Vitamin D

Introduction

Vitamin D is the general name given to a group of fat-soluble compounds that are essential for maintaining the mineral balance in the body. The chemical structure of vitamin D was identified in the 1930s. The main forms are vitamin D2 (ergocalciferol: found in plants, yeasts and fungi) and vitamin D3 (cholecalciferol: of animal origin).

As cholecalciferol is synthesised in the skin by the action of ultraviolet light on 7-dehydrocholesterol, a cholesterol derivative, vitamin D does not fit the classical definition of a vitamin. Nevertheless, because of the numerous factors that influence its synthesis, such as latitude, season, air pollution, area of skin exposed, pigmentation, age, etc., vitamin D is recognized as an essential dietary nutrient.

Functions

Following absorption or endogenous synthesis, the vitamin has to be metabolised before it can perform its biological functions. Calciferol is transformed in the liver to 25-hydroxycholecalciferol (25(OH)D, calcidiol). This is the major circulating form, which is metabolised in the kidney to the active forms as required. The most important of these is 1,25-dihydroxy-cholecalciferol (1,25(OH)2D, calcitriol) because it is responsible for most of the biological functions. The formation of 1,25(OH)2D, which is considered a hormone, is strictly controlled according to the body's calcium needs. The main controlling factors are the existing levels of 1,25(OH)2D itself and the blood level of parathyroid hormone, calcium and phosphorus.

To perform its biological functions, 1,25(OH)2D, like other hormones, binds to a specific nuclear receptor (vitamin D receptor, VDR). Upon interaction with this receptor, 1,25(OH)2D regulates more than 50 genes in a wide variety of tissues.

Vitamin D is essential for the control of normal calcium and phosphate blood levels. It is known to be required for the absorption of calcium and phosphate in the small intestine, their mobilisation from the bones, and their reabsorption in the kidneys. Through these three functions it plays an important role for the proper functioning of muscles, nerves and blood clotting and for normal bone formation and mineralisation.

It has been suggested that vitamin D also plays an important role in controlling cell proliferation and differentiation, immune responses and insulin secretion.

Dietary Sources

Vitamin D is found only in a few foods. The richest natural sources of vitamin D are fish liver oils and saltwater fish such as sardines, herring, salmon and mackerel. Eggs, meat, milk and butter also contain small amounts. Plants are poor sources, with fruit and nuts containing no vitamin D at all. The amount of vitamin D in human milk is insufficient to cover infant needs.

Absorption and body stores

Absorption of dietary vitamin D takes place in the upper part of the small intestine with the aid of bile salts. It is incorporated into the chylomicron fraction and absorbed through the lymphatic system. Vitamin D is stored in adipose tissue. It has to be metabolised to become active.

Measurement

Vitamin D status is best determined by the serum 25(OH)D concentration because this reflects dietary sources as well as vitamin D production by UV light in the skin. Usual serum 25(OH)D values are between 25 and 130 nmol/L depending on geographic location.

1 µg vitamin D is equivalent to 40 IU (international unit).

Stability

Vitamin D is relatively stable in foods. Storage, processing and cooking have little effect on its activity, although in fortified milk up to 40% of the vitamin D added may be lost as a result of exposure to light.

Interactions

Positive interactions

Women taking oral contraceptives have been found to have slightly elevated blood levels of 1,25(OH)2D.

Negative interactions

Cholestyramine (a resin used to stop reabsorption of bile salts) and laxatives based on mineral oil inhibit the absorption of vitamin D from the intestine. Corticosteroid hormones, anticonvulsant drugs and alcohol can affect the absorption of calcium by reducing the response to vitamin D.

Animal studies also suggest that anticonvulsant drugs stimulate enzymes in the liver, resulting in an increased breakdown and excretion of the vitamin.

Deficiency

such as bowed legs in children. The ends of the long bones in both the arms and legs are affected, and their growth may be retarded. Rickets also results in inadequate mineralisation of tooth enamel and dentin.

Osteoporosis, a disorder of older age in which there is loss of bone, not just demineralisation, has also been associated with less obvious states of deficiency.

Groups at risk of deficiency:

• Infants who are exclusively breast fed are at high risk of vitamin D deficiency, because human milk is a poor source of vitamin D. In addition, in premature and low-birth-weight infants, liver and kidney function may be inadequate for optimal vitamin D metabolism.
• The elderly have a reduced capacity to synthesise vitamin D in the skin by exposure to sunlight.
• People with diseases affecting the liver, kidneys, the thyroid gland or fat absorption, as well as vegetarians, alcoholics and epileptics on long-term anticonvulsant therapy have a greater risk of deficiency, as do people who are housebound.
• Dark-skinned people produce less vitamin D from sunlight and are at risk of deficiency when living far from the equator.
• Populations living at latitudes of around 40 degrees north or south are exposed to insufficient levels of sunlight to cover vitamin D requirements through endogenous production, especially during winter months.
  

Disease prevention and therapeutic use

In the treatment of rickets, a daily dose of 40 µg (1,600 IU) vitamin D usually results in normal plasma concentrations of calcium and phosphorus within 10 days. The dose can be reduced gradually to 10 µg (400 IU) per day after one month of therapy.

Vitamin D analogues are used in the treatment of psoriasis.

Vitamin D is discussed as a prevention factor for a number of diseases.

Results from epidemiological studies and evidence from animal models suggest that the risk of several autoimmune diseases (multiple sclerosis, insulin-dependent diabetes mellitus, rheumatoid arthritis) may be decreased by adequate vitamin D intake.

Vitamin D plays an important role in the prevention of osteoporosis because vitamin D insufficiency can be an important contributing factor in this disease. A prospective study among 72,000 postmenopausal women over 18 years indicated that women consuming at least 600 IU vitamin D/day from food plus supplements had a 37% lower risk of hip fracture. Evidence from most clinical trials suggests that vitamin D supplementation slows bone density losses and decreases the risk of osteoporotic fracture in men and women.

Various surveys and studies suggest that poor vitamin D intake or status is associated with an increased risk of colon, breast and prostate cancer.

Recommended Dietary Allowance (RDA)

Establishing an RDA for vitamin D is difficult because vitamin D can be endogenously produced in the body through exposure to sunlight. Healthy people regularly exposed to the sun have no dietary requirement for vitamin D, under appropriate conditions. As this is rarely the case in temperate zones, however, a dietary supply is needed.

In 1997, the Food and Nutrition Board based adequate intake levels (AI) on the assumption that no vitamin D is produced by UV light in the skin. An AI of 5 µg (200 IU)/day is recommended for infants, children and adults (ages 19-50 years). For the elderly, higher intakes are recommended to maintain normal calcium metabolism and maximise bone health. In other countries, adult recommendations range from 2.5 µg (100 IU) to 10 µg (400 IU).

Safety

Hypervitaminosis D is a potentially serious problem as it can cause permanent kidney damage, growth retardation, calcification of soft tissues and death. Mild symptoms of intoxication are nausea, weakness, constipation and irritability. In general, the toxic dose for adults is around 1.25 mg (50,000 IU) per day. However, certain individuals have an increased sensitivity to vitamin D and present with toxic symptoms after 50 µg (2,000 IU) per day. Hypervitaminosis D is not associated with overexposure to the sun because a regulating mechanism prevents overproduction of vitamin D.

The Food and Nutrition Board (FNB) and the EU Scientific Committee on Food have set the tolerable upper intake level (UL) for vitamin D at 50 µg/day for adolescents and adults.

Supplements and food fortification

Monopreparations of vitamin D and related compounds are available as tablets, capsules, oily solutions and injections. Vitamin D is also incorporated in combinations with vitamin A, calcium, and in multivitamins.

In many countries, milk and milk products, margarine and vegetable oils fortified with vitamin D serve as a major dietary source of the vitamin.

Industrial production

Cholecalciferol is produced commercially by the action of ultraviolet light on 7-dehydrocholesterol, which is obtained from cholesterol by various methods. Ergocalciferol is produced in a similar manner from ergosterol, which is extracted from yeast. Starting material for the production of caIcitriol is the cholesterol derivative pregnenolone.

History

» History of Vitamin D