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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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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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The effects of dietary patterns and food groups on symptomatic osteoarthritis: A systematic review.
Zeng, J, Franklin, DK, Das, A, Hirani, V
Nutrition & dietetics: the journal of the Dietitians Association of Australia. 2023;80(1):21-43
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Osteoarthritis is a chronic joint disease that can lead to disability, characterised by the deterioration and loss of joint cartilage, inflammation, pain, aches, and stiffness. Research has shown a positive association between osteoarthritis progression and pro-inflammatory diets, such as Western diets, and a negative association with anti-inflammatory diets, such as the DASH and Mediterranean diets. This systematic review evaluated the evidence from the literature to show the positive and negative associations between osteoarthritis and diet. The Prudent diet, Mediterranean diet, and increased fibre intake were effective in reducing the progression of osteoarthritis and alleviating its symptoms, while the Western diet increased the progression of symptomatic osteoarthritis. The Prudent diet was found to be particularly effective in alleviating symptomatic osteoarthritis. The beneficial effects of anti-inflammatory diets and increased fibre intake are thought to be due to the reduction and suppression of inflammatory cytokines, while inflammatory diets have the opposite effect. Although there is high heterogeneity between the studies, healthcare professionals can use the results of this systematic review to understand the therapeutic clinical utility of anti-inflammatory diets and high-fibre intake in reducing the progression of symptomatic osteoarthritis in people above the age of 45 years. Further robust studies are needed to evaluate the effectiveness of other therapeutic dietary strategies.
Abstract
AIM: To systematically review current literature to determine the association between symptomatic osteoarthritis and dietary patterns, diet quality and food groups in adults aged ≥45 years. METHODS The review was registered on PROSPERO (CRD42021270891). Cochrane Central Library, Cumulative Index of Nursing and Allied Health Literature, Embase, Medline and Web of Science databases were searched. A total of 3816 records were identified. Eligible articles involved populations aged ≥45 years with symptomatic osteoarthritis, assessing dietary patterns, diet quality or food groups, with pain in joints as outcomes. The Joanna Briggs Institute Critical Appraisal Checklists were used for quality assessment. Grading of Recommendations, Assessment, Development and Evaluation was used to assess the certainty of evidence. RESULTS Six cohort studies were included. The Prudent dietary pattern and the Mediterranean dietary pattern reduced the progression of osteoarthritis symptoms. The Western dietary pattern increased symptomatic osteoarthritis progression. Increased total fibre consumption reduced symptomatic osteoarthritis progression and pain worsening, but the effects of fibre from each food group were inconclusive. Diet with high inflammatory potential increased risk of new onset symptomatic osteoarthritis, but the effects of overall diet quality were inconclusive. CONCLUSIONS The Prudent dietary pattern showed the highest protection on symptomatic osteoarthritis in adults aged 45 years and over. The body of evidence is limited, suggesting that further research is needed to corroborate the estimated effect at a high certainty of evidence, and to incorporate previously unstudied dietary patterns and food groups. Identifying the most beneficial dietary pattern may inform future guidelines for reducing symptomatic osteoarthritis in middle aged and older adults.
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Effects of acute sleep loss on leptin, ghrelin, and adiponectin in adults with healthy weight and obesity: A laboratory study.
van Egmond, LT, Meth, EMS, Engström, J, Ilemosoglou, M, Keller, JA, Vogel, H, Benedict, C
Obesity (Silver Spring, Md.). 2023;31(3):635-641
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A lack of sleep may be a risk factor for weight gain. Leptin is an adipocyte-derived hormone that activates satiety networks within the brain. Ghrelin, as opposed to leptin, is mainly produced by the stomach and it acts as a hunger hormone, signalling fuel status to the central nervous system. Some studies have found either no alterations or higher leptin and lower ghrelin blood levels following experimental sleep deprivation. The aim of this study was to investigate whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. This study is a laboratory study based on blood samples from 44 participants, mainly university students. Results show that: - acute total sleep deprivation is linked to lower serum levels of the adipokine leptin and higher blood levels of ghrelin. - following sleep deprivation, serum adiponectin levels were elevated. - the drop in serum leptin was larger in women after total sleep deprivation; however, there wasn’t a significant association between biological sex and experimental condition. - the increase in blood levels of adiponectin was slightly more pronounced among women, whereas there weren’t any differences in the effects of sleep loss on plasma ghrelin. Authors conclude that acute total sleep deprivation shifts the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin. However, further investigation in larger samples focusing on their findings linked to sex- and weight-specific differences in leptin, ghrelin, and adiponectin are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
Sleep deprivation may shift the balance of appetite controlling hormones causing an increase in hunger and decreased satiety and therefore resulting in increased food intake. These changes may be more pronounced in biological females.
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:
Introduction
Sleep deprivation may contribute to weight gain and obesity through its effect on the hormonal pathways promoting hunger and satiety. Research has also linked chronic sleep loss with an increase in the brain reward response to food, thus driving an increase in daily food intake. Leptin and ghrelin are hormones involved in the control of food intake. Some research has associated alterations in these hormones following sleep loss, whilst others have not.
This study aimed to investigate whether biological sex and weight status affect fasting serum levels of leptin, ghrelin and adiponectin following chronic sleep deprivation in a supervised laboratory setting.
Methods
This randomised crossover design study included n=44 mixed sex participants with a mean age of 24.9 years. A total of 19 of the participants were classed as obese, with the remaining n= 25 participants were considered normal weight. Participants completed 2 nights in experimental sessions under continuously supervised conditions in a laboratory. One night was spent awake and the other asleep. Fasting blood samples were taken the morning after each session to measure levels of leptin, ghrelin and adiponectin.
Results
Serum levels of leptin after one night’s sleep loss were around 7% lower than those measured after sleep (17.3 = +/-2.6 vs 18.6 +/- 2.8 ng/mL, p = 0.037). Adjustments using sex-stratified analysis showed significantly lower levels of serum leptin in women (25.8 +/_4.3 vs 28.1 +/_ 4.7 ng/mL, p = 0.030) but not for men (10.1 +/_ 2.4 vs 10.6 +/_ 2.3 ng/mL, p = 0.458). However, when comparing individual participant differences between sleep and wake sessions, the results were not significant. Additionally, no significant differences were found between normal weight and obese participants.
Higher levels of ghrelin were found following sleep deprivation in both sexes and weight sub-groups (839.4 +/-77.5 vs 741.4+/-63.2 pg/mL, p= 0.003). Adiponectin was also found to be elevated in all participants regardless of biological sex or weight status (7.5 +/- 0.6 vs 6.8 +/- 0.6ug/mL, p= 0.003). However, ghrelin was observed to increase slightly more in participants with obesity, whereas elevations in adiponectin were slightly greater in those of normal weight.
Conclusion
In this study, sleep loss was associated with lowered levels of leptin and higher levels of ghrelin. Analysis between biological sexes indicated that there may be a greater decrease in leptin in females. Serum levels of adiponectin were also found to be elevated after sleep deprivation for both sexes with a slightly larger increase in women. These changes may result in increased hunger and food intake and decreased satiety. No significant differences were found between normal weight and obese participants.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Sleep deprivation may lead to lower levels of leptin in both sexes with a greater decrease for females. Ghrelin and adiponectin levels may be increased in both men and women after sleep loss with a slightly larger increase in adiponectin for women. This could lead to an increase in appetite, food consumption and therefore weight gain, particularly in women.
Considerations for future research:
- Larger studies are needed to investigate sex and weight status related differences in serum levels of ghrelin, leptin and adiponectin.
- It may be beneficial for blood samples to be taken at different points during the day to allow for fluctuations in hormone levels.
- Food intake should be measured to monitor any increases in food intake.
Abstract
OBJECTIVE This study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. METHODS A total of 44 participants (mean age 24.9 years; 20 women; 19 with obesity) participated in a crossover design, including one night of sleep deprivation and one night of sleep in the laboratory. After each night, fasting blood was collected. RESULTS After sleep deprivation, fasting levels of leptin were lower (mean [SE], vs. sleep: 17.3 [2.6] vs. 18.6 [2.8] ng/mL), whereas those of ghrelin and adiponectin were higher (839.4 [77.5] vs. 741.4 [63.2] pg/mL and 7.5 [0.6] vs. 6.8 [0.6] μg/mL, respectively; all p < 0.05). The changes in leptin and adiponectin following sleep loss were more pronounced among women. Furthermore, the ghrelin increase was stronger among those with obesity after sleep loss. Finally, the sleep loss-induced increase in adiponectin was more marked among normal-weight participants. CONCLUSIONS Acute sleep deprivation reduces blood concentrations of the satiety hormone leptin. With increased blood concentrations of ghrelin and adiponectin, such endocrine changes may facilitate weight gain if persisting over extended periods of sleep loss. The observed sex- and weight-specific differences in leptin, ghrelin, and adiponectin call for further investigation.
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Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomized controlled trial.
Schneider, E, Doll, JPK, Schweinfurth, N, Kettelhack, C, Schaub, AC, Yamanbaeva, G, Varghese, N, Mählmann, L, Brand, S, Eckert, A, et al
Journal of psychiatry & neuroscience : JPN. 2023;48(1):E23-E33
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Major depressive disorder (MDD) is often thought of as being solely a mood disorder. However, several studies have shown that sufferers can also experience decreased brain function such as memory loss and poor attention. Current therapies for MDD focus on the balancing of mood and leaves the problem of reduced brain function unattended. The gut microbiota has recently been shown to influence brain function and altered gut microbiota composition has been seen in individuals with MDD. Targeting the gut microbiota may therefore represent a novel target for MDD treatments. This secondary analysis of a randomised control trial aimed to determine whether a probiotic multistrain supplement could improve brain function in 60 individuals with depression. The results showed that probiotics improved the brain function in two different ways, the immediate recall of words, and the improvement of decreased neural function in the hippocampal part of the brain, which has been associated with MDD. It was concluded that probiotic supplementation can enhance verbal episodic memory and improve neural function associated with impaired brain function in MDD. This study could be used by healthcare professionals to understand that the health of the gut microbiota can have an influence on brain function and that probiotics may help individuals with MDD who are suffering from poorer memory.
Abstract
BACKGROUND In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing cognitive symptoms in depression are needed. As the gut microbiota-brain axis is linked to depression and cognition, we investigated the effect of a 4-week high-dose probiotic supplementation on cognitive symptoms in depression. METHODS This randomized controlled trial included 60 patients with MDD, of whom 43 entered modified intention-to-treat analysis. A probiotic supplement or indistinguishable placebo containing maltose was administered over 31 days in addition to treatment as usual for depression. Participant scores on the Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, and both Trail Making Test versions as well as brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after and 4 weeks after intervention. Additionally, brain activation changes during working memory processing were investigated before and immediately after intervention. RESULTS We found a significantly improved immediate recall in the VLMT in the probiotic group immediately after intervention, and a trend for a time × group interaction considering all time points. Furthermore, we found a time × group interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. Other measures did not reveal significant changes. LIMITATIONS The modest sample size resulting from our exclusion of low-compliant cases should be considered. CONCLUSION Additional probiotic supplementation enhances verbal episodic memory and affects neural mechanisms underlying impaired cognition in MDD. The present findings support the importance of the gut microbiota-brain axis in MDD and emphasize the potential of microbiota-related regimens to treat cognitive symptoms in depression. CLINICAL TRIAL REGISTRATION clinicaltrials.gov identifier NCT02957591.
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The efficacy of morning versus evening exercise for weight loss: A randomized controlled trial.
Brooker, PG, Gomersall, SR, King, NA, Leveritt, MD
Obesity (Silver Spring, Md.). 2023;31(1):83-95
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Despite considerable efforts to promote a healthy lifestyle, rates of overweight and obesity are continuing to rise worldwide, and obesity is now considered a pandemic. Although dietary intervention is the most effective lifestyle intervention for weight loss, exercise plays an important role in weight management. The aim of this study was to investigate the influence of a 12-week exercise programme, performed in either the morning or evening, on weight loss, cardiometabolic health risk factors, and components of energy balance in inactive adults with overweight and obesity. This study is a three-armed randomised controlled trial. Participants allocated to the two intervention conditions were prescribed 250 minutes per week of self-paced aerobic (treadmill-based) exercise for 12 weeks. Results show that there was no compelling evidence to support or encourage exercise exclusively at a particular time of day for weight loss. However, there were improvements in cardiometabolic health, such as weight reduction and increased cardiorespiratory fitness, increased levels of physical activity, and positive changes to dietary intake in both intervention groups. Following the intervention, both exercise groups continued to lose weight, and the improvements in cardiorespiratory fitness were sustained. Authors conclude that consistent reporting of time of day of exercise interventions among high-quality studies would significantly contribute to the literature and provide critical insight into the relative importance (or lack thereof) of prescribing exercise at a particular time of day.
Abstract
OBJECTIVE The aim of this study was to investigate the influence of morning versus evening exercise on weight loss, cardiometabolic health, and components of energy balance. METHODS A total of 100 inactive adults with overweight or obesity were randomized to morning exercise (AMEx; 06:00-09:00), evening exercise (PMEx; 16:00-19:00), or wait-list control (CON). AMEx and PMEx were prescribed 250 min·wk-1 of self-paced aerobic exercise for 12 weeks. Anthropometry and body composition, physical activity, and dietary intake were assessed at baseline, 6 weeks, and 12 weeks. Cardiorespiratory fitness (V̇O2 peak), resting metabolic rate, and blood markers were assessed at baseline and 12 weeks. Body composition and V̇O2 peak were also measured at 3- and 6-month follow-up. RESULTS AMEx and PMEx lost weight during the intervention (mean [SD], AMEx, -2.7 [2.5] kg, p < 0.001; PMEx, -3.1 [3.4] kg, p < 0.001). V̇O2 peak significantly increased in both intervention groups, and these changes were different from CON (AMEx, +4.7 mL·kg-1 ·min-1 , p = 0.034; PMEx, +4.2 mL·kg-1 ·min-1 , p = 0.045). There were no between-group differences for resting metabolic rate or physical activity. At 12 weeks, total energy intake was significantly reduced in both AMEx and PMEx versus CON (AMEx, -3974 kJ, p < 0.001; PMEx, -3165 kJ, p = 0.001). CONCLUSIONS Adults with overweight and obesity experience modest weight loss in response to an exercise program, but there does not appear to be an optimal time to exercise.
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Acute beetroot juice reduces blood pressure in young Black and White males but not females.
Grosicki, GJ, Flatt, AA, Cross, BL, Vondrasek, JD, Blumenburg, WT, Lincoln, ZR, Chall, A, Bryan, A, Patel, RP, Ricart, K, et al
Redox biology. 2023;63:102718
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Cardiovascular (CV) disease is the leading cause of death in the United States. Out of all ethnic groups, CV disease is particularly common in black Americans. High blood pressure (BP) is one of the main contributors to CV disease, and black Americans exhibit a disproportionally higher incident rate of high BP when compared to other ethnic groups. Partly this is due to genetic and physiological differences, yet is also influenced by social, socioeconomic, and environmental factors. One physiological difference that may contribute to higher BP in black adults appears to be a reduced availability of nitric oxide (NO). NO is a gas that is abundant in the human body. It regulates vascular tone and elasticity of the arteries, and therefore helps to manage blood pressure. Nitrates that occur in foods can be converted to NO and thus contribute to NO levels in the body. Beetroot juice (BRJ) is rich in nitrates. This study examined whether BRJ supplementation can reduce resting BP and cardiovascular reactivity in adults. The randomized, placebo-controlled, crossover-design study was completed by 18 black and 20 white young adults, male and female, with an average age of 21. The study monitored heart rate, BP and arterial stiffness in a variety of settings. The study also assessed socioeconomic status, perceived discrimination, sleep and dietary intake. The main findings from this investigation were that despite young black adults having higher resting BP, acute BRJ supplementation reduced the pressure to a similar extent in young black and white adults, but primarily in males. This reduction correlated with increased levels of circulating nitrites. However, acute BRJ supplementation did not influence resting arterial stiffness. The result also highlighted previously seen racial differences relating to social determinants of health and lifestyle, which may contribute to the elevated BP values seen in black participants. The study demonstrated that dietary nitrate from beetroot juice has the potential to be a cost-effective blood pressure-lowering strategy for young black and white males. Yet the findings also highlighted the complex interplay of social, lifestyle, and underlying physiological factors that influence racial differences when it comes to CV health
Abstract
A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.
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The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial.
Moore, AE, Dulnoan, D, Voong, K, Ayis, S, Mangelis, A, Gorska, R, Harrington, DJ, Tang, JCY, Fraser, WD, Hampson, G
Archives of osteoporosis. 2023;18(1):83
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Osteoporosis is the most common bone disease leading to weakening of the bones and is particularly prevalent in postmenopausal women. Osteoporosis-related fractures cause severe pain and disability, and strains on the healthcare systems. The typical treatment in postmenopausal osteoporosis involves the prescription of oral bisphosphonate medications. An important regulator in bone health is Vitamin K. Low vitamin K levels and intake are linked to reduced bone mineral density (BMD) and increased fractures. Some findings suggest that a combination treatment of bisphosphonate and vitamin K2 (MK-4) may enhance treatment efficacy and hence this randomised placebo-controlled trial sought further evidence. The study enrolled 105 women, between 55–85 years old, with osteoporosis and low vitamin K status. The women received either vitamin K1 (1 mg/day), vitamin K2 arm (MK-4; 45 mg/day) or a placebo for 18 months, alongside oral bisphosphonate and calcium and/or vitamin D treatment. Outcomes were measured in bone mineral density (BMD), structural characteristics of the hips (hip geometry) and bone turnover markers (BTMs). 91 candidates completed the trial. The results showed that the combination of vitamin K1 or MK-4 and oral bisphosphonate did not lead to significant improvement in bone mineral density or bone turnover. However it showed significant changes in hip geometry in the vitamin K1 group, suggesting a potential synergy here. Whereby there were positive trends in BMD too with vitamin K1 supplementation, the results did not reach significance. In the discussion the authors review the outcomes in the context of existing research, suggesting that perhaps a longer duration of treatment with vitamin K may be required to boost mineralisation and BMD outcomes. The effect of MK-4 on bone cells may also have been hindered by its poor bioavailability and the suppression of bone remodelling caused by long-term bisphosphonate therapy. Larger and longer-term studies are needed to confirm the effects of Vitamin K on hip remodelling and prevention of bone fractures and help clarify the mixed results in existing research.
Abstract
UNLABELLED This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION The study was registered at Clinicaltrial.gov:NCT01232647.
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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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Plain language summary
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 2-year exercise training on neuromuscular system health in older individuals with low muscle function.
Monti, E, Tagliaferri, S, Zampieri, S, Sarto, F, Sirago, G, Franchi, MV, Ticinesi, A, Longobucco, Y, Adorni, E, Lauretani, F, et al
Journal of cachexia, sarcopenia and muscle. 2023;14(2):794-804
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Ageing is accompanied by a progressive decline in muscle mass and functionality, associated with an increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality, possibly leading to a clinical syndrome known as sarcopenia. Among the causes of sarcopenia, motoneuron and neuromuscular junction (NMJ) degeneration have been proposed as key determinants. The aim of this study was to investigate the effects of a 2-year multimodal training intervention involving aerobic, strength and balance exercises on muscle mass and function, motoneuronal and NMJ health in a population of older individuals classified as sarcopenic. This study was a randomised controlled trial which enrolled 45 sarcopenic participants (34 females and 11 males) who were randomly assigned to one of the two groups: intervention or control group. Results show that the 2-year multimodal training intervention seemingly preserved NMJ stability, preventing serum C-terminal agrin fragment (CAF) [a biomarker of muscle wasting and weakness] concentration rise in the intervention group, although this biomarker increased significantly only in the control group. Conversely, neurofilament light chain (NfL) [clinical biomarker of many neurodegenerative diseases] concentration did not change in either group. Finally, improvements of physical performance were correlated with changes of serum biomarkers of NMJ stability. Authors conclude that a 2-year multimodal training intervention including aerobic, strength and balance exercises is effective for preventing CAF concentration increments, suggesting a positive effect on NMJ stability.
Abstract
BACKGROUND Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. METHODS Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. RESULTS At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (-8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. CONCLUSIONS The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.