Vitamin D

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(Redirected from 7-dehydrocholesterol)

Vitamin D is a fat-soluble steroid hormone precursor that contributes to the maintenance of normal levels of calcium and phosphorus in the bloodstream. Strictly speaking, it is not a vitamin, but is referred to as one for historical reasons.

Often known as calciferol.

Contents

Forms of Vitamin D

Overview

Vitamin D2 is derived from ergosterol in the diet, whereas vitamin D3 is derived from cholesterol via 7-dehydrocholesterol. Ultraviolet light (UVB, which is wavelengths 290 to 315 nm), found in sunlight, is responsible for the production of the vitamin - 20,000 IU in one minimal erythemal dose of exposure. However, in certain parts of the world with reduced sunlight intensity there is the possibility that the quantity of vitamin D is not always sufficient. To prevent this possibility, milk may be fortified with vitamin D2. A deficiency of vitamin D leads to rickets, which is a softening of the bones owing to faulty mineralization.

The active form of the vitamin is calcitriol which is synthesized from either D2 or D3 in the kidneys. Calcitriol binds to a protein transcription factor which then regulates gene expression. The outcome is the maintenance of calcium and phosphorus levels in the bone and blood with the assistance of parathyroid hormone and calcitonin.

Diseases

Vitamin D deficiency is known to cause several bone diseases, due to insufficient calcium in the bones:

  • Rickets: a childhood disease characterized by "soft" bones
  • Osteoporosis: a condition characterized by fragile bones.
  • Osteomalacia: a bone-thinning disorder in adults that is similar to rickets.

Pioneering work in isolating vitamin D and determining its role in rickets was done by Edward Mellanby in 1918-1920.

Vitamin D malnutrition may also be linked to chronic diseases such as cancer (breast, ovarian, colon, prostate, lung and skin), chronic pain, weakness, chronic fatigue, autoimmune diseases like multiple sclerosis and Type 1 diabetes, high blood pressure, mental illnesses (depression, seasonal affective disorder and possibly schizophrenia) heart disease, rheumatoid arthritis, psoriasis, tuberculosis, periodontal disease and inflammatory bowel disease.

Who may need extra vitamin D to prevent a deficiency?

Older people (greater than age 50) have a higher risk of developing vitamin D deficiency. The ability of skin to convert 7-dehydrocholesterol to pre-vitamin D3 is decreased in older people. The kidneys, which help convert calcidiol to its active form, sometimes do not work as well when people age. Therefore, many older people may need vitamin D supplementation.

Newborn infants who are exclusively breastfed may require vitamin D supplements. Breast milk does not contain significant levels of the vitamin, and although infants could receive this vitamin from sunlight, it is usually not recommended that small infants be exposed to sunlight in the levels required to produce a sufficient amount of vitamin D. Infant formula is generally fortified with vitamin D, so this requirement only applies to breastfed infants.

Those who avoid or are not exposed to the midday sunshine may also require Vitamin D supplements. In particular, recent studies have shown Australians and New Zealanders are Vitamin D deficient [1], particularly after the successful "Slip-Slop-Slap" health campaign encouraging Australians to cover up when exposed to sunlight to prevent skin cancer. Ironically, a vitamin D deficiency too may lead to skin cancer. Still, only a few minutes of exposure is all that is required; the production is very rapid.

Recent research suggests that adult human beings can handle up to 5,000 international units (IU) per day long-term, although the metabolic pathways have not yet been identified. Given this, and given that humans on vitamin pills of 200 IU per day become deficient if not exposed to sunlight, there is reasonably convincing evidence that the Recommended Dietary Allowance (RDA) of 200 IU (5 micrograms) may be rather too small.

Human skin production of vitamin D

Human skin exposed to sunlight can, under the right conditions, produce quantities as large as 20,000 IU in just a few minutes without any apparent toxicity. This is easily enough to avoid deficiency and builds up the body's stores.

Exposure to sunlight also destroys vitamin D, so long term exposure to sunlight cannot cause toxicity, as levels are self-adjusting.

However merely being exposed to sunlight does not automatically mean that vitamin D is produced, only the UVB in sunlight triggers vitamin D production, but UVB only reaches ground level when the sun is high in the sky. This only ever occurs a few hours around solar midday (1 pm summertime). Further, at higher latitudes, the sun is only high enough in the sky in summer. For example, in the US, those living above a line from San Francisco to Atlanta will not be able to produce it at all for 3 to 6 months a year.

Therefore from the end of summertime to the following spring humans run on stores which gradually deplete. By some estimates 10-20% of the population become at least mildly deficient by the end of winter, and deficiency is high even in very sunny countries like India. People that never go out in the midday sun become deficient even on supplementation at 100% of the RDA.

In addition, suntan lotion blocks production. Deficiencies are now much more common in Australia, which had a very successful 'slip slop slap' campaign. Additionally, due to the opacity of melanin, black skin is much less efficient at generating vitamin D. It would be expected that black people would suffer greatly from deficiencies, but this has not been established. Some genetic and physiological differences in the way that vitamin D is handled may be involved, and research is ongoing to investigate this.

Oral overdose of vitamin D3

Overdose is extremely rare; in fact, mild deficiencies are pretty common.

While the sunshine-generated quantity is self-limiting, vitamin pills were thought not to be; and this has led to widespread concern, which may well be misplaced.

In practice, the human body has enormous storage capacity for vitamin D, and in any case all common foods and correctly-formulated vitamin pills contain far too little for overdose to ever occur in normal circumstances and normal doses. Indeed, Stoss therapy involves taking a dose over a thousand times the daily RDA once every few months, and even then often fails to normalise vitamin D3 levels in the body.

However, oral overdose has been recorded due to manufacturing and industrial accidents and leads to hypercalcemia and atherosclerosis and ultimately death, so overdose is very definitely possible.

Acute one-time overdose requires over 50mg (ten thousand times the RDA, 2,000,000 IU). For overdose to occur in adults, chronic doses of 1-2mg (over 200 times the RDA, 40,000 IU) over many months are normally required. Intriguingly, the RDA itself is in fact more than 100x less than the amount that may be generated in about 20 minutes of midday sunshine.

Exactly what the long term safe dose is, is not entirely known, but intakes of up to 2000 IU (10x the RDA) are believed to be safe, and some researchers believe that 10,000 IU does not lead to long term overdose. It seems that there are chemical processes that destroy excess vitamin D, even when taken orally, although these processes have not been identified (in experiments blood levels of vitamin D do not continue to increase over many months at these doses as presumably would be needed for toxicity to occur.)

Note, that although normal foods and pills are too small to be toxic, cod-liver oil if taken in more than the normal dose could in fact reach poisonous levels.

Vitamin D and cancer recovery

Recent research suggests that cancer patients who have their surgery/treatment in the summer - and therefore get more vitamin D - have a much better chance of surviving the disease than those who have their treatment in the winter when they are exposed to less sunlight. [2]

Vitamin D food sources

Fortified foods are the major dietary sources of vitamin D. Prior to the fortification of milk products in the 1930s, rickets was a major public health problem. In the United States milk is fortified with 10 micrograms (400 IU) of vitamin D per quart, and rickets is now uncommon in the US.

One cup of vitamin D fortified milk supplies about one-fourth of the estimated daily need for this vitamin for adults. Although milk is fortified with vitamin D, dairy products made from milk (cheese, yogurt, ice cream, etc.) are generally not fortified with vitamin D. Only a few foods naturally contain significant amounts of vitamin D, including:

  • fish oils, such as cod liver oil, 1 Tbs., 1,360 IU
  • fatty fish, such as:
    • salmon, cooked, 3.5 oz, 360 IU
    • mackerel, cooked, 3.5 oz, 345 IU
    • sardines, canned in oil, drained, 3.5 oz, 270 IU
    • eel, cooked, 3.5 oz, 200 IU
  • one whole egg, 25 IU
  • Beef liver, cooked, 3½ ounces 15 IU
  • One (100% RDA) vitamin pill, 200 IU

Sources: National Institutes of Health, National Osteoporosis Society

Synthesis

Vitamin D3

Vitamin D3 is synthesized from 7-dehydrocholesterol, a derivative of cholesterol, which is then photolyzed by ultraviolet light. The product is Previtamin D3. Image:Reaction-Dehydrocholesterol-PrevitaminD3.png

Previtamin D3 then spontaneously isomerizes to Vitamin D3 Image:Reaction-PrevitaminD3-VitaminD3.png

Vitamin D3 (cholecalciferol) is then hydroxylated in the liver to 25-hydroxycholecalciferol (calcidiol) and then further hydroxylated in the kidneys to the main biologically active form 1,25-dihydroxycholecalciferol (calcitriol): Image:Reaction-VitaminiD3-Calcitriol.png

External links


Vitamins
All B vitamins | All D vitamins
Retinol (A) | Thiamine (B1) | Riboflavin (B2) | Niacin (B3) | Pantothenic acid (B5) | Pyridoxine (B6) | Biotin (B7) | Folic acid (B9) | Cyanocobalamin (B12) | Ascorbic acid (C) | Ergocalciferol (D2) | Cholecalciferol (D3) | Tocopherol (E) | Naphthoquinone (K)
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