High-dose oral vitamin D(3) supplementation in the elderly

Department of Medicine, University of Auckland, Auckland, New Zealand.
Osteoporosis International (Impact Factor: 4.17). 12/2008; 20(8):1407-15. DOI: 10.1007/s00198-008-0814-9
Source: PubMed


Daily dosing with vitamin D often fails to achieve optimal outcomes, and it is uncertain what the target level of 25-hydroxyvitamin D should be. This study found that large loading doses of vitamin D(3) rapidly and safely normalize 25OHD levels, and that monthly dosing is similarly effective after 3-5 months. With baseline 25OHD > 50 nmol/L, vitamin D supplementation does not reduce PTH levels.
There is concern that vitamin D supplementation doses are frequently inadequate, and that compliance with daily medication is likely to be suboptimal.
This randomized double-blind trial compares responses to three high-dose vitamin D(3) regimens and estimates optimal 25-hydroxyvitamin D (25OHD) levels, from changes in parathyroid hormone (PTH), and procollagen type I amino-terminal propeptide (P1NP) in relation to baseline 25OHD. Sixty-three elderly participants were randomized to three regimens of vitamin D supplementation: a 500,000-IU loading dose; the loading dose plus 50,000 IU/month; or 50,000 IU/month.
The Loading and Loading + Monthly groups showed increases in 25OHD of 58 +/- 28 nmol/L from baseline to 1 month. Thereafter, levels gradually declined to plateaus of 69 +/- 5 nmol/L and 91 +/- 4 nmol/l, respectively. In the Monthly group, 25OHD reached a plateau of ~80 +/- 20 nmol/L at 3-5 months. There were no changes in serum calcium concentrations. PTH and P1NP were only suppressed by vitamin D treatment in those with baseline 25OHD levels <50 and <30 nmol/L, respectively.
Large loading doses of vitamin D(3) rapidly and safely normalize 25OHD levels in the frail elderly. Monthly dosing is similarly effective and safe, but takes 3-5 months for plateau 25OHD levels to be reached.

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    • "The largest increase was seen in subjects in the first tertile (10–34 nmol/L), followed by those in the second tertile (35–49 nmol/L) and then those in the third tertile (50–86 nmol/L); +30.6 ± 16.2, +25.5 ± 11.7 and +13.3 ± 13.9 nmol/L, respectively (p = 0.02). Bacon et al. (2009) demonstrated that deficient subjects (<50 nmol/L) receiving a loading dose of 500,000 IU had larger incremental change in their 25(OH)D concentrations at one month than non-deficient subjects (≥50 nmol/L), 71.0 [95% CI, 58.0–84.0] "
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    ABSTRACT: Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.
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    • "Plasma calcium and urinary calcium excretion both are recognized markers of vitamin D toxicity [5]. In the few clinical studies that have analyzed plasma calcium levels and/or urinary calcium excretion within a month after dosing, calcium levels were found to be unchanged or only slightly elevated within the reference range following a loading dose of 300,000 IU [9], 500,000 IU [10], 540,000 IU [11], or 600,000 IU [12,13]. "
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    ABSTRACT: Background Administration of intermittent high doses of vitamin D3 is increasingly used as a strategy for rapid normalization of low 25-hydroxyvitamin D (25(OH)D) blood concentrations in patients with vitamin D deficiency. Here, we describe the pharmacokinetics of an accidental single oral overdose of 2,000,000 IU of vitamin D3 in two elderly nursing home patients and discuss safety issues. Case presentation Two patients, a Caucasian 90-year old man and a 95-year old woman, were monitored from 1 h up to 3 months after intake for clinical as well as biochemical signs of vitamin D intoxication. Blood vitamin D3 concentrations showed a prompt increase with the highest peak area already hours after the dose, followed by a rapid decrease to undetectable levels after day 14. Peak blood 25(OH)D3 concentrations were observed 8 days after intake (527 and 422 nmol/L, respectively (ref: 50–200 nmol/L)). Remarkably, plasma calcium levels increased only slightly up to 2.68 and 2.73 mmol/L, respectively (ref: 2.20–2.65 mmol/L) between 1 and 14 days after intake, whereas phosphate and creatinine levels remained within the reference range. No adverse clinical symptoms were noted. Conclusion A single massive oral dose of 2,000,000 IU of vitamin D3 does not cause clinically apparent toxicity requiring hospitalization, with only slightly elevated plasma calcium levels in the first 2 weeks. Toxicity in the long term cannot be excluded as annual doses of 500,000 IU of vitamin D3 for several years have shown an increase in the risk of fractures. This means that plasma calcium levels may not be a sensitive measure of vitamin D toxicity in the long term in the case of a single high overdose. To prevent a similar error in the future, the use of multiple-dose bottles need to be replaced by smaller single-unit dose formulations.
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    • "Obese patients require higher doses of vitamin D (>3,000 IU daily) because of a larger volume of distribution and the accumulation of vitamin D in the adipose tissue. Since the adherence to daily regimens of vitamin D supplementation may be low, higher intermittent doses (25,000 IU monthly or 100,000 every 4 months) have been proposed, which should improve treatment adherence.54 However, recent studies reported that the use of vitamin D boluses exceeding 100,000–300,000 IU may be associated with an unexpected increase in bone resorption and in fracture rate.55 "
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    ABSTRACT: Obesity was commonly thought to be advantageous for maintaining healthy bones due to the higher bone mineral density observed in overweight individuals. However, several recent studies have challenged the widespread belief that obesity is protective against fracture and have suggested that obesity is a risk factor for certain fractures. The effect of obesity on fracture risk is site-dependent, the risk being increased for some fractures (humerus, ankle, upper arm) and decreased for others (hip, pelvis, wrist). Moreover, the relationship between obesity and fracture may also vary by sex, age, and ethnicity. Risk factors for fracture in obese individuals appear to be similar to those in nonobese populations, although patterns of falling are particularly important in the obese. Research is needed to determine if and how visceral fat and metabolic complications of obesity (type 2 diabetes mellitus, insulin resistance, chronic inflammation, etc) are causally associated with bone status and fragility fracture risk. Vitamin D deficiency and hypogonadism may also influence fracture risk in obese individuals. Fracture algorithms such as FRAX(®) might be expected to underestimate fracture probability. Studies specifically designed to evaluate the antifracture efficacy of different drugs in obese patients are not available; however, literature data may suggest that in obese patients higher doses of the bisphosphonates might be required in order to maintain efficacy against nonvertebral fractures. Therefore, the search for better methods for the identification of fragility fracture risk in the growing population of adult and elderly subjects with obesity might be considered a clinical priority which could improve the prevention of fracture in obese individuals.
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