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Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.
Li, S, Yin, S, Ding, H, Shao, Y, Zhou, S, Pu, W, Han, L, Wang, T, Yu, H
Cell proliferation. 2023;56(1):e13346
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Multiple risk factors could lead to the development of liver cancer, one of the most common malignant tumours in the world. These risk factors include hepatitis infection, non-alcoholic fatty liver disease and excessive alcohol consumption. Polyphenols are bioactive compounds with antioxidant, anti-inflammatory, anti-mutagenic, anti-viral, hypoglycaemic, anti-hypertensive, antibacterial and anti-proliferative properties. Polyphenols may be effective in reducing the risk of developing liver cancer by altering the metabolism. This review evaluated the effectiveness of polyphenols in protecting the liver and inhibiting hepatocarcinoma development. In addition, the review evaluated several mechanisms by which polyphenols affect glucose and lipid metabolism and mitochondrial metabolism and reduce the effects of oxidative stress, inflammation and toxic metabolites. Further robust studies are required to assess the beneficial effects of polyphenols as a therapeutic agent, as the current knowledge is limited. However, healthcare professionals can use the results of this study to understand the protective effects of polyphenols against liver disease.
Abstract
BACKGROUND Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and liver cancer prevention. RESULTS Targeting metabolic dysregulation in organisms prevents and resists the development of liver cancer, which has important implications for identifying new therapeutic strategies for the management and treatment of cancer. Polyphenols are a class of complex compounds composed of multiple phenolic hydroxyl groups and are the main active ingredients of many natural plants. They mediate a broad spectrum of biological and pharmacological functions containing complex lipid metabolism, glucose metabolism, iron metabolism, intestinal flora imbalance, as well as the direct interaction of their metabolites with key cell-signalling proteins. A large number of studies have found that polyphenols affect the metabolism of organisms by interfering with a variety of intracellular signals, thereby protecting the liver and reducing the risk of liver cancer. CONCLUSION This review systematically illustrates that various polyphenols, including resveratrol, chlorogenic acid, caffeic acid, dihydromyricetin, quercetin, catechins, curcumin, etc., improve metabolic disorders through direct or indirect pathways to protect the liver and fight liver cancer.
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Acute beetroot juice reduces blood pressure in young Black and White males but not females.
Grosicki, GJ, Flatt, AA, Cross, BL, Vondrasek, JD, Blumenburg, WT, Lincoln, ZR, Chall, A, Bryan, A, Patel, RP, Ricart, K, et al
Redox biology. 2023;63:102718
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Cardiovascular (CV) disease is the leading cause of death in the United States. Out of all ethnic groups, CV disease is particularly common in black Americans. High blood pressure (BP) is one of the main contributors to CV disease, and black Americans exhibit a disproportionally higher incident rate of high BP when compared to other ethnic groups. Partly this is due to genetic and physiological differences, yet is also influenced by social, socioeconomic, and environmental factors. One physiological difference that may contribute to higher BP in black adults appears to be a reduced availability of nitric oxide (NO). NO is a gas that is abundant in the human body. It regulates vascular tone and elasticity of the arteries, and therefore helps to manage blood pressure. Nitrates that occur in foods can be converted to NO and thus contribute to NO levels in the body. Beetroot juice (BRJ) is rich in nitrates. This study examined whether BRJ supplementation can reduce resting BP and cardiovascular reactivity in adults. The randomized, placebo-controlled, crossover-design study was completed by 18 black and 20 white young adults, male and female, with an average age of 21. The study monitored heart rate, BP and arterial stiffness in a variety of settings. The study also assessed socioeconomic status, perceived discrimination, sleep and dietary intake. The main findings from this investigation were that despite young black adults having higher resting BP, acute BRJ supplementation reduced the pressure to a similar extent in young black and white adults, but primarily in males. This reduction correlated with increased levels of circulating nitrites. However, acute BRJ supplementation did not influence resting arterial stiffness. The result also highlighted previously seen racial differences relating to social determinants of health and lifestyle, which may contribute to the elevated BP values seen in black participants. The study demonstrated that dietary nitrate from beetroot juice has the potential to be a cost-effective blood pressure-lowering strategy for young black and white males. Yet the findings also highlighted the complex interplay of social, lifestyle, and underlying physiological factors that influence racial differences when it comes to CV health
Abstract
A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.
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Sugar-sweetened beverages, low/no-calorie beverages, fruit juice and non-alcoholic fatty liver disease defined by fatty liver index: the SWEET project.
Naomi, ND, Ngo, J, Brouwer-Brolsma, EM, Buso, MEC, Soedamah-Muthu, SS, Pérez-Rodrigo, C, Harrold, JA, Halford, JCG, Raben, A, Geleijnse, JM, et al
Nutrition & diabetes. 2023;13(1):6
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Non-alcoholic fatty liver disease (NAFLD) refers to a broad range of liver disorders and the major determinants of NAFLD include sedentary lifestyles and poor-quality diets, namely high sugar intake. The main aim of this study was to investigate the association between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice (FJ) intakes and fatty liver index (FLI)-defined NAFLD. This study represents harmonised data of four European studies; Lifelines Cohort study, the Nutrition Questionnaire Plus study, the PREDIMED-Plus study, and the Alpha Omega Cohort. Results showed adverse associations between SSB and LNCB intakes and FLI-defined NAFLD prevalence, as well as between replacement of SSB with the same amount of LNCB and FLI-defined NAFLD. Furthermore, there was a beneficial association between moderate intake of FJ and FLI-defined NAFLD at intake level of ≤2 servings/day when compared to no intake. Authors conclude that long-term prospective studies with objective methods determining the intake of sugar and sweeteners are warranted to further substantiate the findings of their study.
Abstract
BACKGROUND Sweetened beverage intake may play a role in non-alcoholic fatty liver disease (NAFLD) development, but scientific evidence on their role is limited. This study examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB) and fruit juice (FJ) intakes and NAFLD in four European studies. METHODS Data for 42,024 participants of Lifelines Cohort, NQPlus, PREDIMED-Plus and Alpha Omega Cohort were cross-sectionally analysed. NAFLD was assessed using Fatty Liver Index (FLI) (≥60). Restricted cubic spline analyses were used to visualize dose-response associations in Lifelines Cohort. Cox proportional hazard regression analyses with robust variance were performed for associations in individual cohorts; data were pooled using random effects meta-analysis. Models were adjusted for demographic, lifestyle, and other dietary factors. RESULTS Each additional serving of SSB per day was associated with a 7% higher FLI-defined NAFLD prevalence (95%CI 1.03-1.11). For LNCB, restricted cubic spline analysis showed a nonlinear association with FLI-defined NAFLD, with the association getting stronger when consuming ≤1 serving/day and levelling off at higher intake levels. Pooled Cox analysis showed that intake of >2 LNCB servings/week was positively associated with FLI-defined NAFLD (PR 1.38, 95% CI 1.15-1.61; reference: non-consumers). An inverse association was observed for FJ intake of ≤2 servings/week (PR 0.92, 95% CI: 0.88-0.97; reference: non-consumers), but not at higher intake levels. Theoretical replacement of SSB with FJ showed no significant association with FLI-defined NAFLD prevalence (PR 0.97, 95% CI 0.95-1.00), whereas an adverse association was observed when SSB was replaced with LNCB (PR 1.12, 95% CI 1.03-1.21). CONCLUSIONS Pooling results of this study showed that SSB and LNCB were positively associated with FLI-defined NAFLD prevalence. Theoretical replacement of SSB with LNCB was associated with higher FLI-defined NAFLD prevalence. An inverse association was observed between moderate intake of FJ and FLI-defined NAFLD. Our results should be interpreted with caution as reverse causality cannot be ruled out.
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Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials.
Wang, T, Zhang, X, Zhou, N, Shen, Y, Li, B, Chen, BE, Li, X
Journal of the American Heart Association. 2023;12(11):e029512
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Dyslipidaemia is considered to be a risk factor for cardiovascular disease (CVD) and the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to confer benefits for both dyslipidaemia and CVD, although results from clinical trials and meta-analyses (studies pooling data from smaller studies to increase statistical power) are mixed. The aim of this meta-analysis, using a particular statistical method, was to evaluate whether dose-response relationships may be non-linear. This meta-analysis included 90 randomised controlled trials with 72,598 participants overall. Lipids evaluated were triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and non-HDL cholesterol. A near linear relationship was seen between intake of combined EPA and DHA and a decrease in TG and non-HDL, both overall and for the subgroups of patients with and without hyperlipidaemia and overweight. For LDL and HDL, J-shaped relationships were seen, with an increase followed by a decrease with increasing EPA + DHA intake, both overall and in the subgroups with and without hyperlipidaemia. The authors also pooled data from studies which used the red blood cell omega index (a measure of omega-3 status) and found that with increasing omega-3 status, TG and non-HDL declined whilst HDL increased in a near linear fashion, whilst there was still a J-shaped curve for LDL. The authors consider that a medium dose of EPA + DHA may be needed for the management of dyslipidaemia, and a high dose for people at high risk of developing CVD.
Abstract
Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.
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An Open-Label Case Series of Glutathione Use for Symptomatic Management in Children with Autism Spectrum Disorder.
Radwan, K, Wu, G, Banks-Word, K, Rosenberger, R
Medical sciences (Basel, Switzerland). 2023;11(4)
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause impaired social–emotional interactions, impaired language and communication skills, repetitive or restrictive behaviours, and sometimes aggressive behaviour. The causes of ASD are complex and unclear. There is an increasing recognition that ASD might be associated with oxidative stress and the toxic build-up of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. The aim of this 12-week open-label pilot study was to investigate the tolerability and effectiveness of oral supplementation with OpitacTM glutathione as a treatment for patients with ASD. Six participants took part. Glutathione was generally well-tolerated except in the case of one subject. Some subjects showed improved total antioxidant capacity, and there was a mild improvement in the severity of ASD symptoms in 66.7% of the patients. However, none of the observed changes in the pre- and post-treatment oxidative laboratory markers and Aberrant Behaviour Checklist (ABC) scores were statistically significant. An imbalance in redox reactions is only one of the many factors contributing to ASD. Further studies are necessary to investigate the other factors.
Abstract
Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. The existing data suggest that early diagnosis and intervention can improve ASD outcomes. The causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. There is an increasing recognition that ASD might be associated with oxidative stress through several mechanisms including abnormal metabolism (lipid peroxidation) and the toxic buildup of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. This open-label pilot study investigates the tolerability and effectiveness of oral supplementation with OpitacTM gluthathione as a treatment for patients with ASD. The various aspects of glutathione OpitacTM glutathione bioavailability were examined when administered by oral routes. The absorption of glutathione from the gastrointestinal tract has been recently investigated. The results of this case series suggest that oral glutathione supplementation may improve oxidative markers, but this does not necessarily translate to the observed clinical improvement of subjects with ASD. The study reports a good safety profile of glutathione use, with stomach upset reported in four out of six subjects. This article discusses the role of the gut microbiome and redox balance in ASD and notes that a high baseline oxidative burden may make some patients poor responders to glutathione supplementation. In conclusion, an imbalance in redox reactions is only one of the many factors contributing to ASD, and further studies are necessary to investigate other factors, such as impaired neurotransmission, immune dysregulation in the brain, and mitochondrial dysfunction.
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Exploring choices of early nutritional support for patients with sepsis based on changes in intestinal microecology.
Yang, XJ, Wang, XH, Yang, MY, Ren, HY, Chen, H, Zhang, XY, Liu, QF, Yang, G, Yang, Y, Yang, XJ
World journal of gastroenterology. 2023;29(13):2034-2049
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Sepsis is a condition brought about by infection and results in organ dysfunction and gut microbiota imbalance. Nutrition plays a large part in recovery from sepsis, however it is unclear as to the optimal diet for gut microbial balance in individuals with sepsis. This randomised control trial of 30 individuals with sepsis aimed to determine the optimal delivery of nutrition for gut microbial health either through a gastric tube (TEN), through the jugular vein (TPN), or a mixture of the two modes (SPN). The results showed differences in gut microbiota composition between the different modes of nutrition. Enterococcus increased in TEN, Campylobacter decreased in TPN, and Dialister decreased in SPN groups. Fermentation products produced by gut microbiota also changed depending on the mode of nutrition, with the TEN group showing improvements amongst the most fermentation products. Individuals in the TEN group also showed improved immune system function alongside those in the SPN group. It was concluded that based upon improvements to the immune system and gut microbiota, TEN is the most suitable mode for nutrition in individuals with sepsis. This study could be used by healthcare professionals to understand that nutrition methods for individuals with sepsis aren’t equally effective and recovery may be faster if individuals receive nutrition through a gastric tube.
Abstract
BACKGROUND Sepsis exacerbates intestinal microecological disorders leading to poor prognosis. Proper modalities of nutritional support can improve nutrition, immunity, and intestinal microecology. AIM: To identify the optimal modality of early nutritional support for patients with sepsis from the perspective of intestinal microecology. METHODS Thirty patients with sepsis admitted to the intensive care unit of the General Hospital of Ningxia Medical University, China, between 2019 and 2021 with indications for nutritional support, were randomly assigned to one of three different modalities of nutritional support for a total of 5 d: Total enteral nutrition (TEN group), total parenteral nutrition (TPN group), and supplemental parenteral nutrition (SPN group). Blood and stool specimens were collected before and after nutritional support, and changes in gut microbiota, short-chain fatty acids (SCFAs), and immune and nutritional indicators were detected and compared among the three groups. RESULTS In comparison with before nutritional support, the three groups after nutritional support presented: (1) Differences in the gut bacteria (Enterococcus increased in the TEN group, Campylobacter decreased in the TPN group, and Dialister decreased in the SPN group; all P < 0.05); (2) different trends in SCFAs (the TEN group showed improvement except for Caproic acid, the TPN group showed improvement only for acetic and propionic acid, and the SPN group showed a decreasing trend); (3) significant improvement of the nutritional and immunological indicators in the TEN and SPN groups, while only immunoglobulin G improved in the TPN group (all P < 0.05); and (4) a significant correlation was found between the gut bacteria, SCFAs, and nutritional and immunological indicators (all P < 0.05). CONCLUSION TEN is recommended as the preferred mode of early nutritional support in sepsis based on clinical nutritional and immunological indicators, as well as changes in intestinal microecology.
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Effects of prebiotics, probiotics and synbiotics on serum creatinine in non-dialysis patients: a meta-analysis of randomized controlled trials.
Liu, F, Liu, Y, Lv, X, Lun, H
Renal failure. 2023;45(1):2152693
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Creatinine is a biomarker of kidney function and is used to diagnose chronic kidney disease. The aim of this meta-analysis of randomised controlled trials was to evaluate the effect of supplementation with prebiotics, probiotics and synbiotics on serum creatinine levels in patients not receiving dialysis. 12 RCTs were included in the meta-analysis of which seven were judged to have a low risk of bias whilst 1 was judged to have a high risk of bias. Overall, there was no significant effect of supplementation on serum creatinine levels. The following three subgroup analyses also showed no significant effects on creatinine levels: 1) by probiotics, prebiotics and synbiotics separately; 2) by duration: two months or less or longer than two months, 3) subgroup of 7 studies which included patients with non-dialysis kidney disease. The authors concluded that probiotics, prebiotics and synbiotics do not decrease serum creatinine levels.
Abstract
OBJECTIVE Serum creatinine level are influenced by many factors. Although accumulated data suggested that prebiotics, probiotics and synbiotics supplements could affect serum creatinine level, the results remained controversial. The aim of the present paper was to evaluate the effects of prebiotics, probiotics and synbiotics on serum creatinine in non-dialysis patients. METHODS PubMed, EMBASE (Excerpta Medica Database) and the Cochrane Library databases were searched for eligible randomized, controlled trials (RCTs) which were limited to English language studies until 30 September 2022. A random-effects model was performed to analyze the impact of pooled trials. RESULT Twelve randomized, controlled trial studies were included in the meta-analysis. Prebiotics, probiotics or synbiotics supplementation did not significantly decrease the serum creatinine levels in non-dialysis patients compared to placebo [standardized mean difference (SMD) = 0.05; 95% confidence interval (CI): (-0.21, 0.31); p = 0.72; I2 = 61%]. CONCLUSION The present meta-analysis indicated that supplementation with prebiotics, probiotics and synbiotics could not act as promising adjuvant therapies to decrease the serum creatinine levels in non-dialysis patients.
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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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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
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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10.
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.