Critique of the consideration for establishing the tolerable upper intake level for vitamin D: Critical need for revision upwards

Department of Nutritional Sciences, University of Toronto, Mount Sinai Hospital, Toronto, M5G 1L5, Canada.
Journal of Nutrition (Impact Factor: 3.88). 04/2006; 136(4):1117-22.
Source: PubMed


The tolerable upper intake level (UL) for vitamin D is 50 mcg/d (2000 iu/d) in North America and in Europe. In the United Kingdom a guidance level exists for vitamin D, 25 mcg/d (1000 iu/d), defined as the dose "of vitamins and minerals that potentially susceptible individuals could take daily on a life-long basis, without medical supervision in reasonable safety." Exposure of skin to sunshine can safely provide an adult with vitamin D in an amount equivalent to an oral dose of 250 mcg/d. The incremental consumption of 1 mcg/d of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D ] by approximately 1 nmol/L (0.4 microg/L). Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L (200 microg/L). Older adults are advised to maintain serum 25(OH)D concentrations >75 nmol/L. The preceding numbers indicate that vitamin D3 intake at the UL raises 25(OH)D by approximately 50 nmol/L and that this may be more desirable than harmful. The past decade has produced separate North American, European, and U.K. reports that address UL or guidance-level values for vitamin D. Despite similar well-defined models for risk assessment, each report has failed to adapt its message to new evidence of no adverse effects at higher doses. Inappropriately low UL values, or guidance values, for vitamin D have hindered objective clinical research on vitamin D nutrition, they have hindered our understanding of its role in disease prevention, and restricted the amount of vitamin D in multivitamins and foods to doses too low to benefit public health.

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    • "Serum phosphate (>2.0 mmol/L), CaP product (>4.4 mmol2/L2) and magnesium (>1.0 mmol/L) were monitored throughout the study [48]. Vitamin D toxicity was addressed in the following ways: a) discontinuation of vitamin D3 supplement and b) notification to the Qualified Investigator (PS) and other members of the health care team in NARP/DNPC. "
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    ABSTRACT: Background Suboptimal vitamin D status is highly prevalent in Northern communities, particularly in those patients with chronic diseases such as diabetes and chronic renal disease. Emerging literature suggests that adherence to daily vitamin D supplementation may be an important factor influencing vitamin D status and overall bone health, but compliance with therapies for bone health is a major challenge. It is unknown what level of vitamin D supplementation will ameliorate or improve suboptimal vitamin D status in patients with diabetic nephropathy or contribute to improved bone health, particularly for those living in northern climates. Methods/Design The study purpose was to examine two different strategies of vitamin D3 supplementation; daily dosing of 2000 IU per day verses monthly dosing of 40,000 IU per month on markers of vitamin D status, bone health and to examine whether adherence, quality of life and patient satisfaction with the supplementation strategy differs between the two vitamin D strategies in adults diagnosed with diabetic nephropathy. Discussion The need for RCTs assessing higher doses of vitamin D3 supplementation at varying frequencies of administration and its impact on bone health in adults with diabetes and chronic kidney disease are needed. Trial registration NCT01476501.
    BMC Endocrine Disorders 08/2014; 14(1):66. DOI:10.1186/1472-6823-14-66 · 1.71 Impact Factor
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    • "Existing guidelines on vitamin D supplementation are conservative, and refer mainly to bone health [33], with 4,000 IU considered the upper limit of tolerability, despite the fact that sun exposure can provide an adult with up to 20,000 IU per day [34]. Older adults are now advised to sustain 25(OH) D concentrations of greater than 75 nmol/l for optimal bone health and, in order to achieve that, they need to consume approximately 4,000 IU/day of vitamin D [18,35]. "
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    ABSTRACT: There is increasing evidence linking vitamin D deficiency to both susceptibility to, and severity of, multiple sclerosis (MS). Patients with the clinically isolated syndrome represent the initial presentation of a demyelinating disorder, and those with asymptomatic lesions on magnetic resonance imaging (MRI) are at risk of progression to clinically definite MS. The aims of this study are to examine the immunologic effects of vitamin D in both healthy individuals and in patients with clinically isolated syndrome, and in the latter group the effects on disease progression assessed by MRI and clinical measures. This is a single-center double-blind randomized placebo-controlled clinical trial. The primary endpoint is the immunologic effects of two doses of vitamin D compared with placebo over 24 weeks in both healthy control participants and patients presenting with the clinically isolated syndrome. Healthy control participants (n = 39) and patients with clinically isolated syndrome (n = 45) will be randomized to one of three arms, namely 1) vitamin D 5,000 IU daily, 2) vitamin D 10,000 IU daily, or 3) placebo, and followed up for 24 weeks. In both patients and healthy control participants, the primary outcome will be immunologic measures of the frequency of CD4 T-cell subsets and cytokine responses in peripheral blood mononuclear cells, assessed at baseline, and after 16 and 24 weeks of treatment. Secondary endpoints, in the patients with clinically isolated syndrome, will be relapse activity, and the number of new T2 lesions and gadolinium-enhancing lesions assessed by MRI in the two vitamin D-treated groups compared with the placebo-treated group over the 24 weeks of the study.Trial registration: EU Clinical Trials Register: EudraCT: 2012-000635-68. identifier: NCT01728922.
    Trials 08/2013; 14(1):272. DOI:10.1186/1745-6215-14-272 · 1.73 Impact Factor
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    • "Levels of 25(OH)D ≥150 ng/dL are potentially harmful and are associated with elevated risk of hypercalcemia, vascular soft tissue calcification, and hyperphosphatemia [53]. Vitamin D intoxication can potentially be life-threatening but the majority of officially recorded cases could be related to prolonged intakes of >40,000 IU per day [54]. One small study looking at the short-term metabolic effect of high dose oral vitamin D3 replacement in the intensive care unit did not reveal any complications [55]. "
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    ABSTRACT: The incidence of vitamin D deficiency in critically ill patients has been reported to range from as low as 17% to as high as 79%. Data regarding the relationship between 25-hydroxyvitamin D levels and outcomes in the medical intensive care unit are sparse. The goal of the study was to evaluate the prevalence of 25-hydroxyvitamin D deficiency in the medical intensive care unit and its relationship with outcomes. This was a retrospective study in a medical intensive care unit (MICU) at an inner city community hospital. The study period was between October 2009 and February 2010. Of the 932 patients admitted during the study period, 25-hydroxyvitamin D vitamin D (25(OH)D) levels were available in 523 (53%); 86 of them were excluded from the study due to readmission to the intensive care unit. Deficiency was defined as 0 to 19.9 ng/dL 25(OH)D levels, insufficiency as 20 to 29.9 ng/dL, and normal levels as ≥30 ng/dL. Of the 437 patients studied, 25(OH)D deficiency was identified in 340 (77.8%), insufficiency in 74 (16.9%), and normal levels in 23 (5.3%) patients. Patients with 25(OH)D deficiency/insufficiency were younger (P = 0.015), were male (P = 0.001), and had kidney disease (P = 0.017) and lower total serum calcium levels (P = 0.003). Hospital mortality was higher in patients with 25(OH)D deficiency (P = 0.01). No differences in ventilator days or length of stay in the MICU were evident among the three groups. Analysis by multiple logistic regression demonstrated that acute physiology and chronic health evaluation (APACHE) IV score ((odds ratio (OR) 1.036; 95% confidence interval (CI) 1.024-1.048, P < 0.0001), ventilator requirement (OR 7.7; 95% CI 4.3-13.98, P < 0.0001), 25(OH) D levels(OR 0.942; 95% CI 0.942-0.904, P < 0.0005) and 25(OH) D deficiency (OR 8.7; 95% CI 1.03-72.8, P < 0.0469) showed statistical significance. There was no association between 25(OH)]D insufficiency and hospital mortality. The mean 25(OH)D level of survivors (27.9 ± 9.7 ng/dL) was higher than for non-survivors (9.7 ± 4.7 ng/dL; P < 0.0001). The study results demonstrate an association between 25(OH)D deficiency and hospital mortality in MICU patients. A randomized prospective study to evaluate the effect of vitamin D replacement therapy on mortality is warranted.
    Critical care (London, England) 12/2011; 15(6):R292. DOI:10.1186/cc10585 · 4.48 Impact Factor
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