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Effects of Intermittent Energy Restriction Compared with Those of Continuous Energy Restriction on Body Composition and Cardiometabolic Risk Markers - A Systematic Review and Meta-Analysis of Randomized Controlled Trials in Adults.
Schroor, MM, Joris, PJ, Plat, J, Mensink, RP
Advances in nutrition (Bethesda, Md.). 2024;15(1):100130
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Intermittent energy restriction (IER) diets, such as the 5:2 diet, time-restricted eating (TRE), and alternate-day fasting (ADF), are gaining popularity. According to previous research, IER protocols effectively manage obesity and may have many other health benefits, including improving metabolic health. This systematic review and meta-analysis of twenty-eight parallel-design randomised controlled trials looked at the benefits of IER protocols, such as ADF, TRE, and the 5:2 diet, and the effects of continuous energy restriction (CER) on anthropometric and cardiometabolic outcomes. The results of this systematic review and meta-analysis showed that both the IER and CER are equally beneficial. However, IER protocols showed greater but clinically insignificant improvements in fat-free mass and waist circumference in healthy adults. IER and CER protocols were not different in improving the lipid profile, glucose and insulin levels and blood pressure. Different IER diets showed different positive effects on metabolic parameters. Future robust studies are required to assess the effects of these energy-restriction diets on metabolic and anthropometric parameters because of the high variability in the included studies. However, healthcare professionals can use the results of this review to understand the potential clinical utility of various energy-restriction diets.
Abstract
The interest in intermittent energy restriction (IER) diets as a weight-loss approach is increasing. Different IER protocols exist, including time-restricted eating (TRE), alternate-day fasting (ADF), and the 5:2 diet. This meta-analysis compared the effects of these IER diets with continuous energy restriction (CER) on anthropometrics and cardiometabolic risk markers in healthy adults. Twenty-eight trials were identified that studied TRE (k = 7), ADF (k = 10), or the 5:2 diet (k = 11) for 2-52 wk. Energy intakes between intervention groups within a study were comparable (17 trials), lower in IER (5 trials), or not reported (6 trials). Weighted mean differences (WMDs) were calculated using fixed- or random-effects models. Changes in body weight [WMD: -0.42 kg; 95% confidence interval (CI): -0.96 to 0.13; P = 0.132] and fat mass (FM) (WMD: -0.31 kg; 95% CI: -0.98 to 0.36; P = 0.362) were comparable when results of the 3 IER diets were combined and compared with those of CER. All IER diets combined reduced fat-free mass (WMD: -0.20 kg; 95% CI: -0.39 to -0.01; P = 0.044) and waist circumference (WMD: -0.91 cm; 95% CI: -1.76 to -0.06; P = 0.036) more than CER. Effects on body mass index [BMI (kg/m2)], glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), serum lipid and lipoprotein concentrations, and blood pressure did not differ. Further, TRE reduced body weight, FM, and fat-free mass more than CER, whereas ADF improved HOMA-IR more. BMI was reduced less in the 5:2 diet compared with CER. In conclusion, the 3 IER diets combined did not lead to superior improvements in anthropometrics and cardiometabolic risk markers compared with CER diets. Slightly greater reductions were, however, observed in fat-free mass and waist circumference. To what extent differences in energy intakes between groups within studies may have influenced these outcomes should be addressed in future studies.
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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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The effects of saffron supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis.
Zamani, M, Zarei, M, Nikbaf-Shandiz, M, Gholami, F, Hosseini, AM, Nadery, M, Shiraseb, F, Asbaghi, O
Frontiers in nutrition. 2022;9:1055517
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Cardiovascular disease (CVD) is a leading cause of death and disability around the world and presents a significant burden for healthcare systems. CVD has many risk factors, including diet and lifestyle habits. Hence, favourable interventions in those areas can help prevent and manage CVD. This systematic review examined the effects of saffron crocus on cardiovascular risk factors. Saffron is derived from the flowering plant Saffron Crocus (Crocus sativus). It contains many active compounds such as crocetin, crocin, picrocrocin, and safrana, which in various studies demonstrated positive effects on blood glucose levels, insulin resistance and sensitivity and blood fats, besides also having antioxidant and anti-inflammatory qualities. Yet, results were not always consistent, and hence this meta-analysis gathered evidence from 32 randomised controlled trials (RCTs) which included a total of 1674 subjects and investigated the effect of saffron supplements on cardiovascular risk factors such as blood fats, blood glucose control, blood pressure, anthropometric measures, and inflammatory markers. In conclusion, the analysis showed that saffron supplementation aided the reduction of some inflammatory markers (CRP, TNF-α), had favourable effects on antioxidant capacity, reduced blood fats except high-density lipoprotein (HDL), enhanced blood control and insulin sensitivity, reduced blood pressure and was linked to a reduction in waist circumference but with no significant effect on weight itself, BMI or fat mass. The authors discussed how their results relate to previous research and what underlying mechanisms can explain the effects or discrepancies. Given the positive results, saffron presents itself as a promising supplement and adjunct therapy for managing CVD and its risk factors.
Abstract
INTRODUCTION Cardiovascular disease (CVD) is one of the leading causes of death and disability in the world and is estimated to involve more people in the next years. It is said that alternative remedies such as herbs can be used to manage the complications of this disease. For this reason, we aimed to conduct this meta-analysis to systematically assess and summarize the effects of saffron supplementation as an important herb on cardiovascular risk factors in adults. METHODS A systematic search was done in PubMed, Scopus, and Web of Science to find eligible articles up to September 2022. Randomized controlled trials (RCTs) that evaluated the effects of saffron on lipid profiles, glycemic control, blood pressure, anthropometric measures, and inflammatory markers were included. In the meta-analysis, 32 studies were taken into account (n = 1674). RESULTS Consumption of saffron significantly decreased triglyceride (TG) (WMD = -8.81 mg/dl, 95%CI: -14.33, -3.28; P = 0.002), total cholesterol (TC) (WMD = -6.87 mg/dl, 95%CI: -11.19, -2.56; P = 0.002), low density lipoprotein (LDL) (WMD = -6.71 mg/dl, 95%CI: -10.51, -2.91; P = 0.001), (P = 0.660), fasting blood glucose (FBG) level (WMD = -7.59 mg/dl, 95%CI: -11.88, -3.30; P = 0.001), HbA1c (WMD = -0.18%, 95%CI: -0.21, -0.07; P < 0.001), homeostasis model assessment-insulin resistance (HOMA-IR) (WMD = -0.49, 95%CI: -0.89, -0.09; P = 0.016), systolic blood pressure (SBP) (WMD = -3.42 mmHg, 95%CI: -5.80, -1.04; P = 0.005), tumor necrosis factor α (TNF-α) (WMD = -2.54 pg/ml, 95%CI: -4.43, -0.65; P = 0.008), waist circumference (WC) (WMD = -1.50 cm; 95%CI: -2.83, -0.18; P = 0.026), malondialdehyde (MDA) (WMD = -1.50 uM/L, 95%CI: -2.42, -0.57; P = 0.001), and alanine transferase (ALT) (WMD = -2.16 U/L, 95%CI: -4.10, -0.23; P = 0.028). Also, we observed that saffron had an increasing effect on total antioxidant capacity (TAC) (WMD = 0.07 mM/L, 95%CI: 0.01, 0.13; P = 0.032). There was linear regression between FBG and the duration of saffron intake. Additionally, the non-linear dose-response analysis has shown a significant association of saffron intervention with HDL (P = 0.049), HOMA-IR (P = 0.002), weight (P = 0.036), ALP (P = 0.016), FBG (P = 0.011), HbA1c (P = 0.002), and TNF-α (P = 0.042). A non-linear association between the length of the intervention and the level of HDL and DBP was also found. DISCUSSION That seems saffron could effectively improve TG, TC, LDL, FBG, HbA1c, HOMA-IR, SBP, CRP, TNF-α, WC, MDA, TAC, and ALT.
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Association of dietary patterns, anthropometric measurements, and metabolic parameters with C-reactive protein and neutrophil-to-lymphocyte ratio in middle-aged and older adults with metabolic syndrome in Taiwan: a cross-sectional study.
Syauqy, A, Hsu, CY, Rau, HH, Chao, JC
Nutrition journal. 2018;17(1):106
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Metabolic syndrome, which is classified as having high blood pressure, obesity, high blood glucose and high cholesterol, is believed to be a consequence of the Westernised diet and lifestyle, which has become increasingly common place in several countries worldwide. The Westernised diet comprises of a high intake of saturated fats, meats, processed foods, sweets, salt and food additives, all of which can add to the burden of inflammatory processes. The objective of this cross-sectional study was to investigate associations evident between diet, body composition and metabolic measurements (such as BMI and blood pressure) with inflammatory markers; C-reactive protein and neutrophil-to-lymphocyte ratio (inflammatory markers that increase in response to inflammation), in adults diagnosed with metabolic syndrome. Researchers found that regardless of gender or age, there was a direct association with C-reactive protein and neutrophil-to-lymphocyte ratio and metabolic syndrome. The subjects who consumed a higher amount of ‘Westernised foods’ showed higher levels of inflammatory markers when compared to those who a consumed a more healthful diet.
Abstract
BACKGROUND Metabolic syndrome is commonly associated with inflammation. The underlying factors of inflammation in metabolic syndrome are not fully understood. The objective of the study was to determine the association of dietary patterns, anthropometric measurements, and metabolic parameters with inflammatory markers in middle-aged and older adults with metabolic syndrome in Taiwan. METHODS A total of 26,016 subjects aged ≥35 y with metabolic syndrome were recruited from Mei Jau institution between 2004 and 2013 for a cross sectional study. Metabolic syndrome was defined by the International Diabetes Federation. Multivariate logistic regression was performed to evaluate the association of dietary patterns, anthropometric measurements, and metabolic parameters with C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in men and women with metabolic syndrome. Crude and adjusted models were analyzed by gender. RESULTS The western dietary pattern, obesity, high body fat, high waist or hip circumference, and high waist-to-hip ratio were significantly associated with increased odds ratios of high CRP and NLR in both genders. High systolic or diastolic blood pressure (BP), low high-density lipoprotein-cholesterol (HDL-C), high low-density lipoprotein-cholesterol (LDL-C), high total cholesterol (TC), high serum triglycerides (TG), and high fasting blood glucose (FBG) were significantly correlated with increased odds ratios of high CRP in both genders. Low HDL-C, high LDL-C, high serum TG, and high FBG were significantly associated with increased odds ratios of high NLR in both genders. However, high systolic (OR = 1.124, 95% CI 1.047-1.206, P < 0.01) or diastolic BP (OR = 1.176, 95% CI 1.087-1.273, P < 0.001) and high TC (OR = 1.138, 95% CI 1.062-1.220, P < 0.001) were significantly correlated with increased odds ratios of high NLR only in men. CONCLUSIONS The western dietary pattern, obese-related anthropometric parameters, and most components of metabolic syndrome are positively associated with CRP levels and NLR in men and women with metabolic syndrome.
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Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Demark-Wahnefried, W, Nix, JW, Hunter, GR, Rais-Bahrami, S, Desmond, RA, Chacko, B, Morrow, CD, Azrad, M, Frugé, AD, Tsuruta, Y, et al
BMC cancer. 2016;16:61
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There is a strong body of evidence associating obesity and increased risk for more aggressive and progressive cancer. This paper aims to assess the feasibility of a presurgical diet and exercise weight loss intervention in men with newly-diagnosed prostate cancer who elected for prostatectomy. It also aims to explore the intervention’s effects on tumour proliferation rates and other biomarkers. The 3-weeks randomised controlled study included 40 overweight or obese men newly-diagnosed with prostate cancer. Participants in experimental arm were assigned to a healthy energy-restricted diet versus wait-list control arm. All feasibility endpoints were achieved with accrual completed within 2 years, retention of 85%, adherence of 95% and no adverse events. Biologic outcomes were not included in this paper, as biological testing was still ongoing. Authors concluded that this study’s methods and data on feasibility could provide useful framework for the design of future trials. They also highlighted the importance of presurgical trials as a feasible and safe means to assess the impacts of diet and exercise on tumour tissue.
Abstract
BACKGROUND Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION NCT01886677.
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L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study.
Zhang, JJ, Wu, ZB, Cai, YJ, Ke, B, Huang, YJ, Qiu, CP, Yang, YB, Shi, LY, Qin, J
Nutrition journal. 2014;13:110
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Metabolic syndrome increases the risk of heart disease and diabetes. Modified fasting therapy, such as a very-low-calorie diet is considered an effective way to tackle obesity and metabolic syndrome. When fasting, calorie restriction may cause fatigue and intense hunger, which may tempt individuals to stop fasting. L-Carnitine is an amino acid that transports long-chain fatty acids to mitochondria and helps them be oxidised to produce energy. L-Carnitine intravenous therapy is more bioavailable, better absorbed, and cleared than oral supplementation. This randomised, single-blinded, placebo-controlled pilot study included 30 individuals with metabolic syndrome who were randomly assigned to receive either 4 g/day of intravenous L-carnitine or saline for seven days to evaluate the effect of L-Carnitine on fatigue, hunger, body mass, lipid profile, and other CHD risk factors during a modified fasting period. The L-Carnitine group showed a significant reduction in waist-hip ratio, body mass, serum insulin levels, γ-glutamyltransferase, mental and physical fatigue, fatigue severity, weight loss, and greater reduction in waist circumference, total cholesterol and hunger when compared to the control group. Healthcare professionals can use the results of this study to understand the beneficial effects of L-Carnitine administration during modified fasting therapy in reducing weight, metabolic risk factors, hunger and fatigue. Long-term studies are required to confirm the benefits of L-carnitine.
Abstract
BACKGROUND The present study aimed to determine that whether L-carnitine infusion could ameliorate fasting-induced adverse effects and improve outcomes. METHOD In this 7-day, randomized, single-blind, placebo-controlled, pilot study, 15 metabolic syndrome (MetS) patients (11/4 F/M; age 46.9 ± 9.14 years; body mass index [BMI] 28.2 ± 1.8 kg/m2) were in the L-carnitine group (LC) and 15 (10/5 F/M; age 46.8 ± 10.9 years; BMI 27.1 ± 2.3 kg/m2) were in the control group (CT). All participants underwent a 5-day modified fasting therapy introduced with 2-day moderate calorie restriction. Patients in the LC group received 4 g/day of intravenous L-carnitine, while patients in the CT group were injected with saline. Blood pressure (BP), anthropometric characteristics, markers of liver function, metabolic indices (plasma glucose, lipid profiles, uric acid, free fatty acid and insulin) and hypersensitivity C-reactive protein were measured. Perceived hunger was recorded daily by self-rating visual analogue scales. Fatigue was evaluated by Wessely and Powell scores. RESULTS In contrast to the CT group, total cholesterol, alanine aminotransferase, systolic and diastolic BP did not change significantly in the LC group after prolonged fasting. There were significant differences in weight loss (LC -4.6 ± 0.9 vs. CT -3.2 ± 1.1 kg, P = 0.03), and waist circumference (LC -5.0 ± 2.2 vs. CT -1.7 ± 1.16 cm, P < 0.001), waist hip ratio (LC -0.023 ± 0.017 vs. CT 0.012 ± 0.01, P < 0.001), insulin concentration (LC -9.9 ± 3.58 vs. CT -6.32 ± 3.44 µU/mL, P = 0.046), and γ-glutamyltransferase concentration (LC -7.07 ± 6.82 vs. CT -2.07 ± 4.18, P = 0.024). Perceived hunger scores were significantly increased (P < 0.05) in the CT group during starvation, which was alleviated with L-carnitine administration in the LC group. Physical fatigue (LC -3.2 ± 3.17 vs. CT 1.8 ± 2.04, P < 0.001) and fatigue severity (LC -11.6 ± 8.38 vs. CT 8.18 ± 7.32, P < 0.001) were significantly reduced in the LC group but were aggravated in the CT group. CONCLUSION Intravenous L-carnitine can ameliorate fasting-induced hunger, fatigue, cholesterol abnormalities and hepatic metabolic changes and facilitate fasting-induced weight loss in MetS patients. TRIAL REGISTRATION ChiCTR-TNRC-12002835.