energy metabolism15 options reviewed

What actually helps with chronic fatigue

Persistent, unexplained tiredness lasting weeks or months that is not relieved by rest and significantly impairs daily functioning.

CoQ10
antioxidantwith_food
Strong

CoQ10 is essential for mitochondrial electron transport chain function, directly participating in ATP synthesis. Ubiquinol also protects mitochondrial membranes from oxidative damage. Fatigue patients often show depleted CoQ10 levels.

Dose: 100–300 mg

Iron
mineralempty_stomach
Strong

Iron is essential for hemoglobin (oxygen transport) and myoglobin (muscle oxygen storage). It is also a cofactor in mitochondrial cytochrome enzymes for ATP production. Iron deficiency is the most common cause of correctable fatigue worldwide.

Dose: 18–36 mg

Vitamin D
vitaminmorning
Strong

Vitamin D receptors are present in skeletal muscle mitochondria. Vitamin D supports mitochondrial function, reduces inflammatory cytokines (IL-6, TNF-alpha) that drive fatigue, and modulates neuromuscular function for energy production.

Dose: 2000–4000 IU

Vitamin B12
vitaminmorning
Strong

B12 is a cofactor for methylmalonyl-CoA mutase and methionine synthase, essential for mitochondrial energy metabolism and the citric acid cycle. Deficiency impairs fatty acid oxidation and myelin maintenance, causing profound fatigue.

Dose: 1000–5000 mcg

ALA
antioxidant
Strong

Serves as mitochondrial cofactor in energy metabolism, regenerates vitamins C and E, enhances electron transport chain efficiency.

Dose: 300–600 mg

PQQ
antioxidant
Strong

Stimulates formation of new mitochondria, enhances cellular energy production, reduces oxidative stress.

Dose: 10–20 mg

PQQ disodium salt on fatigue, sleep quality, and cognitive function · 2012
NMN
other
Strong

NAD+ precursor restores mitochondrial function, enhances cellular energy production, supports sirtuin-mediated longevity pathways.

Dose: 250–500 mg

Iodine
mineral
Strong

Essential substrate for thyroid hormones T3 and T4, which regulate basal metabolic rate and cellular energy production.

Dose: 150–300 mcg

Vitamin B1
vitaminmorning
Strong

Essential cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, enabling cellular energy production from glucose.

Dose: 50–100 mg

Vitamin B2
vitaminmorning
Strong

FAD and FMN are essential coenzymes in electron transport chain (Complex I and II), enabling mitochondrial ATP synthesis.

Dose: 50–100 mg

Riboflavin and ubiquinone in chronic fatigue: a randomized controlled trial · 2016
Creatine
amino_acid
Strong

Maintains cellular energy reserves by replenishing ATP stores. May reduce perceived fatigue via improved mitochondrial function.

Dose: 5 g

L-Carnitine
amino_acid
Strong

Transports long-chain fatty acids into mitochondria for beta-oxidation. Enhances ATP production from fat metabolism.

Dose: 500–2000 mg

EGCG
herb
Strong

Promotes thermogenesis and catechin-mediated mitochondrial biogenesis, enhancing cellular energy production.

Dose: 400–800 mg

Strong

Adaptogenic activity reduces fatigue perception via hormonal optimization and improved stress resilience.

Dose: 200–400 mg

Copper
mineral
Moderate

Ceruloplasmin mobilizes iron from storage, enabling hemoglobin synthesis. Cytochrome c oxidase supports mitochondrial ATP production.

Dose: 1–2 mg

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