Mikkelsen, Kathleen ORCID: 0000-0001-9166-4109 (2022) The Effects of Vitamin B6 and B12 on Inflammation and Cancer. PhD thesis, Victoria University.

Abstract

We are only just beginning to understand the intricate relationship between nutrition, immune health, inflammation, and cancer. Epidemiological studies have demonstrated a clear association between inflammation and cancer development. Both undernutrition and overnutrition (malnutrition) have been shown to have a significant impact on immune health and function. Even in countries where food is plentiful, a diet high in processed food can be high in calories whilst being nutritionally deficient. The emergence of B vitamins as anti-inflammatory and anti-cancer agents is an area which in recent years has gained interest within the scientific community and as the development of genetic and epigenetic investigative techniques becomes more available to a greater number of researchers, there is ongoing investigation occurring concerning how nutrition affects gene expression. Low blood serum vitamin B6 is frequently noted in patients with high inflammatory markers and vitamin B6 supplementation has previously been shown to downregulate inflammation and oxidative stress in both inflammation and as an anti-cancer mechanism. In contrast, the effects of vitamin B12 supplementation have been shown within the literature to be ambiguous with links both to cancer progression and pro-inflammatory actions versus tumour regression and anti-inflammatory properties. The purpose of this thesis was to ascertain, with greater clarity, the mechanisms of action of high dose vitamin B6 and B12 on inflammation and cancer. This was achieved by conducting studies on both cancer and immune cells and using protein and gene studies to ascertain the effects of high-dose vitamin B supplementation. It was found that high dose vitamin B6 was shown to have an anti-proliferative effect on promonocytic lymphoma cells, likely due to a downregulation of the mevalonate pathway (MVP) whereby vitamin B6 acted in a ‘steroid-like' fashion to reduce MVP, restoring mutant p53 function and re-establishing the G1/S checkpoint. Vitamin B6 2 was also shown to have a broad-spectrum, anti-inflammatory effect on key inflammatory pathways in lipopolysaccharide (LPS) stimulated monocytes. In contrast, vitamin B12 supplementation produced an upregulation in key inflammatory gene expressions and showed a dose-dependent effect on inflammation. The important and novel findings from this thesis conclude, that high dose vitamin B6 may prove to be an important nutraceutical agent in both inflammatory and oncological medicine and that B12 over-supplementation may potentially contribute to inflammation and tumourigenesis so caution should be taken when supplementing in dosages above the recommended daily intake.

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