Dosing Units

ng/ml versus nmol/liter

10 ng/ml equals 25 nmol/l
20 ng/ml equals 50 nmol/l
30 ng/ml equals 75 nmol/l
40 ng/ml equals 100 nmol/l
50 ng/ml equals 125 nmol/l
60 ng/ml equals 150 nmol/l
100 ng/ml equals 250 nmol/l

Which Doses Are Safe and Effective?

Bischoff-Ferrari 2010 concluded: “In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU /d…” [2]. One of the dangers of excess vitamin D is excessively high blood calcium levels.

Hathcock 2007 recommended that the tolerable upper limit (TUL) for vitamin D be raised to 10,000 IU/day [3].

McCullough 2019: “In summary, long-term supplementation with vitamin D3 in doses ranging from 5000 to 50,000 IUs/day appears to be safe.” [4]

Ekwaru 2014: “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.” [1]

Holick 2015: “The Endocrine Practice Guideline Committee recommendations for patients at risk for vitamin D deficiency” set an Upper Limit (UL) for vitamin D daily intake at 2000 IU for infants, 4000 IU for ages 1 to 18, and 10,000 IU for all adults over 18 years. [5] “In pregnant women supplementation with 2,000 and 4,000 IU/d during pregnancy improve maternal/neonatal vitamin D status.” [5]

Hollis 2004: They recommended 4000 IU/day for mothers who are nursing infants, so as to provide adequate vitamin D for both mother and child.

Tau 2007: Children ages 1 to 14 were given 100k IU of vitamin D in two doses, three months apart. One month after the first dose, vitamin D levels were normal (mean 35 ng/ml). But three months after the second dose, levels fell to insufficient 22.4 ng/ml mean. This suggests that 100k of vitamin D every 3 months is insufficient.

Arpadi 2009: Children 6 to 16 received 100k IU of vitamin D every other month; 6.7% of children still had vitamin D levels below 20 ng/ml, as compared to 50% on placebo. So 100k IU every 2 months is not sufficient to guarantee that all children/teens will have sufficient vitamin D levels, nor that all will avoid vitamin D deficiency.

Malihi 2019: Adults 50 to 84 were given 100k IU of vitamin D monthly for 4 years, with no additional adverse events as compared to placebo.

Wicherts 2011: Adults given 100k IU vitamin D every three months still had insufficient levels of vitamin D.

Khan 2014: “25OHD levels >40 ng/ml were achieved in all 42 subjects who received 12 weeks of supplementation with 50,000 IU vitamin D3 weekly, with no adverse effects.” A dosage of 50k IU vitamin D per week is safe and effective in adults. Other studies with higher dosing confirm the safety of this lower dosing.

Conclusion: A dosing schedule of 50,000 IU of Vitamin D3 once per week is safe and effective in maintaining a healthy level of vitamin D in the blood.

Fastest Way To Treat Vitamin D deficiency?

What is the fastest way to raise very low blood vitamin D levels to within the normal range? This question is necessary as 48% of the U.S. population has vitamin D deficiency in winter [12].

Pepper 2009: “regimens that contained at least 600,000 IU of ergocalciferol appeared to be the most effective in achieving vitamin D sufficiency [13].” The highest dosing regimen was 50k IU 3x/week, which only provided vitamin D sufficiency in 82% of test subjects.

Middleton 2014: 50,000 IU of vitamin D per week corrected vitamin D deficiency in only 82% of subjects.

Wasse 2012: Patients mostly deficient or insufficient in vitamin D were given 200k IU vitamin D3 weekly for 3 weeks; 90% achieved vitamin D sufficiency.

Kaur 2015: Cases of vitamin D toxicity had cumulative doses ranging from 2.2 million to 6.3 million IU. A dose of 73k IU/day for 30 days would be needed to reach 2.2 million IU.

De Niet 2018: “A daily administration of the same cumulative dose is similarly effective but takes two weeks longer to reach the desirable level of 20 ng/mL.”

This conclusion of De Niet 2018 [17] that a bolus dose corrects vitamin D deficiency faster than a daily dose, with the same cumulative dose.

Etemadifar 2015: A dose of 50k IU/week was safe and effective in pregnant women.

Diamond 2013: A comparison of 2000 IU or 5000 IU per day for 3 months; all reached at least 20 ng/ml. Nearly three times as many in the 5000 IU group reached 30 ng/ml or more. But even at 5000 IU/day for 3 months, some persons did not reach vitamin D sufficiency.

Conclusion: 5,000 IU/day is not sufficient to correct vitamin D deficiency in all persons, and when it does correct vitamin D deficiency, it does so too slowly to use during the pandemic. Since 5,000 IU/day is 35,000 IU/week, it seems likely that 50,000 IU/week will also be too slow to meet our needs.

Matthews 2017: Patients were given 50,000 IU of vitamin D3 weekly, or daily for 5 days, or daily for 7 days; the more vitamin D, the lower the ICU mortality: 11.0%, 9.4%, and 6.4%. This studies tends to support a similar treatment regimen for Covid-19, especially in the ICU of 50,000 IU daily for 7 days (or more).

Melhem 2015: Patients with vitamin D deficiency were given 50k IU vitamin D3 daily for 10 days. “Conclusion: Overall, the 10-day oral D3 regimen rapidly and effectively normalized 25(OH)D levels. The shortened dosing interval over 10 consecutive days might result in higher compliance.” The average increase in vitamin D level per day was about 1.25 ng/ml with the 10-day dosing schedule.

Griend 2012: “patients prescribed 50,000–100,000 IU/week were significantly more likely to attain vitamin D sufficiency compared with those prescribed less than 50,000 IU/week (OR 2.61, 95% CI 1.37–4.99).”

Jetty 2016: “Vitamin D3 therapy (50,000-100,000 IU/week) was safe and effective when given for 12 months to reverse statin intolerance in patients with vitamin D deficiency. Serum vitamin D rarely exceeded 100 ng/mL, never reached toxic levels, and there were no significant change in serum calcium or eGFR.”

Jetty 2016: “In our most recent study of 146 vitamin D-deficient, statin-intolerant patients, the amount of vitamin D3 supplementation used was 50,000-100,000 units/week, and there was no adverse effect at this level of supplementation.”

Discussion and Conclusion

A deadly pandemic has killed over a million persons. Many are suffering from LongCovid, for month after month. Some risks must be taken to reduce the risk of death and great suffering. It is not very risky to propose a high dose of vitamin D at levels that studies have proven is generally safe. The side effects and risks are small. The benefits are vast. Medicine cannot be done with the usual great caution. We must take modest risks in order to tame the pandemic.

Even a dosing schedule of 50k IU/week is not sufficient to bring everyone out of vitamin D deficiency within a month or less. We cannot wait 2 to 3 months to raise people’s vitamin D levels to normal. Too many persons will die in the mean time. We need fast correction of deficiency, and a strong maintenance dosing.

Of all the dosing schedules so far, 50,000 IU of vitamin D3 daily for 10 days provides the fastest safe rise in blood levels of vitamin D. A week after the 10th day, 50k or 100k IU once a week is a good maintenance dose during the pandemic The lower dose of 50k IU/week is for persons of lower body weight, and the higher dose of 100k IU/week is for higher body weight (including excess body fat). . That dosing will also continue to correct vitamin D deficiency in the small percentage of persons not corrected by the 50k IU/day x 10 days loading dose. After the pandemic, 50k IU every week or every other week will be sufficient.

Ronald L. Conte Jr.
Covid.us.org
an author, not a doctor
un auteur, pas un médecin
um autor, não um médico
یک نویسنده ، نه یک دکتر

Endnotes:

1. Ekwaru, John Paul, et al. “The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers.” PLoS One 9.11 (2014): e111265.

2. Bischoff-Ferrari, Heike A., et al. “Benefit–risk assessment of vitamin D supplementation.” Osteoporosis International 21.7 (2010): 1121-1132.

3. Hathcock, John N., et al. “Risk assessment for vitamin D.” The American journal of clinical nutrition 85.1 (2007): 6-18.

4. McCullough, Patrick J., Douglas S. Lehrer, and Jeffrey Amend. “Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience.” The Journal of steroid biochemistry and molecular biology 189 (2019): 228-239.

5. Holick, Michael F., et al. “Vitamin D deficiency and possible role in multiple sclerosis.” Eur Neurol Rev 10.2 (2015): 131-138.

6. Hollis, Bruce W., and Carol L. Wagner. “Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant.” The American journal of clinical nutrition 80.6 (2004): 1752S-1758S.

7. Tau, Cristina, et al. “Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina.” The Journal of steroid biochemistry and molecular biology 103.3-5 (2007): 651-654.

8. Arpadi, Stephen M., et al. “Effect of bimonthly supplementation with oral cholecalciferol on serum 25-hydroxyvitamin D concentrations in HIV-infected children and adolescents.” Pediatrics 123.1 (2009): e121-e126.

9. Malihi, Zarintaj, et al. “Monthly high-dose vitamin D3 supplementation and self-reported adverse events in a 4-year randomized controlled trial.” Clinical Nutrition 38.4 (2019): 1581-1587.

10. Wicherts, I. S., et al. “Sunlight exposure or vitamin D supplementation for vitamin D-deficient non-western immigrants: a randomized clinical trial.” Osteoporosis International 22.3 (2011): 873-882.

11. Khan, Qamar J., et al. “Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer.” Breast cancer research and treatment 119.1 (2010): 111.

12. Kroll, Martin H., et al. “Temporal relationship between vitamin D status and parathyroid hormone in the United States.” PloS one 10.3 (2015): e0118108.

13. Pepper, Kara, et al. “Evaluation of vitamin D repletion regimens to correct vitamin D status in adults.” Endocrine Practice 15.2 (2009): 95-103.

14. Middleton, Laura, et al. “Vitamin D deficiency: A simple algorithm employing weekly administration of 50,000 IU of vitamin D.” American Journal of Otolaryngology 35.2 (2014): 85-88.

15. Wasse, Haimanot, et al. “Efficacy and safety of a short course of very-high-dose cholecalciferol in hemodialysis.” The American journal of clinical nutrition 95.2 (2012): 522-528.

16. Kaur, Parjeet, Sunil Kumar Mishra, and Ambrish Mithal. “Vitamin D toxicity resulting from overzealous correction of vitamin D deficiency.” Clinical endocrinology 83.3 (2015): 327-331.

17. De Niet, Sophie, et al. “A randomized study to compare a monthly to a daily administration of vitamin D3 supplementation.” Nutrients 10.6 (2018): 659.

18. Etemadifar, Masoud, and Mohsen Janghorbani. “Efficacy of high-dose vitamin D3 supplementation in vitamin D deficient pregnant women with multiple sclerosis: preliminary findings of a randomized-controlled trial.” Iranian journal of neurology 14.2 (2015): 67.

19. Melhem, Samar Jamal, Khaled Mohammad Aiedeh, and Kamal Abdelhamid Hadidi. “Effects of a 10-day course of a high dose calciferol versus a single mega dose of ergocalciferol in correcting vitamin D deficiency.” Annals of Saudi medicine 35.1 (2015): 13-18.

20. Diamond, T., Y. K. Wong, and T. Golombick. “Effect of oral cholecalciferol 2,000 versus 5,000 IU on serum vitamin D, PTH, bone and muscle strength in patients with vitamin D deficiency.” Osteoporosis International 24.3 (2013): 1101-1105.

21. Matthews, L. R., et al. “Aggressive Treatment of Vitamin D Deficiency in Hispanic an d African American Critically Injured Trauma Patients Reduces Health Care Disparities (Length of stay, Costs, and Mortality) in a Level I trauma center surgical intensive care unit.” Glob J Medical Clin Case Rep 4.2 (2017): 042-046.

22. Vande Griend, Joseph P., et al. “Prescription ergocalciferol dosing for vitamin D repletion: a retrospective evaluation.” Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 32.2 (2012): 135-141.

23. Jetty, Vybhav, et al. “Safety of 50,000-100,000 units of vitamin D3/week in vitamin D-Deficient, hypercholesterolemic patients with reversible statin intolerance.” North American journal of medical sciences 8.3 (2016): 156.