It has recently been shown that creatine supplementation can lower serum homocysteine levels (see reference below). This effect of creatine would be particularly potent when combined with targeted B-vitamin intervention, which similarly lowers serum homocysteine levels and replenishes cellular methylation reserves.
Highlighted Scientific Reference
Creatine Reduces Serum Homocysteine Levels
Below is the reference to the first published study showing that creatine supplementation reduces plasma homocysteine levels.
Stead, L. M. et al. (2001) Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. American Journal of Physiology – Endocrinology and Metabolism, Volume 281, pages E1095-E1100.
Below are a few examples of the many recent studies revealing a positive correlation between serum homocyteine levels and neurological (and psychiatric) disorders including depression, dementia, demyelinating myelopathy and, of course, Alzheimer’s disease. Creatine and vitamin B supplementation may thus prove a worthwhile adjuvant strategy to decrease the damage resulting from these neurologic conditions because of elevated serum levels of homocysteine.
Psychiatric Disorders: Recently, a clear positive correlation has been demonstrated between the existence of psychiatric disorders in the elderly and serum homocysteine levels. One Swedish study showed that nearly half of the elderly patients reporting to a psychogeriatric hospital for treatment had homocyteine levels above 20 microMolar, only 5 microMolar higher than the average for this particular demographic (1). In fact, no other blood-borne molecule was as reliable a predictor for psychiatric disorders as homocysteine.
Dementia: More than 70% of all cases of dementia arise from Alzheimer’s disease. The remaining forms of dementia are predominantly vascular in origin. Vascular dementia causes small infarcts of the brain vasculature, depriving entire regions of the brain of blood. One study showed that cerebral microangiopathy (reduced blood flow) is most pronounced in patients with elevated homocysteine (2).
Alzheimer’s disease: Another recent study found that serum homocysteine levels above 14 microMolar nearly doubled the chances of developing Alzheimer’s disease (3). Since 8-12 microMolar is the “normal” range of homocysteine in the population, it is correct to assume that most individuals are dangerously close to developing some form of mental health disorder (such as, Alzheimer’s disease) because of elevated homocysteine levels, otherwise known as hyperhomocysteinemia.
Poor Memory: Another study showed that hyperhomocysteinemia was associated with poor memory. Here, subjects over 60 years of age with higher homocysteine levels scored lower in short-delay recall tests (4). The onset of senescence is also likely be largely a consequence of the increase in serum homocysteine levels resulting from a characteristic decline in methylation capacity in the elderly. Indeed, cognitive impairment appears to be a common outcome of hyperhomocysteinemia.
Neuropathy: Depletion of our methyl reserves can have devastating consequences on nervous system function. For instance, one very important product of cellular methylation is myelin basic protein. Myelin is the fatty sheath that insulates our nerve cells (neurons) from one another, preventing cross-talk and allowing efficient bi-directional communication between peripheral targets (arms and legs, for example) and the brain. This function of myelin is especially important within the brain and spinal cord where hundreds of thousands of neurons are packed tightly together. Severe defects of methylation capacity produce demyelination (unsheathing of neurons) giving rise to a neuropathy that is characterized by ataxia (lack of motor coordination), paralysis, and, if left untreated, death (5). The best described clinical example of such a metabolic condition is pernicious anemia, an inability of the body to absorb vitamin B12 from the intestinal compartment into the blood stream. Remember, vitamin B12 is required to recycle our methyl reserves and when it is lacking in the diet causes profound physiological abnormalities. On the other hand, the synthesis of creatine is our greatest drain of methyl groups. Therefore, creatine supplementation, by sparing the body’s methyl reserves, helps protect against the awful consequences of methylation deficiencies (for example, neuropathies) especially when accompanied by targeted B-vitamin supplementing. Creatine and B-vitamins are thus essential to sustain healthy nervous system functioning.
Brain Health Through Creatine and B-Vitamin Supplementation
Folic Acid: Each day new supportive evidence is emerging indicating that folic acid supplementation can be an effective measure at reducing serum homocysteine levels and at mitigating the dangerous consequences of hyperhomocysteinemia. In particular, one pioneering study demonstrated that subjects with mild-to-moderate dementia and associated hyperhomocysteinemia improved in cognitive capacity after folic acid and vitamin B12 supplementation (6). Minimally therefore, it is extremely important to maintain healthful folate levels for proper brain functioning, especially when considering that this is the only pathway available to the nervous system to regenerate SAM from homocysteine.
Creatine Monohydrate: Creatine has also been proven important in improving the body’s methylation status as well as in maintaining brain energy levels, both these processes work in cohorts to fortify cognitive capacity. The dangers of elevated homocysteine levels (resulting from compromised methylation capacity) should now be clearly evident. However, it is also worth noting that excessive neuronal activity requires a surplus of cellular energy to prevent a form of neuronal death known as excitotoxicity. Creatine supplementation, by way of enhancing cellular energy levels, has been shown to protect against certain forms of excitotoxicity. Furthermore, ischemia is a state of reduced blood flow that deprives entire brain regions of oxygen (hypoxia). Ischema-hypoxia causes substantial neuronal death that in adults produces stroke and in newborn infants (neonates) gives rise to enduring neurological disorders such as cerebral palsy. Creatine supplementation, again by increasing neuronal energy metabolism, has been recently shown to combat brain cell death because of ischemia-hypoxia. Therefore, combining creatine supplementation with targeted B-vitamin intervention should preserve the proper functioning of our nervous systems for longer in life. The importance of creatine and B-vitamins in combating elevated homocysteine levels is discussed here.
Selected Scientific References:
1. Nilsson K. et al. (2005) Plasma homocysteine concentration and its relation to symptoms of vascular disease in psychogeriatric patients. Dementia and Geriatric Cognitive Disorders, Volume 20, pages 35-41.
2. Evers S. et al. (1997) Features, symptoms, and neurophysiological findings in stroke associated with hyperhomocysteinemia. Archives of Neurology, Volume 54 (10), pages 1276-1282.
3. Seshadri S. et al. (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. New England Journal of Medicine, Volume 346 (7), pages 476-483.
4. Morris M. S. et al. (2001) Hyperhomocysteinemia associated with poor recall in the third National Health and Nutrition Examination Survey. American Journal of Clinical Nutrition, Volume 73, pages 927-933.
5. Stabler S. P. and Allen R. H. (2004) Vitamin B12 deficiency as a worldwide problem. Annual Reviews of Nutrition, Volume 24, pages 299–326.
6. Nilsson K. et al. (2001) Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. International Journal of Geriatric Psychiatry, Volume 16 (6), pages 609-614.
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