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.
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:
- “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.
- 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.
- Hypervitaminosis D first produces cell injury followed by calcium deposition. This process is reversible and reparable if administration is discontinued promptly.
- 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.