Turbo-Farmer said:
miameow said:
Turbo-Farmer said:
chewonmysac said:
8mg EOD MOTS-c is what I go with, alternating with NAD+ 100mg. Fasted, both in the AM pre workout. After lunch, SS31 10mg daily. Optimal is what my mitochondria is now. 6 months of running so far.
Have you run that calculation yourself,
HOMA-IR (the Homeostatic Model Assessment for Insulin Resistance)
as a way to gauge mitochondrial function?
What HOMA-IR actually tells you is how well your cells respond to insulin — nothing more. It is derived purely from fasting glucose plus fasting insulin. So while poor mitochondrial function often travels with insulin resistance, that does not turn HOMA-IR into a readout of mitochondrial health. The two can move together without one driving the other.
chewonmysac said:
Turbo-Farmer said:
chewonmysac said:
8mg EOD MOTS-c is what I go with, alternating with NAD+ 100mg. Fasted, both in the AM pre workout. After lunch, SS31 10mg daily. Optimal is what my mitochondria is now. 6 months of running so far.
Have you run that calculation yourself,
HOMA-IR (the Homeostatic Model Assessment for Insulin Resistance)
as a way to gauge mitochondrial function?
Labs came back today and my HOMA-IR landed at .80, right in the range it should be.
chewonmysac said:
Turbo-Farmer said:
chewonmysac said:
Turbo-Farmer said:
chewonmysac said:
8mg EOD MOTS-c is what I go with, alternating with NAD+ 100mg. Fasted, both in the AM pre workout. After lunch, SS31 10mg daily. Optimal is what my mitochondria is now. 6 months of running so far.
Have you run that calculation yourself,
HOMA-IR (the Homeostatic Model Assessment for Insulin Resistance)
as a way to gauge mitochondrial function?
Labs came back today and my HOMA-IR landed at .80, right in the range it should be.
That's great news — sounds like your mitochondria are already running well enough that extra MOTS-c may not add all that much.
Taking a 90-day break from MOTS-c starting now. This past week I kept crashing after lunch and could not work out which compound was responsible — ruling things out one at a time, MOTS-c was the one. Once my body has had its fill of it, homocysteine starts climbing, which is the usual pattern for me. NAD+ every other day and SS-31 daily will carry on as before. Being a lab rat is a grind.
Good to know — thanks for laying that out. Mine comes in at 0.5, and even so I would swear the daily MOTS-c (5mg) is doing something for me. NAD+ is the awkward one in my case: it flattens me, so I handle it with real caution. Looks like my experience is nearly the mirror image of yours.
Where the Mitochondria Jam Up
Skeletal muscle and the liver are where this mostly plays out. Under normal conditions their mitochondria oxidise fatty acids and glucose into ATP. But once the incoming fuel — especially fats and refined carbs — outpaces what the cell actually needs in ATP, the electron transport chain starts to queue up.
Once the fuel arriving outruns what the mitochondria can process, a chain of events follows:
1. Beta-oxidation stalls: fatty acids enter the process but the mitochondria cannot carry them through to completion.
2. Lipid spillover turns toxic: partially oxidised fatty acids escape into the intracellular space as lipotoxic intermediaries — Diacylglycerols (DAGs) and Ceramides in particular.
3. Signalling gets blocked: DAGs and ceramides are deeply disruptive. They switch on stress enzymes such as Protein Kinase C (PKC), which in turn phosphorylates the Insulin Receptor Substrate 1 (IRS-1) at the wrong residue — serine where tyrosine was needed.
What That Shows Up As: An Elevated HOMA-IR
With IRS-1 chemically altered by the lipid spillover, insulin can no longer get through to it — it has effectively gone deaf.
Insulin still docks at the receptor on the cell surface, but the downstream signal that would move the glucose channels into place (GLUT4 translocation) never arrives. The pancreas responds by pouring out large volumes of compensatory insulin to shove glucose out of the bloodstream and into a cell that is resisting it.
That mechanism is precisely what a fasting lab panel captures. An elevated HOMA-IR is a strong hint that hepatic and muscle mitochondria are overloaded in practice and are leaking DAGs and ceramides as a result.
If insulin resistance is at root a mitochondrial problem, then bringing a HOMA-IR down comes back to two levers: cut the substrate arriving at the mitochondria (fasting, a calorie deficit), or raise how fast they burn.
Hence the intense clinical appetite for agents that push mitochondria to spend energy. Drugs that activate AMPK — prompting fresh, healthy mitochondria to be built — or that act as uncouplers, deliberately wasting the proton gradient as heat to force mitochondria through a lipid backlog, can clear intracellular DAGs quickly and bring insulin sensitivity back.
