Abstract: The neurotropic B vitamins B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) are essential for proper functioning of the nervous system. Deficiencies may induce neurological disorders like peripheral neuropathy (PN) and mainly occur in vulnerable populations (eg, elderly, diabetics, alcoholics). As epidemiologic cohort studies raised safety concerns about vitamin B6/B12 intake being potentially associated with increased risks of hip fracture (HF) and lung cancer (LC), we explored these aspects and performed comprehensive literature searches. However, we suggest not to neglect actual high-risk factors (eg, smoking in LC, higher age in HF) by focusing on individual nutrients, but to examine the complex interaction of numerous factors involved in disease development. Because it warrants continued consideration, we also provide an update on neurotoxicity associated with vitamin B6. We consider that neurological side effects due to vitamin B6 intake are rare and only occur with high daily doses and/or longer treatment duration. The benefit-risk ratio of high-dose treatment with neurotropic B vitamins in indications like PN is therefore considered advantageous, particularly if dosing recommendations are followed and serum levels monitored. Keywords: neurotropic B vitamins, safety, thiamine, pyridoxine, cobalamin, neurotoxicity, hip fracture, lung cancer