Boosting Mitochondria May Not Only Increase Energy, But Also Lead To Complete Viral Clearance New study: The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis. The above study compared mice strains that were able to completely clear coxsackievirus B (CVB) infection, to mice strains that could not clear this virus and had lingering infection with immune activation. The study was in the context of coxsackievirus B3-induced myocarditis, but I think CVB myocarditis may be an excellent viral model for studying chronic fatigue syndrome, since chronic lingering CVB infection is strongly associated with ME/CFS. After 90 days, the study authors found that the non-clearing mice showed permanently restricted mitochondrial complex I activity, whereas the mice that cleared the virus normalized all four mitochondrial complexes. In general, the authors found that reduced CVB3 titers correlated with increased complex I and III activity. So mitochondrial complexes I and III are possibly the ones you want to boost the most, to try to get viral clearance, if you have enterovirus / coxsackievirus B associated chronic fatigue syndrome. Supplements that boost mitochondrial complexes I and III include: pyrroloquinoline quinone, gingko biloba, and melatonin (at night). The paper concluded: "the regulation of energy metabolism appears crucial for an effective virus elimination and may be of prognostic and therapeutic significance." So intriguingly, it seems that low energy output from mitochondria may not only cause fatigue, but worse still, it seems to prevent the clearance of enterovirus from the tissues. So boosting mitochondria, particularly complexes I and III, may not only provide a welcome increase in energy, but may also help clear viral infections. Boosters of Mitochondrial Complexes: Gingko biloba stimulates complexes I and III. Ref: 1 Melatonin stimulates complexes I and IV. Ref: 1 Pyrroloquinoline quinone (PQQ) stimulates complex I. Ref: 1 Decylubiquinone (co-enzyme Q10 analogue) increases complex I / III and complex II / III activities by 64% and 80% respectively. Ref: 1 Metformin partially inhibits complex I. Haloperidol inhibits mitochondrial complex I. Pyrethroids pesticides permethrin and cyhalothrin potent inhibitors of mitochondrial complex I. Rotenone (an insecticide, pesticide and piscicide) inhibits complex I. MDMA ("ecstasy") inhibits mitochondrial complex I activity in mice. Cocaine inhibits complex I . Vitamin B2 (riboflavin) boosts complex II in patients with complex II deficiency (but not in healthy controls).Ref: 1 Methylphenidate (Ritalin) stimulates complexes II and IV. Refs: 1 2 Rapamycin (sirolimus) stimulates complex II. Ref: 1 Decylubiquinone (co-enzyme Q10 analogue) increased complex I / III and complex II / III activities by 64% and 80% respectively. Ref: 1 Poliovirus infection inhibits Complex II. Decylubiquinone (a co-enzyme Q10 analogue) increases complex I/III and complex II/III activities by 64 and 80%, respectively. Ref: 1 Gingko biloba stimulates complexes I and III. Ref: 1 Resveratrol it is not clear whether it increases or decreases complex III. Ref: 1 2 Azoxystrobin fungicide inhibits complex III. Methylene blue increases mitochondrial complex IV by 30%. Ref: 1 Deprenyl (selegiline) increases complex IV activity by 42% in the presence of 25 microM deprenyl in a condition of maximal nitric oxide synthase activity. Ref: 1 Methylphenidate (Ritalin) stimulates complexes II and IV. Refs: 1 2 Melatonin stimulates complexes I and IV. Ref: 1 Bezafibrate stimulates complex IV. Ref: 1 Red and infrared light stimulate complex IV cytochrome c oxidase (NASA research). Ref: 1 Malathion (organophosphate pesticide) significantly inhibits mitochondrial complex IV. Ref: 1 Supplements That Boost General Mitochondrial Function: Creatine. Glutamine protects mitochondrial structure and function in oxygen toxicity. High doses of nicotinamide prevent oxidative mitochondrial dysfunction in a cellular model and improve motor deficit in a Drosophila model of Parkinson's. Piracetam improves mitochondrial dysfunction following oxidative stress (ref: 1). Q10 Take co-enzyme Q10 with food! Q10 facilitates the conversion of nutrients into energy in the mitochondria. So take with meals. Alpha lipoic acid + acetyl-L-carnitine. Magnesium. Malic acid. Coconut oil / MCT oil. Taurine. D-ribose. Supplements That Boost Mitochondrial Biogenesis: Mitochondrial biogenesis = creation of new mitochondria. There are around a few hundred to a few thousand mitochondria in each cell, and the average lifespan of a mitochondrion is around 2 to 4 weeks, after which it needs replacement with a new mitochondrion (ref: 1). Dave Whitlock thinks that ME/CFS may not just be linked to reduced mitochondrial function, but also to reduced mitochondrial numbers, due to not enough replacement mitochondria being made. So generating new mitochondria may be a good idea. Quercetin promotes mitochondrial biogenesis. Resveratrol. Leucine (and Branched Chain Amino Acids). R-alpha-lipoic acid and acetyl-L-carnitine. Isoflavones (daidzein, genistein, biochanin A). Caffeine. Hydroxytyrosol (from olive oil, and olive leaf extract). Commercial name: Hidrox. Pioglitazone (Actos), an antihyperglycemic, antidiabetic drug. Estradiol (hormone). Pyrroloquinoline quinone (possibly a new vitamin). Caloric Restriction (fasting) promotes mitochondrial biogenesis. Erythropoietin. Cold exposure. Hypoxia. SRT1720 (new drug from Sirtris Pharmaceuticals). Telmisartan enhances mitochondrial biogenesis in human endothelial cell. Triiodothyronine (T3). DHEA. Pyruvate. Lactate. Lithium. Also of interest: Wikipedia's article on complex III says: "mutations in complex III cause exercise intolerance". Given this, I wonder if virally induced restrictions in complex III might explain the post exertional malaise (PEM) in ME/CFS, which is an exercise intolerance? It possibly adds weight to the idea of boosting complex I and III as a ME/CFS treatment.