Life Extension Magazine®

Issue: Feb 2004

The “Strength Supplement” that Improves Brain Power

Long used by athletes to increase endurance, creatine has now been found to be a vital ingredient in fighting various neurological diseases. Parkinson’s, Huntington’s, and Alzheimer’s diseases can all be potentially helped by proper creatine supplementation.

By Dr. Edward R. Rosick.

image

Some in mainstream medicine believe that anti-aging researchers and physicians are a hedonistic lot, interested only in preserving their young and supple physiques at any cost. In my experience, however, nothing could be further from the truth. I find that a vast majority of anti-aging physicians are proponents not only of keeping their patients looking and feeling their best, but also of keeping their minds sharp and their memories intact.

For those interested in maintaining a sharp mind and a supple figure, creatine is a must-take supplement. Many know creatine only as a popular supplement used by athletes, bodybuilders, and other fitness enthusiasts to maintain muscle mass and improve exercise performance. But exciting new scientific evidence shows that creatine not only can help people with degenerative neurological disorders, but also may help just about everyone maintain a healthy, clear-thinking mind.

Keeping Muscles Strong and Healthy
Creatine, a compound comprising the amino acids methionine, glycine, and arginine, was discovered and isolated from meat extract in 1835. Humans produce creatine in the kidney, liver, and pancreas, but store most of it in muscles, including the heart. While creatine has been known since the early 1800s, not until the end of the 20th century did scientists discover that when taken as a supplement, creatine can be of significant help in adding muscle mass.

More than 500 well-researched studies have been conducted showing that creatine supplements can help everyone—men and women, young and old—maintain muscular fitness and ward off some of the most debilitating effects of aging, such as sarcopenia, the age-related loss of muscle mass and strength. A study published in February 2003 examined the effect of 250 supplements on lean muscle mass and strength gains with resistance exercise. Of all the supplements, creatine was one of the few that consistently augmented lean muscle mass and strength in both the young and old.1 Another study published in 2003, which reviewed over 300 studies on the potential ergonomic value of creatine supplementation, concluded: “the preponderance of scientific evidence indicates that creatine supplementation appears to be a generally effective nutritional ergonomic aid for a variety of exercise tasks in a number ”2

Essential for Maintaining Energy
Creatine increases exercise capacity and muscle mass through its role in regenerating adenosine triphosphate, or ATP. ATP is the body’s primary “energy molecule” and is used in cells as energy. A useful analogy is to think of ATP as the body’s natural fuel in the same way natural gas is burned in a modern power plant to produce electricity. In the body, ATP is broken down, or “burned,” to produce biochemical energy. During this biochemical process, ATP loses one of its phosphate molecules and is changed to adenosine diphosphate, or ADP, and it is here that creatine becomes so vitally important. Creatine, which is stored in the body as creatine phosphate, or phosphocreatine, recharges ADP by giving up, or donating, a phosphate molecule to ADP, which produces more ATP that can then be used to make more energy. Without creatine to recharge ATP, we literally would be “starved” for energy.

The Brain’s Thirst for Energy
The next time you watch a football game, take a close look at one of the larger players on the offensive or defensive lines. Then try to imagine what part of his body consumes the most energy. Is it his tree-like arms? His barrel-sized chest? Or is it his massive legs, which have to carry that 350-pound frame all over the playing field?

The surprising answer is none of the above. The part of the human body that needs the most energy is the small, three-pound mass of gray matter residing in the skull—the brain. While the human brain makes up only 1-3% of a person’s total body weight, its billions of neurons (the brain’s active nerve cells) use 15-20% of the body’s total ATP-derived energy.

Energy derived from ATP is used by the brain for neuronal repair, to produce, package, and secrete neurotransmitters, and to power the bioelectrical discharges that occur when neurons communicate with one another. This bioelectrical process, which is active every second of every day, occurs via the rapid, continuous exchange of sodium and potassium ions across neuronal membranes, a process that depends on biochemical “pumps” inside the membrane to move the sodium and potassium ions back and forth. It has been estimated that as much as 45% of a neuron’s ATP may be used to power these all-important sodium-potassium pumps.

Creatine and Neurodegenerative Disorders
When you realize how important ATP and thus creatine is to brain function, it should come as no surprise that certain genetic disorders characterized by inborn errors in brain creatine metabolism can cause significant neurological defects. The first inborn error of brain creatine metabolism, GAMT (guanidinoacetate methyltransferase) deficiency, was clinically described in 1994.3

GMAT deficiency is an autosomal recessive disorder in which creatine levels in the brain are almost undetectable. This genetic deficiency manifests early in life as developmental delay, mental retardation, speech disabilities, and muscular weakness. Studies have shown that oral creatine supplementation by patients with this disorder can help slow or even reverse some of its most debilitating symptoms. AGAT (arginine: glycine amidinotransferase) deficiency is another autosomal genetic disorder in which minimal or no creatine metabolism in the brain results in mental retardation, language disorders, and poor fine motor skills.3 In a study of two sisters aged four and six years with AGAT deficiency, creatine supplementation caused rapid progress in fine motor skills and an increase in general cognitive development.

Three Deadly Neurological Diseases
Recent studies have shown that creatine can help not only in genetic disorders of creatine metabolism but also in nongenetic disorders of the central nervous system. It is now postulated by many brain researchers that dev-astating neurological disorders such as Parkinson’s, Huntington’s, and Alzheimer’s diseases share fundamental biochemical processes in their pathogenesis, such as oxidative stress and the impairment of creatine-powered ATP energy metabolism. To support this theory, varieties of animal models and, in some cases, human studies have shown that creatine supplementation can significantly ameliorate various common symptoms of many neurological diseases. It is believed that creatine may accomplish this by acting as a “booster” to the ATP energy system and also as a direct antioxidant.4

Parkinson’s is a chronic neurological disease that was first described in 1817 by Dr. James Parkinson, a London physician. Since that time, some limited medical therapies have been developed to treat this progressive disease, yet scientists still do not know what causes Parkinson’s disease. What is known is that neurons in the area of the brain known as the substantia nigra degenerate and die, causing reduced levels of dopamine, a vital brain neurochemical. Common symptoms of Parkinson’s include resting tremors, rigidity, balance problems, and depression.

While scientists continue to search for the cause of Parkinson’s, some medical researchers are postulating that impairment of the ATP energy-generated system and oxidative damage to neurons may play key roles in the pathogenesis of this disease affecting 1.5 million Americans.5 Supplements such as creatine, which can help boost ATP levels and work as antioxidants, are being examined as possibly safe and effective fighters of Parkinson’s disease. Recent animal studies are quite promising and show that creatine supplementation can protect against both the dopamine depletion and neuronal loss seen in Parkinson’s.5,6 While no human studies have been published, it makes sense to think that supplements such as creatine, which can act as a potent brain antioxidant and boost ATP function, may prove to be valuable tools in combating Parkinson’s.

Creatine supplementation also may prove to be a valuable weapon in the fight against Huntington’s disease. This devastating, irreversible neurological and genetic disorder affects a quarter of a million Americans and robs them of the ability to walk, think, talk and reason. At present, no effective cure exists for Huntington’s disease. Yet here again, creatine supplementation may prove to be useful in ameliorating some of the disease’s most debilitating effects. A 1998 study found creatine supplementation offered significant protection against Huntington’s-like brain damage in rats.7 The study’s authors concluded, “oral administration of either creatine or cyclocreatine can buffer cellular ATP concentrations and can attenuate cell death in animal models that mimic the neuropathological and clinical phenotype of Huntington’s disease.” More good news emerged from a study published in July 2003 that examined the effects of 10 grams a day of creatine on patients with Huntington’s disease.8 After one year, patients who took supplemental creatine showed no measurable change in their mental condition, a sign that creatine was able to stop the neurological degeneration associated with Huntington’s disease.

image

Some researchers believe that creatine may even be useful in combating the debilitating mental effects of Alzheimer’s disease. In cultured rat neurons, creatine has been shown to prevent the toxic effects of b-amyloid, a significant component of Alzheimer’s disease. With this in mind, the authors of a recent study that examined elderly patients who have the ApoE4 genotype (known to be a genetic risk factor for Alzheimer’s) stated: “… the potentially therapeutic effects of creatine in cognitive impairment and AD [Alzheimer’s disease] might merit further inquiry and should perhaps best not be overlooked.”9

Keeping Mind and Memory Strong
While creatine may prove useful in combating some of our most debilitating neurological diseases, recently published research highlights how creatine can help people without neurological disorders maintain optimal brain function and even improve memory.

Several well-researched studies have conclusively demonstrated that brain creatine levels are tied to optimal memory ability and retention. One study published in 2000 examined working memory ability—defined as the brain’s capacity to “hold” information for future use without the use of external cues—in children using magnetic resonance spectroscopy to measure various brain neurochemicals.10 The researchers found that children with the highest levels of creatine had the most robust working memory, and concluded: “… we speculate that higher resting creatine levels may allow for greater in-task activation [and] facilitate processing.”

Brain creatine levels also have been found to correlate with memory ability in older adults. A study published in February 2003 examined via magnetic resonance spectroscopy changes in the brain in 20 older adults (average age of 70) during memory training tasks.11 The researchers found that brain creatine levels rose during memory training. Another article published recently in Neuroscience Research examined the effects of supplemental creatine on mental fatigue in 24 adult men and women.12 In this double-blind, placebo-controlled trial, subjects who took 8 grams of creatine daily over a five-day period showed significantly less mental fatigue while performing simple mathematical calculations compared to the subjects who did not take creatine. The authors noted that while they did not know the specific mechanism of action, creatine appeared to help increase oxygen utilization in the brain.

Maintaining Optimal Brain Health
A study published in October 2003 sheds additional light on creatine’s ability to increase memory and even intelligence.13 The researchers used vegetarians as their subjects, postulating that creatine supplementation might be more effective in vegans because they do not derive much creatine from their diet (creatine is found mainly in meat). Forty-five subjects (12 men and 33 women) aged 19 to 37 were enrolled in a double-blind, placebo-controlled, cross-over study for a period of six weeks, during which some subjects were supplemented with 5 grams per day of creatine while the others received placebo. Both groups then took a battery of tests examining their memory and analytical skills. This was followed by a six-week “washout” period, during which no creatine or placebo was given, and then another six­-week trial during which subjects who received creatine in the first trial were given placebo, and vice versa. Following this, another battery of tests for memory and intelligence was administered.

As in earlier studies, subjects who took creatine scored significantly higher on tests for both memory and analytical skills compared to those who took placebo. The study’s authors concluded: “creatine supplementation had a significant positive effect on both working memory and intelligence, both tasks that require [mental] speed of processing. These findings underline a dynamic and significant role of brain energy capacity [and creatine] in influencing brain performance.”

However begrudgingly and slow, mainstream medicine appears to be coming to the acceptance that the brain and body are one. Many have long held the notion that one has to forsake the brain to develop the body, and vice versa. Creatine, however, has been shown in multiple studies to be a safe, effective supplement that nourishes both the mind and body, helping each to achieve greater levels of functioning.

References

1. Nissen SL, Sharp RL. Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta analysis. J Appl Physiol. 2003 Feb;94(2):651-9. Epub 2002 Oct 25.

2. Kreider RB. Effects of creatine supplementation on performance and training adaptations. Mol Cell Biochem. 2003 Feb;244(1-2): 89-94.

3. Wyss M, Schulze A. Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease? Neuroscience. 2002;112(2):243-60.

4. Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem Biophys Res Commun. 2002 Jan;290(1):47-52.

5. Beal MF. Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann N Y Acad Sci. 2003 Jun;991:120-31.

6. Tarnopolsky MA, Beal MF. Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol. 2001 May;49(5):561-74.

7. Matthews RT, Yang L, Jenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci. 1998 Jan 1;18(1):156-63.

8. Tabrizi SJ, Blamire AM, Manners DN, et al. Creatine therapy for Huntington’s disease: Clinical and MRS findings in a 1 year pilot study. Neurology. 2003 Jul 8;61(1):141-2.

9. Laakso MP, Hiltunen Y, Kononen M, et al. Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers. J Neural Transm. 2003 Mar;110(3):267-75.

10. Yeo RA, Hill D, Campbell R, Vigil J, Brooks WM. Developmental instability and working memory ability in children: a mag- netic resonance spectroscopy investigation. Dev Neuropsychol. 2000;17(2):143-59.

11. Valenzuela MJ, Jones M, Wen W, et al. Memory training alters hippocampal neuro- chemistry in healthy elderly. Neuroreport. 2003 Jul 18;14(10):1333-7.

12. Watanabe A, Kato N, Kato T. Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res.
2002 Apr;42(4):279-85.

13. Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc R Soc Lond B Biol Sci. 2003 Oct 22;270(1529):2147-50.