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Restricting sugar or carbohydrate intake does not impact physical activity level or energy intake over 24 h despite changes in substrate use: a randomised crossover study in healthy men and women.
Hengist, A, Davies, RG, Rogers, PJ, Brunstrom, JM, van Loon, LJC, Walhin, JP, Thompson, D, Koumanov, F, Betts, JA, Gonzalez, JT
European journal of nutrition. 2023;62(2):921-940
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Diets high in carbohydrates especially when consumed in sugar-sweetened food and beverages has been shown to result in increased energy intakes in the diet. However, diets low in sugar and carbohydrates have been shown to have a limited effect on changes in body mass and weight loss. In this instance, some other mechanism is preventing weight loss. Diets low in carbohydrates have been shown to decrease physical activity levels and energy expenditure, which may be responsible for the limited weight loss seen with carbohydrate restricted diets. This randomised control trial of 25 individuals aimed to determine whether carbohydrate restriction would reduce physical activity energy expenditure over a 24-hour period compared to diets higher in sugar and/or carbohydrates. Individuals with a low dietary intake of sugar and carbohydrates and moderate intake of sugar all showed similar physical activity energy expenditure levels. Interestingly low carbohydrate intake resulted in the highest 24 hour increase in low density lipoprotein concentrations and decreased satiety hormones. It was concluded that when energy density is controlled, restricting sugar or carbohydrates has no effect on physical activity levels over a 24-hour period. This study could be used by healthcare professionals that in the very short-term low sugar and carbohydrate diets have no effect on physical activity levels but does affect metabolic changes. However studies need to be performed to determine long-term effects.
Abstract
PURPOSE To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h. METHODS In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning. RESULTS The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d-1; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d-1; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01). CONCLUSION When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes. CLINICAL TRIALS REGISTRATION ID NCT03509610, https://clinicaltrials.gov/show/NCT03509610.
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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.
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The effect of periodic ketogenic diet on newly diagnosed overweight or obese patients with type 2 diabetes.
Li, S, Lin, G, Chen, J, Chen, Z, Xu, F, Zhu, F, Zhang, J, Yuan, S
BMC endocrine disorders. 2022;22(1):34
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Currently, the ketogenic diet is gaining popularity in managing Type 2 diabetes (T2D). Ketogenic diets replace carbohydrates with fat and include limited carbohydrates and adequate protein. This randomised controlled trial evaluated the effects of the 12-week ketogenic diet on sixty overweight or obese T2D patients. Both the ketogenic and control diabetes diet groups achieved significant reductions in weight, body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting blood glucose, fasting insulin, and HbA1c. However, the ketogenic group showed significantly greater reductions in body mass, blood lipids, and blood glucose than the control group. In the ketogenic diet group, serum uric acid levels were higher than those in the control diet group. It was found that the control diet group adhered to the diet for a longer period than the ketogenic diet group, whose willingness to adhere to the diet long-term was weaker. More robust long-term studies are needed to evaluate the long-term effects of a ketogenic diet. In this study, more patients who followed the ketogenic diet experienced hypoglycaemic events during the first four weeks. Healthcare providers should exercise caution when recommending a short term therapeutic ketogenic diet.
Abstract
BACKGROUND The ketogenic diet (KD) is characterized by fat as a substitute of carbohydrates for the primary energy source. There is a large number of overweight or obese people with type 2 diabetes mellitus (T2DM), while this study aims to observe periodic ketogenic diet for effect on overweight or obese patients newly diagnosed as T2DM. METHODS A total of 60 overweight or obese patients newly diagnosed as T2DM were randomized into two groups: KD group, which was given ketogenic diet, and control group, which was given routine diet for diabetes, 30 cases in each group. Both dietary patterns lasted 12 weeks, and during the period, the blood glucose, blood lipid, body weight, insulin, and uric acid before and after intervention, as well as the significance for relevant changes, were observed. RESULTS For both groups, the weight, BMI(body mass index), Waist, TG (triglyceride), TC(cholesterol), LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), FBG (fasting glucose), FINS (fasting insulin), HbA1c (glycosylated hemoglobin) were decreased after intervention (P < 0.05), while the decrease rates in the KD group was more significant than the control group. However, UA(serum uric acid) in the KD group showed an upward trend, while in the control group was not changed significantly (P > 0.05).The willingness to adhere to the ketogenic diet over the long term was weaker than to the routine diet for diabetes. CONCLUSION Among the overweight or obese patients newly diagnosed as type 2 diabetes mellitus, periodic ketogenic diet can not only control the body weight, but also control blood glucose and lipid, but long-term persistence is difficult.
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The potential prolonged effect at one-year follow-up after 18-month randomized controlled trial of a 90 g/day low-carbohydrate diet in patients with type 2 diabetes.
Chen, CY, Huang, WS, Ho, MH, Chang, CH, Lee, LT, Chen, HS, Kang, YD, Chie, WC, Jan, CF, Wang, WD, et al
Nutrition & diabetes. 2022;12(1):17
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A low carbohydrate diet (LCD) could be an effective dietary strategy for managing Type 2 Diabetes and body weight. This follow-up of a randomised controlled study evaluated the effect of moderate LCD after 18 months of 90 g/day LCD in 85 poorly controlled Type 2 Diabetic patients and compared it with Traditional Diabetic Diet (TDD). Those who followed the LCD diet ate significantly fewer carbohydrates and more protein and fat at the follow up between 18 and 30 months compared to those who followed the TDD group. The LCD group also showed significant improvements in serum HbA1C, two-hour serum glucose, serum alanine aminotransferase and Medication Effect Score in comparison with the TDD group. However, the level of triglycerides increased, and HDL levels decreased significantly in the LCD group from 18 to 30 months. There was however no significant difference between the groups in the improvement of HbA1C, fasting serum glucose, 2 h serum glucose, as well as serum cholesterol, triglycerides, low-density lipoprotein, ALT, creatinine, and urine microalbumin. To confirm the benefits of LCD on glycaemic control, further robust studies are needed. Results of this study can help healthcare professionals gain a better understanding of the prolonged effects of LCD on glycaemic control, liver function, and medication effect scores.
Abstract
OBJECTIVES To evaluate the effect at a one-year follow-up after an 18-month randomized controlled trial (RCT) of 90 gm/day low-carbohydrate diet (LCD) in type 2 diabetes. RESEARCH DESIGN AND METHODS Eighty-five poorly controlled type 2 diabetic patients with an initial HbA1c ≥ 7.5% who have completed an 18-month randomized controlled trial (RCT) on 90 g/day low-carbohydrate diet (LCD) were recruited and followed for one year. A three-day weighted food record, relevant laboratory tests, and medication effect score (MES) were obtained at the end of the previous trial and one year after for a total of 30 months period on specific diet. RESULTS 71 (83.5%) patients completed the study, 35 were in TDD group and 36 were in LCD group. Although the mean of percentage changes in daily carbohydrate intake was significantly lower for those in TDD group than those in LCD group (30.51 ± 11.06% vs. 55.16 ± 21.79%, p = 0.0455) in the period between 18 months and 30 months, patients in LCD group consumed significantly less amount of daily carbohydrate than patients in TDD group (131.8 ± 53.9 g vs. 195.1 ± 50.2 g, p < 0.001). The serum HbA1C, two-hour serum glucose, serum alanine aminotransferase (ALT), and MES were also significantly lower for the LCD group patients than those in the TDD group (p = 0.017, p < 0.001, p = 0.017, and p = 0.008 respectively). The mean of percentage changes of HbA1C, fasting serum glucose, 2 h serum glucose, as well as serum cholesterol, triglyceride, low-density lipoprotein, ALT, creatinine, and urine microalbumin, however, were not significantly different between the two groups (p > 0.05). CONCLUSIONS The one-year follow-up for patients on 90 g/d LCD showed potential prolonged and better outcome on glycaemic control, liver function and MES than those on TDD for poorly controlled diabetic patients.
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Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission.
Churuangsuk, C, Hall, J, Reynolds, A, Griffin, SJ, Combet, E, Lean, MEJ
Diabetologia. 2022;65(1):14-36
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Type 2 diabetes (T2D) is a global epidemic. Although it is a complex disease, it is mainly driven by weight gain. The benefits of weight loss for T2D are well known, but patients and healthcare practitioners do not have clear guidance as to which dietary strategies may be effective to achieve and to maintain weight loss. The aim of this study is to review a number of studies of weight loss diets in T2D patients to see which ones are the most effective. Also, to see which dietary patterns support type 2 diabetes remission. Greatest weight loss was reported with very low energy diets including formula meal replacements. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets. High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal or no difference from control diets. Diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacements appear to be the most effective. Programmes including a hypocaloric formula ‘total diet replacement’ induction phase were most effective for type 2 diabetes remission. Further research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Authors highlight current evidence on diets for T2D remission is limited but believe remission can be achieved if sufficient weight loss is maintained. The main contributor to HbA1c reduction and remission appears to be weight loss, irrespective of diet type
- Nice Guidelines highlight the remission of diabetes occurs when a patient no longer satisfies the diagnostic criteria, without receiving glucose-lowering medication. By 2019 in one UK GP practice 27% of the practice population with T2D who followed a LCD for 23 months, lost weight and lowered their HbA1c to 48 mmol/mol (NICE target range) in conjunction with prescribed medication
- This review highlights an opportunity for Nutritional Therapy Practitioners to successfully work with LCD approaches to support weight loss and improved HbA1c.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- 19 meta-analyses (MA) on weight-loss diets, involving 23 primary trials were assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies – of Interventions [ROBINS-I]) with GRADE applied
- Weight loss diets in the review included: Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI −3.3, −1.4) greater weight loss over 12–52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3– 2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate)
- Greatest weight loss was reported with very low energy diets (VLED), (400–500 kcal). However, this study found that low-carbohydrate diets (LCD) (21–70g of carbohydrate daily from1000–1500 kcal) were no better for weight loss than higher-carbohydrate/low-fat diets
- Time period of diets / length of observation / intervention: (1) Formula meal replacements (>12–52 wk), (2) LCDs ranged between (>8 wk to 4 years), (3) Very low energy diets (>8–12 wk), (4) High- protein (>4->8 wks), Mediterranean (>4->8 wk), high-monounsaturated-fatty-acid (>2wk), vegetarian (≥3wk) and low-glycaemic-index diets (≥6mo)
- Authors highlight weight reduction is fundamental for T2D management and remission
- This MA found that VLED and formula meal replacement appear the most effective approaches for weight management with T2D by providing less energy than self-administered food-based diets
- Potential pathophysiological mechanisms highlighted by authors are HbA1c reduction and remission which appear to be from weight loss, with only small differences between diet types assessed over 3–12 months, irrespective of diet type
- Study limitations: Many meta-analyses were of ‘low’ and ‘critically low’ AMSTAR 2 quality, predominantly through ‘no protocol reported’ (despite clear and sound methods) and no assessment of publication bias
- Most studies included European participants, such that findings may not be equally applicable to other ethnic and/or deprived communities. Durations of interventions varied, where weight regain is frequent over a longer period. Authors highlight evidence from clinical practice is needed to identify safe and effective approaches to achieve and maintain weight loss
- Authors highlight primary studies should use an RCT design, with data analyses conducted ‘blind’. They should define the intervention clearly (e.g., diets, physical activity, and behavioural and psychological support), and address separately the induction (usually 3–6 months) and maintenance (≥12 months)
- This research received no funding
- The authors declared no conflicts of interest.
Clinical practice applications:
- While this study found a variety of dietary compositions can be used effectively for weight management with T2D, VLED was successfully used to achieve remission for T2D
- Programmes with a ’total diet replacement’ induction phase were the most effective dietary approach for T2D remission (up to 61% of participants at 1 year).
Considerations for future research:
- Authors state future research should provide implementation with optimal support in real-life settings for weight loss, prevention of weight regain and remissions, rather than seek subtle differences from macronutrient compositions
- Future studies should report sufficient detail about macronutrient or micronutrient contents, or prescribed and reported energy intakes, including energy intake of nutrient-restricted diets.
Abstract
AIMS/HYPOTHESIS Weight reduction is fundamental for type 2 diabetes management and remission, but uncertainty exists over which diet type is best to achieve and maintain weight loss. We evaluated dietary approaches for weight loss, and remission, in people with type 2 diabetes to inform practice and clinical guidelines. METHODS First, we conducted a systematic review of published meta-analyses of RCTs of weight-loss diets. We searched MEDLINE (Ovid), PubMed, Web of Science and Cochrane Database of Systematic Reviews, up to 7 May 2021. We synthesised weight loss findings stratified by diet types and assessed meta-analyses quality with A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. We assessed certainty of pooled results of each meta-analysis using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (PROSPERO CRD42020169258). Second, we conducted a systematic review of any intervention studies reporting type 2 diabetes remission with weight-loss diets, in MEDLINE (via PubMed), Embase and Cochrane Central Register of Controlled Trials, up to 10 May 2021. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies - of Interventions [ROBINS-I]), with GRADE applied (PROSPERO CRD42020208878). RESULTS We identified 19 meta-analyses of weight-loss diets, involving 2-23 primary trials (n = 100-1587), published 2013-2021. Twelve were 'critically low' or 'low' AMSTAR 2 quality, with seven 'high' quality. Greatest weight loss was reported with very low energy diets, 1.7-2.1 MJ/day (400-500 kcal) for 8-12 weeks (high-quality meta-analysis, GRADE low), achieving 6.6 kg (95% CI -9.5, -3.7) greater weight loss than low-energy diets (4.2-6.3 MJ/day [1000-1500 kcal]). Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI -3.3, -1.4) greater weight loss over 12-52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3-2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate). For type 2 diabetes remission, of 373 records, 16 met inclusion criteria. Remissions at 1 year were reported for a median 54% of participants in RCTs including initial low-energy total diet replacement (low-risk-of-bias study, GRADE high), and 11% and 15% for meal replacements and Mediterranean diets, respectively (some concerns for risk of bias in studies, GRADE moderate/low). For ketogenic/very low-carbohydrate and very low-energy food-based diets, the evidence for remission (20% and 22%, respectively) has serious and critical risk of bias, and GRADE certainty is very low. CONCLUSIONS/INTERPRETATION Published meta-analyses of hypocaloric diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets. Programmes including a hypocaloric formula 'total diet replacement' induction phase were most effective for type 2 diabetes remission. Most of the evidence is restricted to 1 year or less. Well-conducted research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications.
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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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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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Effect of a Personalized Diet to Reduce Postprandial Glycemic Response vs a Low-fat Diet on Weight Loss in Adults With Abnormal Glucose Metabolism and Obesity: A Randomized Clinical Trial.
Popp, CJ, Hu, L, Kharmats, AY, Curran, M, Berube, L, Wang, C, Pompeii, ML, Illiano, P, St-Jules, DE, Mottern, M, et al
JAMA network open. 2022;5(9):e2233760
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Postprandial glycaemic response (PPGR) to foods can be different from person to person. This could be the reason why people experience different weight loss outcomes with standardised diets such as a low glycaemic index diet, low-fat diet or a low carbohydrate diet. In this single-centre, population-based, randomised, blinded clinical trial, 204 participants with irregular glucose metabolism and obesity were randomised to consume either a low-fat or personalised diet for six months in combination with fourteen behavioural change counselling sessions. The participants in the personalised diet group received a colour-coded meal score to indicate their estimated PPGR for different foods. The results of this study showed no significant weight reduction in the personalised diet group compared to the low-fat diet. Further robust studies are required to develop appropriate precision nutrition interventions for weight loss and energy balance. However, healthcare professionals can use the results of this study to understand that both a low-fat diet and a personalised diet, coupled with behavioural counselling, may be effective in promoting weight loss in obese populations with irregular glucose metabolism.
Abstract
IMPORTANCE Interindividual variability in postprandial glycemic response (PPGR) to the same foods may explain why low glycemic index or load and low-carbohydrate diet interventions have mixed weight loss outcomes. A precision nutrition approach that estimates personalized PPGR to specific foods may be more efficacious for weight loss. OBJECTIVE To compare a standardized low-fat vs a personalized diet regarding percentage of weight loss in adults with abnormal glucose metabolism and obesity. DESIGN, SETTING, AND PARTICIPANTS The Personal Diet Study was a single-center, population-based, 6-month randomized clinical trial with measurements at baseline (0 months) and 3 and 6 months conducted from February 12, 2018, to October 28, 2021. A total of 269 adults aged 18 to 80 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) ranging from 27 to 50 and a hemoglobin A1c level ranging from 5.7% to 8.0% were recruited. Individuals were excluded if receiving medications other than metformin or with evidence of kidney disease, assessed as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation, to avoid recruiting patients with advanced type 2 diabetes. INTERVENTIONS Participants were randomized to either a low-fat diet (<25% of energy intake; standardized group) or a personalized diet that estimates PPGR to foods using a machine learning algorithm (personalized group). Participants in both groups received a total of 14 behavioral counseling sessions and self-monitored dietary intake. In addition, the participants in the personalized group received color-coded meal scores on estimated PPGR delivered via a mobile app. MAIN OUTCOMES AND MEASURES The primary outcome was the percentage of weight loss from baseline to 6 months. Secondary outcomes included changes in body composition (fat mass, fat-free mass, and percentage of body weight), resting energy expenditure, and adaptive thermogenesis. Data were collected at baseline and 3 and 6 months. Analysis was based on intention to treat using linear mixed modeling. RESULTS Of a total of 204 adults randomized, 199 (102 in the personalized group vs 97 in the standardized group) contributed data (mean [SD] age, 58 [11] years; 133 women [66.8%]; mean [SD] body mass index, 33.9 [4.8]). Weight change at 6 months was -4.31% (95% CI, -5.37% to -3.24%) for the standardized group and -3.26% (95% CI, -4.25% to -2.26%) for the personalized group, which was not significantly different (difference between groups, 1.05% [95% CI, -0.40% to 2.50%]; P = .16). There were no between-group differences in body composition and adaptive thermogenesis; however, the change in resting energy expenditure was significantly greater in the standardized group from 0 to 6 months (difference between groups, 92.3 [95% CI, 0.9-183.8] kcal/d; P = .05). CONCLUSIONS AND RELEVANCE A personalized diet targeting a reduction in PPGR did not result in greater weight loss compared with a low-fat diet at 6 months. Future studies should assess methods of increasing dietary self-monitoring adherence and intervention exposure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03336411.
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Effects of Low-Carbohydrate versus Mediterranean Diets on Weight Loss, Glucose Metabolism, Insulin Kinetics and β-Cell Function in Morbidly Obese Individuals.
Tricò, D, Moriconi, D, Berta, R, Baldi, S, Quinones-Galvan, A, Guiducci, L, Taddei, S, Mari, A, Nannipieri, M
Nutrients. 2021;13(4)
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Both low-carbohydrate and Mediterranean style diets are used to prevent lifestyle associated diseases such as obesity and type 2 diabetes. However, which diet is more effective is unclear. The aim of this randomised control trial of 36 morbidly obese individuals was to compare the effectiveness of Mediterranean diets and low-carbohydrate diets to improve metabolic measures such as blood sugar levels, pre-diabetes, and the body’s ability to use sugar. The results showed that in the short-term both diets were equally effective at improving biochemical dysfunctions that contribute to type 2 diabetes. The low-carbohydrate diet did result in higher weight loss than the Mediterranean diet. Studies on long-term effects are warranted. It was concluded that a low-carbohydrate diet is in the short-term a feasible alternative to the Mediterranean diet for improved weight loss and biological contributors to type 2 diabetes. This study could be used by healthcare professionals to understand that the Mediterranean diet and low-carbohydrate diet are both effective in the short-term for improvements to contributors to type 2 diabetes, however the low-carbohydrate diet may be superior if weight loss is required.
Abstract
Low-calorie Mediterranean-style or low-carbohydrate dietary regimens are widely used nutritional strategies against obesity and associated metabolic diseases, including type 2 diabetes. The aim of this study was to compare the effectiveness of a balanced Mediterranean diet with a low-carbohydrate diet on weight loss and glucose homeostasis in morbidly obese individuals at high risk to develop diabetes. Insulin secretion, insulin clearance, and different β-cell function components were estimated by modeling plasma glucose, insulin and C-peptide profiles during 75-g oral glucose tolerance tests (OGTTs) performed at baseline and after 4 weeks of each dietary intervention. The average weight loss was 5%, being 58% greater in the low-carbohydrate-group than Mediterranean-group. Fasting plasma glucose and glucose tolerance were not affected by the diets. The two dietary regimens proved similarly effective in improving insulin resistance and fasting hyperinsulinemia, while enhancing endogenous insulin clearance and β-cell glucose sensitivity. In summary, we demonstrated that a low-carbohydrate diet is a successful short-term approach for weight loss in morbidly obese patients and a feasible alternative to the Mediterranean diet for its glucometabolic benefits, including improvements in insulin resistance, insulin clearance and β-cell function. Further studies are needed to compare the long-term efficacy and safety of the two diets.
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Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial.
Peeke, PM, Greenway, FL, Billes, SK, Zhang, D, Fujioka, K
Nutrition & diabetes. 2021;11(1):6
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Time-restricted eating (TRE) has been identified as an effective method of losing weight in the face of rising obesity worldwide. Fasting for at least 12 hours has a beneficial effect on weight management and cardiometabolic health. Overnight fasting longer than 12 hours may result in fat-burning or ketosis. A high-fat, low-protein, low-carbohydrate snack during a 14-hour fast is believed not to raise blood sugar levels and helps with hunger management. This 8-week virtual, pilot, randomised, comparator-controlled clinical trial evaluated the benefits of following a commercial weight loss programme combined with TRE on body weight and fasting blood glucose (FBG) levels. The commercial weight loss programme included calculated calories and macronutrient content in their customised meal plans, as well as coaching and troubleshooting sessions. The participants were randomly assigned to 14-hour fasting (14:10) or 12-hour fasting (control). The 14:10 group also consumed 200 kcal of mixed nuts as a snack at hour 12 to determine the effect on blood glucose levels. After the intervention for 8 weeks, the 14:10 group showed a significant reduction in body weight (11kg) and FBG (8mg/dl), and the 12:12 group significantly lost 9kg of body weight and showed a non-significant reduction in FBG (3mg/dl). Participants with higher baseline FBG levels showed a greater reduction in FBG, indicating potential greater improvements in people with diabetes. A comparison of the two groups did not show a statistically significant difference in intervention effects. A fasting snack at 12 hours did not affect FBG in the 14:10 group, which may help adherence. Due to the exploratory nature of this study, larger robust studies are needed to assess the effectiveness of 14:10 and 12:12 time-restricted fasting regimens with commercial weight loss programmes. However, healthcare professionals can use the results of this study to understand the beneficial effects of different time-restricted fasting regimens on cardiometabolic health.
Abstract
BACKGROUND Time restricted eating (TRE) is an emerging dietary intervention for weight loss that is hypothesized to reinforce the metabolic benefits of nightly fasting/ketosis. This pilot study investigated the effectiveness of a daily 14-h metabolic fast (14:10 TRE beginning after dinner, a "fasting snack" at hour 12, and ending with breakfast 14 h later) combined with a commercial weight management program on body weight and fasting blood glucose (FBG) in individuals with obesity. We also investigated the effect of the low-calorie, high-fat, low-carbohydrate, and low-protein "fasting snack" on blood glucose. METHODS This 8-week, randomized, controlled, clinical trial included men and women (BMI ≥ 30 kg/m2) between June and October 2020. Study procedures were conducted remotely. Participants were randomized to 14:10 or 12-h TRE (12:12, active comparator) and prescribed a diet (controlled for calories and macronutrient composition) and exercise program that included weekly customized counseling and support. The primary outcome was change from baseline in body weight in the 14:10 group. RESULTS Of the 78 randomized participants, 60 (n = 30/group) completed 8 weeks. The LS mean change from baseline in weight in the 14:10 group was -8.5% (95% CI -9.6 to -7.4; P < 0.001) and -7.1% (-8.3 to -5.8; P < 0.001) in the 12:12 group (between group difference -1.4%; -2.7 to -0.2; P < 0.05). There was a statistically significant LS mean change from baseline to week 8 in FBG in the 14:10 group of -7.6 mg/dl (95% CI -15.1 to -0.1; P < 0.05) but not in the 12:12 group (-3.1 mg/dl, -10.0 to 3.7; P = NS). Both interventions resulted in a larger reduction in FBG in participants with elevated FBG (≥100 mg/dl) at baseline (both P < 0.05). CONCLUSIONS In participants with obesity who completed 8 weeks of the 14:10 TRE schedule combined with a commercial weight loss program, there was statistically significant and clinically meaningful weight loss and improvements in FBG.