Diets and drugs for weight loss and health in obesity - An update.

Numerous combinations of diets and pharmacological agents, including lifestyle changes, have been launched to treat obesity. There are still ambiguities regarding the efficacies of different approaches despite many clinical trials and the use of animal models to study physiological mechanisms in weight management and obesity comorbidities, Here, we present an update on promising diets and pharmacological aids. Literature published after the year 2005 was searched in PubMed, Medline and Google scholar. Among recommended diets are low-fat (LF) and low-carbohydrate (LC) diets, in addition to the Mediterranean diet and the intermittent fasting approach, all of which presumably being optimized by adequate contents of dietary fibers. A basic point for weight loss is to adopt a diet that creates a permanently negative and acceptable energy balance, and prolonged dietary adherence is a crucial factor. As for pharmacological aids, obese patients with type 2 diabetes or insulin resistance seem to benefit from LC diet combined with a GLP-1 agonist, e.g. semaglutide, which may improve glycemic control, stimulate satiety, and suppress appetite. The lipase inhibitor orlistat is still used to maintain a low-fat approach, which may be favorable e.g. in hypercholesterolemia. The bupropion-naltrexone-combination appears promising for interruption of the vicious cycle of addictive over-eating. Successful weight loss seems to improve almost all biomarkers of obesity comorbidities. Until more support for specific strategies is available, clinicians should recommend an adapted lifestyle, and when necessary, a drug combination tailored to individual needs and comorbidities. Different diets may change hormonal secretion, gut-brain signaling, and influence hunger, satiety and energy expenditure. Further research is needed to clarify mechanisms and how such knowledge can be used in weight management.

Effect of intermittent and continuous caloric restriction on Sirtuin1 concentration depends on sex and body mass index.

BACKGROUND & AIMS: The favorable effect of caloric restriction (CR) on health span is well known and partly mediated by the sirtuin system. Sirtuin1, a regulator of energy homeostasis in response to nutrient availability, is activated by CR. We therefore investigated effects of two different CR regimens on Sirtuin1 concentrations. METHODS & RESULTS: The study included 112 abdominally obese subjects, randomized to intermittent or continuous CR for 1 year. Blood samples and anthropometric measures were collected at baseline and after 12 months. Sirtuin1 concentrations were measured by ELISA. Sirtuin1 correlated significantly to BMI at baseline (r = .232, p = 0.019). Mean reduction in body-weight was 8.0 and 9.0 kg after intermittent and continuous CR, respectively. After 1 year, no significant between-group differences in Sirtuin1 levels were observed according to regimen (p = 0.98) and sex (p = 0.41). An increase in median Sirtuin1 concentrations (pg/mL) [25, 75 percentiles] from baseline was observed after intermittent CR in the total population (884 [624, 1285] vs.762 [530, 1135]; p = 0.041), most marked in men (820 [623, 1250] vs. 633 [524, 926]; p = 0.016). Improvement in BMI after 1 year correlated to Sirtuin1 changes, but varied according to sex. In women, Spearman's rho = .298, p = 0.034, with stronger correlation in the intermittent CR group (r = .424, p = 0.049). In men, there was an inverse relation to Sirtuin1 changes, only in the intermittent CR group (r = -.396, p = 0.045). CONCLUSIONS: Effects on Sirtuin1 concentrations after 1 year of CR are sex and BMI-related. Intermittent CR regimen affected Sirtuin1 to a stronger extent than continuous CR, suggesting individualized dietary intervention.

BMI modifies the effect of dietary fat on atherogenic lipids: a randomized clinical trial.

BACKGROUND: SFA intake increases LDL cholesterol whereas PUFA intake lowers it. Whether the lipid response to dietary fat differs between normal-weight and obese persons is of relevance to dietary recommendations for obese populations. OBJECTIVES: We compared the effect of substituting unsaturated fat for saturated fat on LDL cholesterol and apoB concentrations in normal-weight (BMI ≤ 25 kg/m2) and obese (BMI: 30-45) subjects with elevated LDL cholesterol. METHODS: We randomly assigned 83 men and women (aged 21-70 y) stratified by BMI (normal: n = 44; obese: n = 39) and elevated LDL cholesterol (mean ± SD, normal weight 4.6 ± 0.9 mmol/L; obese 4.4 ± 0.8 mmol/L) to either a PUFA diet enriched with oil-based margarine ( n = 42) or an SFA diet enriched with butter (n = 41) for 6 wk. RESULTS: Seven-day dietary records showed differences of ∼9 energy percent (E%) in SFA and ∼4 E% in PUFA between the SFA and PUFA groups. In the total study population, the PUFA diet compared with the SFA diet lowered LDL cholesterol (-0.31 mmol/L; 95% CI: -0.47, -0.15 mmol/L, compared with 0.32 mmol/L; 95% CI: 0.18, 0.47 mmol/L; P < 0.001) and apoB (-0.08 g/L; 95% CI: -0.11, -0.05 g/L, compared with 0.07 g/L; 95% CI: 0.03, 0.10 g/L; P < 0.001). Tests of the BMI × diet interaction were significant for total cholesterol, LDL cholesterol, and apoB ( P values ≤ 0.009). In normal-weight compared with obese participants post-hoc comparisons found that the respective changes in LDL cholesterol were 9.7% (95% CI: 5.3%, 14.2%) compared with 5.3% (95% CI: -0.7%, 11.2%), P = 0.206, in the SFA group, and -10.4% (95% CI: -15.2%, -5.7%) compared with -2.3% (95% CI: -7.4%, 2.8%), P = 0.020, in the PUFA group. ApoB changes were 7.5% (95% CI: 3.5%, 11.4%) compared with 3.0% (95% CI: -1.7%, 7.7%), P = 0.140, in the SFA group, and -8.9% (95% CI: -12.6%, -5.2%) compared with -3.8% (95% CI: -6.3%, -1.2%), P = 0.021, in the PUFA group. Responses to dietary fat were not associated with changes in polyprotein convertase subtisilin/kexin type 9 concentrations. CONCLUSIONS: BMI modifies the effect of PUFAs compared with SFAs, with smaller improvements in atherogenic lipid concentrations in obese than in normal-weight individuals, possibly supporting adjustment of dietary recommendations according to BMI. This trial was registered with www.clinicaltrials.gov as NCT02589769.

[Nutritional status after surgical treatment of obesity]. / Ernaeringsstatus etter operativ behandling for fedme.

BACKGROUND: Biliopancreatic bypass with duodenal switch is a treatment for morbid obesity that combines restriction of dietary intake with a high degree of malabsorption. The operation involves the risk of losing important nutritional elements. MATERIAL AND METHODS: 64 women and 14 men who had a biliopancreatic bypass with duodenal switch performed in 2002 - 2005 and were followed up at least once, six months or later after surgery, were examined with 3 to 6-month intervals for the following; body weight, clinical status, haematological variables, ferritin, folate, albumin, creatinine, retinol, alpha-tocopherol/lipids, vitamin D metabolites, parathyroid hormone, vitamin B1, lipids, glucose and other clinical chemical variables. RESULTS: Weight loss after surgery was substantial and rapid, from a mean of 153.8 kg (SD 30.2) to 92.7 kg (SD 21.6) after one year (n = 74). Low values of serum albumin, creatinine, retinol, 25-OH vitamin D and elevated parathyroid hormone were very common. Four women and three men (9 % of all) with common channels of < 100 cm, required a surgical revision mainly due to hypoalbuminemia. Two women became pregnant before the recommended 18 months after surgery. INTERPRETATION: Biliopancreatic bypass with duodenal switch in patients with common channels < 100 cm, has a high rate of complications and nutritional deficiencies. This surgery should be used restrictively.

Effect of lifestyle changes on atherogenic lipids and endothelial cell adhesion molecules in young adults with familial premature coronary heart disease.

Guidelines have recommended that a family history of premature coronary heart disease (CHD) warrants screening and preventive efforts, including lifestyle change. The objective of this study was to evaluate the effects of a lifestyle modification program on lipids and novel risk markers in young relatives of patients with premature CHD. In a parallel, randomized, intervention trial, intensified support to quit smoking and dietary modification was compared with general lifestyle advice in 172 men and women aged 18 to 39 years with a total cholesterol of 5 to 8 mmol/L and >or=1 lipid abnormality (high low-density lipoprotein [LDL] cholesterol, triglycerides or lipoprotein(a), or low high-density lipoprotein cholesterol). All had a first-degree relative with premature CHD or with hyperlipidemia and other relative(s) with premature CHD, and 40% were daily smokers. After a mean of 8 months, the intervention group reduced the dietary intake of saturated fat and cholesterol compared with controls (p = <0.01). Ten smokers in the intervention group quit, whereas 2 subjects in the control group started and none quit. LDL cholesterol (p = 0.007), oxidized LDL (p = 0.03), and E-selectin (p = 0.02) concentrations were reduced in the intervention group compared with controls. In subjects who quit smoking, concentrations of intercellular adhesion molecule-1 decreased (261 +/- 66 to 228 +/- 30 ng/ml) compared with that in continuing smokers (308 +/- 106 ng/ml to 304 +/- 109 ng/ml) (p = 0.05 between groups). These findings indicate that dietary modification and smoking cessation are feasible in young adults with familial premature CHD and document novel mechanisms by which lifestyle modification may reduce CHD risk.