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More recent studies, in vitro and in vivo in animals, have found creatine to be highly neuroprotective against other neurotoxic agents such as N-methyl-D-aspartate (NMDA) and malonate.4 Another study found that feeding rats creatine helped protect them against tetrahydropyridine (MPTP), which produces parkinsonism in animals through impaired energy production.
The results were impressive enough for these researchers to conclude, "These results further implicate metabolic dysfunction in MPTP neurotoxicity and suggest a novel therapeutic approach, which may have applicability in Parkinson's disease."5 Other studies have found creatine protected neurons from ischemic (low oxygen) damage as is often seen after strokes or injuries.6
Yet more studies have found creatine may play a therapeutic and or protective role in Huntington's disease7, 8 as well as ALS (amyotrophic lateral sclerosis).9 This study found that "? oral administration of creatine produced a dose-dependent improvement in motor performance and extended survival in G93A transgenic mice, and it protected mice from loss of both motor neurons and substantia nigra neurons at 120 days of age.
Creatine administration protected G93A transgenic mice from increases in biochemical indices of oxidative damage. Therefore, creatine administration may be a new therapeutic strategy for ALS." Amazingly, this is only tip of iceberg showing creatine may have therapeutic uses for a wide range of neurological disease as well as injuries to brain.
One researcher who has looked at effects of creatine commented, "This food supplement may provide clues to mechanisms responsible for neuronal loss after traumatic brain injury and may find use as a neuroprotective agent against acute and delayed neurodegenerative processes."
Creatine and heart function
Because it is known that heart cells are dependent on adequate levels of ATP to function properly, and that cardiac creatine levels are depressed in chronic heart failure, researchers have looked at supplemental creatine to improve heart function and overall symptomology in certain forms of heart disease.
It is well known that people suffering from chronic heart failure have limited endurance, strength and tire easily, which greatly limits their ability to function in everyday life. Using a double blind, placebo-controlled design, 17 patients aged 43 to 70 years with an ejection fraction <40 were supplemented with 20 grams of creatine daily for 10 days.
Before and after creatine supplementation, researchers looked at:
1) Ejection fraction of heart (blood present in ventricle at end of diastole and expelled during contraction of heart)
2) 1-legged knee extensor (which tests strength)
3) Exercise performance on cycle ergometer (which tests endurance)
Biopsies were also taken from muscle to determine if there was an increase in energy-producing compounds (i.e., creatine and creatine phosphate). Interestingly, but not surprisingly, ejection fraction at rest and during exercise phase did not increase.
However, biopsies revealed a considerable increase in tissue levels of creatine and creatine phosphate in patients getting supplemental creatine. More importantly, patients getting creatine had increases in strength and peak torque (21%, P < 0.05) and endurance (10%, P < 0.05).
Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). After just one week of creatine supplementation, researchers concluded: "Supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance.
This new therapeutic approach merits further attention."10
Another study looked at effects of creatine supplementation on endurance and muscle metabolism in people with congestive heart failure.11 In particular researchers looked at levels of ammonia and lactate, two important indicators of muscle performance under stress.
Lactate and ammonia levels rise as intensity increases during exercise and higher levels are associated with fatigue.
High-level athletes have lower levels of lactate and ammonia during a given exercise than non-athletes, as athletes' metabolism is better at dealing with these metabolites of exertion, allowing them to perform better.
This study found that patients with congestive heart failure given 20 grams of creatine per day had greater strength and endurance (measured as handgrip exercise at 25%, 50% and 75% of maximum voluntary contraction or until exhaustion) and had lower levels of lactate and ammonia than placebo group.
This shows that creatine supplementation in chronic heart failure augments skeletal muscle endurance and attenuates abnormal skeletal muscle metabolic response to exercise.
It is important to note that whole-body lack of essential high energy compounds (e.g. ATP, creatine, creatine phosphate, etc.) in people with chronic congestive heart failure is not a matter of simple malnutrition, but appears to be a metabolic derangement in skeletal muscle and other tissues.
Supplementing with high energy precursors such as creatine monohydrate appears to be a highly effective, low cost approach to helping these patients live more functional lives, and perhaps extend their life spans.
Creatine is quickly becoming one of most well researched and promising supplements for a wide range of diseases. It may have additional uses for pathologies where a lack of high energy compounds and general muscle weakness exist, such as fibromyalgia.
People with fibromyalgia have lower levels of creatine phosphate and ATP levels compared to controls.13 Some studies also suggest it helps with strength and endurance of healthy but aging people as well.
Though additional research is needed, there is a substantial body of research showing creatine is an effective and safe supplement for a wide range of pathologies and may be next big find in anti-aging nutrients.
Although doses used in some studies were quite high, recent studies suggest lower doses are just as effective for increasing overall creatine phosphate pool in body.
Two to three grams per day appears adequate for healthy people to increase their tissue levels of creatine phosphate. People with aforementioned pathologies may benefit from higher intakes, in 5-to-10 grams per day range.
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