Overview
Vitamin D is one of the most important regulators of inflammation and energy production, inseparable from calcium and thyroid in its action. Most people are deficient, either due to sun phobia and sunscreen, or the fact that aging skin has only half the cholesterol of young skin, or because the official dietary recommendations of a few hundred units a day are essentially nothing. The form that matters is cholecalciferol, measured in the blood as 25-hydroxy D. The so-called "active" form, 1,25-dihydroxy D or calcitriol, is actually a stress signal produced when parathyroid hormone is high, and most of the published harms attributed to vitamin D are really harms of the stress form. Adequate cholecalciferol, calcium and magnesium ensures that parathyroid hormone stays suppressed, calcium goes into bones rather than into arteries and soft tissues, and cells settle into the high-energy resting state that resists infection, inflammation, and degeneration.
Key Points
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The "active" 1,25-dihydroxy form of vitamin D is a stress signal. Parathyroid hormone turns on the enzyme that converts 25-hydroxy D into 1,25-dihydroxy D, and once that activated form is dominant, it drives bone breakdown, lactic acid production, and a shift towards fat metabolism. The form of Vitamin D to keep high is cholecalciferol or its 25-hydroxy storage form, which suppresses the inflammatory pathway. Most of the literature warning against vitamin D is built on confusing these two.
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The protective range for 25-hydroxy D is roughly 50 to 70 nanograms per milliliter. Sunburn resistance, better sleep, lower viral susceptibility and the buffer that lets you handle stress without pulling calcium out of bones all appear above 50. Lifeguards working outdoors have measured 130 ng/mL and higher with no harm evident, and 150 ng/mL is probably an upper healthy limit. Ray Peat recommended around 50-60 ng/ml.
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The original RDA of 400 IU was based on a calculation error and is off by a factor of 10. The 400 IU figure is roughly what is appropriate for a young child. Adults, who weigh four to five times what children weigh, need around 4,000 IU daily, especially in winter, just to avoid frank deficiency. The original studies the FDA based RDA on contained statistical errors that have since been exposed in published critiques.
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Twenty minutes of midday summer sun on bare skin produces ten to fifteen thousand IU, and five thousand IU per day from a supplement is harmless for almost anyone. A quart of fortified milk only contains around 300 IU, so reaching the protective range from food alone is essentially impossible. The body has its own brake when synthesizing from sunlight, so overdose from sun isn't really possible at sea level latitudes.
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Vitamin D, calcium, magnesium, and thyroid have to be addressed together. Without enough dietary calcium, vitamin D won't suppress parathyroid hormone, and PTH will keep pulling calcium out of bones into soft tissues. The remedy isn't less D, it's more dietary calcium from milk, cheese, and leafy greens, getting enough magnesium, and lowering phosphate intake from meat, grains, legumes, and nuts.
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Vitamin D is a steroid that activates progesterone, thyroid, cortisol, and estrogen receptors. It activates the progesterone receptor, which is why it can substitute for progesterone in post-menopausal women. It potentiates thyroid hormone activity at the thyroid receptor. It blocks cortisol at the glucocorticoid receptor, mirroring the action of drugs like RU-486. It antagonises estrogen receptor alpha, making it a natural selective estrogen receptor modulator (SERM) without the toxic side effects of synthetic SERMs like tamoxifen, clomiphene, and raloxifene. This four-receptor profile is why a single nutrient can affect so many systems.
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The central protective function of vitamin D is to keep parathyroid hormone suppressed. PTH dissolves bone by generating lactic acid in it, releasing calcium into the bloodstream, and depositing that calcium in arteries, heart valves, nerves, and other soft tissues. With enough calcium and 25-hydroxy D, PTH stays low, the kidneys don't have to ramp up the activated form and cells return to a self-maintaining state.
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Aging skin has roughly half the cholesterol of young skin and produces correspondingly less vitamin D from the same sun exposure. Over the age of 60, it takes about twice as much sunlight to make the same amount of D. Statins compound the problem by blocking cholesterol synthesis upstream, and low thyroid further reduces cholesterol production. People in nursing homes are doubly hit by indoor confinement and reduced skin synthesis.
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Low vitamin D shows up as muscle weakness, depression, insulin resistance, high blood pressure, viral susceptibility, atrial fibrillation, and calcification of arteries and valves. A woman in her 60s with a level of 7 to 8 ng/mL was so weak she could hardly walk; within a week of starting 5,000 IU daily, she could walk around. Hospital admissions with higher vitamin D are more likely to leave alive. Brain-injured patients consistently show very low vitamin D.
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Vitamin D is the strongest predictor of all-cause mortality, including non-disease death. Higher vitamin D levels correlate with lower risk of dying from any cause, but the correlation extends beyond illness. People with higher vitamin D levels are safer drivers, less prone to drug and alcohol abuse, and less likely to die from accidents and risky behaviour. This systemic protective effect parallels the action of thyroid hormone and progesterone, which makes sense given vitamin D activates both their receptors.
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The cold and flu season is essentially a vitamin D deficiency season. Sun exposure drops in winter at temperate latitudes, vitamin D drops with it, and viral susceptibility climbs. Hawaii doesn't have a flu season. Vitamin A and vitamin D supplementation are comparable in effect to vaccination campaigns for many of the common viral illnesses, because cathelicidin (an antimicrobial peptide) and natural interferon (signalling proteins, part of the immunte system) production both depend on D status.
Notable Quotes
"The thyroid, vitamin D and calcium are intimately interrelated, you can't separate the thyroid from the vitamin D and calcium metabolism."
[Ray Peat — Vitamin D, Calcium and Mineral Metabolism, Win at Life Podcast]
"Being in a bathing suit in the sun for 20 or 30 minutes enough to start turning pink, that can make 10 or 15,000 units."
[Ray Peat — KMUD: Vitamin D]
"I've never heard of 10,000 a day being harmful."
[Ray Peat — KMUD: Vitamin D]
"The calcitriol (1,25-dihydroxy D) is the extreme stress form of vitamin D."
[Ray Peat — KMUD: Skin Cancer Part 2]
"Vitamin D is one of the factors that was shown to be most strongly negatively correlated with all-cause mortality."
[Georgi Dinkov — Doctor Age Reversal: Vitamin D & Cortisol]
"Vitamin D has been shown to be one of the two or three factors together with aspirin and progesterone that are able to force that cell to go back to normal."
[Georgi Dinkov — Cancer, Differentiation & Vitamin D]
"Vitamin D, because of its structure, it's actually a steroid or partially broken steroid... It's capable of activating some of the same enzymes and pathways that testosterone does. So you can think of vitamin D as acting as a testosterone mimetic into the male body and as a progesterone mimetic in the female body."
[Georgi Dinkov — Rooted in Resilience: Male Fertility]
Important Things To Consider
Don't take vitamin D without enough calcium and magnesium. A diet skewed toward meat, grains, legumes, and nuts is high in phosphate and low in calcium, which drives parathyroid hormone up. Without a calcium base from milk, cheese, or leafy greens, raising vitamin D can pull calcium from bones rather than storing it properly. Magnesium deficiency creates the same kind of inflammatory background.
The 1,25-dihydroxy D test is a stress marker, not a vitamin D adequacy test. A doctor who measures 1,25 and reads a high value as "enough vitamin D" has it exactly backwards. The 25-hydroxy form is the test that reflects supply. A high 1,25 with a low 25 is a typical pattern of deficiency plus stress.
Vitamin D supplements based in MCT oil have caused severe reactions in some people. Ray described a woman who thought she was approaching death with neurological symptoms; everything resolved within days of stopping all MCT-containing supplements. There's evidence MCT can disrupt the immune lining of the intestine and create food allergies. Olive-oil-based vitamin D drops or capsules are a safer alternative for sensitive people.
Vitamin D needs vitamin K to direct calcium into bones rather than soft tissue. Vitamin D and vitamin K are co-factors for producing osteocalcin, a protein made in the bone that vitamin K activates. Activated osteocalcin binds the calcium and shuttles it into bone.
D3 is the form to use, not D2. Around 1970 a series of papers raised concerns about D2 contributing to atherosclerosis and arterial calcification, and milk producers quietly switched to D3 fortification at that point.
Phosphate excess produces the same signs as vitamin D deficiency. High parathyroid hormone, high 1,25 D, and the inflammatory cascade follow either too much phosphate or too little calcium and D. Reducing phosphate intake works in the same protective direction as raising D and calcium.
The activated form, calcitriol, can promote cancer metastasis under stress. A Polish study showed that 1,25-hydroxyvitamin D suppresses immunity and creates the environment for mammary gland cancer metastasis. Adequate 25-hydroxy keeps the kidneys from having to convert it into the cancer-friendly active form.
Most published anti-vitamin-D papers fail to distinguish 25-hydroxy from 1,25. Klotho, the anti-aging protein, is supported by 25-hydroxy and knocked down by 1,25. The activated form (1,25) raises angiotensin and parathyroid hormone, while the storage form does the opposite. Reading the literature requires checking which form was studied.
Sun phobia and sunscreen have driven the population back into vitamin D deficiency. Rickets rates have increased in England. Many of the chronic conditions that have doubled or tripled in the last two or three decades correspond to widespread D deficiency. The phobia is itself a major risk factor.
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