Nutritional Interventions for Patients with Mitochondrial POLG-Related Diseases: A Systematic Review on Efficacy and Safety.

Ketogenic diet is recommended as a treatment to reduce seizure frequency in patients with intractable epilepsy. The evidence and safety results are sparse for diet interventions in patients with pathogenic polymerase gamma (POLG) variants and intractable epilepsy. The aim of this systematic review is to summarize the efficacy of diet treatment on seizure frequency, clinical symptoms, and potential deleterious effect of liver involvement in patients with mitochondrial diseases caused by pathogenic POLG variants. Literature was searched in PubMed, Embase; and Cochrane in April 2022; no filter restrictions were imposed. The reference lists of retrieved studies were checked for additional literature. Eligibility criteria included verified pathogenic POLG variant and diet treatment. Overall, 880 studies were identified, providing eight case-reports representing nine patients eligible for inclusion. In eight of nine cases, clinical symptoms were improved; six out of nine cases reported improvements in seizure frequency. However, increasing levels of liver enzymes after initiating ketogenic diet were found in four of the nine cases, with one case revealing decreased levels of liver enzymes after initiating long-chain triglyceride restriction. Viewed together, the studies imply that ketogenic diet can have a positive impact on seizure frequency, but may induce progression of liver impairment in patients with pathogenic POLG variants.

Medical management of children with type 1 diabetes on low-carbohydrate or ketogenic diets.

OBJECTIVES: Low-carbohydrate and ketogenic diets are becoming increasingly popular choices for people with type 1 diabetes (T1D) aiming to achieve optimal glycemic control. A carbohydrate-restricted diet in children has been associated with negative health effects including poor linear growth and inadequate bone mineralization. Guidelines for monitoring children and adolescents choosing to follow a carbohydrate-restricted diet do not exist. We aimed to create a clinical protocol outlining how to clinically and biochemically follow patients choosing a carbohydrate-restricted diet with the goal of medical safety. METHODS: An interdisciplinary committee was formed and reviewed current consensus guidelines for pediatric patients on carbohydrate-restricted diets for epilepsy and metabolic disorders. A literature search was done to determine management strategies for children with T1D on a low-carbohydrate or ketogenic diet. Key health parameters that require monitoring were identified: growth, glycemic control, bone health, cardiometabolic health, and nutritional status. These health outcomes were used to develop a protocol for monitoring children on carbohydrate-restricted diets. RESULTS: A one-page protocol for medical providers and educational materials for families interested in following a low-carbohydrate or ketogenic diet were developed and successfully implemented into clinical care. CONCLUSION: Implementing a protocol for children on carbohydrate-restricted diets in clinic allows medical providers to ensure medical safety while being open to discussing a family's dietary preferences. Following children in the protocol over time will lead to informed clinical guidelines for patients with T1D who choose to follow a carbohydrate-restricted diet.

Distinct effects of carbohydrate ingestion timing on glucose fluctuation and energy metabolism in patients with type 2 diabetes: a randomized controlled study.

This randomized, open-label, and parallel-group study aimed to investigate the effects of altering the timing of carbohydrate intake at breakfast or dinner on blood glucose fluctuations and energy metabolism. A total of 43 participants with type 2 diabetes were assigned to either the breakfast or dinner group. Participants were provided an isocaloric carbohydrate-restricted diet constituting 10% carbohydrate only at breakfast or dinner for 2 days during the study. Glucose fluctuations were compared using a continuous glucose monitoring system (iPro2) and body composition, energy expenditure, blood biochemistry, and endocrine function changes. The carbohydrate restriction either at breakfast or dinner significantly decreased postprandial glucose excursion and mean 24-h blood glucose levels. The incremental blood glucose area under the curve (AUC) for 2 h (iAUC0-2h) at lunch significantly increased in the breakfast group, whereas no significant differences were observed in the iAUC0-2h between breakfast and lunch in the dinner group. Carbohydrate restriction reduced diet-induced thermogenesis at breakfast (intragroup comparison; 223 ± 117 to 109 ± 104 kcal, p = 0.002) but did not affect diet-induced thermogenesis at dinner. However, fasting plasma free fatty acids were comparable in both groups, prelunch free fatty acids increased significantly only in the breakfast group (0.20 ± 0.09 to 0.63 ± 0.19 mEq/L, p < 0.001). Carbohydrate restriction in the diet once daily decreases mean 24-h blood glucose levels and exerts unique metabolic effects depending on the timing.

Effects of a low-carbohydrate ketogenic diet on health parameters in resistance-trained women.

PURPOSE: The aim of this study was to evaluate the effect of a ketogenic diet on blood pressure, visceral adipose tissue (VAT), bone mineral content (BMC), and bone mineral density (BMD) in trained women. METHODS: Twenty-one resistance-trained women performed an 8-week resistance training program after a 3-week familiarization phase. Participants were randomly assigned to a non-ketogenic diet (n = 11, NKD) or ketogenic diet (n = 10, KD) group. Health parameters were measured before and after the nutritional intervention. Blood pressure was measured using a digital automatic monitor, while VAT, BMC, and BMD changes were measured by dual-energy X-ray absorptiometry. RESULTS: There was a significant reduction in systolic blood pressure in KD (mean ± SD [IC 95%], P value, Hedges' g; - 6.3 ± 6.0 [- 10.5, - 2.0] mmHg, P = 0.009, g = - 0.81) but not in NKD (- 0.4 ± 8.9 [- 6.8, 6.0] mmHg, P = 0.890, g = - 0.04). The results on VAT showed no changes in both groups. The KD showed a small favorable effect on BMD (0.02 ± 0.02 [0.01, 0.03] g·cm-2, P = 0.014, g = 0.19) while NKD did not show significant changes (0.00 ± 0.02 [- 0.02, 0.02] g·cm-2, P = 0.886, g = 0.01). No differences in group or in the time × group interaction were found in any of the variables. CONCLUSIONS: Consuming a low-carbohydrate high-fat KD in conjunction with a resistance training program might help to promote the improvement of health-related markers in resistance-trained women. Long-term studies are required to evaluate the superiority of a KD in comparison to a traditional diet.

Lower carbohydrate and higher fat intakes are associated with higher hemoglobin A1c: findings from the UK National Diet and Nutrition Survey 2008-2016.

PURPOSE: Evidence of low-carbohydrate, high-fat diets (LCHF) for type 2 diabetes (T2DM) prevention is scarce. We investigated how carbohydrate intake relates to HbA1c and T2DM prevalence in a nationally representative survey dataset. METHODS: We analyzed dietary information (4-day food diaries) from 3234 individuals aged ≥ 16 years, in eight waves of the UK National Diet and Nutrition Survey (2008-2016). We calculated LCHF scores (0-20, higher score indicating lower  %food energy from carbohydrate, with reciprocal higher contribution from fat) and UK Dietary Reference Value (DRV) scores (0-16, based on UK dietary recommendations). Associations between macronutrients and diet scores and diabetes prevalence were analyzed (in the whole sample) using multivariate logistic regression. Among those without diabetes, analyses between exposures and %HbA1c (continuous) were analyzed using multivariate linear regression. All analyses were adjusted for age, sex, body mass index, ethnicity, smoking status, total energy intake, socioeconomic status and survey years. RESULTS: In the overall study sample, 194 (6.0%) had diabetes. Mean intake was 48.0%E for carbohydrates, and 34.9%E for total fat. Every 5%E decrease in carbohydrate, and every 5%E increase in fat, was associated with 12% (95% CI 0.78-0.99; P = 0.03) and 17% (95% CI 1.02-1.33; P = 0.02) higher odds of diabetes, respectively. Each two-point increase in LCHF score is related to 8% (95% CI 1.02-1.14; P = 0.006) higher odds of diabetes, while there was no evidence for association between DRV score and diabetes. Among the participants without diagnosed diabetes (n = 3130), every 5%E decrease in carbohydrate was associated with higher %HbA1c by + 0.016% (95% CI 0.004-0.029; P = 0.012), whereas every 5%E increase in fat was associated with higher  %HbA1c by + 0.029% (95% CI 0.015-0.043; P < 0.001). Each two-point increase in LCHF score is related to higher  %HbA1c by + 0.010% (0.1 mmol/mol), while each two-point increase in the DRV score is related to lower  %HbA1c by - 0.023% (0.23 mmol/mol). CONCLUSIONS: Lower carbohydrate and higher fat intakes were associated with higher HbA1c and greater odds of having diabetes. These data do not support low(er) carbohydrate diets for diabetes prevention.

Carbohydrate-restricted diet promotes skin senescence in senescence-accelerated prone mice.

This study used senescence-accelerated prone mice (SAMP8) to examine the effects of a carbohydrate-restricted diet on aging and skin senescence, to determine how long-term carbohydrate restriction affects the aging process. Three-week-old male SAMP8 mice were divided into three groups after 1 week of preliminary feeding: one was given a controlled diet, the other was given a high-fat diet, and the third was given a carbohydrate-restricted diet. Ad libitum feeding was administered until the mice reached 50 weeks of age. Before the end of the test period, a grading test was used to evaluate visible aging in the mice. After the test period, serum and skin samples in mice were obtained and submitted for analysis. As a result, the grading test demonstrated that there was significant progression of visible aging in the carbohydrate-restricted group, as well as a decreased survival rate. Histological examination of the skin revealed that the epidermis and dermis in the carbohydrate-restricted group had become thinner. Analysis of the mechanisms involved demonstrated an increase in serum interleukin-6, aggravated skin senescence, inhibition of skin autophagy and activation of skin mTOR. Therefore, this study proved that a carbohydrate-restricted diet promoted skin senescence in senescence-accelerated mice.

The relationship between pretreatment dietary composition and weight loss during a randomised trial of different diet approaches.

BACKGROUND: Identifying pretreatment dietary habits that are associated with weight-loss intervention outcomes could help guide individuals' selection of weight-loss approach among competing options. A pretreatment factor that may influence weight-loss outcomes is macronutrient intake. METHODS: Overweight and obese Durham Veterans Affairs outpatients were randomised to a weight-loss intervention with a low-carbohydrate diet (n = 71) or orlistat medication therapy plus a low-fat diet (n = 73). Percentage fat, carbohydrate and protein intake prior to treatment were measured using 4-day food records. Linear mixed-effects models were used to determine whether pretreatment percentage macronutrient intake influenced weight trajectories and weight loss in each weight-loss condition. RESULTS: Participant's mean age was 53 years, baseline body mass index was 39.3 kg m(-2) and 72% were male. A higher pretreatment percentage carbohydrate intake was associated with less rapid initial weight loss (P = 0.02) and less rapid weight regain (P = 0.03) in the low-carbohydrate diet condition but was not associated with weight trajectories in the orlistat plus low-fat diet condition. In both conditions, a higher pretreatment percentage fat intake was associated with more rapid weight regain (P < 0.01). Pretreatment percentage protein intake was not associated with weight trajectories. None of the pretreatment macronutrients were associated with weight loss on study completion in either condition. CONCLUSIONS: Selection of a weight-loss approach on the basis of pretreatment macronutrient intake is unlikely to improve weight outcomes at the end of a 1-year treatment. However, pretreatment macronutrient intake may have implications for tailoring of interventions to slow weight regain after weight loss.

The impact of dietary fat type on lipid profiles in lean mass hyper-responder phenotype.

Key Clinical Message: Although the lean mass hyper-responder (LMHR) phenotype is well known, its diagnosis is impeded by the influence of fat type and intake on the lipid profile. Accordingly, a detailed assessment is warranted if LMHR is suspected. Abstract: A 47-year-old man with suspected familial hypercholesterolemia presented with elevated triglyceride and low-density lipoprotein cholesterol levels. He had adhered to a ketogenic diet and was suspected of a lean mass hyper-responder phenotype; however, his lipid profile did not meet the definition. His lipid profile improved through dietary management without medication.

The Effect of a Moderately Restricted Carbohydrate Diet on Cardiometabolic Risk Factors in Overweight and Obese Women With Metabolic Syndrome: A Randomized Controlled Trial.

PURPOSE: Metabolic syndrome (MetS) is a major public health concern that increases the risk of cardiovascular disease and mortality. In previous studies of MetS management, low-carbohydrate diets have been strongly emphasized, despite the fact that many apparently healthy individuals have difficulties adhering to these diets on a long-term basis. The purpose of the present study was to elucidate the effects of a moderately restricted carbohydrate diet (MRCD) on cardiometabolic risk factors in women with MetS. METHODS: This parallel 3-month, single-blind randomized controlled trial was conducted in Tehran, Iran, among 70 women with overweight or obesity aged 20 to 50 years with MetS. Patients were randomly allocated to receive either MRCD (42%-45% carbohydrates and 35%-40% fats) (n = 35) or a normal weight loss diet (NWLD) (52%-55% carbohydrates and 25%-30% fats) (n = 35). Both diets contained the same quantity of protein, which accounted for 15% to 17% of total energy. Anthropometric measurements, blood pressure, lipid profile, and glycemic indices were all assessed before and after the intervention. FINDINGS: Compared with the NWLD group, following an MRCD significantly decreased weight (-4.82 vs -2.40 kg; P = 0.01), body mass index (-1.88 vs -0.94 kg/m2; P = 0.01), waist circumference (-5.34 vs -2.75 cm; P = 0.01), hip circumference (-2.58 vs -1.11 cm; P = 0.01), serum triglyceride (-26.8 vs -7.19 mg/dL; P = 0.01), and increased serum HDL-C levels (1.89 vs. 0.24 mg/dL; P = 0.01). There was no significant difference between the 2 diets in waist-to-hip ratio, serum total cholesterol, serum LDL-C, systolic and diastolic blood pressure, fasting blood glucose, insulin levels, or the homeostasis model assessment for insulin resistance. IMPLICATIONS: Moderate carbohydrate replacement with dietary fats significantly improved weight, body mass index, waist circumference, hip circumference, serum triglyceride, and HDL-C levels among women with MetS. Iranian Registry of Clinical Trials identifier: IRCT20210307050621N1.

The effect of "moderately restricted carbohydrate" diet on gut microbiota composition and metabolic parameters in women with metabolic syndrome: a study protocol for a randomized controlled trial.

BACKGROUND: Metabolic syndrome (MetS) is a group of risk factors that increase the risk of death and a variety of chronic diseases. Recent studies have indicated that the imbalance of gut microbiota might contribute to development and progression of metabolic syndrome. Carbohydrate restriction in the diet has been proven to be one of the most effective methods in the management of metabolic syndrome, even in the absence of weight loss. However, no study has examined the effects of a carbohydrate-restricted diet on gut microbiota composition in metabolic syndrome patients. Thus, we will examine the effects of a "moderately restricted carbohydrate (MRC)" diet on gut microbiota, insulin resistance, and components of MetS among Iranian women. In addition, the stability of changes in dependent variables, including gut microbiota, will also be assessed. METHODS: This is a parallel randomized clinical trial in which 70 overweight or obese women aged 20-50 years with MetS will be randomly assigned to receive either MRC diet (42-45% carbohydrate, 35-40% fats) or a normal weight loss (NWL) diet (52-55% carbohydrate, 25-30% fats) for 3 months. Protein accounted for 15-17% of total energy in both diets. The quantity of gut microbiota including Firmicutes, Bacteroidetes, Bifidobacteria, Lactobacillus, Clostridium, Prevotella, Bacteroidetes, and Akkermansia muciniphila, as well as anthropometric, blood pressure, and metabolic parameters will be measured at study baseline and the end of trail. At the end of this phase, all participants will be placed on a weight maintenance diet for an additional 6 months. After following up study subjects in this duration, all dependent variables will be examined again to assess their stability over this period. DISCUSSION: To the best of our knowledge, this is the first randomized controlled trial investigating the effects of a moderately restricted carbohydrate diet on gut microbiota composition and several metabolic parameters during the weight loss and maintenance phases in women with MetS. TRIAL REGISTRATION: Iranian Registry of Clinical Trials ( www.irct.ir , IRCT20210307050621N1). Registered on May 31, 2021.

Dietary Changes Leading to Euglycemic Diabetic Ketoacidosis in Sodium-Glucose Cotransporter-2 Inhibitor Users: A Challenge for Primary Care Physicians?

BACKGROUND: The use of euglycemic diabetic ketoacidosis (EDKA) related to sodium-glucose cotransporter 2 inhibitors (SGLT2i) use in people with diabetes has been increasingly reported. The causes are multifactorial, and dietary changes in SGLT2i users were observed to trigger EDKA. A ketogenic diet or very low-carbohydrate diet (VLCD) enhances body ketosis by breaking down fats into energy sources, causing EDKA. This study aimed to understand the patient specific risk factors and clinical characteristics of this cohort. METHODS: Several databases were carefully analyzed to understand the patients' symptoms, clinical profile, laboratory results, and safety of dietary changes in SGLT2i's. Thirteen case reports identifying 14 patients on a ketogenic diet and SGLT2i's diagnosed with EDKA were reviewed. RESULTS: Of the 14 patients, 12 (85%) presented with type-2 diabetes mellitus (DM) and 2 (15%) presented with type-1 DM. The duration of treatment with SGLT2i before the onset of EDKA varies from 1 to 365 days. The duration of consuming a ketogenic diet or VLCD before EDKA onset varies from 1 to 90 days, with over 90% of patients hospitalized <4 weeks after starting the diet. At presentation, average blood glucose was 167.50±41.80 mg/dL, pH 7.10±0.10, HCO3 8.1±3.0 mmol/L, potassium 4.2±1.1 mEq/L, anion-gap 23.6±3.5 mmol/L, and the average hemoglobin A1c was 10%±2.4%. The length of hospital stay ranged from 1 to 15 days. None of the patients were reinitiated on SGLT2i's, and 50% (2/4) of the patients reported were on the ketogenic diet or VLCD upon patient questioning. CONCLUSION: Despite the popularity of the ketogenic diet and VLCD for weight loss, their use in diabetics taking SGLT2i's is associated with EDKA. Physicians should educate patients with diabetes taking SGLT2i's about the risk of EDKA. In addition, patients should be encouraged to include their physicians in any decision related to significant changes in diet or exercise routines. Further research is needed to address if SGLT2i's should be permanently discontinued in patients with diabetes on SGLT2i and whether the ketogenic diet developed EDKA.

Severe Hypertriglyceridemia-Induced Necrotizing Pancreatitis Associated With Ketogenic Diet in a Well-Controlled Patient With Type 2 Diabetes Mellitus.

The ketogenic diet (keto diet) has become an increasingly popular approach for both weight loss and as an alternative diet for type 2 diabetes mellitus (T2DM). Owing to the nature of the keto diet, patients are at risk of developing hypertriglyceridemia (HTG) due to the high amount of triglycerides consumed by individuals during the initiation of this diet. Acute pancreatitis can result from HTG. We present a case of a 19-year-old African American male with well-controlled T2DM and no history of HTG who developed severe necrotizing HTG-induced pancreatitis after an unsupervised three-month trial of the keto diet.

Carbohydrate-Restricted Diet: A Successful Strategy for Short-Term Management in Youth with Severe Obesity-An Observational Study.

Background: Obesity affects ∼20% of children in the United States and reports of successful dietary treatment are lacking. This study aimed to determine the change in body weight in severely obese youth after carbohydrate-restricted dietary intervention. Methods: This single-center study of a carbohydrate-restricted diet (≤30 grams per day), with unlimited calories, fat, and protein for 3-4 months, examined two groups of severely obese youth of ages 5-18 years: Group A, retrospectively reviewed charts of severely obese youth referred to the Pediatric Obesity Clinic at Hoops Family Children's Hospital and the Ambulatory Division of Marshall Pediatrics, Marshall University School of Medicine, in Huntington, WV, between July 1, 2014 and June 30, 2017 (n = 130), and Group B, prospective participants, referred between July 1, 2018 and December 31, 2018, followed with laboratory studies pre- and postdietary intervention (n = 8). Results: In Group A, 310 participants began the diet, 130 (42%) returned after 3-4 months. Group B had 14 enrollees who began the diet, and 8 followed up at 3-4 months (57%). Girls compared with boys were more likely to complete the diet (P = 0.02). Participants <12 years age were almost twice as likely to complete the diet compared with those 12-18 years (64% vs. 36%, P < 0.01); however, the older group subjects who completed the diet had the same percentage of weight loss compared with those <12 years (6.9% vs. 6.9%). Group A had reductions in weight of 5.1 kg (P < 0.001), body mass index (BMI) 2.5 kg/m2 (P < 0.001), and percentage weight loss 6.9% (P < 0.001). Group B had reductions in weight 9.6 kg (P < 0.01), BMI 4 kg/m2 (P < 0.01), and percentage weight loss 9% (P < 0.01). In addition, participants had significant reductions of fasting serum insulin (P < 0.01), triglycerides (P < 0.01), and 20-hydroxyeicosatetraenoic acid (P < 0.01). Conclusions: This study demonstrated a carbohydrate-restricted diet, utilized short term, effectively reduced weight in a large percentage of severely obese youth, and can be replicated in a busy primary care office.

Optimal Diet Strategies for Weight Loss and Weight Loss Maintenance.

Obesity has become one of the most important public health problems worldwide, which suggests the need for evidence-based dietary strategies for weight loss and its maintenance. Weight management depends upon complex factors such as amount of food eaten, type of food eaten, and timing of meals. In this review, we identified evidence-based dietary strategies for weight management based on these three components. An energy deficit is the most important factor in weight loss. A low-calorie diet with a low fat or carbohydrate content has been recommended; however, in some cases, a very-low-calorie diet is required for a short period. Some macronutrient composition-based diets, such as the ketogenic diet or high-protein diet, could be considered in some cases, although the potential risks and long-term effectiveness remain unknown. Meal timing is also an important factor in weight management, and higher-calorie breakfasts in combination with overnight fasting may help to prevent obesity. Our review indicated that there is no single best strategy for weight management. Hence, strategies for weight loss and its maintenance should be individualized, and healthcare providers must choose the best strategy based on patient preferences.

Non-alcoholic Fatty Liver Disease and Carbohydrate Restricted Diets: A Case Report and Literature Review.

Non-alcoholic fatty liver disease is the accumulation of excessive fat in the liver. Various treatment options are available to manage the condition, among which carbohydrate restriction has been shown to reduce liver fat accumulation, liver inflammation, serum liver enzyme levels, and hepatic de-novo lipogenesis in people with non-alcoholic fatty liver disease. Here, we present a case report of a 25-year-old South Asian patient presenting with right upper quadrant pain, fatigue, and headaches. After confirmation of non-Alcoholic fatty liver disease (NAFLD) diagnosis by biopsy, the patient initiated a low-carbohydrate diet. Four months after which significant improvement was noticed in clinical and laboratory parameters. Peer-reviewed publications were then sourced from online databases to explore the efficacy of low-carbohydrate diets for NAFLD. Our results were compared with the existing data. However, limited literature existed for such an intervention in the South Asian population therefore, the case report is novel. Combined with findings from the literature, our results from the case report supported our hypothesis that carbohydrate restriction might promote a reduction in hepatic fat accumulation and inflammation in patients with NAFLD and diabetes in various ethnicities including South Asians.

A carbohydrate-restricted diet for patients with irritable bowel syndrome lowers serum C-peptide, insulin, and leptin without any correlation with symptom reduction.

Alterations in gut endocrine cells and hormone levels have been measured in patients with irritable bowel syndrome (IBS). The hypothesis of the present study was that hormone levels would change after 4 weeks of a starch- and sucrose-reduced diet (SSRD) intervention corresponding to decreased carbohydrate intake and symptoms. Among 105 IBS patients from primary and tertiary healthcare, 80 were randomized to SSRD, while 25 followed their ordinary diet. Food diaries, Rome IV, and IBS-symptom severity score (IBS-SSS) questionnaires were completed, and blood samples were collected at baseline and after the intervention. Serum C-peptide, gastric inhibitory peptide, glucagon, glucagon-like peptide-1, insulin, leptin, luteinizing hormone, polypeptide YY, and glucose were measured, along with the prevalence of autoantibodies against gonadotropin-releasing hormone; its precursor, progonadoliberin-2, and receptor; and tenascin C. Carbohydrate intake was lower in the intervention group than in controls at week 4 (median: 88 [66-128] g vs 182 [89-224] g; P < .001). The change in carbohydrate intake, adjusted for weight, was associated with a decrease in C-peptide (ß: 14.43; 95% confidence interval [CI]: 4.12-24.75) and insulin (ß: 0.18; 95% CI: 0.04-0.32) levels. Glucose levels remained unchanged. The IBS-SSS scores were lower in the intervention group but not in controls (P < .001), without any association with changes in hormone concentrations. There was no difference in autoantibody prevalence between patients and healthy controls. In conclusion, the hypothesis that reduced carbohydrate intake corresponded to altered hormonal levels in IBS was accepted; however, there was no relationship between hormonal concentrations and symptoms.

The Effects of Low-Energy Moderate-Carbohydrate (MCD) and Mixed (MixD) Diets on Serum Lipid Profiles and Body Composition in Middle-Aged Men: A Randomized Controlled Parallel-Group Clinical Trial.

Carbohydrate-restricted diets have become very popular due to their numerous health benefits. The aim of this study was to determine the influence of 4 weeks of a well-planned, low-energy moderate-carbohydrate diet (MCD) and a low-energy mixed diet (MixD) on the lipoprotein profile, glucose and C-reactive protein concentrations, body mass, and body composition in middle-aged males. Sixty middle-aged males were randomly assigned to the following groups: hypocaloric MCD (32% carbohydrates, 28% proteins, and 40% fat), hypocaloric MixD (50% carbohydrates, 20% proteins, and 30% fat), and a conventional (control) diet (CD; 48% carbohydrates, 15% proteins, and 37% fat). The participants who were classified into the MCD and MixD groups consumed 20% fewer calories daily than the total daily energy expenditure (TDEE). Baseline and postintervention fasting triacylglycerol (TG), LDL (low-density lipoprotein) cholesterol (LDL-C), HDL (high-density lipoprotein) cholesterol (HDL-C), total cholesterol (tCh), glucose (Gl), and C-reactive protein were evaluated. Body mass (BM) and body composition changes, including body fat (BF), % body fat (PBF), and muscle mass (MM), were monitored. Compared with MixD and CD, MCD significantly changed the fasting serum concentrations of TG (p < 0.05), HDL-C (p < 0.05), LDL-C (p < 0.05), tCh (p < 0.05), and glucose (p < 0.01). Additionally, body fat content (kg and %) was significantly reduced (p < 0.05) after MCD compared with MixD and CD. After the MixD intervention, BM and MM decreased (p < 0.05) compared with baseline values. Compared with baseline, after the MixD, BM, MM, tCh, LDL-C, and TG changed significantly. The 4 week low-energy MCD intervention changed lipoproteins, glucose, and body fat to a greater extent than the low-energy MixD. A hypocaloric MCD may be suggested for middle-aged male subjects who want to lose weight by reducing body fat content without compromising muscle mass.

Low and reduced carbohydrate diets: challenges and opportunities for type 2 diabetes management and prevention.

Low-carbohydrate diets (LCD) have been promoted for weight control and type 2 diabetes (T2D) management, based on an emerging body of evidence, including meta-analyses with an indication of publication bias. Proposed definitions vary between 50 and 130 g/d, or <10 and <40 % of energy from carbohydrate, with no consensus on LCD compositional criteria. LCD are usually followed with limited consideration for other macronutrients in the overall diet composition, introducing variance in the constituent foods and in metabolic responses. For weight management, extensive evidence supports LCD as a valid weight loss treatment, up to 1-2 years. Solely lowering carbohydrate intake does not, in the medium/long term, reduce HbA1c for T2D prevention or treatment, as many mechanisms interplay. Under controlled feeding conditions, LCD are not physiologically or clinically superior to diets with higher carbohydrates for weight-loss, fat loss, energy expenditure or glycaemic outcomes; indeed, all metabolic improvements require weight loss. Long-term evidence also links the LCD pattern to increased CVD risks and mortality. LCD can lead to micronutrient deficiencies and increased LDL-cholesterol, depending on food selection to replace carbohydrates. Evidence is limited but promising regarding food choices/sources to replace high-carbohydrate foods that may alleviate the negative effects of LCD, demanding further insight into the dietary practice of medium to long term LCD followers. Long-term, high-quality studies of LCD with different food sources (animal and/or plant origins) are needed, aiming for clinical endpoints (T2D incidence and remission, cardiovascular events, mortality). Ensuring micronutrient adequacy by food selection or supplementation should be considered for people who wish to pursue long-term LCD.

Effect of a Moderate Carbohydrate-Restricted Diet on DPP-4 Inhibitor Action among Individuals with Type 2 Diabetes Mellitus: A 6-Month Intervention Study.

To decrease body weight and insulin resistance, a calorie-restricted diet-with minimal caloric intake required for daily activities-is the primary treatment strategy for patients with type 2 diabetes (T2D) in Japan. However, many patients cannot continue with this diet for long, because calorie restriction is difficult and nutritional balance is hard to understand. Carbohydrate-restricted diets are easier for patients than conventional calorie-restricted diet. In this study we aimed to elucidate the effects of a moderate carbohydrate-restricted diet on glucose metabolism and renal function in patients with T2D on dipeptidyl peptidase-4 (DPP-4) inhibitors. Nineteen outpatients with T2D continued on a moderate carbohydrate-restricted diet (targeting 50% of calories) for 6 mo. Meanwhile, 10 other outpatients with T2D on DPP-4 inhibitors had the conventional calorie-restricted diet using the food exchange table. No change in prescription drugs occurred for both groups during the study period. After the intervention, the carbohydrate content in dietary intake was lowered significantly from 56.8±8.3 to 46.8±10.1%, while the lipid concentration, primarily n-6 polyunsaturated fatty acids, was significantly increased. There was no significant change in protein intake. Hemoglobin A1c (HbA1c) fell from 7.22±0.74% to 6.95±0.72% (mean±SD). Furthermore, salt intake decreased significantly from 6.8±2.5 g prior to the intervention, to 5.7±1.9 g after the intervention. The estimated glomerular filtration rates (eGFR) decreased slightly, while serum creatinine levels did not change. These findings suggest that a moderate carbohydrate-restricted diet (50%) is effective in patients with T2D, without affecting kidney function.

Carbohydrate-restricted diet alters the gut microbiota, promotes senescence and shortens the life span in senescence-accelerated prone mice.

This study examined the effects of a carbohydrate-restricted diet on aging, brain function, intestinal bacteria and the life span to determine long-term carbohydrate-restriction effects on the aging process in senescence-accelerated prone mice (SAMP8). Three-week-old male SAMP8 were divided into three groups after a week of preliminary feeding. One group was given a controlled diet, while the others fed on high-fat and carbohydrate-restricted diets, respectively. The mice in each group were further divided into two subgroups, of which one was the longevity measurement group. The other groups fed ad libitum until the mice were 50 weeks old. Before the test period termination, passive avoidance test evaluated the learning and memory abilities. Following the test period, serum and various mice organs were obtained and submitted for analysis. The carbohydrate-restricted diet group exhibited significant decrease in the survival rate as compared to the other two diet groups. The passive avoidance test revealed a remarkable decrease in the learning and memory ability of carbohydrate-restricted diet group as compared to the control-diet group. Measurement of lipid peroxide level in tissues displayed a marked increase in the brain and spleen of carbohydrate-restricted diet group than the control-diet and high-fat diet groups. Furthermore, notable serum IL-6 and IL-1ß level (inflammation indicators) elevations, decrease in Enterobacteria (with anti-inflammatory action), increase in inflammation-inducing Enterobacteria and lowering of short-chain fatty acids levels in cecum were observed in the carbohydrate-restricted diet group. Hence, carbohydrate-restricted diet was revealed to promote aging and shortening of life in SAMP8.