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Habitual daily intake of a sweet and fatty snack modulates reward processing in humans.
Edwin Thanarajah, S, DiFeliceantonio, AG, Albus, K, Kuzmanovic, B, Rigoux, L, Iglesias, S, Hanßen, R, Schlamann, M, Cornely, OA, Brüning, JC, et al
Cell metabolism. 2023;35(4):571-584.e6
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The prolific amount of sugar and fat in modern Western diets is regarded as a significant contributor to overeating and consequential weight gain. Dopamine, a neurotransmitter involved in learning and reward signalling, is also important in regulating food intake. Energy-dense foods, often high in both sugar and fat, stimulate pleasure-signalling dopamine to encourage eating, even if no more energy is needed. It is acknowledged that in many cases of obesity, the function of dopamine appears to be altered. Yet it is uncertain whether this was pre-existing to obesity, a result of obesity or whether it was re-shaped though exposure to high sugar and high-fat diets. To gain more insights, this study evaluated whether adding a high-fat/high-sugar (HF/HS) snack or a low-fat/low-sugar (LF/LS) snack to a regular diet could change the candidates liking for fat, their brain responses to likeable foods like fat and sugar and if it impacted on sensory associative learning. The randomised controlled study was conducted for 8-weeks and included 49 people of normal-weight. The candidates were also monitored for any changes in weight and body fat, insulin resistance, leptin levels, and blood fats, and all completed self-reported dietary intake forms. The findings demonstrated that repeated exposure to HF/HS food reduced the preference for low-fat foods and up-regulated the brain responses when anticipating and consuming such highly palatable, energy-dense foods. Beyond increased brain response to HF/HS food, HF/HS exposure also induced a general rewiring of the brain by enhancing new sensory associations and behavioural adaptations that were unrelated to food. Notably, these changes all occurred independent of weight gain or alterations in metabolic function, thus suggesting that repeated exposure to HF/HS foods can change the physiology in healthy weight individuals to reduce their liking of healthier foods whilst at the same time increasing the reward responses to more palatable HF/ HS foods. The authors highlighted this as a risk for overeating and weight gain, arguing that reducing the exposure to energy-dense HF/HS food items therefore is critical in the prevention and management of obesity.
Abstract
Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity, or (3) directly attributable to repeated exposure to western diet. To close this gap, we performed a randomized, controlled study (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for 8 weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain.
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The effectiveness of diet intervention in improving the metabolism of overweight and obese women: a systematic review and meta-analysis.
Chen, M, Chen, Q, Liu, W, Tong, H, Wu, Y
American journal of translational research. 2022;14(5):2926-2938
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At present, the treatment for obesity includes regular physical activity, diet intervention, medication and bariatric surgery. The aim of this study was to summarise the current literature and investigate whether different dietary interventions influence the metabolic indicators of overweight or obesity. This study is a systematic review and meta-analysis of twelve papers, eight of which were of medium quality. The duration of dietary therapy was usually an average of 19 weeks, from 4 weeks to 24 weeks. Dietary interventions included a calorie-restricted diet, a Mediterranean diet, a low-carb diet, a low-fat diet, and a ketogenic diet. Results show that dietary intervention had a significant effect on changes in fasting insulin, fasting glucose and insulin resistance changes in women. Additionally, dietary intervention also had a positive effect on triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Authors conclude that obese women should follow dietary interventions to improve their metabolic index. Furthermore, future large-scale randomised controlled trial experiments should be performed on specific diet therapies.
Abstract
OBJECTIVES Dietary therapy may improve glucose and lipid metabolism function in women. However, there is no systematic review to investigate the association between metabolic effects and different dietary interventions in obese women. The main purpose of this study is to summarize the current literature and investigate whether different dietary interventions have an effect on glucose and metabolic indicators of overweight or obese women. METHODS We conducted a scoping review of randomized controlled trial (RCT) studies from 1991 to 2022 by adopting a systematic review and meta-analysis. The database includes Google Scholar, PubMed, Embase and Web of Science. Literature screening, data extraction, and quality assessment were independently completed by 2 researchers. Meta-analysis was performed with RevMan. RESULTS Twelve articles were extracted and the meta-analysis results showed that the mean difference of metabolic indexes of obese women before and after dietary intervention, including fasting glucose, fasting insulin, HOMA-IR (Homeostasis model assessment-insulin resistance), TG (triglyceride), TC (total cholesterol), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol) are -0.13 [-0.15, -0.10], -2.41 [-3.44, -1.38], -0.13 [-0.15, -0.10], -21.71 [-24.19, -19.22], -21.71 [-24.19, -19.22], -13.29 [-17.86, -8.72], 3.31 [2.22, 4.40], respectively. CONCLUSIONS Different dietary interventions benefit glucose and lipid metabolism of overweight or obese women. Further study is needed to determine which specific dietary effects have the greatest effect on improving metabolic indicators.
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The Effect of Ketogenic Diet on Shared Risk Factors of Cardiovascular Disease and Cancer.
Mohammadifard, N, Haghighatdoost, F, Rahimlou, M, Rodrigues, APS, Gaskarei, MK, Okhovat, P, de Oliveira, C, Silveira, EA, Sarrafzadegan, N
Nutrients. 2022;14(17)
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Cardiovascular disease and cancer are major causes of mortality worldwide and share common pathophysiological mechanisms and risk factors. The ketogenic diet, a low-carbohydrate and high-fat diet, may alter metabolic pathways, potentially lowering the risk of developing these diseases. Specifically, the ketogenic diet improves energy metabolism by promoting the use of body ketones for energy production. This review examines the protective effects of the ketogenic diet in reducing cardiovascular disease and cancer risk and explores the underlying mechanisms. The ketogenic diet may suppress oxidative stress and inflammation while improving common risk factors such as obesity, hypertension, diabetes, and dyslipidaemia. It is important to conduct further rigorous studies to assess the long-term effects of the ketogenic diet. However, healthcare professionals can use these findings to understand the short-term benefits of the diet in managing metabolic abnormalities and reducing the risk of developing cardiovascular disease and cancer.
Abstract
Cardiovascular disease (CVD) and cancer are the first and second leading causes of death worldwide, respectively. Epidemiological evidence has demonstrated that the incidence of cancer is elevated in patients with CVD and vice versa. However, these conditions are usually regarded as separate events despite the presence of shared risk factors between both conditions, such as metabolic abnormalities and lifestyle. Cohort studies suggested that controlling for CVD risk factors may have an impact on cancer incidence. Therefore, it could be concluded that interventions that improve CVD and cancer shared risk factors may potentially be effective in preventing and treating both diseases. The ketogenic diet (KD), a low-carbohydrate and high-fat diet, has been widely prescribed in weight loss programs for metabolic abnormalities. Furthermore, recent research has investigated the effects of KD on the treatment of numerous diseases, including CVD and cancer, due to its role in promoting ketolysis, ketogenesis, and modifying many other metabolic pathways with potential favorable health effects. However, there is still great debate regarding prescribing KD in patients either with CVD or cancer. Considering the number of studies on this topic, there is a clear need to summarize potential mechanisms through which KD can improve cardiovascular health and control cell proliferation. In this review, we explained the history of KD, its types, and physiological effects and discussed how it could play a role in CVD and cancer treatment and prevention.
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A double-blinded, randomized, parallel intervention to evaluate biomarker-based nutrition plans for weight loss: The PREVENTOMICS study.
Aldubayan, MA, Pigsborg, K, Gormsen, SMO, Serra, F, Palou, M, Galmés, S, Palou-March, A, Favari, C, Wetzels, M, Calleja, A, et al
Clinical nutrition (Edinburgh, Scotland). 2022;41(8):1834-1844
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Obesity, and particularly abdominal adiposity, is associated with various metabolic abnormalities. Diet has a vital role in preventing and managing obesity, but evidence from clinical studies demonstrates there is a great interindividual variability in response to the same dietary intervention, which likely indicates that no one diet is superior to another. The aim of this study was to examine the efficacy of the PREVENTOMICS (empowering consumers to PREVENT diet-related diseases through OMICS sciences) platform, incorporated in an e-commerce digital tool, for producing more favourable health outcomes over dietary plans based on general diet recommendations, in subjects with overweight or obesity and elevated waist circumference. This study is a 10-week randomised single-centre, parallel-group, double-blinded intervention study. Participants were allocated in a 1:1 ratio, stratified by cluster to either the intervention group (personalised plan) or the control group (generic recommendations). Results show that there isn’t any additional benefit of personalising dietary plans, over a generic approach, on the change in fat mass and body weight in individuals with overweight or obesity and elevated waist circumference. Accordingly, personalisation of the diet did not significantly improve health parameters beyond the changes induced by the control diet. Participants in both groups lost approximately 3 kg of body weight. Authors conclude that based on their findings evidence to translate personalised nutrition approaches into clinical practice is insufficient.
Abstract
BACKGROUND & AIMS Growing evidence suggests that biomarker-guided dietary interventions can optimize response to treatment. In this study, we evaluated the efficacy of the PREVENTOMCIS platform-which uses metabolomic and genetic information to classify individuals into different 'metabolic clusters' and create personalized dietary plans-for improving health outcomes in subjects with overweight or obesity. METHODS A 10-week parallel, double-blinded, randomized intervention was conducted in 100 adults (82 completers) aged 18-65 years, with body mass index ≥27 but <40 kg/m2, who were allocated into either a personalized diet group (n = 49) or a control diet group (n = 51). About 60% of all food was provided free-of-charge. No specific instruction to restrict energy intake was given. The primary outcome was change in fat mass from baseline, evaluated by dual energy X-ray absorptiometry. Other endpoints included body weight, waist circumference, lipid profile, glucose homeostasis markers, inflammatory markers, blood pressure, physical activity, stress and eating behavior. RESULTS There were significant main effects of time (P < 0.01), but no group main effects, or time-by-group interactions, for the change in fat mass (personalized: -2.1 [95% CI -2.9, -1.4] kg; control: -2.0 [95% CI -2.7, -1.3] kg) and body weight (personalized: -3.1 [95% CI -4.1, -2.1] kg; control: -3.3 [95% CI -4.2, -2.4] kg). The difference between groups in fat mass change was -0.1 kg (95% CI -1.2, 0.9 kg, P = 0.77). Both diets resulted in significant improvements in insulin resistance and lipid profile, but there were no significant differences between groups. CONCLUSION Personalized dietary plans did not result in greater benefits over a generic, but generally healthy diet, in this 10-week clinical trial. Further studies are required to establish the soundness of different precision nutrition approaches, and translate this science into clinically relevant dietary advice to reduce the burden of obesity and its comorbidities. CLINICAL TRIAL REGISTRY ClinicalTrials.gov registry (NCT04590989).
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Effects of the 5:2 intermittent fasting diet on non-alcoholic fatty liver disease: A randomized controlled trial.
Kord Varkaneh, H, Salehi Sahlabadi, A, Găman, MA, Rajabnia, M, Sedanur Macit-Çelebi, M, Santos, HO, Hekmatdoost, A
Frontiers in nutrition. 2022;9:948655
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Non-alcoholic fatty liver disease (NAFLD) is associated with modifiable risk factors such as obesity, diabetes and metabolic syndrome. The 5:2 diet is an intermittent fasting regimen in which you fast for two days and eat liberally for five days per week. Time-restricted eating or intermittent fasting is a great way to limit energy intake and manage metabolic markers, making fasting diets like the 5:2 a viable option for the treatment of NAFLD. In this study, fifty patients with NAFLD were randomly assigned to either the intermittent fasting (5:2) or the control group. In the 5:2 group, the intervention resulted in a modest reduction in calorie intake. Participants on the 5:2 diet showed significant improvements in biomarkers of NAFLD, inflammatory markers, and body composition after 12 weeks of intervention. An evaluation of the effectiveness of a 5:2 diet on improving lipid profiles and diabetes requires further robust research. This study provides healthcare professionals insight into the benefits of implementing intermittent fasting as a cost-effective and safe therapeutic method.
Abstract
Background and aims: Dietary regimens are crucial in the management of non-alcoholic fatty liver disease (NAFLD). The effects of intermittent fasting (IF) have gained attention in this regard, but further research is warranted. Thus, we aimed to ascertain the overall effects of the 5:2 IF diet (5 days a week of normal food intake and 2 consecutive fasting days) in patients with NAFLD compared to a control group (usual diet). Methods and results: A 12-week randomized controlled trial was performed to evaluate the effects of the 5:2 IF diet on anthropometric indices, body composition, liver indices, serum lipids, glucose metabolism, and inflammatory markers in patients with NAFLD. The IF group (n = 21) decreased body weight (86.65 ± 12.57-82.94 ± 11.60 kg), body mass index (30.42 ± 2.27-29.13 ± 1.95 kg/m2), waist circumference (103.52 ± 6.42-100.52 ± 5.64 cm), fat mass (26.64 ± 5.43-23.85 ± 5.85 kg), fibrosis (6.97 ± 1.94-5.58 ± 1.07 kPa), steatosis scores/CAP (313.09 ± 25.45-289.95 ± 22.36 dB/m), alanine aminotransferase (41.42 ± 20.98-28.38 ± 15.21 U/L), aspartate aminotransferase (34.19 ± 10.88-25.95 ± 7.26 U/L), triglycerides (171.23 ± 39.88-128.04 ± 34.88 mg/dl), high-sensitivity C-reactive protein (2.95 ± 0.62 -2.40 ± 0.64 mg/L), and cytokeratin-18 (1.32 ± 0.06-1.19 ± 0.05 ng/ml) values compared to the baseline and the end of the control group (n = 23)-p ≤ 0.05 were considered as significant. However, the intervention did not change the levels of high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, fasting blood sugar, insulin, HOMA-IR, and total antioxidant capacity. Conclusion: Adhering to the 5:2 IF diet can reduce weight loss and related parameters (fat mass and anthropometric indicators of obesity), as well as hepatic steatosis, liver enzymes, triglycerides, and inflammatory biomarkers in patients with NAFLD.
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Morphological Adaptation in the Jejunal Mucosa after Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers: Data from a Randomized Crossover Study.
Casselbrant, A, Wallenius, V, Elebring, E, Marschall, HU, Johansson, BR, Helander, HF, Fändriks, L
Nutrients. 2022;14(19)
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The small intestinal mucosa is a large organ which acts as an intestinal barrier. The jejunal mucosa is the largest part of the small intestinal mucosa, and its functions include digestion and absorption of food. Epithelium cells on the surface of the small intestine renew every few days. Therefore, this single-centre, randomised, unblinded, crossover study looked at how jejunal mucosal cells change after two weeks of an isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) in fifteen healthy people. The study also measured ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and mitochondria following the isocaloric HFD and HCD. Neither HFD nor HCD changes the mucosal surface enlargement factor. However, at the ultrastructural level, there was a significant surface enlargement in the bases of the villi after following HCD than HFD. In addition, HFD increased the number of mitochondrial cristae in the erythrocytes than HCD. The increased number of mitochondrial cristae in the erythrocytes was associated with the increased expression of HMGCS2. Healthcare professionals can use the results of this study to understand how short-term implementation of different diets affects jejunal mucosal morphology at the ultrastructural level. Further robust studies are required to evaluate the long-term effects of HFD and HCD in jejunal mucosa and how the morphological adaptations impact people with obesity.
Abstract
BACKGROUND AND AIMS The conditions for jejunal glucose absorption in healthy subjects have not been thoroughly studied. In this study we investigated differences in the jejunal villi enlargement factor, as well as ultrastructural aspects of the surface enterocytes and mitochondria, comparing 2 weeks of high-carbohydrate (HCD) versus high-fat diets (HFD). We also measured the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in relation to jejunal mitochondria. METHODS A single-centre, randomized, unblinded crossover study in 15 healthy volunteers ingesting strictly controlled equicaloric diets (either HCD or HFD), with 60% energy from the respective source. An enteroscopy was carried out after 2 weeks of each diet and jejunal mucosal biopsies were acquired. Conventional histology, immunofluorescent staining, transmission electron microscopy and confocal microscopy were used. RESULTS The villi did not demonstrate any change in the epithelial enlargement factor. Despite an increased mitosis, there were no changes in apoptotic indices. However, the ultrastructural analysis demonstrated a significant increase in the enlargement factor at the bases of the villi. The mitochondria demonstrated increased amounts of cristae after the HFD. The confocal microscopy revealed increased HMGCS2 per mitochondrial marker at the top of the villi after the HFD compared to the HCD. CONCLUSION There is a morphometric adaption in the jejunal mucosa following the 2-week diets, not only on a histological level, but rather on the ultrastructural level. This study supports the notion that mitochondrial HMGCS2 is regulated by the fat content of the diet and is involved in the expression of monosaccharide transporters.
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Time-restricted eating and exercise training improve HbA1c and body composition in women with overweight/obesity: A randomized controlled trial.
Haganes, KL, Silva, CP, Eyjólfsdóttir, SK, Steen, S, Grindberg, M, Lydersen, S, Hawley, JA, Moholdt, T
Cell metabolism. 2022;34(10):1457-1471.e4
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A healthy diet and regular physical activity are primary lifestyle strategies for the prevention and treatment of obesity and its associated conditions. However, poor adherence rates to these strategies limit their effectiveness. Time-restricted eating (TRE) is a popular dietary strategy that emphasises the timing of meals in alignment with diurnal circadian rhythms, permitting ad libitum energy intake during a restricted eating window (8–10 h between the first and last energy intake of the day). The aim of this study was to investigate the isolated and combined effects of TRE and high-intensity interval training (HIIT) on glycaemic control and cardiometabolic health outcomes in women with overweight/obesity. This study is a 7-week randomised controlled trial with four parallel groups: TRE (energy intake limited to a %10-h eating window every day), HIIT (three supervised treadmill exercise sessions per week), a combination (TREHIIT), and a control group (CON, no intervention). Participants (n=131) were randomly assigned to one of the four groups. . Results show that 7 weeks of TRE, HIIT, or a combination failed to improve glycaemic control in reproductive-aged women with overweight/obesity. However, the combination of TRE and HIIT significantly reduced glycated haemoglobin levels compared with CON and induced greater losses in body weight, fat mass, and visceral fat area compared with either intervention alone. Isolated TRE resulted in lower nocturnal glucose concentrations compared with CON. Authors conclude that combining TRE with HIIT can rapidly induce several health benefits and decrease metabolic disease risk in women with overweight/obesity. In fact, the high rates of compliance and adherence shown in their findings, highlight the potential of these diet-exercise (TRE and HIIT) protocols to be implemented in clinical practice for treatment and primary prevention of overweight/ obesity.
Abstract
Diet modification and exercise training are primary lifestyle strategies for obesity management, but poor adherence rates limit their effectiveness. Time-restricted eating (TRE) and high-intensity interval training (HIIT) improve cardiometabolic health in at-risk individuals, but whether these two interventions combined induce superior improvements in glycemic control than each individual intervention is not known. In this four-armed randomized controlled trial (ClinicalTrials.gov NCT04019860), we determined the isolated and combined effects of 7 weeks of TRE (≤10-h daily eating window, with ad libitum energy intake) and HIIT (three exercise sessions per week), compared with a non-intervention control group, on glycemic control and secondary cardiometabolic outcomes in 131 women (36.2 ± 6.2 years) with overweight/obesity. There were no statistically significant effects after isolated TRE, HIIT, or a combination (TREHIIT) on glucose area under the curve during an oral glucose tolerance test (the primary outcome) compared with the control group (TRE, -26.3 mmol/L; 95% confidence interval [CI], -82.3 to 29.7, p = 0.36; HIIT, -53.8 mmol/L; 95% CI, -109.2 to 1.6, p = 0.057; TREHIIT, -41.3 mmol/L; 95% CI, -96.4 to 13.8, p = 0.14). However, TREHIIT improved HbA1c and induced superior reductions in total and visceral fat mass compared with TRE and HIIT alone. High participant adherence rates suggest that TRE, HIIT, and a combination thereof may be realistic diet-exercise strategies for improving markers of metabolic health in women at risk of cardiometabolic disease.
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Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial.
Iacovides, S, Maloney, SK, Bhana, S, Angamia, Z, Meiring, RM
PloS one. 2022;17(6):e0269440
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The ketogenic diet (KD) has been shown in several studies to result in weight loss compared to a conventional high-carbohydrate, low-fat diet (HCLF). It is thought that this sort of diet may inhibit the appetite and increase feelings of being fuller for longer. However, its effects on other biological functions which can lead to weight loss are unclear. This randomised control trial of 11 individuals aimed to determine the effect of the KD on thyroid function, which controls the conversion of calories into energy and therefore has a role in fat storage. The results showed that KD resulted in a higher loss of body mass than the HCLF diet and one of the thyroid hormones (T3) was decreased. However, hormones which stimulate thyroid function remained unchanged. It was concluded that changes in metabolism can occur following the KD, which may contribute to a greater loss of weight compared to a HCLF diet. This study could be used by healthcare professionals to understand that the ketogenic diet may be more effective at weight loss than a standard HCLF diet. However larger scale trials are warranted.
Abstract
BACKGROUND The ketogenic diet (KD) has been shown to result in body mass loss in people with disease as well as healthy people, yet the effect of the KD on thyroid function and metabolism are unknown. OBJECTIVE We aimed to determine the effects of a KD, compared with an isocaloric high-carbohydrate low-fat (HCLF) diet, on resting metabolic rate and thyroid function in healthy individuals. DESIGN Eleven healthy, normal-weight participants (mean(SD) age: 30(9) years) completed this randomized crossover-controlled study. For a minimum of three weeks on each, participants followed two isocaloric diets: a HCLF diet (55%carbohydrate, 20%fat, 25%protein) and a KD (15%carbohydrate, 60%fat, 25% protein), with a one-week washout period in-between. Importantly, while on the KD, the participants were required to remain in a state of nutritional ketosis for three consecutive weeks. Crossover analyses and linear mixed models were used to assess effect of diet on body mass, thyroid function and resting metabolic rate. RESULTS Both dietary interventions resulted in significant body mass loss (p<0.05) however three weeks of sustained ketosis (KD) resulted in a greater loss of body mass (mean (95%CI): -2.9 (-3.5, -2.4) kg) than did three weeks on the HCLF diet (-0.4 (-1.0, 0.1) kg, p < 0.0001). Compared to pre-diet levels, the change in plasma T3 concentration was significantly different between the two diets (p = 0.003), such that plasma T3 concentration was significantly lower following the KD diet (4.1 (3.8, 4.4) pmol/L, p<0.0001) but not different following the HCLF diet (4.8 (4.5, 5.2) pmol/L, p = 0.171. There was a significant increase in T4 concentration from pre-diet levels following the KD diet (19.3 (17.8, 20.9) pmol/L, p < 0.0001), but not following the HCLF diet (17.3 (15.7, 18.8) pmol.L, p = 0.28). The magnitude of change in plasma T4 concentration was not different between the two diets (p = 0.4). There was no effect of diet on plasma thyroid stimulating hormone concentration (p = 0.27). There was a significantly greater T3:T4 ratio following the HCLF diet (0.41 (0.27, 0.55), p < 0.0001) compared to pre-diet levels but not following the KD diet (0.25 (0.12, 0.39), p = 0.80). CONCLUSIONS Although the diets were isocaloric and physical activity and resting metabolic rate remained constant, the participants lost more mass after the KD than after the HCLF diet. The observed significant changes in triiodothyronine concentration suggest that unknown metabolic changes occur in nutritional ketosis, changes that warrant further investigation. TRIAL REGISTRATION Pan African Clinical Trial Registry: PACTR201707002406306 URL: https://pactr.samrc.ac.za/.
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Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia-a randomized controlled feeding trial.
Ebbeling, CB, Knapp, A, Johnson, A, Wong, JMW, Greco, KF, Ma, C, Mora, S, Ludwig, DS
The American journal of clinical nutrition. 2022;115(1):154-162
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Diets high in carbohydrates and particularly processed carbohydrates can increase the risk for developing a dysfunction in the body’s ability to take up sugar from the blood, known as insulin resistance. However how this relates to insulin resistance can contribute to the development of many diseases such as type 2 diabetes, heart disease and stroke, which highlights the importance in preventing this dysfunction. This randomised control trial of 148 individuals aimed to determine the role of low, medium, and high carbohydrate diets with varying saturated fat content on measures for insulin resistance. The results showed that regardless of the fat content, it was the level of carbohydrate that determined the effect on measures of insulin resistance. High saturated fat and low-carbohydrate diets improved insulin resistance and low saturated fat high carbohydrate diets worsened insulin resistance. Improvements were also observed in blood lipids with a high fat low carbohydrate diet. It was concluded that a diet low in carbohydrates, but high in saturated fat improved insulin resistance and blood lipid levels. This study could be used by healthcare professionals to understand that a diet, which replaces fat with carbohydrates may be worsening insulin resistance and that low carbohydrate diets may be of benefit.
Abstract
BACKGROUND Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption. OBJECTIVES This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance. METHODS After 10-14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis. RESULTS Retention was 90%. Mean change in LPIR (scale 0-100) differed by diet in a dose-dependent fashion: Low-Carb (-5.3; 95% CI: -9.2, -1.5), Moderate-Carb (-0.02; 95% CI: -4.1, 4.1), High-Carb (3.6; 95% CI: -0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [-14.7% (95% CI: -19.5, -9.5), -2.1 (95% CI: -8.2, 4.3), and 0.2 (95% CI: -6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet. CONCLUSIONS A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.
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Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial.
Thomsen, MN, Skytte, MJ, Samkani, A, Carl, MH, Weber, P, Astrup, A, Chabanova, E, Fenger, M, Frystyk, J, Hartmann, B, et al
Diabetologia. 2022;65(3):506-517
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The carbohydrate restricted diet has been shown to be beneficial for Type 2 diabetes (T2D) management and reducing cardiovascular disease risk. This open-label, parallel randomised controlled trial involved Type 2 diabetic patients taking antidiabetic medications who restricted their energy intake by following either a carbohydrate-reduced high protein diet or a conventional diabetic diet. Participants in both groups had a 5.9% reduction in body weight, similar changes in fasting NEFA, apoB, apoA-1, total cholesterol, LDL-cholesterol, HDL-cholesterol, and non-HDL cholesterol, and a significant reduction in fasting glucose, insulin, C-peptide, and HOMA2-IR after 6 weeks of intervention. Carbohydrate-reduced high protein diet group showed a greater reduction in HbA1c and diurnal mean glucose, glycaemic variability, fasting triacylglycerol concentration and liver fat content. Carbohydrate-reduced high protein diet caused an adverse reaction in some patients, and those following a carbohydrate-reduced high protein diet excreted more urea than those eating a conventional diabetic diet. To confirm the results of this study, long-term robust studies are needed. This study can assist healthcare professionals in understanding the benefits of following a carbohydrate-reduced high protein diet in improving glycaemic control, triglyceride levels, and reducing body weight in Type 2 diabetes patients.
Abstract
AIMS/HYPOTHESIS Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. METHODS This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), BMI >25 kg/m2, eGFR >30 ml min-1 [1.73 m]-2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). RESULTS Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] -4.1 [-5.9, -2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] -18 [-29, -6]%, p < 0.01) and liver fat content (by mean [95% CI] -26 [-45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. CONCLUSIONS/INTERPRETATION Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. TRIAL REGISTRATION ClinicalTrials.gov NCT03814694. FUNDING The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.