Article 14: Vit D in Preventative Medicine - Are we Ignoring the Evidence?

This is an excerpt taken from the paper by Armin Zittermann of Bonn University.

Please note, this is an abridged version of this paper. A copy of the full paper can be downloaded, in pdf format, by clicking on "Click here for more information" at the bottom of this article.

Introduction.

Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal la-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme la-hydroxylase, which is able to use circulating 25(OH)D as a substrate.

Serum levels of 25(OH)D arc the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range.

There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able:

1. to reduce blood pressure in hypertensive patients
2. to improve blood glucose levels in diabetics
3. to improve symptoms of rheumatoid arthritis and multiple sclerosis.

The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 ug/d.

Vitamin D insufficiency.

Rickets, the clinical outcome of a severe vitamin D deficiency in infants, was endemic in Europe and North America during the 19th century and during the first two decades of the 20th century. Based on the observations that skin exposure to u.v. light as well as oral vitamin D intake could cure rickets, several very effective prevention strategies were performed. The so-called 'stossprophylaxis' was based on the administration of high amounts of vitamin D several times during infancy (Markestad et al.1987). Moreover, young children were regularly exposed to artificial u.v. light.

Present prophylaxes of rickets include a daily vitamin D supplement of 10 ug in Germany(Deutsche Gesellschaft fur Emahrung et al. 2000), the UK (Department of Health, 1998), the Netherlands (Health Council of the Netherlands, 2000), Sweden (Axelsson et al. 1999), and Finland (National Nutrition Council, 1999). In the USA, the adequate intake for infants is 5 ug/d (Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board and Institute of Medicine, 1997).

Nowadays, rickets is rare in Europe and North America, but there is still a risk, especially if parents are not aware of preventive measures or neglect them (Hellebostad et al. 1985; Hartman, 2000).

There is now growing evidence that the adult European population is also at risk for an inadequate vitamin D status (see p. 554-555). The present review summarizes the evidence of an involvement of a low vitamin D status in the pathogenesis of several chronic diseases. Moreover, the amount of oral vitamin D intake to maintain an adequate vitamin D status is discussed.

Multiple Sclerosis.

Multiple sclerosis (MS) is a demyellinating disease of the central nervous system that is debilitating and can be fatal (Hayes et al. 1997). Manifestation of the disease is typically between the years of 20 and 40. It appears that the pathological demyellinating of the central nervous system is caused by T-cell-mediated autoimmune processes. These alterations are obviously promoted by a genetic component and by virus infections and traumas. The prevalence of MS is nearly zero close to the equator and is markedly increased in regions of more northern latitudes (Dichgans & Diener, 1987).

Moreover, there is a North to South gradient of the MS prevalence in the USA (Schwartz, 1992). Exceptions from this general North to South gradient in the MS prevalence of the Northern hemisphere are some Swiss districts at high altitude (> 2000m), Greenland and the costal regions of Norway. In these regions a low MS prevalence was reported (Dichgans & Diener, 1987; Hayes et al. 1997).

Results are consistent with the hypothesis that an inadequate vitamin D status is an important pathogenetic factor in MS. Annual u.v.B irradiation is more intensive in Swiss districts of high altitude than in regions of low altitudes. In Greenland and at the costal regions of Norway there is a traditionally high consumption of vitamin D-rich fatty fish (Hayes et al. 1997).

A study set up to investigate bone health in MS patients revealed a prevalence of insufficient serum 25(OH)D levels (< 50 nmol/1) in 77 of the patients (Nieves et al. 1994). Experimental studies have shown that diets high in Ca and calcitriol can completely suppress the induction of autoimmune encephalomyelitis, which is a model of MS (Cantoma et al.1996). Moreover, calcitriol can prevent the progression of autoimmune encephalomyelitis when Ca is high, but not when Ca is low in the diet (Cantoma et al. 1999).

An intervention study in MS patients has demonstrated that daily supplementation with 16mg Ca/kg body weight, 10 mg Mg/kg body weight and 125 ug vitamin D/d for 1-2 years was able to decrease the relapse rate of MS patients compared with the expected exacerbations (Goldberg et al. 1986).

Several mechanisms have been held responsible for the beneficial effects of vitamin D in MS including an inhibition of inflammatory T-helper cells, an inhibition of the production of inflammatory cytokines by activated macrophages, an enhanced production of anti-inflammatory cytokines, and an anti-proliferative action in lymphocytes by the expression of VDR (Hayes et al. 1997). In line with these assumptions it has recently been demonstrated that vitamin D supplementation is able to reduce IL-2 mRNA in peripheral blood mononuclear cells of MS patients (Cantoma et al. 2001).

Conclusions:

Calcitriol is a very potent steroid hormone and is, on a molar basis, the most effective vitamin D metabolite. Nevertheless, an adequate serum 25(OH)D level is also necessary to achieve full physiological vitamin D activity. Obviously, the serum 25(OH)D level and not the serum calcitriol level is the best indicator for vitamin D insufficiency, adequacy, or toxicity.

Because only a few foods, especially some fatty fishes, naturally contain vitamin D in relevant amounts circulating 25(OH)D levels normally largely depend on u.v.B exposure.

In tropical and subtropical regions, where more than 90% of human evolution took place, u.v.B irradiation is abundant throughout the year.

Reasons for a low vitamin D status in Europe are:

1. the seasonal lack of u.v.B irradiation.
2. low outdoor activities.
3. the ageing process leading to a reduced vitamin D synthesis in the skin.
4. the low vitamin D content of most foods.

Probably, the prevalence of a low vitamin D status will increase in future due to the rising number of elderly individuals in European societies, and due to the migration of dark-skinned people and veiled women to Europe.

The relevance of the frequently low vitamin D status is not completely clear. However, there is growing evidence for the contribution of a circulating 25(OH)D level below 50nmol/l to the development of various chronic diseases which are frequent in Western societies.

Current estimations for an adequate oral intake are obviously much too low to achieve an optimal vitamin D status and thus to effectively prevent chronic vitamin D-dependent diseases.