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Dietary polyphenols, metabolic syndrome and cardiometabolic risk factors: An observational study based on the DCH-NG subcohort.
Lanuza, F, Zamora-Ros, R, Bondonno, NP, Meroño, T, Rostgaard-Hansen, AL, Riccardi, G, Tjønneland, A, Landberg, R, Halkjær, J, Andres-Lacueva, C
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2023;33(6):1167-1178
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Metabolic syndrome (MetS) is a cluster of metabolic disorders that increases the risk of developing chronic diseases. Cardiometabolic risk factors include high waist circumference (WC), insulin resistance, hypertension, dysglycaemia, dyslipidaemia, and altered inflammatory markers. The aim of this study was to investigate the associations between intakes of polyphenols (total polyphenols and their main classes) and the prevalence of MetS and cardiometabolic risk factors. This study is an observational sub-cohort study of 676 Danish participants of the MAX study from the Danish Diet, Cancer and Health - Next Generations (DCH-NG) cohort. Results showed that individuals with higher total polyphenol and phenolic acid intakes, were less likely to have MetS. Furthermore, for cardiovascular risk factors, intakes of total polyphenols, flavonoids and phenolic acids were associated with a lower risk of higher systolic blood pressure and lower high-density lipoprotein cholesterol. Authors conclude by suggesting that intervention studies should be undertaken to establish whether a polyphenol-rich diet can improve some cardiometabolic risk factors and can reduce or delay the onset of cardiometabolic diseases in free-living populations.
Abstract
BACKGROUND AND AIMS Polyphenol-rich foods have beneficial properties that may lower cardiometabolic risk. We aimed to prospectively investigate the relationship between intakes of dietary polyphenols, and metabolic syndrome (MetS) and its components, in 676 Danish residents from the MAX study, a subcohort of the Danish Diet, Cancer and Health-Next Generations (DCH-NG) cohort. METHODS AND RESULTS Dietary data were collected using web-based 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). The Phenol-Explorer database was used to estimate dietary polyphenol intake. Clinical variables were also collected at the same time point. Generalized linear mixed models were used to investigate relationships between polyphenol intake and MetS. Participants had a mean age of 43.9y, a mean total polyphenol intake of 1368 mg/day, and 75 (11.6%) had MetS at baseline. Compared to individuals with MetS in Q1 and after adjusting for age, sex, lifestyle and dietary confounders, those in Q4 - for total polyphenols, flavonoids and phenolic acids-had a 50% [OR (95% CI): 0.50 (0.27, 0.91)], 51% [0.49 (0.26, 0.91)] and 45% [0.55 (0.30, 1.00)] lower odds of MetS, respectively. Higher total polyphenols, flavonoids and phenolic acids intakes as continuous variable were associated with lower risk for elevated systolic blood pressure (SBP) and low high-density lipoprotein cholesterol (HDL-c) (p < 0.05). CONCLUSIONS Total polyphenol, flavonoid and phenolic acid intakes were associated with lower odds of MetS. These intakes were also consistently and significantly associated with a lower risk for higher SBP and lower HDL-c concentrations.
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Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.
Lai, H, Li, Y, He, Y, Chen, F, Mi, B, Li, J, Xie, J, Ma, G, Yang, J, Xu, K, et al
Gut microbes. 2023;15(1):2197837
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Functional constipation is characterised by continuously difficult, incomplete, or infrequent defecation, without an organic origin. Effective intervention strategies are required to relieve the functional constipation difficulties, particularly in rapidly aging populations, such as Chinese populations. The aim of this study was to evaluate the effectiveness of three dietary fibre formulas (polydextrose, psyllium husk, and wheat bran + psyllium husk) and one probiotic supplement on the improvement of constipation symptoms among Chinese adults with functional constipation. This study was a double-blinded randomised placebo-controlled trial which enrolled 250 participants who were randomly assigned to one of the five groups. Results showed: - that daily supplement of three prebiotic formulas with dietary fibres, or a probiotic formula effectively relieved hard stool in functional constipation patients after 4 weeks intervention. - the capacity of gut microbial genera in shaping the intervention responsiveness in the improvement of bowel movement frequency, Bristol stool scale score, and degree of defecation straining. Authors conclude that the pre or probiotic interventions may modulate gut microbiota, associated with intestinal health.
Abstract
Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884. What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber – gut microbiota (Anaerostipes)—constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.
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Probio-X Relieves Symptoms of Hyperlipidemia by Regulating Patients' Gut Microbiome, Blood Lipid Metabolism, and Lifestyle Habits.
Wang, H, Ma, C, Li, Y, Zhang, L, A, L, Yang, C, Zhao, F, Han, H, Shang, D, Yang, F, et al
Microbiology spectrum. 2023;11(3):e0444022
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A long-term high-fat diet will not only disrupt the balance of lipid metabolism in the body and cause metabolic disorders but also lead to chronic diseases, such as hyperlipidaemia, type 2 diabetes, hypertension, and obesity. Hyperlipidaemia is also an important contributing factor in cardiovascular disease. The aim of this study was to analyse the effects of a mixed probiotic formulation on hyperlipidaemia, with focus on changes in patients’ gut microbiota and their metabolic potential. This study was a 3-month randomised controlled intervention trial. A total of 56 hyperlipidaemic patients were recruited and randomised into either the placebo or probiotic (receiving a mixed probiotic formulation) group. Results show that the intake of the probiotic mix effectively reduced the serum levels of total cholesterol and low-density lipoprotein cholesterol, while increasing serum high-density lipoprotein cholesterol levels, in patients with hyperlipidaemia. In fact, there was a strong association between the desirable changes in patients’ lifestyle habits and lowering of these indexes. Furthermore, although insignificant changes were observed in the lipid metabolome and gut microbiota structure, some interesting fecal bacteria and blood metabolites increased significantly after Probio-X intervention. Authors conclude that their findings show that probiotic administration is a promising approach in managing hyperlipidaemia and improving public health.
Abstract
Hyperlipidemia is a key risk factor for cardiovascular disease, and it is associated with lipid metabolic disorders and gut microbiota dysbiosis. Here, we aimed to investigate the beneficial effects of 3-month intake of a mixed probiotic formulation in hyperlipidemic patients (n = 27 and 29 in placebo and probiotic groups, respectively). The blood lipid indexes, lipid metabolome, and fecal microbiome before and after the intervention were monitored. Our results showed that probiotic intervention could significantly decrease the serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol (P < 0.05), while increasing the levels of high-density lipoprotein cholesterol (P < 0.05) in patients with hyperlipidemia. Probiotic recipients showing improved blood lipid profile also exhibited significant differences in their lifestyle habits after the 3-month intervention, with an increase in daily intake of vegetable and dairy products, as well as weekly exercise time (P < 0.05). Moreover, two blood lipid metabolites (namely, acetyl-carnitine and free carnitine) significantly increased after probiotic supplementation cholesterol (P < 0.05). In addition, probiotic-driven mitigation of hyperlipidemic symptoms were accompanied by increases in beneficial bacteria like Bifidobacterium animalis subsp. lactis and Lactiplantibacillus plantarum in patients' fecal microbiota. These results supported that mixed probiotic application could regulate host gut microbiota balance, lipid metabolism, and lifestyle habits, through which hyperlipidemic symptoms could be alleviated. The findings of this study urge further research and development of probiotics into nutraceuticals for managing hyperlipidemia. IMPORTANCE The human gut microbiota have a potential effect on the lipid metabolism and are closely related to the disease hyperlipidemia. Our trial has demonstrated that 3-month intake of a mixed probiotic formulation alleviates hyperlipidemic symptoms, possibly by modulation of gut microbes and host lipid metabolism. The findings of the present study provide new insights into the treatment of hyperlipidemia, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.
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Effects of Diet on 10-Year Atherosclerotic Cardiovascular Disease Risk (from the DASH Trial).
Jeong, SY, Wee, CC, Kovell, LC, Plante, TB, Miller, ER, Appel, LJ, Mukamal, KJ, Juraschek, SP
The American journal of cardiology. 2023;187:10-17
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Determining the 10-year risk of heart disease can be used as tool to determine appropriate treatment plans. This study of 459 adults aged 22-75 years with obesity aimed to compare the effects on the 10-year risk for the development heart disease of an 8-week dietary approaches to stop hypertension (DASH) diet, with the standard American diet (AD) and a diet high in fruits and vegetables (F/V). The results showed that the DASH diet significantly improved risk factors such as systolic blood pressure and total cholesterol. However, the F/V diet had an improvement in good cholesterol, which the DASH diet did not. This equated to a similar 10% reduction in the 10-year heart disease risk compared to the AD. It was concluded that compared to a typical AD, DASH and F/V diets reduced the risk for heart disease over a 10-year period. However, the actual risk reduction was only small and individuals with obesity may need to reduce their risk further with other therapies. This study could be used by healthcare professionals to recommend a DASH diet or a diet high in fruits and vegetables to reduce the long-term risk for heart disease alongside other proven therapies or methods to reduce risk.
Expert Review
Conflicts of interest:
None
Take Home Message:
- DASH and F/V diets may be of benefit to obese individuals to decrease their risk for ASCVD
- The DASH diet did reduce HDL cholesterol and recommendations should be made to limit this effect (e.g. exercise and more fruit and vegetables in the diet).
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:
Introduction
This study aimed to determine the effect of the Dietary Approaches to Stop Hypertension (DASH) diet compared to a standard American diet (AD) and a diet emphasising fruits and vegetables (F/V) on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and how adopting these diets affect specific risk factors (e.g systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids).
Methods
- Secondary analysis from the DASH trial which ran for 8 weeks in 459 adults aged 22-75 years with obesity
- All meals were provided and dietary intake was adjusted to prevent weight loss
- The primary outcome was an absolute and relative difference in 10-year ASCVD risk from baseline.
Participants were randomised to one of three diets:
1) DASH diet
2) F/V diet, similar to AD but with more fruits and vegetables and higher potassium and magnesium
3) Standard AD.
Results
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to F/V (absolute difference SBP: -2.8, (95% confidence interval [CI]-4.5, -1.2), total cholesterol: 9.3 (-14.7, 3.9), and HDL cholesterol: -3.5 (-5.0, -2.1) P=<0.05 for all)
- DASH significantly lowered SBP, total cholesterol, and HDL cholesterol compared to AD (absolute difference SBP: -5.3 (-7.0, -3.7), total cholesterol: -13.1 (-18.5, -7.7), and HDL cholesterol: -3.8 (-5.2, -2.4) P=<0.05 for all)
- Compared to AD, DASH and F/V diets reduced 10-year ASCVD relative risk by -10.3%
( −14.4 to −5.9) and −9.9% ( −14.0 to −5.5) respectively
- This translated into low actual risk reductions of -0.21% for the F/V diet and -0.17% for the DASH diet
- Although DASH improved SBP, and total cholesterol compared to F/V, no differences in ASCVD risk between DASH and F/V were apparent. This was attributable to the detrimental effect of the DASH diet on HDL cholesterol, which was not seen in the F/V diet
- The effects of the DASH diet were more pronounced in black participants and in women.
Conclusion
Compared to the AD, DASH and F/V reduced 10-year ASCVD risk by approximately 10% over 8-weeks. The DASH diet was more effective for women and black adults.
Clinical practice applications:
- DASH and F/V diets decrease risk factors and an individual’s risk of ASCVD, and should be encouraged in individuals with obesity, especially women and black adults
- However, these diets do still leave obese individuals at risk for ASCVD.
Considerations for future research:
- Research on these diets in combination with weight loss regimes may give more pronounced results
- It may also be interesting to understand the mechanisms behind why the DASH diet reduces HDL cholesterol.
Abstract
Although modern risk estimators, such as the American College of Cardiology/American Heart Association Pooled Cohort Equation, play a central role in the decisions of patients to start pharmacologic therapy to prevent atherosclerotic cardiovascular disease (ASCVD), there is limited evidence to inform expectations for 10-year ASCVD risk reduction from established lifestyle interventions. Using data from the original DASH (Dietary Approaches to Stop Hypertension) trial, we determined the effects of adopting the DASH diet on 10-year ASCVD risk compared with adopting a control or a fruits and vegetables (F/V) diet. The DASH trial included 459 adults aged 22 to 75 years without CVD and not taking antihypertensive or diabetes mellitus medications, who were randomized to controlled feeding of a control diet, an F/V diet, or the DASH diet for 8 weeks. We determined 10-year ASCVD risk with the American College of Cardiology/American Heart Association Pooled Cohort Equation based on blood pressure and lipids measured before and after the 8-week intervention. Compared with the control diet, the DASH and F/V diets changed 10-year ASCVD risk by -10.3% (95% confidence interval [CI] -14.4 to -5.9) and -9.9% (95% CI -14.0 to -5.5) respectively; these effects were more pronounced in women and Black adults. There was no difference between the DASH and F/V diets (-0.4%, 95% CI -6.9 to 6.5). ASCVD reductions attributable to the difference in systolic blood pressure alone were -14.6% (-17.3 to -11.7) with the DASH diet and -7.9% (-10.9 to -4.8) with the F/V diet, a net relative advantage of 7.2% greater relative reduction from DASH compared with F/V. This was offset by the effects on high-density lipoprotein of the DASH diet, which increased 10-year ASCVD by 8.8% (5.5 to 12.3) compared with the more neutral effect of the F/V diet of -1.9% (-5.0 to 1.2). In conclusion, compared with a typical American diet, the DASH and F/V diets reduced 10-year ASCVD risk scores by about 10% over 8 weeks. These findings are informative for counseling patients on both choices of diet and expectations for 10-year ASCVD risk reduction.
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Ameliorating effects of L-carnitine and synbiotic co-supplementation on anthropometric measures and cardiometabolic traits in women with obesity: a randomized controlled clinical trial.
Fallah, F, Mahdavi, R
Frontiers in endocrinology. 2023;14:1237882
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Obesity is a multifactorial relapsing chronic disease attributed to the complicated interaction of behavioural, environmental, and genetic factors. Given the adverse effects of anti-obesity medications, there has been a great appeal in the consumption of weight loss supplements among individuals suffering from obesity seeking a “magic bullet,” which is less demanding than conventional weight management protocols. The aim of this study was to assess the effects of concomitant supplementation of L-carnitine and a multistrain/multispecies synbiotic compared with L-carnitine single therapy on the anthropometric and cardiometabolic indices in healthy women with obesity. This study was a double-blind, controlled, randomised clinical trial. Following a 2-week run-in period, the participants were randomly allocated to the “L-carnitine + synbiotic” or “L-carnitine + placebo” groups (1:1 ratio). Results showed that supplementation of multistrain/multispecies synbiotic (250 mg/day) concomitant with L-carnitine (2 × 500 mg/day) for 8 weeks led to greater amendments in anthropometric and glycaemic indices, and high-density lipoprotein cholesterol in healthy female individuals with obesity without any severe side effects. Authors concluded that co-administration of L-carnitine and synbiotic may be an encouraging therapeutic strategy for obesity and related cardiometabolic complications.
Abstract
BACKGROUND Obesity, a multifactorial disorder with pandemic dimensions, is conceded a major culprit of morbidity and mortality worldwide, necessitating efficient therapeutic strategies. Nutraceuticals and functional foods are considered promising adjuvant/complementary approaches for weight management in individuals with obesity who have low adherence to conventional treatments. Current literature supports the weight-reducing efficacy of pro/pre/synbiotics or L-carnitine; however, the superiority of the nutraceutical joint supplementation approach over common single therapies to counter obesity and accompanying comorbidities is well documented. This study was designed to assess the effects of L-carnitine single therapy compared with L-carnitine and multistrain/multispecies synbiotic co-supplementation on anthropometric and cardiometabolic indicators in women with obesity. METHODS The current placebo-controlled double-blind randomized clinical trial was performed on 46 women with obesity, randomly allocated to either concomitant supplementation [L-carnitine tartrate (2 × 500 mg/day) + multistrain/multispecies synbiotic (1 capsule/day)] or monotherapy [L-carnitine tartrate (2 × 500 mg/day) + maltodextrin (1 capsule/day)] groups for 8 weeks. Participants in both groups received healthy eating dietary advice. RESULTS Anthropometric, lipid, and glycemic indices significantly improved in both intervention groups; however, L-carnitine + synbiotic co-administration elicited a greater reduction in the anthropometric measures including body mass index (BMI), body weight, and neck, waist, and hip circumferences (p < 0.001, <0.001, <0.001, = 0.012, and =0.030, respectively) after adjusting for probable confounders. Moreover, L-carnitine + synbiotic joint supplementation resulted in a greater reduction in fasting blood sugar (FBS), insulin (though marginal), and homeostatic model assessment of insulin resistance (HOMA-IR) and more increment in quantitative insulin sensitivity check index (QUICKI; p = 0.014, 0.051, 0.024, and 0.019, respectively) compared with the L-carnitine + placebo monosupplementation. No significant intergroup changes were found for the lipid profile biomarkers, except for a greater increase in high-density lipoprotein-cholesterol concentrations (HDL-C) in the L-carnitine + synbiotic group (p = 0.009). CONCLUSION L-carnitine + synbiotic co-supplementation was more beneficial in ameliorating anthropometric indices as well as some cardiometabolic parameters compared with L-carnitine single therapy, suggesting that it is a promising adjuvant approach to ameliorate obesity or associated metabolic complications through potential synergistic or complementary mechanisms. Further longer duration clinical trials in a three-group design are demanded to verify the complementary or synergistic mechanisms. CLINICAL TRIAL REGISTRATION www.irct.ir, Iranian Registry of Clinical Trials IRCT20080904001197N13.
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Can dementia risk be reduced by following the American Heart Association's Life's Simple 7? A systematic review and dose-response meta-analysis.
Wu, J, Xiong, Y, Xia, X, Orsini, N, Qiu, C, Kivipelto, M, Rizzuto, D, Wang, R
Ageing research reviews. 2023;83:101788
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The American Heart Association (AHA) has defined ideal levels of seven modifiable cardiovascular health (CVH) factors, known as Life's Simple 7, that consist of smoking, physical activity, diet, body mass index, fasting blood glucose, total cholesterol, and blood pressure. Maintaining ideal levels of these factors has been recommended as a prevention strategy against not only cardiovascular diseases but also neurodegenerative disorders, e.g., cognitive decline and dementia. However, studies exploring the beneficial effects of the AHA’s CVH metrics on cognitive outcomes, especially among older populations, have been uncertain, and solid evidence is lacking in this field. This systematic review and meta-analysis aimed to quantify the relationship between the AHA’s CVH metrics and cognitive outcomes. 14 longitudinal studies were included in the meta-analysis. The results showed a considerable effect of a favourable total CVH score on reduced risk of incident dementia in adults aged 70 years or older. When looking at the individual factors, dementia risk can be reduced significantly if older adults achieved the recommended level of physical activity, blood glucose, or total cholesterol. The association with smoking appeared to be borderline, and there was no association between diet, body mass index hazard ratio or blood pressure and dementia risk. The authors concluded that their findings provide evidence that maintaining a favourable level of CVH score, either in mid- or late- life, would substantially reduce the risk of dementia among older adults. Preserving cardiovascular health by quitting smoking, engaging in physical exercise, controlling blood glucose and total cholesterol might be especially effective for forestalling cognitive decline and dementia.
Abstract
This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.
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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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X
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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8.
Distribution of energy intake across the day and weight loss: A systematic review and meta-analysis.
Young, IE, Poobalan, A, Steinbeck, K, O'Connor, HT, Parker, HM
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2023;24(3):e13537
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Obesity increases an individual's risk of metabolic disease, such as diabetes and cardiovascular disease, musculoskeletal disorders such as osteoarthritis, and some cancers. “Chrononutrition” relates to the timing of meals and distribution of total energy intake across the day. Evidence is building chrononutrition as a potential target in both weight loss and metabolic disease interventions. The aim of this study was to examine the impact of earlier versus later distribution of total daily energy intake on weight loss, and to evaluate the potential for utilizing altered energy distribution as a tool in weight loss interventions. This study is a systematic review and meta-analysis of nine clinical studies. Total number of participants was 485 (earlier distributed total energy intakes: n = 244, later distributed total energy intakes; n = 241). Results show that energy intakes with a focus on earlier distribution resulted in significantly greater weight loss when compared with similarly energy-restricted diets with individuals consuming a larger proportion of their total energy intake later in the day and into the evening. Authors conclude that earlier energy intakes may be a promising tool to be used in conjunction with other weight loss strategies such as energy restriction to enhance weight loss. However, further research is required to elucidate the additional positive impacts that earlier distributed total energy intakes may have on weight and metabolic health.
Expert Review
Conflicts of interest:
None
Take Home Message:
Implementing a dietary strategy where a higher proportion of energy is consumed earlier in the day may offer additional benefits to an energy restricted diet for weight loss, blood glucose, improve markers of insulin resistance, increase satiety and improve hunger management. Based on the findings, earlier distribution of energy intake may serve as an effective component of a weight loss protocol.
Evidence Category:
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X
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:
Background
Chrononutrition refers to the timing and distribution of total daily energy intake across the day. It has been proposed that consuming a greater proportion of total daily energy intake earlier in the day as opposed to the evening may be beneficial for weight loss and metabolic health.
Aims
This systematic review and meta-analysis aimed to assess the impact of earlier versus later distribution of total daily energy intake on weight loss.
Results
A total of 9 randomised controlled trials involving 485 participants were included in this analysis. The study durations ranged from 5-16 weeks. All of the studies included in this analysis applied energy-restricted diets to both intervention arms. The mean percentages of energy intake in 8 of the 9 studies per meal were:
- Earlier distributed intakes: breakfast: 34% ± 16%, lunch: 38% ± 7%, dinner: 20% ± 6%.
- Later distributed intakes: breakfast: 19% ± 6%, lunch: 30% ± 10%, dinner; 40% ± 11%.
One of the studies advised percentage of energy intakes as either:
- Earlier: 70% for breakfast, morning tea and lunch and 30% for afternoon tea and dinner
- Late: 55% for breakfast, morning tea and lunch and 45% for afternoon tea and dinner.
The earlier distributed energy intake groups demonstrated significantly greater weight loss when compared with later distributed energy intake groups ( Mean Difference (MD) −1.23 kg; 95% CI −2.40, −0.06, p = 0.04;
I2 = 98%).
The earlier energy intake groups also displayed lower fasting and bedtime glucose levels (fasting: −0.83 vs. −0.27 mmol/L, p = 0.001; before sleep: −1.70 vs. −0.28 mmol/L, p = 0.009).
A random-effects model demonstrated that the earlier intake groups displayed greater reductions in LDL (MD: −0.11 mmol/L; 95% CI −0.14, −0.07, p < 0.01), fasting glucose (MD: 0.15 mmol/L, 95% CI −0.23, −0.06, p < 0.001) and HOMA-IR (MD: −0.38; 95% CI −0.64, −0.11, p = 0.005).
One study reported that earlier distribution energy intake also led to a greater reduction in medications following the intervention for type 2 diabetics (31% vs. 0%, P=0.002).
Two of the studies assessed both appetite and hunger and identified that earlier distribution of energy led to improvements in their urge to eat, preoccupation with food and cravings for sweets and fats.
Clinical practice applications:
Earlier distribution of energy intake may be beneficial for:
- Weight loss
- Improve fasting insulin, HOMA-IR, fasting glucose and HbA1c
- Reducing LDL
- Improving satiety and hunger management
- Supporting the reduction of medications for individuals with type 2 diabetes
- Improving regularity of sleep and waking times
Considerations for future research:
As the included studies only ranged from 5-16 weeks, longer duration studies would be useful to identify the effect of earlier distribution of energy intake on body weight, metabolic health and appetite over a longer period of time. There was a high degree of heterogeneity between the studies and a lack of uniformity in the distributions of energy intake across the day. Further studies with more uniformity of energy distribution would be needed to identify the optimal distribution of energy across the day to improve body weight and metabolic health.
Abstract
Consuming a greater proportion of total energy intake earlier in the day rather than in the evening is proposed to positively influence weight loss and health, potentially due to greater synchronization of human body circadian rhythms. This systematic review provides an update on existing evidence regarding earlier distributed eating patterns in weight loss interventions. Using a robust search strategy in five electronic databases, nine randomized controlled trials investigating the impact of energy intake distribution on weight loss were identified. Following critical appraisal, a random-effects meta-analyses found that, in the context of an energy-reduced diet, distributing energy intake with a focus on earlier intake resulted in significantly greater weight loss (-1.23 kg; 95% CI 2.40, -0.06, p = 0.04). Improvements in HOMA-IR, fasting glucose, and LDL cholesterol were also seen. The current study provides a timely update on the evidence linking distribution of total daily energy intake and health, showing that a focus on earlier intakes can result in greater short-term weight loss compared with later intakes. Future studies are needed to elucidate the impact that earlier intakes may have on weight management and metabolic health.
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9.
Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial.
Thomsen, MN, Skytte, MJ, Samkani, A, Carl, MH, Weber, P, Astrup, A, Chabanova, E, Fenger, M, Frystyk, J, Hartmann, B, et al
Diabetologia. 2022;65(3):506-517
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The carbohydrate restricted diet has been shown to be beneficial for Type 2 diabetes (T2D) management and reducing cardiovascular disease risk. This open-label, parallel randomised controlled trial involved Type 2 diabetic patients taking antidiabetic medications who restricted their energy intake by following either a carbohydrate-reduced high protein diet or a conventional diabetic diet. Participants in both groups had a 5.9% reduction in body weight, similar changes in fasting NEFA, apoB, apoA-1, total cholesterol, LDL-cholesterol, HDL-cholesterol, and non-HDL cholesterol, and a significant reduction in fasting glucose, insulin, C-peptide, and HOMA2-IR after 6 weeks of intervention. Carbohydrate-reduced high protein diet group showed a greater reduction in HbA1c and diurnal mean glucose, glycaemic variability, fasting triacylglycerol concentration and liver fat content. Carbohydrate-reduced high protein diet caused an adverse reaction in some patients, and those following a carbohydrate-reduced high protein diet excreted more urea than those eating a conventional diabetic diet. To confirm the results of this study, long-term robust studies are needed. This study can assist healthcare professionals in understanding the benefits of following a carbohydrate-reduced high protein diet in improving glycaemic control, triglyceride levels, and reducing body weight in Type 2 diabetes patients.
Abstract
AIMS/HYPOTHESIS Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. METHODS This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48-97 mmol/mol (6.5-11%), BMI >25 kg/m2, eGFR >30 ml min-1 [1.73 m]-2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). RESULTS Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol [-0.18 (-0.32, -0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] -0.8 [-1.2, -0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] -4.1 [-5.9, -2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] -18 [-29, -6]%, p < 0.01) and liver fat content (by mean [95% CI] -26 [-45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. CONCLUSIONS/INTERPRETATION Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. TRIAL REGISTRATION ClinicalTrials.gov NCT03814694. FUNDING The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg.
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10.
Time-restricted eating and exercise training improve HbA1c and body composition in women with overweight/obesity: A randomized controlled trial.
Haganes, KL, Silva, CP, Eyjólfsdóttir, SK, Steen, S, Grindberg, M, Lydersen, S, Hawley, JA, Moholdt, T
Cell metabolism. 2022;34(10):1457-1471.e4
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A healthy diet and regular physical activity are primary lifestyle strategies for the prevention and treatment of obesity and its associated conditions. However, poor adherence rates to these strategies limit their effectiveness. Time-restricted eating (TRE) is a popular dietary strategy that emphasises the timing of meals in alignment with diurnal circadian rhythms, permitting ad libitum energy intake during a restricted eating window (8–10 h between the first and last energy intake of the day). The aim of this study was to investigate the isolated and combined effects of TRE and high-intensity interval training (HIIT) on glycaemic control and cardiometabolic health outcomes in women with overweight/obesity. This study is a 7-week randomised controlled trial with four parallel groups: TRE (energy intake limited to a %10-h eating window every day), HIIT (three supervised treadmill exercise sessions per week), a combination (TREHIIT), and a control group (CON, no intervention). Participants (n=131) were randomly assigned to one of the four groups. . Results show that 7 weeks of TRE, HIIT, or a combination failed to improve glycaemic control in reproductive-aged women with overweight/obesity. However, the combination of TRE and HIIT significantly reduced glycated haemoglobin levels compared with CON and induced greater losses in body weight, fat mass, and visceral fat area compared with either intervention alone. Isolated TRE resulted in lower nocturnal glucose concentrations compared with CON. Authors conclude that combining TRE with HIIT can rapidly induce several health benefits and decrease metabolic disease risk in women with overweight/obesity. In fact, the high rates of compliance and adherence shown in their findings, highlight the potential of these diet-exercise (TRE and HIIT) protocols to be implemented in clinical practice for treatment and primary prevention of overweight/ obesity.
Abstract
Diet modification and exercise training are primary lifestyle strategies for obesity management, but poor adherence rates limit their effectiveness. Time-restricted eating (TRE) and high-intensity interval training (HIIT) improve cardiometabolic health in at-risk individuals, but whether these two interventions combined induce superior improvements in glycemic control than each individual intervention is not known. In this four-armed randomized controlled trial (ClinicalTrials.gov NCT04019860), we determined the isolated and combined effects of 7 weeks of TRE (≤10-h daily eating window, with ad libitum energy intake) and HIIT (three exercise sessions per week), compared with a non-intervention control group, on glycemic control and secondary cardiometabolic outcomes in 131 women (36.2 ± 6.2 years) with overweight/obesity. There were no statistically significant effects after isolated TRE, HIIT, or a combination (TREHIIT) on glucose area under the curve during an oral glucose tolerance test (the primary outcome) compared with the control group (TRE, -26.3 mmol/L; 95% confidence interval [CI], -82.3 to 29.7, p = 0.36; HIIT, -53.8 mmol/L; 95% CI, -109.2 to 1.6, p = 0.057; TREHIIT, -41.3 mmol/L; 95% CI, -96.4 to 13.8, p = 0.14). However, TREHIIT improved HbA1c and induced superior reductions in total and visceral fat mass compared with TRE and HIIT alone. High participant adherence rates suggest that TRE, HIIT, and a combination thereof may be realistic diet-exercise strategies for improving markers of metabolic health in women at risk of cardiometabolic disease.