Even enormous doses of vitamin D, applied topically, do not produce toxicity

I mentioning this study mainly for two reasons. First, there has been quite a bit of bad press over the last couple of years (more precisely, since 2020, coinciding with the COVID-19 pandemic) in regards to vitamin D, claiming that while the vitamin (actually a (seco)steroid) may be effective for a large number of conditions (including COVID-19 prevention and treatment) the risk of toxicity is too high, and thus vitamin D should not be recommended for widespread, unsupervised supplementation. The toxicity claims refer mainly to the risk of hypercalcemia and subsequent calcification of major blood vessels, as well as kidneys and other soft tissues – a hallmark of cardiovascular disease. However, the published case studies on such toxicity are very few and usually involve absurdly high doses, often as a suicide attempt. Be that as it may, I may still be worthwhile to some people (and doctors) to find ways to limit the risk of vitamin D toxicity as much as possible, as a way to reduce supplementation hesitancy.

The old study below demonstrated that when vitamin D is applied topically it not only prevents rickets, but can also reverse it. AFAIK, the latter effect has not been recognized yet by medicine, as it currently claims that once rickets has set in the bone deformities remain for life. Just as importantly, absolutely massive human-equivalent doses of viosterol (ergocalciferol, vitamin D2) applied topically every other day for more than a month, produced absolutely no toxicity or side effects even though plenty of calcium was also consumed in the form of milk. The reason I am mentioning calcium consumption is that it is officially listed as a risk factor for increasing/enabling the toxicity/hypercalcemia induced by vitamin D. The human-equivalent doses applied every other day were around 1,600 IU / kg of bodyweight. That means 120,000 IU – 160,000 IU every-other-day doses for most people. In comparison, typical oral doses prescribed for treating vitamin D deficiency are in the range of 50,000 IU once weekly. Thus, it seems that the topical route has some unique metabolic pathways that largely prevent the conversion of vitamin D precursors such as D2 and D3 (cholecalciferol) into the “active” form calcitriol (which is the metabolite responsible for the hypercalcemia from vitamin D supplementation). Given that several human studies have demonstrated that even 5,000 IU daily applied topically for 3 months can raise vitamin D levels from insufficiency to almost the middle of the normal range, it appears that topical vitamin D administration may be an effective and safer method for raising vitamin D levels even in people at risk of hypercalcemia or with already established soft-tissue calcification.

http://www.doi.org/10.1001/archpedi.1935.01970040080010

“…Vitamin D by inunction not only prevented rickets but produced well advanced healing. Therefore, the experiments cited strongly suggest that the skin is capable of absorbing vitamin D. Since the amount of vitamin D given by inunction is so much larger than that given orally, the question of hypervitaminosis must be considered. Kreitman and Moll [9] produced hypervitaminosis in rats by feeding excessive doses of viosterol (D2). None of the toxic symptoms indicative of hypervitaminosis, such as loss of weight, diarrhea and anorexia, were present in our series; in fact, all of the animals receiving the highest doses gained weight and showed no gastro-intestinal disturbances. Microscopic examination of the aorta and kidneys of these animals showed no calcification. The amount of viosterol used was therefore not excessive.”

“…It has been shown by a number of investigators that large doses of vitamin D are necessary before signs of toxicity become manifest. Even enormous doses cannot produce toxic symptoms in experimental animals kept on a normal diet. As much as 80,000 times the therapeutic dose failed to produce toxic [10] symptoms in rats kept on a diet of milk and bread. Further experiments to determine the minimum dose necessary to produce hypervitaminosis by inunction are under way. The danger of hypervitaminosis is exceedingly slight if preparations of viosterol of a strength of 250 D are used. According to these experiments, rats can tolerate at least 1,620 times the oral therapeutic dose without showing toxic symptoms. On the basis of direct proportional ratios by weight, a man weighing 70 Kg. (154 pounds) may absorb by inunction 700,000 rat units (daily). This is equivalent to 335 cc. of viosterol 250 D, or \}i gallons (66 liters) of viosterol 25 D, plus the internal consumption of a loaf of commercial vitamin D bread and a quart (946 cc.) of vitamin D milk daily. How much more can be tolerated is not yet certain. Experiments are in progress to determine this point. Preliminary reports indicate that enormous doses may be used by inunction without the production of symptoms of hypervitaminosis.”

Author: haidut