Even enormous doses of vitamin D, applied topically, do not produce toxicity
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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.”
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@haidut The full study appears paywalled. I'd like to verify if they used D2 or D3 topically or (better) tested both? I've only ever used D3 orally but would love to know topically is safer.
thanks for all you do! -
@zorba990 Let me know if the following link works: The study Haidut posted
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@NotShanalotte Yes thanks! I see the term Viosterol used which is not clear to me on D2 v D3. However based purely on the age of the study I would guess D2.
"As an inunction we made a compound of : yellow wax, 5 parts ; spermaceti, 5 parts ; viosterol in oil 250 D, 26 parts ; 5 olive oil, 10 parts, and lecithin, 0.75 parts, in a cold cream base. This mixture contained 1,800 rat units 6 of vitamin D per gram. Another compound using an irradiated mineral oil instead of viosterol was employed to determined the mechanism of the action of vitamin D by inunction. This preparation of an irradiated mineral oil is known to be a source of secondary radiation in that it is capable of fogging a photographic plate."
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@zorba990 said in Even enormous doses of vitamin D, applied topically, do not produce toxicity:
Viosterol
Ergosterol activated by ultraviolet irradiation; vitamin D2.
A fat-soluble vitamin that prevents rickets.
https://duckduckgo.com/?q=Viosterol&ia=web -
@DavidPS thanks
So until we have more information only D2 would be safe in such high dose topical formulations as its conversion to D3 can have a limitation -
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@zorba990 You're welcome! If you ever need to get a full study, sci-hub lets you put in a link and if there's a legal copy it'll fetch it for you.
Right now the country code is st, (sci-hub.st) but that has changed in the past and a quick search will usually find the working version.
@DavidPS thanks for posting that info!
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https://www.sciencedaily.com/releases/2014/01/140127164559.htm
Has anyone seen this, which shows D2 supplementation in athletes resulted in poor outcomes, including lowering serum d3?
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@NotShanalotte
Interesting. Though muscle damage is the goal to most progressive weightlifting routines as this signals adaptation and strength/size increases. The key is not training until sufficiently recovered -- so if this allows milder training to inflict more damage it might be a net positive. -
@zorba990 I was kinda thinking that. A long time ago when I did weightlifting for power (as opposed to physique or reps) I did very few reps at 70-90% capacity. Was far more efficient than the routines the weights coach had me doing. So maybe use the short half-life of D2 to coincide with a lifting session and get away with closer to the 70% and see how that ends up. I dunno, just throwing an idea out there.
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It found a significant and prolonged increase in creatine phosphokinase after exercise. A significantly greater serum myoglobin during exercise. No difference in DOMS. This could potentially increase the stressfulness of exercise to the body, but potentially one could exercise more lightly and less frequency and get the same benefits. Along the lines of what you're saying.
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@basebolt For sure, that's the chart I was looking at.
