Modulation of Human Hydrogen Sulfide Metabolism by Micronutrients, Preliminary Data

BACKGROUND: Hydrogen sulfide (H(2)S) is a pivotal gasotransmitter networking with nitric oxide (NO) and carbon monoxide (CO) to regulate basic homeostatic functions. It is released by the alternative pathways of transulfuration by the enzymes Cystathionine Beta Synthase (CBS) and Cystathionine Gamma Lyase (CSE), and by Cysteine AminoTransferase (CAT)/ 3-Mercaptopyruvate Sulfur Transferase (3MPST). A non-enzymatic, intravascular release is also in place. We retrospectively investigated the possibility to modulate the endogenous H(2)S release and signaling in humans by a dietary manipulation with supplemented micronutrients (L-cystine, Taurine and pyridoxal 5-phopsphate/P5P). METHODS: Patients referring for antiaging purposes underwent a 10-day supplementation. Blood was collected at baseline and after treatment and the metabolome was investigated by mass spectrometry to monitor the changes in the metabolites reporting on H(2)S metabolism and related pathways. RESULTS: Data were available from 6 middle aged subjects (2 women). Micronutrients increased 3-mercaptopyruvate (P = .03), reporting on the activity of CAT that provides the substrate for H(2)S release within mitochondria by 3MPST, decreased lanthionine (P = .024), reporting the release of H(2)S from CBS, and had no significant effect of H(2)S release from CSE. This is compatible with a homeostatic balancing. We also recorded a strong increase of reporters of H(2)S-induced pathways including 5-MethylTHF (P = .001) and SAME (P = .022), reporting on methylation capacity, and of BH4 (P = .021) and BH2 (P = .028) reporting on nitric oxide metabolism. These activations may be explained by the concomitant induction of non-enzymatic release of H(2)S. CONCLUSIONS: Although the current evidences are weak and will need to be confirmed, the effect of micronutrients was compatible with an increase of the H(2)S endogenous release and signaling within the control of homeostatic mechanisms, further endorsing the role of feeding in health and disease. These effects might result in a H(2)S boosting effect in case of defective activity of pathologic origin, which should be checked in duly designed clinical trials.