Vitamin D is not a hormone

Before I resume about the topic “ Why Vitamin D is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids” , Let’s pay attention to understand the term of calcidiol, calcitriol, and vitamin D.

Calcifediol / calcidiol / hydroxycholecalciferol / 25-hydroxyvitamin D (abreviated 25(OH)D) is a prehormone which is produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) by the enzyme cholecalciferol 25-hydroxylase. Calcifediol is then converted in the kidneys (by the enzyme 25(OH)D-1α-hydroxylase)into calcitriol (1,25-(OH)2D3), a secosteroid hormone that is the active from of vitamin D. It can also be converted into 24-hydroxycalcidiol in the kidneys via 24-hydroxylation.

Calcidiol is used to determine how much vitamin D is in the body.

Calcitriol (C27H44O3) / 1,25 dihydroxycholecalciferol / 1,25 dihydroxyvitaminD3 is the hormonally active form of vitamin D with three hydroxyl groups (abbreviated 1,25-(OH)2D3 or simply 1,25-(OH)2D), it increases the level of calcium in the blood. 

Vitamin D

is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis . Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol.

Vitamin D is essential for promoting calcium absorption in the gut and maintaining adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults. Together with calcium, vitamin D also helps protect older adults from osteoporosis.

Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D. Many laboratory-cultured human cells have vitamin D receptors and some convert 25(OH)D to 1,25(OH)2D. It remains to be determined whether cells with vitamin D receptors in the intact human carry out this conversion.

Serum concentration of 25(OH)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements [4] and has a fairly long circulating half-life of 15 days [11]. However, serum 25(OH)D levels do not indicate the amount of vitamin D stored in other body tissues. Circulating 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate [11]. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe.

Why “Vitamin D” is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids

The official nutrition committee reports in both North America and Europe now state that Vitamin D is more of a hormone than a nutrient. These statements are wrong, and do not reflect the definitions of either vitamin or hormone. 

Researchers often compound the problem by referring to calcitriol or other deltanoids as “Vitamin D”. These things have serious consequences:

• The literature is burdened by an ongoing confusion that presumes that the reader will somehow“know” what the writer refers to by “Vitamin D”.
• Medical practitioners not familiar with the ambiguities administer Vitamin D inappropriately when calcitriol or a deltanoid analog would be correct, or vice versa.
• Attempts to promote VitaminD nutrition are hindered by alarmist responses justifiably associated with the widespread administration of any hormone.

In several ways, Vitamin D falls between the cracks of definitions applied to it. First, there is confusion about whether Vitamin D is truly a vitamin or nutrient, and that perhaps the word, hormone, is more suitable. Second, the “Vitamin D” is used in the generic sense far too often, to substitute for 1,25-dihydroxyvitamin D (calcitriol) or for any molecule based upon Vitamin D’s secosteroid structure. 

Vitamin D is a vitamin in the truest sense of the word, because “insufficient amounts in the diet may cause deficiency diseases”. Too little vitamin D in the diet can lead to weakened bones and an increased risk of fractures. Over consuming vitamin D can cause nausea, vomiting, poor appetite, constipation, weakness and weight loss. Calcinosis, the deposition of calcium and phosphate in soft tissues like the kidney, can be caused by vitamin D toxicity. Antacids, some cholesterol lowering drugs, mineral oil, some anti-seizure medications, and steroids interfere with the absorption of vitamin D. 

The term, prohormone, is not relevant to the Vitamin D system, but 25-hydroxy-vitaminD (calcidiol) is appropriately described as a prehormone, i.e. a glandular secretory product, having little or no inherent biologic potency, that is converted peripherally to an active hormone.

Vitamin D is not alone as a vitamin attainable by other than dietary means, since niacin can also be synthesized, and vitamin A can be generated in the body from beta–carotene.

For most of the 20th century, there was no debate that Vitamin D was a nutrient. It was “the sunshine vitamin”. A focus on a poor definition of the word, vitamin, in some dictionaries is no excuse to allow the misconception to continue, that Vitamin D might be regarded as a hormone instead of a nutrient. It should be evident from this that Vitamin D is no more a hormone than cholesterol is—both are the structural raw material that one or more hormones are made from. Vitamin D is a vitamin in the truest sense of the word, because “insufficient amounts in the diet may cause deficiency diseases”.

So, we can conclude that :

Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is obtained from sun exposure, food, and supplements is biologically inert and it must undergo two hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol.

Vitamin D is not a hormone, vitamin D is indeed a vitamin because “insufficient amounts in the diet may cause deficiency diseases”, it meet the definition of vitamin. Meanwhile, the characteristics of calcidiol match the definition of prehormone, and calcitriol matches the definition of hormone.