Article

High-Risk Nutrients in the Aging Population

Authors:
To read the full-text of this research, you can request a copy directly from the author.

Abstract

Many aging individuals have chronic health concerns, including type 2 diabetes, heart disease, osteoporosis, physical frailty and cognitive decline. As a modifiable risk factor, healthy diet offers tremendous promise for improving health and wellbeing with age. Unfortunately, intakes of several nutrients are inadequate for a large segment of the older population. These "shortfall nutrients" include macronutrients: protein, n-3 fatty acids, dietary fiber; vitamins: vitamins B6, B12, D, E, and carotenoids (vitamin A precursors); and minerals: calcium, magnesium, and potassium. Other nutrients tend to be consumed in excess, increasing risk of obesity, hypertension and related chronic conditions. These include: saturated fats (i.e. fatty meats, processed meat, full fat dairy products), trans fat (i.e. hydrogenated oils, margarine, shortening, many processed baked products, crackers), refined carbohydrate foods (i.e. soft drinks, fruit drinks, white bread and products with white flour, white rice), sodium (salt and sodium compounds in canned and other processed foods, table salt), and phosphorus (cola, processed meats and commercial baked products). Relative to food group intake recommendations, older adults tend to report inadequate intakes of fruit, vegetables, legumes, whole grains, nuts or seeds, fish, lean meat, poultry, and low fat fluid dairy products. Because of lower energy needs, but higher needs for some nutrients, the importance of these nutrient dense food groups is of central importance. Supplements may be needed in the case of nutrient deficiencies, and when health conditions or medications interfere with absorption or effective nutrient utilization of specific nutrients, making it difficult or impossible to obtain adequate intakes from diet alone. Examples of these include vitamin B-12 with atrophic gastritis, use of acid blocking medication, metformin or other interfering medications, and vitamin D for individuals who get inadequate sun exposure, and during the winter months in northern latitudes. For most nutrients, however, increasing intakes of nutrient dense whole foods, while reducing energy dense refined and processed foods, is the best way to optimize metabolism, protect cellular and organ function and maintain health with aging.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Studies have reported that protein and micronutrients are among the nutrients associated with health risks related to inadequate intake in elderly [37,38]. However, in the absence of a specific nutrient deficiency, micronutrients can be provided in accordance with the recommendations of the European Food Safety Authority (EFSA) or national nutrition associations for healthy elderly individuals [39]. ...
Article
Full-text available
Background: This study aimed to develop a highly consumable collagen-containing bar that contributes to enriching the diets of elderly individuals, in terms of energy and nutrients. Method: For this purpose, five different bar samples (C, P1, P2, D1, D2) containing different amounts of collagen, date puree, and pumpkin puree were developed and subsequently evaluated in terms of their sensory and nutritional properties by a panel of 30 adult trained sensorial analysists. Results: The bars with the highest flavor score were those with high levels of collagen and pumpkin puree (P2) and date puree (D2). For the analyses of multiple criteria among multiple samples, the TOPSIS technique showed that among the snack bar samples with different contents, the most liked sample was the one with a high level of collagen and date puree (D2). One serving of the developed bars contains approximately 300-400 kcal of energy and 6.8-8.8 g of protein. Considering age-related decreased appetite, as well as chewing and swallowing problems in elderly individuals, regular consumption of nutrient-rich small meals or snacks with enhanced sensory characteristics could contribute to improving nutritional and functional status.
... In addition, in elderly individuals, energy-rich snacks in small volumes are another way to cope with early satiety [23]. Studies report that protein and micronutrients are among the nutrients associated with health risks related to inadequate intake in elderly [24,25]. It is thought that the snack bars developed within the scope of the study may contribute to micronutrient intake. ...
Preprint
Full-text available
Background: This study aimed to develop a highly consumable collagen-containing bar that contributes to enriching the diets of elderly individuals in terms of energy and nutrients. Method: For this purpose, after the development of 5 different bar samples (C, P1, P2, D1, D2) containing different amounts of collagen, date puree, and pumpkin puree, they were evaluated in terms of sensory and nutritional properties. Results: The highest flavor score bars were those with high levels of pumpkin puree (P2) and date puree (D2). By applying the TOPSIS technique, which is used when there are multiple crite-ria among multiple samples, to the snack bar samples with different contents, the most liked sample was found to be the snack bar (D2) with a high level of date puree. One serving of the developed bars contains approximately 300-400 kcal of energy and 6.8-8.8 g of protein. Consid-ering age-related decreased appetite and chewing and swallowing problems in elderly individ-uals, regular consumption of nutrient-rich small meals or snacks with enhanced sensory charac-teristics will contribute to improving their nutritional and functional status.
... Both caloric excess and nutrient inadequacy have been shown to be associated with increased risks of age-related chronic diseases and mortality (3,6) . There is accumulating evidence to suggest that prevalence of obesity among older adults is increasing (7)(8)(9) , and saturated fats, trans fat, added sugars and sodium have been found to be consumed in excess by older adults (10,11) . Risk of protein-energy malnutrition is also prevalent in older adults. ...
Article
Full-text available
Poor nutritional intake is common among older adults. Given that nutrition knowledge is an important determinant of eating behaviour and nutritional status, understanding areas of inadequate knowledge can guide educational interventions to reduce risk of nutritional deficiencies and promote healthy aging. This review investigated tools assessing general nutritional knowledge of older adults and their carers. Following the Joanna Briggs for Scoping Reviews guidelines, four databases (MEDLINE, CINAHL, Global Health, and Embase) and grey literature were searched. Studies of any type containing general nutrition knowledge assessment tools for older adults or their carers were included. 6934 articles were identified; 24 met the eligibility criteria; and 23 unique nutrition knowledge assessment tools were included. Of these tools, 14 were original, six were modified from other tools and three used dietary-related responses from national dietary survey questions. Six tools were developed for carers (mostly nurses) and 17 tools for older adults. Tools had between four to 110 items. The most common topics for general nutrition knowledge questions were related to nutrients and roles, food sources of nutrients and diet-disease relationships. Eight tools were developed prior to 2000. Most studies did not specify or assess psychometric properties of the tool, with only nine (38%) and six (26%) studies testing for reliability and validity respectively, and only one tool was considered reliable. Additional research for the development of reliable and validated tools or the validation of existing tools to assess nutrition knowledge of older adults and their carers is needed across different healthcare settings.
... Taken together, several national surveys and observational cohort studies have identified several nutrients that may be inadequately consumed among older adults, including protein, omega-3 fatty acids, dietary fiber, carotenoids (vitamin A precursors), calcium, magnesium, potassium, and vitamins B6, B12, D, and E (Tucker, 2014). Apart from the physiological decline in energy requirements and possible inefficiencies in gastrointestinal absorption and utilization, older adults are predisposed to nutrient deficiency due to commonly used medications that can alter nutrient requirements by interacting in ways that may affect absorption or metabolism (Chan, 2013). ...
Book
Full-text available
This edited volume provides a broad ranging view of the challenges and responses to the increasing age and age-associated morbidity of Malta's population, from considerations about the provision of a sustainable income in retirement to end-of-life and long-term care. The chapters range in scope from an overview of Malta's ageing population to considerations of various aspects of healthcare, ranging from oral health to dementia, nutrition to coronary disease, with a nice mix of both objective and subjective perspectives. The ageing of society will differ from country to country, and it is particularly valuable for countries with relatively well established programmes of gerontological education and training to be able to access information about the ageing of other, smaller countries. The opportunities afforded to small nations for developing a coherent, holistic approach to healthy active ageing enrich the field of gerontology, and this edited volume provides an excellent illustration of what can be done and what scope there is for further developments. This edited collection provides a full and comprehensive coverage of key issues related to health and activity in the context of ageing. With its broad perspective on the determinants and scope of health in later life, the collection is genuinely focused on preventive strategies as well as seeking to maximize the quality of life of older people who depend on health and care systems. The book will be of benefit to those working with older people in health and social care services in Malta as well as to researchers and students of gerontology. It is a unique and original contribution to gerontology. Active and Healthy Ageing in Malta: Gerontological and Geriatric Inquiries documents the outstanding progress in living conditions for older persons in Malta which resulted from policy advances in social and health care policies, and charts the challenges faced by Maltese society in providing improved and more equitable gerontological and geriatric services.
... Furthermore, older adults commonly fall below recommendations for intake. National surveys and observational cohort studies have identified several nutrients that may be inadequately consumed in relation to health risk among older adults, including protein, n-3 FAs, dietary fiber, carotenoids (vitamin A precursors), calcium, magnesium, potassium, and vitamins B-6, B-12, D, and E (25). Furthermore, it is important to consider that even RDA intake levels may not always provide optimal intake for the older population because, generally, RDAs were determined on the basis of studies conducted in younger, healthy populations. ...
Article
Full-text available
A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥ 60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed.
Article
Full-text available
Aging is associated with intrinsic and extrinsic changes which affect the nutrient intake and nutritional status of an older individual. Suboptimal nutritional status is linked with adverse health outcomes. There are limited data in this area for community-dwelling older adults who are not at risk of malnutrition. The objective of this study was to describe the nutritional biomarkers in 400 community-dwelling older adults (aged ≥65 years) with normal nutritional status (Malnutrition Universal Screening Test score of 0) in Singapore and to identify factors associated with these biomarkers. The majority of the participants had normal levels of pre-albumin, albumin, total protein, creatinine, zinc, corrected calcium, vitamin B12, ferritin and hemoglobin. Females had significantly higher levels of corrected calcium and vitamin B12 than males, whereas males had significantly higher levels of pre-albumin, albumin, creatinine, serum ferritin, 25-hydroxyvitamin D (25(OH)D) and hemoglobin than females. About half of the participants (52%) had low level of 25(OH)D (<30 µg/L) and 10% had low zinc level (<724 µg/L). Among those with low level of 25(OH)D, 74% had 25(OH)D insufficiency (20-<30 µg/L) and 26% had 25(OH)D deficiency (<20 µg/L). Younger age, female gender, non-Chinese ethnicity and no intake of vitamin D supplement were associated with lower serum 25(OH)D level, whereas higher body mass index (BMI) was associated with low zinc level. These findings highlight the problem of hidden nutritional insufficiencies can be missed in seemingly normal nourished community-dwelling older adults.
Article
There is continuous ageing in world population. Although life expectancy still increases there is no similar trend in maintaining quality of life. The number of disabilities due to age is expected to double in 2060. Muscle mass is one of the most important factors of health and nutrition in old age and it constant loss is characteristic for process of ageing. Muscle mass is controlled by number of different factors. The most important of which is balance between muscle protein synthesis and degradation. Ageing has no influence on muscle protein degradation so for maintaining muscle mass it is better to target muscle protein synthesis. Optimal protein dose in the meal is the minimal amount of protein effecting in maximal anabolic response. Threshold for anabolic response increase with age. This process, named anabolic resistance can be overwhelmed with high amount of protein in diet. Experts in the field of ageing and nutrition recommend 1,2-1,5 g/kg/d protein for the maintaining of muscle mass, 1,2-1,5 g/kg/d for older with additional risk factors, 2,0 g/kg/d for seriously ill and malnourished. Physical training has synergistic influence with diet protein. Physical training improves muscle performance, muscle strength and prevents muscle wasting. Physical training combined with increased amount of protein in diet results with increased muscle mass.
Article
Full-text available
Osteoarthritis is the disease connected with aging which is characterised by progressive degeneration of all elements building the joint but also influencing the muscles constituting motor unit with the affected joint. The effective and unified therapy has not been yet introduced despite the broad multi-site studies concentrating on metabolic pathways responsible for the development of the disease. The reason of which is probably its multifactorial aetiology. The treatment methods are based on decreasing of cartilage destruction activity, retardation of proinflammatory factors activity and fighting with pain. Physiotherapy, movement rehabilitation, painkillers, anti-inflammatory drugs, glucosamine sulphates and hyaluronic acids are used as therapeutic strategies. The methods recently introduced are platelet rich plasma concentrates and stem cells injected directly into the affected joint. The aim of this review article was the presentation of differential therapeutic options offered to patients in different stages of osteoarthritis.
Article
Full-text available
Metabolic syndrome (MS) and hypovitaminosis D represent two of the most diffuse condition worldwide, reaching pandemic proportions in industrialized countries, and are both strongly associated with obesity. This study set out to evaluate the presence of an independent association between hypovitaminosis D and MS in an adult population of obese subjects with/without MS. We recruited 107 consecutive obese subjects, 61 with MS (age(mean±SD) 45.3±13.3 years, BMI(mean±SD): 43.1±8.3 kg/m(2)) and 46 without MS (age: 41.8±11.5, p = n.s., BMI:41.6±6.5 kg/m(2), p = n.s.) comparable for sex, BMI, waist circumference and body fat mass, evaluated by bioimpedentiometry. 25(OH) vitamin D3 levels were measured by colorimetric method. Insulin resistance was estimated by fasting blood insulin, HOMA-IR and ISI. Serum 25(OH)D3 levels were significantly lower in MS obese patients than in obese subjects without MS (median(range) 13.5(3.3-32) vs 17.4(5.1-37.4), p<0.007). Low 25(OH)D3 levels correlated with glycaemia (p<0.007), phosphate (p<0.03), PTH (p<0.003) and the MS (p<0.001). Multivariate model confirmed that low 25(OH)D3 levels were associated with the diagnosis of MS in obese patients independently from gender, age, serum PTH and body fat mass. After stratifying the study population according to 25(OH)D3 concentrations, patients in the lowest quartile showed a markedly increased prevalence of MS compared to those in the highest quartile (OR = 4.1, CI 1.2-13.7, p = 0.02). A powerful association exists between hypovitaminosis D and MS in obese patients independently from body fat mass and its clinical correlates. This indicates that the association between low 25(OH) D3 levels and MS is not merely induced by vitamin D deposition in fat tissue and reinforces the hypothesis that hypovitaminosis D represent a crucial independent determinant of MS.
Article
Full-text available
Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols, and vitamin A may play a role in the prevention or delay in cognitive decline. In this study, sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian Study. Brain tissues were obtained from 47 centenarian decedents. Samples were analyzed for carotenoids, α-tocopherol, and retinol using HPLC. Analyte concentrations were compared with cognitive tests designed to evaluate global cognition, dementia, depression and cognitive domains (memory, processing speed, attention, and executive functioning). Serum lutein, zeaxanthin, and β-carotene concentrations were most consistently related to better cognition (P < 0.05) in the whole population and in the centenarians. Only serum lutein was significantly related to better cognition in the octogenarians. In brain, lutein and β-carotene were related to cognition with lutein being consistently associated with a range of measures. There were fewer significant relationships for α-tocopherol and a negative relationship between brain retinol concentrations and delayed recognition. These findings suggest that the status of certain carotenoids in the old may reflect their cognitive function. The protective effect may not be related to an antioxidant effect given that α-tocopherol was less related to cognition than these carotenoids.
Article
Full-text available
Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.
Article
Full-text available
This review explores the potential adverse impact of the increasing phosphorus content in the American diet on renal, cardiovascular, and bone health of the general population. Increasingly, studies show that phosphorus intakes in excess of the nutrient needs of a healthy population may significantly disrupt the hormonal regulation of phosphate, calcium, and vitamin D, which contributes to disordered mineral metabolism, vascular calcification, impaired kidney function, and bone loss. Moreover, large epidemiologic studies suggest that mild elevations of serum phosphate within the normal range are associated with cardiovascular disease (CVD) risk in healthy populations without evidence of kidney disease. However, few studies linked high dietary phosphorus intake to mild changes in serum phosphate because of the nature of the study design and inaccuracies in the nutrient composition databases. Although phosphorus is an essential nutrient, in excess it could be linked to tissue damage by a variety of mechanisms involved in the endocrine regulation of extracellular phosphate, specifically the secretion and action of fibroblast growth factor 23 and parathyroid hormone. Disordered regulation of these hormones by high dietary phosphorus may be key factors contributing to renal failure, CVD, and osteoporosis. Although systematically underestimated in national surveys, phosphorus intake seemingly continues to increase as a result of the growing consumption of highly processed foods, especially restaurant meals, fast foods, and convenience foods. The increased cumulative use of ingredients containing phosphorus in food processing merits further study given what is now being shown about the potential toxicity of phosphorus intake when it exceeds nutrient needs.
Article
Full-text available
To investigate the association between long term intake of dietary and supplemental calcium and death from all causes and cardiovascular disease. Prospective longitudinal cohort study. Swedish mammography cohort, a population based cohort established in 1987-90. 61 433 women (born between 1914 and 1948) followed-up for a median of 19 years. Primary outcome measures, identified from registry data, were time to death from all causes (n=11 944) and cause specific cardiovascular disease (n=3862), ischaemic heart disease (n=1932), and stroke (n=1100). Diet was assessed by food frequency questionnaires at baseline and in 1997 for 38 984 women, and intakes of calcium were estimated. Total calcium intake was the sum of dietary and supplemental calcium. The risk patterns with dietary calcium intake were non-linear, with higher rates concentrated around the highest intakes (≥1400 mg/day). Compared with intakes between 600 and 1000 mg/day, intakes above 1400 mg/day were associated with higher death rates from all causes (hazard ratio 1.40, 95% confidence interval 1.17 to 1.67), cardiovascular disease (1 49, 1.09 to 2.02), and ischaemic heart disease (2.14, 1.48 to 3.09) but not from stroke (0.73, 0.33 to 1.65). After sensitivity analysis including marginal structural models, the higher death rate with low dietary calcium intake (<600 mg/day) or with low and high total calcium intake was no longer apparent. Use of calcium tablets (6% users; 500 mg calcium per tablet) was not on average associated with all cause or cause specific mortality but among calcium tablet users with a dietary calcium intake above 1400 mg/day the hazard ratio for all cause mortality was 2.57 (95% confidence interval 1.19 to 5.55). High intakes of calcium in women are associated with higher death rates from all causes and cardiovascular disease but not from stroke.
Article
Full-text available
To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention. Systematic review and meta-analysis. Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases. ELIGIBILITY CRITERIA: Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible. 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups. Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.
Article
Full-text available
Vitamin D is characterized as a regulator of homeostasis of bone and mineral metabolism, but it can also provide nonskeletal actions because vitamin D receptors have been found in various tissues including the brain, prostate, breast, colon, pancreas, and immune cells. Bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation are all biological functions of vitamin D. Vitamin D may play an important role in modifying the risk of cardiometabolic outcomes, including diabetes mellitus (DM), hypertension, and cardiovascular disease. The incidence of type 2 DM is increasing worldwide and results from a lack of insulin or inadequate insulin secretion following increases in insulin resistance. Therefore, it has been proposed that vitamin D deficiency plays an important role in insulin resistance resulting in diabetes. The potential role of vitamin D deficiency in insulin resistance has been proposed to be associated with inherited gene polymorphisms including vitamin D-binding protein, vitamin D receptor, and vitamin D 1alpha-hydroxylase gene. Other roles have been proposed to involve immunoregulatory function by activating innate and adaptive immunity and cytokine release, activating inflammation by upregulation of nuclear factor κB and inducing tumor necrosis factor α, and other molecular actions to maintain glucose homeostasis and mediate insulin sensitivity by a low calcium status, obesity, or by elevating serum levels of parathyroid hormone. These effects of vitamin D deficiency, either acting in concert or alone, all serve to increase insulin resistance. Although there is evidence to support a relationship between vitamin D status and insulin resistance, the underlying mechanism requires further exploration. The purpose of this paper was to review the current information available concerning the role of vitamin D in insulin resistance.
Article
Full-text available
In a study of the pathogenesis and clinical features of megaloblastic anaemia in southern Africa, we evaluated 144 consecutive Zimbabwean patients with megaloblastic haemopoiesis. Vitamin B12 deficiency was diagnosed in 86.1% of patients and was usually due to pernicious anaemia; isolated folate deficiency accounted for only 5/5% of cases. Anaemia was present in 95.8% of patients; the haemoglobin (Hb) was 6 g/dl in 63.9%. Neurological dysfunction was noted in 70.2% of vitamin B12-deficient patients and was most striking in those with Hb values > 6 g/dl. Serum levels of methylmalonic acid, homocysteine, or both, were increased in 98.5% of patients. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe and, contrary to textbook statements, is often due to pernicious anaemia. Isolated folate deficiency is less common. As reported in industrialized countries 75 years ago, anaemia is almost always present and often severe. Neurological dysfunction due to vitamin B12 deficiency is most prominent in patients with mild to moderate anaemia.
Article
Full-text available
Parkinson's disease (PD) is the second most common form of neurodegeneration in the elderly population. Clinically, it is characterized by tremor, rigidity, slowness of movement, and postural imbalance. A significant association between low serum vitamin D and PD has been demonstrated, suggesting that elevated vitamin D levels might provide protection against PD. Genetic studies have helped identify a number of proteins linking vitamin D to PD pathology, including the major histocompatibility complex (MHC) class II, the vitamin D receptor (VDR), cytochrome P450 2D6 (CYP2D6), chromosome 22, the renin-angiotensin system (RAS), heme oxygenase-1 (HO-1), poly(ADP-ribose) polymerase-1 gene (PARP-1), neurotrophic factor (NTF), and Sp1 transcription factor. Vitamin D has also been implicated in PD through its effects on L-type voltage-sensitive calcium channels (L-VSCC), nerve growth factor (NGF), matrix metalloproteinases (MMPs), prostaglandins (PGs) and cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), and nitric oxide synthase (NOS). A growing body of evidence suggests that vitamin D supplementation may be beneficial for PD patients. Among the different forms of vitamin D, calcitriol (1,25-dihydroxyvitamin D(3)) is best indicated for PD, because it is a highly active vitamin D(3) metabolite with an appropriate receptor in the central nervous system (CNS).
Article
Full-text available
The role of vitamin D in skeletal health is well established, but more recent findings have also linked vitamin D deficiency to a range of non-skeletal conditions such as cardiovascular disease, cancer, stroke and metabolic disorders including diabetes. Cognitive impairment and dementia must now be added this list. Vitamin D receptors are widespread in brain tissue, and vitamin D's biologically active form [1,25(OH)(2)D3] has shown neuroprotective effects including the clearance of amyloid plaques, a hallmark of Alzheimer's Disease. Associations have been noted between low 25-hydroxyvitamin D [25(OH)D] and Alzheimer's disease and dementia in both Europe and the US. Similarly, the risk of cognitive impairment was up to four times greater in the severely deficient elders (25(OH)D < 25 nmol/L) in comparison with individuals with adequate levels (≥ 75 nmol/L). Further studies have also shown associations between low 25(OH)D concentrations and cerebrovascular events such as large vessel infarcts, risk of cerebrovascular accident and fatal stroke. Cross-sectional studies cannot establish temporal relationships because cognitive decline and the onset of dementia itself may influence vitamin D concentrations through behavioural and dietary changes. However, two large prospective studies recently indicated that low vitamin D concentrations may increase the risk of cognitive decline. Large, well designed randomized controlled trials are now needed to determine whether vitamin D supplementation is effective at preventing or treating Alzheimer's disease and dementia.
Article
Full-text available
The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. Prostate cancer incidence. This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. Clinicaltrials.gov Identifier: NCT00006392.
Article
Full-text available
To assess the association between serum 25-hydroxyvitamin D (25-OHD) and incident type 2 diabetes and to determine whether the association is mediated by subclinical inflammation. Using a case-cohort design, baseline levels of 25-OHD were measured in 416 case subjects with incident type 2 diabetes and 1,267 noncase subjects selected from a source population of 7,936 middle-aged participants in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) study. A significant inverse association was observed between serum 25-OHD and incident type 2 diabetes after adjustment for diabetes risk factors and season. The hazard ratio (HR) and 95% CI comparing tertile extremes was 0.63 (0.44-0.90) (P(trend) = 0.010). Further adjustment for C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, and interferon-γ-inducible protein-10 attenuated this association by 16% (HR 0.73 [0.50-1.05], P = 0.090). Vitamin D status is inversely related to type 2 diabetes risk and our data suggest that this association may be partially mediated by subclinical inflammation.
Article
Recent studies demonstrated associations between occlusive vascular disease and hyperhomocysteinemia of both genetic and nutritional origin. In the present study we analyzed plasma samples from the 20th blannual examination of the Framingham Heart Study cohort to determine distribution of plasma homocysteine concentrations with emphasis on relationships to B vitamins and prevalence of carotid artery stenosis. Results showed that homocysteine exhibited strong inverse association with plasma folate and weaker associations with plasma vitamin B-12 and pyridoxal-5′-phosphate (PLP). Homocysteine was also inversely associated with intakes of folate and vitamin B-6, but not vitamin B-12. Prevalence of high homocysteine (> 14 µmol/l) was 29.3% in this cohort, and inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine. Prevalence of stenosis ≥25% was 43% in men and 34% in women with an odds ratio of 2.0 for individuals in the highest homocysteine quartile (≥14.4 µmol/l) compared with those in the lowest quartile (≤9.1 µmol/l), after adjustment for sex, age, high density lipoprotein cholesterol, systolic blood pressure and cigarette smoking (Ptrend < 0.001). Plasma concentrations of folate and pyridoxal-5′-phosphate and folate intake were inversely associated with extracranial carotid stenosis after adjustment for age, sex and other risk factors.
Article
Background: Obesity is associated with vitamin D insufficiency and secondary hyperparathyroidism. Objective: This study assessed whether obesity alters the cutaneous production of vitamin D3 (cholecalciferol) or the intestinal absorption of vitamin D2 (ergocalciferol). Design: Healthy, white, obese [body mass index (BMI; in kg/m²) ≥ 30] and matched lean control subjects (BMI ≤ 25) received either whole-body ultraviolet radiation or a pharmacologic dose of vitamin D2 orally. Results: Obese subjects had significantly lower basal 25-hydroxyvitamin D concentrations and higher parathyroid hormone concentrations than did age-matched control subjects. Evaluation of blood vitamin D3 concentrations 24 h after whole-body irradiation showed that the incremental increase in vitamin D3 was 57% lower in obese than in nonobese subjects. The content of the vitamin D3 precursor 7-dehydrocholesterol in the skin of obese and nonobese subjects did not differ significantly between groups nor did its conversion to previtamin D3 after irradiation in vitro. The obese and nonobese subjects received an oral dose of 50000 IU (1.25 mg) vitamin D2. BMI was inversely correlated with serum vitamin D3 concentrations after irradiation (r = −0.55, P = 0.003) and with peak serum vitamin D2 concentrations after vitamin D2 intake (r = −0.56, P = 0.007). Conclusions: Obesity-associated vitamin D insufficiency is likely due to the decreased bioavailability of vitamin D3 from cutaneous and dietary sources because of its deposition in body fat compartments.
Article
Background: Elevated homocysteine concentrations may contribute to cognitive impairment. Most elevations in homocysteine result from inadequate folate, vitamin B-12, or vitamin B-6 intake. It is not clear whether the observed associations between homocysteine and cognitive measures are causal or whether they are due to homocysteine, to independent actions of the B vitamins, or to both. Objective: We aimed to assess the individual and independent effects of baseline plasma homocysteine, folate, vitamin B-12, and vitamin B-6 and of dietary B vitamin intakes on 3-y changes in cognitive measures in 321 aging men. Design: Participants were from the Veterans Affairs Normative Aging Study. Cognitive function was assessed with the Mini-Mental State Examination and on the basis of measures of memory, verbal fluency, and constructional praxis, which were adapted from the revised Wechsler Adult Intelligence Scale and the Consortium to Establish a Registry for Alzheimer’s Disease batteries at 2 time points. At baseline, dietary intakes were assessed with a food-frequency questionnaire, and blood was drawn for the measurement of B vitamins and homocysteine. Results: Over a mean 3-y follow-up, declines in constructional praxis, measured by spatial copying, were significantly associated with plasma homocysteine, folate, and vitamins B-6 and B-12 and with the dietary intake of each vitamin. Folate (plasma and dietary) remained independently protective against a decline in spatial copying score after adjustment for other vitamins and for plasma homocysteine. Dietary folate was also protective against a decline in verbal fluency. A high homocysteine concentration was associated with a decline in recall memory. Conclusions: Low B vitamin and high homocysteine concentrations predict cognitive decline. Spatial copying measures appear to be most sensitive to these effects in a general population of aging men.
Article
Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800–1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.
Article
Background There is conflicting evidence on the benefits of foods rich in vitamin E (alpha-tocopherol), n-3 polyunsaturated fatty acids (PUFA), and their pharmacological substitutes. We investigated the effects of these substances as supplements in patients who had myocardial infarction. Methods From October, 1993, to September, 1995, 11324 patients surviving recent (less than or equal to 3 months) myocardial infarction were randomly assigned supplements of n-3 PUFA (Ig daily, n=2836), vitamin E (300 mg daily, n=2830), both (n=2830), or none (control, n=2828) for 3.5 years. The primary combined efficacy endpoint was death, non-fatal myocardial infarction, and stroke. Intention-to-treat analyses were done according to a factorial design (two-way) and by treatment group (four-way). Findings Treatment with n-3 PUFA, but not vitamin E, significantly lowered the risk of the primary endpoint (relative risk decrease 10% [95% CI 1-18] by two-way analysis, 15% [2-26] by four-way analysis). Benefit was attributable to a decrease in the risk of death (14% [3-24] two-way, 20% [6-33] four-way) and cardiovascular death (17% [3-29] two-way, 30% [13-44] four-way). The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint (14% [1-26]) and for fatal events (20% [5-33]). Interpretation Dietary supplementation with n-3 PUFA led to a clinically important and satistically significant benefit. Vitamin E had no benefit. Its effects on fatal cardiovascular events require further exploration.
Article
Background. Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables, as well as high serum levels of vitamin E (alpha-tocopherol) and beta carotene, are associated with a reduced risk of lung cancer. Methods. We performed a randomized, double-blind, placebo-controlled primary-prevention trial to determine whether daily supplementation with alpha-tocopherol, beta carotene, or both would reduce the incidence of lung cancer and other cancers. A total of 29,133 male smokers 50 to 69 years of age from southwestern Finland were randomly assigned to one of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo. Follow-up continued for five to eight years. Results. Among the 876 new cases of lung cancer diagnosed during the trial, no reduction in incidence was observed among the men who received alpha-tocopherol (change in incidence as compared with those who did not, -2 percent; 95 percent confidence interval, -14 to 12 percent). Unexpectedly, we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not (change in incidence, 18 percent; 95 percent confidence interval, 3 to 36 percent). We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer. Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not. Beta carotene had little or no effect on the incidence of cancer other than lung cancer. Alpha- tocopherol had no apparent effect on total mortality, although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not. Total mortality was 8 percent higher (95 percent confidence interval, 1 to 16 percent) among the participants who received beta carotene than among those who did not, primarily because there were more deaths from lung cancer and ischemic heart disease. Conclusions. We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene. In fact, this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects.
Article
The role of dietary protein in osteoporosis is unclear, with previous studies having suggested both protection and harm. The associations of total, animal, and vegetable protein with bone mineral density (BMD) and the variations in these associations with calcium intake were studied in a community-dwelling cohort of 572 women and 388 men aged 55-92 years (Rancho Bernardo, California). Multiple linear regression analyses adjusted for standard osteoporosis covariates showed a positive association between animal protein consumption, assessed by food frequency questionnaires in 1988-1992, and BMD, measured 4 years later. This association was statistically significant in women. For every 15-g/day increase in animal protein intake, BMD increased by 0.016 g/cm 2 at the hip (p = 0.005), 0.012 g/cm 2 at the femoral neck (p = 0.02), 0.015 g/cm 2 at the spine (p = 0.08), and 0.010 g/cm 2 for the total body (p = 0.04). Conversely, a negative association between vegetable protein and BMD was observed in both sexes. Some suggestion of effect modification by calcium was seen in women, with increasing protein consumption appearing to be more beneficial for women with lower calcium intakes, but evidence for this interaction was not consistently strong. This study supports a protective role for dietary animal protein in the skeletal health of elderly women.
Article
New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance- and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, ≥1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults who have acute or chronic diseases need even more dietary protein (ie, 1.2-1.5 g/kg body weight/d). Older people with severe kidney disease (ie, estimated GFR <30 mL/min/1.73m(2)), but who are not on dialysis, are an exception to this rule; these individuals may need to limit protein intake. Protein quality, timing of ingestion, and intake of other nutritional supplements may be relevant, but evidence is not yet sufficient to support specific recommendations. Older people are vulnerable to losses in physical function capacity, and such losses predict loss of independence, falls, and even mortality. Thus, future studies aimed at pinpointing optimal protein intake in specific populations of older people need to include measures of physical function.
Article
Although the tocopherol content in food has been shown to be inversely associated with mortality from cardiovascular disease, dietary supplementation with α-tocopherol alone has a modest protective effect. The lack of natural tocopherols such as γ- and δ-tocopherol most vitamin E preparations may be a limiting factor for promoting health. Although α-tocopherol and γ-tocopherol are 2 principle tocopherols in vegetable oils, the latter is in greater abundance in the edible oils processed in the United States. In contrast to α-tocopherol, γ-tocopherol has biologic activity that potentially protects against chronic diseases such as inflammation. Evidence indicates that the mixed tocopherols found in native vegetable oils afford additive and synergistic activities that support their broader beneficial biologic functions. Both γ- and δ-tocopherol may be necessary for preventing lipid peroxidation and in counteracting the prooxidant effect of α-tocopherol. Moreover, all tocopherols except β-tocopherol inhibit smooth muscle proliferation. In our research, a preparation of mixed tocopherols, containing γ-, δ-, and α-tocopherol (5:2:1), has been shown to have better antioxidant and anti-inflammatory actions than α-tocopherol alone. This mixture did not have any adverse effects in a limited number of preliminary clinical investigations. Thus, among the tocopherols, α-tocopherol is not the only important isomer for human health. Based on the evidence in this review, further research and additional clinical studies should be conducted on mixed tocopherol preparations.
Article
Since the first AHA Science Advisory “Fish Consumption, Fish Oil, Lipids, and Coronary Heart Disease,”1 important new findings, including evidence from randomized controlled trials (RCTs), have been reported about the beneficial effects of omega-3 (or n-3) fatty acids on cardiovascular disease (CVD) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function (including antiarrhythmic effects), hemodynamics (cardiac mechanics), and arterial endothelial function have helped clarify potential mechanisms of action. The present Statement will address distinctions between plant-derived (α-linolenic acid, C18:3n-3) and marine-derived (eicosapentaenoic acid, C20:5n-3 [EPA] and docosahexaenoic acid, C22:6n-3 [DHA]) omega-3 fatty acids. (Unless otherwise noted, the term omega-3 fatty acids will refer to the latter.) Evidence from epidemiological studies and RCTs will be reviewed, and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid (plant- and marine-derived) supplementation. This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration (FDA) about the presence of environmental contaminants in certain species of fish. ### Coronary Heart Disease As reviewed by Stone,1 three prospective epidemiological studies within populations reported that men who ate at least some fish weekly had a lower coronary heart disease (CHD) mortality rate than that of men who ate none.3–6⇓⇓⇓ More recent evidence that fish consumption favorably affects CHD mortality, especially nonsudden death from myocardial infarction (MI), has been reported in a 30-year follow-up of the Chicago Western Electric Study.7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33. In an …
Article
Vitamin E is a generic term that refers to a family of compounds that is further divided into two subgroups called tocopherols and tocotrienols. Although all natural forms of vitamin E display potent antioxidant activity, tocotrienols are significantly more potent than tocopherols in inhibiting tumor cell growth and viability, and anticancer activity of tocotrienols is mediated independently of their antioxidant activity. In addition, the anticancer effects of tocotrienols are observed using treatment doses that have little or no effect on normal cell function or viability. This review will summarize experimental studies that have identified the intracellular mechanism mediating the anticancer effects of tocotrienols. Evidence is also provided showing that combined treatment of tocotrienol with other cancer chemotherapies can result in a synergistic inhibition in cancer cell growth and viability. Taken together, these findings strongly indicate that tocotrienols may provide significant health benefits in the prevention and/or treatment of cancer when used either alone as monotherapy or in combination with other anticancer agents. © 2013 BioFactors, 2013.
Article
Background —A high plasma homocysteine concentration is a risk factor for atherosclerosis, and circulating concentrations of homocysteine are related to levels of folate and vitamin B 6 . This study was performed to explore the interrelationships between homocysteine, B vitamins, and vascular diseases and to evaluate the role of these vitamins as risk factors for atherosclerosis. Methods —In a multicenter case-control study in Europe, 750 patients with documented vascular disease and 800 control subjects frequency-matched for age and sex were compared. Plasma levels of total homocysteine (before and after methionine loading) were determined, as were those of red cell folate, vitamin B 12 , and vitamin B 6 . Results —In a conditional logistic regression model, homocysteine concentrations greater than the 80th percentile for control subjects either fasting (12.1 μmol/L) or after a methionine load (38.0 μmol/L) were associated with an elevated risk of vascular disease independent of all traditional risk factors. In addition, concentrations of red cell folate below the lowest 10th percentile (<513 nmol/L) and concentrations of vitamin B 6 below the lowest 20th percentile (<23.3 nmol/L) for control subjects were also associated with increased risk. This risk was independent of conventional risk factors and for folate was explained in part by increased homocysteine levels. In contrast, the relationship between vitamin B 6 and atherosclerosis was independent of homocysteine levels both before and after methionine loading. Conclusions —Lower levels of folate and vitamin B 6 confer an increased risk of atherosclerosis. Clinical trials are now required to evaluate the effect of treatment with these vitamins in the primary and secondary prevention of vascular diseases.
Article
Drug-nutrient interactions are defined as physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient. The causes of most clinically significant drug-nutrient interactions are usually multifactorial. Failure to identify and properly manage drug-nutrient interactions can lead to very serious consequences and have a negative impact on patient outcomes. Nevertheless, with thorough review and assessment of the patient's history and treatment regimens and a carefully executed management strategy, adverse events associated with drug-nutrient interactions can be prevented. Based on the physiologic sequence of events after a drug or a nutrient has entered the body and the mechanism of interactions, drug-nutrient interactions can be categorized into 4 main types. Each type of interaction can be managed using similar strategies. The existing data that guide the clinical management of most drug-nutrient interactions are mostly anecdotal experience, uncontrolled observations, and opinions, whereas the science in understanding the mechanism of drug-nutrient interactions remains limited. The challenge for researchers and clinicians is to increase both basic and higher level clinical research in this field to bridge the gap between the science and practice. The research should aim to establish a better understanding of the function, regulation, and substrate specificity of the nutrient-related enzymes and transport proteins present in the gastrointestinal tract, as well as assess how the incidence and management of drug-nutrient interactions can be affected by sex, ethnicity, environmental factors, and genetic polymorphisms. This knowledge can help us develop a true personalized medicine approach in the prevention and management of drug-nutrient interactions.
Article
Context It has been suggested that total blood homocysteine concentrations are associated with the risk of ischemic heart disease (IHD) and stroke.Objective To assess the relationship of homocysteine concentrations with vascular disease risk.Data Sources MEDLINE was searched for articles published from January 1966 to January 1999. Relevant studies were identified by systematic searches of the literature for all reported observational studies of associations between IHD or stroke risk and homocysteine concentrations. Additional studies were identified by a hand search of references of original articles or review articles and by personal communication with relevant investigators.Study Selection Studies were included if they had data available by January 1999 on total blood homocysteine concentrations, sex, and age at event. Studies were excluded if they measured only blood concentrations of free homocysteine or of homocysteine after a methionine-loading test or if relevant clinical data were unavailable or incomplete.Data Extraction Data from 30 prospective or retrospective studies involving a total of 5073 IHD events and 1113 stroke events were included in a meta-analysis of individual participant data, with allowance made for differences between studies, for confounding by known cardiovascular risk factors, and for regression dilution bias. Combined odds ratios (ORs) for the association of IHD and stroke with blood homocysteine concentrations were obtained by using conditional logistic regression.Data Synthesis Stronger associations were observed in retrospective studies of homocysteine measured in blood collected after the onset of disease than in prospective studies among individuals who had no history of cardiovascular disease when blood was collected. After adjustment for known cardiovascular risk factors and regression dilution bias in the prospective studies, a 25% lower usual (corrected for regression dilution bias) homocysteine level (about 3 µmol/L [0.41 mg/L]) was associated with an 11% (OR, 0.89; 95% confidence interval [CI], 0.83-0.96) lower IHD risk and 19% (OR, 0.81; 95% CI, 0.69-0.95) lower stroke risk.Conclusions This meta-analysis of observational studies suggests that elevated homocysteine is at most a modest independent predictor of IHD and stroke risk in healthy populations. Studies of the impact on disease risk of genetic variants that affect blood homocysteine concentrations will help determine whether homocysteine is causally related to vascular disease, as may large randomized trials of the effects on IHD and stroke of vitamin supplementation to lower blood homocysteine concentrations. Figures in this Article The hypothesis that elevated blood concentrations of the sulfur-containing amino acid homocysteine may be a risk factor for cardiovascular disease was suggested by the observation that children with homozygous homocystinuria, a rare inborn error of metabolism causing markedly elevated blood total homocysteine concentrations, had a high incidence of premature occlusive vascular disease.1 The initial epidemiological evidence in support of this hypothesis came from retrospective case-control studies.2- 4 More recently, however, inconsistent results have been reported from prospective observational studies, including cohort and nested case-control studies, with some showing highly significant associations but others showing none.5 The aim of this collaborative meta-analysis was to combine individual participant data from all relevant observational studies to produce reliable estimates of the associations of total plasma homocysteine with ischemic heart disease (IHD) and stroke, with adjustment for confounding caused by known cardiovascular risk factors and correction for regression dilution caused by random variation in homocysteine measurements.6- 7 The chief emphasis in this report is on combined analyses of the prospective studies (which involve the measurement of homocysteine in blood collected before the onset of disease) rather than on the retrospective studies, since the former should be less prone to artifacts produced by any effects of preexisting vascular disease on homocysteine levels (referred to as reverse causality).
Article
A variety of inflammatory disease conditions have been found to be associated with low levels of plasma pyridoxal 5'-phosphate (PLP), the active form of vitamin B6 , without any indication of a lower dietary intake of vitamin B6 , excessive catabolism of the vitamin, or congenital defects in its metabolism. The present review was conducted to examine the existing literature in this regard. Current evidence suggests that the inverse association between plasma PLP and inflammation may be the result of mobilization of this coenzyme to the site of inflammation, for use by the PLP-dependent enzymes of the kynurenine pathway of tryptophan degradation, metabolism of the immunomodulatory sphingolipids, ceramide and sphingosine 1-phosphate, and for serine hydroxymethylase for immune cell proliferation.
Article
Unlabelled: Previous research from our lab has demonstrated that dietary walnut supplementation protects against age-related cognitive declines in rats; however, the cellular mechanisms by which walnuts and polyunsaturated fatty acids (PUFAs) may affect neuronal health and functioning in aging are undetermined. Objectives: We assessed if pretreatment of primary hippocampal neurons with walnut extract or PUFAs would protect cells against dopamine- and lipopolysaccharide-mediated cell death and calcium dysregulation. Methods: Rat primary hippocampal neurons were pretreated with varying concentrations of walnut extract, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, or docosahexaenoic acid prior to exposure to either dopamine or lipopolysaccharide. Viability was assessed using the Live/Dead Cellular Viability/Cytotoxicity Kit. Also, the ability of the cells to return to baseline calcium levels after depolarization was measured with fluorescent imaging. Results: Results indicated that walnut extract, alpha-linolenic acid, and docosahexaenoic acid provided significant protection against cell death and calcium dysregulation; the effects were pretreatment concentration dependent and stressor dependent. Linoleic acid and eicosapentaenoic acid were not as effective at protecting hippocampal cells from these insults. Discussion: Walnut extract and omega-3 fatty acids may protect against age-related cellular dysfunction, but not all PUFAs are equivalent in their beneficial effects.
Article
Context and objective: A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system. Therefore, we thought to prospectively assess the association between serum 25-hydroxyvitamin D, the most commonly used index of vitamin D status, and incident coronary heart disease. Design, setting, and patients: We measured serum levels of 25[OH]D in 1783 healthy middle-aged subjects (964 men, 819 women) in the population-based Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg studies. A total of 298 coronary heart disease cases were identified over a mean follow-up period of 11 yr. Results: After adjustment for age, survey, and season of blood sampling, the hazard ratio (HR) and 95% confidence interval comparing tertile extremes of serum levels of 25[OH]D was 0.32 (0.16-0.65) (P for trend = 0.001) in women and 0.56 (0.38-0.82) (P for trend = 0.005) in men. Further adjustment for traditional cardiovascular risk factors slightly attenuated the association in women [HR 0.39 (0.18-0.84); P for trend = 0.013], whereas it became nonsignificant in men [HR 0.76 (0.49-1.17); P for trend = 0.215]. After additional adjustment for C-reactive protein, IL-6, soluble intercellular adhesion molecule-1, and interferon-γ-inducible protein-10, the association still remained significant in women [HR 0.42 (0.19-0.93); P for trend = 0.028], and it was further reduced in men [HR 0.84 (0.52-1.35); P for trend = 0.461]. Conclusion: Our findings suggest that higher vitamin D levels are associated with decreased risk of coronary heart disease. This effect is more pronounced in women than in men. Further clinical and experimental studies are needed to investigate the sex differences and whether vitamin D supplementation could contribute to the prevention of coronary heart disease.
Article
Vitamin D3is biologically inert. To become active, it requires two successive hydroxylation steps catalyzed by two cytochrome P450 enzymes, first to synthesize the pro-hormone 25-hydroxyvitamin D3 [25(OH)D3] and then the active hormone 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3]. 1α,25(OH)2D3 has high affinity for the vitamin D receptor (VDR), a transcription factor and a member of the steroid receptor superfamily.Through VDR, 1α,25(OH)2D3regulates more than 200 genes in mammals, including those involved in the calcium and phosphorus homeostasis, immune function, reproduction, cardiovascular, central nerve system, inflammation, angiogenesis, and cellular proliferation, differentiation and apoptosis. Due to its versatile roles in maintaining and regulating normal cellular phenotypes and functions, 1α,25(OH)2D3 has been implicated as an anti-cancer agent. In fact, ecological and epidemiologic data have linked vitamin D deficiencywith the incidence and mortality of many types of cancer. More importantly, in vitro and invivo animal model studies have clearly demonstrated the anti-tumor effects of vitamin D. In this review, we describe the anti-cancer actions of vitamin D, with special emphasis on different pathways underlying the VDR-mediated genomic as well as less-defined non-genomic actions of vitamin D.
Article
To determine whether the levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (AA), total n-3 polyunsaturated fatty acids (PUFAs), and total n-6 PUFAs were changed in patients with dementia or predementia syndrome. PubMed was searched for studies from first date available to July 2011 using the following search terms: (dementia OR cognitive impairment OR mild cognitive impairment) AND (omega-3 OR omega-6 OR polyunsaturated fatty acid OR docosahexaenoic acid OR DHA OR eicosapentaenoic acid OR EPA). The search was limited to literature in English and to human studies. The references of relevant articles and review articles were searched for citations not indexed in PubMed. Studies were included if they measured levels of EPA, DHA, AA, total n-3 PUFAs, or total n-6 PUFAs from peripheral blood tissues in subjects with cognitive deficits (dementia or predementia syndrome) and elderly controls and were published in peer-reviewed journals. The search yielded 10 articles including 2,280 subjects. The study design, sample size, PUFA levels for both patients and control subjects, sampling tissue, diagnoses and diagnostic criteria for cognitive deficits, and distribution of mean age and gender of included subjects were extracted for each study. In a random-effects model, we found that the levels of EPA (effect size [ES] = -0.47, P < .0001), DHA (ES = -0.33, P = .017), and total n-3 PUFAs (ES = -0.46, P = .001) were decreased in patients with dementia. However, the levels of EPA (ES = -0.44, P = .002), but not DHA or other PUFAs, were significantly lower in patients with predementia syndrome. Our results support the important role of n-3 PUFAs in the pathophysiology of dementia. In addition, the analyses of predementia studies indicate that EPA might be not only a disease-state marker but also a risk factor for cognitive impairment.
Article
Loss of bone is an almost universal accompaniment of aging that proceeds at an average rate of 0.5-1% per annum from midlife onwards. There are at least four nutrients involved in this process: calcium, salt, protein, and vitamin D, at least in women. The pathogenesis of osteoporosis in men is more obscure. Calcium is a positive risk factor because calcium requirement rises at the menopause due to an increase in obligatory calcium loss and a small reduction in calcium absorption that persist to the end of life. A metaanalysis of 20 calcium trials shows that this process can generally be arrested by calcium supplementation, although there is some doubt about its effectiveness in the first few years after menopause. Salt is a negative risk factor because it increases obligatory calcium loss; every 100 mmol of sodium takes 1 mmol of calcium out of the body. Restricting salt intake lowers the rate of bone resorption in postmenopausal women. Protein is another negative risk factor; increasing animal protein intake from 40 to 80 g daily increases urine calcium by about 1 mmol/day. Low protein intakes in third world countries may partially protect against osteoporosis. Vitamin D (sometimes called a nutrient and sometimes a hormone) is important because age-related vitamin D deficiency leads to malabsorption of calcium, accelerated bone loss, and increased risk of hip fracture. Vitamin D supplementation has been shown to retard bone loss and reduce hip fracture incidence in elderly women.
Article
Patients with systemic lupus erythematosus (SLE) have a high prevalence of abnormal bone metabolism and vitamin D deficiency. Genetic studies have provided the opportunity to determine the specific proteins linking vitamin D to SLE pathology [i.e., major histocompatibility complex (MHC) class II molecules, the vitamin D receptor (VDR), microRNAs (miRNAs), the renin-angiotensin system (RAS), apolipoprotein E (ApoE), liver X receptor (LXR), and toll-like receptors (TLRs)]. Vitamin D also exerts protective effects against SLE through non-genomic factors, such as ultraviolet radiation (UV) exposure, matrix metalloproteinase (MMPs), heme oxygenase-1 (HO-1), the prostaglandins (PGs), cyclooxygenase-2 (COX-2), and oxidative stress. Thus, vitamin D may play a beneficial role in SLE. Moreover, the use of calcitriol or 1α,25-dihydroxyvitamin D(3) is optimal for the treatment of SLE patients because this active form of the vitamin D(3) metabolite can modulate inflammatory cytokine production. However, further investigation into the effects of calcitriol with SLE is warranted.
Article
Few studies have evaluated protein intake and bone loss in elders. Excess protein may be associated with negative calcium balance, whereas low protein intake has been associated with fracture. We examined the relation between baseline dietary protein and subsequent 4-year change in bone mineral density (BMD) for 391 women and 224 men from the population-based Framingham Osteoporosis Study. BMD (g/cm2) was assessed in 1988-1989 and in 1992-1993 at the femur, spine, and radius. Usual dietary protein intake was determined using a semiquantitative food frequency questionnaire (FFQ) and expressed as percent of energy from protein intake. BMD loss over 4 years was regressed on percent protein intake, simultaneously adjusting for other baseline factors: age, weight, height, weight change, total energy intake, smoking, alcohol intake, caffeine, physical activity, calcium intake, and, for women, current estrogen use. Effects of animal protein on bone loss also were examined. Mean age at baseline (±SD) of 615 participants was 75 years (±4.4; range, 68-91 years). Mean protein intake was 68 g/day (±24.0; range, 14-175 g/day), and mean percent of energy from protein was 16% (±3.4; range, 7-30%). Proportional protein intakes were similar for men and women. Lower protein intake was significantly related to bone loss at femoral and spine sites (p ≤ 0.04) with effects similar to 10 lb of weight. Persons in the lowest quartile of protein intake showed the greatest bone loss. Similar to the overall protein effect, lower percent animal protein also was significantly related to bone loss at femoral and spine BMD sites (all p < 0.01) but not the radial shaft (p = 0.23). Even after controlling for known confounders including weight loss, women and men with relatively lower protein intake had increased bone loss, suggesting that protein intake is important in maintaining bone or minimizing bone loss in elderly persons. Further, higher intake of animal protein does not appear to affect the skeleton adversely in this elderly population.
Chapter
Dietary fiber intake protects against chronic disease, especially cardiovascular disease. Usual dietary fiber intake is less than half of recommended levels, so most consumers need to increase consumption of high-fiber foods, such as whole grains, legumes, vegetables, and fruits. Fiber may have a role in the prevention and treatment of digestive disorders such as constipation. For more complicated digestive disorders, such as irritable bowel syndrome and ulcerative colitis, fiber may be helpful. While some health benefits of dietary fiber clearly pertain to its physical properties (e.g., colonic bulk), fiber and phytochemicals are almost impossible to separate in epidemiologic studies. Much of the health effect of fiber may be due to the phytochemicals with which it is associated. Therefore, best medical practice is to encourage fiber consumption from foods. Fiber supplements may be recommended for laxation and cholesterol lowering, but whole foods high in dietary fiber also contain phytochemicals that provide additional health benefits.
Article
This review provides a brief update of new research findings on the role of vitamin D in multiple sclerosis (MS). Evidence continues to accumulate supporting a protective role for vitamin D in MS risk and progression. Notable recent findings are that high 25-hydroxyvitamin D [25(OH)D] at the time of a first demyelinating event predicts a lower MS risk and a decreased risk of MS among offspring whose mothers had high predicted 25(OH)D levels. While a small vitamin D intervention study did not find an association between vitamin D and MS progression, this study had little statistical power, and larger trials will be needed to assess the therapeutic potential of vitamin D. Recent immunological studies also show modulation of the immune system by vitamin D that may be favorable for preventing or slowing the progression of MS. The demonstration that rare variants in CYP27B1, which encodes the enzyme that converts vitamin D to its active form, are strongly associated with MS risk supports a causal role of vitamin D deficiency as a risk factor for MS. Research on the nature of the association between vitamin D and MS risk and progression continues to progress; however, additional research on the timing and dose-response relationship will be crucial for designing future prevention and treatment trials.
Article
In comparison with calcium, magnesium is an "orphan nutrient" that has been studied considerably less heavily. Low magnesium intakes and blood levels have been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive protein, hypertension, atherosclerotic vascular disease, sudden cardiac death, osteoporosis, migraine headache, asthma, and colon cancer. Almost half (48%) of the US population consumed less than the required amount of magnesium from food in 2005-2006, and the figure was down from 56% in 2001-2002. Surveys conducted over 30 years indicate rising calcium-to-magnesium food-intake ratios among adults and the elderly in the United States, excluding intake from supplements, which favor calcium over magnesium. The prevalence and incidence of type 2 diabetes in the United States increased sharply between 1994 and 2001 as the ratio of calcium-to-magnesium intake from food rose from <3.0 to >3.0. Dietary Reference Intakes determined by balance studies may be misleading if subjects have chronic latent magnesium deficiency but are assumed to be healthy. Cellular magnesium deficit, perhaps involving TRPM6/7 channels, elicits calcium-activated inflammatory cascades independent of injury or pathogens. Refining the magnesium requirements and understanding how low magnesium status and rising calcium-to-magnesium ratios influence the incidence of type 2 diabetes, metabolic syndrome, osteoporosis, and other inflammation-related disorders are research priorities.
Article
Omega-3 fatty acids, which are found abundantly in fish oil, exert pleiotropic cardiometabolic effects with a diverse range of actions. The results of previous studies raised a lot of interest in the role of fish oil and omega-3 fatty acids in primary and secondary prevention of cardiovascular diseases. The present review will focus on the current clinical uses of omega-3 fatty acids and provide an update on their effects. Since recently published trials in patients with coronary artery diseases or post-myocardial infarction did not show an effect of omega-3 fatty acids on major cardiovascular endpoints, this review will examine the limitations of those data and suggest recommendations for the use of omega-3 fatty acids.
Article
The 2005 Dietary Guidelines Advisory Committee (DGAC) recognized calcium, potassium and magnesium, all found in high levels in dairy foods, among the shortfall nutrients in both children and adults' diets. The objectives were to determine: 1) the percentage of the population with intakes greater than the Adequate Intakes (AI) for calcium and potassium and the percentage of the population with inadequate magnesium intake (based on Estimated Average Requirement [EAR]) and 2) the impact of various levels of dairy consumption on intake of calcium, potassium and magnesium. Secondary analysis of data from the 1999-2004 NHANES. SUBJECTS/ SETTING: Participants 2 years of age and older. Percentage of the population meeting current recommendations for calcium, potassium and magnesium. Percentage of EAR/AI for nutrients was calculated based on age/gender specific values. All analyses were weighted using the NHANES six-year sample weights and adjusted for the complex sample design of NHANES with the statistical package SUDAAN. The most recent NHANES data demonstrated that a significant proportion of the American population did not meet recommendations for calcium, potassium, and magnesium. Less than 3% of the population consumed the recommended level or more of potassium. Only 30% of the US population 2 years of age and older obtained the recommended level of calcium or more and 55% consumed less than the EAR for magnesium. Recommending 3-4 servings from the dairy group for all people greater than 9 years of age may be necessary in order to ensure adequate intake of calcium and magnesium, assuming the current diet remains the same. More than 4 servings of dairy would be needed to meet the potassium recommendation at all ages. For those individuals who do not consume dairy products, we need to better understand the barriers to consuming specific dairy products. In addition, more research is needed to examine whether food-based recommendations are practical, feasible and cost effective to meet nutrient needs.
Article
This report presents Healthy Eating Index (HEI) scores for adults, 60 years of age and over, from the National Health and Nutrition Examination Survey (NHANES), 1999-2002, and examines the association between the HEI scores and sex, age, race and ethnicity, education, smoking status, tooth retention, self-reported health, and body mass index (BMI). The percentage of older adults meeting the recommendations for the HEI components and dietary quality based on the overall score were estimated. Means and standard errors were calculated for selected sociodemographic and health characteristics for the total population and stratified by sex. A two-tailed t-test or analysis of variance was used to test the effects of the sociodemographic and health characteristics on the HEI scores. When a characteristic consisted of three levels, the Bonferroni method of adjustment was used to assess significant differences in the mean scores. Seventy-two percent of older adults met the guidelines for cholesterol intake and 56% met the recommendation for diet variety, but less than one-third met the recommendations for HEI's five food groups. Only 17% of older adults consumed a "good" quality diet. Males had higher scores for some components, but females had higher scores for others. Age significantly influenced several HEI components, but not in a consistent fashion. Non-Hispanic white persons usually had the highest scores and non-Hispanic black persons had the lowest scores. Adults with more years of education usually had higher scores but smokers usually had lower scores. Edentulous persons and those who rated their health as fair or poor generally ate fewer servings of fruits and vegetables, ate a less varied diet, and had a poorer quality diet than persons with teeth or who rated their health higher. Females with a BMI of 30 or higher ate fewer servings of dairy products, consumed a higher percentage of calories from total and saturated fat, and had a lower quality diet than those whose BMI was less than 30. This research demonstrates that many older adults' diets need improvement, and that many sociodemographic and health characteristics were associated with their intake of food and nutrient groups and overall dietary quality.
Article
Consumption of omega 3 fatty acids is known to have health benefits. For many years, the importance of the only member of the omega 3 family considered to be essential, alpha-linolenic acid (ALA), has been overlooked. Current research indicates that ALA, along with its longer chain metabolites, may play an important role in many physiological functions. Potential benefits of ALA include cardioprotective effects, modulation of the inflammatory response, and a positive impact on both central nervous system function and behavior. Recommended levels for ALA intake have been set, yet the possible advantages of its consumption are just being revealed.