Lots at the IACFS/ME conference about mitochondria and I'm wondering what the implications are, if any, for the use of CoQ10. I tried this years ago to no effect but now am wondering if higher doses are indicated.
@ZeroGravitas kindly produced this summary of part of Nancy Klimas's talk at the conference:
Useful info from Cort's blog:
From this 2009 paper on the treatment of mitochondrial disease:
Does anyone have info about the Klimas study (actually, I'm not sure if it's her study or just one she was mentioning)?
Wondering whether to try this and if so, what product/dose/schedule, how long to give it, etc.
I'd been going to do this a couple of months ago and got sidetracked onto something else.
Wondering if our state of knowledge has now improved about the role of mitochondria in ME/CFS to inform consideration of this.
@ZeroGravitas kindly produced this summary of part of Nancy Klimas's talk at the conference:
ZeroGravitas said:We've done studies with patients on an exercise bike. When you push energy production to the anaerobic state it initiates an inflammatory cascade in CFS patients.
All metabolism pathways turn off (opposite of normal) and cell communication turns off (e.g. cortisol production turns *off*).
Cells are jam packed with mitochondria. But here there are fewer, and so should metabolite levels (like glutathione) related to per cell, or per mito? (We don't know.)
Is this (mitochondrial dysfunction) adaptive (protective) or just the problem? Down-regulating to protect against increasing oxidative stress that would be very damaging, causing cell death and tissue degeneration.
CoQ10 supplementation produced effect if measured levels also improved...(?) It takes a lot to replenish stores (but then you're topped up and then you're there).
In current study they're using 400mg ubuiquinol (equivalent to 1200ml ubiquinone). Then will measure results, reduce to 200mg, then re-meausure(?).
But substances like this that aid energy make sleep worst, dose dependently.
Useful info from Cort's blog:
Cort on Health Rising said:Co-enzyme Q10 (CoQ10)
CoQ10 is a potent antioxidant that plays an important role in producing ATP. [CoQ10 is one of the few supplements endorsed by virtually all ME/CFS practitioners]. It comes in two forms: ubiquinone or ubiquinol.
- Ubiquinone – is the oxidized form of CoQ10. The body has to transform ubiquinone back into its unoxidized form to use it.
- Ubiquinol – is CoQ10 In its biologically active ready-to-use form.
From this 2009 paper on the treatment of mitochondrial disease:
paper said:Coenzyme Q10
The evidence supporting the use of coenzyme Q10 (CoQ10, also known as ubiquinone) in mitochondrial disease was reviewed in 2007 [11••, Class IV]. CoQ10 is endogenously synthesized in mammalian mitochondria and is an integral component of the mitochondrial electron transport chain, shuttling electrons from complexes I or II and a number of other electron donors, including electron transfer factor, which moves electrons from fatty acid beta oxidation.
CoQ10 is found in all cell and organelle membranes, where it can participate in redox shuttling. It has an important intracellular signaling role, as well as both antioxidant and pro-oxidant roles. CoQ10 modulates the mitochondrial permeability transition pore involved in apoptosis and activates uncoupling proteins.
CoQ10 biosynthetic defects underlie several different phenotypes of human mitochondrial disease. These include neonatal encephalopathy with nephropathy (COQ2) [12, Class IV]; Leigh syndrome, lactic acidosis, and nephropathy (PDSS2) [13, Class IV]; infantile nephropathy, hepatopathy, retardation (PDSS1) [14, Class IV]; and recessive ataxia, cerebellar atrophy ± retardation, lactic acidosis, and exercise intolerance (ADCK3) [15, Class IV]. These disorders, which may respond to exogenous CoQ10 administration, represent an important group of treatable mitochondrial diseases.
Pharmacokinetics
CoQ10 is insoluble in water. Powder formulations of CoQ10 have very poor intestinal absorption. No increase in CoQ10 plasma levels was achieved when 3000 mg/d was compared with administration of 2400 mg/d, suggesting a block to gastrointestinal absorption above 2400 mg in adults [16, Class IV]. Improved bioavailability has been seen with the use of nano-particles in suspension [17].
Recently, reduced CoQ has become commercially available in the form of ubiquinol. This formulation is three to five times better absorbed when compared with the oxidized form of CoQ, ubiquinone.
CoQ is carried in the blood in white cells and platelets. In plasma, CoQ is largely (95%) bound to lipoproteins in the reduced ubiquinol form.
The plasma half-life of administered CoQ10 is about 36 hours. Following 1 month of oral administration of two relatively bioavailable CoQ10 formulations (a liquid and a wafer), blood levels returned to baseline 2 weeks following CoQ10 cessation (Haas, unpublished data, Class IV).
Catabolic pathways for CoQ have not yet been characterized.
CoQ levels in blood and tissues fall with normal aging. CoQ levels in a 70-year-old are about 50% of those in a 20-year-old.
- Standard dosage Ubiquinol doses of 2 to 8 mg/kg per day (administered twice daily with meals) seem prudent; this form of CoQ10 in a solubilized, bioavailable form is preferred over ubiquinone. Ubiquinone doses of 5 to 30 mg/kg per day (administered in two divided doses daily with meals) is an available alternative.
- Contraindications None known.
- Main drug interactions May lower warfarin concentrations.
- Main side effects Wakefulness.
- Special points CoQ10 has been approved by the US Food and Drug Administration (FDA) for treatment of mitochondrial disease. Although animal and human experience with CoQ10 treatment has shown no toxicity, it is not known whether supratherapeutic blood levels are safe. Pro-oxidant and physiologic signaling roles of CoQ are a concern [18].
- Cost/cost-effectiveness CoQ treatment is expensive (about $200/mo for 400 mg/d of ubiquinol). However, the prevalent expert view is that CoQ supplemental theraphy is beneficial in mitochondrial disease.
Does anyone have info about the Klimas study (actually, I'm not sure if it's her study or just one she was mentioning)?
Wondering whether to try this and if so, what product/dose/schedule, how long to give it, etc.
I'd been going to do this a couple of months ago and got sidetracked onto something else.
Wondering if our state of knowledge has now improved about the role of mitochondria in ME/CFS to inform consideration of this.