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Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.
Chávez-Hidalgo, LP, Martín-Fernández-de-Labastida, S, M de Pancorbo, M, Arroyo-Izaga, M
World journal of gastroenterology. 2023;29(7):1219-1234
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Colorectal cancer (CRC) is the third most frequent type of cancer and yet has the second highest mortality rate in cancer patients worldwide. Hence there is an urgency to understand more about dietary and lifestyle factors that can help to prevent this type of cancer. It is known that folate has a preventive function in CRC, possibly due to its role in DNA methylation. Methylation is the addition of methyl groups to DNA, which influences gene expression and regulation. This systematic review investigated how folate and other dietary methyl groups and methyl influencers such as B vitamins and alcohol influence the development of CRC, whilst also considering various genetic variants in methyl-metabolising enzymes (polymorphisms). The analysis included a total of 19 case-control and cohort studies and highlighted that potential interactions between methyl donor nutrients, genetic variants, and alcohol influence CRC risk. For most, high levels of folate intake were considered a protective factor, while high alcohol consumption proved to be a risk factor. Yet these interactions appear to be complex, with gender, genetic variations and folate status appearing to contribute to variable and, in some cases, contradictory outcomes. The authors suggested in their findings that Vitamin B6, Vitamin B3 (Niacin), and alcohol may affect CRC by influencing its risk by acting on both the genetic code itself and the epigenetic factors that control gene activity. Further research is needed to better understand the complexity of these mechanisms, and to help clarify the influence of methyl group donors as epigenetic regulators of gene activity in CRC development.
Abstract
BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
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Nutritional intervention for diabetes mellitus with Alzheimer's disease.
Li, Z, Li, S, Xiao, Y, Zhong, T, Yu, X, Wang, L
Frontiers in nutrition. 2022;9:1046726
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Diabetes Mellitus (DM) affects more than 463 million people worldwide. Similarly, the number of deaths related to Alzheimer’s disease (AD) has increased by 145%. There are several common risk factors for Type 2 Diabetes and AD, including obesity, insulin resistance, and ageing, as well as common pathological mechanisms, including altered insulin signalling, oxidative stress, neuroinflammation, mitochondrial dysfunction, formation of glycated proteins and metabolic syndrome. This review aims to summarize the therapeutic effects of different nutritional therapy strategies on the reduction of DM and AD risk. Controlling blood sugar levels and reducing calorie intake is crucial to preventing diabetes and Alzheimer's disease. The low-carbohydrate, ketogenic, and Mediterranean diets have been found to improve glucose control in people with Type 2 diabetes (T2D). In addition, MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) and a ketogenic diet may improve cognition in AD patients. Lactobacillus, Bifidobacterium probiotics, and prebiotics, such as inulin, may inhibit the progression of T2D and AD diseases by suppressing inflammation and modulating gut microbes. In addition, vitamins A, C, D, E, B6, B12, folate, long-chain polyunsaturated fatty acids, zinc, magnesium, and polyphenols may improve cognitive decline, homocysteine levels, and insulin resistance in AD and T2D patients. Healthcare professionals can use the results of this review to understand the beneficial effects of dietary strategies and multi-nutrient supplementation on DM and AD. However, further robust studies are required to investigate the risk factors and underlying mechanisms behind DM-combined AD progression.
Abstract
The combined disease burden of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing, and the two diseases share some common pathological changes. However, the pharmacotherapeutic approach to this clinical complexity is limited to symptomatic rather than disease-arresting, with the possible exception of metformin. Whether nutritional intervention might extend or synergize with these effects of metformin is of interest. In particular, dietary patterns with an emphasis on dietary diversity shown to affect cognitive function are of growing interest in a range of food cultural settings. This paper presents the association between diabetes and AD. In addition, the cross-cultural nutritional intervention programs with the potential to mitigate both insulin resistance (IR) and hyperglycemia, together with cognitive impairment are also reviewed. Both dietary patterns and nutritional supplementation showed the effects of improving glycemic control and reducing cognitive decline in diabetes associated with AD, but the intervention specificity remained controversial. Multi-nutrient supplements combined with diverse diets may have preventive and therapeutic potential for DM combined with AD, at least as related to the B vitamin group and folate-dependent homocysteine (Hcy). The nutritional intervention has promise in the prevention and management of DM and AD comorbidities, and more clinical studies would be of nutritional scientific merit.
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Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial.
Noah, L, Dye, L, Bois De Fer, B, Mazur, A, Pickering, G, Pouteau, E
Stress and health : journal of the International Society for the Investigation of Stress. 2021;37(5):1000-1009
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Stress and low magnesemia are shown to be linked by previous research evidence. Additionally, Vitamin B6 (pyridoxine) has been shown to have stress-relieving and neuromodulating effects. This 1:1 randomised, investigator-blinded, parallel-group trial compared the effectiveness of magnesium alone and a combination of magnesium and vitamin B6 in participants with moderate to severe stress on mental and physical health. Participants consumed 300 mg magnesium lactate dihydrate daily with 30 mg Vitamin B6 or 300 mg magnesium lactate dihydrate daily for 8 weeks. Treatment with magnesium with or without vitamin B6 improved depression and anxiety, specifically a significant improvement observed after week four of the intervention. Quality of life improvements were sustained over 8 weeks among participants with magnesemia. Combined supplementation of magnesium and vitamin B6 increased the perceived capacity for physical activity in participants. Further robust research is needed to evaluate the combined effects of vitamin B6 and magnesium on stress-related mental health in people with magnesemia. However, healthcare professionals can use the results of this study to better understand magnesium and vitamin B6 supplementation's positive effects on stress-related mental health.
Abstract
Magnesium status and vitamin B6 intake have been linked to mental health and/or quality of life (QoL). In an 8-week Phase IV randomised controlled study in individuals with low magnesemia and severe/extremely severe stress but who were otherwise healthy, greater stress reduction was achieved with magnesium combined with vitamin B6 than with magnesium alone. We present a previously unreported secondary analysis of the effect of magnesium, with and without vitamin B6, on depression, anxiety, and QoL. Adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 were randomised 1:1 to magnesium + vitamin B6 combination (Magne B6® ; daily dose 300 and 30 mg, respectively) or magnesium alone (Magnespasmyl® ; daily dose 300 mg). Outcomes included changes from baseline in DASS-42 depression and anxiety scores, and QoL (Short Form-36 Health Survey). DASS-42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks. Improvement in QoL continued over 8 weeks. Participants' perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than magnesium alone (Week 4). In conclusion, magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia.
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Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections.
Calder, PC, Carr, AC, Gombart, AF, Eggersdorfer, M
Nutrients. 2020;12(4)
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Acute respiratory tract infections are a major cause of morbidity and mortality across the globe with seasonal influenza epidemics and outbreaks of viruses, such as Covid-19. The authors support public hygiene practices and the development of vaccinations however call for further strategies in order to reduce the impact that these infections have on societies. The role nutrition plays in supporting the immune system is well established. This review article and opinion piece presents the evidence for Vitamins A, B6, B12, C, D, E and folate; trace elements including zinc, selenium, magnesium and copper; and omega-3 fatty acids in supporting the immune system. The authors call for the consumption of a well-balanced diet, with additional supplementation of key immune supportive nutrients. Well referenced and with a helpful table of the rationale and recommended nutrient intake levels, Nutrition Practitioners will find this article useful when working to support client immune health.
Abstract
Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, were responsible for approximately 2.38 million deaths worldwide in 2016. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: (1) supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; (2) supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and (3) public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.
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Nutrition amid the COVID-19 pandemic: a multi-level framework for action.
Naja, F, Hamadeh, R
European journal of clinical nutrition. 2020;74(8):1117-1121
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This Lebanese articled provides a commentary on the evolving COVID-19 pandemic and aims to give a framework for Nutritional action to help the physical and mental health of individuals, communities, and nations. At an individual level the focus is on the link between diet and immunity and the profound effect diet has on people’s immune system and disease susceptibility. An adequate intake of iron, zinc, and vitamins A, E, B6, and B12 is predominantly vital for the maintenance of immune function. Individuals should aim to eat as healthily as possible, including a wide range of fruits and vegetables, limit snacking, take regular exercise and get an adequate amount of sleep to support their health. Single foods promising cures or prevention of infection are unfounded claims which can give a false sense of security. The focus for communities is on food availability, for nations its food security and on a global level it is about food trade agreements. Its important to protect against hoarding and panic buying to ensure enough food for everyone. National economic instability during COVID-19 can lead to a risk of food security so governments are advised to support local agricultural produce and reduce their reliance on imported goods. Global supply chains and agreements need to be respected to lessen the impact further down the supply chain. The health of each individual has a direct impact on the community and nation and is a direct consequence of their dietary awareness and choices.
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Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.
Pouteau, E, Kabir-Ahmadi, M, Noah, L, Mazur, A, Dye, L, Hellhammer, J, Pickering, G, Dubray, C
PloS one. 2018;13(12):e0208454
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Magnesium (Mg) plays a role in over 600 biochemical reactions. It is depleted during stress, and a lack of Mg increases the release of stress hormones, leading to a vicious cycle of lowered resistance to stress and further Mg depletion. Vitamin B6 influences neurotransmitters involved in depression and anxiety, and may improve the uptake of magnesium into cells. The aim of this randomised control trial was to evaluate the effects of combined magnesium and vitamin B6 supplementation in stressed people with low blood levels of magnesium. 260 adults aged 18-50 completed the 8-week study. At the beginning of the trial, all participants had suboptimal blood serum magnesium (0.45 mmol/L to 0.85 mmol/L) and reported moderate to extremely severe stress levels. Participants were divided into two groups. One group received magnesium supplementation (465mg magnesium lactate dihydrate, equivalent to 300mg elemental magnesium; Mg), whilst the other received a combined magnesium and vitamin B6 supplement (470 mg magnesium lactate dihydrate plus 5 mg pyridoxine hydrochloride; Mg-B6). After 8 weeks, the Mg-B6 group reported a reduction in stress levels of 44.9%, and the Mg group reported a reduction of 42.4%, with no statistical difference between the two groups overall. However, participants who reported severe or extremely severe stress levels at the start of the study experienced 24% greater improvement with Mg-B6 versus Mg. Researchers concluded that in people with low magnesium levels experiencing severe or extremely severe stress, combining vitamin B6 with magnesium appears to be of greater benefit than supplementing Mg alone.
Abstract
INTRODUCTION Animal and clinical studies suggest complementary effects of magnesium and high-dose pyridoxine (vitamin B6) on stress reduction. This is the first randomized trial evaluating the effects of combined magnesium and vitamin B6 supplementation on stress in a stressed population with low magnesemia using a validated measure of perceived stress. METHODS In this Phase IV, investigator-blinded trial (EudraCT: 2015-003749-24), healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L-0.85 mmol/L, were randomized 1:1 to magnesium-vitamin B6 combination (Magne B6 [Mg-vitamin B6]; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl [Mg]; daily dose 300 mg). Outcomes included change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (AEs). RESULTS In the modified intention-to-treat analysis (N = 264 subjects), both treatment arms substantially reduced DASS-42 stress subscale score from baseline to Week 8 (Mg-vitamin B6, 44.9%; Mg 42.4%); no statistical difference between arms was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; N = 162) had a 24% greater improvement with Mg-vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). Consistent results were observed in the per protocol analysis and at Week 4. Overall, 12.1% of Mg-vitamin B6 treated and 17.4% of Mg-treated subjects experienced AEs potentially treatment related. CONCLUSIONS These findings suggest oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6.
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The Effect of a High-Dose Vitamin B Multivitamin Supplement on the Relationship between Brain Metabolism and Blood Biomarkers of Oxidative Stress: A Randomized Control Trial.
Ford, TC, Downey, LA, Simpson, T, McPhee, G, Oliver, C, Stough, C
Nutrients. 2018;10(12)
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A diet rich in vitamins and micronutrients, particularly B vitamins, is essential for body and brain functionality. B vitamin supplementation has been found to reduce depression, enhance mood, lessen anxiety and improve cognition. New neuroimaging techniques have shed light on the relationship between blood and neural biomarkers, connecting diet quality and brain function. The aim of this randomised, placebo-controlled, double-blind trial was to investigate the effect of 6-month high-dose B-vitamin supplementation on neural and blood biomarkers of metabolism in 32 healthy adults. Participants were randomised to consume either B-vitamin supplementation or placebo pills twice a day for six months and underwent blood tests and brain imaging before and after supplementation. This study found supplementation effectively increased vitamin B6 and B12 levels and reduced homocysteine with no changes in folate as compared with placebo. Supplementation promoted neural metabolic pathways and reduced oxidative stress and inflammation. Based on these findings, the authors conclude B-group vitamins are important for maintaining brain health in healthy adults and may play a role in prevention and alleviation of neural disease and disability.
Abstract
A diet rich in B-group vitamins is essential for optimal body and brain function, and insufficient amounts of such vitamins have been associated with higher levels of neural inflammation and oxidative stress, as marked by increased blood plasma homocysteine. Neural biomarkers of oxidative stress quantified through proton magnetic spectroscopy (1H-MRS) are not well understood, and the relationship between such neural and blood biomarkers is seldom studied. The current study addresses this gap by investigating the direct effect of 6-month high-dose B-group vitamin supplementation on neural and blood biomarkers of metabolism. Using a randomized, double-blind, placebo-controlled design, 32 healthy adults (20 female, 12 male) aged 30⁻65 years underwent blood tests (vitamin B6, vitamin B12, folate, and homocysteine levels) and 1H-MRS of the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) before and after supplementation. Results confirmed the supplement was effective in increasing vitamin B6 and vitamin B12 levels and reducing homocysteine, whereas there was no change in folate levels. There were significant relationships between vitamin B6 and N-acetylaspartate (NAA), choline, and creatine, as well as between vitamin B12 and creatine (ps < 0.05), whereas NAA in the PCC increased, albeit not significantly (p > 0.05). Together these data provide preliminary evidence for the efficacy of high-dose B-group supplementation in reducing oxidative stress and inflammation through increasing oxidative metabolism. It may also promote myelination, cellular metabolism, and energy storage.
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Functional biochemical and nutrient indices in frail elderly people are partly affected by dietary supplements but not by exercise.
de Jong, N, Chin A Paw, MJ, de Groot, LC, de Graaf, C, Kok, FJ, van Staveren, WA
The Journal of nutrition. 1999;129(11):2028-36
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Elderly people are at risk of nutritional deficiencies for a variety of reasons including reduced appetite, increased medication, and alterations in the absorption and metabolism of vitamins and minerals with age. The aim of this study was to measure the influence of exercise, and supplementing the diet with vitamins and minerals, on indicators of nutritional and health status in frail elderly people. A 17-week randomised controlled trial was carried out on 145 frail elderly people living in the community. Participants were given either; 1) food products enriched with vitamins D, E, thiamine, riboflavin, B6, folic acid, B12, calcium, magnesium, zinc, iron and iodine; 2) an exercise programme; 3) both enriched food products and exercise programme; or 4) food products that had not been enriched and a social programme (the control group). At the end of the study, significant improvements in the blood levels of vitamins B6, B12, C and D were detected in the groups receiving the enriched food products compared to the controls. There was no additional benefit to be gained from exercise. The improvement in nutritional status did not appear to influence several other biological indicators of health, perhaps because these indicators were already within normal levels at the start of the study. Despite this, the authors concluded that long-term supplementation may help to maintain optimal vitamin and mineral levels in elderly people, and therefore reduce the chance of this population developing health problems related to malnutrition.
Abstract
A decline in dietary intake due to inactivity and, consequently, development of a suboptimal nutritional status is a major problem in frail elderly people. However, benefits of micronutrient supplementation, all-round physical exercise or a combination of both on functional biochemical and hematologic indicators of nutritional and health status in frail elderly subjects have not been tested thoroughly. A 17-wk randomized controlled trial was performed in 145 free-living frail elderly people (43 men, 102 women, mean age, 78 +/- 5.7 y). Based on a 2 x 2 factorial design, subjects were assigned to one of the following: 1) nutrient-dense foods, 2) exercise, 3) both (1) and (2) or 4) a control group. Foods were enriched with micronutrients, frequently characterized as deficient [25-100% of the recommended daily allowance (RDA)] in elderly people. Exercises focused on skill training, including strength, endurance, coordination and flexibility. Dietary intake, blood vitamin levels and nutritional and health indicators, including (pre)albumin, ferritin, transferrin, C-reactive protein, hemoglobin and lymphocytes were measured. At baseline, 28% of the total population had an energy intake below 6.3 MJ, up to a maximum of 93% having vitamin intakes below two thirds of the Dutch RDA. Individual deficiencies in blood at baseline ranged from 3% for erythrocyte glutathione reductase-alpha to 39% for 25-hydroxy vitamin D and 42% for vitamin B-12. These were corrected after 17 wk in the two groups receiving the nutrient-dense foods, whereas no significant changes were observed in the control or exercise group. Biochemical and hematologic indicators at baseline were within the reference ranges (mean albumin, 46 g/L; prealbumin, 0.25 g/L; hemoglobin, 8.6 mmol/L) and were not affected by any of the interventions. The long-term protective effects of nutrient supplementation and exercise, by maintaining optimal nutrient levels and thereby reducing the initial chance of developing critical biochemical values, require further investigation. Other indicative functional variables for suboptimal nutritional status, in addition to those currently selected, should also be explored.