Taking vitamin D3 with K2 in the morning

post by ChristianKl · 2018-11-30T19:00:59.563Z · score: 45 (19 votes) · LW · GW · 34 comments

Contents

  tl,dr:
  Introduction
  The importance of Vitamin D
  Which Vitamin D should be supplemented?
  How much Vitamin D3 should be taken?
  The effect of timing of Vitamin D supplementation
  Which K2?
  Conclusion
None
33 comments

Epistemological status: I studied bioinformatics but I'm no domain expert and lay out my current view on the issue based on the facts I found in the literature. This is not health advice.

tl,dr:

There’s strong evolutionary selection for producing enough Vitamin D. Vitamin D works together with Vitamin K2, and as a result high Vitamin D supplementation should come with Vitamin K2 supplementation.

Personally, I decided to consume every morning 10 000 IU of Vitamin D3 and 200 µg of K2 (all-trans MK7) and believe that it’s likely beneficial for many fellow rationalists who don’t spend a lot of time exposing a lot of skin to the sun to take the same supplements.

Introduction

Before reading further, I want you to look at the graphic below and assess to what extend you believe the two maps are the same or differ:

p2001c3c8g175001

It's interesting how similar those two maps happen to be. The map is from the chapter Human Skin Pigmentation as an Adaptation to UV Radiation written by Nina G. Jablonski and George Chaplin. A is a map for UVB intensity over the world. On the other hand, B is about the skin color of the residents of the area by their sensitivity for the wavelength of 305mn.

There's a lot of human migration. Given that human likely only arrived in Australia in 65000 ago, evolution didn't have much time to evolve skin color to be able to allow different Australian natives to have a skin color that matches the the UVB radiation. This illustrates that there's huge selection pressure on skin color and this is likely selection pressure that's driven by the need to produce Vitamin D3 via UVB radiation.

Take a look at the two maps again and ponder how well they are aligned.

The importance of Vitamin D

Given that Vitamin D3 seems important enough to get the skin color changed to match UVB radiation it's reasonable to assume reducing the amount of UVB radiation humans get produces Vitamin D3 deficiency that has negative health consequences. Gwern's meta-analysis on Vitamin D suggests that the existing academic publications suggest that this costs 0.33 years of life. Later in this article I will make the case why I believe that the literature is likely biased to underrate the effect for systematic reasons.

Which Vitamin D should be supplemented?

Humans produce Vitamin D3. While Vitamin D2 that gets produced by mushrooms can also be used by humans, it makes sense to supplement Vitamin D3 as it’s the form of Vitamin D around which evolution optimized us given that it’s what’s available in the natural environment. Besides the evolutionary argument The case against ergocalciferol (vitamin D2) as a vitamin supplement lists a few other reasons as well.

How much Vitamin D3 should be taken?

According to the Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline:

For clinical care, it appears that all current methodologies are adequate if one targets a 25(OH)D value higher than current cut points; for example, a value of 40 ng/ml (100 nmol/L) is without toxicity and virtually ensures that the individual's “true” value is greater than 30 ng/ml (75 nmol/L). A clinical approach of targeting a higher 25(OH)D value seems prudent in that improving vitamin D status should reduce multiple adverse consequences of vitamin D deficiency at extremely low cost with minimal toxicity risk.

In a German study they found median 25(OH)D levels of 19.8 ng/ml. While this isn't a meta-review it illustrates that plenty of people are strongly under the recommendation of the Endocrine Society. I'm German and I used to take 5000 IU vitamin D3 per day and got tested by my doctor and got a value of 33ng/ml. That's a bit over the recommended minimum of 30 ng/ml but not enough to get over the inherent error of the essay. As a result I upped my daily D3 intake to 10000 IU which is maintenance tolerable upper limits recommended by the Endocrine Society Guideline.

How high is 10000 IU? According the Endocrine Society Guideline, when an adult wearing a bathing suit is exposed to one minimal erythemal dose of UV radiation (a slight pinkness to the skin 24 h after exposure), the amount of vitamin D produced is equivalent to ingesting between 10,000 and 25,000 IU. At the same time 10000 IU is much higher than the recommended daily intake of 600 IU by IOM (US), 600 IU by EFSA (EU) and 800 IU (20 µg Vitamin D) by the DGE in Germany.

Dimitrios T. Papadimitriou argues in The Big Vitamin D Mistake that 10 000 IU should be consumed to reach the 40 ng/ml 25(OH)D blood level and that due to statistical errors it’s assumed in the official guidelines that less Vitamin D3 supplementation is required to reach that level.

Above I spoke about my belief, that the existing studies underrate the benefits of Vitamin D3 supplementation. I believe that for two reasons. The first is about the timing of Vitamin D3 supplementation and the second is about K2.

The effect of timing of Vitamin D supplementation

The studies we have generally make the assumption that timing doesn't matter and blood 25(OH)D levels are the only interesting variable. Given that we don’t have an routine clinical essay to measure vitamin D3 or vitamin D2 serum concentration we can’t focus on their serum levels.

Another name for 25(OH)D level is Calcifediol (or 25-hydroxyvitamin D / calcidiol) while the substance we supplement or that our skin produces in response to UVB light exposure is cholecalciferol (or Vitamin D3). Calcifediol gets produced in our liver from cholecalciferol. Additionally our kidney turns calcifediol into calcitriol (1,25-dihydroxyvitamin D). Both calcifediol and calcitriol are used in many different pathways. Calcifediol has a biological half-life of 2–3 weeks while calcitriol has a half-life of 4–15 h.

The mainstream belief that timing is irrelevant is supported by the fact that calcitriol levels doesn’t get directly affected affected by Calcifediol levels. At the same time Seth Roberts gathered examples of multiple people whose sleep improved when they took Vitamin D3 in the morning and whose sleep got worse when they took it in the evening. Multiple folks in Quantified Self replicated that effect for themselves but unfortunately there aren’t studies that investigated it deeper.

Given that there’s no harm in taking it in the morning I personally take my Vitamin D3 in the morning even when there’s no high quality evidence for it.

The role of K2

The second important variable is K2. Atli Arnarson makes the case in Is Vitamin D Harmful Without Vitamin K? that Vitamin D toxicity at high doses is usually about K2 deficiency because both are needed in the same pathways and more K2 is needed when there's more Vitamin D. Vitamin D toxicity leads to hypercalcemia where there's too much Calcium in the blood. Calcifediol moves some calcium from the bone to the blood and K2 is needed to put the calcium in the bones. Hypercalcemia is bad because it lead to blood vessel calcification. Observational studies link low Vitamin K2 levels to blood vessel calcification with K2 being more important than K1.

Why might we have a K2 deficiency compared to the ancestral environment? K2 is found in animal liver and fermented foods which means food in which bacteria grew. In the ancestral environment it was hard to prevent bacteria from growing in the food that was consumed and thus the related consumption was higher. Seth Roberts makes here the point that we value the taste of umami that primarily comes from eating microbe-rich foot in the ancestral environment. Today, most westerners also don't eat animal liver while ancestral humans consumed it.

Which K2?

There are multiple forms of K2 (menaquinone) that can theoretically be used to supplement. The most commonly discussed are MK-4 and MK-7. According to Sato et al that MK-4 has from supplements has no direct bioavailability coming to the conclusion “MK-7 is a better supplier for MK-4 in vivo than MK-4 itself.” Schurgers et all writes however that he has unpublished data that suggest MK-4 bioavailability. It would be good to have more research to get more clear about MK-4 bioavailability. There’s also MK-5, MK-8 and MK-9 however it’s not widely used as a supplement and there’s more research needed.

Given the current research it seems sensible to me to go with pure MK-7 supplements.

MK-7 exists in a trans- and a cis-form where only the trans-form is used by humans. Given that some supplements contain a mix of both forms it’s desirable to buy a MK-7 supplement that specifies that it’s all-trans (or 99% all-trans).

Conclusion

On that basis I have decided for myself to consume for now 10000 IU Vitamin D3 per day and 200 µg Vitamin K2 (all-trans MK-7)*. I take it every morning. I don’t have strong reasons for 200 µg but it’s the default size of supplements and there’s no known toxicity of it. While going out into the sun would also be a way to acquire Vitamin D3, it causes wrinkles in the face that while I don’t try to minimize sun exposure I won’t maximize it when I can get my Vitamin D3 through a cheap supplement.

* I brought me current K2 supplement before doing this research and it doesn’t specify trans vs. cis but I will buy all-trans MK7 the next time.

34 comments

Comments sorted by top scores.

comment by UnplannedCauliflower · 2018-12-02T16:29:55.732Z · score: 3 (2 votes) · LW(p) · GW(p)

You have omitted the fact that vitamin K2 is produced not just by bacteria fermenting our food before we eat it, but also by bacteria in our intestines. Have you researched this source of K2? Do you have any reason to believe intestinal flora does not produce enough K2?

At university I was taught that vitamin K deficiency is extremely rare due to its production by inestinal bacteria and that is why normally only newborns (who simply don't yet have gut bacteria) receive K2 supplementation.

comment by ChristianKl · 2018-12-05T12:40:38.698Z · score: 4 (3 votes) · LW(p) · GW(p)

I don't think that my argument about bacteria being a source of Vit K2 is alone sufficient for arguing that we are commonly insufficient in it. The argument however makes it plausible that we get less of it then in paleo times.

My main reason is that it seems that people who take a lot of Vitamin D3 but no Vitamin K2 show symptoms that correspond to Vitamin K2 deficiency and as a result it's prudent to suppelement K2 when supplementing Vitamin D3 seriously.

A lot of K2 research also happened quite recently and our existing system of thinking about RDA unfortunately treats substances as being independent from each other which makes things harder.

comment by rayalez · 2018-11-30T20:43:22.644Z · score: 3 (2 votes) · LW(p) · GW(p)

Thank you for a great post!

Taking a D3 supplement, even in small amounts, seems to cause a horrible insomnia for me. I have problems with sleep even without it, but on D3 it gets a lot worse, I sleep like 3 hours per night. I'm like 80-90% sure it's D3, when I take it it gets worse, a few days after I stop it gets better.

Do you have any ideas on what could cause this and how could I fix it? I already take magnesium and choline, and I take D3 in the morning, but that don't seem to help much. Melatonin doesn't do anything, it gets me to sleep in the evening, but then I wake up anyway.

comment by Elo · 2018-11-30T22:14:10.658Z · score: 3 (2 votes) · LW(p) · GW(p)

Have you ever taken zinc. Are you sure you need vit D? Are you taking d with or without food?

comment by rayalez · 2018-11-30T23:55:04.304Z · score: 1 (1 votes) · LW(p) · GW(p)

I used to take calcium-magnesium-zink supplement, not sure if it was durig the time I took D3. Could lack of zink be an issue, should I try it?

I don't know if I need it, never took the blood test, I tried it based on all the artiles about how good it is and how most people are deficient in it. Also I live in a cold climate and definitely don't go out enough, so I don't get a lot of sunlight.

I took D3 with light breakfast, in the morning.

comment by Elo · 2018-12-01T00:15:13.424Z · score: 3 (2 votes) · LW(p) · GW(p)

I don't know. (maybe Christiankl can comment here)

Zinc has been a factor for me.

Maybe get a blood test?

comment by rayalez · 2018-12-01T01:42:00.509Z · score: 1 (1 votes) · LW(p) · GW(p)

Thanks, Ill try zink again, and one day get around to doung blood test.

comment by ChristianKl · 2018-11-30T21:27:29.558Z · score: 3 (2 votes) · LW(p) · GW(p)

How fast do you get the insomnia after taking a supplement? What do you mean with small amounts?

Do you take K2?

comment by rayalez · 2018-11-30T23:58:53.853Z · score: 2 (2 votes) · LW(p) · GW(p)

I think insomnia starts gradually and progressively gets worse after a few days, maybe a week, my hypothesis was that D3 was building up, apparently it has a very long half life. I took about 2000-3000 IU, it's not that much, right?

I didn't try K2 supplement, but I've just googled and turns out spinach and kale have a lot of K, and I eat a lot of those.

comment by ChristianKl · 2018-12-01T10:13:11.148Z · score: 3 (2 votes) · LW(p) · GW(p)

Whether something is a lot depends on your baseline. Mainstream researchers would say that's a lot as it's 250% of the RDA of D3. From my perspective it however isn't a lot.

Spinach and kale contain K1 and not K2. You could still be K2 deficient if you get a lot of K2.

Vitamin A is also plausible but given that too much Vitamin A is bad (on average Vitamin A supplements increase the death rate) I wouldn't supplement it in a targeted way without blood tests.

comment by Sasha Mayer (sasha-mayer) · 2019-08-16T04:42:18.617Z · score: 1 (1 votes) · LW(p) · GW(p)

K2 you cannot get from spinach or kale. Only from fermented natto, cabage but mostly from animal fat in brie and gouda cheese, organ meats, eggs, butter, milk and meat but ONLY from grass fed animals (K1 transforms to K2 when animals eat grass). Brie and Gouda could be from milk that is not from grass fed animals since in these 2 types of cheese bacteria produces the K2.

comment by squirrel · 2020-03-07T20:29:15.361Z · score: 2 (2 votes) · LW(p) · GW(p)

I learned the hard way to ONLY take D3 in the mornings. Otherwise if I wait it causes sleeplessness.

comment by Un Ariete (un-ariete) · 2019-08-20T21:33:00.108Z · score: 1 (1 votes) · LW(p) · GW(p)

Non lichen based D3 supplements have been found to contain toxic levels of D3 per pill. 200000ius per pill instead of 2000iu. It's in the scientific literature.

Insomnia is due to D3 inhibiting prostaglandin synthesis and the production of PGD2, which induces sleep.

comment by ChristianKl · 2019-08-20T22:17:13.405Z · score: 3 (2 votes) · LW(p) · GW(p)

Which paper in the scientific literature are you referring to?

comment by adam demirel · 2018-12-04T03:31:06.310Z · score: 1 (1 votes) · LW(p) · GW(p)

What time did you take it? D3 is a strong cellular modulator of our clock genes https://www.vitamindcouncil.org/new-research-finds-activated-vitamin-d-regulates-genes-involved-in-the-circadian-rhythm/

comment by ChristianKl · 2018-12-05T12:49:57.443Z · score: 2 (1 votes) · LW(p) · GW(p)

After reading a bit about Vitamin D3, I also thought that you can justify taking Vitamin D3 in the morning this way.

I however had to rewrite my post because it doesn't seem to be as easy. The Wikipedia article used to suggest that cholecalciferol gets directly transformed into calcitriol but it seems it has to be converted to calcifediol first. This process takes time and as a result it's harder to make the argument about Vitamin D3 that you take (cholecalciferol) directly effecting the circadian rhythm.

comment by adam demirel · 2018-12-20T04:20:42.500Z · score: 1 (1 votes) · LW(p) · GW(p)

Do you have any data on how long the conversion takes?

comment by ChristianKl · 2018-12-20T13:36:42.155Z · score: 3 (2 votes) · LW(p) · GW(p)

Unfortunately, I don't.

I have opened a biology.SE question about the question of how long it takes till Vitamin D3 is biologically active a while ago.

comment by Sylvain Gravejat (sylvain-gravejat) · 2020-01-19T21:11:25.014Z · score: 1 (1 votes) · LW(p) · GW(p)

Thank you for the great article. Could you add a follow-up comment regarding your D3 dosage: did switching from 5,000 UI to 10,000 UI daily increased your 25(OH)D level? It must have, but by how much, and how fast? Did you lower your dosage once your goal was reached, or did you keep the 10,000 UI daily going?

comment by ChristianKl · 2020-01-18T21:10:47.188Z · score: 2 (1 votes) · LW(p) · GW(p)

I haven't measured my 25(OH)D level since.

comment by VN · 2019-12-28T14:17:14.549Z · score: 1 (1 votes) · LW(p) · GW(p)

I take EVERY Day BEFORE BEDTIME: D3 10,000 UI , K2 MK7 200mcg, Zinc 30mg, Copper 0.3mg & Magnesium Glycinate 300mg, and I SLEEP LIKE A BABY. My Polar heart rate monitor shows the same and that my heart rate is steady at ~50 pulses throughout the night. BTW- I have psoriasis and my psoriasis with combination above is much, much better. Replies/ comments are welcome ...

comment by VN · 2019-12-28T14:12:19.459Z · score: 1 (1 votes) · LW(p) · GW(p)

I take EVERY Day BEFORE BEDTIME: D3 10,000 UI , K2 MK7 200mcg, Zinc 30mg, Copper 0.3mg & Magnesium Glycinate 300mg, and I SLEEP LIKE A BABY. My Polar heart rate monitor shows the same and that my heart rate is steady at ~50 pulses throughout the night. BTW- I have psoriasis and my psoriasis with combination above is much, much better. Replies/ comments are welcome ...

comment by ChristianKl · 2019-12-28T14:16:37.275Z · score: 2 (1 votes) · LW(p) · GW(p)

The heart rate being steady instead of following a Hammock curve would be evidence that you are not sleeping well.

comment by VN · 2019-12-28T18:02:10.556Z · score: 1 (1 votes) · LW(p) · GW(p)

Well, when the chart is approximated, the average is ~50 pulses. And my wife can testimony to this, that I sleep like a baby, if that is more convincing ... :)

comment by Ben Done (ben-done) · 2019-12-10T00:54:16.379Z · score: 1 (1 votes) · LW(p) · GW(p)

I asked about studies regarding K2 and D3 and it auto wipes?

comment by Ben Done (ben-done) · 2019-12-09T13:30:18.031Z · score: 1 (1 votes) · LW(p) · GW(p)

I'm trying to find studies that show the effect of "low" 25-0H vitamin D levels, what happens when supplementing with vitamin K2.

The opposite has been studies well enough, most search returns at vitamin D supplements with K2 or simply that both are needed.

Of the things I recommend, supplementing Vitamin D is definately a potent neurosteroid and having it dumped into your body in that way instead of via skin reacting to a light spectrum...

Similar to calcium and fluoride, I say avoid Vitamin D supplements. Plenty of people are in the oldest age spans and have had low levels of vitamin D for longer years then we have been alive...

comment by Hafeez Ahmad Halwoor (hafeez-ahmad-halwoor) · 2019-07-26T03:15:13.233Z · score: 1 (1 votes) · LW(p) · GW(p)

I am taking Amlodipine and telmasartan for blood pressure,Are they any side effects of taking Vit D3&K2???

comment by ChristianKl · 2019-07-26T07:00:17.013Z · score: 2 (1 votes) · LW(p) · GW(p)

I don't know. I would ask a doctor or pharmacist. Pharmacists are generally trained to be able to tell you about drug side effects. Feel free to report back what they told you, so that other people can share in the knowledge.

comment by James S. Kantor (james-s-kantor) · 2019-07-22T16:36:23.965Z · score: 1 (1 votes) · LW(p) · GW(p)

Thank you for writing this informative article.

comment by Dibo1978 · 2019-06-26T01:16:12.831Z · score: 1 (1 votes) · LW(p) · GW(p)

Dear Christian KL Can I take vitamin C at the same time as l take D3 & K2 (MK7) in the morning? What is daily intake of Vit C for adults? Kind regards Peter

comment by ChristianKl · 2019-06-26T10:26:35.539Z · score: 2 (1 votes) · LW(p) · GW(p)

I don't believe that there's a good reason to supplement Vitamin C for adults with a normal diet. There wasn't enough evolutionary pressure a few million years ago when our ancestors lost the Vitamin C producing genes to combat that capability loss.

At the same time I also don't believe that any problems are going to arise from Vitamin C supplementation either alone or in combination with D3 & K2.

comment by bandwagonsmasher · 2018-12-03T00:34:03.600Z · score: 1 (1 votes) · LW(p) · GW(p)

I've been taking Sports Research K2 + D3 with coconut oil -- 100 mcg K2 and 123 mcg D3 -- nowhere on the bottle does it specify if the K2 is trans. Any ideas on where to get this info? Website is useless: https://sportsresearch.com/products/vitamin-k2-d3?variant=35117890696

comment by ChristianKl · 2018-12-03T09:56:02.754Z · score: 2 (1 votes) · LW(p) · GW(p)

I think it's quite recent that the information that the cis form isn't useful for human propagated through the net.

From what I saw when searching throught he products at the moment most of them make statements about being 95/99% trans. If company doesn't write this on the bottle for new pills that would a negative signal for me. You could also just send an email to their support and ask.

95% also isn't a huge problem as the cis stuff seems to do nothing, you just have to be aware that you are getting effectively 5% less of what you are looking for. If you would only get 30% trans, that would be a problem as you might not get enough.