Vitamin D and bone health in postmenopausal women

Osteoporosis, a disease of increased skeletal fragility, is becoming increasingly common as the U.S. population ages. Adequate vitamin D and calcium intake is the cornerstone of osteoporosis prevention and treatment. Age-related changes in vitamin D and calcium metabolism increase the risk of vitamin D insufficiency and secondary hyperparathyroidism. Although longitudinal data have suggested a role of vitamin D intake in modulating bone loss in perimenopausal women, studies of vitamin D and calcium supplementation have failed to support a significant effect of vitamin D and calcium during early menopause. There is a clearer benefit in vitamin D and calcium supplementation in older postmenopausal women. Vitamin D intake between 500 and 800 IU daily, with or without calcium supplementation, has been shown to increase bone mineral density (BMD) in women with a mean age of approximately 63 years. In women older than 65, there is even more benefit with vitamin D intakes of between 800 and 900 IU daily and 1200-1300 mg of calcium daily, with increased bone density, decreased bone turnover, and decreased nonvertebral fractures. The decreases in nonvertebral fractures may also be influenced by vitamin D-mediated decreases in body sway and fall risk. There are insufficient available data supporting a benefit from vitamin D supplementation alone, without calcium, to prevent osteoporotic fracture in postmenopausal women.     

Prevention of fractures in older people with calcium and vitamin D

The greatest cause of fracture in older people is osteoporosis which contributes to increased morbidity and mortality in older people. A number of meta-analyses have been performed assessing the effectiveness of calcium supplementation alone, vitamin D supplementation alone and the combined therapy on bone loss and fracture reduction in older people. The results of these meta-analyses indicate that vitamin D supplementation alone is unlikely to reduce fracture risk, calcium supplementation alone has a modest effect in reducing total fracture risk, but compliance with calcium supplements is poor in the long term. The combination of calcium supplementation with vitamin D supplementation, particularly in those at risk of marginal and low vitamin D status reduces total fractures, including hip fractures. Therefore older people would be recommended to consume adequate dietary calcium (>1100 mg/day) together with maintaining adequate vitamin D status (>60 nmol/L 25(OH)D) to reduce risk of fracture. It is a challenge to consume sufficient dietary calcium from dietary sources, but the increasing range of calcium fortified foods could assist in increasing the dietary calcium intake of older people. In addition to the usual dairy based food sources, vitamin D supplements are likely to be required for older people with reduced mobility and access to sunlight.     

Supplementation with vitamin D and calcium in long-term care residents

Vitamin D deficiency is a common finding in institutionalized older persons. Vitamin D-deficient elderly persons are at higher risk of falls and fractures. Long-term care residents should be considered at high risk of vitamin D deficiency and therefore vitamin D supplementation is highly recommended in this population. The minimal effective dose is 800 IU per day. It is recommended that vitamin D supplementation should be implemented in all patients in residential aged care facilities. In addition to vitamin D, calcium supplementation has shown to enhance the effect of vitamin D on bone. Calcium intake should be optimized (1200-1500 mg per day recommended) and supplementation offered to those with inadequate intake. The addition of calcium depends on tolerance, history of kidney stones, and emerging data regarding its cardiovascular safety.     

Osteoporosis: the role of micronutrients

Osteoporosis and low bone mass are currently estimated to be a major public health threat. Adequate nutrition plays a major role in the prevention and treatment of osteoporosis; the micronutrients of greatest importance are calcium and vitamin D. Calcium has been shown to have beneficial effects on bone mass at all ages, although the results are not always consistent. Higher doses than the current US recommendation (600 IU) of vitamin D in the elderly (age > or = 65 y) may actually be required for optimal bone health (800-1000 IU/d). The elderly can clearly benefit from increased vitamin D intakes; however, the potential importance of vitamin D in peak bone mass is just being investigated. Vitamin D has been related to falls, with supplementation reducing the number of falls. There are clear fracture benefits demonstrated in randomized clinical trials of calcium and vitamin D supplementation. The other micronutrient needs for optimizing bone health can be easily met by a healthy diet that is high in fruits and vegetables to ensure adequate intakes for magnesium, potassium, vitamin C, vitamin K, and other potentially important nutrients. Healthcare professionals need to be aware of the importance of adequate calcium and vitamin D intakes (easily monitored by serum 25(OH)D) for optimal bone health, as well as the prevention of falls and fractures. In addition, a healthy diet that includes 5 servings a day of fruits and vegetables should optimize the intake of micronutrients required for bone health.     

Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety

For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.     

Effects of vitamin D in the elderly population: current status and perspectives

Besides its well-known effect on bone metabolism, recent researches suggest that vitamin D may also play a role in the muscular, immune, endocrine, and central nervous systems. Double-blind RCTs support vitamin D supplementation at a dose of 800 IU per day for the prevention of falls and fractures in the senior population. Ecological, case–control and cohort studies have suggested that high vitamin D levels were associated with a reduced risk of autoimmune diseases, type 2 diabetes, cardio-vascular diseases and cancer but large clinical trials are lacking today to provide solid evidence of a vitamin D benefit beyond bone health. At last, the optimal dose, route of administration, dosing interval and duration of vitamin D supplementation at a specific target dose beyond the prevention of vitamin D deficiency need to be further investigated.     

Vitamin D deficiency in residents of academic long-term care facilities despite having been prescribed vitamin D

OBJECTIVES: Vitamin D is vitally important in maintaining skeletal health. A low plasma vitamin D concentration is associated with increased parathyroid hormone secretion, increased bone turnover, osteomalacia, and osteoporosis. As a result, vitamin D deficiency is associated with a higher incidence of hip and other fractures. Although Vitamin D deficiency has been reported in long-term care facilities, optimal methods of replenishment have not been defined. The objective of the present study was to identify the pattern of calcium and vitamin D supplementation in nursing home residents and to identify vitamin D deficiency in residents already on supplement therapy. DESIGN: Retrospective chart review. SETTING: Five academic nursing homes staffed by faculty from the University of Arkansas for Medical Sciences. PARTICIPANTS: Elderly residents aged 65 and older receiving calcium and vitamin D supplements. MEASUREMENTS: Data on dose, frequency, and levels of calcium and vitamin D were collected. The medication list and creatinine levels were also recorded. RESULTS: Forty-four (40%) residents were receiving 1000 mg, 48 (44%) were receiving 1200 mg, and 9 (8.2%) were receiving 1500 mg of calcium carbonate. Similarly, 79 (72%) residents were on 400 IU, 13 (12%) were on 600 IU, and only 8 (7%) were on 800 IU of vitamin D3 (cholecalciferol). Low levels of Vitamin D 25 (OH) D (values <30 ng/mL) were identified in 49.4% of residents; 16% were found to have deficiency (<20 ng/mL). CONCLUSION: Despite clear benefit, nursing home residents were not supplemented adequately with calcium and vitamin D.     

Abstracts on Calcium and Bone Metabolism

Objective: Vitamin D supplementation may be required for certain subgroups in the United States in whom status and intake are inadequate, but the impact of various doses, and whether calcium administration jointly or independently influences vitamin D metabolite levels, is unclear.

Methods: In a pilot chemoprevention trial of biomarkers of risk for colorectal adenoma, we measured the impact of vitamin D supplementation and/or calcium supplementation on plasma vitamin D metabolite concentrations. Ninety-two adult men and women living in the southeastern United States were randomized to 800 IU vitamin D₃, 2000 mg elemental calcium, both, or placebo daily for 6 months. We examined vitamin D status at baseline and postintervention and compared the change in plasma 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)₂D levels by intervention group using general linear models.

Results: Eighty-two percent of the study population had insufficient plasma 25(OH)D concentrations (<75 nmol/L) at baseline, with the lowest levels observed among African American participants. Vitamin D supplements, with or without calcium supplementation, raised plasma 25(OH)D concentrations, on average, by 25 to 26 nmol/L. Half of the study participants were classified as having sufficient 25(OH)D status after 6 months of 800 IU of vitamin D₃ daily. Calcium alone did not influence 25(OH)D concentrations.

Conclusion: In this southeastern U.S. population, half of the study participants receiving 800 IU vitamin D₃ daily had blood 25(OH)D concentrations of ≤75 nmol/L after a 6-month intervention period, supporting higher vitamin D dose requirements estimated by some groups. More research is needed to identify the optimal vitamin D dose to improve 25(OH)D status in various at-risk populations.     

Efficacy of optimization of vitamin D in preventing osteoporosis and osteoporotic fractures: A systematic review

Increased intake or supplementation of vitamin D is often recommended for normal bone health; however, its preventive effect on osteoporosis has not been fully evaluated. The aim of this review is to gather evidence of the efficacy of the optimization of vitamin D nutrition in preventing osteoporosis and osteoporotic fractures. PubMed was used for searching the relevant literature using the MeSH terms “Bone Density (limited to “human”, “female”, and “English” literature)” or “Fractures (limited to “human”, “age ≥45 years”, and “English” literature)”, and “Vitamin D”. The searches yielded 19 randomized controlled trials (RCTs), nine cohort studies, 19 case-control studies, 19 cross-sectional studies, and one meta-analysis. We attempted to answer three questions: 1) does increased vitamin D intake prevent bone loss in peri- and postmenopausal women?, 2) does increased vitamin D intake prevent osteoporotic fractures in the elderly?, and 3) does increased vitamin D in take positively affect peak bone mass attainment in young women? The answer to questions 1 and 2 is that a vitamin D intake of 10–17.5 μg/day (400–700 IU/day) or more is effective in preventing bone loss in late postmenopausal women and an intake of 17.5–20 μg/day (700–800 IU/day) or more together with a calcium supplement reduces the risk of osteoporotic fractures. For question 3, some lines of evidence support the negative effect of low vitamin D nutrition on the attainment of peak bone mass in young women. Further studies are needed to clarify the effect of vitamin D in this age group.Key words: bone density, fractures, osteoporosis, systematic review, vitamin D     

Combined Calcium and Vitamin D Supplementation Reduces Bone Loss and Fracture Incidence in Older Men and Women

A recent supplementation study of 389 men and women over the age of 65 years was conducted to address the impact of combined calcium and vitamin D supplementation on nonvertebral fracture incidence and maintenance of bone mass. Daily supplementation with 500 mg calcium and 700 IU vitamin D for 3 years moderately reduced bone loss at several sites and significantly decreased the rate of nonvertebral fractures, compared with a placebo group. Optimal intake of both calcium and vitamin D may be an easily implemented strategy to maintain existing bone mass and reduce the risk of fracture in older men and women.     

Serum 25-hydroxyvitamin D and muscle atrophy in the elderly

The objective of this review is to consider the mechanisms by which vitamin D affects muscle and the evidence that vitamin D status is important for muscle performance and fall prevention in older adults. Vitamin D receptors have been identified in human skeletal-muscle cells. Activation of these receptors by 1,25-dihydroxyvitamin D is involved in the action of vitamin D on the myocyte. Several studies have examined the effect of supplemental vitamin D on muscle strength, balance and falls. Among those examining muscle strength, results have been either positive for vitamin D or null. A recent meta-analysis of seventeen such trials revealed no significant effect of vitamin D overall, but a significant improvement in strength was observed in the trials in which the mean starting level of 25-hydroxyvitamin D was 25 nmol/l or below. Evidence for an effect of vitamin D on balance, measured as sway, is less abundant but more consistently positive. Many trials have evaluated the effect of supplemental vitamin D on falls. Overall, there is about a 20% lower risk of falling with supplementation. One meta-analysis considered the vitamin D dose administered and concluded that doses up through 15 μg (600 IU) were ineffective and doses of 17·5-25 μg/d (700-1000 IU/d) significantly lowered fall risk. The minimal 25-hydroxyvitamin D level needed for benefit was 60 nmol/l.     

Vitamin D supplementation versus combined calcium and vitamin D in older female patients — An observational study

Background

In most developed countries overt vitamin D deficiency, characterized by rickets or osteomalacia, is now uncommon However, subclinical vitamin D insufficiency is extremely common and may contribute to the development of skeletal and non-skeletal problems. Standard practice involves supplementation with a combination of vitamin D and calcium although the benefit of adding calcium to vitamin D supplements has not been fully established and may reduce adherence due to its bulky and chalky consistency.

Purpose of study

To compare the effects of vitamin D alone versus vitamin D/calcium supplements on vitamin D levels, bone profile and parathyroid hormone level.

Population

Older (>65 years) female patients living in the community and long term care institutions.

Interventions

Either 800 iu of vitamin D3 or a composite supplement of 800 iu vitamin D3 and 1000mg calcium were given to patients in an open-labelled observational study. Serum 25-hydroxy-vitamin D, parathyroid hormone, calcium, phosphate and alkaline phosphatase levels were assessed at baseline and after 3 months of treatment.

Results

Serum 25-hydroxy-vitamin D levels rose from baseline levels of 25 ± 16 to 79 ± 16 in those treated with vitamin D alone and from 35 ± 24 nmol/L to 70 ± 24 nmol/L in those treated with vitamin D and calcium Serum PTH levels fell by similar amounts in both groups. In both community dwellers and institutionalised patients, those treated with vitamin D alone were at least as likely to achieve normalisation of serum vitamin D levels as those on combined calcium/vitamin D treatment.

Conclusion

Vitamin D alone appears as effective as combined calcium/vitamin D treatment in restoring serum vitamin D levels in older community dwelling and institutionalised patients. A prospective randomised trial would help confirm these findings.     

Vitamin D supplementation and depression in the women's health initiative calcium and vitamin D trial

While observational studies have suggested that vitamin D deficiency increases risk of depression, few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms. The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3) combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women. The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at randomization (1995-2000). Two years later, women again reported on their antidepressant use, and 2,263 completed a second Burnam scale. After 2 years, women randomized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms (Burnam score ≥0.06) of 1.16 (95% confidence interval: 0.86, 1.56) compared with women in the placebo group. Supplementation was not associated with antidepressant use (odds ratio = 1.01, 95% confidence interval: 0.92, 1.12) or continuous depressive symptom score. Results stratified by baseline vitamin D and calcium intake, solar irradiance, and other factors were similar. The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3) along with calcium and depression in older women. Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression.     

Vitamin D Supplementation for Extraskeletal Indications in Older Persons

Low levels of vitamin D have been implicated in a wide variety of conditions highly prevalent in the geriatric population, including fractures, functional limitations, cancer, cardiovascular disease, and depression. Vitamin D supplementation is often considered integral to the prevention of falls and fractures in the setting of osteoporosis. For other conditions, however, consensus is lacking, and the clinician may struggle to balance competing recommendations around screening, supplementation, and monitoring. This review seeks to provide an overview of the available evidence on the use of vitamin D supplementation to ameliorate sarcopenia, enhance cognition, treat depression, prevent cancer, and reduce mortality—outcomes that are common concerns in the geriatric population for which the merits of treatment are not always certain.Evidence suggests vitamin D supplementation may decrease mortality. Therefore, it may be reasonable to prescribe routine supplementation with oral cholecalciferol 800 to 1000 IU daily to all patients aged ≥65 years who do not have a contraindication. No screening or monitoring would be recommended for this population. We additionally recommend the use of oral cholecalciferol over ergocalciferol for any routine supplementation as this benefit was only observed with cholecalciferol. For patients with depression or cognitive disorders, we recommend screening for vitamin D deficiency, treating with oral cholecalciferol if present, and monitoring periodically to target a level of >30 ng/mL as an adjunct to usual care. The level of evidence certainly would not justify the use of vitamin D in place of more evidence-based therapies, but given the burden of these conditions in the geriatric population, we believe the potential benefit justifies the minimal risk.     

A food frequency questionnaire for the assessment of calcium, vitamin D and vitamin K: a pilot validation study

The study objective was to validate a food frequency questionnaire (FFQ) to assess calcium, vitamin D and vitamin K intakes in overweight and obese postmenopausal community-dwelling women. The FFQ was validated against intakes derived from a 5-day diet record (5DDR) that also included assessment of supplement intake. Strong correlations between methods were observed for all nutrients (r = 0.63, 0.89, 0.54 for calcium, vitamin D and vitamin K, respectively) and cross-classification analyses demonstrated no major misclassification of participants into intake quartiles. Bland-Altman analysis showed that the FFQ overestimated intakes for calcium, by 576 mg/day (95% CI, -668 to 1,821 mg/day), for vitamin D by 75 IU/day (95% CI, -359 to 510 IU/day), and for vitamin K by 167 mcg/day (95% CI, -233 to 568 mcg/day). This pilot study showed promising validation evidence for the use of this FFQ, which focuses on calcium, vitamin D and vitamin K intakes in postmenopausal women, as a screening tool in clinical and research settings.     

The 2011 Dietary Reference Intakes for Calcium and Vitamin D: what dietetics practitioners need to know

The Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D comprehensively reviewed the evidence for both skeletal and nonskeletal health outcomes and concluded that a causal role of calcium and vitamin D in skeletal health provided the necessary basis for the 2011 Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) for ages older than 1 year. For nonskeletal outcomes, including cancer, cardiovascular disease, diabetes, infections, and autoimmune disorders, randomized clinical trials were sparse, and evidence was inconsistent, inconclusive as to causality, and insufficient for Dietary Reference Intake (DRI) development. The EAR and RDA for calcium range from 500 to 1,100 and 700 to 1,300 mg daily, respectively, for ages 1 year and older. For vitamin D (assuming minimal sun exposure), the EAR is 400 IU/day for ages older than 1 year and the RDA is 600 IU/day for ages 1 to 70 years and 800 IU/day for 71 years and older, corresponding to serum 25-hydroxyvitamin D (25OHD) levels of 16 ng/mL (40 nmol/L) for EARs and 20 ng/mL (50 nmol/L) or more for RDAs. Prevalence of vitamin D inadequacy in North America has been overestimated based on serum 25OHD levels corresponding to the EAR and RDA. Higher serum 25OHD levels were not consistently associated with greater benefit, and for some outcomes U-shaped associations with risks at both low and high levels were observed. The Tolerable Upper Intake Level for calcium ranges from 1,000 to 3,000 mg daily, based on calcium excretion or kidney stone formation, and from 1,000 to 4,000 IU daily for vitamin D, based on hypercalcemia adjusted for uncertainty resulting from emerging risk relationships. Urgently needed are evidence-based guidelines to interpret serum 25OHD levels relative to vitamin D status and intervention.     

Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial

Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford–AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8–34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1–58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.     

Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults

OBJECTIVE: To assess the vitamin D status of healthy young people living in Northern Ireland and the effect of vitamin D supplementation on vitamin D status and bone turnover. DESIGN: Double-blinded randomised controlled intervention study. SETTING: University of Ulster, Coleraine, Northern Ireland. SUBJECTS: In total, 30 apparently healthy students (15 male and 15 female subjects), aged 18-27 years, were recruited from the university, with 27 completing the intervention. INTERVENTIONS: Subjects were randomly assigned, to receive either 15 microg (600 IU) vitamin D(3) and 1,500 mg calcium/day (vitamin D group), or 1,500 mg calcium/day (control group) for 8 weeks between January and March. Vitamin D status, bone turnover markers, serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention. RESULTS: At baseline, vitamin D status was low in both the vitamin D group (47.9 (s.d. 16.0)) and the control group (55.5 (s.d. 18.6) nmol/l 25(OH)D). Post intervention vitamin D status was significantly higher in the vitamin D-treated group (86.5 (s.d. 24.5)) compared to the control group (48.3 (s.d. 16.8) nmol/l) (P<0.0001). There was no significant effect of supplementation on bone turnover markers or PTH concentrations. CONCLUSIONS: This study suggests that young adults in Northern Ireland do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime. A daily supplement of 15 microg vitamin D(3) significantly increased vitamin D status in these individuals to levels of sufficiency. Achievement of an optimum vitamin D status among young adults may have future positive health implications.     

Dietary Vitamin D Supplementation Does Not Reduce the Incidence or Severity of Asbestos-Induced Mesothelioma in a Mouse Model

Epidemiological studies suggest that vitamin and mineral intake is associated with cancer incidence. A prevention strategy based on diet or dietary supplementation could have enormous benefit, both directly, by preventing disease, and indirectly by alleviating fear in millions of people worldwide who have been exposed to asbestos. We have previously shown that dietary supplementation with the antioxidants vitamins A, E, and selenium does not affect overall survival nor the time to progression of asbestos-induced mesothelioma in MexTAg mice. Here we have extended our analysis to vitamin D. We compared survival of asbestos-exposed MexTAg mice provided with diets that were deficient or supplemented with 4500 IU/kg vitamin D (cholecalciferol). Survival of supplemented mice was significantly shorter than mice given a standard AIN93 diet containing 1000 IU/kg cholecalciferol (median survival was 29 and 32.5 weeks respectively). However, mice deficient in vitamin D had the same rate of mesothelioma development as control mice. Neither the latency time from asbestos exposure to diagnosis nor disease progression after diagnosis were significantly different between mice on these diets. We conclude that vitamin D is unlikely to moderate the incidence of disease in asbestos-exposed populations or to ameliorate the pathology in patients with established mesothelioma.