Peptides for Energy: What the Mitochondrial Claims Rest On

“Energy” is the vaguest claim in this field and the hardest to test. It can mean subjective alertness, exercise capacity, mitochondrial ATP production or absence of fatigue — and these are measured entirely differently, with results that do not necessarily agree.

The compounds sold for it fall into three groups with different amounts of evidence behind them.

MOTS-c

MOTS-c is a mitochondrial-derived peptide — encoded in mitochondrial rather than nuclear DNA, which is genuinely unusual. The 2015 Cell Metabolism paper that introduced it described effects on metabolic homeostasis, obesity and insulin resistance in mice.

A 2024 systematic review and meta-analysis examined the correlation between mitochondrial-derived peptides and metabolic states in humans — an observational relationship between circulating levels and metabolic status.

See the MOTS-c dosage guide and MOTS-c side effects guide.

SS-31 (elamipretide)

SS-31 is the one compound in this group that has been through real clinical trials. Under the name elamipretide it has been studied in mitochondrial disease — targeting cardiolipin in the inner mitochondrial membrane, which is a specific and testable mechanism.

See the SS-31 guide.

NAD+ and its precursors

NAD+ is not a peptide. It is a coenzyme central to cellular redox reactions, and it declines with age — which is the basis of the entire category.

• The decline is real and well documented.

• Whether raising it reverses anything is a much less settled question, and the human trial evidence is mixed and mostly small.

• Route matters enormously. NAD+ is a large, charged molecule with poor oral bioavailability, which is why injection and IV protocols exist at all.

• It is dosed in hundreds of milligrams, so the low per-milligram price does not make it cheap per use. See the cost guide.

The NAD+ injection guide covers this in detail.

The measurement problem

Every compound here is sold against a subjective outcome, and subjective outcomes in an unblinded, self-administered context are the most placebo-responsive endpoints that exist.

The alternative explanations

Before attributing fatigue to mitochondrial function, the common and treatable causes are worth excluding — because they are far more prevalent and actually respond to treatment:

1. Iron deficiency and anaemia, particularly in menstruating women.

2. Thyroid dysfunction.

3. Sleep apnoea and sleep debt.

4. Vitamin D and B12 status.

5. Depression, which commonly presents as fatigue.

6. Medication effects.

Each of these has a test and a treatment. None of the compounds above has either. A basic panel is the cheaper first step by a wide margin.