Metabolic therapy of heart failure: which role for B vitamin

Heart failure (HF) is a major cause of death worldwide. It is clear that profound modulations of energy metabolism are involved in the development of this disease since major disruptions of mitochondrial functions were described. This disease is also associated with alteration of metabolic products and enzymes in mitochondrial ATP generation. The link has to be considered for understanding the metabolic myopathy in HF and ultimately for the development of a metabolic therapy of HF. In order to develop such a therapy, we previously showed, in a model of HF, the protective effect of a food supplementation with the vitamins (B3, B9, and B12), which seem to have a synergistic beneficial effect on restoring metabolic function. Inasmuch as the effects of these treatments were assessed before the appearance of the first symptoms of HF in these studies, we propose in the present project to test the efficiency of a treatment with a cocktail of these B vitamins in HF in order to propose an eventual curative use of these compounds. Considering the sex differences in cardiovascular diseases and in treatment responses, biological sex differences will be one of central point of this project.

The Effects of B-vitamins on Heart Failure Heart failure (HF) is a serious condition where the heart struggles to pump blood effectively, leading to significant health complications and reduced quality of life. Our study investigated whether a combination of three B vitamins-B3, B9, and B12-could improve outcomes in heart failure, focusing on survival rates, heart function, and cellular processes. While the findings showed limited benefits in some areas, they provided valuable insights that could help tailor future treatments to individual patients. Our study was conducted on a large group of mice in which heart failure was induced through a targeted surgical procedure that narrowed the aorta. A smaller control group with healthy hearts served as a comparison. Mice that developed clear heart failure as a result of this procedure were divided into two groups: one received treatment with a combination of vitamins B3, B9, and B12, while the other remained untreated. Over a period of 20 weeks, we monitored survival rates and conducted regular assessments of heart function. Overall, the B vitamin combination did not significantly improve survival rates. While some initial benefits were observed, these effects were inconsistent across the study. This suggests that these vitamins alone may not directly enhance survival in heart failure. In terms of heart function, heart ultrasound measurements were performed to measure how well the heart pumped blood and how its size changed over time. Surprisingly, treated animals showed faster declines in heart function and greater increases in heart size compared to untreated animals. These findings indicate that the combination of B3, B9, and B12 may influence how the heart adapts to stress, though not necessarily in a positive manner. On a cellular level, we examined heart muscle cells to understand these changes. Cells in failing hearts were abnormally large, with enlargement patterns differing between males and females. Treated animals showed partial improvements in important calcium-related cellular processes-calcium being crucial for heart contraction-particularly in males. However, other key functions remained unchanged upon vitamin treatment. In conclusion, the tested combination of B3, B9, and B12 did not provide clear overall benefits for heart failure. However, the study highlighted important differences in how male and female hearts respond to treatment. This underscores the need for personalized approaches to managing heart failure. A deeper understanding of these underlying processes could lead to more targeted therapies in the future.