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Vitamin D, nervous system, and aging

Written by: Ana Iturbides, Health Writer, Acupuncture Atlanta

P. Tuohimaa, T. Keisala, A. Minasyan, J. Cachat, A. Kalueff

        Scientists’ knowledge regarding the effects of Vitamin D3 has increased significantly in recent decades. This vitamin is essential in providing the human hormonal system with a precursor to producing calcipherol hormones, which are active metabolites. Calcipherol hormones include calcidiol, which is primarily synthesized in the liver and skin. This group also includes calcitriol, which is synthesized in the kidney and other tissues, and 24-calcitriol, which is synthesized in various tissues (Tuohimaa et al., S278). It has been hypothesized that all hydroxylated forms of calcipherol can bind to the Vitamin D receptor (VDR) to regulate gene expression (Tuohimaa et al, S278).
        Hormonal systems are dependent on endogenous supplies of Vitamin D3. In particular, the calcipherol hormone system is dependent on exogenous sun-induced or dietary Vitamin D3. The thyroid is dependent on dietary iodine and retinoic acid is dependent on dietary Vitamin A. Scientists also believe that calcipherol hormones are not only important for bone development, but are also instrumental in preventing the onset of several diseases related to aging (Tuohimaa et al., S279). Endocrinological feedback mechanisms have been shown to balance the effect of calcipherol hormones in the body.
        The endocrinology community has widely accepted the fact that circulating calcitriol is an active hormone, while calcidiol must be activated within the cell by 1a-hydroxylase. This view, however, is in conflict with several important recent findings. The authors suggest a model for calcipherol hormone action in which calcidiol actively circulates with 24-calcitriol; both work with calcitriol on target cells. The authors claim that their hypothesis will help scientists understand why serum calcidiol is associated with chronic aging-related diseases and Vitamin D treatment.

2. U-shaped risk of chronic diseases to serum calcidiol
        Evidence that both high and low serum calcidiol concentrations are associated with a variety of chronic diseases has accumulated in recent years. For example, a study of 20,000 Nordic men showed that prostate cancer and serum calcidiol levels are related in a U-shape (Tuohimaa et al., S279). Other epidemiological cancer and cardiovascular disease studies support these findings by showing a U –shaped relationship. As the body ages, an increase in overall body fat leads to a larger distribution volume for fat-soluble calcidiol. This causes many patients to appear Vitamin D deficient, when in fact they have adequate levels in their bodies.

3. Calcipherol hormones and diseases of the central nervous system
        Evidence also suggests that calcipherol hormones play an integral role in human brain function. This hormone is expressed in neurons and glial cells and is part of a neuro-active compound that regulates behavioral functions such as anxiety. This same compound has also been associated with multiple sclerosis, seasonal affective disorder, and Alzheimer’s. Mood and cognitive performance also appear to be linked to Vitamin D. Calcipherol hormone insufficiency can lead to aging-related diseases such as osteoporosis, cancers, muscle weakness, respiratory infections, autoimmune disease, hypertension, cardiovascular disease, and congestive heart failure (Tuohimaa et al., S280). Hypovitaminosis D has also been shown to be fatal.

4. Calcipherol hormones and aging of the central nervous system
        Aging causes the cutaneous production of calcipherol hormones to decrease in elderly people, thus increasing the rate of metabolic clearance due to a high expression of 24-hydroxylase. Additionally, elderly people are less exposed to sunlight. This makes Vitamin D3 deficiency more common in the population. The precise role of calcipherol hormones in aging has yet to be explored thoroughly. Because gene expression changes in aging neurons, it is generally hypothesized that the mechanisms underlying CNS aging involve “genomic instability, neuroendocrine dysfunction, production of oxidative compounds, altered calcium metabolism, and inflammatory neuron damage” (Tuohimaa et al, S281). Calcipherol hormones and VDR are involved in regulating most of these aging mechanisms.
        Calcitriol and Vitamin D3 have been shown to counteract negative aging-related effects in the body. For example, after experimentally induced ischemia, calcitriol was shown to increase the activity of glial heme exygenase-1, which is an enzyme responsible for converting free heme into powerful antioxidants (Tuohimaa et al., S281). Vitamin D metabolites also assist in various neuronal-glial cell pathways that support calcipherol hormones in waste management.
        Vitamin D deficiency has been suggested as a primary indicator in the development of autoimmune diseases such as Crohn’s Disease, rheumatoid arthritis, and inflammatory bowel disease. The authors have also discovered important support to the Vitamin D-CNS aging hypothesis by conducting a study using two strains of the Vitamin D receptor on mice and studying behavioral, biological, and morphological effects.
5. Both hypervitaminosis D3 and hypovitaminosis D3 cause premature aging
        Fibroblast growth factor 23 (FGF-23) hormone has emerged in the last decade as a mediator in aging. Its effects appear to be lessened by an excess of calcitriol. Symptoms of early aging as a result of the presence of FGF-23 include thin skin, intestinal atrophy, spleen atrophy, muscle atrophy, weight loss, short life prognosis, osteoporosis, and atherosclerosis (Tuohimaa et al., S281). Many of these effects were seen in mice that were given the Vitamin D receptor knockout strain.
        Due to the physiological regulation of hormones, hypervitaminosis D3 is rare in humans. However, hypervitaminosis D3 has been proven to cause premature aging. These effects were seen in post-World War II Europe, where many children were given extremely high doses of Vitamin D3. In adulthood, these children experienced symptoms identical to those brought about by FGF-23 earlier than other adults in their same age group. Because the phenotypes of hypovitaminosis mice are similar to those of hypervitaminosis D3, the authors conclude that both a lack and an excess of calcipherol hormones are responsible for enhanced aging. Aging shows a U-shaped response curve to calcipherol hormone concentrations, meaning that normovitaminosis D3 is important for delaying aging.

6. Conclusion
        Hormonal forms of Vitamin D appear to delay symptoms of aging-related diseases. Determining the optimal serum concentration of calcidiol is an important question for the preventive medicine community (Tuohimaa et al., S282). The U-shaped relationship between hypovitaminosis, hypervitaminosis D3, and aging shows that an excess or shortage of calcipherol speeds the effects of aging.

[1.] Tuohimaa, P., Keisala, T., Minasyan, A., Cachat, J., and Kalueff, A. “Vitamin D, nervous system, and aging”. Psychoneuroendocrinology 34S (2009); S278-S286.         

This article was published on 01/05/2011 21:12.
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