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Information on the latest vitamin D news and research.

Find out more information on deficiency, supplementation, sun exposure, and how vitamin D relates to your health.

Looking back: A vitamin D toxicity review from 1937

A few days ago I ran across a unique 1937 paper. It was commissioned, in part, by the American Medical Association and appeared in the prestigious Annals of Internal Medicine. The paper was about the toxicity of mega doses of vitamin D.

E. STECK, H. DEUTSCH, C. I. REED, H. C. STRUCK; FURTHER STUDIES ON INTOXICATION WITH VITAMIN D*†. Annals of Internal Medicine. 1937 Jan;10(7):951-964.

It was a study of mega doses in both humans and dogs.  The authors made the point that the toxicity of vitamin D is similar in dogs and humans; that is, similar per pound doses are required to elicit toxicity. I am unaware if that is still commonly believed to be true today.

They gave 64 dogs doses of vitamin D that ranged from 15,000 IU/kg/day to 500,000 IU/kg/day for up to 3 months. That is, the equivalent doses in a 50 kg human (~120 lbs) would be 750,000 to 25 million IUs/day. They found that the equivalent human dose of 750,000 IU/day caused slight clinical toxicity in one of the eleven dogs given that dose but no deaths. One of these 11 dogs also developed dangerous high blood calcium.

On the other extreme, all the dogs given the human equivalent of 25 million IUs per day were dead within a week. The objective symptoms of toxicity were similar in dogs as in humans, weakness and lassitude, loss of appetite, excessive thirst, excessive drinking and urination, and psychic disturbances. One of the characteristic features of fatal clinical toxicity is coma. This condition is usually, though not always, preceded by partial paralysis, slow and shallow respiration, fine, thready and rapid pulse, excessive salivation, and often by psychic changes of such a nature that a previously tame, friendly dog became vicious.

In a second set of experiments, they made dogs toxic with doses that caused calcification of the kidneys but discovered that the kidneys healed after cessation of the vitamin D. That is, even when kidney calcification occurred, simply stopping the vitamin D reversed it.

They also found no correlation between hypercalcemia and clinical toxicity. Some of the vitamin D toxic dogs had normal serum calcium and some of the ones who did not develop clinical toxicity had high serum calcium. The authors questioned if high blood calcium was the mechanism of toxicity. Their experiment showed that injury to the kidney cells came before calcium deposition in the kidney, not the other way around.

Then they reported on an uncontrolled clinical case series of 773 humans given doses of 200,000 IU/day and higher for varying periods of time, some up to 5 years. On these high doses, about 20% of patients became clinically toxic but none died. When clinical signs of toxicity occurred, the vitamin D was simply stopped for several weeks and then lower mega doses where restarted. The highest short term nontoxic dose was when one of the authors took 3 million units a day for 14 days without any problems.

The authors state that only two human deaths from vitamin D toxicity had been reported in the literature up to 1937. One may have been idiosyncratic but the other, a physician, aged 74, weight 290 pounds, undertook self-medication with a concentrated solution of vitamin D2, apparently intent on taking around 200,000 IU/day. However, he calculated the dose wrong and gave himself 2,300,000 units daily for 18 days and died with hypercalcemia.

The authors concluded:

  1. “Observations on 64 dogs and 773 human subjects receiving massive doses of vitamin D have been made and data recorded as to dose per unit of body weight, and on the nature of the process of intoxication.
  2. Both human subjects and dogs generally survive the administration of 20,000 units per kilogram per day (1,000,000 IU/day for a 50 kg human) for indefinite periods without intoxication.
  3. Hypervitaminosis D first produces cell injury followed by calcium deposition. This process is reversible and reparable if administration is discontinued promptly.
  4. Intoxication for short periods does not result in any permanent injury that can be recognized by the methods employed in this investigation.”

As a dog owner, I hope no modern day researchers will try to reproduce these results. Also, keep in mind that this study was conducted over 80 years ago and accurate measurement of the content of vitamin D supplements was not available. Also, we now know that high blood calcium, when moderate to severe, is associated with heart arrhythmias and premature death.

We thought a long time before publishing this blog. I wanted to publish this blog because I think it’s an interesting piece of research, but I warn that this is not our endorsement of mega doses.

There have been more up to date systematic reviews on vitamin D toxicity that look at more recent research. What do those reviews show? It seems likely that the current No Observed Adverse Effects Level of 10,000 IU/day, set by the 2011 Food and Nutrition Board is conservative.

Again, the Vitamin D Council does not recommend these mega doses, or anywhere close to them.

  About: John Cannell, MD

Dr. John Cannell is founder of the Vitamin D Council. He has written many peer-reviewed papers on vitamin D and speaks frequently across the United States on the subject. Dr. Cannell holds an M.D. and has served the medical field as a general practitioner, emergency physician, and psychiatrist.

9 Responses to Looking back: A vitamin D toxicity review from 1937

  1. Rita and Misty says:

    I enjoyed this article very much.

    A word on canines and vitamin D:

    Mistygirl, my Australian Shepherd, is a rescue dog. We estimate that she is between 13-15 years old. She is approximately 60 lbs. And, she has been supplementing with D3 for going on 3 years now. She takes a conservative 4,000 iu D3 WEEKLY.

    Misty is an old dog. But, she has no health problems associated with her breed. She has no hip dysplasia…no dental or gum problems…no eye problems. She is extremely healthy.

    Misty used to run 6 miles every day. But just this past year she can no longer keep this pace. Now, I am sad to say, she can only walk 3 miles a day. But, she truly looks forward to these walks. She has no idea she is old. She has the heart of a much younger dog. I would venture to say few Australian Shepherds make it to age 15 with no health problems whatsoever. I think Mistygirl is truly lucky.

    I often consider upping her dosage of D3, but I am afraid. I would take more health risks on myself than on Mistygirl.

    (If people were more like dogs the world would be a happier place).

    Be well,
    Rita

  2. IAW says:

    To: Vitamin D Council
    Just wanted to say thanks so much to you for deciding to publish this blog. I really do understand that you do not want people to get “carried away” by how much Vitamin D they take and yet you really do need to give information to dispel the “myth” that it is dangerous!.

  3. Magic says:

    I worked in the investment business. I was always disappointed when a small company with great ideas in health care wouldn’t have enough money to continue. Enough was often a couple of hundred million dollars which they ran out of. I felt it was the FDA’s fault in requiring a company to spend in the billions to get a hot product approved. Now as I have reason to see lots of end of life situations I am firmly convinced that IAW is right. Vitamin D3 is suffering from such a myth. We were fired by one doctor who said that 1000 IUs a day was toxic and wouldn’t listen to or read about anything different.. My wife’s next doctor told her the same thing…(A pretty good chance that both doctors have the same sales rep.)

    Our health care situation will keep the US in the middle of the pack and our costs will continue to rise until somehow things are changed. I do not give it much hope.

    Magic

  4. Rita and Misty says:

    I choose to keep my 25(OH)D level at the higher end of optimal, range defined as between 50 ng/mg –80 ng/ml….

    I am always grateful for the Vitamin D Council, and the courage of Dr. John Cannell to post articles such as this one, upon which we are, all of US, commenting.

    I understand that the Vitamin D Council is in no way recommending mega doses, or anywhere close to them.

    Here is the problem as I see it (and I am not a researcher nor am I a physician–just an outspoken woman–though I have tried to tone my outspokenness down to an appropriate level):

    There is no consensus within the vitamin D community as to optimal reference range for the 25(OH)D level. If there is little agreement amongst those who have studied vitamin D, how does anyone propose we go about educating others in mainstream medicine…those who have historically been taught in med school that vitamin D can be toxic?

    Yes, studies like this 1937 study do help…but it isn’t enough….

    I have said it before…I will say it again (BTW, I am turning blue): consensus within the vitamin D community is the first step….

    (NB: When I talk to those in my daily virtual existence, they are quick to point out lack of consensus.)

  5. I have to assume that the D used in this study was D3, not D2 because 1937 was before development of the patent drug D2. Y/N?

    Pressure to ignore Steck et al’s work obviously comes from the Medical Industry because it is an old study and old scientific studies like these lose relevancy with age for some mysterious reason. In addition, the MI has nothing to gain and a lot to lose, financially, if a significant proportion of the populace normalizes their 25(OH)-D3 levels and they are well aware of that.

  6. Rogerio Luz Coelho says:

    I am thrilled by this study …

    Body of evidence has been poring on ideal 25-OH … but people are still very scared to publish their findings, and publishing anything in Vitamin D is not a easy task. I have an epidemiologic study with professional football (soccer players) that show that even in pro footballers in Brazil we have somewhat of >20% deficiency (and I assume 30 ng/dL as enough) and am having trouble to publish it (even in english journals).

    So is the difficulty right now for Vitamin D research.

    Cheers :)

  7. Rita and Misty says:

    So Misty went to the vet’s office yesterday morning. The vet said that for around 15 years of age Misty is doing fantastic. Much more like a 10 year old doggie than a 15 year old. The vet thought it perfectly fine for Misty to take vitamin D3 supplements…and said that my giving Misty 4,000 iu D3 per week was quite conservative…and that this dose in all likelihood could be raised by weight…. Misty weighs 50 lbs… (the appropriate dosage wasn’t discussed, unfortunately…so I am left to guess whether canines can be dosed similarly to humans…) BTW–the vet herself is a big (huge) advocate of D for humans…but she refused to comment on her daily dosage…. (sigh)… bittersweet… :) :( 😉

  8. eelisabethpuur@gmail.com says:

    hello Rita and Misty

    I gave my Golden 50 000 IU per month and I will do the same again, when I get a new one.

    Elisabeth :-)

  9. Rita and Misty says:

    Thanks Elisabeth ! I’ve already started to give Misty 2,000 iu every other day. I am going to start her on 2,000 iu daily….

    She is an awesome Australian Shepherd, and I would like her to make 20–only in good health, of course.

    :)