I assume that’s without GFJ?
DMD, I suggest a CBC blood panel during the time you’re feeling cold. Rapamycin lowers my red blood cell count to below normal, and it may affect yours, too. As for NMN, I took it for several years and thought it helped, but now I’m not so sure. I continue experimenting with the supply I have in different ways (amount, time of day, etc.) to see if I can find any discernible improvement in energy or strength levels, but have not found any evidence yet. So, I’m on the fence, too.
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Anything that supplements NAD levels will depend on how low your levels are in the first instance.
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Most of the observational studies are weak and I’ve seen pretty over-exaggerated claims on higher end of Vitamin D from scientists like Dr. Rhonda Patrick (she is sensational and overhypes some things, but not to the point of a quack) to the random typical quacks claiming ultra mega-dosing vitamins are good for you when there is no “gold standard” trial proving this and a few trials against this.
The current “official” recommendation is 600-800 IU depending on adult vs older adult. Generally, Vitamin D levels are not tested unless there is a good reason to due to cost effectiveness and issues with assays commonly used in commercial labs. (For reference, I use LC-MS/MS based on NIST standard to be as confident as possible on the accuracy since I’m trying to go for a fairly tight window to minimize any potential harms)
I’m going a bit against the official rec by taking Vitamin D 2,000 IU USP grade with cold water fish/roe & quality fish oil (which adds a labeled tiny amount of mixed tocopherols - with frequent independent third party testing and my own tests to avoid rancidity) based on the VITAL trial on NEJM.
Keep in mind - I’ve been really careful with genetics before and tested baseline as well as ongoing levels which is not generally cost-effective. I also avoid sunlight exposure from all angles as much as possible for skin cancer prevention (only have a tiny amount in the early morning indirectly). So individual supplementation will vary with a lot of caveats.
https://www.nejm.org/doi/full/10.1056/NEJMoa2202106
In this vitamin D and omega 3 (VITAL) trial, 25,871 participants (mean age 67 years and mean baseline of approximately 30 ng/mL) were randomly assigned to vitamin D 2000 IU or placebo. After a median follow-up of 5.7 years, the cumulative incidence of autoimmune disease was lower in the treatment group (0.95 versus 1.2 percent, HR 0.78, 95% 0.61-0.99). I have family that has autoimmune disorders so I’ve been following many options for things like “pre-RA” and other proposed pre-disease states based on known genetics associated with HLA (which can vary by reference population and ethnicity) and other issues. I’m quite familiar with the immune system in general. If I’m right, then I might make a big gain on life expectancy, since autoimmune disorders like RA add 3x CV risk. Other people might not find that potential gain compelling enough in their circumstance.
There are no prospective studies to define optimal Vitamin D levels for extraskeletal health with widespread definitive conclusions though but I suspect >=80 ng/mL is very likely “bad” because there isn’t enough of a feedback mechanism for this hormone and <80 is what one would get if from all-day constant direct sun exposure. We also saw decreases in bone mineral density at >=40 ng/mL or around 4,000 IU, so may be potential harmful dose if it gets you to >40. >50 is a common agreed upon upper limit, where >60 is where more associations of potential negative effects occur.
We also have an official recommended upper limit of 4,000 IU (assuming no malabsorption etc). So I aim for 30-40 personally with 2,000 IU per day. Preferably closer to 35-40 based on some small association with tiny additional cancer prevention. That’s my personal interpretation of the literature where benefit and harm is balanced towards possibly insignificant likelihood of harm for me personally. Some experts previously claimed around 25-30 is best for maximum PTH suppression - a fair position to take.
Vitamin D levels have a genetic basis for variations with a high degree of heritability in twin studies. Some may have malabsorption but it’s much less likely if you are “healthy”. So when you talk to your doc, must take that and a lot of other things into account. Not as simple as it’s made out as there are actually still knowledge gaps on this hormone. Don’t let the “vitamin” name make it seem like it must be innocuous - it’s always about getting close to the “right” amount at the “right” time often with limited imperfect data anytime you take anything. The deepest experts in the field for new therapies often get it wrong statistically and the likelihood of a non-expert getting it wrong is probably even more likely on average, especially if they are an influencer trying to sell you something with an affiliate link or they are tied to some ideology.
The thing is contrarianism is usually wrong and if one is trading one potential small benefit for a small likely known harm, one is probably bad at math, risk management, and recognizing cognitive biases. So if you are going contrarian against official guidelines like myself, you better be pretty darn familiar with the potential tradeoff and evidence.
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Why is that? Most capsules contain liquid vitamin D. Do you have any supporting data that the capsules prevent the proper absorption of vitamin D?
I am not necessarily disputing you, but suppliers of competing products such as raw fish oil, etc., are course touting their own products.
Thank you for your detailed response! The last time I had my vitamin D measured, I was deficient as I too avoid sunlight due to a family history of skin cancer (both parents). Also, I have heard the many negatives about a deficiency. I had my parents taking 5000 IU daily as well, but they tested too high. Therefore I switched them to 1000 IU.
I need to get a new blood test done to see if 5000 IU is too much for me as well. I had tried 1000 IU, but then I read about the Mexican Vitamin D COVID study, and they used 4000 IU to prevent COVID, so I switched back to 5000 IU. I am now concerned that 5000 IU may be too much. My youngest son, 10 yo is very concerned about COVID, so I give him some as well. What do you think? I really want to give everyone in my family an optimal amount. Thank you for your time and consideration .
DeStrider
Review the following;
“Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)”
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I hope you can understand I don’t practice medicine over the internet. You have pretty much most of the general information and literature interpretation already in the response for a large headstart for your doc to determine an appropriate plan, especially if your doc isn’t that familiar with the current body of research.
If you want another doc, there are plenty to choose from as a second opinion, which can be from an academic center where they have access to a deep expert that has done research on this topic to make that clinical judgment. The general official recommendation is 800 IU for “healthy” older adults (>70 years old) and 600 IU for “healthy” adults. I can’t make a precise individualized recommendation of “optimal” in my view, especially when I don’t even have all the data I need in front of me.
Even if it’s likely rare, there are just a ton of possible complicated caveats with avoiding say Hypervitaminosis D and as a result, covering up another reason for hypercalcemia which could point to a deadly malignancy that isn’t investigated early enough - just as an example of what could go wrong when one foolishly offers individualized medical advice over the internet.
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If one reads the main BMJ, the editorial actually goes through this and sums it nicely:
“Two new trials find no effect but aren’t the final word”
Far larger and more recent Vitamin D trial in the UK in BMJ on COVID shows no difference between 800 IU and 3,200 IU with much, much longer follow-up and much, much larger sample size, as opposed to your citation that admits “vitamin D levels were neither available at baseline nor during follow-up in the study” for North India trial participants (where it is known the population is very commonly deficient) and “the dose of cholecalciferol used in the present study is high compared to conventional treatment, that warrants close follow up to look for vitamin D toxicity”:
"What is already known on this topic
- Vitamin D metabolites support innate immune responses to SARS-CoV-2 and other respiratory pathogens
- Suboptimal vitamin D status (25-hydroxyvitamin D <75 nmol/L) is associated with increased susceptibility to all cause acute respiratory tract infections and covid-19
- Phase 3 randomised controlled trials of vitamin D to prevent covid-19 have not yet reported
What this study adds
- This phase 3 randomised controlled trial (6200 participants) shows that implementation of a population level test-and-treat approach to oral vitamin D replacement at daily doses of 800 IU or 3200 IU was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19 among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status"
“The difference in findings might be because participants in the Mexican trial [4,000 IU] had not been vaccinated against SARS-CoV-2, or it may reflect the relatively short duration of follow-up (one month).”
I’ll also note a rare CYP24A1 mutation can actually mess up your vitamin D breakdown. Rare hypersensitivity to vitamin D can occur. It could take several months to develop vitamin D toxicity when you look at most people. If one is say in one of the milder ranges of possible toxicity i.e. hypercalciuria (which can lead to highly painful kidney stones) - it is difficult to prove that vitamin D is the cause. Once again, there are a lot of caveats.
So basically, your cited small trial (where the placebo wasn’t very well designed) suggests with weak evidence that in the very short term - trying to build up vitamin D levels in 14 days only with high doses until >50 levels are reached might help already deficient asymptomatic COVID patients to clear virus levels in the short term with no guarantee of safety in the long term. It’s not generalizable, which the study readily admits. It’s not particularly useful to people who most likely aren’t already deficient - they are aiming to help people mainly in developing or third world countries who are far more likely to be deficient or severely deficient - yet there are plenty of bunk claims from quacks on social media generalizing it to mean high dose Vitamin D is great for COVID in the long run for everyone (mainly the target audience being developed countries) because few people actually read it through. We see that with the far larger Norway study with a low dose 400 IU showing null results (for COVID) with long follow-up.
The much larger trials with close monitoring and longer follow-up already show safety issues that were expected - a few people got hypercalcemia on the 3,200 IU and they had to stop the dose right away. It’s pretty clear even the upper limit of 4,000 IU is not equivalent to 100% safe (the definition of upper limit is the tolerable safe upper limit for “most” adults - so the results fit with official guidelines) in the shorter run of several months - and that’s assuming you get supplements that are high quality without mislabeling. The individual variability is large as mentioned, so obviously this translates to a small number of people having mild issues under the official upper limit.
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For some reason, I am sometimes oblivious to the obvious.
Vitamin D3 is a fat-soluble vitamin, so it is typically dissolved in an oil-based liquid in order to be encapsulated in a capsule.
So, I went to Amazon and looked at the ingredient list in some of their brands.
I soon got bored so I didn’t look at all that many, but I did find mostly soybean oil, safflower oil, sunflower oil, coconut oil, and olive oil.
I think I will opt for olive oil. Unfortunately, I have a large bottle of Costco Kirkland D3 which soybean-based. That would be my last choice. NOW brand D3 is dissolved in olive oil, which is what I will switch to.
BTW: Oil-based supplements are not readily absorbed through the mucous membrane, which is designed to absorb water-soluble compounds.
Oil base supplements are typically absorbed in the gut.
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I think that the issue is that a large percentage of the human population (approx. 50%) has a vitamin D deficiency (myself included). When you are deficient, COVID affects you much more dramatically. Therefore, bringing vitamin D levels up to normal will greatly reduce the chances of getting COVID and having long COVID. With a 5,000 IU dosage, my parents have levels of 75 and 104 respectively. The question is, is that bad? According to their health reports, levels between 30-100 are sufficient. If 104 will not cause any health effects, it appears 5,000 IU of vitamin D daily may take you to the high end of sufficient. Which is my target.
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Hong Kong uses nmol/L. Read the studies and talk to your doc.
My parents are in the USA, so their numbers match with yours. 
Some places report nmol/L here actually - but since they are here - then I suspect you are referring to 30-100 as the typical “reference range” in lab reports where they would flag an “abnormal result” as defined by the lab people, it does not actually mean that levels are “sufficient” at all or that the range applies or is reliable for medical purposes. If you read through the terms and conditions, it would become apparent.
They use 30 as the lower limit cutoff because that got a person to weigh in that thinks >30 is ideal and under that is “deficient” - but the actual recommended number varies by professional organizations, some use 20.
There is literally no official definition of what is a “healthy” upper limit cutoff so whoever they got probably just didn’t actually feel comfortable weighing in.
What the “100” really means is probably the upper end of the “normative range” which includes people out in the sun the whole day and people taking large doses of supplements to define 95% of the people tested, minus the lower limit of 30. It’s not useful in this context. Relying on the upper limit of the reference range can be harmful if one doesn’t actually understand what it means. You can also be within the “normative range” and have medically abnormal or non-optimal levels that don’t get flagged. An example is “normal” reticulocyte labs in anemia.
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Actually I am quite surprised by the variation in D3 levels. I do believe my dad gets out in the sun more, so that may explain it. My dad said that the lab report range of 30-100 was labelled as 'sufficient '. I think they should continue with 5000 IU based on the data available .
Unfortunately most doctors aren’t really supportive of supplements and will only advise changes to them when they are outside the prescribed ranges. If you are within normal ranges, they don’t try to optimize even if you are near the lower bounds. Preventative health care has a long way to go.
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You are entitled to your opinion and choice not to consult anyone regardless of whether your decision has merit or not. If your doctor is not familiar with the preventative research side I’ve already mentioned what you can do. Some of the reasons supplements get a bad rap are partly because of commonplace quality issues and potentially causing harm through drug interactions. These are real, nontrivial concerns.
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Thank you for all of your advice. I truly appreciate it!
Actually the doctor was never going to test Vitamin D levels as it’s not standard practice where my parents lived. They got the test because they insisted on it. My mothers doctor actually recommended to reduce her vitamin D intake as he thought 74 was too high even though it is in the sufficient range. If a level of 74 could cause any health problems, I would ask her to reduce it. The same for my father.
The problem is all the conflicting advice and evidence. Health issues at 3,200 IU is worrisome. Maybe 2000 or 1000 IU would be better.
As mentioned, testing Vitamin D levels are literally not standard practice due to cost-effectiveness issues. I already mentioned common assay accuracy issues. I suggest you read the terms of the lab company and what “sufficient” even means. Somewhere buried in the terms is probably something along the lines of “we’re not liable for anything and don’t rely on anything”, even if it says “sufficient”. They always tell you to talk to your doctor to avoid any potential medical issues.
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Due to the health issues of a vitamin D deficiency, and the prevalence of the deficiency, I feel that it almost negligent for doctors not to test their patient’s vitamin D levels. I wonder how many other vitamins or minerals people are deficient in but are unaware due to the cost of testing. For those of us with a little more available resources, what other things should we be testing for that are not standard?
I always believe that prevention is much more cost effective than treatment. Thank you for your wise remarks. It gives me something to think about and will hopefully provide better health outcomes for my family.
I do weekly blood tests which include a vitamin D analysis. The labs vary and I am not always certain as to the accuracy of the results. I take 3,000 iu per day in a specific oil based capsule. From time to time I also take 25OHD (Dedrogyl). I track my consumption of 25OHD and I did manage to get a formula based upon varied amounts of capsules and dedrogyl which enabled me to predict the next week’s serum 25OHD from consumed dedrogyl and capsules. (Ie I had a week in which I took no capsule or dedrogyl). Unsurprisingly dedrogyl is more effective IU for IU than the capsules.
My hypothesis about vitamin D is that we evolved to have a metabolism that had an annual sun based cycle because the creatures that started depending upon vitamin D had more food available when it was sunny. As the summer’s resources went away then the metabolism would gradually shut down less essential elements. Therefore needing less food.
Hence there are perhaps 1,000 genes that only function when there is sufficient vitamin D.
My view is that I would prefer that those genes function hence I aim to have a 25OHD level at the top end of normal. What I do is continue with 3,000 iu per day which sees a gradual reduction in serum 25OHD and then top up with 25OHD (Dedrogyl) when I get a bit low.
If I stopped the weekly blood tests I would use my formula to predict how much I should take.
I have had vitamin D levels more than twice the top end of normal so I stopped supplementation and the level of 25OHD went down quite rapidly.
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