Vitamin D is a remarkably controversial topic, not regarding whether low Vitamin D is associated with all manner of bad things … but in regard to whether supplementation and normalization of Vitamin D levels eliminates or mitigates risks associated with low levels.
We are going to take the long road to talking about Vitamin D in relation to neurocognitive decline, as we first must address the “Supplementation doesn’t help” claim.
The published literature on this topic has been interpreted to demonstrate no benefit to supplementation. The mainstream approach, in physician references such as UpToDate, MedScape, or in this consumer facing article in Scientific American which states “no evidence of benefit for supplementation.” The approach is however one that cautions those with low levels that they risk significant bad health outcomes, and advises trying to improve this through increased sun exposure, possibly optimizing dietary magnesium and consuming foods naturally containing vitamin D. Foods high in vitamin D
The write-up on this topic on UpToDate seems sensible and detailed, including stating that low Vitamin D levels are associated with worse outcomes in cancer, infection, autoimmune disease, cardiovascular disease, diabetes, and with all-cause mortality. A direct quote from their write-up is “However, there are no convincing randomized trial data that vitamin D supplements can decrease cancer risk or prognosis, decrease the risk or severity of infections or autoimmune diseases, or decrease cardiovascular risks or metabolic diseases. In addition, there are no prospective studies to define optimal 25(OH)D levels for extra-skeletal health. Thus, we do not suggest vitamin D supplementation above and beyond what is required for osteoporosis management.”
So, I guess the question is, why would Vitamin D in a pill be different from the natural mechanisms which are primarily food + sun exposure? Is there some other confounder? We know that in the past with some other items, supplementation didn’t result in the expected results as ingesting beta carotene, for example, naturally was different than getting it in a pill. However, this was primarily because foods that contain beta-carotene typically have lots of other phytonutrients, and supplementing just the beta-carotene was not equivalent. Please click on this text to watch a video with Dr. Hart, which details why simply adding vitamin D MIGHT NOT fix the issue.
Are the studies that UpToDate and others looked at flawed? The answer is almost certainly YES. So what mistakes were made? The first is that the patients often didn’t have levels measured or tracked, and the studies didn’t start with individuals who had documented low levels. The doses given (will be detailed later) were not sufficient to resolve a deficiency in patients with low levels (often supplementing just 800-2000 IU daily). Additionally, as it takes a long time for Vitamin D levels to rise, often not waiting long enough to assess outcomes.
The appropriate way to design a study is to identify a group of subjects with low serum values, supplement the intervention group with sufficient Vitamin D to get their level of 25-hydroxy Vitamin D [25(OH)D] level up to probably 50 ng/mL (125 nmol/L) and see if differences in clinical outcome occur. Current studies are looking at a different question, which is what is the utility of giving everyone a fixed dose of Vitamin D?
This trial looked at patients with a low vitamin D level <=20 ng/mL (50 nmol/L) and repetitively tested to understand what dose of vitamin D supplementation would get them to a minimal acceptable level for disease mitigation. The results are interesting. Note that USRDA recommendations at 600-800 IU/day. However, only 13.5% got to >40 ng/mL (100 nmol/L) on <2,000 IU/day, 20.8% did so on 3,000-4,000 IU/day, 51% needed 5,000-8,000 IU/day, and 14.6% required>10,000 IU/day. Additionally, on supplementation, <65% got to the target level by 3 months, and 25% still weren’t at target level after 6 months. So, there is a time factor, and also a need for testing and dose modification. None of these key items were done on prior published trials.
Looking at the studies that showed no effect on outcomes that UpToDate and others are relying on to say don’t supplement, supplemented at <=2,000 IU/day. They also didn’t separate out those deficient or monitor blood levels to show adequate response. It is thus no surprise that we have a lack of evidence for supplementation. The reason is self-evident.
Based upon this what should one do?
We are left with the situation of lack of proof for supplementation, but there are some areas suggestive, and the risks of having a low vitamin D are substantial.
Test your Vitamin D level
If it is low, consider improving dietary consumption, and get 15 minutes of sun to a good amount of your body surface area daily (if very intense sun, naturally less)
Retest in 3 months
If not at least >30 ng/mL (75 nmol/L), supplement and retest in 3 months, if >30 ng/mL (75 nmol/L), then monitor, including in winter to make sure a seasonal supplement isn’t required
If taking a supplement, monitor for response being aware that simply taking a typical dose may be insufficient - it also is not generally a good idea to have very high levels of vitamin D, so if above the laboratory range, one needs to decrease the dose
*Please note that the normal range at Quest Laboratories is 30-100 ng/mL (75-250 nmol/L).
*Dr Fraser likes to see patients in the 50-70 ng/mL (125-175 nmol/L) range to provide a safety margin from going low.
A great read on this is available here detailing a consensus statement on management and risks of vitamin D deficiency.
So just looking at whether supplementation has any benefit on severity of Covid-19 - so this is really an immune modulation effect. This first look including multiple trials (albeit often not done adequately) showed supplementation decreased death by 52%, and decreased risk of needing intensive care by 65%. Article Link
Here is another with suggestion of benefit Article Link
Then we have the NIH guidelines saying no evidence for benefit with Covid-19. Article Link
Dementia
This article simply looked at supplementation - no levels were measured. One confounder could be that people who supplemented were better educated or affluent. Either way, supplementation was associated with a 40% decrease in likelihood of dementia diagnosis. Article Link
Despite supplementing just 800 IU/day, and not measuring levels or response, this study of patients who already had Alzheimer’s Disease (AD) demonstrated statistically and clinically meaningful benefits to those in the treatment group. Article Link
This one looks a bit better done, simply looking at levels of Vitamin D and whether supplemented or not. The protective effect of not being deficient appeared to be around 25%, and those who supplemented with vitamin D specifically had a 17% lower risk. Article Link
This one is yet another one that failed to recognize the needed dosing and didn’t show a positive result. Article Link
Here is an “Expert” review on use of Vitamin D in Dementia. Sadly none of the experts understood that the trials were using ineffective dosing, not measuring before or after supplementation, which would be critical in forming an opinion. Article Link
This study is an association study, but those who had a Vitamin D level >=20 ng/mL (>=50 nmol/L) had less than 45% the rate of Alzheimer’s Disease compared to those who were severely deficient. Article Link
I won’t go through all the articles here, but these are a decent group of articles showing a relationship between both incidence of PD and even improvement in motor function with adequate Vitamin D levels.
#1 Measure Vitamin D levels, if inadequate address this by:
Sunlight - Dietary Vitamin D and if level is <30 ng/mL (75 nmol/L) by 3 months recheck THEN
Supplement using this formula, modified for ease of use from this paper: https://pubmed.ncbi.nlm.nih.gov/20139241/ which was targeting a goal of 75 nmol/L (30 ng/mL).
In U.S. units using ng/mL and using weight in Pounds here is the formula:
0.811 x [30-serum 25(OH)D] x wt in lbs = Daily Dose
In SI Units using nmol/L and using weight in Kilograms here is the formula:
0.714 x [75-serum - 25(OH)D] x wt in kgs = Daily Dose
So this formula attempts to get vitamin D levels to 30 ng/mL (75 nmol/L) by 8 weeks, so using this, 8 weeks would be the recheck time; although probably fine to do 3 months and recheck.
Example use of the U.S. formula. If you weigh 200 lbs, and your 25(OH)D is 10 ng/mL then: 0.811 x [30-10] x 200 = 3244 Units/day.
This being stated, I’d look at this and think 5,000 units per day would be great as my goal is more in the 50-70 ng/mL range for most patients.
#2 Recheck level based on adjusting supplementation every 3 months until steady in the range 30-100 ng/mL (75-250 nmol/L) THEN
#3 Recheck yearly (probably best in mid-Winter to get your low point)
In general, for most patients, it is sensible to add Vitamin K2 MK7 to their vitamin D to protect their bones. This option is cost effective and at a good dose.
Widespread recommendations that there is no evidence that Vitamin D supplementation improves health outcomes are not based upon studies designed to determine this. It is technically correct that supplementation hasn’t been proven to help, however, this is because we don’t have studies designed to determine this yet.
The clock is ticking, and the overwhelming likelihood of a risk/benefit analysis, favors normalizing your Vitamin D. Have a trial of doing it naturally first, but if that isn’t successful (year round including especially winter) then seriously consider supplementing until a properly performed study shows supplementation to be of no value - which I doubt will be the outcome.
Disclaimer:
This blog provides general education only and should not be used to diagnose or replace the advice of a qualified medical professional.
This content is not intended to be a substitute for consultation with a qualified and licensed physician or another medical provider.
Readers should consult a medical professional for advice, diagnosis and treatment relating to their individual case.
You should discuss any supplement/medication being considered with your medical professional before starting it.
This post contains affiliate links. I may receive a small commission if you click on the links of the products and make a purchase.
Credit:
Special thanks to Antoine Dusséaux for his assistance with co-authoring this blog. www.adssx.com
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