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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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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.
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Metabolic, hormonal and performance effects of isomaltulose ingestion before prolonged aerobic exercise: a double-blind, randomised, cross-over trial.
Notbohm, HL, Feuerbacher, JF, Papendorf, F, Friese, N, Jacobs, MW, Predel, HG, Zacher, J, Bloch, W, Schumann, M
Journal of the International Society of Sports Nutrition. 2021;18(1):38
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Isomaltulose is a low-glycaemic index carbohydrate that lowers insulin and glucose levels postprandially. The benefits of taking Isomaltulose in an exercise setting are not well studied. This double-blinded, randomised, crossover study evaluated the effects of Isomaltulose intake on metabolic responses, hormonal responses, exercise performance and gastrointestinal disturbances in runners. Twenty-one male recreational endurance runners took part in four separate experimental sessions to compare Isomaltulose to maltodextrin and glucose. Fat and carbohydrate oxidation rates were not different among groups. This might be because the lower dose of Isomaltulose (50g) was used in this trial. Compared to glucose and maltodextrin, isomaltulose lowered metabolic and hormonal responses to exercise. In the study, Isomaltulose, glucose, and maltodextrin did not differ in exercise performance or gastrointestinal disturbances. A higher dose may be needed in order to demonstrate exercise performance, but caution should be exercised since a higher dose may cause gastrointestinal upset. A robust investigation of Isomalulose dose and its effects on glucose, insulin, and glucose-dependent insulinotropic polypeptides is required to determine if exercise leads to hypoglycaemia in the clinical population. Healthcare practitioners can use the findings of this study to understand the advantageous effects of 50g Isomaltulose in regulating glucose, insulin and glucose-dependent insulinotropic polypeptide during aerobic exercise.
Abstract
BACKGROUND Isomaltulose has been discussed as a low glycaemic carbohydrate but evidence concerning performance benefits and physiological responses has produced varying results. Therefore, we primarily aimed to investigate the effects of isomaltulose ingestion compared to glucose and maltodextrin on fat and carbohydrate oxidation rates, blood glucose levels and serum hormone concentrations of insulin and glucose-dependent insulinotropic polypeptide (GIP). As secondary aims, we assessed running performance and gastrointestinal discomfort. METHODS Twenty-one male recreational endurance runners performed a 70-min constant load trial at 70% maximal running speed (Vmax), followed by a time to exhaustion (TTE) test at 85% Vmax after ingesting either 50 g isomaltulose, maltodextrin or glucose. Fat and carbohydrate oxidation rates were calculated from spiroergometric data. Venous blood samples for measurement of GIP and insulin were drawn before, after the constant load trial and after the TTE. Capillary blood samples for glucose concentrations and subjective feeling of gastrointestinal discomfort were collected every 10 min during the constant load trial. RESULTS No between-condition differences were observed in the area under the curve analysis of fat (p = 0.576) and carbohydrate oxidation rates (p = 0.887). Isomaltulose ingestion led to lower baseline postprandial concentrations of blood glucose compared to maltodextrin (percent change [95% confidence interval], - 16.7% [- 21.8,-11.6], p < 0.001) and glucose (- 11.5% [- 17.3,-5.7], p = 0.001). Similarly, insulin and GIP concentrations were also lower following isomaltulose ingestion compared to maltodextrin (- 40.3% [- 50.5,-30.0], p = 0.001 and - 69.1% [- 74.3,-63.8], p < 0.001, respectively) and glucose (- 32.6% [- 43.9,-21.2], p = 0.012 and - 55.8% [- 70.7,-40.9], p < 0.001, respectively). Furthermore, glucose fluctuation was lower after isomaltulose ingestion compared to maltodextrin (- 26.0% [- 34.2,-17.8], p < 0.001) and glucose (- 17.4% [- 29.1,-5.6], p < 0.001). However, during and after exercise, no between-condition differences for glucose (p = 0.872), insulin (p = 0.503) and GIP (p = 0.244) were observed. No between-condition differences were found for TTE (p = 0.876) or gastrointestinal discomfort (p = 0.119). CONCLUSION Isomaltulose ingestion led to lower baseline postprandial concentrations of glucose, insulin and GIP compared to maltodextrin and glucose. Consequently, blood glucose fluctuations were lower during treadmill running after isomaltulose ingestion, while no between-condition differences were observed for CHO and fat oxidation rates, treadmill running performance and gastrointestinal discomfort. Further research is required to provide specific guidelines on supplementing isomaltulose in performance and health settings.
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Comparing Acute, High Dietary Protein and Carbohydrate Intake on Transcriptional Biomarkers, Fuel Utilisation and Exercise Performance in Trained Male Runners.
Furber, M, Pyle, S, Roberts, M, Roberts, J
Nutrients. 2021;13(12)
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Dietary modification to improve exercise endurance has become a popular strategy. The reduction of carbohydrates to enhance adaptations due to training has been shown on a cellular level. In low carbohydrate diets, fat is the usual substitute, however long-term adherence to this is often difficult. Using protein instead of fat may be an alternative, but there is little research on this. This study aimed to investigate the impact of a short-term high-protein, reduced carbohydrate diet compared to a high-carbohydrate diet in combination with endurance running on exercise performance and cellular adaptations. The results showed that any cellular adaptations were due to fuel availability, rather than the fuel type and that a high protein diet compromised high intensity exercise performance. It was concluded that a high-protein, low-carbohydrate diet in combination with endurance training is of no benefit to endurance running performance. This study could be used by healthcare professionals to recommend that athletes and especially runners who wish to improve endurance do not switch to a high-protein, low carbohydrate diet and that other dietary modifications are investigated.
Abstract
Manipulating dietary macronutrient intake may modulate adaptive responses to exercise, and improve endurance performance. However, there is controversy as to the impact of short-term dietary modification on athletic performance. In a parallel-groups, repeated measures study, 16 trained endurance runners (maximal oxygen uptake (V˙O2max): 64.2 ± 5.6 mL·kg-1·min-1) were randomly assigned to, and provided with, either a high-protein, reduced-carbohydrate (PRO) or a high-carbohydrate (CHO) isocaloric-matched diet. Participants maintained their training load over 21-consecutive days with dietary intake consisting of 7-days habitual intake (T1), 7-days intervention diet (T2) and 7-days return to habitual intake (T3). Following each 7-day dietary period (T1-T3), a micro-muscle biopsy was taken for assessment of gene expression, before participants underwent laboratory assessment of a 10 km treadmill run at 75% V˙O2max, followed by a 95% V˙O2max time to exhaustion (TTE) trial. The PRO diet resulted in a modest change (1.37-fold increase, p = 0.016) in AMPK expression, coupled with a significant increase in fat oxidation (0.29 ± 0.05 to 0.59 ± 0.05 g·min-1, p < 0.0001). However, a significant reduction of 23.3% (p = 0.0003) in TTE post intervention was observed; this reverted back to pre levels following a return to the habitual diet. In the CHO group, whilst no change in sub-maximal fuel utilisation occurred at T2, a significant 6.5% increase in TTE performance (p = 0.05), and a modest, but significant, increase in AMPK (p = 0.042) and PPAR (p = 0.029) mRNA expression compared to T1 were observed; with AMPK (p = 0.011) and PPAR (p = 0.044) remaining significantly elevated at T3. In conclusion, a 7-day isocaloric high protein diet significantly compromised high intensity exercise performance in trained runners with no real benefit on gene markers of training adaptation. A significant increase in fat oxidation during submaximal exercise was observed post PRO intervention, but this returned to pre levels once the habitual diet was re-introduced, suggesting that the response was driven via fuel availability rather than cellular adaptation. A short-term high protein, low carbohydrate diet in combination with endurance training is not preferential for endurance running performance.
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Dietary Patterns in Secondary Prevention of Heart Failure: A Systematic Review.
Dos Reis Padilha, G, Sanches Machado d'Almeida, K, Ronchi Spillere, S, Corrêa Souza, G
Nutrients. 2018;10(7)
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Diet is recognised as an important factor in the prevention of heart failure, however there is no consensus about which dietary protocol is the most effective. This systematic review aims to clarify links between different dietary measures and markers of heart failure. The review included 12 studies of different types (randomised controlled trials, cross-sectional studies and cohort studies), which examined the DASH diet, Mediterranean diet, high protein diet and low carbohydrate diet. The studies examining the DASH diet demonstrated improvements in various measures of cardiac function and may have benefits for secondary prevention of heart failure. The Mediterranean diet was associated with lower levels of inflammation and improved cardiac function in cross-sectional studies only. High protein and low carbohydrate diets also demonstrated positive effects on markers of heart function however, only one study for each was included. The authors conclude that the current science suggests a positive role for diet in relation to prevention of heart failure and call for further RCTs to be conducted to identify which elements of these different diets are impacting on markers of heart failure.
Abstract
BACKGROUND Diet is an important factor in secondary prevention of heart failure (HF) but there is still no consensus as to which dietary model should be adopted by this population. This systematic review aims to clarify the relationship between dietary patterns and secondary prevention in HF. METHODS We searched the Medline, Embase and Cochrane databases for studies with different dietary patterns and outcomes of secondary prevention in HF. No limitation was used in the search. RESULTS 1119 articles were identified, 12 met the inclusion criteria. Studies with Dietary Approaches to Stop Hypertension (DASH), Mediterranean, Hyperproteic and Low-carb diets were found. The DASH pattern showed improvement in cardiac function, functional capacity, blood pressure, oxidative stress and mortality. The Mediterranean diet had a correlation with inflammation, quality of life and cardiac function but just on cross-sectional studies. Regarding the Hyperproteic and Low-carb diets only one study was found with each pattern and both were able to improve functional capacity in patients with HF. CONCLUSIONS DASH pattern may have benefits in the secondary prevention of HF. The Mediterranean diet demonstrated positive correlation with factors of secondary prevention of HF but need more RCTs and cohort studies to confirm these effects. In addition, the Hyperproteic and Low-carb diets, despite the lack of studies, also demonstrated positive effects on the functional capacity in patients with HF.
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The effects of a low-carbohydrate diet on oxygen saturation in heart failure patients: a randomized controlled clinical trial.
González-Islas, D, Orea-Tejeda, A, Castillo-Martínez, L, Olvera-Mayorga, G, Rodríguez-García, WD, Santillán-Díaz, C, Keirnes-Davis, C, Vaquero-Barbosa, N
Nutricion hospitalaria. 2017;34(4):792-798
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Nutritional therapy in heart failure patients has been focused on fluid and sodium restriction with the aim of decreasing volume overload. However, these recommendations are not well established and sometimes controversial. The objective of this study was to evaluate the effect of a low-carbohydrate diet on oxygen saturation, body composition and clinical variables in chronic, stable heart failure patients. In this randomised controlled clinical trial, 88 heart failure patients were randomly assigned to a low-carbohydrate diet group (40% carbohydrates, 20% protein and 40% fats) or a standard diet group (50% carbohydrates, 20% protein and 30% fats) for two months. At baseline and at two months of follow-up, the variables evaluated were: oxygen saturation, dietary intake, body composition and handgrip strength. After two months, the low-carbohydrate diet group had improved their oxygen saturation levels (from 93.0% to 94.6%), whilst oxygen saturation in the standard diet group had fallen (from 94.9% to 94.0%). The difference between the groups at the end of the study was significant. There were no significant differences in blood pressure, body weight and composition or handgrip strength between the groups or within the groups from the start of the study to the end. The authors concluded that a low-carbohydrate diet may improve the oxygen saturation in patients with chronic stable heart failure.
Abstract
INTRODUCTION Nutritional therapy in heart failure (HF) patients has been focused on fluid and sodium restriction with the aim of decreasing volume overload. However, these recommendations are not well established and sometimes controversial. OBJECTIVE To evaluate the effect of the consumption of a low-carbohydrate diet on oxygen saturation, body composition and clinical variables during two months of follow-up in chronic, stable heart failure patients. METHODS In a parallel group randomized controlled clinical trial, 88 ambulatory patients were randomly assigned to a low-carbohydrate diet group (40% carbohydrates, 20% protein and 40% fats [12% saturated, 18% monounsaturated and 10% polyunsaturated]) or a standard diet group (50% carbohydrates, 20% protein and 30% fats [10% saturated, 10% monounsaturated and 10% polyunsaturated]) for two months. Diets were normocaloric in both groups. At baseline and at two months of follow-up, the variables evaluated were: oxygen saturation, dietary intake, body composition and handgrip strength. RESULTS After two months of follow-up, the low-carbohydrate diet group decreased the carbohydrate consumption and had improved oxygen saturation (93.0 ±4.4 to 94.6 ± 3.2, p = 0.02), while the standard diet group had decreased (94.90 ± 2.4 to 94.0 ± 2.9, p = 0.03). There were also differences between the groups at the end of the study (p = 0.04). No significant differences showed in handgrip strength in both groups, low-carbohydrate diet group (26.4 ± 8.3 to 27.2 ± 8.3 kg, p = 0.07) and standard diet group (25.4 ± 8.9 to 26.1 ± 9.5 kg, p = 0.14). CONCLUSIONS Low-carbohydrate diet may improve the oxygen saturation in patients with chronic stable heart failure.