Margreet Vissers

The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent.

Identifying how specific nutrients can impact fertility, pregnancy, and neonatal outcomes will yield important insights into the biological mechanisms linking diet and reproductive health. Our study investigates how dietary vitamin C intake affects various fertility parameters and pregnancy and neonatal outcomes in the guinea pig, a natural model of vitamin C dependency. Dunkin Hartley guinea pigs were fed an optimal (900 mg/kg feed) or low (100 mg/kg feed) vitamin C diet ad libitum for at least three weeks prior to mating and throughout pregnancy. We found that animals receiving the low vitamin C diet had an increased number of unsuccessful matings, a higher incidence of foetal reabsorption, and, among pregnancies resulting in delivery at term, produced fewer offspring. Neonates from mothers on the low vitamin C diet had significantly decreased plasma vitamin C concentrations at birth and exhibited mild growth impairments in a sex-dependent manner. We conclude that a diet low of vitamin C induces a state of subfertility, reduces overall fecundity, and adversely impacts both pregnancy outcomes and growth in the offspring. Our study provides an essential foundation for future investigations to determine whether these findings translate to humans. If so, they could have important clinical implications for assisted reproductive technologies and nutritional recommendations for couples trying to conceive, pregnant women, and breastfeeding mothers.