Effects of a Low Carbohydrate Weight Loss Diet on Exercise Capacity and Tolerance in Obese Subjects

Dietary restriction and increased physical activity are recommended for obesity treatment. Very low carbohydrate diets are used to promote weight loss, but their effects on physical function and exercise tolerance in overweight and obese individuals are largely unknown. The aim of this study was to compare the effects of a very low carbohydrate, high fat (LC) diet with a conventional high carbohydrate, low fat (HC) diet on aerobic capacity, fuel utilization during submaximal exercise, perceived exercise effort (RPE) and muscle strength. Sixty subjects (age: 49.2 ± 1.2 years; BMI: 33.6 ± 0.5 kg/m²) were randomly assigned to an energy restricted (～6–7 MJ, 30% deficit), planned isocaloric LC or HC for 8 weeks. At baseline and week 8, subjects performed incremental treadmill exercise to exhaustion and handgrip and isometric knee extensor strength were assessed. Weight loss was greater in LC compared with HC (8.4 ± 0.4% and 6.7 ± 0.5%, respectively; P = 0.01 time × diet). Peak oxygen uptake and heart rate were unchanged in both groups (P > 0.17). Fat oxidation increased during submaximal exercise in LC but not HC (P < 0.001 time × diet effect). On both diets, perception of effort during submaximal exercise and handgrip strength decreased (P ≤ 0.03 for time), but knee extensor strength remained unchanged (P > 0.25). An LC weight loss diet shifted fuel utilization toward greater fat oxidation during exercise, but had no detrimental effect on maximal or submaximal markers of aerobic exercise performance or muscle strength compared with an HC diet. Further studies are required to determine the interaction of LC diets with regular exercise training and the long‐term health effects.     

Variations in Body Composition and Plasma Lipids in Response to a High‐Carbohydrate Diet

Objective: To examine the extent to which variations in body composition modulate changes in the lipid profile in response to the ad libitum consumption of a diet rich in carbohydrates (CHOs) (high‐CHO diet: 58% of energy as CHOs) or high in fat and in monounsaturated fatty acids (MUFAs) (high‐MUFA diet: 40% of energy as fat, 23% as MUFAs). Research Methods and Procedures: Sixty‐three men were randomly assigned to one of the two diets that they consumed for 6 to 7 weeks. Body composition and fasting plasma lipid levels were measured at the beginning and the end of the dietary intervention. Results: The high‐CHO and high‐MUFA diets induced significant and comparable reductions in body weight and waist circumference. These changes were accompanied by significant and comparable (p < 0.01) reductions in total plasma cholesterol and low‐density lipoprotein cholesterol levels. However, the high‐MUFA diet had more beneficial effects on plasma triglyceride concentrations (p < 0.01) and on plasma high‐density lipoprotein cholesterol levels (p = 0.02) compared with the high‐CHO diet. Diet‐induced changes in waist circumference were significantly associated with changes in low‐density lipoprotein cholesterol levels in the high‐CHO group (r = 0.39, p = 0.03) but not in the high‐MUFA group (r = 0.16, p = 0.38). Discussion: Improvements in plasma lipids induced by the ad libitum consumption of a high‐CHO diet seem to be partly mediated by changes in body weight, whereas lipid changes induced by the high‐MUFA diet seem to be independent of changes in body weight.     

Gender Differences in the Relationship between Personality Dimensions and Relative Body Weight

Objective: The relationship between body mass index (BMI: kg/m²) and personality seems to differ for men and women, although these effects may be driven by the extremes of the BMI distribution. It is unclear whether these associations exist for most individuals in the relatively normal range of BMI scores, excluding the thinnest and heaviest extremes in the population. We tested the association of BMI with neuroticism, extraversion, and psychoticism with a trimmed BMI sample. Research Methods and Procedures: Using a cross‐sectional design, we tested the association of BMI with the aforementioned psychological variables in a British population‐based sample. Participants were 7889 adult men and women (30 to 50 years old) selectively sampled from four counties in west England. Participants reported their height and weight and completed the Eysenck Personality Inventory (EPQ). We tested the association of BMI with the EPQ subscales among individuals with BMI ≥19.16 kg/m² and ≤37.78 kg/m², i.e., the approximate 5th and 95th percentiles. Results: Despite elimination of extreme BMIs, different associations between BMI and EPQ subscales emerged for men and women. Among women, increasing BMI was significantly associated with increased neuroticism and reduced extraversion. Among men, increasing BMI was associated with increased extraversion and psychoticism. In all cases, the magnitude of the association was very small. Discussion: Increasing BMI was associated with potentially poorer adjustment among women but better adjustment among men. These findings are consistent with recent reports and, taken together, suggest that these patterns are not accounted for solely by the extremes of the BMI distribution.     

A Low Sympathoadrenal Activity is Associated with Body Weight Gain and Development of Central Adiposity in Pima Indian Men

TATARANNI P ANTONIO JAMES B YOUNG, CLIFTON BOGARDUS, ERIC RAVUSSIN. A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men. To investigate the possible role of impaired sympathetic nervous system and/or adrenal medullary function in the etiology of human obesity, we studied 64 Pima Indian men (28 ± 6 years, 101 ± 25 kg, 34 ± 9% body fat, mean ± SD) in whom sympathoadrenal function was estimated at baseline by measurements of 24-hour urinary norepinephrine (NE) and epinephrine (Epi) excretion rates under weight-maintenance conditions. Body weight, body composition (hydrodensitometry), and body fat distribution (waist-to-thigh circumference ratio, W/T) were measured at baseline and follow-up. Follow-up data were available on 44 subjects who gained on average 8.4 ± 9.5 kg over 3.3 ± 2.1 years. In these subjects, baseline NE excretion rate, adjusted for its determinants (i.e., fat free mass, fat mass, and W/T), correlated negatively with bodyweight gain (r=?0.38; p=0.009). Baseline Epi excretion rate correlated negatively with changes in W/T (r=?0.44; p=0.003). In conclusion, our data show for the first time that a low sympathetic nervous system activity is associated with body weight gain in humans. Also, a low activity of the adrenal medulla is associated with the development of central adiposity.     

Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice

We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C∶P∶F = 63∶15∶22), a low carbohydrate (LC, C∶P∶F = 38∶25∶37) diet and a severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies.     

A Randomized Pilot Trial of a Moderate Carbohydrate Diet Compared to a Very Low Carbohydrate Diet in Overweight or Obese Individuals with Type 2 Diabetes Mellitus or Prediabetes

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (−0.6%, 95% CI, −1.1% to −0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications.This clinical trial was registered with ClinicalTrials.gov, number {"type":"clinical-trial","attrs":{"text":"NCT01713764","term_id":"NCT01713764"}}NCT01713764.     

A Randomized Trial of Lifestyle Modification and Taranabant for Maintaining Weight Loss Achieved With a Low‐Calorie Diet

Improving the maintenance of weight loss remains a critical challenge for obesity researchers. The present 1‐year, randomized, placebo‐controlled trial evaluated the safety and efficacy of weight maintenance counseling combined with either placebo or the cannabinoid‐1 receptor inverse agonist, taranabant, for sustaining prior weight loss achieved on a low‐calorie diet (LCD). Seven hundred eighty‐four individuals who had lost ≥6% of body weight during six initial weeks of treatment with an 800 kcal/day liquid LCD were randomly assigned to placebo or once‐daily taranabant in doses of 0.5, 1, or 2 mg. All participants were provided monthly, on‐site behavioral weight maintenance counseling, as well as monthly phone calls. The primary end point was change in body weight from randomization to week 52. The randomized participants lost an average of 9.6 kg (9.5% of initial weight) during the 6‐week LCD. The model‐adjusted mean change in body weight during the subsequent 1 year was +1.7 kg for placebo, compared with ?0.1, ?0.6, and ?1.2 kg for the taranabant 0.5, 1, and 2 mg doses, respectively (all P values ≤0.007 vs. placebo). The incidences of psychiatric‐related adverse events, including irritability, were higher for taranabant 1 and 2 mg vs. placebo (P ≤ 0.038). In addition to reporting data on the safety and efficacy of taranabant, this study provides a method for studying the combination of lifestyle modification and pharmacotherapy for weight maintenance after diet‐induced weight loss.     

Topiramate: Long‐Term Maintenance of Weight Loss Induced by a Low‐Calorie Diet in Obese Subjects

Objective: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low‐calorie diet. Research Methods and Procedures: Obese subjects (30 ≤ BMI < 50 kg/m²) 18 to 75 years old received a low‐calorie diet for 8 weeks. Those who lost ≥8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled‐release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. Results: Of the 701 subjects enrolled, 80% lost ≥8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run‐in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. Discussion: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low‐calorie diet—and produced additional clinically significant weight loss beyond that achieved by a low‐calorie diet.     

PPARG Genotype Accounts for Part of Individual Variation in Body Weight Reduction in Response to Calorie Restriction

Several studies indicate that expression of the peroxisome proliferator–activated receptor γ (PPARG) gene is influenced by calorie restriction. The aim of this study was to investigate whether PPARG gene variations are associated with weight reduction and changes in coronary heart disease (CHD) risk factors in response to a 14‐week calorie restriction. In total, 95 middle‐aged, Japanese women (BMI ≥25 kg/m²) enrolled as subjects for 14 weeks and attended weekly dietary lectures instructing them on how to consume a nutritionally balanced diet of 1,200 kcal/day. Eight single‐nucleotide polymorphisms (SNPs) in the PPARG gene (rs1801282 (Pro/Ala), rs2292101, rs2959272, rs1386835, rs709158, rs1175540, rs1175544, and rs1797912) were analyzed. Body weight decreased significantly (?7.7 ± 3.1 kg; ?11.3 ± 4.4%) during the intervention. Six PPARG SNPs (rs2959272, rs1386835, rs709158, rs1175540, rs1175544, and rs1797912) were significantly associated with the weight reduction, with rs1175544 having the strongest association (P = 0.004). No differences across the rs1175544 genotypes were observed in any of the blood analyses or in blood pressure. In a multiple regression analysis, the rs1175544 genotypes accounted for 7% of the total weight reduction variance. These data suggest that one SNP of the PPARG genotype accounted for a significant portion of the total body weight reduction variance in response to a short‐term intervention consisting of calorie restriction; however, no relationship was found between these SNPs and the changes in CHD risk factors which accompanied weight loss.     

Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss

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Rapid Changes of Body Weight after a Headstand: A Metrological Analysis

Despite recent rules from amateur wrestling sport-governing bodies intended to discourage extreme weight loss measures, wrestling culture still includes varied methods to make weight, including holding a headstand position immediately before stepping on the scale. The procedure, according to the notion, will reduce reported mass anywhere between 250 and 500g (weight between 2.45 and 4.89 N). The aim of this study was to compare any possible differences between the headstand procedure (HS) and a normal (CON) weight measure, using a metrological approach defined by the European Association of National Metrology Institutes. Seventeen adult men were weighed on a force plate before and after doing a headstand or standing normally for 30s. The order of treatment application was assigned randomly. Post-test weight was significantly larger than pre-test (mean±s.d.) (640.7±62.8 N and 640.3±62.7 N, respectively, p<0.0001) under both treatments. No treatment vs. time of test interaction was found. No significant difference was found between CON and HS weight (640.6±62.8 N and 640.9±62.9 N, respectively, p=0.3815). The metrological tests suggest that the statistical differences found are related to the force plate measuring errors in every pre-established time interval. The 45g (0.44 N) difference found between pretest and post-test lies within the uncertainty range identified for the equipment (±110 g or 1.08 N). In conclusion, a 30-second headstand has no significant effect on registered body weight. The small variations obtained were due to equipment-associated measuring errors. This experiment offers systematic empirical evidence to aid in the elimination of this unjustified practice among the wrestling community.     

Endocrine Determinants of Changes in Insulin Sensitivity and Insulin Secretion during a Weight Cycle in Healthy Men

ObjectiveChanges in insulin sensitivity (IS) and insulin secretion occur with perturbations in energy balance and glycemic load (GL) of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear.MethodsIn a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m²) followed 1wk of overfeeding (OF), 3wks of caloric restriction (CR) containing either 50% or 65% carbohydrate (CHO) and 2wks of refeeding (RF) with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI), insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose) and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion) were assessed.ResultsIS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05). Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05) whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05) and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only). After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant.ConclusionWeight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and ghrelin seem to be the major endocrine determinants of IS, leptin/adiponectin-ratio and fT4 levels may impact changes in insulin secretion with weight cycling.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01737034","term_id":"NCT01737034"}}NCT01737034     

Proteomic Analysis in Type 2 Diabetes Patients before and after a Very Low Calorie Diet Reveals Potential Disease State and Intervention Specific Biomarkers

Very low calorie diets (VLCD) with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼450 kcal/day). Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS) and targeted multiple reaction monitoring (MRM) and a large scale isobaric tags for relative and absolute quantitation (iTRAQ) approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin), obesity-associated (complement C3), and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV). To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers.

Trial Registration

Controlled-Trials.com ISRCTN76920690     

内蒙古草原布氏田鼠和长爪沙鼠体重及身体成分的季节变化

研究了内蒙古草原布氏田鼠(Lasiopodomys brandtii)和长爪沙鼠(Meriones unguiculatus)的体重、身体脂肪、水分含量及身体热值等指标的季节变化.2种动物的体重都是在春季最高,布氏田鼠的体重具显著的季节变化,长爪沙鼠的鲜重具季节变化,但干重则基本维持恒定.2种动物的脂肪含量和身体热值都...     

Cost‐Effectiveness of a Low‐Carbohydrate Diet and a Standard Diet in Severe Obesity

Objective: Low‐carbohydrate diets have become a popular alternative to standard diets for weight loss. Our aim was to compare the cost‐effectiveness of these two diets. Research Methods and Procedures: The patient population included 129 severely obese subjects (BMI = 42.9) from a randomized trial; participants had a high prevalence of diabetes or metabolic syndrome. We compared within‐trial costs, quality‐adjusted life years (QALYs), and the incremental cost‐effectiveness ratio (CER) for the two study groups. We imputed missing values for QALYs. The CER was bootstrapped to derive 95% confidence intervals and to define acceptability cut‐offs. We took a societal perspective for our analysis. Results: Total costs during the one year of the trial were $6742 ± 6675 and $6249 ± 5100 for the low‐carbohydrate and standard groups, respectively (p = 0.78). Participants experienced 0.64 ± 0.02 and 0.61 ± 0.02 QALYs during the one year of the study, respectively (p = 0.17 for difference). The point estimate of the incremental CER was $?1225/QALY (i.e., the low‐carbohydrate diet dominated the standard diet). However, in the bootstrap analysis, the wide spread of CERs caused the 95% confidence interval to be undefined. The probabilities that the low‐carbohydrate diet was acceptable, using cut‐offs of $50, 000/QALY, $100, 000/QALY, and $150, 000/QALY, were 72.4% 78.6%, and 79.8%, respectively. Discussion: The low‐carbohydrate diet was not more cost‐effective for weight loss than the standard diet in the patient population studied. Larger studies are needed to better assess the cost‐effectiveness of dietary therapies for weight loss.