Peter J. H. Jones

Reduction in Obesity and Related Comorbid Conditions after Diet-Induced Weight Loss or Exercise-Induced Weight Loss in Men: A Randomized, Controlled Trial

In 1997, the World Health Organization published a landmark document recognizing obesity as a worldwide disease that poses a serious threat to public health (1). Persons who are overweight or obese have substantially increased risk for morbidity from numerous chronic disorders, such as diabetes (2, 3), hypertension (4, 5), and cardiovascular disease (6, 7). Obesity-related health risk is greater when excess fat is deposited in the abdomen region because this phenotype is a stronger predictor of cardiovascular disease and type 2 diabetes mellitus than general obesity is (8-11). This may be partially explained by excess accumulation of visceral fat, an independent correlate of insulin resistance (9-11) and dyslipidemia (8, 9). These observations highlight the need to identify appropriate treatment strategies to prevent and reduce obesity and suggest that the effectiveness of these treatments would be enhanced if abdominal obesity, particularly visceral fat, was substantially reduced. Diet restriction remains the most common method of obesity reduction (12). Despite the observation that low levels of physical activity are a major cause of obesity (13), increased physical activity alone is not thought to be a useful strategy for obesity reduction. Some reports have suggested that physical activity in obese adults results in only modest weight loss (approximately 1 to 2 kg) independent of the effects of diet restriction (14). However, these conclusions are drawn from studies in which individual energy intake and expenditure were not rigorously controlled or accurately measured (15-17). Moreover, in most studies, the negative energy balance induced by exercise was modest enough that substantial weight loss was not expected (15-17). Currently, no compelling evidence supports the observation that exercise alone is not a useful method for reducing total or abdominal obesity. It is well known that a single exercise session is associated with a significant improvement in insulin-stimulated glucose uptake (18, 19). It is also clear that weight loss is associated with an improvement in insulin action (20-24). It is unclear, however, whether regular exercise improves glucose metabolism after the short-term effects of exercise and changes in body fat distribution are considered. Segal and colleagues (25) controlled for the confounding effect of the last exercise session and body composition changes and found that exercise had no independent effect on insulin sensitivity (25). Given the established importance of insulin resistance as an antecedent to both cardiovascular disease and type 2 diabetes mellitus (26), it is important to clarify whether exercise improves insulin action independent of fat loss. We performed a randomized, controlled trial to determine the independent effect of diet-induced or exercise-induced weight loss on obesity and insulin resistance in moderately obese men. We also evaluated whether exercise without weight loss was associated with reductions in abdominal obesity and insulin resistance. Methods Participants Participants were recruited from Kingston, Ontario, Canada, a typical suburban region, through the general media. We selected men with a body mass index greater than 27 kg/m2 and a waist circumference greater than 100 cm whose weight had been stable (2 kg) for 6 months before study entry. Participants were nonsmokers who consumed an average of fewer than two alcoholic beverages per day, had a sedentary lifestyle, and took no medications known to affect the principal outcome measures. All participants had a preparticipation medical examination that included screening for normal glucose tolerance and plasma lipid profile. A computer program was used to randomly assign eligible men to one of the following four groups: control, diet-induced weight loss, exercise-induced weight loss, and exercise without weight loss (Figure 1). Of the 101 participants who were randomly assigned to groups, 34 chose not to participate because they were dissatisfied with their assigned group, 5 were diabetic or dyslipidemic, and 3 were relocated because of job transfers. Those who chose not to participate and those who completed the trial were similar with regard to anthropometric variables. In addition, those who completed the trial were similar to those who did not in each group (P >0.10). Baseline characteristics among groups were similar for all participants (Table 1). All participants gave fully informed written consent. The study was conducted in accordance with the ethical guidelines of Queens University. The participants did not receive monetary compensation. Figure 1. Flow of participants through the study. Table 1. Selected Anthropometric, Magnetic Resonance Imaging, and Metabolic Variables before Treatment and 3 Months after Treatment Diet and Exercise Regimen During the baseline period, daily energy requirements for all participants were determined by estimating resting energy expenditure and multiplying the obtained value by a factor of 1.5 (27). All participants followed a weight maintenance diet (55% to 60% carbohydrate, 15% to 20% protein, and 20% to 25% fat) for a 4- to 5-week baseline period. During this period, body weight was monitored to determine the accuracy of the prescribed energy requirement, which was adjusted accordingly to maintain body weight. Controls were asked to maintain body weight throughout the 12-week treatment period. Participants in the diet-induced weight loss group were asked to reduce the isocaloric diet by 700 kcal/d during the treatment period to achieve a weekly weight loss of approximately 0.6 kg. To lose the same amount of weight, participants in the exercise-induced weight loss group were asked to maintain the isocaloric diet for the duration of the treatment period and to perform exercise that expended 700 kcal/d. Participants assigned to exercise without weight loss were asked to maintain body weight. Therefore, they consumed enough calories to compensate for the energy expended during the daily exercise sessions (approximately 700 kcal). At the end of the treatment period, isocaloric requirements were determined and prescribed for a 2-week weight stabilization period. All participants were free-living and consumed self-selected foods. No vitamins or other nutritional supplements were prescribed. Each person participated in a series of weekly 1-hour seminars in which a dietitian taught proper food selection and preparation. Participants were told that the composition of the maintenance and energy-reduced diets should be approximately 55% to 60% carbohydrate, 15% to 20% protein, and 20% to 25% fat. Participants kept and analyzed daily, detailed food records for the duration of the study period (approximately 20 weeks); the study dietitian also reviewed these records. For the 2-week period during which doubly labeled water measurements were acquired (weeks 6 and 7), the diet records were analyzed by using a computerized program (Food Processor, Esha Research, Salem, Oregon). Participants in both exercise groups performed daily exercise (brisk walking or light jogging) on a motorized treadmill for the duration of the 12-week trial. The length of each exercise session was determined by the time required to expend 700 kcal. Participants were asked to exercise at an intensity not greater than 70% of their peak oxygen uptake (Vo 2) (approximately 80% of maximal heart rate). Energy expenditure was determined by using the heart rate and oxygen consumption data that were obtained from the pretreatment graded exercise test and were adjusted according to the results of two subsequent tests performed at weeks 4 and 8. During each session, heart rate was monitored every 5 minutes by using an automated heart rate monitor (Polar Oy, Kempele, Finland). All exercise sessions were by appointment and were supervised. Peak Vo 2 was determined by using a graded treadmill test and standard open-circuit spirometry techniques (SensorMedics, Yorba Linda, California). Energy Expenditure Total energy expenditure for 14 days was measured by using a two-point doubly labeled water method (28). Deuterium enrichment was analyzed by using a 903 deuterium dual-inlet isotope ratio mass spectrometer (VG Isogas, Cheshire, United Kingdom). Oxygen-18 was determined by using a SIRA 12 isotope ratio mass spectrometer (VG Isogas). Total energy expenditure was calculated by using the DeWeir formula (29). After an overnight stay in the hospital, resting metabolic rate was measured at 7:00 a.m. by using indirect calorimetry with a modified mask system (Teem 100, Aerosport, Inc., Ann Arbor, Michigan). Values were obtained for 30 minutes, and the last 25 minutes were used to determine resting metabolic rate. Resting systolic and diastolic blood pressure were measured when the participant was supine. Magnetic Resonance Imaging and Anthropometric Measurements Whole-body data from magnetic resonance imaging (approximately 45 equidistant images) were obtained with a General Electric 1.5-Tesla magnet (Milwaukee, Wisconsin) by using an established protocol described in detail elsewhere (30). Once acquired, the data were transferred to a stand-alone work station (Silicon Graphics, Mountain View, California) for analysis with specially designed computer software (Tomovision, Inc., Montreal, Canada), the procedures for which are described elsewhere (31). For adipose tissue (fat) and skeletal muscle, volume units (L) were converted to mass units (kg) by multiplying the volumes by the assumed constant density for fat (0.92 kg/L) and fat-free skeletal muscle (1.04 kg/L) (32). All anthropometric circumference measurements were obtained by using standard procedures described elsewhere (30). Insulin Sensitivity and Glucose Tolerance Participants consumed a weight-maintenance diet consisting of at least 200 g of carbohydrate for a minimum of 4 days and were asked to avoid strenuous physical activity for 3 days before insulin sens

Efficacy and Safety of Plant Stanols and Sterols in the Management of Blood Cholesterol Levels

Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.

Dietary phytosterols: a review of metabolism, benefits and side effects.

Most animal and human studies show that phytosterols reduce serum/or plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels. Phytosterols are structurally very similar to cholesterol except that they always contain some substitutions at the C24 position on the sterol side chain. Plasma phytosterol levels in mammalian tissue are normally very low due primarily to poor absorption from the intestine and faster excretion from liver compared to cholesterol. Phytosterols are able to be metabolized in the liver into C21 bile acids via liver other than normal C24 bile acids in mammals. It is generally assumed that cholesterol reduction results directly from inhibition of cholesterol absorption through displacement of cholesterol from micelles. Structure-specific effects of individual phytosterol constituents have recently been shown where saturated phytosterols are more efficient compared to unsaturated compounds in reducing cholesterol levels. In addition, phytosterols produce a wide spectrum of therapeutic effects in animals including anti-tumour properties. Phytosterols have been shown experimentally to inhibit colon cancer development. With regard to toxicity, no obvious side effects of phytosterol have been observed in studies to date, except in individual with phytosterolemia, an inherited lipid disorder. Further characterization of the influence of various phytosterol subcomponents on lipoprotein profiles in humans is required to maximize the usefulness of this non-pharmacological approach to reduction of atherosclerosis in the population.

Dietary phytosterols as cholesterol-lowering agents in humans

Phytosterols (plant sterols), abundant in fat-soluble fractions of plants, are consumed at levels of 200-400 mg/day in Western diets. Chemically resembling cholesterol, phytosterols inhibit the absorption of cholesterol. Phytosterol consumption in human subjects under a wide range of study conditions has been shown to reduce plasma total and low density lipoprotein (LDL) cholesterol levels; however, the response varies widely. Greater cholesterol-lowering efficacy occurs with consumption of the saturated phytosterol sitostanol versus sitosterol or campesterol. Most studies report no effect of phytosterol administration in high density lipoprotein (HDL) cholesterol or triglyceride levels, although certain evidence exists for an HDL cholesterol raising effect of sitostanol. Phytosterol absorption is limited, although serum phytosterol levels have proven to be important indicators of both cholesterol absorption and synthesis. Serum phytosterols correlate with HDL cholesterol level. In addition, higher phytosterol/cholesterol ratios appear in HDL versus LDL particles, suggesting the existence of an intrinsic phytosterol action, in addition to the extrinsic effect on cholesterol absorption. In conclusion, addition to diet of the phytosterol sitostanol represents an effective means of improving circulating lipid profiles to reduce risk of coronary heart disease.

Short sleep duration increases energy intakes but does not change energy expenditure in normal-weight individuals

BACKGROUND Evidence suggests a relation between short sleep duration and obesity. OBJECTIVE We assessed energy balance during periods of short and habitual sleep in normal-weight men and women. DESIGN Fifteen men and 15 women aged 30-49 y with a body mass index (in kg/m(2)) of 22-26, who regularly slept 7-9 h/night, were recruited to participate in this crossover inpatient study. All participants were studied under short (4 h/night) and habitual (9 h/night) sleep conditions, in random order, for 5 nights each. Food intake was measured on day 5, and energy expenditure was measured with the doubly labeled water method over each period. RESULTS Participants consumed more energy on day 5 during short sleep (2813.6 ± 593.0 kcal) than during habitual sleep (2517.7 ± 593.0 kcal; P = 0.023). This effect was mostly due to increased consumption of fat (20.7 ± 37.4 g; P = 0.01), notably saturated fat (8.7 ± 20.4 g; P = 0.038), during short sleep. Resting metabolic rate (short sleep: 1455.4 ± 129.0 kcal/d; habitual sleep: 1486.5 ± 129.5 kcal/d; P = 0.136) and total energy expenditure (short sleep: 2589.2 ± 526.5 kcal/d; habitual sleep: 2611.1 ± 529.0 kcal/d; P = 0.832) did not differ significantly between sleep phases. CONCLUSIONS Our data show that a reduction in sleep increases energy and fat intakes, which may explain the associations observed between sleep and obesity. If sustained, as observed, and not compensated by increased energy expenditure, the dietary intakes of individuals undergoing short sleep predispose to obesity. This trial is registered at clinicaltrials.gov as NCT00935402.

Conjugated linoleic acid and obesity control: efficacy and mechanisms

Obesity is associated with high blood cholesterol and high risk for developing diabetes and cardiovascular disease. Therefore, management of body weight and obesity are increasingly considered as an important approach to maintaining healthy cholesterol profiles and reducing cardiovascular risk. The present review addresses the effects of conjugated linoleic acid (CLA) on fat deposition, body weight and composition, safety, as well as mechanisms involved in animals and humans. Animal studies have shown promising effects of CLA on body weight and fat deposition. The majority of the animal studies have been conducted using CLA mixtures that contained approximately equal amounts of trans-10, cis-12 (t10c12) and cis-9, trans-11 (c9t11) isomers. Results of a few studies in mice fed CLA mixtures with different ratios of c9t11 and t10c12 isomers have indicated that the t10c12 isomer CLA may be the active form of CLA affecting weight gain and fat deposition. Inductions of leptin reduction and insulin resistance are the adverse effects of CLA observed in only mice. In pigs, the effects of CLA on weight gain and fat deposition are inconsistent, and no adverse effects of CLA have been reported. A number of human studies suggest that CLA supplementation has no effect on body weight and insulin sensitivity. Although it is suggested that the t10c12 CLA is the antiadipogenic isomer of CLA in humans, the effects of CLA on fat deposition are marginal and more equivocal as compared to results observed in animal studies. Mechanisms through which CLA reduces body weight and fat deposition remain to be fully understood. Proposed antiobesity mechanisms of CLA include decreased energy/food intake and increased energy expenditure, decreased preadipocyte differentiation and proliferation, decreased lipogenesis, and increased lipolysis and fat oxidation. In summary, CLA reduces weight gain and fat deposition in rodents, while produces less significant and inconsistent effects on body weight and composition in pigs and humans. New studies are required to examine isomer-specific effects and mechanisms of CLA in animals and humans using purified individual CLA isomers.

Plant sterols: factors affecting their efficacy and safety as functional food ingredients

Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status.

Plant sterols/stanols as cholesterol lowering agents: A meta-analysis of randomized controlled trials.

Background Consumption of plant sterols has been reported to reduce low density lipoprotein (LDL) cholesterol concentrations by 5–15%. Factors that affect plant sterol efficacy are still to be determined. Objectives To more precisely quantify the effect of plant sterol enriched products on LDL cholesterol concentrations than what is reported previously, and to identify and quantify the effects of subjects’ characteristics, food carrier, frequency and time of intake on efficacy of plant sterols as cholesterol lowering agents. Design Fifty-nine eligible randomized clinical trials published from 1992 to 2006 were identified from five databases. Weighted mean effect sizes were calculated for net differences in LDL levels using a random effect model. Results Plant sterol containing products decreased LDL levels by 0.31 mmol/L (95% CI, –0.35 to –0.27, P= < 0.0001) compared with placebo. Between trial heterogeneity was evident (Chi-square test, P = <0.0001) indicating that the observed differences between trial results were unlikely to have been caused by chance. Reductions in LDL levels were greater in individuals with high baseline LDL levels compared with those with normal to borderline baseline LDL levels. Reductions in LDL were greater when plant sterols were incorporated into fat spreads, mayonnaise and salad dressing, milk and yoghurt comparing with other food products such as croissants and muffins, orange juice, non-fat beverages, cereal bars, and chocolate. Plant sterols consumed as a single morning dose did not have a significant effect on LDL cholesterol levels. Conclusion Plant sterol containing products reduced LDL concentrations but the reduction was related to individuals’ baseline LDL levels, food carrier, and frequency and time of intake.

Medium chain fatty acid metabolism and energy expenditure: obesity treatment implications.

Fatty acids undergo different metabolic fates depending on their chain length and degree of saturation. The purpose of this review is to examine the metabolic handling of medium chain fatty acids (MCFA) with specific reference to intermediary metabolism and postprandial and total energy expenditure. The metabolic discrimination between varying fatty acids begins in the GI tract, with MCFA being absorbed more efficiently than long chain fatty acids (LFCA). Subsequently, MCFA are transported in the portal blood directly to the liver, unlike LCFA which are incorporated into chylomicrons and transported through lymph. These structure based differences continue through the processes of fat utilization; MCFA enter the mitochondria independently of the carnitine transport system and undergo preferential oxidation. Variations in ketogenic and lipogenic capacity also exist. Such metabolic discrimination is supported by data in animals and humans showing increases in postprandial energy expenditure after short term feeding with MCFA. In long term MCFA feeding in animals, weight accretion has been attenuated. These differences in metabolic handling of MCFA versus LCFA are considered with the conclusion that MCFA hold potential as weight loss agents.

Anticancer effects of phytosterols

Phytosterol and stanol (or phytosterols) consumption reduces intestinal cholesterol absorption, leading to decreased blood LDL-cholesterol levels and lowered cardiovascular disease risk. However, other biological roles for plant sterols and stanols have also been proposed. The objective of this review is to critically examine results from recent research regarding the potential effects and mechanisms of action of phytosterols on forms of cancer. Considerable emerging evidence supports the inhibitory actions of phytosterols on lung, stomach, as well as ovarian and breast cancer. Phytosterols seem to act through multiple mechanisms of action, including inhibition of carcinogen production, cancer-cell growth, angiogenesis, invasion and metastasis, and through the promotion of apoptosis of cancerous cells. Phytosterol consumption may also increase the activity of antioxidant enzymes and thereby reduce oxidative stress. In addition to altering cell-membrane structure and function, phytosterols probably promote apoptosis by lowering blood cholesterol levels. Moreover, consumption of phytosterols by healthy humans at the recommended level of 2 g per day does not cause any major health risks. In summary, mounting evidence supports a role for phytosterols in protecting against cancer development. Hence, phytosterols could be incorporated in diet not only to lower the cardiovascular disease risk, but also to potentially prevent cancer development.