Periodontal Disease and Other Adverse Health Outcomes Share Risk Factors, including Dietary Factors and Vitamin D Status.

For nearly a century, researchers have associated periodontal disease (PD) with risks of other adverse health outcomes such as cardiovascular disease, diabetes mellitus, and respiratory diseases, as well as adverse pregnancy outcomes. Those findings have led to the hypothesis that PD causes those adverse health outcomes either by increasing systemic inflammation or by the action of periodontopathic bacteria. However, experiments largely failed to support that hypothesis. Instead, the association is casual, not causal, and is due to shared underlying modifiable risk factors, including smoking, diet, obesity, low levels of physical activity, and low vitamin D status. Diabetes mellitus is also considered a risk factor for PD, whereas red and processed meat are the most important dietary risk factors for diabetes. Because PD generally develops before other adverse health outcomes, a diagnosis of PD can alert patients that they could reduce the risk of adverse health outcomes with lifestyle changes. In addition, type 2 diabetes mellitus can often be reversed rapidly by adopting an anti-inflammatory, nonhyperinsulinemic diet that emphasizes healthful, whole plant-based foods. This review describes the evidence that proinflammatory and prohyperinsulinemia diets and low vitamin D status are important risk factors for PD and other adverse health outcomes. We also make recommendations regarding dietary patterns, food groups, and serum 25-hydroxyvitamin D concentrations. Oral health professionals should routinely inform patients with PD that they could reduce their risk of severe PD as well as the risks of many other adverse health outcomes by making appropriate lifestyle changes.

Evidence That Increasing Serum 25(OH)D Concentrations to 30 ng/mL in the Kingdom of Saudi Arabia and the United Arab Emirates Could Greatly Improve Health Outcomes.

Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer's disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.

Vitamin D deficiency in British South Asians, a persistent but avoidable problem associated with many health risks (including rickets, T2DM, CVD, COVID-19 and pregnancy complications): the case for correcting this deficiency.

High vitamin D deficiency rates, with rickets and osteomalacia, have been common in South Asians (SAs) arriving in Britain since the 1950s with preventable infant deaths from hypocalcaemic status-epilepticus and cardiomyopathy. Vitamin D deficiency increases common SA disorders (type 2 diabetes and cardiovascular disease), recent trials and non-linear Mendelian randomisation studies having shown deficiency to be causal for both disorders. Ethnic minority, obesity, diabetes and social deprivation are recognised COVID-19 risk factors, but vitamin D deficiency is not, despite convincing mechanistic evidence of it. Adjusting analyses for obesity/ethnicity abolishes vitamin D deficiency in COVID-19 risk prediction, but both factors lower serum 25(OH)D specifically. Social deprivation inadequately explains increased ethnic minority COVID-19 risks. SA vitamin D deficiency remains uncorrected after 70 years, official bodies using 'education', 'assimilation' and 'diet' as 'proxies' for ethnic differences and increasing pressures to assimilate. Meanwhile, English rickets was abolished from ~1940 by free 'welfare foods' (meat, milk, eggs, cod liver oil), for all pregnant/nursing mothers and young children (<5 years old). Cod liver oil was withdrawn from antenatal clinics in 1994 (for excessive vitamin A teratogenicity), without alternative provision. The take-up of the 2006 'Healthy-Start' scheme of food-vouchers for low-income families with young children (<3 years old) has been poor, being inaccessible and poorly publicised. COVID-19 pandemic advice for UK adults in 'lockdown' was '400 IU vitamin D/day', inadequate for correcting the deficiency seen winter/summer at 17.5%/5.9% in White, 38.5%/30% in Black and 57.2%/50.8% in SA people in representative UK Biobank subjects when recruited ~14 years ago and remaining similar in 2018. Vitamin D inadequacy worsens many non-skeletal health risks. Not providing vitamin D for preventing SA rickets and osteomalacia continues to be unacceptable, as deficiency-related health risks increase ethnic health disparities, while abolishing vitamin D deficiency would be easier and more cost-effective than correcting any other factor worsening ethnic minority health in Britain.

Comparing the Evidence from Observational Studies and Randomized Controlled Trials for Nonskeletal Health Effects of Vitamin D.

Although observational studies of health outcomes generally suggest beneficial effects with, or following, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations, randomized controlled trials (RCTs) have generally not supported those findings. Here we review results from observational studies and RCTs regarding how vitamin D status affects several nonskeletal health outcomes, including Alzheimer's disease and dementia, autoimmune diseases, cancers, cardiovascular disease, COVID-19, major depressive disorder, type 2 diabetes, arterial hypertension, all-cause mortality, respiratory tract infections, and pregnancy outcomes. We also consider relevant findings from ecological, Mendelian randomization, and mechanistic studies. Although clear discrepancies exist between findings of observational studies and RCTs on vitamin D and human health benefits these findings should be interpreted cautiously. Bias and confounding are seen in observational studies and vitamin D RCTs have several limitations, largely due to being designed like RCTs of therapeutic drugs, thereby neglecting vitamin D's being a nutrient with a unique metabolism that requires specific consideration in trial design. Thus, RCTs of vitamin D can fail for several reasons: few participants' having low baseline 25(OH)D concentrations, relatively small vitamin D doses, participants' having other sources of vitamin D, and results being analyzed without consideration of achieved 25(OH)D concentrations. Vitamin D status and its relevance for health outcomes can usefully be examined using Hill's criteria for causality in a biological system from results of observational and other types of studies before further RCTs are considered and those findings would be useful in developing medical and public health policy, as they were for nonsmoking policies. A promising approach for future RCT design is adjustable vitamin D supplementation based on interval serum 25(OH)D concentrations to achieve target 25(OH)D levels suggested by findings from observational studies.

An Exploration of How Solar Radiation Affects the Seasonal Variation of Human Mortality Rates and the Seasonal Variation in Some Other Common Disorders.

Many diseases have large seasonal variations in which winter overall mortality rates are about 25% higher than in summer in mid-latitude countries, with cardiovascular diseases and respiratory infections and conditions accounting for most of the variation. Cancers, by contrast, do not usually have pronounced seasonal variations in incidence or mortality rates. This narrative review examines the epidemiological evidence for seasonal variations in blood pressure, cardiovascular disease rates and respiratory viral infections in relation to atmospheric temperature and humidity, and solar UV exposure through vitamin D production and increased blood concentrations of nitric oxide. However, additional mechanisms most likely exist by which solar radiation reduces the risk of seasonally varying diseases. Some studies have been reported with respect to temperature without considering solar UV doses, although studies regarding solar UV doses, such as for respiratory infections, often consider whether temperature can affect the findings. More research is indicated to evaluate the relative effects of temperature and sun exposure on the seasonality of mortality rates for several diseases. Since solar ultraviolet-B (UVB) doses decrease to vanishingly small values at higher latitudes in winter, the use of safe UVB lamps for indoor use in winter may warrant consideration.

A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health.

Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world's population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative review examines the evidence for the major causes of death including cardiovascular disease, hypertension, cancer, type 2 diabetes mellitus, and COVID-19 with regard to sub-optimal 25(OH)D concentrations. Evidence for the beneficial effects comes from a variety of approaches including ecological and observational studies, studies of mechanisms, and Mendelian randomization studies. Although randomized controlled trials (RCTs) are generally considered the strongest form of evidence for pharmaceutical drugs, the study designs and the conduct of RCTs performed for vitamin D have mostly been flawed for the following reasons: they have been based on vitamin D dose rather than on baseline and achieved 25(OH)D concentrations; they have involved participants with 25(OH)D concentrations above the population mean; they have given low vitamin D doses; and they have permitted other sources of vitamin D. Thus, the strongest evidence generally comes from the other types of studies. The general finding is that optimal 25(OH)D concentrations to support health and wellbeing are above 30 ng/mL (75 nmol/L) for cardiovascular disease and all-cause mortality rate, whereas the thresholds for several other outcomes appear to range up to 40 or 50 ng/mL. The most efficient way to achieve these concentrations is through vitamin D supplementation. Although additional studies are warranted, raising serum 25(OH)D concentrations to optimal concentrations will result in a significant reduction in preventable illness and death.

A Review of the Potential Benefits of Increasing Vitamin D Status in Mongolian Adults through Food Fortification and Vitamin D Supplementation.

Serum 25-hydroxyvitamin D (25(OH)D) concentrations are low in Mongolia, averaging 22 ng/mL in summer and only 8 ng/mL in winter. Mongolians have high incidence and/or prevalence of several diseases linked to low 25(OH)D concentrations, including ischemic heart disease, malignant neoplasms, cirrhosis of the liver, ischemic stroke, lower respiratory tract infections, preterm birth complications, and diabetes mellitus. Fortifying regularly consumed foods such as flour, milk, and edible oils with vitamin D3 could raise 25(OH)D concentrations by about 10 ng/mL. However, to achieve 25(OH)D concentrations of 30-40 ng/mL in adults, vitamin D intakes of 1000 to 4000 IU/day would be required, making personal supplement use necessary. On the basis of prospective observational studies and clinical trials of disease incidence or known mortality rates and adverse pregnancy and birth outcomes, raising mean serum 25(OH)D concentrations to 40 ng/mL would likely reduce incidence and mortality rates for those and other diseases, reduce the rate of adverse pregnancy and birth outcomes, and increase mean life expectancy by one year or more.

Why Secondary Analyses in Vitamin D Clinical Trials Are Important and How to Improve Vitamin D Clinical Trial Outcome Analyses-A Comment on "Extra-Skeletal Effects of Vitamin D, Nutrients 2019, 11, 1460".

Dear Editor, [...].

Vitamin D status and its management for achieving optimal health benefits in the elderly.

INTRODUCTION: Vitamin D deficiency is common, world-wide, but vitamin D repletion throughout life, and into older age, has accepted health benefits for bone. Many mechanisms through which vitamin D also benefits soft tissues are understood, and clinical evidence of such benefits is now accumulating, especially following re-analyses of trial data, which are revealing previously missed health benefits with correction of deficiency. AREAS COVERED: The sources of vitamin D, its activation, mechanistic effects; problems of trials of supplementation for reducing health risks, the benefits shown for mortality, cardiovascular disease, infection and cancer; the global problem of vitamin D deficiency; age-related reductions in vitamin D efficacy, and currently recommended intakes. EXPERT COMMENTARY: High prevalence of vitamin D deficiency and insufficiency worldwide have proven ill-effects on health. Governmental efforts to improve population repletion by recommending minimal daily intakes does benefit some but is not effective at the population-level. However, food fortification with vitamin D3, already implemented in some countries, can solve this highly avoidable problem cost-effectively and is probably the best way to abolish vitamin D inadequacy, allowing public health benefits to emerge over time, thereby allowing future research on vitamin D to be directed at emerging issues on vitamin D.

Randomized controlled trials of vitamin D and cancer incidence: A modeling study.

Although geographic ecological studies and observational studies find that ultraviolet B exposure and 25-hydroxyvitamin D [25(OH)D] concentrations are inversely correlated with 15-20 types of cancer, few randomized controlled trials (RCTs) of vitamin D support those findings. The poor design of some RCTs may account for that lack of support. Most vitamin D RCTs to date have considered the vitamin D dose, rather than initial, final, or changes in, serum 25(OH)D concentrations. Here a model is developed for use in designing and analyzing vitamin D RCTs with application to cancer incidence. The input variables of the model are vitamin D dose, baseline and achieved 25(OH)D concentrations, known rates of cancer for the population, and numbers of participants for the treatment and placebo arms is estimated-vitamin D dosage and numbers of participants are varied to achieve desired hazard ratio significance, using information from two vitamin D RCTs on cancer incidence conducted in Nebraska with good agreement between the model estimates and reported hazard ratios. Further improvements to the conduct of vitamin D RCTs would be to start the trial with a moderate bolus dose to achieve the desired 25(OH)D concentrations, and bloodspot 25(OH)D assay use in summer and winter annually to monitor seasonal and long-term changes in 25(OH)D concentration and compliance, and to allow dosage adjustment for achievement of desired vitamin D status.

Vitamin D and chronic diseases: the current state of the art.

The objective was to provide the current state of the art regarding the role of vitamin D in chronic diseases (osteoporosis, cancer, cardiovascular diseases, dementia, autism, type 1 and type 2 diabetes mellitus, male and female fertility). The document was drawn up by panelists that provided their contribution according to their own scientific expertise. Each scientific expert supplied a first draft manuscript on a specific aspect of the document's topic that was subjected to voting by all experts as "yes" (agreement with the content and/or wording) or "no" (disagreement). The adopted rule was that statements supported by ≥75 % of votes would be immediately accepted, while those with <25 % would be rejected outright. Others would be subjected to further discussion and subsequent voting, where ≥67 % support or, in an eventual third round, a majority of ≥50 % would be needed. This document finds that the current evidence support a role for vitamin D in bone health but not in other health conditions. However, subjects with vitamin D deficiency have been found to be at high risk of developing chronic diseases. Therefore, although at the present time there is not sufficient evidence to recommend vitamin D supplementation as treatment of chronic diseases, the treatment of vitamin D deficiency should be desiderable in order to reduce the risk of developing chronic diseases.

Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects?

Several reports describe U-shaped 25-hydroxyvitamin D [25(OH)D] concentration-health outcomes, including musculo-skeletal disorders such as falls and fractures, several cancers, cardiovascular disease (CVD), cognitive function, all-cause mortality rates, birth outcomes, allergic reactions, frailty, and some other disorders. This paper reviews reports of U-shaped outcome associations with vitamin D status for evidence of underlying pathophysiological processes, or of confounding, finding that some U-shaped associations appear to be biologically meaningful, but that many could well reflect confounding by factors such as lifestyle, or hypovitaminosis D-related disease onset being masked by self-supplementation that was begun too late to correct developing health problems but before baseline vitamin D status assessment. However, the various U-shaped associations for allergic reactions may be due to vitamin D modulation of the phenotype of the immune response, shifting the Th1-Th2 balance toward Th2 formation. For prostate cancer, there seems to be little effect of 25(OH)D concentration on incidence; however, there is an inverse correlation between 25(OH)D concentration and mortality rates. Future observational studies, and randomized controlled trial data analyses, should include adjustment for data collected on prior long-term vitamin D supplementation and solar UVB exposure, as well as other potential confounders.

Longer Duration and Earlier Age of Onset of Paternal Betel Chewing and Smoking Increase Metabolic Syndrome Risk in Human Offspring, Independently, in a Community-Based Screening Program in Taiwan.

BACKGROUND: Transgenerational effects of paternal Areca catechu nut chewing on offspring metabolic syndrome (MetS) risk in humans, on obesity and diabetes mellitus experimentally, and of paternal smoking on offspring obesity, are reported, likely attributable to genetic and epigenetic effects previously reported in betel-associated disease. We aimed to determine the effects of paternal smoking, and betel chewing, on the risks of early MetS in human offspring. METHODS: The 13 179 parent-child trios identified from 238 364 Taiwanese aged ≥20 years screened at 2 community-based integrated screening sessions were tested for the effects of paternal smoking, areca nut chewing, and their duration prefatherhood on age of detecting offspring MetS at screen by using a Cox proportional hazards regression model. RESULTS: Offspring MetS risks increased with prefatherhood paternal areca nutusage (adjusted hazard ratio, 1.77; 95% confidence interval [CI], 1.23-2.53) versus nonchewing fathers (adjusted hazard ratio, 3.28; 95% CI, 1.67-6.43) with >10 years paternal betel chewing, 1.62 (95% CI, 0.88-2.96) for 5 to 9 years, and 1.42 (95% CI, 0.80-2.54) for <5 years betel usage prefatherhood (Ptrend=0.0002), with increased risk (adjusted hazard ratio, 1.95; 95% CI, 1.26-3.04) for paternal areca nut usage from 20 to 29 years of age, versus from >30 years of age (adjusted hazard ratio,1.61; 95% CI, 0.22-11.69). MetS offspring risk for paternal smoking increased dosewise (Ptrend<0.0001) with earlier age of onset (Ptrend=0.0009), independently. CONCLUSIONS: Longer duration of paternal betel quid chewing and smoking, prefatherhood, independently predicted early occurrence of incident MetS in offspring, corroborating previously reported transgenerational effects of these habits, and supporting the need for habit-cessation program provision.

Calcium, vitamin D, casein and whey protein intakes and periodontitis among Danish adults.

OBJECTIVE: To investigate whether intakes of Ca, vitamin D, casein and whey are associated with periodontitis and to investigate the possibility of interactions between them. DESIGN: Cross-sectional study. An Internet-based, 267-item FFQ was used to assess dietary intake. Intakes of casein (32.0 g/d), whey proteins (9.6 g/d) and vitamin D (5.8 µg/d) were classified as within v. above the 50th percentile. Ca intake was classified as within v. below age-specific recommendations. Severe periodontitis was defined as having ≥2 inter-proximal sites with clinical attachment loss ≥6 mm (not on the same tooth) and ≥1 inter-proximal site with pocket depth ≥5 mm. Since vitamin D influences Ca absorption, models were stratified by lower and higher (<5.8 v. ≥5.8 µg/d) vitamin D intake. SETTING: Danish Health Examination Survey (DANHES) 2007-2008. SUBJECTS: Adult participants (n 3287) in the oral health study of DANHES 2007-2008. RESULTS: Intakes of Ca within recommendations (OR=0.76; 95% CI 0.58, 0.99), whey ≥9.6 g/d (OR=0.75; 95% CI 0.58, 0.97) and casein ≥32 g/d (OR=0.75 95% CI 0.58, 0.97) were associated with lower likelihood of severe periodontitis after adjustment for age, gender, education, smoking, sucrose intake, alcohol consumption, number of teeth, daily brushing, regular visits to the dentist and chronic illness, irrespective of vitamin D intake levels. Intake of vitamin D alone was not associated severe with periodontitis. CONCLUSIONS: Intakes of Ca, casein and whey protein were inversely associated with periodontitis. Consumption of foods rich in Ca, casein and whey (e.g. dairy foods) should be promoted, as they may contribute to the prevention of periodontitis. Further longitudinal studies are required to confirm these associations.

Niacin-induced hyperglycemia is partially mediated via niacin receptor GPR109a in pancreatic islets.

The widely used lipid-lowering drug niacin is reported to induce hyperglycemia during chronic and high-dose treatments, but the mechanism is poorly understood. Recently, the niacin receptor [G-protein-coupled receptor, (GPR) 109a], has been localized to islet cells while its potential role therein remains unclear. We, therefore, aimed at investigating how GPR109a regulates islet beta-cell function and its downstream signaling using high-fat diet-induced obese mice and INS-1E beta cells. Eight-week niacin treatment elevated blood glucose concentration in obese mice with increased areas under the curve at oral glucose and intraperitoneal insulin tolerance tests. Additionally, niacin treatment significantly decreased glucose-stimulated insulin secretion (GSIS) but induced peroxisome proliferator-activated receptor gamma (Pparg) and GPR109a expression in isolated pancreatic islets; concomitantly, reactive oxygen species (ROS) were transiently increased, with decreases in GSIS, intracellular cyclic adenosine monophosphate (cAMP) accumulation and mitochondrial membrane potential (ΔΨm), but with increased expression of uncoupling protein 2 (Ucp2), Pparg and Gpr109a in INS-1E cells. Corroborating these findings, the decreases in GSIS, ΔΨm and cAMP production and increases in ROS, Pparg and GPR109a expression were abolished in INS-1E cells by GPR109a knockdown. Our data indicate that niacin-induced pancreatic islet dysfunction is probably modulated through activation of the islet beta-cell GPR109a-induced ROS-PPARγ-UCP2 pathways.

Intakes of calcium, vitamin D, and dairy servings and dental plaque in older Danish adults.

BACKGROUND: To investigate whether intakes of calcium and dairy-servings within-recommendations were associated with plaque score when allowing for vitamin D intakes. METHODS: In this cross-sectional study, including 606 older Danish adults, total dietary calcium intake (mg/day) was classified as below vs. within-recommendations and dairy intake as <3 vs. ≥3 servings/ d. Dental plaque, defined as the percentage of tooth surfaces exhibiting plaque, was classified as < median vs. ≥median value (9.5%). Analyses were stratified by lower and higher (≥6.8 µg/d) vitamin D intake. FINDINGS: Intakes of calcium (OR = 0.53; 95% CI = 0.31-0.92) and dairy servings (OR = 0.54; 95% CI = 0.33-0.89) within-recommendations were significantly associated with lower plaque score after adjustments for age, gender, education, intakes of alcohol, sucrose and mineral supplements, smoking, diseases, number of teeth, visits to the dentist, use of dental floss/tooth pick and salivary flow, among those with higher, but not lower, vitamin D intake. CONCLUSION: Intakes of calcium dairy-servings within-recommendations were inversely associated with plaque, among those with higher, but not lower, vitamin D intakes. Due to the cross-sectional nature of the study, it is not possible to infer that this association is causal.

Diabetes and cancer: Could vitamin D provide the link?

Diabetes and cancer are common diseases that may co-exist in the same individual. There is significant evidence that patients with diabetes have increased risk of developing certain cancers, especially colorectal, pancreatic and primary hepatic cancer. There is also good evidence that low levels of vitamin D are associated with increased risk of diabetes and increased risk of colorectal, and possibly other, cancers. In this article we propose that low levels of vitamin D may increase the risk of cancer in people with diabetes and describe potential molecular pathways. We suggest that large scale randomised trials of vitamin D supplementation in patients at risk of diabetes, and in patients with established diabetes to examine the effect on cancer risk, are required.

Intake of dairy products in relation to periodontitis in older Danish adults.

This cross-sectional study investigates whether calcium intakes from dairy and non-dairy sources, and absolute intakes of various dairy products, are associated with periodontitis. The calcium intake (mg/day) of 135 older Danish adults was estimated by a diet history interview and divided into dairy and non-dairy calcium. Dairy food intake (g/day) was classified into four groups: milk, cheese, fermented foods and other foods. Periodontitis was defined as the number of teeth with attachment loss ≥3 mm. Intakes of total dairy calcium (Incidence-rate ratio (IRR) = 0.97; p = 0.021), calcium from milk (IRR = 0.97; p = 0.025) and fermented foods (IRR = 0.96; p = 0.03) were inversely and significantly associated with periodontitis after adjustment for age, gender, education, sucrose intake, alcohol consumption, smoking, physical activity, vitamin D intake, heart disease, visits to the dentist, use of dental floss and bleeding on probing, but non-dairy calcium, calcium from cheese and other types of dairy food intakes were not. Total dairy foods (IRR = 0.96; p = 0.003), milk (IRR = 0.96; p = 0.028) and fermented foods intakes (IRR = 0.97; p = 0.029) were associated with reduced risk of periodontitis, but cheese and other dairy foods intakes were not. These results suggest that dairy calcium, particularly from milk and fermented products, may protect against periodontitis. Prospective studies are required to confirm these findings.

The problems of vitamin d insufficiency in older people.

This report reviews evidence on disorders related to inadequate vitamin D repletion in older people. Vitamin D is as essential for bone health in adults as in children, preventing osteomalacia and muscle weakness and protecting against falls and low-impact fractures. Vitamin D is provided by skin synthesis by UVB-irradiation from summer sunshine and to a small extent by absorption from food. However, these processes become less efficient with age. Loss of mobility or residential care restricts solar exposure. Reduced appetite and financial problems often add to these problems. Thus, hypovitaminosis D is common world-wide, but is more common and more severe in older people. Non-classical effects of vitamin D, depending on serum circulating 25-hydroxyvitamin D concentrations, are present in most non-bony tissues; disorders associated with hypovitaminosis D include increased risks of sepsis [bacterial, mycobacterial and viral], cardiovascular and metabolic disorders [e.g. hyperlipidemia, type 2 diabetes mellitus, acute vascular events, dementia, stroke and heart failure]. Many cancer risks are associated with vitamin D inadequacy, though causality is accepted only for colo-rectal cancer. Maintenance of repletion in healthy older people requires intakes of ≥800IU/day [20µg], as advised by the Institute of Medicine [IOM], but achieving such intakes usually requires supplementation. Excessive intakes are dangerous, especially in undiagnosed primary hyperparathyroidism or sarcoidosis, but the IOM finds doses <4000 IU/day are safe. Many experts suggest that ≥1000-2000 IU [25-50µg] of vitamin D daily is necessary for older people, especially when independence is lost, or hypovitaminosis D could add to the clinical problem[s]. Much higher doses than these are needed for treatment of established deficiency or insufficiency.