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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    • "On average, serum 25(OH)D was estimated to increase by approximately 12.0 nmol/L per 1,000 IU in the supplementation interval 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. Other studies reported that an additional 1,000 IU of vitamin D could increase serum 25(OH)D by approximately 20 to 25 nmol/L[24,32]. The substantial differences may arise from their focus on subjects with low baseline serum 25(OH)D levels, whereas our study had enrolled healthy volunteers. "
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    ABSTRACT: Unlike vitamin D recommendations by the Institute of Medicine, the Clinical Practice Guidelines by the Endocrine Society acknowledge body weight differentials and recommend obese subjects be given two to three times more vitamin D to satisfy their body's vitamin D requirement. However, the Endocrine Society also acknowledges that there are no good studies that clearly justify this. In this study we examined the combined effect of vitamin D supplementation and body weight on serum 25-hydroxyvitamin (25(OH)D) and serum calcium in healthy volunteers. We analyzed 22,214 recordings of vitamin D supplement use and serum 25(OH)D from 17,614 healthy adult volunteers participating in a preventive health program. This program encourages the use of vitamin D supplementation and monitors its use and serum 25(OH)D and serum calcium levels. Participants reported vitamin D supplementation ranging from 0 to 55,000 IU per day and had serum 25(OH)D levels ranging from 10.1 to 394 nmol/L. The dose response relationship between vitamin D supplementation and serum 25(OH)D followed an exponential curve. On average, serum 25(OH)D increased by 12.0 nmol/L per 1,000 IU in the supplementation interval of 0 to 1,000 IU per day and by 1.1 nmol/L per 1,000 IU in the supplementation interval of 15,000 to 20,000 IU per day. BMI, relative to absolute body weight, was found to be the better determinant of 25(OH)D. Relative to normal weight subjects, obese and overweight participants had serum 25(OH)D that were on average 19.8 nmol/L and 8.0 nmol/L lower, respectively (P<0.001). We did not observe any increase in the risk for hypercalcemia with increasing vitamin D supplementation. We recommend vitamin D supplementation be 2 to 3 times higher for obese subjects and 1.5 times higher for overweight subjects relative to normal weight subjects. This observational study provides body weight specific recommendations to achieve 25(OH)D targets.
    Full-text · Article · Nov 2014 · PLoS ONE
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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.
    Full-text · Article · Aug 2014 · BMC Endocrine Disorders
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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.
    Full-text · Article · Aug 2013 · Trials
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