Creatine plus CoQ10 for neuroprotection?

[CaliReader]

I found this article browsing. It doesn't study MS directly, but suggests that Creatine plus Coenzyme Q 10 give better neuroprotection in Parkinsons and Huntingdons than either do alone. I use both. I stumbled on the article while looking at Glutathione and thought I'd share.

Does anyone else use these?

Here is the abstract plus intro.

J Neurochem. Author manuscript; available in PMC 2010 June 1.
Published in final edited form as:
J Neurochem. 2009 June; 109(5): 1427–1439.
Published online 2009 March 28. doi: 10.1111/j.1471-4159.2009.06074.x
PMCID: PMC2866530
NIHMSID: NIHMS106242
Combination Therapy with Coenzyme Q10 and Creatine Produces Additive Neuroprotective Effects in Models of Parkinson’s and Huntington’s Diseases
Lichuan Yang,1 Noel Y. Calingasan,1 Elizabeth J. Wille,1 Kerry Cormier,2,3 Karen Smith,2,3 Robert J. Ferrante,2,3 and M. Flint Beal1

Abstract
Coenzyme Q10 (CoQ10) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants. We examined whether a combination of CoQ10 with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson’s disease (PD), a 3-NP rat model of Huntington’s disease (HD) and the R6/2 transgenic mouse model of HD. The combination of the two agents produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP. The combination treatment resulted in significant reduction in lipid peroxidation and pathologic α-synuclein accumulation in the SNpc neurons of the MPTP-treated mice. We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats. The combination treatment showed significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum. Lastly, the combination of CoQ10 and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice. These findings suggest that combination therapy using CoQ10 and creatine may be useful in the treatment of neurodegenerative diseases such as PD and HD.


Introduction
There is substantial evidence that mitochondrial dysfunction and bioenergetic abnormalities play a role in the pathogenesis of neurodegenerative disease (Lin and Beal 2006). It is, therefore, possible that agents, which improve mitochondrial and cellular bioenergetics may be useful in the treatment of neurodegenerative disease. Two agents which show particular promise are Coenzyme Q10 (CoQ10) and creatine.

CoQ10 is an essential cofactor of the electron transport chain where it accepts electrons from complex I and complex II (Ernster and Dallner 1995; Turunen et al. 2004). CoQ10, which is also known as ubiquinone, is composed of a redox active quinoid moiety and a hydrophobic ‘tail’. It is soluble and mobile in the hydrophobic core of the phospholipid bilayer of the inner membrane of mitochondria, where it transfers electrons one at a time, to complex III of the electron transport chain. CoQ10 also serves as an important antioxidant in both mitochondria and in lipid membranes (Noack et al. 1994; Forsmark-Andree et al. 1997). In the inner mitochondrial membranes and microsomal lipid membranes, it reduces α-tocopheroxyl radical and regenerates α-tocopherol (Kagan et al. 1990). CoQ10 is also an obligatory cofactor of mitochondrial uncoupling proteins, which regulate ATP production and reduce free radical generation (Echtay et al. 2002).

Creatine is a guanidine compound, which plays a key role in energy buffering within the cell, which is thought to be particularly important in tissues with high and fluctuating energy requirements such as brain and muscle (Burklen et al. 2006). The creatine/phosphocreatine (PCr) system functions as a spatial energy buffer between the cytosol and mitochondria using a unique mitochondrial creatine kinase (CK) isoform, which is found in the intermembrane space of mitochondria. Creatine kinase can generate ATP from phosphocreatine and adenosine diphosphate (ADP) at the sites of high energy demand and restore phosphocreatine for energy storage (Burklen et al. 2006).

We and others showed that both CoQ10 and creatine exert neuroprotective effects both in vitro and in vivo in animal models of neurodegenerative diseases (Beal and Shults 2003). This has led to clinical trials in both Parkinson’s disease (PD) and Huntington’s disease (HD) (Huntington-Study-Group 2001; Shults et al. 2002). Due to initial promising results, both CoQ10 and creatine are entering phase III trials for the treatment of PD and HD. It is possible that combinations of agents targeting different disease mechanisms may show improved efficacy, and allow agents to be utilized at lower doses to minimize side effects.

Although both CoQ10 and creatine have effects on bioenergetics, they act on different pathways. In the present study, we, therefore, examined whether CoQ10 and creatine can exert additive neuroprotective effects. We examined the combination of CoQ10 and creatine in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) model of PD, the 3-nitropropionic acid (3-NP) model of HD, and in the R6/2 transgenic mouse model of HD.

[jimmylegs]

musings on creatine

wiki:
"Creatine is naturally produced in the human body from amino acids primarily in the kidney and liver. It is transported in the blood for use by muscles. Approximately 95% of the human body's total creatine is located in skeletal muscle.[4] Creatine is not an essential nutrient, as it is manufactured in the human body from L-arginine, glycine, and L-methionine.[5] .... Given the fact that creatine can be synthesized from the above mentioned amino acids, protein sources rich in these amino acids can be expected to provide adequate capability of native biosynthesis in the human body.[5] The enzyme GATM (L-arginine:glycine amidinotransferase (AGAT), EC 2.1.4.1) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas.[7] The second enzyme in the pathway (GAMT, Guanidinoacetate N-methyltransferase, EC:2.1.1.2) is primarily expressed in the liver and pancreas.[7] Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[8]"
i'd say that nutrient deficiencies affecting the creatine biosynthetic pathway would also have the potential to lead to various severe neuro defects.. ok so looking at what's required for proper creatine status..

1) research shows adding testosterone increased activity (in female rats anyway)
INFLUENCE OF SEX HORMONES ON AMIDINOTRANSFERASE LEVELS. METABOLIC CONTROL OF CREATINE BIOSYNTHESIS
http://www.eje-online.org/content/53/4/655.abstract
"The administration of testosterone propionate to young adult female rats resulted in a significant increase in enzyme activity."

2) testosterone has been demonstrated to be abnormally low in MS
Dysregulation of the hypothalamic-pituitary-gonadal axis in experimental autoimmune encephalomyelitis and multiple sclerosis
http://www.ncbi.nlm.nih.gov/pubmed/12864974
"Abnormally low serum testosterone levels were found in male mice with EAE and in male MS patients"

3) zinc status influences testosterone levels
Zinc status and serum testosterone levels of healthy adults
http://www.sciencedirect.com/science/ar ... 079680058X
"Zinc supplementation of marginally zinc-deficient normal elderly men for six months resulted in an increase in serum testosterone from 8.3 ± 6.3 to 16.0 ± 4.4 nmol/p (p = 0.02). We conclude that zinc may play an important role in modulating serum testosterone levels in normal men."

so, I would lean towards giving the body the basic tools for its processes ie replete zinc->more testosterone->more AGAT->more creatine route (not forgetting GAMT but I haven't dug into that part of the pathway at all yet) rather than dumping in extra creatine at the end of the line.

i have to get back to my other work but basically i would approach coQ10 in the same way. same with glutathione. I've already unpacked glutathione from a couple different angles.. more zinc AND more selenium = more glutathione. all so interesting

[CaliReader]

Thanks for the reply. : )

I did my share of digging last Fall. Now, I'm just browsing. I don't understand all the connections.
But there was a trend in the research that mitochondrial problems are part of MS.
Both CoQ10 and Creatine promote ATP, taking some of the load off the mitochondria in the cell.
At the symptom level, my fatigue is less and I exercise and move more if I use Creatine.

Some day I'll read your book on MS and Nutrition. But I'm just looking to play whatever cards I can find. If they are duplicative, that's ok with me also.

[CureOrBust]

Does anyone else use these?

I have taken CoQ10 for a while now as I am taking Statins for my MS. By Chance, I have just started taking Creatine Monohydrate. I also use DHEA irregularily.