musings on creatine
"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. Creatine is not an essential nutrient, as it is manufactured in the human body from L-arginine, glycine, and L-methionine. .... 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. The enzyme GATM (L-arginine:glycine amidinotransferase (AGAT), EC 22.214.171.124) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas. The second enzyme in the pathway (GAMT, Guanidinoacetate N-methyltransferase, EC:126.96.36.199) is primarily expressed in the liver and pancreas. Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects."
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 BIOSYNTHESIShttp://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 adultshttp://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