what can I do to promote mitochondrial health?

The short version: exercise is the most proven lever for mitochondrial health, and carbohydrate restriction shows strong supporting evidence, but the studies that would settle the question for a healthy person are thin.

The evidence here is dominated by exercise studies, and they are consistent. A single bout of high-intensity interval training increases the nuclear abundance of PGC-1α, the master regulator of mitochondrial biogenesis, by 66% at three hours of recovery, and drives a 750% increase in PGC-1α mRNA [4]. High-volume training raises citrate synthase activity by about 50% and mitochondrial respiration by 44%, but those gains reverse rapidly when training volume drops [3]. A 2025 rat study confirms that HIIT reverses the mitochondrial damage from a high-fat diet, increasing fusion genes (Mfn2, Opa1) and decreasing fission genes (Drp1, Fis1) [2]. The mechanism is well-established: exercise creates a demand signal that forces the cell to build more and better mitochondria.

Dietary carbohydrate restriction appears to work through a different route. In a 12-week randomized trial, a carbohydrate-restricted diet (about 45 grams per day) produced a 51% drop in fasting triglycerides, a 13% rise in HDL, and a 54% reduction in the triglyceride-to-HDL ratio, compared to minimal changes on a low-fat diet [17]. These are markers of improved metabolic health, which correlates with mitochondrial function. A 2011 study in people with fatty liver found that carbohydrate restriction reduced liver fat by 42% versus 28% with calorie restriction alone, and raised plasma ketones more than twofold [10]. Ketones are a cleaner fuel for mitochondria and reduce oxidative stress.

Fish oil supplementation also shows promise. In a mouse model, fish oil increased mitochondrial fusion proteins (Mfn2, Opa1), decreased the fission protein Fis1, and improved complex I and II activity by about 23-26% [19]. It also cut mitochondrial ROS by 52% and doubled NO bioavailability [19]. But this is a mouse study on a high-fat diet background, not a human trial.

What is missing: no study here directly measures mitochondrial function in a healthy person before and after a dietary intervention. The exercise evidence is strong for muscle mitochondria. The diet evidence is strong for metabolic markers that imply mitochondrial improvement. The sleep evidence is weak: one small study (43 people) found that lower sleep efficiency correlated with a lower Bioenergetic Health Index, but that is correlational [20].

My call: exercise, especially HIIT, is the most proven intervention for mitochondrial health. Carbohydrate restriction and fish oil are reasonable adjuncts supported by metabolic markers but not by direct mitochondrial measurements in healthy humans. The evidence for sleep is too thin to act on. Confidence: moderate for exercise, low for diet and supplements.