Mitochondrial peptides (5-Amino-1MQ, SS-31, and MOTS-c, et al), work in essentially two ways. They either increase mitochondrial function and activity, increase the number of mitochondria in the cell, or both.
SS-31 is a peptide found “in the inner membrane of mitochondria,, an area where free radicals are produced. Animals studies have shown that SS-31 reduces free radical production and decreases oxidative stress, improving diseases stemming from mitochondria dysfunction.” SS-31 is also an orphaned drug, so due to patent status, it is not readily available for use.
These peptides can be synergized by supplementation with CoQ10, PQQ, and Forskolin to increase mitochondrial biogenesis and activity.
Photobiomodulation with 660 and 850nm wavelengths can improve mitochondrial function in brain, muscle, and organ tissues. [5]
- CoQ10, and PQQ may work synergistically with 5 amino 1mq to improve neurological function and increase energy turnover.[1][2]
- PQQ Pyrroloquinoline Quinone works synergistically stimulate Mitochondrial Biogenesis through cAMP Response Element-binding Protein Phosphorylation and Increased PGC-1α Expression.[3]
- Forskolin increases the number of mitochondria and their activity.[4]
Creatine may be used to increase power output by an increase ATP, another metabolic product that is the result of the citric acid cycle which takes place in the mitochondria.[7]
Niacin and its derivative NMN may also be used synergistically increase mitochondrial NAD(P)H production under higher workload.[8][9]
“Although NMN and SS‐31 both target mitochondria, they do so via different mechanisms of action. Thus, we hypothesized that the drugs would differ in effect on the heart and may have a synergistic effect when applied together. We sought to compare and contrast the mechanism and effects of these drugs in order to better understand each individually and how age‐related deficits in heart function can be addressed.”
“Niacin, after undergoing biochemical reactions in the mitochondria with nicotinamide, and tryptophan forms nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP). NAD and NADP are the active forms of niacin which, when reduced to NAD(H) and NADP(H) respectively, participates in catabolic redox reactions and are cofactors in anabolic redox reactions.” [8][9]
When niacin is metabolized, it uses a methyl group. This can be offset by supplementation of 200–400mg Sam-e, a methyl donor. Sam-e also restores intracellular GSH stores, especially in mitochondria.[10]
[1] Coenzyme Q10 Supplementation and Exercise in Healthy Humans: A Systematic Review
[2] Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects
[3] Pyrroloquinoline Quinone Stimulates Mitochondrial Biogenesis through cAMP Response Element-binding Protein Phosphorylation and Increased PGC-1α Expression
[4] Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro
[5] Effects of photobiomodulation on mitochondria of brain, muscle, and C6 astroglioma cells
[6] Far red/near infrared light-induced protection against cardiac ischemia and reperfusion injury remains intact under diabetic conditions and is independent of nitric oxide synthase
[7] Creatine supplementation with specific view to exercise/sports performance: an update
[8] Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure
[9] SS‐31 and NMN: Two paths to improve metabolism and function in aged hearts
[10] Synergistic protection by S-adenosylmethionine with vitamins C and E on liver injury induced by thioacetamide in rats