortical axis function, is a useful measure in research. Newer technology involving the measurement of cortisol in saliva is being utilized in research studies. Salivary cortisol measurement is inexpensive and noninvasive and offers many advantages over serum testing. Although there are various methods of saliva collection, it is relatively easy to perform in both infants and children. Salivary cortisol testing may offer a significant measure for pediatric stress, coping, and health research.

Physiol Behav 1998 Jun 1;64(3):311-5

ACTH and beta-endorphin in transcendental meditation.

Infante JR, Peran F, Martinez M, Roldan A, Poyatos R, Ruiz C, Samaniego F, Garrido F

We have evaluated the effect of Transcendental Meditation (TM) on the hypothalamo-hypophyseal-adrenal axis diurnal rhythms through the determination of hormone levels. Blood samples were taken at 0900 hours. and at 2000 hours. These samples were taken from 18 healthy volunteers who regularly practice TM and from nine healthy non-meditators. Cortisol, beta-endorphin, and adrenocorticotropic hormone (ACTH) were measured at both hours. TM practitioners showed no diurnal rhythm for ACTH and for beta-endorphin (ACTH, pg/mL, mean +/- SE; 13.8+/-1.2 - 12.1+/-1.5/beta-endorphin, pg/mL; 14.4+/-1.5 - 17.2+/-1.9, at 0900 hours and 2000 hours, respectively), in contrast to control subjects, who showed normal diurnal rhythm for these hormones and for cortisol (ACTH, pg/mL; 19.4+/-1.9 - 11.9+/-2.2/beta-endorphin, pg/mL; 25.4+/-1.7 - 17.7+/-1.1/Cortisol, ng/mL; 201.4+/-13.2 - 71.3+/-6.5, at 0900-2000 hours, respectively, p < 0.01 in the three cases). Practitioners of TM with similar anxiety levels to those of the control group showed a different pattern in the daytime secretion of pituitary hormones. TM thus appears to have a significant effect on the neuroendocrine axis. Because cortisol levels had a normal pattern in the TM group, these results may be due to a change in feedback sensitivity caused by this mental technique.

Appetite 1998 Aug;31(1):49-65

Does carbohydrate-rich, protein-poor food prevent a deterioration of mood and cognitive performance of stress-prone subjects when subjected to a stressful task?

Markus CR, Panhuysen G, Tuiten A, Koppeschaar H, Fekkes D, Peters ML

This study investigates whether in stress-prone subjects, carbohydrate-rich, protein-poor food (CR/PP) prevents a deterioration of mood and performance under uncontrollable laboratory stress conditions. The assumption was that in stress-prone subjects there is a higher risk of serotonin deficiency in the brain and that carbohydrates may prevent a functional shortage of central serotonin during acute stress, due to their potentiating effect on brain tryptophan. Twenty-four subjects with a high stress-proneness (HS) and 24 subjects with a low stress-proneness (LS) participated in an uncontrollable stress situation under both a CR/PP and a protein-rich, carbohydrate-poor (PR/CP) diet condition. The plasma ratio of tryptophan to the other large neutral amino acids (LNAA) (ratio Tryptophan/ summation operatorLNAA) was determined as a measure indicating the dietary effect on brain tryptophan and serotonin levels. Significant increases were found in the ratio tryptophan/ summation operatorLNAA during the CR/PP diet compared with the PR/CP diet. Experimental stress had significant effects on pulse rate, skin conductance, cortisol and mood in all subjects. During the CR/PP diet only the HS subjects did not show the stress-induced rise in depression, decline in vigour and cortisol elevation that they showed after the PR/CP diet. With respect to cognitive performance, significant dietary effects were found on reaction time. It is suggested that CR/PP food in HS subjects may increase personal control, probably under the influence of higher levels of brain tryptophan and serotonin. Copyright 1998 Academic Press.

Clin Chem Lab Med 1998 Jun;36(6):355-9

Engineering of an anti-steroid antibody: amino acid substitutions change antibody fine specificity from cortisol to estradiol.

Chames P, Baty D

Immunoassays are widely used for determination of the concentration of steroid hormones. However, obtaining specific anti-steroid monoclonal antibodies remains difficult. We used antibody engineering and phage display methods to change the specificity of an anti-cortisol monoclonal antibody towards estradiol. This work demonstrates that production of recombinant antibodies may be a valuable way of obtaining the high-specificity antibodies required for steroid immunoassays.

Psychoneuroendocrinology 1998 May;23(4):401-11

Neuroendocrine and cardiovascular response to sexual arousal and orgasm in men.

Kruger T, Exton MS, Pawlak C, von zur Muhlen A, Hartmann U, Schedlowski M

Data regarding the neuroendocrine response pattern to sexual arousal and orgasm in man are inconsistent. In this study, ten healthy male volunteers were continuously monitored for their cardiovascular and neuroendocrine response to sexual arousal and orgasm. Blood was continuously drawn before, during and after masturbation-induced orgasm and analyzed for plasma concentrations of adrenaline, noradrenaline, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, growth hormone (GH), beta-endorphin and testosterone. Orgasm induced transient increases in heart rate, blood pressure and noradrenaline plasma levels. Prolactin plasma levels increased during orgasm and remained elevated 30 min after orgasm. In contrast, none of the other endocrine variables were significantly affected by sexual arousal and orgasm.

Psychoneuroendocrinology 1998 May;23(4):353-70

Stressors and mood measured on a momentary basis are associated with salivary cortisol secretion.

Smyth J, Ockenfels MC, Porter L, Kirschbaum C, Hellhammer DH, Stone AA

Effects of past, current, and anticipated naturalistic daily stressors and of affect on salivary cortisol levels were examined. Participants (120) reported on stressors and affect 6 x /day in response to a preprogrammed wristwatch. Twenty min after each assessment they took a sample of saliva for cortisol analysis. Both the experience of a current stressor and anticipating a stressor were associated with increased salivary cortisol levels. Average increases in cortisol were relatively low, but inter-individual variability in this response existed. Stressors also were associated with lower positive affect and higher negative affect. Negative affect was associated with higher cortisol levels and positive affect was associated with lower cortisol levels. Daily stressors were not significant predictors of cortisol secretion when affect was controlled. Momentary assessment of daily stressors and of salivary cortisol proved to be a useful tool for examining psychoendocrinological processes in the natural environment.

Clin Endocrinol (Oxf) 1998 May;48(5):603-12

Pulsatile secretion of ACTH and cortisol in premenopausal women: effect of obesity and body fat distribution.

Pasquali R, Biscotti D, Spinucci G, Vicennati V, Genazzani AD, Sgarbi L, Casimirri F

OBJECTIVE: There is emerging evidence that women with visceral obesity may have hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. There are no studies on basal daily secretory pattern of ACTH and cortisol in subjects with different obesity phenotypes.

DESIGN AND PATIENTS: In this study we examined daytime pulsatile secretion of ACTH and cortisol in two groups of premenopausal obese women with visceral (V-BFD) (BMI 37.1 +/- 1.7) and subcutaneous (S-BFD) (BMI 38.8 +/- 1.5) body fat distribution (measured by CT scan) and in a group of normal weight healthy controls (BMI 21.1 +/- 0.5). After an overnight fast, blood samples were taken at 15-minute intervals for 12 h (49 samples, from 0800 h until 2000 h). All women avoided breakfast but had a normal lunch and dinner, both containing similar food, energy and nutrient composition. ACTH and cortisol responses to mixed meals at noon and in the evening were also investigated.

RESULTS: Mean values of ACTH and cortisol did not differ between the groups. However, ACTH pulse frequency was significantly higher in V-BFD (P < 0.06) and S-BFD (P < 0.02) obese women than in controls, without any significant differences between the two obese subgroups. Mean ACTH pulse amplitude was lower in the V-BFD than in S-BFD obese (P < 0.02) and control (P < 0.05) groups. Cortisol episodic characteristics did not differ between V-BFD and S-BFD obese and controls. All differences in ACTH pulsatile parameters between obese and controls and between the two obese subgroups were evident only in the morning, with no further significant differences during the early and late afternoon. There were no significant differences in cortisol parameters during the three periods of the day between the various groups, apart from late afternoon cortisol pulse frequencies, which were significantly lower in V-BFD than in controls. After lunch, ACTH and cortisol levels significantly increased in all groups, but the cortisol increase tended to be more rapid in V-BFD than in the other two groups. After dinner, ACTH significantly increased in V-BFD and controls but not in the S-BFD group, whereas cortisol rose significantly in all groups, but significantly less in S-BFD than in V-BFD and controls. CortisolAUC (but not ACTHAUC) after lunch was significantly higher than after dinner in all groups. ACTH response after each meal was similar in all groups, but cortisolAUC after dinner was significantly lower in S-BFD than in V-BFD women.

CONCLUSION: This study demonstrates that in premenopausal women, obesity, particularly the visceral phenotype, is associated with several abnormalities of ACTH pulsatile secretion, particularly in the morning. On the contrary, no major differences were present in either blood concentrations, diurnal rhythm or secretory pattern of cortisol between obese and controls. The responses to meals seem to indicate a much more rapid cortisol response after lunch in women with visceral obesity and a reduced activation of the hypothalamic-pituitary-adrenal axis after dinner in women with subcutaneous obesity.

Eur J Appl Physiol 1998 Jun;78(1):69-76

The effects of short-term resistance training on endocrine function in men and women.

Kraemer WJ, Staron RS, Hagerman FC, Hikida RS, Fry AC, Gordon SE, Nindl BC, Gothshalk LA, Volek JS, Marx JO, Newton RU, Hakkinen K

This investigation examined hormonal adaptations to acute resistance exercise and determined whether training adaptations are observed within an 8-week period in untrained men and women. The protocol consisted of a 1-week pre-conditioning orientation phase followed by 8 weeks of heavy resistance training. Three lower-limb exercises for the quadriceps femoris muscle group (squat, leg press, knee extension) were performed twice a week (Monday and Friday) with every other Wednesday used for maximal dynamic 1 RM strength testing. Blood samples were obtained pre-exercise (Pre-Ex), immediately post-exercise (IP), and 5 min post-exercise (5-P) during the first week of training (T-1), after 6 weeks (T-2) and 8 weeks (T-3) of training to determine blood concentrations of whole-blood lactate (LAC), serum total testosterone (TT), sex-hormone binding globulin (SHBG), cortisol (CORT) and growth hormone (GH). Serum TT concentrations were significantly (P < or = 0.05) higher for men at all time points measured. Men did not demonstrate an increase due to exercise until T-2. An increase in pre-exercise concentrations of TT were observed both for men and women at T-2 and T-3. No differences were observed for CORT between men and women; increases in CORT above pre-exercise values were observed for men at all training phases and at T-2 and T-3 for women. A reduction in CORT concentrations at rest was observed both in men and women at T-3. Women demonstrated higher pre-exercise GH values than men at all training phases; no changes with training were observed for GH concentrations. Exercise-induced increases in GH above pre-exercise values were observed at all phases of training. Women demonstrated higher serum concentrations of SHBG at all time points. No exercise-induced increases were observed in men over the training period but women increased SHBG with exercise at T-3. SHBG concentrations in women were also significantly higher at T-2 and T-3 when compared to T-1 values. Increases in LAC concentrations due to exercise were observed both for men and women for all training phases but no significant differences were observed with training. These data illustrate that untrained individuals may exhibit early-phase endocrine adaptations during a resistance training program. These hormonal adaptations may influence and help to mediate other adaptations in the nervous system and muscle fibers, which have been shown to be very responsive in the early phase of strength adaptations with resistance training.

Int J Eat Disord 1995 Nov;18(3):295-8

Distorting reality for children: body size proportions of Barbie and Ken dolls.

Brownell KD, Napolitano MA

Using hip measurements as a constant, calculations were made to determine the changes necessary for a young, healthy adult woman and man to attain the same body proportions as Barbie and Ken dolls, respectively. Among the changes necessary were for the female to increase 24 in. in height, 5 in. in the chest, and 3.2 in. in neck length, while decreasing 6 in. in the waist, and for the male to increase 20 in. in height, 11 in. in the chest, and 7.9 in. in neck circumference. Like adults, children are exposed to highly unrealistic ideals for shape and weight.

Int J Obes Relat Metab Disord 1995 Oct;19 Suppl 4:S122-5

Exercise and obesity treatment: psychological aspects.

Brownell KD

Exercise is clearly beneficial as a means for losing weight and keeping it off. Given recent studies showing its association with maintenance, it would be difficult to argue that any factor is more important than exercise. For an exercise program to be helpful for obese persons, the challenges of exercise adherence must be considered, as must the mechanisms linking exercise to weight control. Both argue for whatever activity an individual will undertake that will produce the psychological effects that promote weight control.

Phen-Fen is phentermine and fenfluramine which has become infamous in recent months. The combination was very effective for many overweight people who were not previously able to control their compulsive overeating no matter what they had tried. Phen-Fen or Ionamin and Pondimin were shown in a four-year study at the University of Rochester by Wintrobe and his colleagues to be very effective in allowing for moderate weight reduction when combined with behavior modification, diet, and exercise . Fenfluramine has now been implicated as the possible cause of heart valve problems. Irreversible primary pulmonary hypertension was already known to be a rare but possible complication. If you have been taking fenfluramine as either Pondimin or Redux and are having difficulty with shortness of breath, it would probably be a good idea to have an echo cardiogram to ruleout heart valve or lung problems.

Venlafaxin marketed as Effexor and Effexor XR (extended release) is an antidepressant which will suppress appetite for some people and either not change appetite or increase appetite for others. It can also be combined with phentermine (Ionamin, Fasten,Adepex, Obenix) frequently with good results.

Wellbutrin or bupropion was considered for use as an appetite suppressant early in its development. This use was never pursued with the FDA, and Wellbutrin became widely used as an antidepressant. More recently it has been approved as Zyban for use as an aid to stopping tobacco use. When combined with a nicotine patch, it is effective about 70% of the time in allowing someone to successfully stop smoking. It often curbs the increase in appetite frequently seen with smoking cessation. Having said all of this, Wellbutrin sometimes will decrease the appetite of someone who compulsively overeats. For others there is no effect on appetite or even an increase in appetite. Some people benefit from a combination of Wellbutrin and phentermine (Ionamin, Fasten, Adepex, Obenix). There seems to be no difference in the appetite-suppressing effects of Wellbutrin and WellbutrinSR, the newer sustained-release version.

It is too early to say just how effective the new medication sibutramine from Knoll Pharmaceutical will be. It appears to be a safe alternative to phen/fen and may work in a similar way to decrease appetite. It comes in 5 mg, 10 mg, and 15 mg doses.

American Society of Bariatric Physicians http://www.sni.net/bariatrics/meds.htm

Notes on various pharmacologic approaches to weight control.