I could definitely experience some anti-depressive effect with both niacin and vinegar (so far with diluted apple cider and balsamic vinegar) and the following are the most likely reason for it. I have to note though that I did not find useful a regular dose of apple cider capsules or L-valin. Even so regular consumption of vinegar may improve depression and could potentially increase lifespan through increasing niacinamide and decreasing L-isoleucine.
Metabolomics analyses revealed increased nicotinamide concentrations and upregulation of the NAD+ salvage pathway for VIN (vinegar consuming) participants compared to controls, metabolic alterations previously linked to improved mood.
The metabolites that most significantly differentiated the groups over time were isobutyric acid, nicotinamide, glutathione, and L-isoleucine. The raw data revealed that niacinamide and L-isoleucine displayed the greatest change during the trial for VIN participants, +86% and ?35% respectively, and these changes were inversely correlated.
When NAD+ is consumed, nicotinamide and adenosine diphosphate ribose are generated, a reaction catalyzed by NAD nucleosidases, metabolite sets noted in the enrichment analyses herein. The conversion of NAD+ to nicotinamide activates sirtuins (e.g., sirtuin-1) and poly[ADP-ribose] polymerases (PARPs), which promote mitochondrial biogenesis, energy expenditure, and antioxidant defenses and DNA repair, respectively. In the brain, mitochondrial quality is linked with reduced risk of neurodegenerative diseases, and emerging evidence suggests that sirtuins play a key role in orchestrating this balanced mitochondrial fusion and fission. Moreover, the PARPs protect neurons from the oxidative stress commonly generated in vivo during metabolic activities. Nicotinamide is readily converted back to NAD+ in a recycling system known as the salvage pathway. Since the cellular requirement for the NAD+ cofactor is greater than that which can be endogenously generated, this salvage pathway has critical significance for cellular energetics and neuroprotection.
Thus, it is plausible that acetic acid ingestion enhances the NAD+ salvage pathway, elevates sirtuin and PARP activity, and promotes mitochondrial biogenesis and cell integrity in the brain.https://www.mdpi.com/2072-6643/16/14/2305Valin and leucine was negatively associated with depression, while isoleucine was not associated or positively associated, although to a lesser extent.
https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.935858/fullRestricting dietary isoleucine increased the lifespan and healthspan of the mice, reduced their frailty, and promoted leanness and glycemic control. Male mice had their lifespans increased 33 percent compared to those whose isoleucine was not restricted, and females had a 7 percent increase.
These mice also scored better in 26 measures of health, including muscle strength, endurance, blood sugar levels, tail use, and hair loss.
The male mice in this group had less age-related prostate enlargement, and were less likely to develop the cancerous tumors that are common in the diverse mice strains.
Curiously, the mice given low isoleucine food also ate significantly more calories than the others. But rather than gaining weight, they actually burned more energy and maintained leaner body weights, even though their activity levels were no different.https://www.sciencealert.com/cutting-back-on-one-amino-acid-increases-lifespan-of-mice-up-to-33
