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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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Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study.
Ma, T, Yang, N, Xie, Y, Li, Y, Xiao, Q, Li, Q, Jin, H, Zheng, L, Sun, Z, Zuo, K, et al
Pharmacological research. 2023;191:106755
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Chronic constipation (CC) is a common gastroenterological problem encountered in clinical practice, and it negatively impacts patients’ quality of life. Growing evidence indicates that the occurrence of CC is closely linked to gut dysbiosis. Several main probiotics have been used to relieve constipation. The main aim of this study was to systematically evaluate the beneficial effects of Lactiplantibacillus plantarum P9 (P9) administration on alleviating CC and impact on the host gut microbiota and its metabolites. This study was a 42-day longitudinal double-blind randomised controlled trial which enrolled a total of 181 patients with CC. Subjects were randomly assigned to the probiotic or placebo group. Subjects in P9 group received one sachet of P9 powder per day after meal. Results show that P9 administration significantly improved patients’ defecation frequency. In fact, P9 administration effectively alleviated constipation, and the symptom relief effects were linked to desired changes and interactions with different types of host microbes. Authors conclude that administering P9 could effectively relieve chronic constipation in adults and improve some aspects of their quality of life.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study suggested that P9-associated constipation symptom relief was not attributed to macroscopic changes in the host gut bacteriome and phageome
- However, results supported that taking P9 could alleviate constipation, with the symptom relief effects linked to desired changes and interactions with different types of host microbes, including the gut commensal bacteria (L. plantarum, Ruminococcus_B gnavus, Oscillospiraceae sp., Lachnospiraceae sp.) and the bacteriophage family, Herelleviridae.
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
This study investigated the effect of a specific probiotic strain in alleviating Chronic Constipation (CC).
Methods
- The study employed a 42-day randomised control trial (RTC) double-blind, placebo-controlled design, with 163 patients, (mean age =22.68 ±5.66 years for the probiotic group and 21.59 ±4.59 years for the placebo group), diagnosed with CC (Rome IV criteria)
- The male to female ratio was 15–63 and 17–68 in probiotic and placebo groups respectively
- Groups were standardised with no differences observed in baseline age, gender ratio, drug treatment, high-fibre diet and smoking between the two groups (P >0.18)
- Participants were randomly assigned to the probiotic Lactiplantibacillis plantarum P9 (n=78; 2 g per sachet, 1 ×1011 CFU/day) or the placebo (n =85; maltodextrin powder) groups.
Results
Primary outcomes: weekly mean complete spontaneous bowel movements (CSBMs):
- At 28-days CSBM was 28% higher in the P9 group (P=0.039) compared with the placebo group
- At 42-days CSBM remained significantly higher in the P9 group (P=0.026) compared with the placebo group, and increased 2-fold compared with baseline (P <0.05)
- Authors noted that the CSBM benefits were maintained even after 14 days of not taking the supplement.
Secondary outcomes: The effects of P9 supplementation on constipation-related parameters, including the weekly mean frequency of spontaneous bowel movements (SBMs) demonstrated:
- After 28-days of P9 supplementation, SBMs were 12% higher than the placebo group (P=0.039)
- No differences were observed in the weekly mean stool consistency and straining scores between groups (P>0.05).
Patients’ quality of life and psychological state, using a PAC-QOL questionnaire related to: worries and concerns (WO), physical discomfort, psychosocial discomfort, and satisfaction and found:
- At day 14 WO in the P9 group was 1.22-fold lower than those in the placebo group (P <0.05)
- No differences in the other 3 items between P9 and placebo groups (P >0.05) were observed
- Supplementation resulted in a significant change in relative abundance of the P9 genome (≥0.01%)
- However, no differences were observed in alpha diversity after P9 consumption compared with placebo.
Conclusion
- The results indicated that P9 administration alleviated patients’ constipation symptoms and improved their quality of life but did not impact on gut bacteria or phageome
- Lactiplantibacillis plantarum P9 supplementation impacted several beneficial bacteria species (e.g. (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), and reduced levels of other bacteria and phage taxa (e.g. Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae) which may be implicated in constipation relief mechanisms.
Clinical practice applications:
- In this study, the use of P9 administration significantly improved patients’ defecation frequency which could have beneficial implications for patients suffering from chronic constipation
- Probiotic effects are known to be strain- and host-specific, and based on this study P9 administration for relief of constipation needs to be taken for at least two weeks to improve aspects of patients’ quality of life and 4 weeks for improvements in constipation.
Considerations for future research:
- Future trials should include factors that impact gut motility and constipation symptoms, such as: a detailed daily diet (dietary composition, fibre content, and water intake) and physical activity scale (intensity and duration), and longer term use of P9 or comparison across strains
- The relatively small study size and short duration of this study, as well as the younger age groups included may be pertinent when considering future research.
Abstract
Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients' quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects' gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.
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Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.
Katayoshi, T, Uehata, S, Nakashima, N, Nakajo, T, Kitajima, N, Kageyama, M, Tsuji-Naito, K
Scientific reports. 2023;13(1):2786
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Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that plays a crucial role in energy metabolism and different biological processes. Sirtuins (SIRT1) are NAD+-dependent deacetylases, an enzyme that plays a key role in enhancing metabolic efficiency. Nicotinamide mononucleotide (NMN) is a precursor to NAD+. NMN supplementation may help to reduce the risk of developing metabolic diseases and cardiovascular diseases. This randomised, double-blinded, and placebo-controlled, parallel trial investigated the effects of 12 weeks of 125 mg NMN supplementation on metabolic health parameters, including CVD risk factors, blood NAD+ metabolites level, and SIRT1 expression in middle-aged men and women. Serum nicotinamide was significantly higher and arterial stiffness was lower in the NMN test group of middle-aged men and women after 12 weeks of NMN supplementation. The results of the study indicate that the administration of 250mg of nicotinamide mononucleotide (NMN) daily for an extended period is considered safe and well-tolerated. Healthcare professionals can use this finding to understand the significant implications of the use of NMN as a potential therapeutic agent in individuals seeking to improve their metabolic and cardiovascular health. Further robust studies are required to evaluate the effects of NMN supplementation due to the limitations and high baseline variability between the participants of this study.
Expert Review
Conflicts of interest:
None
Take Home Message:
- As we age, NAM levels decline, which could have a negative effect on cardiovascular health.
- Middle-aged adults may like to consider NMN supplementation to improve NAM metabolism and arterial stiffness.
- However, without data on CVD events, it is difficult to determine actual risk reductions.
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
- Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in metabolism. When we age, NAD+ levels decline resulting in poorer metabolism and age-related disease such as cardiovascular disease (CVD). Nicotinamide mononucleotide (NMN) is a precursor in the biosynthesis of NAD+.
- This double-blind, randomised control trial aimed to determine the effect of supplementing NMN on NAD+ levels, CVD risk factors and sirtuin 1 (SIRT1) expression, which relies on NAD+ for adequate functioning.
Methods
- 36 healthy male and female individuals aged between 40-65 years of age were assigned to either NMN (125mg/day) or placebo for 12 weeks.
- One capsule was taken twice per day after meals.
- Serum nicotinamide (NAM), NAD+, NMN, advanced glycation end products (AGES), 8-hydroxydeoxyguanosine (8-OHdG) and SIRT1 mRNA expression were measured.
- The condition of blood vessels (arterial stiffness) was also assessed using the ankle brachial index (ABI).
- In a sub-analysis, individuals with hypertension, above average body mass index (BMI), or blood glucose level were also assessed for blood vessel condition using the ABI.
Results
- The results showed that from baseline serum NAM decreased in the placebo group (P=0.014), whereas it increased in the NMN group (P=0.006). This resulted in an increase in the NMN group compared to placebo (P=0.037).
- Interestingly serum NAM was lower in the NMN group compared to placebo at baseline (P=0.001).
- There was no statistically significant difference in ABI with NMN supplementation.
- Amongst those with hypertension there was also no change in ABI. However, those with high BMI or blood glucose, there was an improvement in vascular condition compared to placebo (P=<0.007 and P=0.019 respectively).
- 8-OHdG, SIRT1 mRNA and AGEs remained unchanged by NMN supplementation
Conclusion
- NMN supplementation enhanced NAD+ metabolism in middle-aged adults.
- It also relieved arterial stiffness and reduced CVD risk factors.
Clinical practice applications:
- Apparently healthy middle-aged adults who would like to activate NAD metabolism and decrease their risk for CVD, should consider 12-week supplementation with NMN (125mg/day).
- ABI should be monitored to ensure desired effects.
- It is unclear as to the effects of NMN supplementation after 12-weeks.
Considerations for future research:
- Future research should consider longer supplementation duration and/or adding in a follow-up period to determine duration of effect.
- Different supplemental doses should also be researched to determine an optimal dose.
Abstract
Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.
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Polyphenol supplementation and executive functioning in overweight and obese adults at risk of cognitive impairment: A systematic review and meta-analysis.
Farag, S, Tsang, C, Murphy, PN
PloS one. 2023;18(5):e0286143
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It is recognised that overweight and obesity pose an increased risk for the development of cardiometabolic disease, and increasing evidence indicates a link to cognitive impairment associated with early onset dementia in such populations. This study's aim was to elaborate on existing knowledge of the effectiveness or otherwise of polyphenols in general to improve executive function (EFs) in an obese/ overweight population at risk of cognitive impairment. This study was a systematic review and meta-analysis of twenty-three randomised controlled trials. Results showed a nonsignificant effect of polyphenols on EFs. Authors concluded that further research should consider investigating polyphenols supplementation in a younger population at risk of cognitive impairment.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Overweight and obesity have increasing evidence that indicates a link to compromised executive functions such as memory and decision-making processes and cognitive impairment
- This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations with a susceptibility to cognitive impairment.
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:
A systematic review and meta-analysis were undertaken to investigate the impact of polyphenol supplementation on executive functions (cognitive functions which constitute part of the working memory and decision-making processes) among overweight and/or obese populations.
Method:
A comprehensive literature search was conducted using four electronic databases: PubMed/Medline, PsycInfo, Scopus and the Cochrane Trials Library. Inclusion criteria encompassed primary research studies which investigated the impact of polyphenols versus placebo on executive function in overweight or obese adults.
The review comprised a total of 23 randomised controlled trials (RCTs), incorporating a participant pool of N = 1,976 individuals. The mean ages of participants in all 23 studies receiving polyphenol supplementation were 62.92 years (SD = 8.06 years) and the mean BMIs ranged from 25.5 kg/m2 to 33.7 kg/m2. Various dietary polyphenols were investigated in the studies, with the main groups being isoflavones, flavonoids, resveratrol, phenolic acid, curcumin, walnuts and blueberry powder.
- The JADAD scale was employed to assess the methodological quality of the incorporated studies
- Hedges g, accompanied by 95% confidence intervals (CI) for endpoints, was computed utilising a random effects model whenever applicable
- Various statistical methods were considered for potential application in evaluating publication bias
- Sensitivity analysis was conducted to assess the robustness of the obtained results.
Results
- Meta analysis of the 23 primary studies produced a non-significant effect of polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170)
- A double-blind, randomised, placebo-controlled parallel study reported significant benefits in 60 participants (mean age 67 years) taking 80mg of curcumin over placebo for digital vigilance and serial subtraction tasks (p=0.041)
- A double-blind, randomised, placebo-controlled parallel intervention trial showed significant benefits in 79 patients (mean age of 61 years) taking 150mg of resveratrol for visuospatial working memory double span and trail making test (p= 0.012).
Conclusion:
This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations.
Clinical practice applications:
- Research has documented the association between compromised executive functions and obesity/overweight, emphasising neuroinflammation and oxidative stress as potential mechanisms
- A plausible intervention involves the utilisation of polyphenols, known for their antioxidant and anti-inflammatory properties
- This systematic review and meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions
- A potential beneficial impact for 80mg of curcumin and 150mg of resveratrol was revealed in younger populations (mean ages of 67 and 61 years).
Considerations for future research:
- A potential beneficial impact of 80mg of curcumin and 150mg of resveratrol supplementation was revealed in a younger population (mean ages of 67 and 61 years), highlighting the necessity for in-depth exploration in subsequent studies
- The diversity in tasks employed for assessing executive functions and the comprehensive reporting of the phenolic composition of supplements had limitations that warrant consideration in future research
- The exact constituent and dose of supplementation needs to be described as this is necessary for the identification of the potential beneficial compounds for cognitive health and to support clinical practice.
Abstract
BACKGROUND AND OBJECTIVES Increasing evidence indicates a link between obesity and cognitive impairment. Furthermore, there is limited literature regarding the effect of polyphenols, a plant derived compounds, on executive functioning in an overweight/obese population at-risk of cognitive impairment. The aim of the present systematic review and meta-analysis of randomized controlled trials is to examine the effect of polyphenol supplementation on executive functions in overweight and/or obese populations at risk of cognitive impairment. METHODS A comprehensive literature search was conducted from inception to March 2023 using four electronic databases: PubMed/Medline, PsycInfo, Scopus and Cochrane trials library. Published primary research studies in English that compared the effect of polyphenols with placebo on executive function in overweight/obese adults were considered eligible for the meta-analysis. Jadad scale was used for the methodological quality rating of the included studies. Hedges g with 95% confidence intervals (CI) for endpoints were calculated using random effect model where applicable. Rosenthal's Fail-safe N, funnel plots, the Begg and Mazumdar's rank correlation test (Kendall's S statistic P-Q), Egger's linear regression test, and Duval and Tweedie's trim-and-fill test were identified for potential use as appropriate, to examine publication bias. Sensitivity analysis was conducted to examine the robustness of the results. RESULTS AND CONCLUSION A total of 23 RCT studies involving N = 1,976 participants were included in the review. The results of the meta-analysis revealed a non-significant effect for polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170). Observations from primary studies within the meta-analysis showed a potential positive effect of polyphenol supplementation in a younger population at-risk of cognitive impairment and it is recommended to investigate this further in future studies. Moreover, the variability of the tasks used to examine executive functions as well as the adequate reporting of supplement's phenolic composition is a limitation that future work should also consider.
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5.
Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population.
Berding, K, Bastiaanssen, TFS, Moloney, GM, Boscaini, S, Strain, CR, Anesi, A, Long-Smith, C, Mattivi, F, Stanton, C, Clarke, G, et al
Molecular psychiatry. 2022
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Psychobiotic describe any exogenous intervention that leads to a bacterially mediated impact on the brain. Probiotics and prebiotics have shown promising results as psychobiotic agents in both animal and human studies. The aim of this study was to investigate the potential of a whole diet psychobiotic approach to modulate the microbiota composition and function, affect responses to and feelings of stress and improve mood in a healthy population. This study is a single-blind, randomized, controlled study which recruited healthy adult (male and female) participants with poor dietary habits, aged 18–59 years. Participants were block randomized (block of 4, stratified by gender) into either intervention or control group using randomly permuted blocks and were instructed to follow their respective diet for 4 weeks. Results show that a short term psychobiotic dietary intervention improved perceived stress in a healthy population, while eliciting specific metabolic changes in the gut microbiota. Authors conclude that underlying microbial influences need to be investigated and future preclinical experiments are required to explore causality and decipher mechanistic pathways.
Expert Review
Conflicts of interest:
None
Take Home Message:
Eating foods known to have a positive influence on gut microbial composition could elicit benefits in terms of reducing perceived stress and improving sleep quality.
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:
This RCT explored the impact of a psychobiotic diet, compared to a control diet, on perceived stress, sleep and gut microbiota.
A high psychobiotic diet is one high in prebiotic and fermented foods. In this study, a psychobiotic diet included daily recommended consumption and servings of the following:
- High prebiotic fruit & veg (6-8)
- Grains (5-8)
- Fermented foods (2-3)
- Legumes (3-4 per week)
Methodology:
- A single-blind, randomised, controlled study
- 45 healthy adults (18-59 years) with poor dietary habits
- Sample size determined by previous microbiome research - target not reached due to introduction of covid restrictrictions
- Active intervention (n=24) received dietitian advice to follow psychobitoic diet
- Control intervention (n=21) received dietitian advice largely based on the Irish Healthy Eating Guidelines food pyramid
- Intervention duration 4 weeks.
- Assessed on questionnaire measures of perceived stress and sleep, pre and post-intervention (no primary outcome defined)
- Shotgun microbiome analysis on stool samples, pre and post-intervention
Results:
- Perceived stress improved in the psychobiotic diet group
- Subjective sleep quality improved in the psychobiotic diet group
- Only subtle changes in microbial composition and function
- More stable microbiota throughout the study (regardless of diet) was correlated with greater changes in perceived stress
- Neither cortisol awakening response nor measured immune markers were affected by dietary intervention
Conclusions:
- Using a diet targeted to positively modulate gut-brain communication may have the potential for reducing stress and improving sleep
- Although improvements in stress were only observed for the intervention group – the post-intervention stress levels were not significantly different between the groups.
- Thus, we should interpret the results with some caution
Clinical practice applications:
- Providing advice on dietary intake of foods known to positively impact gut microbiota may be helpful for individuals affected by stress or sleep problems
- The inclusion of the following foods may be helpful:
- High prebiotic fruit & veg (6-8 per day)
- Grains (5-8 per day)
- Fermented foods (2-3 per day)
- Legumes (3-4 per week)
Considerations for future research:
- Important to replicate these results in a larger sample
- It might be helpful to investigate individual aspects of the diet separately, to assess their individual impact
- Objective measures of sleep (such as actigraphy recordings) might provide additionally useful findings
- It would be interesting to explore the effect of the psychobiotic diet in other conditions
- Chronobiology or chrononutrition - i.e. looking at timing of the foods proposed in the section above
Abstract
The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.
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6.
Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity.
Al-Shaer, AE, Regan, J, Buddenbaum, N, Tharwani, S, Drawdy, C, Behee, M, Sergin, S, Fenton, JI, Maddipati, KR, Kane, S, et al
The Journal of nutrition. 2022;152(7):1783-1791
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Specialised pro-resolving mediators (SPMs) are highly potent oxylipins [metabolites] synthesized from omega-3 and omega-6 polyunsaturated fatty acids. SPMs have a critical role in resolving inflammation and returning damaged tissues to homeostasis. The main aim of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. This study is a non-randomised uncontrolled clinical trial in adults with obesity. Twenty-three participants (n = 13 females, 10 males) aged between 50–65 years were enrolled. Only postmenopausal females were included in order to reduce confounding effects of oestrogen on lipid metabolism during supplementation. Results show that: - the marine oil supplement significantly increased some oxylipins of the SPM biosynthetic pathway. - there wasn’t an increase in the concentration of D-series resolvins upon intervention, although several docosahexaenoic acid-derived metabolites were increased. - the supplement decreased some HETEs [metabolites], which are synthesized from arachidonic acid. Authors conclude that their findings provide a framework for futures studies on the use of a marine oil supplement to examine the effects of how SPMs and their metabolic intermediates control varying aspects of inflammation and immunity, including antibody concentrations, in subjects with obesity.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Marine oil enriched with specialised pro-resolving mediators raise levels of EPA, DPA and DHA-metabolites in adult subjects with obesity
- Larger randomised, blinded and placebo-controlled trials are required to inform healthcare practitioner clinical practice decisions relating to SPM enriched marine oil supplementation
- Future research is required to determine if increased concentrations of SPMs control the resolution of inflammation in humans with obesity.
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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X
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:
- Specialised pro-resolving mediators (SPMs) are oxylipins synthesised from omega-3 and -6 PUFAs which play a role in resolving inflammation.
- The authors highlight mouse studies have found that increasing the levels of SPMs and their metabolic intermediates can improve a range of obesity related complications. Thus, there is scientific interest in increasing the levels of SPMs in humans with diseases associated with chronic inflammation, such as obesity.
- This small non-randomised uncontrolled clinical trial of 23 individuals (13 female; 10 male) aged 50-65 years with obesity (BMI 30-40), aimed to determine the impacts of 1 month supplementation with marine oil particularly enriched with 14-hydroxydocosahexanenoic acid (14-HDHA), 17-HDHA and 18-hydroxydocosahenaenoic acid (HEPE) on:
- The change in levels of PUFA-derived oxylipins from baseline
- The change in abundance of circulating peripheral blood mononuclear cells (PBMCs)
- The change in antibody production
Intervention
- 2g enriched marine oil (4 capsules of SPM Active provided by Metagenics, study sponsor) once daily for 28-30 consecutive days.
Inclusion/Exclusion Criteria
- Only post-menopausal women were included to reduce confounding effects of oestrogen on lipid metabolism
- Individuals were excluded if diagnosed with Type 1 or 2 diabetes, autoimmunity, liver disease, coagulopathy, uncontrolled hypothyroid or active malignancy
- Individuals were excluded if they consumed omega-3 PUFA supplements within 3 months of intervention, regularly consumed >2 servings per week of fatty fish, had a fish/shellfish allergy or were taking a predetermined list of medications.
Findings
- Statistically significant increases were found in certain EPA, DPA and DHA-derived metabolites in response to supplementation relative to baseline. However, only 17-HDHA concentrations increased relative to baseline, with no effect on 14-HDHA or 18-HEPE, despite the supplement being enriched with all 3 metabolites
- Statistically significant decreases were found in arachidonic acid (AA)-derived oxylipins post supplementation relative to baseline
- Increases in immune cell populations in circulation did not reach significance post supplementation when measured by PBMCs.
Conclusions
An enriched marine oil supplement increased select SPMs in adults with obesity.
Clinical practice applications:
- Healthcare practitioners working with adults with obesity can use the results from this trial to understand that 1 month supplementation with 4g of enriched marine oil supplementation raises levels of certain EPA, DPA and DHA metabolites
- Practitioners may want to follow the research in this area as larger, controlled trials are conducted and comparisons made with non-enriched fatty acid supplements.
Considerations for future research:
- Future clinical studies of SPM supplementation are required that are double-blind, randomised and placebo-controlled to inform scientific findings in this area
- This study was inadequately powered to assess differences between female and male participants and therefore larger trials are needed to inform the sex differences in oxylipins within the population with obesity
- Further research is required in younger subjects with obesity to assess SPMs as a possible chronic inflammation preventative strategy, due to inflammation complications over time
- Future research should take account of the heterogeneity in the population with obesity, such as microbiome profiles, food intake and baseline metabolic status
- Further studies comparing impacts of standard marine oil with enriched marine oil on chronic inflammation would inform healthcare practitioners in their clinical practice.
Abstract
BACKGROUND Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations, such as subjects with obesity who display dysregulation of SPM metabolism. However, the concentrations of SPMs and their metabolic intermediates in humans with obesity remains unclear. OBJECTIVES The primary objective of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19 + B-cell antibody production was modified by marine oil intervention. METHODS Twenty-three subjects [median age: 56 y; BMI (in kg/m2): 33.1] consumed 2 g/d of a marine oil supplement for 28-30 d. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic (HEPE), 14-hydroxydocosahexaenoic acid (14-HDHA), and 17-HDHA. Blood was collected pre- and postsupplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B-cell isolation. Paired t-tests and Wilcoxon tests were used for statistical analyses. RESULTS Relative to preintervention, the supplement increased 6 different HEPEs and HDHAs accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 concentrations were increased 3.5- and 4.7-fold upon intervention, respectively. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B-cell IgG but not IgM concentrations were lowered postsupplementation. CONCLUSIONS A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased concentrations of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov as NCT04701138.
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7.
Comparative analysis of the efficacies of probiotic supplementation and glucose-lowering drugs for the treatment of type 2 diabetes: A systematic review and meta-analysis.
Liang, T, Xie, X, Wu, L, Li, L, Yang, L, Gao, H, Deng, Z, Zhang, X, Chen, X, Zhang, J, et al
Frontiers in nutrition. 2022;9:825897
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Type 2 diabetes (T2D) is a serious medical condition often requiring antidiabetic drug management. Although commonly used antidiabetic drugs effectively control glucose levels, their tolerability profiles differ, causing various side effects. Probiotics can be used as single or multi strains to reduce glycaemic and lipid indicators and avoid the negative effects of antidiabetic medications. The study included twenty-five randomised controlled trials, of which fourteen studies assessed the effectiveness of probiotics (single probiotics, multi-strain probiotics, and probiotics with co-supplements), and eleven studies included different antidiabetic drugs such as Thiazolidinedione (TZD), Glucagon-like peptide-1 receptor agonists (GLP-1 RA), Dipeptidyl peptidase IV inhibitors (DPP-4i), and Sodium-glucose co-transporter 2 inhibitors (SGLT-2i). This systematic review and meta-analysis compared the effectiveness of probiotic and antidiabetic drugs on glycaemia, lipid profile and blood pressure in T2D patients. Probiotics were less effective than specific antidiabetic drugs in reducing fasting blood sugar levels (FBS), HbA1c levels, and triglycerides. Different probiotic formulations were effective in reducing the HOMA-IR index, total cholesterol (TC), triglycerides (TG), and systolic and diastolic pressure (SBP and DBP). A subgroup analysis showed a greater reduction in FBS, HbA1c, TC, TG, and SBP in obese and elderly participants, those who participated for a longer duration, and those from Eastern origins. Considering the high heterogeneity in baseline study characteristics among the studies included in this systematic review and meta-analysis, further studies are required to evaluate the effects of probiotics and antidiabetic drugs. However, healthcare professionals can use the study to understand the effect of probiotics and antidiabetic drugs in reducing glycaemic, lipid and hypertension profiles.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Glucose-lowering drugs, except for DPP-4i, reduced FBS and HbA1c more than probiotics; and SGLT-2i induced the greatest decrease in HbA1c
- A BMI ≥ 30 kg/m2 showed a significant decrease in FBS and the HOMA-IR index compared with those with lower BMI
- Weight loss induced by glucose-lowering drugs and probiotic supplementation plays an important role in glycaemic control in obese patients with type 2 diabetes.
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
This meta-analysis compared the effects of probiotics and glucose-lowering drugs thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) on various outcome measures in patients with type 2 diabetes (T2D).
Methods
A search was performed on PubMed, Web of science, Embase, and Cochrane Library between January 2015 - April 2021.
Results
25 randomised controlled trials (RCT) were included (2843 participants). 14 RCTs (842 participants) involved the administration of single probiotics, multi-strain probiotics, and probiotics with co-supplements, and 11 RCTs (2001 participants) involved TZD, GLP-1 RA, SGLT-2i, and DPP-4i. Participants in 7 of the studies had T2D, aged ≤ 55 years old. 8 RCTs included participants with a mean BMI ≥ 30 kg/m2, and 11 RCTs participants had a mean BMI < 30 kg/m2.
Effects of probiotics:
- Fasting Blood Sugar (FBS): A reduction (−1.42, −0.32 mg/dL, p=0.000)
- Glycated hemaglobin (HbA1c): No reduction (p = 0.000)
- Insulin Resistance (HOMA-IR): A decrease (−0.64, −0.31; p = 0.780), regardless of probiotic strain or with a co-supplement
- Insulin: Not significant (p = 0.000). Subgroup analysis: no reduction
- Total Cholesterol (TC): No difference (p = 0.941). Subgroup analysis: reduction from multi-species probiotics (−0.36, −0.01 mg/dL, p = 0.871)
- Triglycerides: Difference (−0.25 mg/dL, p = 0.958)
- LDL-C: No changes (p = 0.189)
- HDL-C: No increase (p = 0.014)
- Systolic Blood Pressure (SBP): A decrease (−6.44, −0.08 mmHg, p = 0.044)
- Diastolic Blood Pressure (DBP): A reduction (−4.53, −0.80 mmHg, p = 0.206).
Effects of glucose-lowering drugs:
- FBS: A decrease (−4.22 mg/dL, −1.24 mg/dL, p = 0.000)
- HbA1c: A decrease (−2.51%, −0.52%, p = 0.000) with TZD, GLP-1 RA, SGLT-2i, and DPP- 4i; a reduction with SGLT-2i (p = 0.003)
- TC: No difference (p = 0.000). Subgroup: no decrease with single species probiotics and probiotics with co-supplements, TZD, GLP-1 RA, and DPP-4i)
- TG: No difference (p = 0.000)
- . HDL-C: No increase (p = 0.000). Subgroup: a decrease with TZDs (−2.37, −0.72 mg/dL). No difference with probiotic strains, or probiotics with co-supplements, GLP-1 RA, and DPP-4i
- LDL-C: No changes (p = 0.000), Subgroups: no difference with probiotic strains, probiotics with co-supplements, TZD, GLP-1 RA, and DPP-4i).
Limitations
Limited number of studies for TZD and SGLT-2i, making results potentially unreliable.
Conclusions
Multi species probiotics are worth considering as an adjunct to glucose-lowering drugs, and for improving lipid profiles and hypertension.
Clinical practice applications:
- Probiotic supplementation reduced the HOMA-IR index
- Multi-species probiotics were associated with reduction in TC and TG levels
- DPP-4i only decreased TG levels
- TZD was associated with decrease in HDL-C, whereas probiotic supplementation was associated with higher decrease in SBP and DBP and that GLP-1 RA increases the risk of hypoglycaemia.
Considerations for future research:
- Semaglutide was associated with an increased risk for hypoglycaemia compared with a placebo, indicating that the safety of semaglutide needs further study
- Dietary and physical activity should be considered in future studies
- Heterogeneity in some indicators may be due to differences in study baseline characteristics,Larger trials needed to support the results of this meta-analysis.
Abstract
The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics and glucose-lowering drugs (thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) in patients with type 2 diabetes from randomized con-trolled trials (RCTs). The PubMed, Web of science, Embase, and Cochrane Library databases were searched on the treatment effects of probiotics and glucose-lowering drugs on glycemia, lipids, and blood pressure metabolism published between Jan 2015 and April 2021. We performed meta-analyses using the random-effects model. We included 25 RCTs (2,843 participants). Overall, GLP-1RA, SGLT-2i, and TZD significantly reduce fasting blood sugar (FBS) and glycated hemoglobin (HbA1c), whereas GLP-1 RA increased the risk of hypoglycaemia. Multispecies probiotics decrease FBS, total cholesterol (TC), and systolic and diastolic blood pressure (SBP, DBP). Moreover, subgroup analyses indicated that participants aged >55 years, BMI ≥30 kg/m2, longer duration of intervention, and subjects from Eastern countries, showed significantly higher reduction in FBS and HbA1c, TC, TG and SBP. This meta-analysis revealed that including multiple probiotic rather than glucose-lowering drugs might be more beneficial regarding T2D prevention who suffering from simultaneously hyperglycemia, hypercholesterolemia, and hypertension.
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8.
Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.
Zhu, J, Xun, PC, Kolencik, M, Yang, KF, Fly, AD, Kahe, K
Nutrients. 2022;14(8)
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Dietary intake of B-vitamins or omega-3 polyunsaturated fatty acids (PUFAs) has been found to be inversely related to cardiovascular disease (CVD). The aim of this study was to examine whether the combined supplementation of B-vitamins and omega-3 PUFAs could provide additional beneficial effects on improving risk factors to prevent CVD beyond the effects of either of them alone. This study is a systematic review of fifteen studies. The sample sizes ranged from 12 to 2501 participants with study duration ranging from 4 weeks to 4.7 years. Results show that the combined supplementation with B-vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma homocysteine, triglycerides and low-density lipoprotein cholesterol than each supplementation alone. Authors conclude that: - there is no solid evidence that the joint supplementation of B-vitamins and omega-3 PUFAs can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. - dietetic strategies for preventing CVD need to focus more on the importance of considering effects at the whole food and dietary patterns level. - further well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Combined vitamin B and n3 PUFA supplementation might have favourable health effects
- Combined vitamin B and n3 PUFA supplementation could help in the primary and secondary prevention of cardiovascular disease
- The suggested favourable dose ranges are vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day, and n3 PUFA 0.2–2) g/day.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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:
- The paper reviews whether combined supplementation of vitamin B (B2, B6, B9, and B12) and omega-3 polyunsaturated fatty acids (n3 PUFA) outweighs the individual cardiovascular benefits of each supplement. Registered in PROSPERO under CRD42018085993
- A total of 15 clinical studies including 8,263 individuals published from December 2021, that investigated the combined effects of the supplements met inclusion criteria and were included in the review
- Although the results indicate the beneficial effects of combined supplementation in primary and secondary cardiovascular prevention, firm conclusions cannot be drawn from the existing data, and more studies are needed in this area.
Clinical practice applications:
In comparison with a single supplement alone, the combined administration of vitamin B and n3 PUFA might have:
- Hypolipidemic effects, by reducing triglycerides and LDL-cholesterol. Some of the studies indicate a lowering of LDL-c up to 13% and triglycerides up to 24%
- Anti-inflammatory effects, by reducing homocysteine. Based on some of the studies, the lowering effects might go up to 39%.
Dietary practice might benefit from the following:
- The authors highlighted food-based and healthy dietary pattern-based strategies should include food sources rich in these nutrients such as fish, vegetables, fruit, legumes, nuts, and eggs
- The authors conclude that intake of whole foods and whole diets rich in desirable foods (such as MedDiet) should be encouraged
- The supplementation dose ranges in the studies covered by the review were the following: vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day and n3 PUFA 0.2–2) g/day
- Limitations of the systematic review include different supplementation regimens, variability of study designs in terms of duration of the intervention, existence of placebo group, dosages and the inability to monitor study subjects’ habitual diet.
Considerations for future research:
- Future studies should be designed regarding the need for a uniform methodological approach in testing the combined effects of vitamin B complex and n3 PUFA supplements
- The studies should investigate supplementation strategies and dietary patterns rich in both nutrients.
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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9.
Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: a randomised clinical trial.
San Mauro Martin, I, Sanz Rojo, S, González Cosano, L, Conty de la Campa, R, Garicano Vilar, E, Blumenfeld Olivares, JA
Neurologia. 2022;37(7):513-523
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From a clinical perspective, impulsiveness is an important diagnostic characteristic of several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). ADHD is a neurodevelopmental disorder characterised by a persistent pattern of lack of attention and/or hyperactivity and impulsiveness. Dietary approaches to the treatment of ADHD include fatty acid supplementation, particularly with omega-3 polyunsaturated fatty acids (n-3 PUFA) The aim of this study was to analyse changes in the Barratt Impulsiveness Scale (BIS-11c) scores in children with ADHD after an 8-week intervention with the Mediterranean diet, omega-3 fatty acid supplementation, or Mediterranean diet plus omega-3 fatty acid supplementation, as compared to a control group. This study is a cross-sectional, observational cohort study of an 8-week dietary intervention in children with ADHD. Participants (n= 60) were divided into 4 groups, with a control group and 3 intervention groups. Results show that participants with ADHD taking n-3 PUFA supplements (550 mg EPA and 225 mg DHA daily) showed significantly lower levels of impulsiveness than those adopting a Mediterranean diet and controls. These participants also scored lower on all subscales of the BIS (cognitive, motor, and lack of planning). However, there weren’t any differences in impulsive behaviour between patients taking n-3 PUFA supplements and those taking supplements and adhering to the Mediterranean diet. Authors conclude that omega-3 rich (EPA/DHA) supplements should be considered for paediatric patients with ADHD, particularly those with the predominantly hyperactive-impulsive subtype.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The results from this study show no statistically significant differences between groups, except for the group of children receiving omega-3 supplementation.
- Patients with ADHD receiving omega 3 fatty acids (550 mg eicosatetraenoic acid [EPA] and 225 mg docosahexaenoic acid [DHA]) daily presented with less impulsive behaviour than controls with ADHD and patients who adopted a Mediterranean diet.
- EPA/DHA supplements may be considered for paediatric patients with ADHD, particularly those with the predominantly hyperactive-impulsive subtype.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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
A randomized, cross-sectional study was conducted to investigate the effects of a Mediterranean diet and Omega-3 supplementation on the impulsiveness in children with attention-deficit/hyperactivity disorder (ADHD).
Methods
76 Children ages 6-16 years of either sex, with a diagnosis of ADHD, were divided into 4 groups, with a control group and 3 intervention groups. Group 1 (controls) followed their usual diet. Group 2 (Mediterranean diet) adopted a Mediterranean diet according to a series of recommendations. Group 3 (omega-3) received omega-3 fatty acid supplements. Group 4 (Mediterranean diet + omega-3) adopted the same diet as group 2 and also received omega 3 fatty acid supplements.
Dieticians provided a tailored Mediterranean diet for each participant. The Omega-3 supplement comprised of 550mg EPA and 225mg of DHA sourced from deep-sea sardines and anchovies.
The Barratt Impulsiveness Scale (BIS-11c) was administered to every child individually to evaluate impulsiveness. The KIDMED questionnaire was administered to evaluate the participant’s adherence to the Mediterranean diet. The study was conducted over 8 weeks. At the endpoint, 60/76 subjects completed the study.
Results
Primary clinical outcomes were:
- Children in the omega-3 supplement group showed a significant drop in the Barratt Impulsiveness Scale score after the intervention (from 49 to 45.10; p =.049).
- Children in the Mediterranean diet and supplement group showed higher cognitive scores (from 2.758 to 2.631).
Limitation
There was a statistically significant difference between groups for the KIDMED score (a measure of adherence to a Mediterranean diet), reflecting a higher adherence to the Mediterranean diet by the control group.
Clinical practice applications:
- Approximately 20%-40% of patients with ADHD do not respond to pharmacological treatment therefore there is a need for alternative options.
- Based on these findings, a practitioner could therefore consider recommending 550mg of eicosatetraenoic acid (EPA) and 225mg of docosahexaenoic acid (DHA) sourced from deep-sea sardines and anchovies for at least 8 weeks to help reduce impulsiveness and improve cognitive function in patients with a hyperactive-impulsive subtype of ADHD.
Considerations for future research:
- This study included combined types of ADHD therefore further investigations are needed on each type of ADHD using different interventions to establish which intervention works best.
- Assessment of diet and omega status before intervention was not conducted, which may have affected outcomes in this study. Further research could consider gathering this data at baseline.
- Larger studies are also needed to determine the relationship between BIS scores and treatments to deepen our understanding of this topic.
- Conflict of interest statement: This study was fully funded by the manufacturer of the provided Omega 3 supplement.
Abstract
INTRODUCTION The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). METHODS This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group and 3 intervention groups (Mediterranean diet; omega-3 supplementation; and Mediterranean diet plus omega-3 supplementation). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. RESULTS The supplementation group showed a fairly significant decrease in the total BIS-11c (P = .049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r > 0.9). CONCLUSION An intake of 550 mg EPA fatty acid and 225 mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population.
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10.
A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT.
Fortier, M, Castellano, CA, St-Pierre, V, Myette-Côté, É, Langlois, F, Roy, M, Morin, MC, Bocti, C, Fulop, T, Godin, JP, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021;17(3):543-552
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Brain energy rescue is emerging as a potential strategy to reduce cognitive decline in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The main aim of this study was to report the complete cognitive outcomes of the BENEFIC (Brain Energy, Functional Imaging, and Cognition) trial. The secondary objectives are to report plasma ketones (free caprylic and capric acids) levels; as well as the metabolic response, safety, and tolerability after the 6-month intervention. This study is a 6-month randomised, placebo-controlled trial. A total of 122 participants were enrolled and randomised into one of the two arms: ketogenic medium chain triglyceride (kMCT) or placebo arm. Results show that performance on widely used tests of episodic memory, executive function, and language improved over 6 months in MCI when consuming 30g/day of a kMCT drink relative to a matching placebo. Moderate to large effect sizes were observed on four cognitive tests in the kMCT group. Furthermore, it is safe and feasible for an MCI population to consume a 15g kMCT supplement twice daily for 6 months. Authors conclude that formulation of a kMCT drink improved four cognitive outcomes in MCI by increasing blood ketone levels.
Expert Review
Conflicts of interest:
None
Take Home Message:
- MCT supplementation is a promising strategy to rescue energy metabolism in the brain for those with MCIs by providing an alternative energy source
- Improvements in cognition were associated with increased blood ketone levels from MCT supplementation
- Practitioners should be mindful that higher intakes of MCTs (>30g/d) may lead to negative GI effects in some individuals.
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:
This randomized controlled trial demonstrates that supplementation of a ketogenic drink containing medium-chain triglycerides (MCTs) is both safe and effective in improving cognitive outcomes in individuals with mild cognitive impairments (MCI), and does so through supporting energy metabolism in the brain.
Clinical practice applications:
These findings might be useful for Nutritional Therapists and Clinical Practitioners as follows:
- The results of this randomised controlled trial demonstrate that MCT supplementation (at 30g per day, split between two doses) is a viable strategy to support brain metabolism in individuals experiencing MCIs
- There was a dose-dependant response on elevated ketones and selected cognitive improvements which may have pertinent applications to therapeutic practice (either dietary or supplemental)
- The paper highlighted the involvement of energy metabolism in cognitive decline; this has potential therapeutic applications in terms of targeted nutritional support for mitochondrial function or energy signalling
- Some individuals experienced negative gastrointestinal effects when consuming MCTs at 30g/d for prolonged periods; practitioners should be mindful of this.
Considerations for future research:
Future research should consider:
- Whether dietary-induced ketosis can therapeutically impact MCI and support patient well-being
- Use of MCTs in those with severe cognitive impairments or those taking medication such as cholinesterase inhibitors
the role of glucose hypometabolism to determine alternative strategies for those who have GI issues with MCTs
- Whether APOE4 status has any impact on therapeutic outcomes to MCT supplementation
- Whether adjunct nutritional support for mitochondrial function alongside MCT could further impact on MCIs.
Abstract
INTRODUCTION Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI). METHODS Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyceride [kMCT]; 15 g twice/day; n = 39) or placebo (n = 44). RESULTS Free and cued recall (Trial 1; P = .047), verbal fluency (categories; P = .024), Boston Naming Test (total correct answers; P = .033), and the Trail-Making Test (total errors; P = .017) improved significantly in the kMCT group compared to placebo (analysis of covariance; pre-intervention score, sex, age, education, and apolipoprotein E4 as covariates). Some cognitive outcomes also correlated positively with plasma ketones. Plasma metabolic profile and ketone response were unchanged. CONCLUSIONS This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression to Alzheimer's disease.