Skip to main content

Main menu

  • Home
  • COVID-19
    • Articles & podcasts
    • Blog posts
    • Collection
    • News
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • Classified ads
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
    • Career Ad Discount
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2021
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN

User menu

Search

  • Advanced search
CMAJ
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN
CMAJ

Advanced Search

  • Home
  • COVID-19
    • Articles & podcasts
    • Blog posts
    • Collection
    • News
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • Classified ads
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
    • Career Ad Discount
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2021
  • Visit CMAJ on Facebook
  • Follow CMAJ on Twitter
  • Follow CMAJ on Pinterest
  • Follow CMAJ on Youtube
  • Follow CMAJ on Instagram
Letters

Misconception about the cause of vitamin D toxicity

Nipith Charoenngam, Arash Hossein-Nezhad, David A. Hanley and Michael F. Holick
CMAJ July 08, 2019 191 (27) E769; DOI: https://doi.org/10.1503/cmaj.72511
Nipith Charoenngam
Postdoctoral research fellow, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, Mass.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arash Hossein-Nezhad
Research assistant professor, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, Mass.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Hanley
Professor emeritus, Departments of Medicine, Community Health Sciences, and Oncology, Cumming School of Medicine, The University of Calgary, Calgary, Alta.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael F. Holick
Professor, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, Boston, Mass.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Responses
  • Metrics
  • PDF
Loading

In the case reported by Auguste and colleagues, 1 we believe that the patient experienced vitamin D intoxication because of an underlying pathologic condition that the authors failed to recognize.

The authors incorrectly concluded that a dose of 8000–12 000 IU daily can result in vitamin D intoxication. Vitamin D toxicity generally occurs when the level of 25-hydroxyvitamin D is greater than 375 nmol/L (150 ng/mL).2 This patient had a 25-hydroxyvitamin D level 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 Daily ingestion of 10 000 IU of vitamin D3 raising blood levels of 25-hydroxyvitamin D above 100 ng/mL was not associated with hypercalcemia, as reported in a review.2 Population studies have also reported that doses of up to 20 000 IU daily were not associated with toxicity.2

Levels of 1,25-dihydroxyvitamin D3 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 was the unregulated extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. The renal 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) is not sensitive to hydroxychloroquine, ketoconazole or glucocorticoids as suggested by the authors. Only the extrarenal CYP27B1 is sensitive to these medications.4

The authors made a modest effort with imaging studies to rule out granulomatous disorders. However, they did not appreciate the patient’s previous history of urothelial carcinoma, which has been reported to be associated with vitamin D toxicity associated with unregulated extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. This was the likely cause of the patient’s vitamin D intoxication and renal failure, not the dosage of vitamin D.5

Footnotes

  • Competing interests: Michael Holick is a consultant for Quest Diagnostics Inc. and Ontometrics Inc., and is on the Speaker’s Bureau for Abbott Inc. David Hanley has received research funding from the Pure North S’Energy Foundation. No other competing interests were declared.

References

  1. ↵
    1. Auguste BL,
    2. Avila-Casado C,
    3. Bargman JM
    . Use of vitamin D drops leading to kidney failure in a 54-year-old man. CMAJ 2019;191:E390.
    OpenUrlFREE Full Text
  2. ↵
    1. Holick MF
    . Vitamin D is not as toxic as was once thought: a historical and an up-to-date perspective. Mayo Clin Proc 2015;90:561–4.
    OpenUrlPubMed
  3. ↵
    1. Holick MF,
    2. Binkley NC,
    3. Bischoff-Ferrari HA,
    4. et al
    . Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96: 1911–30.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Adams JS,
    2. Hewison M
    . Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 2012;523:95–102.
    OpenUrlCrossRefPubMed
  5. ↵
    1. Asao K,
    2. McHugh JB,
    3. Miller DC,
    4. et al
    . Hypercalcemia in upper urinary tract urothelial carcinoma: a case report and literature review. Case Rep Endocrinol 2013;2013:470890.
PreviousNext
Back to top

In this issue

Canadian Medical Association Journal: 191 (27)
CMAJ
Vol. 191, Issue 27
8 Jul 2019
  • Table of Contents
  • Index by author

Article tools

Print
Download PDF
Article Alerts
To sign up for email alerts or to access your current email alerts, enter your email address below:
Email Article

Thank you for your interest in spreading the word on CMAJ.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Misconception about the cause of vitamin D toxicity
(Your Name) has sent you a message from CMAJ
(Your Name) thought you would like to see the CMAJ web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Misconception about the cause of vitamin D toxicity
Nipith Charoenngam, Arash Hossein-Nezhad, David A. Hanley, Michael F. Holick
CMAJ Jul 2019, 191 (27) E769; DOI: 10.1503/cmaj.72511

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
‍ Request Permissions
Share
Misconception about the cause of vitamin D toxicity
Nipith Charoenngam, Arash Hossein-Nezhad, David A. Hanley, Michael F. Holick
CMAJ Jul 2019, 191 (27) E769; DOI: 10.1503/cmaj.72511
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Footnotes
    • References
  • Responses
  • Metrics
  • PDF

Related Articles

  • Use of vitamin D drops leading to kidney failure in a 54-year-old man
  • The authors respond to “Misconception about the cause of vitamin D toxicity”
  • PubMed
  • Google Scholar

Cited By...

  • The authors respond to "Misconception about the cause of vitamin D toxicity"
  • Google Scholar

More in this TOC Section

  • Building research infrastructure across a health service
  • A safe return to sport and the right to play during COVID-19
  • Simple-language tool to guide patients in recovery after prolonged treatment in the intensive care unit
Show more Letters

Similar Articles

Content

  • Current issue
  • Past issues
  • Collections
  • Sections
  • Blog
  • Podcasts
  • Alerts
  • RSS
  • Early releases

Information for

  • Advertisers
  • Authors
  • Reviewers
  • CMA Members
  • Media
  • Reprint requests
  • Subscribers

About

  • General Information
  • Journal staff
  • Editorial Board
  • Governance Council
  • Journal Oversight
  • Careers
  • Contact
  • Copyright and Permissions

Copyright 2021, Joule Inc. or its licensors. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p)

All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association or its subsidiaries.

To receive any of the resources on this site in an accessible format, please contact us at cmajgroup@cmaj.ca.

Powered by HighWire