Substances and methods of use of substances capable of inhibiting serine-palmitoyltransferase (SPT) and/or capable of competing with L-alanine and glycine, including in the reaction catalysed by SPT, including L-serine and D-serine and other compounds, to suppress cytotoxic sphingolipid metabolites, in particular deoxy-sphingolipids. The substances and methods can be used to prevent and treat disease caused by or associated with elevated levels of deoxy-sphingolipids, namely, diabetes (type 1 and type 2 diabetes), particularly diabetic neuropathy, neurodegenerative diseases such as hereditary and sensory neuropathy type I (HSAN1), amyotrophic lateral sclerosis (ALS), Alzheimer disease, other neurological disorders (e.g. depressive disorders, schizophrenia), medication-induced neuriopathies (e.g. induced by treatment with cytostatics like paclitaxel, cis-platin compounds etc.) and other metabolic disorders such as glycogen storage disease type 1a and asthma.