Vitamin D has been called the “miracle vitamin” by many health experts due to mounting discoveries of its significance in promoting health and fighting numerous diseases, including cancer, heart disease, and diabetes. It may also be therapeutic for neurodegenerative diseases, which may be relevant to Huntington’s disease (HD). This particular vitamin is found in many food sources, including milk, eggs, and fish, and it can also be produced by the skin through sunlight exposure. While vitamin D is widely known for its role in maintaining strong and healthy bones by helping the body absorb calcium, it is much more than a bone-protecting vitamin. Research for the past few decades has shed light on the protective effects of vitamin D on immune and neural cells and has implicated a deficiency of vitamin D as a risk factor for various brain diseases. This article will focus primarily on a form of vitamin D called vitamin D3, also known as cholecalciferol, and how the vitamin may be protective against neurodegenerative diseases such as HD.
What is vitamin D?^
The term “vitamin D” actually refers to a group of fat-soluble vitamins. There are five different forms of vitamin D, but the two major forms are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D2 is produced by plants, while vitamin D3 is produced by the skin of animals in response to sunlight (UV light) exposure. UV light reacts with an enzyme called 7-dehydrocholesterol to create pre-vitamin D, which rearranges its structure to form vitamin D3. An enzyme then converts vitamin D3 into a compound called calcitriol, which is the active form of vitamin D that is responsible for the numerous health benefits.
What is its mechanism of action?^
After its conversion from Vitamin D3, calcitriol exerts its effects on the body by binding to and activating vitamin D receptors (VDRs), which are located in the nuclei of target cells. Once activated, VDRs can function as transcription factors that bind to cellular DNA and control gene expression, ultimately triggering a biological response.
The major physiological role of vitamin D is to facilitate the intestinal absorption of calcium, by stimulating the expression of proteins involved in calcium transport. Vitamin D also plays a crucial role in providing the proper balance of minerals necessary for bone growth and function. However, it turns out that VDRs are present in the cells of most organs in the body, suggesting that there is wide diversity in the types of responses that vitamin D3 can promote.
Vitamin D3 and the brain^
Initially it was believed that only the liver and kidneys contained the enzyme responsible for producing calcitriol from vitamin D3. It is now known that many tissues, including the brain, contain this enzyme. In addition, VDRs are widely present throughout the brain, implicating vitamin D3 as a contributor to a variety of neural processes. Several of these processes are thought to be neuroprotective.
Studies have indicated that calcitriol may possess antioxidant properties and also strengthens the role of existing antioxidants in the body. For instance, Garcion et al. (1997) demonstrated that calcitriol acts similarly to traditional antioxidant nutrients by inhibiting an enzyme called inducible nitric oxide synthase (iNOS), which is overactive in patients with Alzheimer’s and Parkinson’s disease. Baas et al. (2000) showed that calcitriol increases levels of glutathione, a natural antioxidant which protects oligodendrocytes, which are brain cells that provide support and insulation for neurons.
Calcitriol can also protect neurons by producing neurotrophins, including neurotrophin-3 (NT-3), glial cell derived neurotrophic factor (GDNF), and nerve growth factor (NGF) that promote the survival of neurons in aging and with neurological injury. As shown in studies by Naveilhan et al. (1993) and Neveu et al. (1994), calcitriol increases levels of GDNF and NT-3. NT-3 protects nerve transmission and synaptic plasticity, and GDNF influences the survival and differentiation of dopamine-producing cells. In animal models of Parkinson’s disease, treatment with calcitriol increased GDNF levels and reduced oxidative stress (Wang et al., 2001). On the other hand, in newborn rodents, depleting vitamin D3 while they were in their mother’s uterus reduced levels of GDNF and NGF and caused damaging structural brain changes (Becker et al., 2005). (To read more about neurotrophins, click here.)
Vitamin D3 and neurodegenerative disorders^
While there has not been much research focused on its potential role in HD, vitamin D3 deficiency has been implicated as serving a role in a number of neurodegenerative disorders.
For instance, there is compelling evidence that low levels of vitamin D3 are a risk factor for multiple sclerosis (MS), a disease in which the immune system attacks the central nervous system and causes demyelination and axon degeneration. The prevalence of MS is linked with decreasing exposure to solar UV radiation, and a study by Munger et al. suggests that high circulating levels of vitamin D3 correspond to a lower risk of MS.
There is also evidence that vitamin D3 deficiency is relevant for Parkinson’s disease and Alzheimer’s disease. The greatest number of VDRs are found in the substantia nigra, the portion of the brain that primarily degenerates in Parkinson’s disease and can also be affected in HD. Treating substantia nigra neurons with vitamin D3 protects them from Parkinson-like insults (Shinpo et al., 2000). In Alzheimer’s disease, a condition characterized by dementia and neuron loss in the hippocampus, some evidence suggests that there may be a vitamin D3 deficiency early in the disease (Landfield et al., 1991), and, in aging rats, treating with calcitriol reduced hippocampus shrinkage and prevented decreases in neuron density (Landfield and Cadwallader-Neal, 1998). Although more extensive research into this area is needed, these results suggest that vitamin D3 could have a potential role in the prevention of neurodegenerative disorders.
Despite the many exciting findings about this “miracle vitamin” over the years, determining the many health benefits of vitamin D3 is still an active area of research. While the extent to which vitamin D3 contributes to neural processes is not clearly understood, there is currently much evidence to support a neuroprotective role for vitamin D3 in the brain, as well as promising evidence that it may have preventative effects against neurodegenerative disorders.
Becker, Axel et al. “Transient prenatal vitamin D deficiency is associated with subtle alterations in learning and memory functions in adult rats.” Behavioural brain research 161.2 (2005): 306–312.
Garcion, E et al. “1,25-Dihydroxyvitamin D3 inhibits the expression of inducible nitric oxide synthase in rat central nervous system during experimental allergic encephalomyelitis.” Brain research. Molecular brain research 45.2 (1997): 255–267. Print.
Landfield, P W et al. “Phosphate/calcium alterations in the first stages of Alzheimer’s disease: implications for etiology and pathogenesis.” Journal of the neurological sciences 106.2 (1991): 221–229. Print.
Landfield, P W, and L Cadwallader-Neal. “Long-term treatment with calcitriol (1,25(OH)2 vit D3) retards a biomarker of hippocampal aging in rats.” Neurobiology of aging 19.5 (1998): 469–477. Print.
Shinpo, Kazuyoshi et al. “Effect of 1,25-dihydroxyvitamin D3 on Cultured Mesencephalic Dopaminergic Neurons to the Combined Toxicity Caused by L-buthionine Sulfoximine and 1-methyl-4-phenylpyridine.” Journal of Neuroscience Research 62.3 (2000): 374–382. Web. 7 Apr. 2013.
Wang, J Y et al. “Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats.” Brain research 904.1 (2001): 67–75. Print.
J. Nguyen 2013