Damage to the myelin sheath (demyelination) is one of the main manifestations of multiple sclerosis (MS). Interestingly, both MS and vitamin B deficiency results in severe myelin degeneration that leads to loss in neuronal signal transmission. Deficiency in vitamin B complex vary, although common symptoms include fatigue, increased oxidative stress, inflammation and demyelination. In particular, vitamin B12 (cobalamin) has triggered an increased attention for its role in the methylation process, involvement in myelination and remyelination and reversal of MS symptoms. Here we discuss the role of vitamin B complex (B1, B2, B3, B4, B5, B6, B7, B9, B12) in MS. The anti-inflammatory and re-myelinating attributes of vitamin B complex members are promising, although with limited clinical studies. Hence, there is an urgent need for larger scope studies to determine the role of vitamin B supplementation alone, or in combination with other therapeutic agents, in prevention or reversal of MS and aid in improved quality of life of MS patients.

Objectives Very limited information is available on the role of vitamin D in skin carcinogenesis. For most individuals, skin cancer can be readily managed with surgery; however, some patients may face life-threatening neoplasia. Sun exposure, specifically UV radiation, is a causative agent for development of skin cancer, though, somewhat ironically, sunlight through the production of vitamin D may have protective effect against some skin cancers. This review focuses on the development and progression of cutaneous carcinogenesis and the role of vitamin D in the prevention of the initiation and progression of lethal skin cancers. Key findings Vitamin D is involved in regulation of multiple signalling pathways that have implications in carcinogenesis. Skin cancer metastasis depends on the tumour microenvironment, where vitamin D metabolites play a key role in prevention of certain molecular events involved in tumour progression. The vitamin D receptor (VDR) is a well-known potent regulator of cellular growth and differentiation. Summary The VDR's possible involvement in cell death, tumour microenvironment and angiogenesis makes it a candidate agent for cancer regulation.

PEDF is a promising antagonist to osteosarcoma cell metastasis via downregulation of MMP-2, and can induce tumour cells to further adopt differentiative properties, thereby possibly reducing their aggressive growth in vitro and in vivo.

The potential protective effects of vitamin D against cutaneous carcinogenesis are still poorly understood. The inhibition, by vitamin D, of various cancers in in vitro and in vivo models has triggered detailed investigation of vitamin D effects on neoplastic behavior. Recent studies highlight that such neoplastic features as the tumor microenvironment, angiogenesis, DNA mutagenesis, and apoptosis are all connected to vitamin D metabolic pathways. This review discusses these connections. Vitamin D modulation of the cell cycle, DNA repair and apoptosis via its receptors (VDRs) may have a suppressive effect on skin cancer as some studies suggest. The regulation of multiple tumor signaling pathways by vitamin D may have an implication in cutaneous carcinogenesis and tumor progression to malignancy.

Running title: Vitamin D enzymes and non-melanoma skin cancer The relationship between vitamin D metabolic enzymes (CYP27A1, CYP27B1, and CYP24A1) and vitamin D receptor (VDR) in non-melanoma skin cancer (NMSC)