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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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Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review.
Alkurd, R, Mahrous, L, Zeb, F, Khan, MA, Alhaj, H, Khraiwesh, HM, Faris, ME
Medicina (Kaunas, Lithuania). 2024;60(1)
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Brain-derived neurotrophic factor (BDNF) is a protein that plays a crucial role in brain development, cognition and metabolism. Intermittent fasting (IF) is a promising therapeutic strategy for managing metabolic disorders and improving cognitive function. Therefore, this systematic review of sixteen experimental and observational studies investigated the effect of IF on BDNF production and improvements in cognition through the BDNF pathway in healthy adults and people with metabolic disorders. Included studies focused on different IF regimens such as calorie restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE) and Ramadan model of intermittent fasting (RIF) Future, well-controlled, long-term, robust studies are required to assess the effect of different IF regimens on the production of BDNF and cognitive function in people with metabolic disorders, as the current research is inconclusive. However, healthcare professionals can use the review to understand the potential beneficial effects of IF on cognition and metabolic health in humans.
Abstract
Background: The potential positive interaction between intermittent fasting (IF) and brain-derived neurotrophic factor (BDNF) on cognitive function has been widely discussed. This systematic review tried to assess the efficacy of interventions with different IF regimens on BDNF levels and their association with cognitive functions in humans. Interventions with different forms of IF such as caloric restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE), and the Ramadan model of intermittent fasting (RIF) were targeted. Methods: A systematic review was conducted for experimental and observational studies on healthy people and patients with diseases published in EMBASE, Scopus, PubMed, and Google Scholar databases from January 2000 to December 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statements (PRISMA) for writing this review. Results: Sixteen research works conducted on healthy people and patients with metabolic disorders met the inclusion criteria for this systematic review. Five studies showed a significant increase in BDNF after the intervention, while five studies reported a significant decrease in BDNF levels, and the other six studies showed no significant changes in BDNF levels due to IF regimens. Moreover, five studies examined the RIF protocol, of which, three studies showed a significant reduction, while two showed a significant increase in BDNF levels, along with an improvement in cognitive function after RIF. Conclusions: The current findings suggest that IF has varying effects on BDNF levels and cognitive functions in healthy, overweight/obese individuals and patients with metabolic conditions. However, few human studies have shown that IF increases BDNF levels, with controversial results. In humans, IF has yet to be fully investigated in terms of its long-term effect on BDNF and cognitive functions. Large-scale, well-controlled studies with high-quality data are warranted to elucidate the impact of the IF regimens on BDNF levels and cognitive functions.
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Acute feeding with almonds compared to a carbohydrate-based snack improves appetite-regulating hormones with no effect on self-reported appetite sensations: a randomised controlled trial.
Carter, S, Hill, AM, Buckley, JD, Tan, SY, Rogers, GB, Coates, AM
European journal of nutrition. 2023;62(2):857-866
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Long-term regulation of body weight is controlled by balancing energy intake with energy expenditure. Understanding the role of specific food items and their impact on energy intake may assist in promoting weight reduction and weight loss maintenance for people with obesity. The aim of this study was to compare the effects of eating almonds or a carbohydrate-based snack on appetite-regulating hormones, self-reported appetite ratings, and short-term energy intake. This study is based on data obtained from a parallel arm randomised controlled trial. Participants were males and females, aged between 25 and 65 years who were randomly assigned to either the almond or the snack bar treatment groups based on age, sex and body mass index. Results show that the consumption of almonds resulted in a smaller C-peptide response and a larger glucose-dependent insulinotropic polypeptide [pancreatic hormone], glucagon-like peptide 1 [peptide hormone] (timepoint comparisons only), glucagon and pancreatic polypeptide response compared to consuming an isocaloric carbohydrate-rich snack bar. Furthermore, although not significant, the almond group consumed 300 kJ less energy in the meal challenge, 270 kJ of which came from discretionary foods, which may be a clinically important benefit in weight management. Authors conclude that foods that promote satiety help to regulate energy balance and may assist with weight management. However, future studies should consider testing food dose and composition carefully as the volume of food, its sensory qualities, and the acceptance of the food respective of usual meal patterns, may be important in eliciting a feeling of fullness and satisfaction.
Abstract
PURPOSE Early satiety has been identified as one of the mechanisms that may explain the beneficial effects of nuts for reducing obesity. This study compared postprandial changes in appetite-regulating hormones and self-reported appetite ratings after consuming almonds (AL, 15% of energy requirement) or an isocaloric carbohydrate-rich snack bar (SB). METHODS This is a sub-analysis of baseline assessments of a larger parallel-arm randomised controlled trial in overweight and obese (Body Mass Index 27.5-34.9 kg/m2) adults (25-65 years). After an overnight fast, 140 participants consumed a randomly allocated snack (AL [n = 68] or SB [n = 72]). Appetite-regulating hormones and self-reported appetite sensations, measured using visual analogue scales, were assessed immediately before snack food consumption, and at 30, 60, 90 and 120 min following snack consumption. A sub-set of participants (AL, n = 49; SB, n = 48) then consumed a meal challenge buffet ad libitum to assess subsequent energy intake. An additional appetite rating assessment was administered post buffet at 150 min. RESULTS Postprandial C-peptide area under the curve (AUC) response was 47% smaller with AL compared to SB (p < 0.001). Glucose-dependent insulinotropic polypeptide, glucagon and pancreatic polypeptide AUC responses were larger with AL compared to SB (18%, p = 0.005; 39% p < 0.001; 45% p < 0.001 respectively). Cholecystokinin, ghrelin, glucagon-like peptide-1, leptin and polypeptide YY AUCs were not different between groups. Self-reported appetite ratings and energy intake following the buffet did not differ between groups. CONCLUSION More favourable appetite-regulating hormone responses to AL did not translate into better self-reported appetite or reduced short-term energy consumption. Future studies should investigate implications for longer term appetite regulation. ANZCTR REFERENCE NUMBER ACTRN12618001861246 2018.
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Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis.
Arnesen, EK, Thorisdottir, B, Bärebring, L, Söderlund, F, Nwaru, BI, Spielau, U, Dierkes, J, Ramel, A, Lamberg-Allardt, C, Åkesson, A
Food & nutrition research. 2023;67
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Nuts and seeds consumption is associated with a reduced risk of coronary heart disease (CHD) and cardiovascular disease (CVD). Nuts and seeds contain beneficial components to reduce the risk of CVD and CHD; hence dietary addition may benefit heart health. This systematic review and meta-analysis included sixty studies to analyse the effects of the consumption of nuts and seeds on the incidence of mortality from type 2 diabetes (T2D) and CVD and intermediate cardiometabolic risk factors. High nuts and seed consumption showed a 19% reduction in CVD risk and a 23% reduction in CVD mortality. In addition, high consumption lowered the risk of CHD by 25%. Increased nut consumption up to 30 g/day showed a dose-dependent relationship with reduced risk of CVD. Healthcare professionals can use the results of this study to understand the association between nuts and seeds consumption and CHD, CVD and blood lipid levels. However, further robust studies are required to evaluate the effect of specific nuts and seeds on CHD and CVD risk reduction.
Abstract
OBJECTIVES We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults. METHODS A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospective cohort studies and ≥12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I 2. One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria. RESULTS After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low consumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I 2 = 67%), CVD mortality (0.77; 0.72, 0.82; I 2 = 59.3%), CHD (0.82; 0.76, 0.89; I 2 = 64%), CHD mortality (0.75; 0.65, 0.87; I 2 = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I 2 = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I 2 = 24.8%) and 0.95 (0.75, 1.21; I 2 = 82.2%). Intake of nuts (median ~50 g/day) lowered total (-0.15 mmol/L; -0.22, -0.08; I 2 = 31.2%) and LDL-cholesterol (-0.13 mmol/L; -0.21, -0.05; I 2 = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D. CONCLUSION There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated.
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Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
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:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
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The effect of synbiotic supplementation on hypothyroidism: A randomized double-blind placebo controlled clinical trial.
Ramezani, M, Reisian, M, Sajadi Hezaveh, Z
PloS one. 2023;18(2):e0277213
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Despite the increased awareness and the improvements in medical management of hypothyroidism; depression, mood disturbance and poor health-related quality of life (QoL) is common among hypothyroid patients. Synbiotics have been advocated as being beneficial to patients with metabolic diseases. Synbiotics are a mixture of probiotics and prebiotics that beneficially affect the host by improving the survival and stimulating the growth of advantageous and health promoting microbial species in the gastrointestinal tract. The aim of this study was to examine whether synbiotic supplementation could enhance depression, QoL, and blood pressure, as well as thyroid hormones in hypothyroid patients. This study is a 10-week parallel design randomised placebo-controlled trial. Participants – adults with hypothyroidism - were randomly assigned to the synbiotic (n = 28) or the placebo (n = 28) group. Results show that following 10 weeks supplementation with synbiotics (500 mg of 10⁹ CFU/g probiotics plus fructo-oligosaccharide) in comparison to placebo does not affect serum thyroid stimulating hormone level and depression. However, it significantly improved blood pressure levels and various domains and areas of QoL. Authors conclude that further clinical trials are needed to assess the effectiveness of a synbiotic supplementation along with the current routine treatment for hypothyroid patients.
Abstract
OBJECTIVE We hypothesize that synbiotic supplementation could modulate the intestinal microbiota and subsequently, improve the condition of hypothyroid patients. METHODS Fifty-six adult hypothyroid patients were recruited to this double-blind, placebo-controlled, randomized clinical trial. The intervention was 10 weeks of synbiotic (500 mg of 109 CFU/g probiotics plus fructo-oligosaccharide, n = 28) compared to placebo (lactose, magnesium stearate, talc, and silicon dioxide, n = 28). Randomization and allocation to trial groups were carried out using random number sequences drawn from https://sealedenvelope.com/. Primary outcomes were serum thyroid stimulating hormone (TSH) and free thyroxine (FT4), and secondary outcomes were depression, quality of life, and blood pressure (BP). P-values< 0.05 were considered statistically significant. RESULTS Analysis on 51 patients who completed the trial showed that TSH and depression (p> 0.05) did not change significantly, while serum FT4 significantly increased in both groups (p = 0.03 and p = 0.02 in symbiotic and placebo respectively). A significant decrease in systolic BP occurred only in the synbiotic group (p = 0.05). Significant improvements occurred regarding different domains and areas of quality of life in the crude and adjusted analysis, including perceived mental health (p = 0.02), bodily pain (p = 0.02), general health perception (p = 0.002), and wellbeing (p = 0.002), which were significantly higher in the synbiotic group. CONCLUSIONS Ten-week supplementation with synbiotic had no favorable effect on depression and TSH, but it improved blood pressure and quality of life in patients with hypothyroidism. More trials are needed to support or reject these findings. TRIAL REGISTRATION IRCT20210926052583N1, Iranian Registry of Clinical Trials (IRCT), registered October 1st, 2021.
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Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
Li, S, Yin, S, Ding, H, Shao, Y, Zhou, S, Pu, W, Han, L, Wang, T, Yu, H
Cell proliferation. 2023;56(1):e13346
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Multiple risk factors could lead to the development of liver cancer, one of the most common malignant tumours in the world. These risk factors include hepatitis infection, non-alcoholic fatty liver disease and excessive alcohol consumption. Polyphenols are bioactive compounds with antioxidant, anti-inflammatory, anti-mutagenic, anti-viral, hypoglycaemic, anti-hypertensive, antibacterial and anti-proliferative properties. Polyphenols may be effective in reducing the risk of developing liver cancer by altering the metabolism. This review evaluated the effectiveness of polyphenols in protecting the liver and inhibiting hepatocarcinoma development. In addition, the review evaluated several mechanisms by which polyphenols affect glucose and lipid metabolism and mitochondrial metabolism and reduce the effects of oxidative stress, inflammation and toxic metabolites. Further robust studies are required to assess the beneficial effects of polyphenols as a therapeutic agent, as the current knowledge is limited. However, healthcare professionals can use the results of this study to understand the protective effects of polyphenols against liver disease.
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
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Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC).
Sommersten, CH, Gjerde, ES, Laupsa-Borge, J, Andersen, AI, Lawrence-Archer, L, McCann, A, Hansson, P, Raza, GS, Herzig, KH, Lied, GA, et al
The Journal of nutrition. 2023;153(2):459-469
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Diet induced fat loss can result in an increase in appetite, contributing to weight loss regression and reduced diet adherence after successful weight loss. Certain diets such as those very high in fat and low in carbohydrates, which switches the body’s main fuel source to fat instead of sugar, have been shown to suppress feelings of hunger after weight loss. When this occurs it is known as ketosis and these diets may suppress a hormone, which is responsible for feelings of hunger, known as ghrelin. Diets which focus on the quality of the carbohydrate being consumed have also been shown to affect appetite. This randomised control trial of 193 individuals aimed to determine the effect of ketosis and the quality of carbohydrates on ghrelin and feelings of hunger. The results showed that ketosis during a low carbohydrate high fat diet was insufficient to decrease levels of the hunger hormone ghrelin and increased feelings of hunger. Carbohydrate quality also failed to decrease feelings of hunger or the hunger hormone ghrelin. It was concluded that regardless of the diet, fat loss resulted in feelings of hunger, which could not be supressed by a high-quality carbohydrate diet or a low carbohydrate high fat diet. This study could be used by health care professionals to understand that weight loss may be hindered by an increase in appetite. If this occurs, strategies to limit the hunger hormone ghrelin may be successful in maintaining weight loss.
Abstract
BACKGROUND Low-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared. OBJECTIVES To evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, β-hydroxybutyrate (βHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000-2500 kcal/d) and with varying carbohydrate quality or quantity. METHODS We performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on "acellular" carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), "cellular" carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at clinicaltrials.gov as NCT03401970. RESULTS Of the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%-7%) and visceral fat volume (12%-17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: -16, 38). Although βHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: -39.6 pg/mL; 95% CI: -76, -3.3]). No significant between-group differences were seen in feelings of hunger. CONCLUSIONS Modestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3-0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss.
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Probiotics intervention in preventing conversion of impaired glucose tolerance to diabetes: The PPDP follow-on study.
Yan, Q, Hu, W, Tian, Y, Li, X, Yu, Y, Li, X, Feng, B
Frontiers in endocrinology. 2023;14:1113611
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Compared with normal glucose tolerance, people with prediabetes, especially impaired glucose tolerance (IGT), have a higher risk of developing type 2 diabetes mellitus (T2DM). Early intervention can significantly reduce the probability of developing T2DM in the IGT population. The aim of this study was to observe the effect of early probiotic intervention on the conversion of T2DM after 6 years. This study was a follow-on study of the Probiotics Prevention Diabetes Program (PPDP) Study. A total of 39 non-T2DM patients agreed to continue with the follow up of glucose metabolism for the following 4 years. Results showed that supplementation with active probiotics of Bifidobacterium, Lactobacillus acidophilus and Enterococcus faecalis is safe, although it does not reduce the risk of IGT conversion to diabetes mellitus. Authors conclude that more clinical and laboratory studies using large samples and long-term observation are needed to explore the effects of different probiotic strains on IGT.
Abstract
OBJECTIVES The purpose of this study was to assess the incidence of type 2 diabetes mellitus (T2DM) after 6 years in patients with IGT who received early probiotic intervention in the Probiotics Prevention Diabetes Program (PPDP) trial. METHODS 77 patients with IGT in the PPDP trial were randomized to either probiotic or placebo. After the completion of the trial, 39 non-T2DM patients were invited to follow up glucose metabolism after the next 4 years. The incidence of T2DM in each group was assessed using Kaplan-Meier analysis. The 16S rDNA sequencing technology was used to analyze gut microbiota's structural composition and abundance changes between the groups. RESULTS The cumulative incidence of T2DM was 59.1% with probiotic treatment versus 54.5% with placebo within 6 years, there was no significant difference in the risk of developing T2DM between the two groups (P=0.674). CONCLUSIONS Supplemental probiotic therapy does not reduce the risk of IGT conversion to T2DM. CLINICAL TRIAL REGISTRATION https://www.chictr.org.cn/showproj.aspx?proj=5543, identifier ChiCTR-TRC-13004024.
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Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.
Zhang, Y, Qu, Z, Lu, T, Shao, X, Cai, M, Dilimulati, D, Gao, X, Mao, W, Hu, F, Su, L, et al
Nutrients. 2023;15(3)
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Polycystic ovary syndrome (PCOS) is a unification of reproductive endocrine and metabolic disorders. Lifestyle and weight management, particularly dietary intake aimed at weight loss, are initial treatment strategies for PCOS. A calorie-restricted diet (CRD) seems to be the optimal dietary pattern for weight management in the PCOS population. The aim of this study was to evaluate modifications in fat distribution, the androgenic state, and metabolic profiles in the overweight and obese PCOS-affected population, who obtained modest and equivalent weight loss induced by a CRD regimen with or without Dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (RA). This study was a randomised controlled trial which enrolled 68 females diagnosed with PCOS. Participants were randomly assigned to receive to one of the two groups: a GLP-1 RA combined with CRD or CRD alone. Results showed that participants in the GLP-1 RA + CRD group took a shorter time to achieve a 7% weight loss goal than those in the CRD group. Furthermore, both interventions had similar positive effects in improving menstrual frequency and reducing levels of blood pressure, insulin, aminotransferases, lipids, total fat mass, total lean mass, and abdominal subcutaneous adipose tissue mass after equivalent weight loss. Authors conclude that their findings support the importance of dietary intervention as a first-line treatment in women with PCOS, and that GLP-1 RA therapy offers an effective and generally tolerable adjunct therapy to aid in achieving weight targets based on dietary therapy in overweight and obese women with PCOS.
Abstract
The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (-0.97 cm2, 95% confidence interval from -14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.