A Very Low-Calorie Ketogenic Diet Effectively Reduced Cardiovascular Risk

by | Jun 10, 2019 | Cardiovascular Health, Weight Control

Written by Angeline A. De Leon, Staff Writer. A very low-calorie ketogenic diet, combined with a synthetic amino acid protein replacement, increased weight loss and reduced cardiovascular risk, without the development of sarcopenia and activation of inflammatory and oxidative processes.

weight controlCalorie restriction constitutes one of the primary dietary strategies used to target weight loss and can be categorized as involving a low-calorie diet (daily calorie reduction by 800, LCD) or a very-low-calorie diet (daily calorie reduction greater than 800, VLCD). VLCDs are typically used as part of an integrated medical intervention program for select conditions 1, such as obesity, diabetes, and seizures 2,3. One form of VLCD includes the ketogenic diet (KD) which is characterized by very low intake of carbohydrates and high intake of fat and has been linked to mixed findings in terms of its effects on lipid metabolism 4. While some research suggests that long-term adherence to KD may increase dyslipidemia and inflammation without weight loss 5, other work indicates that KD is linked to attenuation of inflammation and oxidative stress 6,7. Although the VLCD form of the ketogenic diet (VLCKD) is gaining traction as a more effective weight loss method than conventional LCD or VLCD, its impact on metabolic state, inflammation, and oxidative stress levels is still not well understood 4. Therefore, in a study 8 published by the European Review for Medical and Pharmacological Sciences (2017), Merra and colleagues compared three different forms of VLCKD and their impact on body composition, metabolic profile, and expression of genes involved in inflammation and oxidative stress in obese subjects.

Using a cross-over, randomized, double-blind, placebo-controlled trial design, researchers recruited a total of 54 obese patients (aged 18 to 65 years) with a body mass index (BMI) of 25 kg/m2 or greater. Patients were randomized to one of three groups: a VLCKD treatment group (involving 450-500 kcal for females and 650-700 kcal for males), with 35-55% of calories coming from protein and 50% of protein intake sourced from synthetic amino acid supplementation (SAS); a VLCKD placebo group (using a flour placebo instead of SAS) with 20-50% of calories coming from protein (VLCKD placebo 1); or a VLCKD placebo group with 25-50% of calories coming from protein (VLCKD placebo 2). Subjects participated in each of the three arms of the study for three weeks, with a three-week washout period separating each arm. At baseline and at the end of each arm, anthropometric measurements were taken, body mass composition analyzed (total body fat, TBF; intermuscular adipose tissue, IMAT), and fasting blood samples collected for analysis of plasma glucose concentration, lipid profile, and serum metabolites, including growth factor, fibrinogen (clotting factor), and C-reactive protein (marker of inflammation). RNA analysis was also conducted to determine gene expression of proteins involved in inflammation response, such as superoxide dismutase 1 (SOD1, antioxidant defense).

Analyses revealed that all three groups had a significant decrease in BMI (p = 0.00 for all). The VLCKD treatment group exhibited a significant decrease in TBF (p = 0.00) and TBF percentage (p = 0.03), as well as in IMAT value (p = 0.00), low-density lipoprotein cholesterol (p = 0.00), and high-density lipoprotein cholesterol (p = 0.00). The VLCKD placebo 1 group showed a significant reduction in waist circumference (p = 0.02) and fat mass in the lumbar area between lumbar spine 2 and lumbar spine 5, FM L2-L5) (p < 0.05). VLCKD placebo 2 group also exhibited a significant reduction in TBF (p = 0.00) and FM L2-L5 (p < 0.05), as well as in glucose levels (p = 0.03) and CRP (p = 0.02), along with a significant increase in red blood cell count (p = 0.03). Gene expression analysis indicated that only the VLCKD placebo 2 group experienced a significant decrease in the expression of the SOD1 gene (p = 0.009).

This exploratory study on the effects of VLCKD provides evidence to suggest that short-term VLCKD (with 50% of protein replaced by SAS) is associated with positive effects on body composition, as demonstrated by reductions in TBF and IMAT, and lipid profile. Variations of VLCKD (not involving SAS) also showed a favorable impact on other cardiometabolic risk factors, including glucose levels, inflammatory markers, and the expression of oxidative stress-related genes. Follow-up studies are needed to evaluate the persistence of such effects, particularly considering the limited sustainability of a VLCKD diet regimen, and to calibrate optimal protein intake. A notable limitation of the study is its use of a relatively small sample size. It would also be beneficial for prospective studies to incorporate biomarkers such as ketogenic bodies to confirm ketosis in the future.

Source: Merra G, Gratteri S, De Lorenzo A, et al. Effects of very-low-calorie diet on body composition, metabolic state, and gene expression: a randomized double-blind placebo-controlled trial. European Review for Medical and Pharmacological Sciences. 2017; 21: 329-345.

Posted June 10, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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