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Genetic variants for personalised management of very low carbohydrate ketogenic diets.

ABSTRACT: The ketogenic diet (KD) is a low-carbohydrate, high-fat, adequate-protein diet proven to be effective for the reversal of obesity, metabolic syndrome and type 2 diabetes, and holding therapeutic potential for the prevention and treatment of other chronic diseases. Genetic and dynamic markers of KD response may help to identify individuals most likely to benefit from KD and point to individuals at higher risk for adverse health outcomes. Here, we provide a clinician-friendly review of state-of-the-art research on biomarkers of KD response for a variety of outcomes including weight loss, body composition and cognitive performance drawing data from both intervention trials and case reports of rare inborn errors of metabolism. We also present a selection of the most promising candidate genes to evaluate in future studies and discuss key aspects of study design and variant interpretation that may help accelerate the implementation of these biomarkers in clinical practice.

SUBMITTER: Aronica L

PROVIDER: S-EPMC7841814 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Genetic variants for personalised management of very low carbohydrate ketogenic diets.

Aronica Lucia L Volek Jeff J Poff Angela A D'agostino Dominic P DP

BMJ nutrition, prevention & health 20201212 2

The ketogenic diet (KD) is a low-carbohydrate, high-fat, adequate-protein diet proven to be effective for the reversal of obesity, metabolic syndrome and type 2 diabetes, and holding therapeutic potential for the prevention and treatment of other chronic diseases. Genetic and dynamic markers of KD response may help to identify individuals most likely to benefit from KD and point to individuals at higher risk for adverse health outcomes. Here, we provide a clinician-friendly review of state-of-th ...[more]

PMID: 33521546

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Project description:OBJECTIVE: To compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK) and low-fat (LF) diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE) in overweight/obese men and women. DESIGN: Randomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day) diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%). SUBJECTS: 15 healthy, overweight/obese men (mean +/- s.e.m.: age 33.2 +/- 2.9 y, body mass 109.1 +/- 4.6 kg, body mass index 34.1 +/- 1.1 kg/m2) and 13 premenopausal women (age 34.0 +/- 2.4 y, body mass 76.3 +/- 3.6 kg, body mass index 29.6 +/- 1.1 kg/m2). MEASUREMENTS: Weight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry), and resting energy expenditure (REE) were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person. RESULTS: Actual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28%) and the LF (~58:22:20%) were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day) compared to the LF (1562 kcal/day) diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake). The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women. Absolute REE (kcal/day) was decreased with both diets as expected, but REE expressed relative to body mass (kcal/kg), was better maintained on the VLCK diet for men only. Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet. CONCLUSION: This study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss, especially in men. A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinically significant but requires further validation. These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution.

Project description:BackgroundLow-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations.ObjectiveTo examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors.DesignA randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271).SettingA large academic medical center.Participants148 men and women without clinical cardiovascular disease and diabetes.InterventionA low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial.MeasurementsData on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months.ResultsSixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet.LimitationLack of clinical cardiovascular disease end points.ConclusionThe low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors.Primary funding sourceNational Institutes of Health.

Project description:BackgroundKetogenic foods limit digestible carbohydrates but contain high fat, and have antioxidant and anti-inflammatory effects as well as improving mitochondrial function. β-Hydroxybutyrate (BHB), 1 of the ketone bodies, reduces the proinflammatory NLR family pyrin domain containing 3 inflammasomes, as well as chemokines in cultures.ObjectivesWe assessed the immune-modulating effects of 2 low-carbohydrate (LoCHO) foods varying in protein and fat and compared their effects with a food replete with high-carbohydrate (HiCHO) in healthy canines.MethodsDogs were fed control food [HiCHO; ketogenic ratio (KR: 0.46) followed by LoCHO_PROT (KR: 0.97), then LoCHO_FAT (KR: 1.63) or LoCHO_FAT followed by LoCHO_PROT. Each food was fed for 5 wk, with collections in the 5th wk; 15 wk feeding total. Gene expression for circulating inflammatory cytokines from 10 dogs was assessed using the Canine RT2 Profiler polymerase chain reaction array, and fold changes were calculated using the ΔΔCt method.ResultsLoCHO_FAT significantly increased circulating β-hydroxybutyrate compared with both HiCHO and LoCHO_PROT. When compared with HiCHO, there was a significant decrease in several proinflammatory cytokines/chemokines in LoCHO_PROT and LoCHO_FAT groups, including chemokine (C-C motif) ligand (CCL)1, CCL8, CCL13, CCL17, CCL24, chemokine (C-X3-C motif) ligand 1, chemokine (C-X-C motif) receptor 1, Interleukin-10 receptor alpha ((IL)-10RA), IL-1 receptor antagonist, IL-5, and secreted phosphoprotein 1 (all P < 0.05). Interestingly, a subset of inflammatory proteins that decreased in LoCHO_PROT but not in LoCHO_FAT included IL-33, IL-6 receptor, IL-7, IL-8, Nicotinamide phosphoribosyltransferase, and tumor necrosis factor (TNF) receptor superfamily member 11B. In contrast, the decrease in inflammatory markers in LoCHO_FAT, but not in LoCHO_PROT, included complement component 5, granulocyte colony-stimulating factor or G-CSF, interferon-γ, IL-3, IL-10RB, IL-17C, Tumor necrosis factor superfamily (TNFSF)13, TNFSF13B, and TNFSF14. Decreased concentrations of selected cytokines indicate that both low-carbohydrate foods exert an anti-inflammatory effect and provide a strong rationale for testing their efficacy in dogs with inflammatory conditions.ConclusionsBoth LoCHO_PROT and LoCHO_FAT foods might be important as part of immune-modulating therapeutic nutritional strategies to reduce inflammation to maintain health in canines. Our study identifies several inflammatory genes that are reduced when fed ketogenic food that were not previously reported.

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Genetic variants for personalised management of very low carbohydrate ketogenic diets.

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Genetic variants for personalised management of very low carbohydrate ketogenic diets.

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