Vitamin K2
TheDevastator
Posts: 1,626 Member
Does anyone supplement with vitamin K2? If so, how much? I'm currently taking about 200 mcg a day with my vitamins D3 and E mixed complex.
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Replies
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There is no concrete science I have found on the subject but your dosage is typical. I shot for at least 100 mcg of MK-7 per 10,000 units of D3. For others in the house I keep an MK-7/D3 mix. A 5000 unit capsule of D3 also contains 180 mcg K2 MK7. Personally I do K1 and K2 MK-4 and MK7 but MK-7 is the one I deem the must do to lower coronary artery calcium scores. My score was 9.8 three years ago so I want to keep it that way. I have been heavy into fish oil since 1996 which helps with arthritis pain in my n=1.
If one does like Coumadin (Warfarin) one needs to be aware of K1. K2 is thought to be positive for diabetes as well as directing calcium from building up in the arteries but going to the bones and teeth if doing high dosage of D3 because a high dosage of D3 is undefined by science at this time and the anecdotal values are all over the board.
I just read read Tiago Henriques book on Vitamin D3 and K2 so there are reviews on Amazon if interested. Hopefully there will be settled science but today we are stuck with anecdotal data.1 -
The book looks good, I bought it on kindle. I've read "vitamin k2 and the calcium paradox" which is a good read and Jeff Bowles book on high dose vitamin d which really was testing the limits of high dose d3 therapy. I just take K2 MK-7 since it can be used by the body for a longer period of time than MK-4. Supplementing K1 would be smart since most of the foods I eat don't have enough.
I'm doing high dose vitamin E treatment (http://www.doctoryourself.com/heartdisease.html) for chest pains related to amlodipine I was taking for high blood pressure. I try to take enough D3 and K2 to balance that.
People on blood thinners need to be wary of K1 and K2 deficiencies. They can increase their CAC score in no time at all. There are newer drugs that don't effect vitamin K status. https://innovixlabs.com/blogs/insights/vitamin-k2-and-coagulation1 -
I know have read Jeff Bowles' book because he talked about taking 100,000 units daily but I will find it or remember loaning it. My memory is recovering after 5 months trial of CBD oil. Just now my Amazon password popped into my vision after trying to remember it for weeks.
Multiple Sclerosis and lots of Vitamin D by Ana Claudia Domene is another book where she talks about being on the Coimbra Protocol for 8 years. It was meaningful to me but read some reveiws before putting up $$$.
I really must get my books organize that I have been ordering and reading for many years on many subjects.
I have a brother-in-law with very serious side effects from Warfarin use long term.0 -
I'm not going to try that high of dose, I just take 5,000 iu d3 a day and 100-200 mcg k2. I think eating well is more important than too many supplements.
Most of my books are on kindle so it's easy to locate, hard to find the right spot of, the book.1 -
TheDevastator wrote: »I'm not going to try that high of dose, I just take 5,000 iu d3 a day and 100-200 mcg k2. I think eating well is more important than too many supplements.
Most of my books are on kindle so it's easy to locate, hard to find the right spot of, the book.
The nice thing testing for Vitamin D levels are normally part of an annual lab work protocol. Personally I consider anything in the 75-150 ng level range to be protective against most premature death causes. Not sure about COVID-19.
In 2013 my Vitamin D level was 22 ng so the doctor had a talk with me. In 2014 it was 28 ng and he let me know if I was serious about showing up at my 110th birthday party that I had to get serious and to shoot for 90 ng.
In 2015 I had a new doctor and she freaked when I hit 120 ng so I started reading research and found there were no proven known toxic levels but just anecdotal remarks. Next year I brought this up with her and she said that was true and that annual conversation ceased.
In another MFP thread I learned about Vitamin D helped move calcium out of the gut and into blood stream where it could build up in the arteries instead of the bones and teeth only leading to heart attacks and strokes. There was a doctor marketing to come to his practice to lower your Coronary Artery Calcium Score which I did not know was even possible.
Here on MFP was when I started to learn about Vitamin K2 for the first time. In earning my OD degree we had pharmacology like MD's have but it was just about Rx meds.
After I learned here that K2 was the steering wheel that puts calcium into the bones and teeth instead of the arteries I learned K2 could move calcium deposits from arteries back into the bones and teeth.
I had moved to using 50,000 unit D3 capsules once a week to save money and effort. When I read daily was better than weekly and I had a boat load of the 50K capsules I started to taking one daily and have not found any reason to change that but I am looking for them all of the time. For the past 3 years my levels have been at 155+ ng since the lab does not test beyond that level. This is just my n=1 experience and I do not promote it for others. I keep Vit K2 with 5K D3 capsules for others in the household.
With the event of COVID-19 I continue to read to see its antiviral roll if any. In the UK a few years ago one larger study showed D3 reduced the odds of getting the common flu better than getting the annual flu shot which was telling in my view.
Your dosage level seems typical and very safe for the general population. If you find some key K2/D3 research please post a link.2 -
For me the Vitamin K2 factors in health still are not fully clear but it does seem if balanced the gut microbiome can make K2 for us. That is the reason I go ahead and supplement.
https://intechopen.com/books/vitamin-k2-vital-for-health-and-wellbeing/menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet
https://timesofindia.indiatimes.com/life-style/health-fitness/weight-loss/vitamin-d-impacts-insulin-metabolism-and-obesity/articleshow/77597662.cms
We know there is a relationship between K2 & D3. We know vit
D levels and the gut microbiome can be a factor in resolving obesity. In time maybe it will all become clear.
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So you take 50,000 iu d3 a day and 500 mcg mk-7 k2? I took 10,000 iu d3 and 100 mcg mk-7 k2 today. I might go up to 15,000 iu a day.
Don't forget vitamin E, it's the antagonist of Vitamin K and helps stop abnormal clotting. I'm taking 1600 iu of alpha tocopherol and one pill of mixed tocotrienols but I was getting chest pains, so this is a high dose.
Vitamin A or retinol is also important for hormones like testosterone but I get it from foods not supplements since it's synthetic. I eat liver and eggs and get over 100% rda almost every day.
Have you looked into borax for arthritis? I take 1/4 teaspoon in a quart of water (recommended men's dose) about 3 times a week for many benefits since I don't have arthritis much yet.
The Borax Conspiracy0 -
TheDevastator wrote: »So you take 50,000 iu d3 a day and 500 mcg mk-7 k2? I took 10,000 iu d3 and 100 mcg mk-7 k2 today. I might go up to 15,000 iu a day.
Don't forget vitamin E, it's the antagonist of Vitamin K and helps stop abnormal clotting. I'm taking 1600 iu of alpha tocopherol and one pill of mixed tocotrienols but I was getting chest pains, so this is a high dose.
Vitamin A or retinol is also important for hormones like testosterone but I get it from foods not supplements since it's synthetic. I eat liver and eggs and get over 100% rda almost every day.
Have you looked into borax for arthritis? I take 1/4 teaspoon in a quart of water (recommended men's dose) about 3 times a week for many benefits since I don't have arthritis much yet.
The Borax Conspiracy
What are your Vit D level at last labs? I know there's no real science regarding Vit D yet I sense around 100 nl may be s sweet spot. Hopefully in the next 3-5 years COVID-19 data will solidify as to Vit D levels that were helpful managing the.symptoms if any.1 -
I think I'll go back to 5,000 iu. I'm not really concerned with a blood test but might get one in a few months. I'd be happy anywhere from 60-100 ng/ml.1
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TheDevastator wrote: »I think I'll go back to 5,000 iu. I'm not really concerned with a blood test but might get one in a few months. I'd be happy anywhere from 60-100 ng/ml.
That sounds like a sweet spot. Some day science hopefully will shed more light on this subject. Magnesium is needed as well.
https://jaoa.org/article.aspx?articleid=2673882
https://jaoa.org/article.aspx?articleid=2673882#:~:text=Magnesium assists in the activation,in the liver and kidneys.1 -
K2 is something I never heard of before info here on MFP as it relates to Vit D safety at higher levels.
https://healthline.com/nutrition/how-much-vitamin-d-is-too-much#section4
"Taking vitamin A, vitamin K and magnesium with vitamin D may therefore improve bone function and reduce the chances of other tissues becoming calcified."
Below is more on K2 value. Keep in mind there is no proven science on this Vit D and related supplements. Actually the link is to article after article.
https://healthline.com/nutrition/vitamin-d-and-vitamin-k
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@TheDevastator the article below shows how unknown Vitamin K2 can be to MD's and how hard science is often missing from their input just because Vit D is not a well studied yet.
If you wish just skip to the readers comments for random thoughts on K2.
https://devaboone.com/post/vitamin-d-part-2-shannon-s-story0 -
Vitamin D has been studied a lot but sometimes the commenters have the most facts versus doctors. I'm just taking 5,000 iu because that is about the highest or slightly more than they recommend in all the books I've read. I don't see how a crazy vitamin D number can be helpful compared to 60-80 ng/ml for mostly healthy people. It's just one nutrient out of many.
I do supplement magnesium and most of the other minerals and eat good salt. "The Magnesium Miracle" is a good book but I think they overdo how much you actually need a day. I think I'm supposed to take 900 mg minimum a day. I'd be in the bathroom all the time with that much.1 -
Probably only if you are supplementing with the cheap magnesium oxide. I take 800 mg a day Mag bisglyconate and have no issues.I'd be in the bathroom all the time with that much.1 -
It's not magnesium oxide, it's magnesium glycinate and lysinate. Mineral drops also can make me go too since they are mostly magnesium.canadjineh wrote: »
Probably only if you are supplementing with the cheap magnesium oxide. I take 800 mg a day Mag bisglyconate and have no issues.I'd be in the bathroom all the time with that much.0 -
TheDevastator wrote: »Vitamin D has been studied a lot but sometimes the commenters have the most facts versus doctors. I'm just taking 5,000 iu because that is about the highest or slightly more than they recommend in all the books I've read. I don't see how a crazy vitamin D number can be helpful compared to 60-80 ng/ml for mostly healthy people. It's just one nutrient out of many.
I do supplement magnesium and most of the other minerals and eat good salt. "The Magnesium Miracle" is a good book but I think they overdo how much you actually need a day. I think I'm supposed to take 900 mg minimum a day. I'd be in the bathroom all the time with that much.
60-80 ng/ml Vit D levels should be good especially in this current pandemic era. Some think a good amount of magnium is required for Vit D3 work well. I was happy with lab results today in light of my D3 intake. I try to take 1200 mg of additional of magnesium daily to help with leg cramps.0 -
@TheDevastator below is a link with a chain of related D3 links below the article. While these published articles are not hard research but I found them helpful over safety concerns at high blood levels at different dosages.
https://pubmed.ncbi.nlm.nih.gov/28012936/
" A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D." This may have been a small diary that was shipped some mislabeled Vit D to add to the milk.
" There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU was safely tolerated. "
The lab report that received yesterday is calling 30-96 ng/ml as the range for D levels.2 -
This morning I Googled magnesium vit d3 paradox and read for a few hours. Many links talked about K2. Some are thinking Vit D3 toxicity is just a side effect of Vit K2 deficiency not of D3 itself. K2 is thought to decrease risk of a cytokine response and if that is the case may be helpful in the case of COVID-19 side effects that is cytokine storm related. Many health problems and premature death cases seem to relate back to a magnesium deficiency since the level in the blood tells nothing of the level in the muscles and bone.0
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I think all the fat soluble vitamins are very important and should be balanced as much as possible. I’ve heard d3 is good to take to fight covid19 so I wouldn’t be surprised if the rest of the fat soluble vitamins might help. I’ve just heard that magnesium oil on the soles of the feet are a good transdermal way of getting your magnesium. I tell my family to use mineral drops also since they have 250 mg magnesium per 40 drops.2
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TheDevastator wrote: »So you take 50,000 iu d3 a day and 500 mcg mk-7 k2? I took 10,000 iu d3 and 100 mcg mk-7 k2 today. I might go up to 15,000 iu a day.
Don't forget vitamin E, it's the antagonist of Vitamin K and helps stop abnormal clotting. I'm taking 1600 iu of alpha tocopherol and one pill of mixed tocotrienols but I was getting chest pains, so this is a high dose.
Vitamin A or retinol is also important for hormones like testosterone but I get it from foods not supplements since it's synthetic. I eat liver and eggs and get over 100% rda almost every day.
Have you looked into borax for arthritis? I take 1/4 teaspoon in a quart of water (recommended men's dose) about 3 times a week for many benefits since I don't have arthritis much yet.
The Borax Conspiracy
@TheDevastator your "The Borax Conspiracy" link contains specific info I have been wondering about for years. Actually I may have read some of that even here in pro Boron post but just did not know enough at the time to know what I did not know but wanted to know.
If someone reads your link and just do not get any value out of it I suggest they save the link at least. I like to be in Google when reading something like this so I can highlight words and right click to get the meaning.
I now have some 3mg boron capsules the way. Thanks for sharing.
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https://allergyresearchgroup.com/ARGFocus_201008_VitaminsDAK_web.pdf
@TheDevastator the above PDF article supports your post about balance the fat soluble vitamins. It mentions how vit D and A can be helpful when it comes to cytok ine storm management which can lead to death in cases of COVID-19.
It is 10 years old so when reading it can be helpful to interpolate the article with newer research findings.0 -
Here's some newer research for you vis a vis Vit D and covid 19:The First Randomized Controlled Trial on Vitamin D and COVID-19
The trial was conducted at the Reina Sofía University Hospital in Córdoba, Spain. The trial included 76 patients with COVID-19 pneumonia. Although this is no longer the standard of care, all patients were treated with hydroxychloroquine and azithromycin and, when needed, a broad-spectrum antibiotic. Admission to the ICU was determined by a multidisciplinary committee consisting of intensive care specialists, pulmonologists, internal medicine specialists, and members of the ethics committee.
The patients were randomly allocated to receive or not receive vitamin D in a 2:1 ratio. This resulted in 50 patients in the vitamin D group and 26 patients in the control group.
The Vitamin D Treatment Protocol
The vitamin D was provided as oral calcifediol, also known as calcidiol, 25(OH)D, and 25-hydroxyvitamin D. This is a metabolite of vitamin D that our livers make. It is is the principle form of vitamin D that circulates in the blood, and we use it as a measure of vitamin D status.
Traces of 25(OH)D occur in food, and it is five times as potent as vitamin D. As described on page 255 of the 1997 DRI Report, 25(OH)D is given an international unit (IU) value that equates it to vitamin D. Whereas one microgram (mcg) of vitamin D is 40 IU, 1 mcg of 25(OH)D is 200 IU.
The treatment in this RCT was soft capsules of 532 mcg 25(OH)D on day 1 of admission to the hospital, followed by 266 mcg on days 3 and 7, and then 266 mcg once a week until discharge, ICU admission, or death.
This is equivalent to 106,400 IU vitamin D on day 1, 53,200 IU on days 3 and 7, and 53,200 IU weekly thereafter. If this were given as daily doses, it would be the equivalent of 30,400 per day for the first week, followed by a maintenance dose of 7,600 IU per day.
The vitamin D status of the patients was not measured. However, the average vitamin D status in this region of Spain during the time of year in which the study was conducted is 16 ng/mL. A single dose of 100,000 IU vitamin D tends to raise a 25(OH)D of 10 ng/mL into the 20-30 ng/mL range. My suspicion is that the bolus dosing in the first week brought the patients' vitamin D status into the 30-40 ng/mL range by the end of the week, and that most of the healing took place in the circa 40 ng/mL range.
The Results: Near Abolition of ICU Risk
The results are absolutely stunning. 50% of the control group (13 people) required admission to the ICU. Only 2% of those in the vitamin D group (one person) required admission to the ICU.
Expressed as relative risk, vitamin D reduced the risk of ICU admission 25-fold. Put another way, it eliminated 96% of the risk of ICU admission. Expressed as an odds ratio, which is a less intuitive concept but is often used in statistics because it gives an estimate of the effect of the treatment that would be constant across scenarios with different levels of risk, vitamin D reduced the odds of ICU admission by 98%. Either way, vitamin D practically abolished the need for ICU admission.
This was statistically significant at p<0.001, and the 95% confidence interval was 0.002-0.17. This means that the probability of observing differences this large or greater if there is no true effect of vitamin D is less than one in a thousand, and that the probability is 95% that the true effect lies somewhere between an 83% and a 99.8% reduction int he odds of ICU admission.
No matter how you slice it, the effect of vitamin D is extremely compelling.
Because the study is small, the potential confounding variables were not perfectly evenly distributed between the two groups. There was more high blood pressure in the control group, and there was a borderline greater number of patients with diabetes in the control group. Though not statistically significant, the vitamin D group had more people over the age of 60 and five times as many people with organ transplants or who were otherwise on immunosuppressive drugs. To account for all of these differences, they adjusted for them statistically. In the adjusted model, vitamin D still reduced the odds of ICU admission by 97%, with the 95% confidence interval ranging from a 75% to a 99.7% reduction in the odds.
Did Vitamin D Also Abolish the Risk of Death?
All of the vitamin D patients were discharged without complications. Half the control group was discharged without ICU admission. Among the other half, 11 were eventually discharged from ICU, and 2 died.
Although there were, thankfully, too few deaths to run statistics on, since patients generally would be admitted to the ICU before dying, and since vitamin D nearly abolished the risk of ICU admission, we can infer that in a larger study with more deaths, vitamin D would probably abolish or nearly abolish the risk of death.
Comparison With Observational Studies
These results are consistent with the first observational study on vitamin D, which found that 96% of severe and critical cases occurred at 25(OH)D under 30 ng/mL, whereas 97.5% of mild cases had 25(OH)D above 30 ng/mL.
This study couldn't measure the effect on mortality, but all two deaths were in the control group and the near abolition of ICU risk suggests that death would also be nearly abolished. This is consistent with the second observational study finding that only 4% of those with vitamin D status above 30 ng/mL died, while 88% of those with vitamin D status at 20-30 ng/mL died, and 99% of those with vitamin D status lower than that died.
It is less consistent with the weaker observational studies that came out later. For example, the fourth observational study found that prevalence of 25(OH)D below 20 ng/mL differed across three categories of severity judged by CT scan in males but not females. It is also less consistent with more recent studies in Iran and England. In Iran, 25(OH)D below 30 ng/mL only increased risk of severe infection by 21%, although mortality was roughly cut in half at that level. In England, ICU patients were half as likely to have 25(OH)D above 20 ng/mL as non-ICU patients, and mortality wasn't associated with vitamin D status.
In other words, the first RCT shows the effect of vitamin D is closer to the more extreme estimates of the first observational studies than it is to the more moderate estimates of the more recent studies.
The observational studies on infection risk are weaker than those on severity and mortality (see here, here, here, and here), but this RCT didn't look at infection risk.
The RCT contradicts the findings of the two Mendelian randomization studies. These found either no evidence for causality in the vitamin D/COVID-19 connection, or only weak evidence. However, these studies infer causality by looking at the effect of genetics. Genetics only explain 4.2% of the variation in 25(OH)D and many of the genes involved have non-specific, indirect relationships to vitamin D status. This RCT overwhelmingly takes precedence over the findings of the Mendelian randomization studies.
This Study Is the Single Most Important Vitamin D and COVID-19 Study
Since the first vitamin D study was released as a preprint* on April 23, we have been waiting for data that could settle whether the association between vitamin D and COVID-19 incidence, severity, and mortality is a causal one.
This study settles the question: yes, it is causal.
It is important for scientists to replicate each other's findings. Future studies with more diverse populations may reveal differences in the response between different populations. Future larger studies will more precisely refine the exact effect of vitamin D. Future studies with different dosing protocols, in different contexts (for example, without the use of hydroxychloroquine and azithromycin, or with the administration of other drugs or nutrients) will add nuances to our understanding of the effect of vitamin D.
However, given the degree to which it is nearly entirely harmless, and almost without exception beneficial, to maintain 25(OH)D above 30 ng/mL, it would be irresponsible not to interpret this study as definitive evidence of causality. At an absolute minimum, maintaining vitamin D status in this range should be part of the public health message to reduce COVID-19 risk, and 25(OH)D should be universally screened in all hospitals to be treated in anyone with COVID-19, and should be universally screened in all testing centers when antibodies and PCR testing is done, so that everyone knows not only their COVID-19 exposure but also their vitamin D status. If it's low, they should be given advice on how to bring it back up to normal.
How I've Changed My Position
On March 17, when I released Version 1 of The Food and Supplement Guide for the Coronavirus, I expressed concern that vitamin D might increase infection risk or severity by increasing ACE2, the entryway of SARS-CoV-2, the coronavirus that causes COVID-19, into our cells. In response to the first observational study of vitamin D released on April 23, which I covered in this newsletter on April 24, I released version 3 of the guide on April 28, in which I revised this stance and took the position that 25(OH)D should be maintained at 30-34 ng/mL.
As observational studies accumulated, they converged on the common point that 30-40 ng/mL is the sweet spot where infection risk, severity, and mortality are all lowest, without any risk of getting too much vitamin D.
I remained concerned that there might be some risk of a U-shaped curve, where risk increases at vitamin D levels higher than 40 ng/mL. Evidence for or against this was scant and contradictory. Data from Switzerland provided hints of an increased infection risk above 40 in those under 70 years old, but not in those older than 70. Data from Chicago suggested no difference in infection risk above 40 ng/mL, but it didn't separate the people by age. Data from Israel suggested that 25(OH)D above 53 ng/mL completely abolishes infection risk, but everyone with levels that high was under the age of 50. In the Israeli study, the relevant data were only in the young, and risk seemed abolished. In the Swiss study, the relevant data existed for all ages, and it suggested risk increased in the young. All of these studies concern infection risk, not severity or mortality, they all have too little data at high 25(OH)D levels, and they contradict each other.
While I remain agnostic whether there is some level of vitamin D above which infection risk is increased, the new RCT concerns severity and mortality. Although 25(OH)D levels weren't measured, they must have hit at least 40 ng/mL by the time the patients were released, and they possibly exceeded 50 ng/mL. That they gave these patients such massive doses of vitamin D without measuring their vitamin D levels, and that this nearly abolished the need for ICU admission, suggests that there should be no concern about a U-shaped curve with severity or mortality for short-term dosing of up to 8,000 IU per day over several weeks or for temporarily pushing 25(OH)D above 50 ng/mL during the course of treatment.
Given that observational studies around infection risk can consistently show that it is increased at low vitamin D status but cannot show any consistent picture at high vitamin D status, I am, for now, relieving myself of concern about this U-shaped curve. If high vitamin D status can almost eliminate severity and mortality, the off-chance that in some people at some high level it could increase infection risk should be tolerated.
I get emails from Chris Masterjohn PhD (for @TheDevastator and @GaleHawkins) https://chrismasterjohnphd.com/1 -
canadjineh wrote: »Here's some newer research for you vis a vis Vit D and covid 19:The First Randomized Controlled Trial on Vitamin D and COVID-19
The trial was conducted at the Reina Sofía University Hospital in Córdoba, Spain. The trial included 76 patients with COVID-19 pneumonia. Although this is no longer the standard of care, all patients were treated with hydroxychloroquine and azithromycin and, when needed, a broad-spectrum antibiotic. Admission to the ICU was determined by a multidisciplinary committee consisting of intensive care specialists, pulmonologists, internal medicine specialists, and members of the ethics committee.
The patients were randomly allocated to receive or not receive vitamin D in a 2:1 ratio. This resulted in 50 patients in the vitamin D group and 26 patients in the control group.
The Vitamin D Treatment Protocol
The vitamin D was provided as oral calcifediol, also known as calcidiol, 25(OH)D, and 25-hydroxyvitamin D. This is a metabolite of vitamin D that our livers make. It is is the principle form of vitamin D that circulates in the blood, and we use it as a measure of vitamin D status.
Traces of 25(OH)D occur in food, and it is five times as potent as vitamin D. As described on page 255 of the 1997 DRI Report, 25(OH)D is given an international unit (IU) value that equates it to vitamin D. Whereas one microgram (mcg) of vitamin D is 40 IU, 1 mcg of 25(OH)D is 200 IU.
The treatment in this RCT was soft capsules of 532 mcg 25(OH)D on day 1 of admission to the hospital, followed by 266 mcg on days 3 and 7, and then 266 mcg once a week until discharge, ICU admission, or death.
This is equivalent to 106,400 IU vitamin D on day 1, 53,200 IU on days 3 and 7, and 53,200 IU weekly thereafter. If this were given as daily doses, it would be the equivalent of 30,400 per day for the first week, followed by a maintenance dose of 7,600 IU per day.
The vitamin D status of the patients was not measured. However, the average vitamin D status in this region of Spain during the time of year in which the study was conducted is 16 ng/mL. A single dose of 100,000 IU vitamin D tends to raise a 25(OH)D of 10 ng/mL into the 20-30 ng/mL range. My suspicion is that the bolus dosing in the first week brought the patients' vitamin D status into the 30-40 ng/mL range by the end of the week, and that most of the healing took place in the circa 40 ng/mL range.
The Results: Near Abolition of ICU Risk
The results are absolutely stunning. 50% of the control group (13 people) required admission to the ICU. Only 2% of those in the vitamin D group (one person) required admission to the ICU.
Expressed as relative risk, vitamin D reduced the risk of ICU admission 25-fold. Put another way, it eliminated 96% of the risk of ICU admission. Expressed as an odds ratio, which is a less intuitive concept but is often used in statistics because it gives an estimate of the effect of the treatment that would be constant across scenarios with different levels of risk, vitamin D reduced the odds of ICU admission by 98%. Either way, vitamin D practically abolished the need for ICU admission.
This was statistically significant at p<0.001, and the 95% confidence interval was 0.002-0.17. This means that the probability of observing differences this large or greater if there is no true effect of vitamin D is less than one in a thousand, and that the probability is 95% that the true effect lies somewhere between an 83% and a 99.8% reduction int he odds of ICU admission.
No matter how you slice it, the effect of vitamin D is extremely compelling.
Because the study is small, the potential confounding variables were not perfectly evenly distributed between the two groups. There was more high blood pressure in the control group, and there was a borderline greater number of patients with diabetes in the control group. Though not statistically significant, the vitamin D group had more people over the age of 60 and five times as many people with organ transplants or who were otherwise on immunosuppressive drugs. To account for all of these differences, they adjusted for them statistically. In the adjusted model, vitamin D still reduced the odds of ICU admission by 97%, with the 95% confidence interval ranging from a 75% to a 99.7% reduction in the odds.
Did Vitamin D Also Abolish the Risk of Death?
All of the vitamin D patients were discharged without complications. Half the control group was discharged without ICU admission. Among the other half, 11 were eventually discharged from ICU, and 2 died.
Although there were, thankfully, too few deaths to run statistics on, since patients generally would be admitted to the ICU before dying, and since vitamin D nearly abolished the risk of ICU admission, we can infer that in a larger study with more deaths, vitamin D would probably abolish or nearly abolish the risk of death.
Comparison With Observational Studies
These results are consistent with the first observational study on vitamin D, which found that 96% of severe and critical cases occurred at 25(OH)D under 30 ng/mL, whereas 97.5% of mild cases had 25(OH)D above 30 ng/mL.
This study couldn't measure the effect on mortality, but all two deaths were in the control group and the near abolition of ICU risk suggests that death would also be nearly abolished. This is consistent with the second observational study finding that only 4% of those with vitamin D status above 30 ng/mL died, while 88% of those with vitamin D status at 20-30 ng/mL died, and 99% of those with vitamin D status lower than that died.
It is less consistent with the weaker observational studies that came out later. For example, the fourth observational study found that prevalence of 25(OH)D below 20 ng/mL differed across three categories of severity judged by CT scan in males but not females. It is also less consistent with more recent studies in Iran and England. In Iran, 25(OH)D below 30 ng/mL only increased risk of severe infection by 21%, although mortality was roughly cut in half at that level. In England, ICU patients were half as likely to have 25(OH)D above 20 ng/mL as non-ICU patients, and mortality wasn't associated with vitamin D status.
In other words, the first RCT shows the effect of vitamin D is closer to the more extreme estimates of the first observational studies than it is to the more moderate estimates of the more recent studies.
The observational studies on infection risk are weaker than those on severity and mortality (see here, here, here, and here), but this RCT didn't look at infection risk.
The RCT contradicts the findings of the two Mendelian randomization studies. These found either no evidence for causality in the vitamin D/COVID-19 connection, or only weak evidence. However, these studies infer causality by looking at the effect of genetics. Genetics only explain 4.2% of the variation in 25(OH)D and many of the genes involved have non-specific, indirect relationships to vitamin D status. This RCT overwhelmingly takes precedence over the findings of the Mendelian randomization studies.
This Study Is the Single Most Important Vitamin D and COVID-19 Study
Since the first vitamin D study was released as a preprint* on April 23, we have been waiting for data that could settle whether the association between vitamin D and COVID-19 incidence, severity, and mortality is a causal one.
This study settles the question: yes, it is causal.
It is important for scientists to replicate each other's findings. Future studies with more diverse populations may reveal differences in the response between different populations. Future larger studies will more precisely refine the exact effect of vitamin D. Future studies with different dosing protocols, in different contexts (for example, without the use of hydroxychloroquine and azithromycin, or with the administration of other drugs or nutrients) will add nuances to our understanding of the effect of vitamin D.
However, given the degree to which it is nearly entirely harmless, and almost without exception beneficial, to maintain 25(OH)D above 30 ng/mL, it would be irresponsible not to interpret this study as definitive evidence of causality. At an absolute minimum, maintaining vitamin D status in this range should be part of the public health message to reduce COVID-19 risk, and 25(OH)D should be universally screened in all hospitals to be treated in anyone with COVID-19, and should be universally screened in all testing centers when antibodies and PCR testing is done, so that everyone knows not only their COVID-19 exposure but also their vitamin D status. If it's low, they should be given advice on how to bring it back up to normal.
How I've Changed My Position
On March 17, when I released Version 1 of The Food and Supplement Guide for the Coronavirus, I expressed concern that vitamin D might increase infection risk or severity by increasing ACE2, the entryway of SARS-CoV-2, the coronavirus that causes COVID-19, into our cells. In response to the first observational study of vitamin D released on April 23, which I covered in this newsletter on April 24, I released version 3 of the guide on April 28, in which I revised this stance and took the position that 25(OH)D should be maintained at 30-34 ng/mL.
As observational studies accumulated, they converged on the common point that 30-40 ng/mL is the sweet spot where infection risk, severity, and mortality are all lowest, without any risk of getting too much vitamin D.
I remained concerned that there might be some risk of a U-shaped curve, where risk increases at vitamin D levels higher than 40 ng/mL. Evidence for or against this was scant and contradictory. Data from Switzerland provided hints of an increased infection risk above 40 in those under 70 years old, but not in those older than 70. Data from Chicago suggested no difference in infection risk above 40 ng/mL, but it didn't separate the people by age. Data from Israel suggested that 25(OH)D above 53 ng/mL completely abolishes infection risk, but everyone with levels that high was under the age of 50. In the Israeli study, the relevant data were only in the young, and risk seemed abolished. In the Swiss study, the relevant data existed for all ages, and it suggested risk increased in the young. All of these studies concern infection risk, not severity or mortality, they all have too little data at high 25(OH)D levels, and they contradict each other.
While I remain agnostic whether there is some level of vitamin D above which infection risk is increased, the new RCT concerns severity and mortality. Although 25(OH)D levels weren't measured, they must have hit at least 40 ng/mL by the time the patients were released, and they possibly exceeded 50 ng/mL. That they gave these patients such massive doses of vitamin D without measuring their vitamin D levels, and that this nearly abolished the need for ICU admission, suggests that there should be no concern about a U-shaped curve with severity or mortality for short-term dosing of up to 8,000 IU per day over several weeks or for temporarily pushing 25(OH)D above 50 ng/mL during the course of treatment.
Given that observational studies around infection risk can consistently show that it is increased at low vitamin D status but cannot show any consistent picture at high vitamin D status, I am, for now, relieving myself of concern about this U-shaped curve. If high vitamin D status can almost eliminate severity and mortality, the off-chance that in some people at some high level it could increase infection risk should be tolerated.
I get emails from Chris Masterjohn PhD (for @TheDevastator and @GaleHawkins) https://chrismasterjohnphd.com/
Chris is a sharp guy.
I know some who are not serious about their Vit D levels like I was before I turned 63. When first tested (2013) I was at 22 ng. Several years ago I read about Vit D/ flu shot trial in the UK and in that case the Vit D users had less flu than the ones that only had the protection of a flu shot. What sold me on Vit D and K2 is how it can lower one's heart arteries calcium scores. Now I am trying to decrease calcium deposits in my spine and joints. Now I can open my mouth wide enough to get dental fillings if needed. The AS (Ankylosing Spondylitis) did a number on me when I was eating food and drinks with added any form of any grain which I stopped cold turkey back in 2014 for pain management to avoid starting on Enbrel injections.0 -
https://vitamindwiki.com/Overview+Magnesium+and+vitamin+D#Consumer_Labs_Review_of_Magnesium_-_as_little_as_2_cents_per_200_mg_of_Mg
I found this when doing some reading this morning and ordered two new Mg books and magnesium bar soap that I never knew existed.
The more I read the more I know how much I don't know.0 -
Magnesium bar soap sounds interesting.... would the magnesium stay on your skin long enough for proper absorption? Usually the liquid magnesium-oil-gel suggests leaving it on for a few minutes and only then wiping with a damp cloth to get rid of the salt sticky feeling (if that bugs you.)0
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My two bars were at door just now when I got home and I have the same question.
Some think Mg may enter best through hair follicles so I use a lot of Mg oil starting at my head and working down while hot out of the shower and just leave it on until the next shower. I do wash my hands if I am going to be using my phone screen. 0 -
Thanks for the study, @canadjineh
I feel sorry for the two in the control group that died when vitamin D could have saved them.
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I couldn’t stand Mg oil so I just use mineral drops mostly. Oysters, sesame seeds, and sunflower seeds are all high in magnesium. I’m about 90% carnivore but started eating nuts and seeds again. Epsom salt baths are great as well.0
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I think Chris Masterjohn is really smart but wrong in some things like most gurus.1
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TheDevastator wrote: »I think Chris Masterjohn is really smart but wrong in some things like most gurus.
That is often the case. What do you see Chris is wrong about specifically?0
