A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery.

PURPOSE: Nutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS). METHODS: EPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. ß-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2-3 months and 4-6 months. RESULTS: It was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS. CONCLUSION: The obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.

MRI estimated changes in visceral adipose tissue and liver fat fraction in patients with obesity during a very low-calorie-ketogenic diet compared to a standard low-calorie diet.

AIM: To compare the changes in visceral adipose tissue (VAT), liver fat fraction, and liver stiffness using quantitative magnetic resonance imaging (MRI) during a very-low-calorie ketogenic (VLCK) diet and a standard low-calorie diet (LC). MATERIALS AND METHODS: The study involved secondary analysis of prospective collected clinical data. Patients undergoing weight loss interventions were randomised to either a LC or a VLCK diet. VAT, liver fat fraction, and stiffness were measured at baseline and after 2 months. RESULTS: Forty-six patients were included; 39 patients were evaluated at baseline and at 2 months follow-up. Mean weight loss was -9.7±3.8 kg (interquartile range [IQR]: -12.3; -7 kg) in the VLCK group and -1.67±2.2 kg (IQR: -3.3, -0.1 kg) in the LC group (p<0.0001). Mean VAT reductions were -39.3±40 cm2 (IQR: -52, -10 cm2) and -12.5±38.3 cm2 (IQR: -29, 5 cm2; p=0.0398), and mean liver proton density fat fraction (PDFF) reductions were -4.77±4.2% (IQR: -7.3, -1.7%) and -0.79±1.7%, (IQR: -1.8, -0.4%; p<0.005) in the VLCK group and in the LC group, respectively. No significant changes in liver stiffness occurred from baseline to follow-up. CONCLUSION: A VLCK diet resulted in greater weight loss than a standard low-calorie diet and in significantly greater reduction in liver PDFF. As anthropometric measurements may not correlate with liver fat changes, it may be advantageous to include quantitative MRI to the monitoring strategies of patients undergoing weight-loss programmes.

Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: a marker of metabolic stress?

BACKGROUND: Fibroblast growth factor 21 (FGF21) has been suggested to be an endocrine signal of nutritional status and an active regulator of metabolism. However, there is no agreement on the effect of weight-loss therapies on circulating levels of FGF21 in humans. OBJECTIVE: To assess FGF21 circulating levels in adiposity excess and after different weight-loss strategies prescribed in five different groups from four independent centers. SUBJECTS AND METHODS: Body composition, ketosis, insulin sensitivity and FGF21 were evaluated in 181 excess body weight and 14 normal-weight subjects. From the excess body weight patients, two independent groups (discovery cohort; n=20 and validation cohort; n=28) undertook a very low-calorie ketogenic (VLCK) diet, a third group followed a low-calorie (LC) diet (n=84) and other two groups underwent bariatric surgery (discovery cohort; n=24 and validation cohort; n=25). The follow-up was 4 to 6 or 12 months, respectively. RESULTS: FGF21 levels were higher in excess body weight patients than in normal-weight subjects. The energy-restriction therapy to lose weight induced a significant decrease, with respect to baseline, in circulating levels of FGF21 (VLCK: -62.5 pg ml-1 or -14.8 pg ml-1 and LC diet: -67.9 pg ml-1). There were no differences in FGF21 levels between both energy-restriction treatments. On the contrary, after bariatric surgery morbidly obese patients showed a significant increase in FGF21, especially 1 month after surgery (148.8 pg ml-1 higher than baseline). The FGF21 differential changes occur concomitantly with a non-induced ketosis situation (0.66±0.56 mm) in bariatric surgery, and an improvement in adiposity and insulin sensitivity induced by the three therapies. CONCLUSIONS: FGF21 levels were reduced after energy-restricted treatments and severely increased after bariatric surgery, independently of the weight reduction magnitude, insulin sensitivity or ketosis. Therefore, FGF21 appears to be a marker of severe nutritional stress.

Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.

UNLABELLED: Brackground:The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. OBJECTIVE: Evaluating the short-term safety and tolerability of a VLCK diet (<50 g of carbohydrate daily) in an interventional weight loss program including lifestyle and behavioral modification support (Diaprokal Method) in subjects with T2DM. METHODS: Eighty-nine men and women, aged between 30 and 65 years, with T2DM and body mass index between 30 and 35 kg m(-)(2) participated in this prospective, open-label, multi-centric randomized clinical trial with a duration of 4 months. Forty-five subjects were randomly assigned to the interventional weight loss (VLCK diet), and 44 to the standard low-calorie diet. RESULTS: No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both P<0.001). The decline in HbA1c and glycemic control was larger in the VLCK diet group (P<0.05). No serious adverse events were reported and mild AE in the VLCK diet group declined at last follow-up. CONCLUSIONS: The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients.