Mitochondrial Changes are exhibited in Polymyositis

Although several studies report on mitochondrial changes occurring more frequently in IBM than in polymyositis, Blume et al report that mitochondrial abnormalities have already been described in polymyositis although devoid of inclusion bodies.

Mitochondrial Toxicity, Oxidative Phosphorylation and Polymyositis
In clinical practice, polymyositis has been misdiagnosed as mitochondrial toxicity causing healthcare workers to be careful when dealing with these different complications. These observations have been supported by studies by Loutfya et al on the several manifestations of mitochondrial toxicity among patients with myopathies.

Treatment with CoQ10
Elzouki et al have suggested the use of coenzyme Q (CoQ10), folinic acid, creatine monohydrate and L-arginine in quenching the free radicals produced during these pathologies such as oxidative phosphorylation(OXPHOS) disorders. ( Blume, Pestronk, Frak, Johns. 1997) [1]

Since it is alleged that a number of myopathies are largely caused by the effects of oxidative free radicals on myofibrils. (Corrado, Canratore, Serlenga, Amati, Petruzzella, Lapadula. 2002) [2] CoQ10 can be one of the supplements which can help reduce symptoms related to polymyositis.

Dosage (Level of supplementation of CoQ10)Individuals with CoQ10 deficiencies have particularly been seen to respond well with CoQ10 treatment. High dosages of CoQ10 may be recommended when individuals have difficulties achieving the appropriate levels of CoQ10 in their tissues. (Loutfya, Sheehana, Goodhewb, Walmsleya. 2003) [6]

 

Absorbtion

CoQ10 has a high molecular weight, is strongly lipophilic, and is almost insoluble in aqueous solution; it is absorbed slowly and incompletely from the small intestine, with a poor bioavailability in humans. (Constantinescu, McDermott, DiCenzo, de Blieck, Christopher, Hyson, Beal, Bednarczyk, Bogdano, Metakis, Browne, Lorenzo, Ravina, Kieburtz. December 2007) [8]

CoQ10 formulated in soft gelatin capsules with liquid fills tend to be better absorbed than the hard gelatin capsules that are powder-filled according to the clinical study conducted on the Bioavailability of two different formulations of CoQ10 in healthy subjects. [9]

Dosage
Ubiquinol provides a first line defense against cellular oxidative damage and needs to be replenished to maintain optimum health. The dosage levels for this reduced CoQ10 form may vary among individual but in general, you can start a dose of 200 to 300mg per day if you are older and suffer chronic disease from oxidative stress. Then, a maintenance dose of 50 to 100mg per day may be taken after two to three weeks. (Reinhardt. March 2007) [10]

Elzouki et al have noted a considerable metabolic and clinical improvement with as low as 30-300mg/day of CoQ10 as observed among patients with OXPHOS disorders. (Prime, Edwards. 2003) [3]

Among children, the recommended dose can be 4.3 mg/kg/day distributed in 2 different oral doses. (Elzouki, Nazer, Stapleton, William, Whitley. 2012) [7]

Blume G, Pestronk A, Frenk B, et al. Polymyositis with cytochrome oxidase negative muscle fibres: Early quadriceps weakness and poor response to immunosuppressive therapy, Brain 120, p.39-45 (1997) as found at http://www.ncbi.nlm.nih.gov/pubmed/9055796

Blume et al. (1997, p.39)

Ibid (p.39-40)

Corrado A, Canratore F.P, Serlenga L, et al. Mitochondrial disease mimicking polymyositis: a case report. Clinical Rheumatology, 21(5)411-414. (2002)

Prime K.P, Edwards S.G, Pakianathan M.R, et al. Polymyositis masquerading as mitochondrial toxicity, Sexually Transmitted Infections, 79(5)417-418. (2003). as found at http://sti.bmj.com/content/79/5/417.full

Loutfya M.R, Sheehana N.L, Goodhewb J.E, et al. Inclusion body myositis: another possible manifestation of antiretroviral-associated mitochondrial toxicity, AIDS, 17(8):1266-1267. 2003. as found at http://www.natap.org/2003/june/060503_1.htm

Elzouki A.Y, Nazer H.M, Stapleton F.B, et al. Textbook of clinical pediatrics (2nd edn).Berlin: Springer-Verlag. 2012

Constantinescu R, McDermott M, DiCenzo R, et al. A Randomized Study of the Bioavailability of Different Formulations of Coenzyme Q10 (Ubiquinone) J Clin Pharmacol vol. 47 no. 12 1580-1586. December 2007. as found at http://jcp.sagepub.com/content/47/12/1580.extract

As found at http://apjcn.nhri.org.tw/server/APJCN/Volume7/vol7.1/Wahlqvist.pdf

Jeffrey Reinhardt. CoQ10-H2 : An Important Constituent of an Over-40 Supplement Regimen Vitamin Research News Vol. 21, Number 3. March 2007. as found at https://www.vrp.com/pdf/March2007News.pdf

 

 

Bioavailability and Role of CoQ10 in Polymyositis

Bioavailability

Ubiquinone, which is in many cases referred to as Coenzyme Q 10 (CoQ10), is in essence one of the three redox states of CoQ10. Ubiquinone is a fully oxidized form CoQ10 which is a small electron carrier of mitochondrial respiratory chain exhibiting antioxidant properties. Other redox states include ubisemiquinone which is a semiquinone and ubiquinol which is a full reduced form of CoQ10. (Stocker 2002) [11]

CoQ10 is usually a lipid soluble antioxidant which can be synthesized in the human bodies but its bioavailability is limited than that of other lipid-soluble antioxidants such as vitamin E. Uptake of CoQ10 takes place in blood vessels, blood and spleen. (Stocker 2002) [12]

Is there evidence of losing ability to convert ubiquinone to ubiquinol known to be a feature of polymyositis?

The heart, skeletal muscle and every other tissue in the body needs energy (ATP) in order for the cells to function properly. The ability of the body cells to recycle compounds that are involved in the production of ATP is fundamental, so when the heart and the skeletal muscles are stressed due to high-intensity exercise or diseases as we age, there will be metabolic dysfunction and energy pool depletion that will affect greatly the overall health of the individual. (Bassett. July 2010) [13]

Ubiquinone must be converted into Ubiquinol in order for faster effect. According to Dr. Sinatra, author of the book entitled ”The CoQ10, L carnitine and D ribose checklist for M.E patients” 15mg of Ubiquinol is bioequivalent or has the same level of effectiveness with Ubiquinone 50mg. But there are factors that slow down or stop the conversion of CoQ10, one of these is aging.

A decrease in CoQ10 levels occurs with genetic mutations, aging, cancer, and the intake of statins, and altered levels are seen in diabetes mellitus, cardiovascular disorders, Alzheimer's disease, and other neurodegenerative disorders. I have not found studies showing the conversion is inhibited in polymyositis.

The body’s ability to reduced CoQ10 (Ubiquinone) to Ubiquinol diminishes with age. Without converting this natural substance, the body produces less energy and lacks strong defense against oxidative stress. So, it was recommended to take CoQ10 as a supplement. [14]

It was concluded in the study “The inhibition of Mitochondrial Peroxidation by Ubiquinone and Ubiquinol” that Ubiquinol-6 was more effective than Ubiquinone-6 in reducing the stable free radical diphenyl-p-picrylhydrazyl. This free radical was used to assay the anti-oxidant property of Ubiquinol. (Mellors and Tappel, April 1966) [15]

CoQ10 is a well-known natural group of lipophilic quinones that has the ability to transfer reducing electrons within a lipid phase of cellular membranes. (Bassett. July 2010) [16]
http://www.google.com.ph/patents?hl=tl&lr=&vid=USPAT6740338&id=A0YQAAAAEBAJ&oi=fnd&dq=Bioavailability+of+lipid-soluble+Ubiquinol&printsec=abstract#v=onepage&q=Bioavailability%20of%20lipid-soluble%20Ubiquinol&f=false

Role in Polymyositis

Deficiency in CoQ10 can lead to mitochondrial dysfunction and toxicity as the molecule plays a critical role in ATP production and the quenching of free radicals which often result into mitochondrial toxicity. These forms of CoQ10 have been known to be essential in human health:

Ubiquinone plays a critical role in the chemical energy production in the mitochondria. A decline of ubiquinone levels in the mitochondria will mean less energy produced thus a breakdown in a number of cellular processes such as muscle functions observed in polymyositis.

Uniquinol serves as an antioxidant primarily by acting to inhibit lipid peroxidation in biological membranes and low density lipoproteins (LDLs). Ubiquinol also acts to protect membrane proteins against harmful oxidative damage.

Contrary, ubisemiquinone which is a semiquinone form of CoQ10 has been suspected to take part in the generation of superoxide radicals during respiration. However, no convincing in vivo evidence to show that CoQ10 can also act as a pro-oxidant

 

Since a decline in the levels of ubiquinone has been associated with a number of myopathies such as polymyositis, dietary CoQ10 supplementation has been shown to improve muscular and organ functions in severe CoQ10 deficiency.

Evidence supporting the role of CoQ10 in fighting oxidative stress has been derived from the use of CoQ10 in protecting keratinocytes from oxidative DNA damage which is induced by UV light. In polymyositis, oxidative stress associated with the condition can also be ameliorated by CoQ10.

Age-related oxidative damage to proteins and lipids has also been associated to a decrease in tissue levels of CoQ10. Supplementation of the compound can therefore prevent oxidative damages to proteins and lipids, often associated in a number of myopathies.

A body of evidence has accumulated over the role of CoQ10 in the treatment of mitochondrial and neurodegenerative disorders such as amyotrophic lateral sclerosis. [17]

Conclusion

The primary role of CoQ10 in polymyositis is in the prevention of mitochondrial dysfunction and oxidative damage. ( Schmelzer, Lindner, Niklowitz et al. 2008) [18]

CoQ10 which is a component of the electron transport chain in the mitochondria manufactures ATP using oxygen. Individuals with Friedreich’s ataxia, a degenerative neurological disorder, treated with 400mg/day of CoQ10 and vitamin E (2100 IU /day) have shown considerable improvement in heart and skeletal muscle bioenergetics. Overall cardiac function and echocardiography has also been recorded.[19]

Because of its energy carrier function, CoQ10 is known to be one of the antioxidants that can be utilized in fighting disorders associated with oxidative stress. CoQ10, as an energy carrier molecule undergoes a continuous process of oxidation and reduction cycle as it changes from one oxidation state to another. The reduced form of CoQ10 readily loses its electrons and thus acting as an excellent antioxidant.

 

 

Stocker, R. Possible health benefits of coenzyme Q10. Accessed 8th February, 2012. (2002) as found at http://lpi.oregonstate.edu/f-w02/coenzymeq10.html

Stocker, R. Possible health benefits of coenzyme Q10. Accessed 8th February, 2012. (2002) as found at http://lpi.oregonstate.edu/f-w02/coenzymeq10.html

Bassett, J. CoQ10 (ubiquinol), L carnitine, D ribose and M.E. July 2010 as found at http://www.hfme.org/researchlccoq10drandme.htm

As found at http://www.kanekaqh.info/studies.html

Mellors and Tappel. The Inhibition of Mitochondrial Peroxidation by Ubiquinone and Ubiquinole. The Journal of Biological Chemistry Vol. 241, 19, Issue of October 10, pp. 4353-4356, 1966. April 1966 as found at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1832150/

Bassett, J. CoQ10 (ubiquinol), L carnitine, D ribose and M.E. July 2010. as found at http://www.hfme.org/researchlccoq10drandme.htm

Ibid

Schmelzer C, Lindner G, Niklowitz P, et al. Functions of coenzyme Q10 in inflammation and gene expression. BioFactors, 32(1-4), p.178-183. Retrieved 11th February, 2012. Original 2008. as found at http://onlinelibrary.wiley.com/doi/10.1002/biof.5520320121/abstract

Schmelzer et al. (2008, p.179)

 

CoQ10 and its role in inflammation

CoQ10, Inflammation and Polymyositis: Strategies for Ameliorating Symptoms

Inflammation of the muscle fibers is one of the most important symptoms in polymyositis. The disease belongs to a large category of conditions collectively referred to as inflammatory myopathies. [20] The term “myopathy” is used to mean myositis.

CoQ10 is one of the potential adjuvant therapies which a number of clinical studies have confirmed to be effective in managing cardiovascular diseases, neurodegenerative diseases and mitochondrial myopathies. [21] Recent studies reported the association of CoQ10 with hundreds of gene expression including those related to inflammation. The effect of CoQ10 on NFkB1-dependedent gene expression was particularly studied by Schmelzer and a team of other researchers. It was concluded that CoQ10 exerts anti-inflammatory effects through the NFkB1-dependent gene expression. [22]

In conclusion, the use of CoQ10 in ameliorating inflammatory symptoms such as those related to polymyositis is safer and appears not to show major side effects, according to University of Maryland Medical Center. [23]CoQ10 can sufficiently be obtained from diet such as oily fish, organ meats and whole grain. Supplementation of CoQ10 can however be recommended in particular health conditions and is available in many forms such as oral spray, soft gel capsules, hard shell capsule as well as tablets. A daily dose of 30-200mg of CoQ10 for patients of 19 years and older is recommended. [24]

Muscular Dystrophy Association (2009). Facts about inflammatory myopathies (myositis). as found at http://www.mda.org/publications/PDFs/FA-IM.pdf

MDA (2009)

Ibid

Ibid

Schmelzer C, Lindner G, Niklowitz, P, et al. (2008). Functions of coenzyme Q10 in inflammation and gene expression. BioFactors, 32(1-4), p.178-183. as found at http://onlinelibrary.wiley.com/doi/10.1002/biof.5520320121/abstract

Schmelzer et al (2008, p.179)

University of Maryland Medical Center (2011). Coenzyme Q10: Overview. as found at http://www.umm.edu/altmed/articles/coenzyme-q10-000295.htm

UMMC (2011)

Footnotes:

1. Blume G, Pestronk A,Frank B, Johns DR.. Polymyositis with cytochrome oxidase negative muscle fibres. Early quadriceps weakness and poor response to immunosuppressive therapy.. Brain, 120 ( Pt 1):39-45., 1997 as found at VIEW

2. Corrado A, Cantatore FP,Serlenga L,Amati A, Petruzzella V. Mitochondrial disease mimicking polymyositis: a case report.. Clinical Rheumatology, 21(5)411-414., 2002 as found at VIEW

3. Prime K.P, Edwards S.G,Pakianathan M.R,S G Edwards1,M R Pakianathan1,J L Holton2,F Scaravilli2,Holton JL,Scaravilli F,Miller RF. Polymyositis masquerading as mitochondrial toxicity. Sexually Transmitted Infections, 79(5)417-418, 2003 as found at VIEW