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Efficacy of a 2-Month Very Low-Calorie Ketogenic Diet (VLCKD) Compared to a Standard Low-Calorie Diet in Reducing Visceral and Liver Fat Accumulation in Patients With Obesity.
Cunha, GM, Guzman, G, Correa De Mello, LL, Trein, B, Spina, L, Bussade, I, Marques Prata, J, Sajoux, I, Countinho, W
Frontiers in endocrinology. 2020;11:607
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Excess fat in the liver, known as non-alcoholic fatty liver disease (NAFLD), has been shown to increase the risk of chronic diseases such as type 2 diabetes. Standard treatment regimens consist of low-calorie (LC) diets and exercise, however these may be ineffective at reversing fat accumulation in the liver. A very low-calorie ketogenic diet (VLCKD) has been proposed as an alternative treatment for NAFLD. This randomised control pilot study of 39 individuals with obesity aimed to compare LC diet and VLCKD on fat accumulation and indicators for NAFLD for two months. The results showed greater weight loss, abdominal fat reduction, liver fat reduction and improvements in liver function with VLCKD compared to the LC diet. Cholesterol was significantly reduced by both diets. However liver stiffness remained unchanged. The authors concluded that VLCKD was more successful at reducing liver fat and abdominal fat accumulation than current standard therapy and has the potential to improve NAFLD. Health care professionals could use this study to improve liver and abdominal fat loss in patients with obesity to improve NAFLD, when standard therapy has been inadequate.
Abstract
Background: Currently the treatment of non-alcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. Objectives: To assess the effects of a commercially available weight loss program based on a very low-calorie ketogenic diet (VLCKD) on visceral adipose tissue (VAT) and liver fat content compared to a standard low-calorie (LC) diet. As a secondary aim, we evaluated the effect on liver stiffness measurements. Methods: Open, randomized controlled, prospective pilot study. Patients were randomized and treated either with an LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction, and liver stiffness were measured at baseline and after 2 months of treatment using magnetic resonance imaging. Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the χ2-test. Pearson correlation was used to assess the association between VAT, anthropometric measures, and hepatic fat fraction. A significance level of the results was established at p < 0.05. Results: Thirty-nine patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87% in the VLCKD group and -1.87 ± 2.4% in the LC group (p < 0.001). Mean reductions in VAT were -32.0 cm2 for VLCKD group and -12.58 cm2 for LC group (p < 0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in the LC group (4.77 vs. 0.79%; p < 0.005). Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to the standard LC diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD could serve as an effective alternative for the treatment of NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04322110.
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Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics.
Demark-Wahnefried, W, Rogers, LQ, Gibson, JT, Harada, S, Frugé, AD, Oster, RA, Grizzle, WE, Norian, LA, Yang, ES, Della Manna, D, et al
International journal of cancer. 2020;146(10):2784-2796
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Obesity directly impacts survival in individuals with breast cancer. Previous studies in animals and at the cellular level have shown that calorie restriction and increased physical activity to achieve a negative energy balance may inhibit cancer progression, however effects in patients are unknown. This randomised control trial aimed to determine the impact of a pre surgery weight loss programme in 32 women with breast cancer on tumour biology and other markers of disease. The results were mixed and showed that proteins which bind to hormones involved in breast cancer were increased, which could decrease severity of disease. However, tumour biology was negatively affected; specific genes involved in breast cancer progression were increased and those involved in tumour suppression were decreased. Although this did result in no net effect on the rate at which new tumours were formed. It was concluded that although the study showed mixed results, ultimately the rate at which new tumours were formed remained unaffected. This trial could be used by healthcare professionals to understand that the role of negative energy intake in breast cancer development is complicated and warrants further research.
Abstract
Obesity adversely impacts overall and cancer-specific survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, feasibility and effects in patients are unknown. A two-arm, single-blinded, randomized controlled weight-loss trial was undertaken presurgery among 32 overweight/obese, Stage 0-II breast cancer patients. The attention control arm (AC) received basic nutritional counseling and upper-body progressive resistance training whereas the weight loss intervention (WLI) arm received identical guidance, plus counseling on caloric restriction and aerobic exercise to promote 0.68-0.92 kg/week weight loss. Anthropometrics, body composition, blood and survey data were collected at baseline and presurgery ∼30 days later. Tumor markers (e.g., Ki67) and gene expression were assessed on biopsy and surgical specimens; sera were analyzed for cytokines, growth and metabolic factors. Significant WLI vs. AC differences were seen in baseline-to-follow-up changes in weight (-3.62 vs. -0.52 kg), %body fat (-1.3 vs. 0%), moderate-to-vigorous physical activity (+224 vs. +115 min/week), caloric density (-0.3 vs. 0 kcal/g), serum leptin (-12.3 vs. -4.0 ng/dl) and upregulation of tumor PI3Kinase signaling and cell cycle-apoptosis related genes (CC-ARG; all p-values <0.05). Cytolytic CD56dim NK cell expression was positively associated with weight loss; CC-ARG increased with physical activity. Increased tumor (nuclear) TNFα and IL-1β, CX3CL1 and CXCL1 gene expression was observed in the WLI. Tumor Ki67 did not differ between arms. Feasibility benchmarks included 80% accrual, 100% retention, no adverse effects and excellent adherence. Short-term weight loss interventions are feasible; however, mixed effects on tumor biology suggest unclear benefit to presurgical caloric restriction, but possible benefits of physical activity.
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Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese.
Edinburgh, RM, Bradley, HE, Abdullah, NF, Robinson, SL, Chrzanowski-Smith, OJ, Walhin, JP, Joanisse, S, Manolopoulos, KN, Philp, A, Hengist, A, et al
The Journal of clinical endocrinology and metabolism. 2020;105(3)
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Following exercise, various metabolic changes occur which may be of benefit in fighting diseases such as type 2 diabetes and obesity. However, the degree of change may vary depending on whether the exercise has been performed pre or post meal consumption. This 6-week randomised crossover trial of 30 overweight or obese men aimed to determine the effect of exercising before or after breakfast on the use of fats and sugars by the body. The results showed that exercise before breakfast increased fat and sugar use in the body and also resulted in the alteration of eight genes associated with metabolism. Exercise before carbohydrate consumption also increased lipid use and improved insulin sensitivity, however body composition was similar regardless of when exercise was performed. It was concluded that exercising in the fasted state can optimise the body’s response without having to change intensity or effort. This study could be used by health care professionals to advise patients with obesity or overweight that exercising whilst in the fasted state could optimise their outcomes without having to increase exercise intensity or frequency.
Abstract
CONTEXT Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. OBJECTIVE To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. DESIGN (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). SETTING General community. PARTICIPANTS Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). INTERVENTIONS Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. RESULTS Acute Study-exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: -3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (-1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study-postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs -21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05). CONCLUSIONS Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.
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Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial.
Safarpour, P, Daneshi-Maskooni, M, Vafa, M, Nourbakhsh, M, Janani, L, Maddah, M, Amiri, FS, Mohammadi, F, Sadeghi, H
BMC family practice. 2020;21(1):26
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Type 2 diabetes (T2D) is often preceded by a condition known as insulin resistance (IR). Recent studies have shown that low levels of vitamin D in the body are related to an increased incidence of IR and individuals with T2D have lower levels of vitamin D than healthy individuals. Vitamin D may have the ability to increase enzymes in the body that breakdown sugar and decrease IR. This 12-month double blind randomised control trial on 90 obese type 2 diabetics, aimed to assess the effects of vitamin D on these enzymes and blood sugar levels. The results showed that individuals on vitamin D had significantly increased enzymes which are involved in sugar breakdown and this translated into improved blood sugar levels, however this did not translate into improved markers for IR. It was concluded that compared to placebo, vitamin D supplementation improved blood sugar levels possibly due to the increase in enzymes involved in sugar breakdown. Healthcare professionals could use this study to recommend vitamin D supplementation to obese type 2 diabetics to improve their blood sugar levels.
Abstract
BACKGROUND Vitamin D (VD) may increase sirtuin 1 (SIRT1) and subsequently PPAR-γ coactivator 1α (PGC-1α) and irisin levels and these improvements may reduce insulin resistance (IR). The aim was to assess the effects of vitamin D supplementation on SIRT1, irisin, and IR in overweight/obese type 2 diabetes (T2D) patients. METHODS Ninety T2D males and females were recruited as a clinical trial study (mean of age and body mass index (BMI) of intervention and placebo groups were 50.05 ± 10.17 and 50.36 ± 10.2 yrs. and 31.37 ± 3.4 and 30.43 ± 3.2 kg/m2, respectively). The inclusion criteria were T2D, VD deficient, BMI > 25 kg/m2, and serum HbA1c < 8.5%. The exclusion criteria were using vitamin and mineral supplements, having any acute disease, recent modifying dose or type of drugs. The supplementation was 50,000 IU/week VD or placebo for 8 weeks. The demographic characteristics, anthropometrics, dietary intakes and physical activity status, sun exposure status, fasting blood sugar (FBS) and insulin, glycosylated hemoglobin (HbA1c), irisin, SIRT1, 25-hydroxy D3 (25(OH)VD), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were determined. The significant P-value was ≤0.05. RESULTS The increase of serum VD, SIRT1, and irisin in the intervention group was significant (p < 0.001). HbA1c was decreased significantly by 1%. The changes in the other glucose indices (FBS, insulin, and IR) were non-significant. CONCLUSIONS VD supplementation may improve T2D by decreasing HbA1c and increasing SIRT1 and irisin in VD deficient T2D patients. Further trials are suggested. TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT201604202365N11. Registered 21/08/2016, http://en.irct.ir/trial/2019.
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Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients With Obesity and Mild Kidney Failure.
Bruci, A, Tuccinardi, D, Tozzi, R, Balena, A, Santucci, S, Frontani, R, Mariani, S, Basciani, S, Spera, G, Gnessi, L, et al
Nutrients. 2020;12(2)
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Very low-calorie ketogenic diets (VLCKD) may be an effective way to lose weight. However, the high amount of protein they contain may harm the kidneys, especially in those who already have impaired kidney function. This observational study of 92 obese men and women aimed to evaluate the effect of VLCKD on weight loss in individuals with mild kidney failure, compared to healthy individuals. A VLCKD diet resulted in significantly decreased BMI and body weight, due to a decrease in fat mass and slight decrease in muscle mass. Improvements were seen in blood pressure, indicators for diabetes and cholesterol levels. No changes to kidney or liver function were apparent and only a few minor adverse events were reported. Interestingly a small percentage of individuals with mildly impaired kidney function reported improvements in their condition. It was concluded that VLCKD is a safe and effective way to lose weight in patients with obesity and mild kidney disease. This study could be used by healthcare professionals to consider recommending a VLCKD to patients who are obese and have mild kidney disease.
Abstract
Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.
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Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial.
Lisboa, JVC, Ribeiro, MR, Luna, RCP, Lima, RPA, Nascimento, RAFD, Monteiro, MGCA, Lima, KQF, Fechine, CPNDS, Oliveira, NFP, Persuhn, DC, et al
Nutrients. 2020;12(2)
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Obesity is associated with low-grade inflammation in the body, which can cause damage to the body’s cells and tissues. In some individuals, a genetic variation exists, which means that the body is unable to process the vitamin folate effectively, resulting in more inflammation. A diet rich in folate may be necessary to reduce the inflammation and subsequent damage, especially in obese individuals who carry this genetic variation. This randomised double-blind control trial over eight-weeks aimed to determine the effect of a folate rich diet (not supplementation) on inflammation in 48 obese women who carry the genetic variation. The results showed that folate levels were increased following consumption of a folate rich diet and in particular, women with a specific genetic make-up showed reduced inflammation. It was concluded that the level of inflammation reduction from a folate rich diet in women who are unable to process folate effectively depends upon the genetics of the individual. This study could be used by healthcare professionals to understand the importance of personalising recommendations to reduce inflammation in women with obesity.
Abstract
Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated with body fat accumulation could possibly trigger an inflammatory process by elevating homocysteine levels and increasing cytokine production, causing several diseases. This study aimed to evaluate the effects of food intervention, and not folate supplements, on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in overweight and obese women with the MTHFR C677T polymorphism. A randomized, double-blind eight-week clinical trial of 48 overweight and obese women was conducted. Participants were randomly assigned into two groups. They received 300 g of vegetables daily for eight weeks containing different doses of folate: 95 µg/day for Group 1 and 191 µg/day for Group 2. MTHFR C677T polymorphism genotyping was assessed by digestion with HinfI enzyme and on 12% polyacrylamide gels. Anthropometric measurements, 24-h dietary recall, and biochemical analysis (blood folic acid, vitamin B12, homocysteine (Hcy), TNF-α, IL-1β, and IL-6) were determined at the beginning and end of the study. Group 2 had a significant increase in folate intake (p < 0.001) and plasma folic acid (p < 0.05) for individuals with the cytosine-cytosine (CC), cytosine-thymine (CT), and thymine-thymine (TT) genotypes. However, only individuals with the TT genotype presented reduced levels of Hcy, TNF-α, IL-6, and IL-1β (p < 0.001). Group 1 showed significant differences in folate consumption (p < 0.001) and folic acid levels (p < 0.05) for individuals with the CT and TT genotypes. Food intervention with folate from vegetables increased folic acid levels and reduced interleukins, TNF-α, and Hcy levels, mainly for individuals with the TT genotype.