The Effects of Neurotropic B Vitamins, Vitamin D3, and Alpha-Lipoic Acid in In Vitro Models of Neurodegeneration

Background: Peripheral neuropathy (PN) is one of the most common disorders of the peripheral nervous system, affecting around 10% of the general adult population. PN results in pain, paraesthesia, and sensory loss, negatively impacting patients’ quality of life. The condition is characterised by damage to peripheral nerves and is often linked to risk factors, among which diabetes is the most common cause. The incidence rate of patients suffering from PN has significantly increased in the last three decades, yet there are currently no pharmacological treatments to reverse or prevent the development of PN. Therefore, neurotropic B vitamins, specifically vitamins B1, B6, and B12, which are essential for protecting nerves from damage, nerve regeneration, and maintaining nerve health, are promising treatment options. Other biofactors with therapeutic potential are vitamin D3, which has been described as a regulator of neuroplasticity and neuroinflammation with indications to promote neuronal regeneration following injury, as well as alpha-lipoic acid (ALA), a well-described treatment option in PN. Methods: The regenerative capacity of vitamins B1, B6, B12, and D3 and ALA was determined following neurite degeneration in vitro induced by either hydrogen peroxide (H2O2) or homocysteine. Results: In line with previous studies, the results show that a combination of vitamins B1, B6, and B12 has a significantly better effect on neurite extension following homocysteine-induced degeneration. In H2O2-insulted neural cells, the combination of all three neurotropic B vitamins was also shown to be superior to that of individual B vitamin treatment, demonstrated by longer neurite length after insult. Vitamin D3 also demonstrated a neuro-regenerative effect on neurites in healthy and insulted neural cells, whereas ALA only appears to provide a protective effect, preventing ongoing damage and supporting neurite outgrowth in healthy cells. No synergistic effects were seen with any treatment combinations. Conclusions: We have established an in vitro model of homocysteine-induced degeneration, and using this model alongside H2O2-induced degeneration, we provide evidence of the neurite regenerative capacity of vitamins B1, B6, B12, and D3.