Vitamin D3

Vitamin D3
Vitamin name	Cholecalciferol
Chemical formula	C₂₇H₄₄O
Solubility	Fat-soluble
Discovery year	1922
Daily requirement (RDA)	2,000–5,000 IU (some need up to 6,000 IU based on blood tests)
Upper limit	10,000 IU daily (conservative); therapeutic doses up to 20,000 IU topically used
Rich food sources	Egg yolks, liver, dairy (from sun-exposed animals),

Introduction

Vitamin D3, also known as cholecalciferol, is not truly a vitamin but rather a secosteroid hormone with broad systemic effects far beyond its well-known role in calcium metabolism. While mainstream medicine often dismisses vitamin D deficiency as clinically irrelevant except for osteoporosis risk, this perspective stems from failure to recognize its true hormonal nature. Vitamin D can interact with virtually all other steroid receptors. The primary function of vitamin D, from a bioenergetic perspective, extends beyond the conventional bone-building narrative. As Ray explained:

"I think its main function, not the calcium bone building function that they talk about, I think its even more basic function is that it reduces the parathyroid hormone"

Structure/Chemical properties

Vitamin D3 is structurally classified as a secosteroid, meaning it has a broken steroid nucleus while retaining essentially steroid-like structure and function.

"Vitamin D is actually a steroid, or more specifically, it's a secosteroid. In other words, it's a broken steroid, part of the steroid nucleus is missing, but the structure is still very much a steroid structure" - Haidut

Metabolic Forms:

1. Cholecalciferol (D3): The starting form from sunlight or supplementation
2. 25-hydroxyvitamin D (calcidiol): The storage form produced by the liver, the main marker of vitamin D status
3. 1,25-dihydroxyvitamin D (calcitriol): The so-called "active" form produced by the kidneys under stress conditions

The relationship between these forms is critical. The 25-hydroxy form is the one that should be measured for vitamin D status.

"We only activate ordinary vitamin D into the dihydroxycholecalciferol under stress. If we're deficient in vitamin D, the curative anti-inflammatory material, our body suddenly starts converting this, any trace of it, to a very small amount of 1,25-dihydroxy, and that happens to do all kinds of destructive calcification things" - Ray Peat

Function/Mechanism of Action

Parathyroid hormone suppression

The most fundamental action of vitamin D is suppressing parathyroid hormone (PTH). When vitamin D (and calcium) are deficient, PTH rises and initiates a cascade of harmful effects:

"The parathyroid hormone, which takes calcium out of your bones, does it by increasing fermentation, by producing lactic acid in the bone. In the presence of carbon dioxide and carbonic acid, calcium goes into your bone, but parathyroid hormone reverses that process, decreasing CO2 and increasing lactic acid, getting the calcium out of your bone, putting it in your bloodstream, and also shifting the balance generally of lactic acid, causing the calcium to accumulate in soft tissues" - Ray Peat

Energy production

Vitamin D deficiency directly impairs mitochondrial energy production:

"This study demonstrated up to 40% reduction of energy production in the muscles of animals deficient in vitamin D, in spite of unchanged number/size/density of mitochondria inside the cells" - Haidut

Thyroid Connection

Vitamin D and thyroid function are intimately connected.

"The thyroid and vitamin D and calcium are intimately interrelated, you can't separate the thyroid from the vitamin D and calcium metabolism" - Ray Peat

Both deficiencies cause parallel inflammatory states:

"All of the inflammations that you get with low thyroid function are structurally and functionally similar to those you get from a vitamin D deficiency" - Ray Peat

Steroid receptor interactions

Vitamin D enhances the function of other steroid hormones:

"Vitamin D is known to have an anti-glucocorticoid effect directly at the receptor level and it increases the sensitivity and the binding affinity of both the thyroid hormone and the androgens and progesterone to their respective receptors" - Haidut

Anti-aging effects

Vitamin D works through the anti-aging Klotho pathway:

"The Klotho gene is now recognized as a regulator of calcium metabolism and it has an anti-parathyroid hormone effect in many parts of the system. And the vitamin D that we take or that we get from the sunlight works to reinforce Klotho, the anti-aging gene or protein, and at the same time it's lowering the parathyroid hormone" - Ray Peat

Medical uses/Effects

Immune function

Vitamin D is essential for proper immune function and viral resistance:

"If you supplement vitamin A and vitamin D, along those two vitamins are just about as effective as a huge vaccination campaign" - Ray Peat

Vitamin D has been shown to reduce the risk of colds and flu.

Autoimmune diseases

"A human study, one of the largest ever conducted, covering virtually all major autoimmune conditions, showed that taking vitamin D does prevent autoimmune diseases" - Haidut

Cancer protection

Vitamin D shows significant anti-cancer effects, particularly for GI cancers:

"A daily dose of 4,000 IU to 8,000 IU vitamin D reduces cancer progression by up to 36%" - Haidut

Cardiovascular and metabolic health

"Deficiency of vitamin D led to increased inflammatory burden as demonstrated by elevated IL-6, etc. Those inflammatory biomarkers correlate perfectly with insulin resistance... chronic deficiency can lead to heart failure, as the heart is perhaps the muscle most sensitive to vitamin D levels" - Haidut

Anti-estrogenic and hormonal effects

The active metabolite calcitriol has anti-estrogenic and anti-prolactin activity. Vitamin D also plays a role in steroidogenesis and testosterone production, with studies showing vitamin D supplementation might increase testosterone levels in men

Dopaminergic activity

"Vitamin D is another potent dopamine agonist, and its dopaminergic activity contributes to its effects on reducing diet-induced obesity and drug addiction behaviors" (Haidut, "").

Side/Adverse effects

The "toxicity" misconception

Much of the fear around vitamin D toxicity relates to confusion between forms. The "activated" 1,25-dihydroxy form increases under stress and deficiency:

"The calcitriol is the extreme stress form of vitamin D. It has its use under stress, but like estrogen, it easily becomes counterproductive and in the case of cancer..."

"Part of the toxicity, people get very confused and fail to work out the ramifications of the so-called active vitamin D and receptor as being associated with a lot of toxic harmful effects that are reduced by adequate calcium and the not-active form of vitamin D. It's actually active, but it isn't what they call active"

Risk factors for problems

Taking vitamin D without adequate calcium and magnesium can be problematic:

"Taking D without calcium and some of the other mechanisms like magnesium can create an atmosphere that isn't very good for you, which could create calcium getting into the tissue, which is what you do not want"

Obese individuals

Vitamin D accumulates preferentially in fat tissue, potentially requiring higher doses in overweight individuals:

"In obese people, vitamin D can accumulate in adipose tissue and thus create a deficiency for the rest of the organs/tissues. In such people, higher doses of vitamin D would be needed to maintain serum levels in the normal range"

Dosing

Target blood levels

"I think 50 ng/ml is a good goal. The point at which it lowers parathyroid hormone would be the right amount"

"I think a blood level of 50 to 55 ng/ml is optimal"

Supplemental doses

Standard maintenance:

• 2,000 IU daily during winter typically makes up for no sunlight
• 5,000 IU daily is appropriate for many adults, particularly in higher latitudes

Higher doses when needed:

• 10,000 IU daily for a couple of months during winter should be safe when combined with adequate calcium and vitamin K
• 20,000 IU topically on skin during winter
• Overweight individuals may require higher doses

Therapeutic doses:

• 50,000 to 100,000 IU orally as a single dose has been used to start treatment for acute inflammatory conditions

Food Sources

Vitamin D is found in small amounts in animal foods including egg yolks, liver, and dairy products. The liver stores considerable vitamin D, making beef liver a good source. However, dietary sources alone are usually insufficient without sunlight or supplementation.

"The reason eating fish liver or beef liver or whatever is a good source of vitamin D is that the liver does store a considerable amount of vitamin D"

Co-factors

Vitamin D works best with:

• Calcium: At least 1,000 mg daily to suppress PTH, Vitamin D promotes it's absorption
• Vitamin K: Directs calcium to bones rather than soft tissues
• Magnesium: Essential for vitamin D metabolism
• Vitamin A: Works synergistically with vitamin D

"The vitamin D itself is part of the calming anti-inflammatory process, so the calcium and magnesium are essential and should be done immediately"

Testing

The proper test is 25-hydroxyvitamin D (calcidiol), not 1,25-dihydroxyvitamin D:

"The 25 hydroxy is a good enough test for almost all purposes"