Why Vitamin D Levels Stay Low
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Vitamin D status is commonly assessed with serum 25-hydroxyvitamin D, but the same supplement dose can produce very different blood levels. In this clip from Dr. Rhonda Patrick's appearance on The Tim Ferriss Show, she describes how baseline status, body size, genetics, sun exposure, and supplement content can contribute to that variation. In a randomized trial of 484 adults with prediabetes, genetic variants, body mass index, and baseline status separated predicted high and low responders by about 60 nanomoles per liter after one year of supplementation. [1]
A second randomized trial provides a closer look at genetic response. Among 1,787 adults assigned vitamin D3 at 1,000 IU per day, calcium, both, or placebo, vitamin D3 raised 25-hydroxyvitamin D by an average 6.1 nanograms per milliliter after one year, with wide person-to-person variation. Common variants near genes involved in vitamin D hydroxylation and signaling modified the response. [2]
The practical message is to avoid treating one dose as universal. A three-year trial of 311 healthy adults found that 4,000 or 10,000 IU per day produced lower radial volumetric bone density than 400 IU per day, without a bone-strength benefit. Current Endocrine Society guidance also does not support routine high-dose supplementation or routine testing for disease prevention in all healthy adults. When a measured level remains low despite reported intake, repeat testing and individualized clinical review can address dose, adherence, body size, absorption, medications, and health conditions. [3] [4]
This clip is excerpted, with permission, from Dr. Rhonda Patrick's appearance on The Tim Ferriss Show. Thank you to The Tim Ferriss Show for allowing us to share it.
- ^ Sollid ST; Hutchinson MY; Fuskevåg OM; Joakimsen RM; Jorde R (2016). Large Individual Differences in Serum 25-Hydroxyvitamin D Response to Vitamin D Supplementation: Effects of Genetic Factors, Body Mass Index, and Baseline Concentration. Results from a Randomized Controlled Trial. Horm Metab Res 48, 1.
- ^ 10.1210/jc.2014-1389
- ^ 10.1001/jama.2019.11889
- ^ Demay MB; Pittas AG; Bikle DD; Diab DL; Kiely ME; Lazaretti-Castro M, et al. (2024). Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 109, 8.
Tim Ferriss: I want to loop back around so people aren't saying, "Ferriss, you forgot about vitamin D." I've taken vitamin D forever, generally 5,000 IU a day. Particularly in the summer, I get at least an hour in the sun without skin protection, and I build up to that gradually. Yet in my labs, I am always barely squeaking by on vitamin D.
Almost all my adult friends who get labs are deficient or just on the border of being deficient, even if they take supplemental vitamin D and get a lot of sunshine. This seems race agnostic. I have to ask what is going on. How is it possible that so many people are deficient if they get sunlight and take vitamin D? Can you shed any light on this?
Dr. Rhonda Patrick: I can.
Tim Ferriss: Or is there a problem with the measurement itself? That is why I was talking earlier about proxies and confounders in other studies. Please educate me.
Dr. Rhonda Patrick: Vitamin D is measured indirectly. Vitamin D is converted into a steroid hormone. That hormone goes inside the nucleus of our cells, where our DNA is, and activates about 5 percent of the protein-coding human genome. Many of the genes it activates include Klotho, which you mentioned. Vitamin D is important for activating Klotho.
Tim Ferriss: Nice.
Dr. Rhonda Patrick: It is also important for dementia risk, which we can discuss. To answer your question, vitamin D levels are measured through a proxy called 25-hydroxyvitamin D, the precursor to the active steroid hormone.
Vitamin D3 made in your skin, or taken as a supplement, enters the bloodstream. It goes to the liver and is converted into 25-hydroxyvitamin D, the major circulating form of vitamin D. It then goes to the kidneys and is converted into the active steroid hormone called 1,25-dihydroxyvitamin D.
The enzymes that convert vitamin D3 into the stable form measured by a vitamin D blood test require magnesium. Studies have shown that this conversion does not happen as readily when magnesium is low.
Tim Ferriss: Interesting.
Dr. Rhonda Patrick: About 50 percent of the US population has insufficient magnesium intake, so you're talking about roughly a coin toss. Low magnesium intake has been associated with circulating vitamin D levels. NHANES studies have found that people with low magnesium intake also have low circulating 25-hydroxyvitamin D.
Another factor is genetics. Many people have common single-nucleotide polymorphisms, or SNPs, that may have come from populations in southern latitudes. Those variants can affect how much vitamin D3 they make from sun exposure, perhaps because those populations historically received so much sun.
Tim Ferriss: Yes.
Dr. Rhonda Patrick: There is a genetic component. I've reviewed many people's SNP profiles, and some people have to take a high dose of vitamin D3 to reach a sufficient blood level.
There is also variation between supplements. Studies of vitamin D supplements have found the same problem seen with melatonin: some products contain a fraction of the vitamin D3 stated on the label.
Tim Ferriss: And some have 10 times as much vitamin D.
Dr. Rhonda Patrick: There can be large variation. A label might say 5,000 IU when the product contains only 500 IU. Several factors can contribute.
Sun exposure also varies. You said you do not wear sunscreen, but some people do. People with darker skin have more melanin, which acts as a natural sunscreen. One University of Chicago study reported that African Americans needed six to 10 times as long in the sun as Caucasians to make the same amount of vitamin D3 from the same exposure.
Tim Ferriss: Because they have natural sunscreen.
Dr. Rhonda Patrick: Yes. Melanin, the darker skin pigment, is a natural sunscreen.
Tim Ferriss: It is also why their skin can look great as they age. I once met an African American man who looked about 25 but was 53 and had five children.
Let me ask about recommended vitamin D brands and how much someone like me should take as a starting point. I'm wary of taking too much because there seem to be risks. You also mentioned magnesium as a rate-limiting factor. What type and how much? How should I think about both?
Dr. Rhonda Patrick: First, we need to talk about vitamin D levels and what the optimal levels are. That is important for determining how much to supplement. I tend to think anywhere from 40 to 80 nanograms per milliliter is an optimal range. I like 40 to 60 as my sweet spot because studies have associated that range with lower all-cause mortality.
Around 50 nanograms per milliliter would be a great place to be. If you are at or just above 30, you might try to reach 40.
Tim Ferriss: For the sake of argument, let's say I'm at 30. I think I'm closer to 40, but let's use 30.
Dr. Rhonda Patrick: For someone at 30 nanograms per milliliter who is taking 5,000 IU a day...
Tim Ferriss: Yes, 5,000 IU a day and an hour of summer sun without sunscreen.
Dr. Rhonda Patrick: You would probably expect to be closer to 50 nanograms per milliliter if you're taking that amount.
Tim Ferriss: I'll check my last labs. I had them drawn two weeks ago.
Dr. Rhonda Patrick: In that case, someone might increase to 7,000 IU and check the level again a month later. If the result is then in the 40 to 50 range, that is the dose that produced that level for that individual.
This is an important conversation because there is an individual component. People want one answer to how much they should take, but you have to get a vitamin D blood test. This is something you have to measure because, as you mentioned, there is huge variation.
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