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- Page navigation anchor for RE: RE: Misconception for the cause of vitamin D toxicityRE: RE: Misconception for the cause of vitamin D toxicity
We thank Charoenngam and colleagues for their prompt feedback on the conclusions from our case study (1). In light of this, it is important provide the readers and the authors further clarity given their stated misperceptions.
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Firstly, the observational studies and opinion pieces referenced by the authors examined acute vitamin D toxicity. Patients received relatively high doses for short periods of time (usually < 6 months) (2-4). Our case study highlights a patient who took vitamin D that exceeded the recommended daily dose for at least 30 months (1,5). The authors of the cited editorial failed to highlight a key statement from the Institute of Medicine, “serum 25 hydroxyvitamin D levels above 125 nmol/L should raise concerns among clinicians about potential adverse effects” (5). Furthermore, the population studies cited by Charoenngam and colleagues did not include patients exposed to large (>10,000 IU) daily doses of vitamin D for 30 consecutive months. One randomized controlled trial highlighted in the cited reviews gave 100,000 IU boluses once every 4 months for 5 years (6). In a 5-year period these patients would have received the equivalent of 1.5 million IU of vitamin D. Our patient’s cumulative dose of vitamin D over a 4-month interval ranged from 960,000 - 1.44 million IU. In a 30-month period, this would equate to 10.8 million IU. Evidently, our patient received nearly 10 times the dose in half the duration of time that was given in comparison to...Competing Interests: None declared. - Page navigation anchor for RE: Hypercalcemia and a No Observed Adverse Effect Level (NOAEL) Intake of Vitamin DRE: Hypercalcemia and a No Observed Adverse Effect Level (NOAEL) Intake of Vitamin D
There are many reasons why the diagnosis of vitamin D toxicity of the recent case report by Auguste et al (1) was probably wrong, and was the result of a red herring. The patient had been taking 8,000-10,000 IU/day of vitamin D for 2.5 yrs while serum creatinine was not an issue. When the serum 25-hydroxyvitamin D ( 25(OH)D ) was first measured, and it was 241 nmol/L, consistent with long-term intake of the patient’s reported vitamin D intake but almost double the top of the reference range for people not taking a supplement. However, the serum 1,25-dihydroxyvitamin D ( 1,25(OH)2D ) was exceptionally high along with serum calcium and creatinine.
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The Institutes of Medicine specifies 10,000 IU/day as the “No Observed Adverse Effect Level” – an intake that is not advisable, but which is not considered objectively harmful either (2). Doses of vitamin D higher than 10,000 IU/day have been used in clinical trials that achieved higher 25(OH)D values and for longer duration, yet there was not one case of hypercalcemia, and certainly no kidney damage reported from among those hundreds of those study subjects (3–9). The case report described by Auguste et al is not consistent with any previous clinical experience with vitamin D intake. What is unusual is the high serum 1,25(OH)2D level, because even in the most extreme cases of vitamin D toxicity, with 25(OH)D exceeding 2,000 nmol/L, the total serum 1,25(OH)2D was only modestly increased (10). The primary cause o...Competing Interests: RV receives patent royalties from Ddrops vitamin D. - Page navigation anchor for RE: Misconception for the cause of vitamin D toxicityRE: Misconception for the cause of vitamin D toxicity
The patient reported by Auguste et al (1) suffered from vitamin D intoxication due to an underlying pathologic condition that the authors failed to recognize. They incorrectly concluded that a dose of 8000-12,000 IUs daily can result in vitamin D intoxication. Vitamin D toxicity generally occurs when the level of 25-hydroxyvitamin D is over 375 nmol/L (150 ng/mL).(2) This patient had a 25-hydroxyvitamin D of 241 nmol/L (96 ng/mL). This concentration is considered to be within the normal limit (30 – 100 ng/mL) according to the Endocrine Society’s Clinical Practice Guideline.(3) Ingestion of 10,000 IU/d of vitamin D3 raising blood levels of 25-hydroxyvitamin D above 100 ng/mL was not associated with hypercalcemia.(4) Population studies also reported doses of up to 20,000 IUs daily was not associated with toxicity.(2) 1,25-dihydroxyvitamin D3 levels are not increased in patients with vitamin D intoxication with hypercalcemia, because of the suppression of parathyroid hormone reducing renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.(2,3) The high levels of 1,25-dihydroxyvitamin D3, and the fact that the authors observed that treatment with hydroxychloroquine resulted in a rapid decline in circulating levels of 1,25-dihydroxyvitamin D3 should have alerted the authors that the likely explanation is due to the unregulated extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. The renal 25-hydroxy vitamin D-1 alpha-hydroxylase (CYP27B1) is...
Show MoreCompeting Interests: N.C. and A.S declare no competing interests. M. H. is a consultant for Quest Diagnostics Inc. and Ontometrics Inc, and on the speaker’s Bureau for Abbott Inc. D. H. has received research funding from Pure North S’Energy Foundation. - Page navigation anchor for RE: Use of vitamin D drops leading to kidney failure in a 54-year-old manRE: Use of vitamin D drops leading to kidney failure in a 54-year-old man
While this article is fascinating, it is difficult to accept the authors' conclusions while one significant piece of evidence is missing, that being, an analysis of the actual vitamin D drops.
A labeling error might be a simpler explanation for this case.
See: https://academic.oup.com/jcem/article/96/12/3603/2834898Competing Interests: None declared.