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Impact of Blueberry Consumption on the Human Fecal Bileacidome: A Pilot Study of Bile Acid Modulation by Freeze-Dried Blueberry.
Gagnon, W, Garneau, V, Trottier, J, Verreault, M, Couillard, C, Roy, D, Marette, A, Drouin-Chartier, JP, Vohl, MC, Barbier, O
Nutrients. 2022;14(18)
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Primary bile acids (BAs) are made in the liver from cholesterol. They are released into the small intestine, where they aid fat digestion and absorption. Most BAs are reabsorbed from the gut, yet a small amount gets modified by the gut bacteria, forming secondary BAs destined for faecal excretion. Excess secondary BAs have negative health consequences. The different types of primary BAs influence many physiological functions. Such as glucose regulation, fat metabolism and absorption, intestinal inflammation and immunity, as well as gut bacteria diversity. For optimal BA metabolism, they are tightly regulated by the body, as minimal changes in BA pool and composition can have a significant impact on overall health. The composition of the BA pool can be influenced by gut bacteria, metabolic disorders, pathologies of the liver and gut, and diet. Dietary polyphenols, a plant-based compound, have been of particular interest here. This study sought to investigate the impact of supplementary freeze-dried blueberry powder (BBP), a rich polyphenol source, on the faecal BA pool composition in people at risk of metabolic syndrome. For this 11 men and 13 women were supplemented for 8 weeks. When compared to the data before the intervention, no significant changes in total BAs were observed. However, the composition of the BA pool changed leading to the accumulation of particular BAs and a reduction in secondary BA levels. This suggested that the consumption of blueberries can be considered a potential clinical intervention to aid the elimination of toxic secondary BAs. As the mechanisms leading to such modifications and their consequences for human health are complex, the authors advocate for investigation in larger population groups and also alert that such changes may be subject to interindividual variability and health status.
Abstract
Cholesterol-derived bile acids (BAs) affect numerous physiological functions such as glucose homeostasis, lipid metabolism and absorption, intestinal inflammation and immunity, as well as intestinal microbiota diversity. Diet influences the composition of the BA pool. In the present study, we analyzed the impact of a dietary supplementation with a freeze-dried blueberry powder (BBP) on the fecal BA pool composition. The diet of 11 men and 13 women at risk of metabolic syndrome was supplemented with 50 g/day of BBP for 8 weeks, and feces were harvested before (pre) and after (post) BBP consumption. BAs were profiled using liquid chromatography coupled with tandem mass spectrometry. No significant changes in total BAs were detected when comparing pre- vs. post-BBP consumption samples. However, post-BBP consumption samples exhibited significant accumulations of glycine-conjugated BAs (p = 0.04), glycochenodeoxycholic (p = 0.01), and glycoursodeoxycholic (p = 0.01) acids, as well as a significant reduction (p = 0.03) in the secondary BA levels compared with pre-BBP feces. In conclusion, the fecal bileacidome is significantly altered after the consumption of BBP for 8 weeks. While additional studies are needed to fully understand the underlying mechanisms and physiological implications of these changes, our data suggest that the consumption of blueberries can modulate toxic BA elimination.
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Healthy Lifestyle Is Associated with Reduced Mortality in Patients with Non-Alcoholic Fatty Liver Disease.
Yu, C, Gao, J, Ge, X, Wang, X, Ding, Y, Tian, T, Xu, X, Guo, W, Wang, Q, Ge, Z, et al
Nutrients. 2022;14(18)
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Non-alcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver disease. Given the association between NAFLD and metabolic syndrome [11,12], lifestyle modification can improve patients’ life quality and prognosis. The aim of this study was to assess the joint association of several modifiable lifestyle factors with overall and cause-specific mortality among NAFLD individuals and depict the mortality risk of varied composite modes of lifestyle. This study is a large, nationally representative, population-based study. It is based on the NHANES III (1988–1994, the National Center for Health Statistics, the Center for Disease Control and Prevention), which used a complex multistage probability design to recruit a representative sample of participants. Results show a protective effect among NAFLD participants following a healthy lifestyle, particularly impacting CVD-related mortality. Notably, among the most common lifestyle factor combinations, the effect of risk reduction on mortality was particularly strong when smoking was avoided. Authors conclude that their findings can be a useful tool to help the general public and patients with NAFLD to understand the importance of maintaining a healthy lifestyle.
Abstract
BACKGROUND AND AIMS It is unclear whether a healthy lifestyle impacts mortality in the presence of non-alcoholic fatty liver disease (NAFLD). The present study aimed to examine the joint association of several modifiable lifestyle factors with mortality risk for NAFLD patients. METHODS We collected lifestyle behavior data form the National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and follow-up data form NHANES III-linked mortality data through 2015. We estimated joint association between four healthy lifestyle factors (non-smoking, non-drinking, regular physical activity, a healthy diet) after NAFLD diagnosis and mortality using Cox proportional hazards regression models. RESULTS During a median of 22.83 years of follow-up, 2932 deaths occurred. The risk of all-cause mortality decreased significantly with the healthy lifestyle scores increasing (p < 0.001). NAFLD patients with a favorable lifestyle (3 or 4 healthy lifestyle factors) reduced 36% of all-cause mortality and 43% of cardiovascular disease (CVD) mortality compared with those with an unfavorable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.64 [95% CI, 0.50-0.81], 0.57 [95% CI, 0.37-0.88]). Compared with the non-NAFLD group, the number of NAFLD patients required to adhere to a favorable lifestyle to prevent one cardiovascular disease death in 20 years was fewer (77 vs. 125). CONCLUSIONS For the NAFLD patients, adopting a healthy lifestyle could significantly reduce their risk of death.
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Association between Mediterranean Diet and Fatty Liver in Women with Overweight and Obesity.
Leone, A, Bertoli, S, Bedogni, G, Vignati, L, Pellizzari, M, Battezzati, A
Nutrients. 2022;14(18)
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Non-alcoholic fatty liver disease (NAFLD) is a condition resulting from excessive lipid accumulation in the liver in individuals with low alcohol consumption. Obesity is an established risk factor for the development of NAFLD, and 50% to 75% of people with obesity also have NAFLD. The aim of this study was to evaluate the association between Mediterranean diet and non-invasive indices of fatty liver in a large sample of women with overweight and obesity. This study is a cross-sectional study of 2967 consecutive women with overweight and obesity. Results show that higher adherence to the Mediterranean diet was associated with lower indices of fatty liver in women with overweight and obesity (particularly obese women than in women who are overweight). Authors conclude that women with obesity, especially during the premenopausal period, may benefit more from following a Mediterranean-style diet.
Abstract
Obesity is a risk factor for NAFLD. However, not all people with obesity have an excessive intrahepatic fat content. Adherence to a high-quality dietary pattern may also promote liver health in obesity. A cross-sectional study of 2967 women with overweight and obesity was carried out to assess the association between a Mediterranean diet and fatty liver. All women underwent clinical examination, anthropometric measurements, blood sampling, ultrasound measurements of abdominal visceral and subcutaneous fat, and assessment of adherence to the Mediterranean diet using the 14-item MEDAS questionnaire. Fatty liver index (FLI), NAFLD fatty liver steatosis (NAFLD-FLS) and hepatic steatosis index (HSI) were calculated. In women with obesity, the MEDAS score was inversely associated with FLI (β = -0.60, 95% CI: -1.04, -0.16, p = 0.008), NAFLD-FLS (β = -0.092, 95% CI: -0.134, -0.049, p < 0.001) and HSI (β = -0.17, 95% CI: -0.30, -0.04, p = 0.011). Stronger associations were observed in premenopausal women with obesity. Mediterranean diet was inversely associated with NAFLD-FLS in women with overweight, independently of menopausal status. In conclusion, Mediterranean diet is associated with a better liver status in women with overweight and obesity. This may have a public health impact and be useful in drafting nutritional guidelines for NAFLD.
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Effect of Serum Lipid Profile on the Risk of Breast Cancer: Systematic Review and Meta-Analysis of 1,628,871 Women.
Nouri, M, Mohsenpour, MA, Katsiki, N, Ghobadi, S, Jafari, A, Faghih, S, Banach, M, Mazidi, M
Journal of clinical medicine. 2022;11(15)
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Elevated fats in the blood have been associated with an increased risk for breast cancer. However, exact relationships between which fats is still unclear. This systematic review and meta-analysis of 26 studies with 36,590 women aimed to investigate the relationship between fat in the blood and breast cancer risk. The results showed that high levels of high-density lipoprotein (HDL) in the blood decreased a woman’s risk of developing breast cancer, however other fats in the blood such as triglycerides, cholesterol and low-density lipoprotein had no relationship with breast cancer risk. It was concluded that low levels of HDL in the blood are related to an increased risk for breast cancer. This study could be used by healthcare professionals to understand that it is important to recommend exercise, which is a way of increasing HDL’s, in women who are at risk of breast cancer development.
Abstract
Dyslipidemia has been linked to breast cancer incidence. The aim of the present meta-analysis was to further investigate the relationship between the serum lipid profile and breast cancer risk. Databases such as PubMed, EMBASE, and Web of Sciences were searched up to the end of January 2021 using certain MeSH and non-MeSH keywords and combinations to extract related published articles. Twenty-six prospective studies involving 1,628,871 women, of whom 36,590 were diagnosed with breast cancer during the follow-up period met the inclusion criteria. A negative and significant association was found between the HDL-C level and the risk of breast cancer (relative risk (RR): 0.85, 95% CI: 0.72-0.99, I2: 67.6%, p = 0.04). In contrast, TG (RR: 1.02, 95% CI: 0.91-1.13, I2: 54.2%, p = 0.79), total cholesterol (TC) (RR: 0.98, 95% CI: 0.90-1.06, I2: 67.2%, p = 0.57), apolipoprotein A (ApoA) (RR: 0.96, 95% CI: 0.70-1.30, I2: 83.5%, p = 0.78) and LDL-C (RR: 0.93, 95% CI: 0.79-1.09, I2: 0%, p = 0.386) were not associated with breast cancer development. In studies adjusting for hormone use and physical activity, breast cancer risk was positively correlated with TC (RR: 1.05, 95% CI: 1.01-1.10). Similarly, TG was significantly related to breast cancer development after adjustment for baseline lipids (RR: 0.92, 95% CI: 0.85-0.99) and race (any races mentioned in each study) (RR: 1.80, 95% CI: 1.22-2.65). In the present meta-analysis, HDL-C was inversely related to breast cancer risk. Overall, data on the links between lipids and breast cancer are conflicting. However, there is increasing evidence that low HDL-C is related to an increased risk for this type of malignancy.
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The effects of conjugated linoleic acid supplementation on lipid profile in adults: A systematic review and dose-response meta-analysis.
Asbaghi, O, Ashtary-Larky, D, Naseri, K, Saadati, S, Zamani, M, Rezaei Kelishadi, M, Nadery, M, Doaei, S, Haghighat, N
Frontiers in nutrition. 2022;9:953012
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Elevated fats circulating in the blood has been shown to be a predictor for heart disease. Conjugated linoleic acid (CLA) is a type of fat that is found in the milk and meat of animals such as cows, sheep and goats. Although classed as a fat, when taken in a supplemental form, some studies have shown it to decrease circulating fats whereas others have shown no beneficial effects. This systematic review and meta-analysis of 56 randomised control trials aimed to explore the effects of CLA on circulating blood profiles. The results showed that CLA increased levels of cholesterols, which may contribute to heart disease, but also increased cholesterol which may help to prevent heart disease. It was concluded that CLA supplementation has little effect on fats in the blood. This study could be used by healthcare professionals to understand that there may be little utility in recommending a supplemental CLA for the management of heart disease.
Abstract
BACKGROUND The findings of trials investigating the effect of conjugated linoleic acid (CLA) administration on lipid profile are controversial. This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of CLA supplementation on lipid profile. METHODS Two authors independently searched electronic databases including PubMed, Web of Science, and Scopus until March 2022, in order to find relevant RCTs. The random effects model was used to evaluate the mean and standard deviation. RESULTS In total, 56 RCTs with 73 effect sizes met the inclusion criteria and were eligible for the meta-analysis. CLA supplementation significantly alter triglycerides (TG) (WMD: 1.76; 95% CI: -1.65, 5.19), total cholesterols (TC) (WMD: 0.86; 95% CI: -0.42, 2.26), low-density lipoprotein cholesterols (LDL-C) (WMD: 0.49; 95% CI: -0.75, 2.74), apolipoprotein A (WMD: -3.15; 95% CI: -16.12, 9.81), and apolipoprotein B (WMD: -0.73; 95% CI: -9.87, 8.41) concentrations. However, CLA supplementation significantly increased the density lipoprotein cholesterol (HDL-C) (WMD: -0.40; 95% CI: -0.72, -0.07) concentrations. CONCLUSION CLA supplementation significantly improved HDL-C concentrations, however, increased concentrations of TG, TC, LDL-C, apolipoprotein A, and apolipoprotein B. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022331100.
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The Influence of Vitamin E and Omega-3 Fatty Acids on Reproductive Health Indices Among Male Workers Exposed to Electromagnetic Fields.
Mohammadi, H, Golbabaei, F, Dehghan, SF, Imani, H, Ramezani Tehrani, F, Khodakarim Ardakani, S
American journal of men's health. 2022;16(1):15579883221074821
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Studies have suggested that low-frequency electromagnetic fields (EMF) may have a detrimental effect on male fertility. Lower hormone levels and higher free radicals in the body damaging sperm cells have been indicated to play a role in this relationship. Supporting the development of sperm cells in individuals who have been subjected to EMF may be an effective therapy. Sperm cells contain large amounts of polyunsaturated fatty acids such as omega-3 and supplementation may be of benefit. Although high amounts of omega-3 can have side effects, which can be limited with the dual supplementation of vitamin E. This randomised control trial aimed to determine the effect of omega-3 and vitamin E supplementation on reproductive indices of individuals who work with EMF. The results showed that EMF exposure affected sperm count, morphology, and motility and that the supplementation of omega-3 and vitamin E in conjunction could limit effects on morphology and motility. It was concluded that simultaneous vitamin E and omega-3 consumption could be of benefit for fertility in men exposed to EMF, however further studies are required to confirm this finding due to study limitations and size. This study could be used by healthcare professionals to understand that EMF is of detriment to fertility in men but there may be ways to limit the effects involving the use of omega-3 and vitamin E supplementation.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Vitamin E and Omega 3 fatty acids have been reported to influence sperm morphology and sperm motility.
- This study reported that the intake of 100 mg of vitamin E accompanied by Omega 3 fatty acids (180 mg eicosatetraenoic acid [EPA] and 120 mg docosahexaenoic acid [DHA]) had a significant improvement in sperm morphology and motility after 3 months.
- In addition, this study also reported that electric magnetic fields may have a negative effect on sperm morphology and motility.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A block-randomized, double-blind, placebo-controlled study was conducted to investigate the effects of using vitamin E and Omega 3 fatty acid supplementation on reproductive indices among workers in an automobile parts manufacturing facility. The effect of exposure to electromagnetic fields on certain sex hormones and sperm parameters was also assessed.
Methodology
92 married males between the ages of 20-50 were deployed into 4 groups. The first group was given vitamin E (100 mg) accompanied by a placebo capsule. The second group was given Omega 3 fatty acids (180 mg eicosatetraenoic acid [EPA] and 120 mg docosahexaenoic acid [DHA]) accompanied by a placebo capsule. The third group was given vitamin E along with Omega 3 fatty acids. Finally, the fourth group acted as a placebo group and was given 2 placebo capsules.
The semen parameters of the participants were analysed before and after three months of consuming the supplements. Sex hormones within the blood serum were also analysed after the 3-month supplement period. At the endpoint, 80/92 subjects completed the study.
Results
Primary clinical outcomes were:
- Certain demographic parameters had significant effects on sluggish and full sperm motility: age (B = −1.344, p = .034); employment duration (B = −1.863, p = .022); and smoking (B = −94.24, p = .003).
- The difference in the level of testosterone before and after the intervention was not statistically significant for any age group.
- The difference in follicle-stimulating hormone (FSH) and Luteinizing Hormone (LH) before and after the intervention were not statistically significant for any of the supplement groups.
- There was a statistically significant effect on sperm count and sperm with full motility before and after the intervention in the vitamin E + Omega 3 group, p =.016.
- The effect of supplement use on sperm morphology was significant in the vitamin E + Omega 3 group (B = -4.961; p = .001).
- The effect of supplement use on full and sluggish sperm motility was also significant in the vitamin E + Omega 3 group (B = 72.211, p = .021).
Secondary clinical outcomes were:
- Electric fields had the largest effect on the percentage of immotile sperm amongst the exposure variables (B = 9.541; p = .053).
Clinical practice applications:
- Prior studies have reported on the antioxidant effects of vitamin E and the effect of Omega 3 fatty acids on the testicles and the hypothalamic-pituitary-gonadal axis.
- This study concluded that participants increased their normal sperm morphology by 16% and their sperm motility by 12% over a 3-month period by supplementing with vitamin E and Omega 3 fatty acids.
- Based on these findings, a practitioner could therefore consider recommending 100 mg of vitamin E accompanied by Omega 3 fatty acids (180 mg eicosatetraenoic acid [EPA] and 120 mg docosahexaenoic acid [DHA]) for at least 3 months to help support the reproductive health of their male patients struggling with sperm morphology and/or sperm motility.
Considerations for future research:
- In this study vitamin E and Omega 3 did not show significant effects on certain sex hormones (testorterone, FSH and LH) therefore, there is a need to investigate if a higher dosage or longer consumption of the supplements could make a difference to these outcomes.
- There are mixed findings on the potential effects of electric magnetic fields on male reproductive indices and therefore there is a need for further clinical studies to be done using the same type of frequency, intensity, and exposure protocols to draw further conclusions.
Abstract
The present study aims to investigate the effects of using the supplementation of vitamin E and Omega 3 fatty acids on reproductive indices among workers in an automobile parts manufacturing plant. The effect of exposure to electromagnetic fields on certain sex hormones and sperm parameters will also be assessed. The participants were deployed into four groups as per the double-blind block randomization method. Semen parameters and sex hormones of the participants were analyzed before and after 3-month consumption of supplements. The level of workers' exposure to low-frequency magnetic and electrical fields was measured through the recommendation of National Institute for Occupational Safety and Health. Univariate analysis of variance indicated that exposure to electric fields had a statistically significant effect on sperm count, morphology, and motility. The simultaneous consumption of vitamin E + Omega 3 had a statistically significant effect on sperm morphology and motility.
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Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial.
Johnstone, JM, Hatsu, I, Tost, G, Srikanth, P, Eiterman, LP, Bruton, AM, Ast, HK, Robinette, LM, Stern, MM, Millington, EG, et al
Journal of the American Academy of Child and Adolescent Psychiatry. 2022;61(5):647-661
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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects about 5-7% of children. Characteristics of ADHD are age-inappropriate hyperactivity, impulsivity, and difficulties in focusing attention which arise from an impaired ability to regulate executive and emotional functions. The condition often persists into adulthood, where it presents an increased risk for poor educational achievements, substance abuse, incarceration, and mental health problems. In many cases, drug treatment can improve ADHD symptoms, yet concern remains about the side effects of these treatments. Some research has investigated the impact of nutrient supplementation on ADHD management, as many nutrients are essential for healthy brain function and are also involved in the production of neurotransmitters. In previous studies, supplementation with nutrients has shown some benefits but likewise also inconsistent results. This eight-week randomised placebo-controlled clinical trial evaluated the effects of a multi-nutrient supplement in 135 children with ADHD, aged 6-12 years. The study specifically focused on irritable mood symptoms. The multi-nutrient formula contained vitamins, minerals, amino acids, and antioxidants. Outcomes were measured by scores rated by clinicians (Clinical Global Impression-Improvement aka CGI-I) and scores rated by parents (Child and Adolescent Symptom Inventory-5 aka CASI-5). The multi-nutrient formula showed overall benefit in the blinded clinician rating but not by parental reports. According to the parents, overall improvement was reported, both in the placebo and intervention groups. The authors discussed how this absence of difference can be explained. Yet, on a subscale, the multi-nutrient group parents were more likely to report improvements. In addition, children with the additional micronutrients demonstrated greater height growth during the intervention. The supplement was well tolerated with good adherence and the monitored blood markers demonstrated safety of use.
Expert Review
Conflicts of interest:
None
Take Home Message:
This fully-blinded RCT of micronutrients addresses several concerns related to existing ADHD treatment, including the possibility of counteracting height suppression and treating associated irritable mood, emotional dysregulation, and aggression.
Although further research is needed, multinutrient supplementation should be considered for children with ADHD.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric condition that can result in low educational performance and achievement. Around 5-7% of children are believed to be affected. Alongside inattention and hyperactivity, emotional dysregulation is a common feature of ADHD. Psychiatric problems can continue into adulthood and an increased risk of incarceration and substance abuse have been reported.
Treatment with prescription medications may improve symptoms of ADHD, however, potential side effects include mild growth suppression, and mood and emotional dysregulation. Non-pharmacological treatments are therefore being investigated.
Previous research on single nutrients have shown mixed results for emotional dysregulation and mood issues in ADHD. The aim of this study was to test whether supplementation with a multi-nutrient could be beneficial to children aged 6-12 years with ADHD and irritability.
Methods
126 unmedicated children from North America with ADHD (mean age 9.8 years) completed this 8-week study. All participants had at least 1 symptom of anger, irritability, peer conflict or Disruptive Mood Dysregulation Disorder (DMDD).
Randomisation was into an intervention (n=71) or placebo (N=55) group with a 3:2 ratio to promote enrolment. Participants were required to take 6-12 capsules daily, depending on age and tolerance, of micronutrients or a placebo. Micronutrient dosages were above the recommended dietary allowance (RDA). Outcomes were measured using clinician and parent rated assessments and by a further adult who knew the child well.
The trial was blinded to all participants, parents and study staff.
Results
The clinician-rated results found 54% of the micronutrient group and 18% of the placebo group had improvements in irritability symptoms (Risk ratio =2.97, 97.5% CI: 1.5, 5.90, p<0.001). This was not replicated in the parent/adult rated results. Children in the micronutrient group grew on average 6mm more than the placebo group (p=0.002). No serious adverse treatment effects were reported. Adherence to protocol was met by >74% of participants (n=93).
Conclusions
In this study, clinicians reported that micronutrients showed greater benefits than placebo for treating irritability and supporting growth in children with ADHD.
The study and authors received funding from several research and association bodies. However, no funder was involved in the study design or reporting. No conflicts of interest were declared.
Clinical practice applications:
- Multinutrient supplementation including vitamins, minerals, amino acids, and antioxidants may support height growth in children who take pharmacologic treatment
- Multi nutrient supplementation may also help with irritable mood, emotional dysregulation, and aggression in ADHD children
- Micronutrients given at doses between the Recommended Dietary Allowance and Upper Tolerable Intake Level appear safe and may be developed into an alternative or complementary treatment for ADHD.
Considerations for future research:
- Further large scale research is needed into the potential benefits of micronutrients for children with ADHD and irritability
Abstract
OBJECTIVE To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred. CONCLUSION Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level. CLINICAL TRIAL REGISTRATION INFORMATION Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.
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Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.
Eichelmann, F, Sellem, L, Wittenbecher, C, Jäger, S, Kuxhaus, O, Prada, M, Cuadrat, R, Jackson, KG, Lovegrove, JA, Schulze, MB
Circulation. 2022;146(1):21-35
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The level of fats in the blood has been implicated as a causal factor in the development of diseases such as heart attack, stroke, and type 2 diabetes. Fat levels are therefore used as a predictor for disease and targeted in treatments. However, recent studies on the involvement of fats in diseases related to metabolic disorder have shortcomings. This secondary analysis of participants in the European Prospective Investigation into Cancer and Nutrition study aimed to determine the association of blood lipids with heart related metabolic diseases and a second randomised control trial aimed to determine the effect of modifying dietary fat intake on fats associated with risk for disease development. The results showed that 69 lipids mostly in the cholesterol ester, free fatty acid, triacylglycerol, phosphatidylcholine, monoacylglycerol, and sphingolmyelin classes were associated with heart disease and type 2 diabetes most of which were specific to one disease. The consumption of a diet rich in unsaturated fats compared to a saturated fat diet altered the blood lipid profile of participants to a one more favourable for metabolic risk. It was concluded that lipids are associated with metabolic disease and that substituting high dietary saturated fats to largely unsaturated fats may prevent the development of disease. Most lipids were specific to either type 2 diabetes or heart disease highlighting potential differing causes. This study could be used by healthcare professionals to better understand the lipids associated with heart disease and type 2 diabetes and that switching to a diet high in unsaturated fat may be of benefit to those suffering from these diseases.
Abstract
BACKGROUND In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. METHODS The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. RESULTS Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4-0.7) SD units. CONCLUSIONS We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.
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A Freshwater Fish-Based Diet Alleviates Liver Steatosis by Modulating Gut Microbiota and Metabolites: A Clinical Randomized Controlled Trial in Chinese Participants With Nonalcoholic Fatty Liver Disease.
He, K, Guo, LL, Tang, H, Peng, X, Li, J, Feng, S, Bie, C, Chen, W, Li, Y, Wang, M, et al
The American journal of gastroenterology. 2022;117(10):1621-1631
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The diagnosis and treatment of non-alcoholic fatty liver disease (NAFLD) is critical, however, there isn’t an effective treatment readily available. On the other hand, lifestyle modifications, particularly a calorie-restricted diet, habitual physical activity, and weight loss, have been advocated for the treatment of NAFLD. The hypothesis of this study was that a freshwater fish-based diet would induce a greater improvement in hepatic steatosis by regulating gut microbiota and its metabolites compared with an alternating combination of freshwater fish-based and red meat-based diets. This study was a randomised, open-label and controlled clinical trial which enrolled participants who were clinically diagnosed of NAFLD with a presence of hepatic steatosis. Participants (n=34) were randomly assigned to either a freshwater fish-based diet or the combination of a freshwater fish-based diet and a red meat-based diet at a daily alternating frequency in a 1:1 ratio. Results showed that dietary freshwater fish consumption: - alleviates liver steatosis in participants with NAFLD; - ameliorates several metabolic phenotypes in participants with NAFLD; - partially redresses gut microbiota dysbiosis in the improvement of the metabolic phenotypes of participants with NAFLD; - improves NAFLD by inducing metabolites alternation. Authors conclude that even though the freshwater fish-based diet showed various positive results for participants with NAFLD, the alternating freshwater fish and red meat consumption may not exacerbate NAFLD, which may be more appropriate to fit the daily eating habits and food diversity for long-term implementation.
Abstract
INTRODUCTION We aimed to assess the effects of 2 isoenergetic intervention diets (a freshwater fish-based diet [F group] or freshwater fish-based and red meat-based diets alternately [F/M group]) on liver steatosis and their relationship with intestinal flora in patients with nonalcoholic fatty liver disease (NAFLD). METHODS In this open-label, 84-day randomized controlled trial, 34 NAFLD patients with hepatic steatosis ≥10% were randomly assigned to the F group or F/M group in a 1:1 ratio using a computer-generated random number allocation by a researcher not involved in the study. Liver fat content and gut microbiota and its metabolites were measured. RESULTS At the end of intervention, the absolute reduction of hepatic steatosis was significantly greater in the F group than in the F/M group (-4.89% vs -1.83%, P = 0.032). Of the 16 secondary clinical outcomes, the improvement in 7 in the F group was greater compared with the F/M group, including alanine aminotransferase and gamma-glutamyl transferase. Furthermore, dietary freshwater fish and red meat consumption alternately did not exacerbate NAFLD. Moreover, changes in the enrichment of Faecalibacterium, short-chain fatty acids, and unconjugated bile acids and the depletion of Prevotella 9 and conjugated bile acids in the F group were significantly greater compared with the F/M group. DISCUSSION Higher intake of freshwater fish may be beneficial to NAFLD by regulating gut microbiota and its metabolites, whereas intake of a similar total of animal protein and fat from the alternating freshwater fish and red meat may not be harmful for NAFLD in the dietary management of patients with NAFLD.
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Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.
Liu, S, D'Amico, D, Shankland, E, Bhayana, S, Garcia, JM, Aebischer, P, Rinsch, C, Singh, A, Marcinek, DJ
JAMA network open. 2022;5(1):e2144279
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Older adults are the fastest growing age group in the world. As we age, we tend to lose muscle mass and strength which has consequences. Studies have shown that mitochondrial dysfunction plays an important part in age-related diseases. A reduction in the cells ability to dispose of its dysfunctional mitochondria (mitophagy) contributes to poor mitochondrial quality. Urolithin A is a natural food metabolite of the gut microbiome and has been shown to boost mitochondrial health by triggering mitophagy in both preclinical models of aging and in older adults. In this double-blind, placebo-controlled randomized clinical trial, 66 older adults were given either 1000mg of urolithin A or a placebo for 4 months. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed using magnetic resonance spectroscopy at baseline and at the end of study at 4 months. This study found that the improvements in the 6-minute walk distance and maximal ATP production in hand muscles were not significant for urolithin A. However, long-term supplementation with urolithin A significantly enhanced skeletal muscle endurance and improved the metabolic markers of mitochondrial function in older adults. This trial suggests that urolithin A may be a promising approach to counteract age-associated muscle decline. Future study is needed to confirm the role of urolithin A supplementation in healthy aging.
Abstract
Importance: Aging is associated with a decline in mitochondrial function and reduced exercise capacity. Urolithin A is a natural gut microbiome-derived food metabolite that has been shown to stimulate mitophagy and improve muscle function in older animals and to induce mitochondrial gene expression in older humans. Objective: To investigate whether oral administration of urolithin A improved the 6-minute walk distance, muscle endurance in hand and leg muscles, and biomarkers associated with mitochondrial and cellular health. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial in adults aged 65 to 90 years was conducted at a medical center and a cancer research center in Seattle, Washington, from March 1, 2018, to July 30, 2020. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed using magnetic resonance spectroscopy at baseline and at the end of study at 4 months. The analysis used an intention-to-treat approach. Interventions: Participants were randomized to receive daily oral supplementation with either 1000 mg urolithin A or placebo for 4 months. Main Outcomes and Measures: The primary end point was change from baseline in the 6-minute walk distance and change from baseline to 4 months in maximal ATP production in the hand skeletal muscle. The secondary end points were change in muscle endurance of 2 skeletal muscles (tibialis anterior [TA] in the leg and first dorsal interosseus [FDI] in the hand). Cellular health biomarkers were investigated via plasma metabolomics. Adverse events were recorded and compared between the 2 groups during the intervention period. Results: A total of 66 participants were randomized to either the urolithin A (n = 33) or the placebo (n = 33) intervention group. These participants had a mean (SD) age of 71.7 (4.94) years, were predominantly women (50 [75.8%]), and were all White individuals. Urolithin A, compared with placebo, significantly improved muscle endurance (ie, increase in the number of muscle contractions until fatigue from baseline) in the FDI and TA at 2 months (urolithin A: FDI, 95.3 [115.5] and TA, 41.4 [65.5]; placebo: FDI, 11.6 [147.4] and TA, 5.7 [127.1]). Plasma levels of several acylcarnitines, ceramides, and C-reactive protein were decreased by urolithin A, compared with placebo, at 4 months (baseline vs 4 mo: urolithin A, 2.14 [2.15] vs 2.07 [1.46]; placebo, 2.17 [2.52] vs 2.65 [1.86]). The mean (SD) increase from baseline in the 6-minute walk distance was 60.8 (67.2) m in the urolithin A group and 42.5 (73.3) m in the placebo group. The mean (SD) change from baseline to 4 months in maximal ATP production in the FDI was 0.07 (0.23) mM/s in the urolithin A group and 0.06 (0.20) mM/s in the placebo group; for the TA, it was -0.03 (0.10) mM/s in the urolithin A group and 0.03 (0.10) mM/s in the placebo group. These results showed no significant improvement with urolithin A supplementation compared with placebo. No statistical differences in adverse events were observed between the 2 groups. Conclusions and Relevance: This randomized clinical trial found that urolithin A supplementation was safe and well tolerated in the assessed population. Although the improvements in the 6-minute walk distance and maximal ATP production in the hand muscle were not significant in the urolithin A group vs the placebo group, long-term urolithin A supplementation was beneficial for muscle endurance and plasma biomarkers, suggesting that urolithin A may counteract age-associated muscle decline; however, future work is needed to confirm this finding. Trial Registration: ClinicalTrials.gov Identifier: NCT03283462.