The Cochrane review on Vitamin D (D2 should be replaced with D3)


#1

I am a bit bothered by the fact that it isn’t using D3 instead. There is no reason to not have used cholecalciferol, and there is definitely enough evidence to support using D3 instead. Fortifying food with D2 did help to eliminate infantile rickets - but that’s about it.

Just in case you don’t know what the cochrane review is:
"Cochrane contributors - 37,000 from more than 130 countries - work together to produce credible, accessible health information that is free from commercial sponsorship and other conflicts of interest. Many of our contributors are world leaders in their fields - medicine, health policy, research methodology, or consumer advocacy - and our groups are situated in some of the world’s most respected academic and medical institutions.Our work is recognized as representing an international gold standard for high quality, trusted information. "

And onwards!

The link to the Cochrane Review:

There’s TONS of results/studies done all pretty much going along the same lines
(in summary, D2 does not have anywhere near as much benefit as D3 does and D3 is what should be regarded as a nutrient worthy of fortification or supplementation - I skimmed the history of how D2 even began as the go-to form of supplementation but will spare you those ‘big pharma’ details)

Just a few snippets (out of many) below and I’ve tried to highlight pertinent things in red for you to see.

*Dose of vitamin D3

A dose of vitamin D3 less than 800 IU a day significantly decreased mortality (RR 0.92 (95% CI 0.87 to 0.97); P = 0.005; I2 = 0%; 50,437 participants; 13 trials; Analysis 1.11). A dose of vitamin D3 equal to or greater than 800 IU a day had no statistically significant effect on mortality (RR 0.96 (95% CI 0.92 to 1.00); P = 0.07; I2 = 0%; 25,558 participants; 26 trials; Analysis 1.11). The difference between the estimate of the effect of vitamin D3 on mortality in the trials using a low dose of vitamin D3 and the trials using a high dose of vitamin D3 was not statistically significant by the test of interaction (Chi2 = 1.37; P = 0.24; Analysis 1.11).

*Intervention effect of vitamin D3 according to vitamin D status at entry

Vitamin D3 significantly decreased mortality in the trials including participants with vitamin D insufficiency (RR 0.95 (95% CI 0.91 to 0.99); P = 0.009; I2 = 0%; 55,883 participants; 20 trials; Analysis 1.13). Vitamin D3 had no statistically significant effect on mortality in the trials including participants with vitamin D adequacy (RR 0.92 (95% CI 0.80 to 1.07); P = 0.29; I2 = 0%; 4979 participants; 10 trials; Analysis 1.13). The difference between the estimate of the effect of vitamin D3 on mortality in the trials including participants with vitamin D insufficiency and the trials including participants with vitamin D adequacy was not statistically significant by the test of interaction (Chi2= 0.1; P = 0.75; Analysis 1.13)

*Dose of vitamin D2

A dose of vitamin D2 less than 800 IU a day, tested in one trial, had no statistically significant effect on mortality (RR 0.82 (95% CI 0.17 to 3.98); P = 0.81; 101 participants; Analysis 1.17). A dose of vitamin D2 equal to or greater than 800 IU a day had no statistically significant effect on mortality (RR 1.02 (95% CI 0.95 to 1.10); P = 0.51; I2 = 9%; 18,273 participants; 12 trials; Analysis 1.17). The difference between the estimate of effect of vitamin D2 on mortality in the trials using a high dose of vitamin D2 and the trial using low-dose vitamin D2 was not statistically significant by the test of interaction (Chi2 = 0.07; P = 0.79; Analysis 1.17).

*Intervention effect of vitamin D2 according to vitamin D status
(now this is a bit disturbing)

Vitamin D2 significantly increased mortality in the trials including participants with vitamin D insufficiency (RR 1.20 (95% CI 1.05 to 1.37); P = 0.008; I2 = 0%; 4413 participants; 6 trials; Analysis 1.19). Vitamin D2 had no statistically significant effect on mortality in the trials including participants with vitamin D adequacy (RR 0.97 (95% CI 0.86 to 1.10); P = 0.62; I2 = 0%; 10,496 participants; 5 trials; Analysis 1.19). The difference between the estimates of effect of vitamin D2 on mortality in the trials including participants with vitamin D insufficiency and the trials including participants with vitamin D adequacy was statistically significant by the test of interaction (Chi2 = 5.23; P = 0.02; Analysis 1.19).

— The review later notes slight potential for bias (but not for certain)

Part of the discussion:

Our review identified a possible difference between the two forms of supplemental vitamin D, that is, vitamin D3 and vitamin D2. Vitamin D3 seemed to significantly decrease mortality, while the effect of vitamin D2 may be neutral or even detrimental. The World Health Organization officially regards these two forms as equivalent, based on the results of quite old studies on rickets prevention (World Health Organization 1950). Biological differences between vitamins D3 and D2 are found in some species such as birds and monkeys (Hoy 1988; Marx 1989). Evidence on biological differences between the two vitamins in humans has been sparse and contradictory. A number of recently published clinical trials found evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than vitamin D2 (Armas 2004; Heaney 2011; Leventis 2009; Romagnoli 2008; Trang 1998). However, a randomised clinical trial found that vitamin D3 and vitamin D2 were comparable in maintaining serum 25-hydroxyvitamin D levels (Holick 2008b). A recently published systematic review and meta-analysis indicated that vitamin D3 is more efficacious than vitamin D2 in raising serum 25-hydroxyvitamin D concentrations (Tripkovic 2012). An emerging body of evidence suggests several plausible explanations for this observation. The plasma half-life of vitamin D3 is longer, and it has higher affinity to the vitamin D binding protein, hepatic vitamin D hydroxylase, and the vitamin D receptor (The fact that it’s absorbed better alone is a good enough reason to have used D3 instead of D2 in my opinion) (Holmberg 1986; Houghton 2006; Mistretta 2008). Vitamin D3 is the only naturally occurring form of vitamin D produced endogenously in our body, while vitamin D2 can be obtained only through the diet (Norman 2008). Vitamin D2 seems to upregulate several enzymes that degrade administered vitamin D2 and endogenous D3 (Heaney 2008). Our result could be of interest to health policy makers in different countries. The predominant supplemental form of vitamin D in the United States is vitamin D2 (Houghton 2006). In Europe, Japan and Canada, vitamin D supplements principally contain vitamin D3 (Holick 2008a), although in some European countries, like France and Great Britain, vitamin D2 is also available on the market.

Another article and it’s abstract here:
Full Article: http://ajcn.nutrition.org/content/84/4/694.full

“Supplemental vitamin D is available in 2 distinct forms: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Pharmacopoeias have officially regarded these 2 forms as equivalent and interchangeable, yet this presumption of equivalence is based on studies of rickets prevention in infants conducted 70 y ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status provides an objective, quantitative measure of the biological response to vitamin D administration. As a result, vitamin D3 has proven to be the more potent form of vitamin D in all primate species, including humans. Despite an emerging body of evidence suggesting several plausible explanations for the greater bioefficacy of vitamin D3, the form of vitamin D used in major preparations of prescriptions in North America is vitamin D2. The case that vitamin D2 should no longer be considered equivalent to vitamin D3 is based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification.”


#2

To add, the outcome they looked for was mortality and the magnitude of treatment impact they found was 150 elderly adults taking D3 supplementation for 5 years would prevent 1 death. There was no treatment impact for D2 supplementation.


#3

If I remember correctly, the reason given for using D2 was that RL couldn’t find an affordable vegan source of D3. I also would prefer D3, but then I’m not vegan. (Most D3 is made from lanolin, grease that is found on wool.)


#4

Instead of upholding highest standards of nutrition supplementation to substitute the human diet, a cheaper alternative with less efficacy is used - and not to mention - for a population of people that is majorly deficient in Vitamin D.

Vitamin D3 sourced from Lichen for this company.


#5

You mean modern humans in a first world country??


#6

Looks interesting, but their prices are many times the cost of other D3 sources (e.g., they charge $16 for 60 pills of 1000IU each, while a quick check on Amazon turns up a bottle with 360 pills of 5000IU each for the same price).

Also, I always have Trouble trusting Companies that don’t Understand the rules of Capitalization.


#7

They clearly didn’t look particularly hard. Baring in mind capsules and tablets at an individual consumer level are going to be more expensive than powders with a larger buy-in quantity, and Soylent 1.6 contains 400 I.U. of vitamin D per day, this could be achieved for a few cents.

For example:

http://www.iherb.com/MRM-Vegan-Vitamin-D3-5-000-IU-60-Vegan-Caps/50385

60 vegecaps with 5000 I.U. of vegan D3 for $11.65.
That’s 300000 I.U. for $11.65.
For 400 I.U. per day then, it would cost (400/300000)*11.65 = $0.0155333333 per day.

Baring in mind the benefits D3 is thought to have, I’m surprised they didn’t go with this and tried to say it was too expensive when it was likely costing less than $0.01 per day when bought in bulk.


#8

Regardless of what kind they use, you should be supplementing with Vitamin D daily anyway. So this really isn’t an issue.


#9

Yeah I agree, it is a little disappointing to see Rosa Labs only targeting 100% of the Daily Values when plenty of evidence suggests they are outdated and need modification (especially in cases such as vitamin D).


#10

You kinda beat me to the point I was going to make.

The fact that Soylent uses 400IU of D2 instead of D3 is irrelevant. 400IU is insufficient for people who don’t go outside enough.


#11

It’s also worth noting that at certain times of year, going outside even in the middle of the day doesn’t allow any vitamin d synthesis from sunlight. I’m unsure about where in the US this is the biggest issue, but in the UK, between October and the end of March, you won’t get any vitamin d from the sun.


#12

My doctor tells me to take 1000IU (25mcg I think?) of vitamin D each day, based on my blood tests. Most friends and family members who have had blood work done have been told to take 1000IU-5000IU (the higher amount for people with naturally darker skin), with 1000IU being the most common recommendation. If Soylent had 1000IU/day of D3, would that ever have any negative effects? A quick browse online indicates you need quite a lot of D3 before it can be harmful, but maybe there is some condition where lower amounts is better? Seems that would cover the dosage that most people need.


#13

1000 I.U. per day is not going to be harmful to the vast majority, if not everyone. Something like Soylent can not account for exceptions like that, so that is certainly not their reasoning for not including 1000 I.U. of D3.

Not including 1000 I.U. is because Soylent aims to give everything you need to live, not everything you need for optimal health (if you want that, check out axcho’s upcoming vitamin mix here: https://m.reddit.com/r/soylent/comments/4gx8bb/full_details_on_upcoming_micronutrient_mix_from/

Not including a source of vegan D3 as opposed to D2 is undoubtedly a matter of price.