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Effects of Wholegrain Compared to Refined Grain Intake on Cardiometabolic Risk Markers, Gut Microbiota, and Gastrointestinal Symptoms in Children: A Randomized Crossover Trial.
Madsen, MTB, Landberg, R, Nielsen, DS, Zhang, Y, Anneberg, OMR, Lauritzen, L, Damsgaard, CT
The American journal of clinical nutrition. 2024;119(1):18-28
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High consumption of wholegrain foods has been linked to a lower risk of cardiovascular disease (CVD) and type 2 diabetes. Some trials have shown benefits to body weight, blood lipids and glucose homeostasis but most of these studies are with adults. Cardiometabolic disease begins in childhood therefore data is needed for this age group to back up dietary recommendations in order to prevent later development of cardiometabolic disease. The aim of this randomized crossover trial was to look at the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL), cholesterol and plasma insulin, other cardiometabolic markers, body composition, the composition of the gut microbiome and gastrointestinal symptoms in children with high body mass index (BMI). 55 healthy Danish children (aged 8 – 13) took part. They ate wholegrain oats and rye (WG) or refined grain products (RG) ad libtum for 8 weeks in random order. Measurements were taken at 0, 8 and 16 weeks. Compared with RG, WG reduced LDL cholesterol as well as total:high-density lipoprotein cholesterol and triacylglycerol. WG also modulated the abundance of specific types of gut bacteria, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. This study supports the recommendation to swap refined grain for wholegrain oats and rye in children. Further studies are needed.
Abstract
BACKGROUND Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. OBJECTIVES This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). METHODS In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye ("WG") or refined grain ("RG") products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). RESULTS Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: -0.24, -0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. CONCLUSION High intake of wholegrain oats and rye reduced LDL cholesterol and triacylglycerol, modulated bacterial taxa, and increased beneficial metabolites in children. This supports recommendations of exchanging refined grain with wholegrain oats and rye among children. This trial was registered at clinicaltrials.gov as NCT04430465.
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Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials.
Shu, Q, Kang, C, Li, J, Hou, Z, Xiong, M, Wang, X, Peng, H
PloS one. 2024;19(1):e0296733
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The gut microbiome is thought to play a role in thyroid disorders, mediated by regulating iodine uptake, degradation and enterohepatic cycling of thyroid hormones, and differences in microbiome composition between patients with thyroid disorders and healthy individuals have been observed. The aim of this systematic review and meta-analysis was to evaluate the effect of pro-, pre- and synbiotics on thyroid function (thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) and thyroid stimulating hormone receptor antibody (TRAb)) in patients with and without thyroid disorders. 8 randomised controlled trials including 367 participants were included in the review and meta-analysis. Neither pro-, pre- nor synbiotics had a significant effect on TSH, fT4 or fT3 but pre- and probiotics lead to a significant reduction in TRAb in patients with Graves’ disease.
Abstract
BACKGROUND Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels. METHODS We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement. RESULTS A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: -0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: -0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: -0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found. CONCLUSIONS Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves' disease.
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Effects of Spirulina supplementation in patients with ulcerative colitis: a double-blind, placebo-controlled randomized trial.
Moradi, S, Bagheri, R, Amirian, P, Zarpoosh, M, Cheraghloo, N, Wong, A, Zobeiri, M, Entezari, MH
BMC complementary medicine and therapies. 2024;24(1):109
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Ulcerative colitis (UC) is a form of inflammatory bowel disease, that may be caused by genetic variations in the gut microbiome, immune dysregulation, and environmental influences. Symptoms include diarrhoea, constipation, cramping, joint pain, bleeding, and anaemia. Inflammation is a direct driver of UC, which if controlled may be of benefit to the individual. Spirulina, which is a species of seaweed, has been shown to have anti-inflammatory properties and this randomised control trial aimed to determine the effects of its supplementation on 80 individuals with UC and associated health outcomes. The results showed that 8-weeks of Spirulina supplementation significantly increased antioxidant capacity compared to placebo. However, an assessment of quality of life and level of disease showed no improvements with Spirulina supplementation. It was concluded that Spirulina supplementation for 8-weeks improved antioxidant status, but it did not affect severity of disease or quality of life. This study could be used by healthcare professionals to understand that Spirulina supplementation for 8-weeks can improve inflammation. However, it would be interesting to see longer studies to determine if this would affect disease status if supplemented for a longer period of time.
Abstract
AIM: We conducted a randomized placebo-controlled trial to assess the efficacy of Spirulina (SP) supplementation on disease activity, health-related quality of life, antioxidant status, and serum pentraxin 3 (PTX-3) levels in patients with ulcerative colitis (UC). METHODS Eighty patients with UC were randomly assigned to consume either 1 g/day (two 500 mg capsules/day) of SP (n = 40) or control (n = 40) for 8 weeks. Dietary intakes, physical activity, disease activity, health-related quality of life, antioxidant status, erythrocyte sedimentation rate (ESR), and serum PTX-3 levels were assessed and compared between groups at baseline and post-intervention. RESULTS Seventy-three patients (91.3%) completed the trial. We observed increases in serum total antioxidant capacity levels in the SP supplementation group compared to the control group after 8 weeks of intervention (p ≤ 0.001). A within-group comparison indicated a trend towards a higher health-related quality of life score after 8 weeks of taking two different supplements, SP (p < 0.001) and PL (p = 0.012), respectively. However, there were no significant changes in participant's disease activity score in response to SP administration (p > 0.05). Similarly, changes in ESR and PTX-3 levels were comparable between groups post-intervention (p > 0.05). CONCLUSIONS SP improved antioxidant capacity status and health-related quality of life in patients with UC. Our findings suggest that SP supplementation may be effective as an adjuvant treatment for managing patients with UC. Larger trials with longer interventions periods are required to confirm our findings.
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Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review.
Alkurd, R, Mahrous, L, Zeb, F, Khan, MA, Alhaj, H, Khraiwesh, HM, Faris, ME
Medicina (Kaunas, Lithuania). 2024;60(1)
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Brain-derived neurotrophic factor (BDNF) is a protein that plays a crucial role in brain development, cognition and metabolism. Intermittent fasting (IF) is a promising therapeutic strategy for managing metabolic disorders and improving cognitive function. Therefore, this systematic review of sixteen experimental and observational studies investigated the effect of IF on BDNF production and improvements in cognition through the BDNF pathway in healthy adults and people with metabolic disorders. Included studies focused on different IF regimens such as calorie restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE) and Ramadan model of intermittent fasting (RIF) Future, well-controlled, long-term, robust studies are required to assess the effect of different IF regimens on the production of BDNF and cognitive function in people with metabolic disorders, as the current research is inconclusive. However, healthcare professionals can use the review to understand the potential beneficial effects of IF on cognition and metabolic health in humans.
Abstract
Background: The potential positive interaction between intermittent fasting (IF) and brain-derived neurotrophic factor (BDNF) on cognitive function has been widely discussed. This systematic review tried to assess the efficacy of interventions with different IF regimens on BDNF levels and their association with cognitive functions in humans. Interventions with different forms of IF such as caloric restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE), and the Ramadan model of intermittent fasting (RIF) were targeted. Methods: A systematic review was conducted for experimental and observational studies on healthy people and patients with diseases published in EMBASE, Scopus, PubMed, and Google Scholar databases from January 2000 to December 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statements (PRISMA) for writing this review. Results: Sixteen research works conducted on healthy people and patients with metabolic disorders met the inclusion criteria for this systematic review. Five studies showed a significant increase in BDNF after the intervention, while five studies reported a significant decrease in BDNF levels, and the other six studies showed no significant changes in BDNF levels due to IF regimens. Moreover, five studies examined the RIF protocol, of which, three studies showed a significant reduction, while two showed a significant increase in BDNF levels, along with an improvement in cognitive function after RIF. Conclusions: The current findings suggest that IF has varying effects on BDNF levels and cognitive functions in healthy, overweight/obese individuals and patients with metabolic conditions. However, few human studies have shown that IF increases BDNF levels, with controversial results. In humans, IF has yet to be fully investigated in terms of its long-term effect on BDNF and cognitive functions. Large-scale, well-controlled studies with high-quality data are warranted to elucidate the impact of the IF regimens on BDNF levels and cognitive functions.
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Transform-Us! cluster RCT: 18-month and 30-month effects on children's physical activity, sedentary time and cardiometabolic risk markers.
Salmon, J, Arundell, L, Cerin, E, Ridgers, ND, Hesketh, KD, Daly, RM, Dunstan, D, Brown, H, Della Gatta, J, Della Gatta, P, et al
British journal of sports medicine. 2023;57(5):311-319
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Regular physical activity is beneficial to children’s physical, social and mental health. However, most children fail to meet the recommended 60+ min of moderate-intensity to vigorous-intensity physical activity every day. The Transform-Us! school-based and home-based intervention was developed to determine the impact of strategies to promote children’s moderate-to-vigorous physical activity versus reduce sedentary behaviour or a combination of these strategies, on behavioural and health outcomes. The main aim of this study was to determine the efficacy of the independent and combined intervention approaches to promoting physical activity and reducing sedentary behaviour on children’s moderate-to-vigorous physical activity and sedentary time after 18 and 30 months compared with usual practice. This study is a 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools with additional home intervention components. After recruitment, schools were then randomly allocated to one of four groups. Results show that Transform-Us! had stronger effects on children’s sedentary behaviour than physical activity in both the physical activity (PA) and sedentary behaviour (SB) interventions, and there were beneficial effects on children’s adiposity for both intervention approaches. However, no clear conclusions could be drawn regarding which intervention (PA or SB) had the strongest or more consistent effects on children’s health outcomes. Authors conclude that, based on their findings, government education departments and schools should consider adopting and implementing whole-of-school programmes to promote children’s physical activity and reduce sitting through active pedagogy and supportive social and physical environments at school and home to benefit children’s sedentary time and some markers of cardiometabolic health.
Abstract
OBJECTIVE To test the efficacy of the Transform-Us! school- and home-based intervention on children's physical activity (PA), sedentary behaviour (SB) and cardiometabolic risk factor profiles. METHODS A 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools (148 Year 3 classes) in Melbourne, Australia (2010-2012), that used pedagogical and environmental strategies to reduce and break up SB, promote PA or a combined approach, compared with usual practice. Primary outcomes (accelerometry data; n=348) were assessed at baseline, 18 and 30 months. Secondary outcomes included body mass index (BMI) and waist circumference (WC) (n=564), blood pressure (BP) (n=537) and biomarkers (minimum n=206). Generalised linear mixed models estimated the interactive effects of the PA and SB interventions on the outcomes. If there was no interaction, the main effects were assessed. RESULTS At 18 months, there were intervention effects on children's weekday SB (-27 min, 95% CI: -47.3 to -5.3) for the PA intervention, and on children's average day PA (5.5 min, 95% CI: 0.1 to 10.8) for the SB intervention. At 30 months, there was an intervention effect for children's average day SB (-33.3 min, 95% CI: -50.6 and -16.0) for the SB intervention. Children's BMI (PA and SB groups) and systolic BP (combined group) were lower, and diastolic BP (PA group) was higher. There were positive effects on WC at both time points (SB intervention) and mixed effects on blood parameters. CONCLUSIONS The Transform-Us! PA and SB interventions show promise as a pragmatic approach for reducing children's SB and adiposity indicators; but achieving substantial increases in PA remains challenging. TRIAL REGISTRATION ISRCTN83725066; ACTRN12609000715279.
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The Effect of Selenium Supplementation on Clinical Outcomes, Metabolic Profiles, and Pulsatility Index of the Uterine Artery in High-Risk Mothers in Terms of Preeclampsia Screening with Quadruple Test: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial : Selenium and preeclampsia.
Mesdaghinia, E, Shahin, F, Ghaderi, A, Shahin, D, Shariat, M, Banafshe, H
Biological trace element research. 2023;201(2):567-576
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Preeclampsia (PE) is a disease related to high blood pressure during pregnancy, which can result in birth complications and even death of the mother and/or infant. Selenium, which is a nutrient derived from the diet is involved in several processes within the body and levels have shown controversial relationships with PE. This randomised control trial of 60 individuals aimed to determine the effects of selenium supplementation for 12 weeks in women at high risk of PE. The results showed that selenium supplementation helped to alleviate inflammation, which is associated with PE. It also helped to improve blood flow to the uterus, sleep quality, depression, and feelings of anxiety. It was concluded that selenium supplementation for 12 weeks in pregnant women at an increased risk of PE had beneficial effects on factors which may contribute to PE. This study could be used by healthcare professionals to understand that nutrient deficiencies may be involved in poorer outcomes during pregnancy and the importance of recommending a nutrient dense diet and pregnancy vitamins which contain adequate amounts of selenium.
Abstract
Data on the effects of selenium (Se) supplementation on clinical outcomes, metabolic profiles, and pulsatility index (PI) in high-risk mothers in terms of preeclampsia (PE) screening with quadruple tests are scarce. This study evaluated the effects of Se supplementation on clinical outcomes, metabolic profiles, and uterine artery PI on Doppler ultrasound in high-risk mothers in terms of PE screening with quad marker. The current randomized, double-blind, placebo-controlled trial was conducted among 60 high-risk pregnant women screening for PE with quad tests. Participants were randomly allocated into two groups (30 participants each group), received either 200 µg/day Se supplements (as Se amino acid chelate) or placebo from 16 to 18 weeks of pregnancy for 12 weeks. Clinical outcomes, metabolic profiles, and uterine artery PI were assessed at baseline and at the end of trial. Se supplementation resulted in a significant elevation in serum Se levels (β 22.25 µg/dl; 95% CI, 18.3, 26.1; P < 0.001) compared with the placebo. Also, Se supplementation resulted in a significant elevation in total antioxidant capacity (β 82.88 mmol/L; 95% CI, 3.03, 162.73; P = 0.04), and total glutathione (β 71.35 µmol/L; 95% CI, 5.76, 136.94; P = 0.03), and a significant reduction in high-sensitivity C-reactive protein levels (β - 1.52; 95% CI, - 2.91, - 0.14; P = 0.03) compared with the placebo. Additionally, Se supplementation significantly decreased PI of the uterine artery in Doppler ultrasound (β - 0.09; 95% CI, - 0.14, - 0.04; P = 0.04), and a significant improvement in depression (β - 5.63; 95% CI, - 6.97, - 4.28; P < 0.001), anxiety (β - 1.99; 95% CI, - 2.56, - 1.42; P < 0.001), and sleep quality (β - 1.97; 95% CI, - 2.47, - 1.46; P < 0.001). Se supplementation for 12 weeks in high-risk pregnant women in terms of PE screening with quad marker had beneficial effects on serum Se level, some metabolic profiles, uterine artery PI, and mental health. IRCT Registration: htpp:// www.irct.ir ; identifier IRCT20200608047701N1.
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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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Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
Li, S, Yin, S, Ding, H, Shao, Y, Zhou, S, Pu, W, Han, L, Wang, T, Yu, H
Cell proliferation. 2023;56(1):e13346
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Multiple risk factors could lead to the development of liver cancer, one of the most common malignant tumours in the world. These risk factors include hepatitis infection, non-alcoholic fatty liver disease and excessive alcohol consumption. Polyphenols are bioactive compounds with antioxidant, anti-inflammatory, anti-mutagenic, anti-viral, hypoglycaemic, anti-hypertensive, antibacterial and anti-proliferative properties. Polyphenols may be effective in reducing the risk of developing liver cancer by altering the metabolism. This review evaluated the effectiveness of polyphenols in protecting the liver and inhibiting hepatocarcinoma development. In addition, the review evaluated several mechanisms by which polyphenols affect glucose and lipid metabolism and mitochondrial metabolism and reduce the effects of oxidative stress, inflammation and toxic metabolites. Further robust studies are required to assess the beneficial effects of polyphenols as a therapeutic agent, as the current knowledge is limited. However, healthcare professionals can use the results of this study to understand the protective effects of polyphenols against liver disease.
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
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Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-kB dependent manner: Results from the ATTACH-study a randomized, controlled, crossover trial in healthy subjects.
Mostafa, H, Behrendt, I, Meroño, T, González-Domínguez, R, Fasshauer, M, Rudloff, S, Andres-Lacueva, C, Kuntz, S
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;158:114076
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Pancreatic cancer is commonly associated with poor prognosis and low overall five-year survival rate (5–7%) due to the early metastatic potential of pancreatic cancer cells. Strategies to improve the health outcomes in pancreatic cancer are challenging. The aims of this study where to investigate: - whether plasma metabolites, isolated after a 28-day intervention, would reduce migration of two pancreatic cancer cell lines (PANC-1 and AsPC-1); - whether expression of adhesion molecules on cancer and endothelial cells were influenced by plasma anthocyanins (ACN) metabolites; - which molecular mechanisms were involved; and - which metabolites in plasma and urine were altered during a long-term ACN intake and how they associate with the inhibitory effects on migration. This study is a randomised, double-blind, placebo-controlled, cross-over, 28-days intervention - ATTACH study (Anthocyanins Target Tumor cell Adhesion—Cancer vs. Endothelial Cell (HUVEC)). Thirty-five (female n = 27 and male n = 8) young, healthy volunteers participated in the intervention. Results show that ACN and metabolites isolated from plasma after a long-term ACN-rich juice intervention reduced the migration and expression of cell adhesion molecules in PANC-1 cancer cells in vitro through activation of two pathways [focal adhesion kinase- and nuclear factor kappa light chain enhancer of activated B cells (NF-kB)-pathways] as well as the reduction of reactive oxygen species. Authors conclude that their findings can lead to the investigation of interactions of ACNs with classical cancer prevention strategies.
Abstract
Pancreatic cancer is primarily considered to be a metastatic disease with a low 5-year survival rate. We aimed to detect if plasma-isolated anthocyanins and their metabolites (PAMs) modulate pancreatic cancer cells migration and to describe molecular targets of PAMs in this process. Plasma metabolites were isolated by solid-phase extraction before and after a 28-days intervention trial involving 35 healthy subjects comparing effects of a daily anthocyanin-rich juice intake vs. placebo. Plasma extracts were used for migration and mechanistic in vitro studies as well as for metabolomic analysis. Pancreatic PANC-1 and AsPC-1 were used for migration studies in a Boyden chamber co-cultured with endothelial cells. Expression of adhesion molecules on cancer and endothelial cells were determined by flow cytometry and NF-kB (nuclear factor-kappa B) p65 and focal adhesion kinase activation were measured by immunoassays. UHPLC-MS/MS metabolomics was done in plasma and urine samples. Plasma extracts isolated after the intake of the anthocyanin-rich juice significantly reduced PANC-1 migration, but not AsPC-1 migration. In PANC-1, and to a lower extent in endothelial cells, plasma extracts after juice intake decreased the expression of ß1- and ß4-integrins and intercellular adhesion molecule-1. Pooled plasma from volunteers with the highest inhibition of PANC-1 migration (n = 10) induced a reduction of NF-kB-p65 and FAK-phosphorylation in cancer and in endothelial cells. Concerning metabolites, 14 were significantly altered by juice intervention and PANC-1 migration was inversely associated with the increase of o-coumaric acid and peonidin-3-galactoside. PAMs were associated with lower PANC-1 cell migration opening new strategies for metastatic pancreatic cancer treatment.
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Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.
Muehlenbein, M, Gassen, J, Nowak, T, Henderson, A, Morris, B, Weaver, S, Baker, E
American journal of men's health. 2023;17(2):15579883221130195
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Plain language summary
A growing body of research finds that in men, testosterone levels may be prognostic of clinical outcomes related to coronavirus disease 2019 (COVID-19 disease). The presence of pre-existing chronic conditions in many patients with COVID-19 disease further complicates the relationship among testosterone and severe outcomes. The aim of this study was to examine whether pre-existing conditions for severe COVID-19 disease were related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This study obtained data from men (n = 142) who participated in the longitudinal study Waco COVID Survey. All data included in the study was collected as part of the initial intake survey and first laboratory appointment. Results show that serum-free testosterone levels decreased as a function of age. In fact, greater burden of pre-existing conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. Furthermore, in men older than 40 years of age the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Authors conclude that their findings add important insights into the complex role of androgens in chronic and infectious diseases and contribute to the growing body of literature on the relationship between chronic disease and men’s testosterone levels.
Abstract
Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.