Annual high-dose vitamin D3 and mental well-being: randomised controlled trial

Background Epidemiological evidence supports a relationship between vitamin D and mental well-being, although evidence from large-scale placebo-controlled intervention trials is lacking.

Aims To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms; and if there is an association between serum 25-hydroxyvitamin D levels and mental health.

Method A double-blind, randomised, placebo-controlled trial of women aged 70 or older (the Vital D Study: ISRCTN83409867 and ACTR12605000658617). Participants were randomly assigned to receive 500 000 IU vitamin D3 (cholecalciferol) orally or placebo every autumn/winter for 3–5 consecutive years. The tools utilised at various time points were the General Health Questionnaire, the 12-item Short Form Health Survey, the Patient Global Impression–Improvement scale and the WHO Well-Being Index. Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants.

Results In this non-clinical population, no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health. Serum 25-hydroxyvitamin D levels in the vitamin D group were 41% higher than the placebo group 12 months following their annual dose. Despite this difference, scores from the questionnaires did not differ. Furthermore, there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups.

Conclusions The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D3 is a practical intervention to prevent depressive symptoms in older community-dwelling women.

Elderly men may benefit from vitamin D

Vitamin D deficiency is associated with a myriad of musculoskeletal disorders in the elderly, including osteoporosis, reduced muscle function, falls and fractures. Recent scientific trials, conducted mostly in elderly or institutionalized women, indicate that supplementation with at least 800 IU/d of vitamin D₃ or a dose required to raise serum 25(OH) D levels to at least 75 nmol/L, and approximately 1200 mg/d of calcium is most effective for improving many of these musculoskeletal and functional performance measures. While further targeted research is still needed in elderly men, vitamin D supplementation should be considered as a safe and low cost strategy to optimize musculoskeletal health and function in both elderly men and women.

Independent and combined effects of exercise and vitamin D on muscle morphology, function and falls in the elderly

Regular exercise, particularly progressive resistance training (PRT), is recognized as one of the most effective strategies to prevent age-related muscle loss (sarcopenia), but its effects on muscle function are mixed. However, emerging data indicates that high velocity PRT (fast concentric muscle contractions) is more effective for improving functional outcomes than traditional PRT. In terms of falls prevention, high-challenging balance training programs appear to be most effective. There is also compelling evidence that supplemental vitamin D is an effective therapeutic option for falls prevention. The findings from a recent meta-analysis revealed that supplemental vitamin D at a dose of at least 700–1,000 IU/d or an achieved serum 25(OH)D level of at least 60 nmol/L was associated with reduced falls risk among older individuals. Based on these findings, it is possible that the combination of exercise and vitamin D could have a synergistic effect on muscle morphology and function, particularly since both interventions have been shown to have beneficial effects on type II “fast twitch” muscle fibers and systemic inflammation, which have both been linked to losses in muscle mass and function. Unfortunately however, the findings from the limited number of factorial 2 × 2 design RCTs indicate that additional vitamin D does not enhance the effects of exercise on measures of muscle morphology, function or falls risk. However, none of these trials were adequately powered to detect a “synergistic” effect between the two treatment strategies, but it is likely that if an exercise-by-vitamin D interaction does exist, it may be limited to situations when vitamin D deficiency/insufficiency is corrected. Further targeted research in “high risk” groups is still needed to address this question, and evaluate whether there is a threshold level of serum 25(OH)D to maximize the effects of exercise on muscle and falls risk.

Vitamin D, obesity, and obesity-related chronic disease among ethnic minorities : a systematic review

Objective : To assess the association between 25-hydroxyvitamin D (25[OH]D) status and obesity, cardiovascular diseases (CVDs), the metabolic syndrome, and type 2 diabetes mellitus (T2DM) in ethnic minorities.

Methods : Databases searched were CINHAL with full text, Global Health, MEDLINE with full text, and PsycINFO from 1980 through 2010 (February). Studies were included if they 1) targeted immigrants from low- to high-income countries or ethnic minorities, 2) focused primarily on 25(OH)D and its relation to obesity, T2DM, and/or CVDs, and 3) were published in peer-reviewed journals. The influences of key confounders such as age, gender, and ethnicity on any observed relations were also assessed. Due to the heterogeneity of study characteristics, only a narrative synthesis was undertaken.

Results : Ethnic minorities had significantly higher rates of vitamin D insufficiency (25[OH]D <50 nmol/L; children 43.6–48.7% versus 10%; adults 30.3–53% versus 13.7–26%) than their white counterparts. None of the studies reported a prevalence of obesity stratified by ethnicity. There was evidence supporting links between vitamin D deficiency and obesity-related chronic diseases, with 14 of 14 studies reporting a statistically significant result with a measurement of obesity, four of five for T2DM, four of five for CVDs, and one of one for the metabolic syndrome. However, the strength of the association varied across ethnic groups depending on the index used to measure adiposity, T2DM, and CVDs. Because most of the included studies were cross-sectional and there were variations in outcome measurements, it was not possible to determine the relative contributions of obesity or vitamin D insufficiency to CVD risk and risk of T2DM or which is the initial driver It is possible both have a role to play.

Conclusion : Further research specific to migrant populations using randomized controlled trials are required to establish whether causal links between 25(OH)D and obesity-related chronic disease exist, and whether vitamin D supplementation could be valuable in the prevention or treatment of obesity-related diseases.

Prevalence of vitamin D insufficiency and risk factors for type 2 diabetes and cardiovascular disease among African migrant and refugee adults in Melbourne

Migration to industrialised countries poses a “double whammy” for type 2 diabetes among sub-Saharan African migrant and refugee adults. This population group has been found to be at an increased risk of obesity and type 2 diabetes, which may be further aggravated by inadequate vitamin D status. Thus, this study aimed to describe the demographics of vitamin D insufficiency, obesity, and risk factors for type 2 diabetes among sub-Saharan African migrants and refugees aged 20 years or older living in Melbourne, Australia (n=49). Data were obtained by a questionnaire, medical assessment, and fasting blood samples. The mean serum 25-hydroxyvitamin D level was 27.3 nmol/L (95% CI: 22.2, 32.4 nmol/L); with 25-hydroxyvitamin D levels <50 nmol/L occurring in 88% of participants. Participants displayed a cluster of risk factors for type 2 diabetes and cardiovascular disease: 62% were overweight or obese, 47% had insulin resistance (HOMA-IR ≥2), 25% had low density lipoprotein cholesterol levels ≥3.5 mmol/L, 24.5% had high density lipoprotein cholesterol levels ≤1.03 mmol/L, 34.6% had borderline or high levels of total cholesterol (≥5.2 mmol/L), 18.2% had borderline or high levels of triglyceride (≥1.7 mmol/L), and 16% had hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg). These findings suggest that sub-Saharan African migrants and refugees may be at risk of type 2 diabetes and atherosclerosis-related diseases such as ischemic heart disease, stroke, and peripheral vascular disease. Well-designed vitamin D interventions that incorporate lifestyle changes are urgently needed in this sub-population.

Overreporting of vitamin D deficiency by the Roche Elecsys vitamin D3 (25-OH) method

Background: Vitamin D deficiency is common. Recently Roche Diagnostics removed their Elecsys Vitamin D3 (25OH) electrochemiluminescence immunoassay (ECLIA) from use, citing deteriorating traceability to the reference method (liquid chromatography tandem mass spectrometry; LCMSMS). We investigated the performance of the Roche assay (2 assay formulations) against an LCMSMS method and the widely used DiaSorin radioimmunoassay (RIA) method.

Methods: Two sets of samples from separate populations were assayed for vitamin D. The first set was assayed using three different methods: RIA (DiaSorin) in 2004, polyclonal ECLIA (Roche) in early 2009 and LCMSMS in early 2010. The second set was assayed using polyclonal and monoclonal ECLIA (Roche) and LCMSMS in mid-2010.

Results: The correlation of the polyclonal ECLIA with the RIA was poor (ECLIA = 0.45 x RIA + 19, r² = 0.59, n = 773). LCMSMS results correlated with RIA (RIA = 0.86 x LCMSMS + 4, r² = 0.69, n = 49) better than with polyclonal ECLIA (polyclonal ECLIA = 0.55 x LCMSMS + 6, r² = 0.62, n = 55) despite a storage interval of 6 years.

In recently collected samples monoclonal and polyclonal immunoassays gave similar results (monoclonal ECLIA = 0.93 polyclonal ECLIA -3, r² = 0.60, n = 153). The correlation between monoclonal Roche ECLIA and LCMSMS in these samples was very poor (monoclonal ECLIA = 0.31 x LCMSMS + 23, r² = 0.27).

Conclusions: At the time of its removal from the market, the Roche Elecsys Vitamin D3 (25OH) assay showed unacceptable performance, underestimating vitamin D levels. It seems that this bias preceded the introduction of the monoclonal assay. The worldwide distribution of the assay and the duration of this bias likely led to a significant number of patients starting supplementation unnecessarily.

Vitamin D and adult bone health in Australia and New Zealand : a position statement

• A significant number of Australians are deficient in vitamin D - it is a fallacy that Australians receive adequate vitamin D from casual exposure to sunlight.

• People at high risk of vitamin D deficiency include elderly people (particularly those in residential care), people with skin conditions where avoidance of sunlight is advised, those with dark skin (particularly if veiled), and those with malabsorption.

• Exposure of hands, face and arms to one-third of a minimal erythemal dose (MED) of sunlight (the amount that produces a faint redness of skin) most days is recommended for adequate endogenous vitamin D synthesis. However, deliberate sun exposure between 10:00 and 14:00 in summer (11:00-15:00 daylight saving time) is not advised.

• If this sun exposure is not possible, then a vitamin D supplement of at least 400IU (10 μg) per day is recommended.

• In vitamin D deficiency, supplementation with 3000-5000 IU ergocalciferol per day (Ostelin [Boots]; 3-5 capsules per day) for 6-12 weeks is recommended.

• Larger-dose preparations of ergocalciferol or cholecalciferol are available in New Zealand, Asia and the United States and would be useful in Australia to treat moderate to severe vitamin D deficiency states in the elderly and those with poor absorption; one or two annual intramuscular doses of 300 000 IU of cholecalciferol have been shown to reverse vitamin D deficiency states.

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand : a consensus statement

• Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture.

• A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions.

• To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life.

• Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown.

• To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150 000 IU may be considered.

• Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/ day if 1-12 months of age; 5000 IU/day if > 12 months of age).

• High-dose bolus therapy (300 000-500 000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures : the Geelong Osteoporosis Study

In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures.

Introduction: In a population of women who reside in a temperate climate and do not generally receive dietary vitamin D supplementation, we investigated whether seasonal vitamin D insufficiency is associated with increased risk of fracture.

Materials and Methods: An observational, cross-sectional, population-based study set in southeastern Australia (latitude 38–39° S). Participants were drawn from a well-defined community of 27,203 women ≥55 years old: 287 randomly selected from electoral rolls, 1635 with incident fractures, and 1358 presenting to a university hospital with falls. The main outcome measures were annual periodicities of ultraviolet radiation, serum 25-hydroxyvitamin D [25(OH)D], serum parathyroid hormone (PTH), serum C-telopeptide (CTx), BMD, falls, and fractures.

Results: Cyclic variations in serum 25(OH)D lagged 1 month behind ultraviolet radiation, peaking in summer and dipping in winter (p < 0.001). Periodicity of serum PTH was the inverse of serum 25(OH)D, with a phase shift delay of 1 month (p = 0.004). Peak serum CTx lagged peak serum PTH by 1–2 months. In late winter, a greater proportion of falls resulted in fracture (p < 0.001). Seasonal periodicity in 439 hip and 307 wrist fractures also followed a simple harmonic model (p = 0.078 and 0.002, respectively), peaking 1.5–3 months after the trough in 25(OH)D.

Conclusions: A fall in 25(OH)D in winter is accompanied by increases in (1) PTH levels, (2) bone resorption, (3) the proportion of falls resulting in fracture, and (4) the frequency of hip and wrist fracture. Whether vitamin D supplementation in winter can reduce the population burden of fractures requires further investigation.

Behavioural and physical characteristics associated with vitamin D status in women

For most people in Australia, the primary source of vitamin D is casual exposure to sunlight. Hypovitaminosis D has been reported for high-risk populations, but little has been documented for women of all ages living in the community. Using cross-sectional data, we aimed to describe physical and behavioural characteristics associated with serum 25-hydroxyvitamin D (25OHD) for such women and to determine the association of serum 25OHD with hypertension and bone health. Serum 25OHD, parathyroid hormone (PTH), blood pressure, bone mineral density (BMD) and anthropometry were measured in a random sample of 861 women aged 20–92 years enrolled in the Geelong Osteoporosis Study, set in a temperate region at latitude 38–39°S. Lifestyle factors (including diet, smoking, medication use, socio-economic status, residence, education, occupation, and physical activity) were documented by questionnaire. In season-adjusted models for women aged 20–54 years, physical activity and living with a partner were independently and positively associated with serum 25OHD; associations with weight and waist–hip ratio were negative. Among older women, physical activity, vitamin D intake and urban dwelling were positively associated with serum 25OHD; age, weight and smoking were negative. Compared with the lowest tertile, those in the highest serum 25OHD tertile were less likely to have elevated serum PTH (adjusted OR = 0.25, 95% CI 0.16–0.41) and high blood pressure (adjusted OR = 0.40, 95% CI 0.22–0.72), and more likely to have normal hip and spine BMD (adjusted OR = 1.65, 95% CI 1.08–2.52). In multivariable models adjusting for season, age, weight (and height), BMD was associated with serum 25OHD at the spine, hip and whole body; no associations were detected at the forearm and no other characteristics were identified as confounders. Factors associated with high vitamin D status generally reflected healthy body habitus and active lifestyles. In contrast, excessive weight and smoking were associated with poorer vitamin D status. Women with high vitamin D were less likely to have elevated PTH, hypertension or bone deficits than women with poor levels.