COVID-19 Supplements: Be Careful When Buying Vitamin D Supplements As There Are Many Forms - Cholecalciferol (D3), Ergocalciferol(D2), Calcifediol, And Calcitriol

COVID-19 Supplements: If you thought that buying supplements was easy, think again. As a result of greed and profitability, many manufacturers especially those in Asia will find ways to put in the cheapest ingredient or form and not really focus on the true effectiveness of the product and whether it will truly help the end consumers.


 
The media has been abuzz recently about the proven benefits of Vitamin D in helping certain aspects of managing the COVID-19 disease but procuring the right product has proven to be a more difficult task and many are simply taking supplements that might not really help them due to lax labeling laws and regulatory measures.
 
When it comes to Vitamin D, most people should first understand that current labeling laws allow any four existing forms of compounds be labeled as Vitamin D Supplements.
 
It has been found that the specific compound that is meant for use in the context of vitamin D supplementation is often ambiguous. The term “supplementation” has been used in the context of cholecalciferol, ergocalciferol, calcidiol, and calcitriol. https://www.nature.com/articles/s41430-020-0697-1
 
The only naturally occurring form of Vitamin D that nurtures the body is cholecalciferol or Vitamin D3. It is produced by the human body in response to sunlight and is also available through dietary sources, such as fish but it is also an expensive product for use in supplements.
 
However a much cheaper version is ergocalciferol ior Vitaminb D2 and is primarily a synthetic and less stable product which is less potent per microgram dose than is cholecalciferol. This is the product that is frequently passed off as Vitamin D by most supplement companies.
 
The compound Calcidol is the major circulating metabolite of cholecalciferol, while Calcitriol is the hormone that upregulates the active transport of calcium from the gut, and which suppresses parathyroid hormone secretion.
 
Typically, nutrition policy papers and guidelines leave unstated the obvious fact that calcidiol and calcitriol are not nutrients, and that those metabolites are not pertinent to food fortification or dietary supplementation. There is however synthetic forms of calcidiol and calcitriol available cheaply and in some countries with clueless regulatory authorities and lax laws, they are sometimes passed off as Vitamin D.  China is one of the few countries that is able to supply these cheaper synthetic forms at extremely cheap rates and their customers includes supplement manufacturing companies in the US and most South-East Asian countries.
 
Numerous recent studies show that ergocalciferol is not stable with storage, and it is far more susceptible to breakdown with cooking and baking than is cholecalciferol.
 
Hence it must be concluded that cholecalciferol is the only form of vitamin D that should be considered in the context of the nutritional functions of fortification and supplementation.
 
Unfortunately in the United States, vitamin D supplementation is primarily available as ergocalciferol and vitamin D3 cholecalciferol but these two have historically been considered interchangeable and equipotent, even though the current body of literature strongly supports th e preference of Vitamin D3 cholecalciferol over ergocalciferol.
 
Initially when the manufacturing method for ergocalciferol was created, binding studies of the vitamin D receptor in rats showed equipotency between ergocalciferol and cholecalciferol. On the basis of this animal data, most resources cite the two being equipotent and interchangeable.
 
However given that both ergocalciferol and cholecalciferol undergo metabolic changes in the human body, which differ from other animals, it should make sense that a binding study in rats may not be sufficient to show equivalence. In fact, recent literature (Trang 1998, Armas 2004, Houghton 2006) convincingly demonstrates that cholecalciferol is 1.7 to 3 times more potent and has a longer-lasting effect than ergocalciferol in increasing serum 25-hydroxyvitamin D levels, the active form of vitamin D in humans. The difference in duration of effect and potency are well demonstrated in a study by Armas et al https://academic.oup.com/ajcn/article/84/4/694/4633079
 
Another reason that ergocalciferol which is less potent and has a shorter duration of effect and cheaper but is mostly used by supplement manufacturing companies and brands is due to dosage formulations. Unlike cholecalciferol, which is typically only available as a maximum dose of 5,000 units per capsule or tablet, ergocalciferol is available as a monster 50,000 unit dose. This larger dose may be seen as more convenient for patients or healthcare providers who want to provide supplementation on a weekly or monthly basis and also good for marketing strategies of unethical supplement brands.
 
While 25-hydroxyvitamin D levels are a better surrogate than a rat binding study, clinical outcomes are the most relevant. Low levels of 25-hydroxyvitamin D (less than 20 ng/mL; Bjelakovic 2014) are very common in North America and have been associated with a wide variety of diseases including osteoporosis, bone fractures, malignancy, cardiovascular disease, infections, and more. The majority of the data supports association, not causation, of low vitamin D levels. In other words, much of the data does not clearly support the idea that vitamin D supplementation in a patient with low vitamin D levels reduces the risk of these diseases.
 
A  Cochrane review (Bjelakovic 2014) analyzed the all-cause mortality benefit of vitamin D supplementation (both D2 and D3) by pooling 95,286 participants from 56 randomized clinical trials. In this meta-analysis, about 80% of participants received cholecalciferol (median dose 800 units/day) and about 20% received ergocalciferol (median 1000 units/day). The vast majority were women (77%), and most were older than 70 years of age.
 
The review calculated an all-cause mortality relative risk (RR) of 0.97 (95% CI 0.94-0.99, p=0.02), which represented a raw difference in mortality of 12.5% (control) vs. 12.7% (vitamin D). The authors calculated a number needed to treat (NNT) of 150 over five years; however, the NNT calculates to 500 over a weighted mean of 4.4 years using the raw difference in mortality rates. Importantly, the difference in mortality was only demonstrated for trials examining cholecalciferol. Although ergocalciferol did make up a minority of the meta-analysis, it was adequately powered to detect a 5% difference in relative risk reduction.
 
The findings were:
 
-Cholecalciferol (vitamin D3) is more potent and longer acting than ergocalciferol (vitamin D2) as measured by the active form of vitamin D in the blood (25-hydroxyvitamin D).
 
-Low vitamin D levels are common in North America; most data supports an association between low vitamin D levels and disease. Much less data supports a cause-and-effect relationship between vitamin D supplementation and prevention of specific diseases.
 
-Vitamin D supplementation with cholecalciferol (D3) appears to have a small but statistically significant benefit in improving all-cause mortality among elderly women. The mortality benefit in younger patients or male patients is not clear.
 
-Ergocalciferol (D2) is less studied than cholecalciferol and was not shown to confer a mortality benefit in a recent Cochrane meta-analysis despite adequate statistical power.
 
-For patients who meet criteria for vitamin D supplementation (which is an entire argument in itself), vitamin D3 (cholecalciferol) should be selected over vitamin D2 (ergocalciferol).
 
Hence when looking around for Vitamin D supplements, read the labels carefully and make sure that you get Vitamin D3 or cholecalciferol, also go for reputable companies and brands like Life Extension products or Now Foods.
 
For more on COVID-19 Supplements, keep on logging to Thailand Medical News.
 
References:

Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. PMID 15531486.
 
Trang HM, Cole DE, Rubin LA, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998 Oct;68(4):854-8. PMID 9771862
 
Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006 Oct;84(4):694-7. PMID 17023693.
 
Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014 Jan 10;1:CD007470. PMID 24414552.
 
Read also:
 
https://www.karger.com/Article/Abstract/430813
 
https://europepmc.org/article/med/28595683
 
https://academic.oup.com/jn/article-abstract/102/8/975/4778708?redirectedFrom=PDF