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1.
Vitamin E: Not only a single stereoisomer.
Eggersdorfer, M, Schmidt, K, Péter, S, Richards, J, Winklhofer-Roob, B, Hahn, A, Obermüller-Jevic, U
Free radical biology & medicine. 2024;:106-111
Abstract
The recent publication by Azzi and colleagues puts forth the argument that only RRR-α-tocopherol should be considered as vitamin E from a physiological point of view. They base their argument primarily on the assertion that only this form has been used to treat stark vitamin E deficiency in humans (known as AVED, or Ataxia with Vitamin E Deficiency). Azzi et al. also argue that other chemically similar molecules, such as tocopherols other than α-tocopherol and tocotrienols do not provide vitamin E activity. Azzi and colleagues are correct on this second point. An investigation into the biological activities of vitamin E, and the mechanisms behind these activities, confirms that physiological vitamin E activity is limited to certain α-tocopherol forms. However, it is also clear that these activities are not restricted only to the RRR-form but include other 2R-forms as well. Indeed, the α-tocopherol transfer protein (α-TTP), which is critical to mediate vitamin E trafficking and biological activity, and genetic defects of which lead to vitamin E deficiency, binds well to all 2R-forms of α-tocopherol. Furthermore, both RRR-α-tocopherol and the other 2R-forms are maintained in human plasma and distributed to tissues and organs, whereas the 2S-stereoisomers are excreted quickly. As such, in recent years the definition of vitamin E including both 2R- and RRR-α-tocopherol has gained both broad scientific and regulatory acceptance. Consistent with this understanding, we provide evidence that AVED has indeed been treated successfully with forms in addition to RRR-α-tocopherol, again arguing against the restriction of the definition to RRR-α-tocopherol only. Finally, we provide evidence against any safety concerns utilizing the currently accepted definition of vitamin E.
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2.
Perspective: Role of Micronutrients and Omega-3 Long-Chain Polyunsaturated Fatty Acids for Immune Outcomes of Relevance to Infections in Older Adults-A Narrative Review and Call for Action.
Eggersdorfer, M, Berger, MM, Calder, PC, Gombart, AF, Ho, E, Laviano, A, Meydani, SN
Advances in nutrition (Bethesda, Md.). 2022;(5):1415-1430
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Abstract
The immune system is weakened by advancing age, often referred to as immunosenescence, increasing the vulnerability to, and frequently the severity of, infectious diseases in older people. This has become very apparent in the current coronavirus disease 2019 (COVID-19) pandemic for which older people are at higher risk of severe outcomes, even those who are fully vaccinated. Aging affects both the innate and adaptive immune systems and is characterized by an imbalanced inflammatory response. Increasing evidence shows that optimal status of nutrients such as vitamins C, D, and E and selenium and zinc as well as the omega-3 (n-3) fatty acids DHA and EPA can help compensate for these age-related changes. While inadequate intakes of these nutrients are widespread in the general population, this is often more pronounced in older people. Maintaining adequate intakes is a challenge for them due to a range of factors such as physical, physiological, and cognitive changes; altered absorption; and the presence of noncommunicable diseases. While nutritional requirements are ideally covered by a balanced diet, this can be difficult to achieve, particularly for older people. Fortified foods and nutritional complements are effective in achieving adequate micronutrient intakes and should be considered as a safe and cost-effective means for older people to improve their nutritional status and hence support their defense against infections. Complementing the diet with a combination of micronutrients, particularly those playing a key role in the immune system such as vitamins C, D, and E and selenium and zinc as well as DHA and EPA, is recommended for older people. Optimal nutrition to support the immune system in older people will remain essential, particularly in the face of the current COVID-19 pandemic and, thus, developing strategies to ensure adequate nutrition for the growing number of older adults will be an important and cost-effective investment in the future.
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Beyond Nutrient Deficiency-Opportunities to Improve Nutritional Status and Promote Health Modernizing DRIs and Supplementation Recommendations.
McBurney, MI, Blumberg, JB, Costello, RB, Eggersdorfer, M, Erdman, JW, Harris, WS, Johnson, EJ, Hazels Mitmesser, S, Post, RC, Rai, D, et al
Nutrients. 2021;(6)
Abstract
The US Dietary Guidelines for Americans (DGA) provide dietary recommendations to meet nutrient needs, promote health, and prevent disease. Despite 40 years of DGA, the prevalence of under-consumed nutrients continues in the US and globally, although dietary supplement use can help to fill shortfalls. Nutrient recommendations are based on Dietary Reference Intakes (DRIs) to meet the nutrient requirements for nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group and many need to be updated using current evidence. There is an opportunity to modernize vitamin and mineral intake recommendations based on biomarker or surrogate endpoint levels needed to 'prevent deficiency' with DRIs based on ranges of biomarker or surrogate endpoints levels that support normal cell/organ/tissue function in healthy individuals, and to establish DRIs for bioactive compounds. We recommend vitamin K and Mg DRIs be updated and DRIs be established for lutein and eicosapentaenoic and docosahexaenoic acid (EPA + DHA). With increasing interest in personalized (or precision) nutrition, we propose greater research investment in validating biomarkers and metabolic health measures and the development and use of inexpensive diagnostic devices. Data generated from such approaches will help elucidate optimal nutrient status, provide objective evaluations of an individual's nutritional status, and serve to provide personalized nutrition guidance.
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The Role of Micronutrients in Ageing Asia: What Can Be Implemented with the Existing Insights.
Inui, T, Hanley, B, Tee, ES, Nishihira, J, Tontisirin, K, Van Dael, P, Eggersdorfer, M
Nutrients. 2021;(7)
Abstract
Life expectancy as a measure of population health does not reflect years of healthy life. The average life expectancy in the Asia-Pacific region has more than doubled since 1900 and is now above 70 years. In the Asia-Pacific region, the proportion of aged people in the population is expected to double between 2017 and 2050. Increased life expectancy leads to an increase in non-communicable diseases, which consequently affects quality of life. Suboptimal nutritional status is a contributing factor to the prevalence and severity of non-communicable diseases, including cardiovascular, cognitive, musculoskeletal, immune, metabolic and ophthalmological functions. We have reviewed the published literature on nutrition and healthy ageing as it applies to the Asia-Pacific region, focusing on vitamins, minerals/trace elements and omega-3 fatty acids. Optimal nutritional status needs to start before a senior age is reached and before the consequences of the disease process are irreversible. Based on the nutritional status and health issues in the senior age in the region, micronutrients of particular importance are vitamins A, D, E, C, B-12, zinc and omega-3 fatty acids. The present paper substantiates the creation of micronutrient guidelines and proposes actions to support the achievement of optimal nutritional status as contribution to healthy ageing for Asia-Pacific populations.
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Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action.
Berger, MM, Herter-Aeberli, I, Zimmermann, MB, Spieldenner, J, Eggersdorfer, M
Clinical nutrition ESPEN. 2021;:39-48
Abstract
BACKGROUND The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.
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Reply to "Overstated Claims of Efficacy and Safety. Comment On: Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients 2020, 12, 1181".
Calder, PC, Carr, AC, Gombart, AF, Eggersdorfer, M
Nutrients. 2020;(9)
Abstract
We thank Vorland et al [...].
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7.
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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Expert Opinion on Benefits of Long-Chain Omega-3 Fatty Acids (DHA and EPA) in Aging and Clinical Nutrition.
Troesch, B, Eggersdorfer, M, Laviano, A, Rolland, Y, Smith, AD, Warnke, I, Weimann, A, Calder, PC
Nutrients. 2020;(9)
Abstract
Life expectancy is increasing and so is the prevalence of age-related non-communicable diseases (NCDs). Consequently, older people and patients present with multi-morbidities and more complex needs, putting significant pressure on healthcare systems. Effective nutrition interventions could be an important tool to address patient needs, improve clinical outcomes and reduce healthcare costs. Inflammation plays a central role in NCDs, so targeting it is relevant to disease prevention and treatment. The long-chain omega-3 polyunsaturated fatty acids (omega-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to reduce inflammation and promote its resolution, suggesting a beneficial role in various therapeutic areas. An expert group reviewed the data on omega-3 LCPUFAs in specific patient populations and medical conditions. Evidence for benefits in cognitive health, age- and disease-related decline in muscle mass, cancer treatment, surgical patients and critical illness was identified. Use of DHA and EPA in some conditions is already included in some relevant guidelines. However, it is important to note that data on the effects of omega-3 LCPUFAs are still inconsistent in many areas (e.g., cognitive decline) due to a range of factors that vary amongst the trials performed to date; these factors include dose, timing and duration; baseline omega-3 LCPUFA status; and intake of other nutrients. Well-designed intervention studies are required to optimize the effects of DHA and EPA in specific patient populations and to develop more personalized strategies for their use.
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Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort: The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study.
Minović, I, Kieneker, LM, Gansevoort, RT, Eggersdorfer, M, Touw, DJ, Voerman, AJ, Connelly, MA, Boer, RA, Hak, E, Bos, J, et al
Nutrients. 2020;(9)
Abstract
BACKGROUND a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation. METHODS we measured plasma pyridoxal 5'-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1-57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8-8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47-0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51-1.01) and 0.74 (95% confidence interval, 0.53-1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted Pinteraction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27-0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65-1.51). CONCLUSIONS in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women.
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The Role of Nutrients in Reducing the Risk for Noncommunicable Diseases during Aging.
Bruins, MJ, Van Dael, P, Eggersdorfer, M
Nutrients. 2019;(1)
Abstract
An increasing aging population worldwide accounts for a growing share of noncommunicable diseases (NCDs) of the overall social and economic burden. Dietary and nutritional approaches are of paramount importance in the management of NCDs. As a result, nutrition programs are increasingly integrated into public health policies. At present, programs aimed at reducing the burden of NCDs have focused mostly on the excess of unhealthy nutrient intakes whereas the importance of optimizing adequate essential and semi-essential nutrient intakes and nutrient-rich diets has received less attention. Surveys indicate that nutrient intakes of the aging population are insufficient to optimally support healthy aging. Vitamin and mineral deficiencies in older adults are related to increased risk of NCDs including fatigue, cardiovascular disease, and cognitive and neuromuscular function impairments. Reviewed literature demonstrates that improving intake for certain nutrients may be important in reducing progress of NCDs such as musculoskeletal disorders, dementia, loss of vision, and cardiometabolic diseases during aging. Current knowledge concerning improving individual nutrient intakes to reduce progression of chronic disease is still emerging with varying effect sizes and levels of evidence. Most pronounced benefits of nutrients were found in participants who had low nutrient intake or status at baseline or who had increased genetic and metabolic needs for that nutrient. Authorities should implement ways to optimize essential nutrient intake as an integral part of their strategies to address NCDs.