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Although creatine offers an array of benefits, most people think of it simply as a supplement that bodybuilders and other athletes use to gain strength and muscle mass. Nothing could be further from the truth.
A substantial body of research has found that creatine may have a wide variety of uses. In fact, creatine is being studied as a supplement that may help with diseases affecting the neuromuscular system, such as muscular dystrophy (MD).
Recent studies suggest creatine may have therapeutic applications in aging populations for wasting syndromes, muscle atrophy, fatigue, gyrate atrophy, Parkinson’s disease, Huntington’s disease and other brain pathologies. Several studies have shown creatine can reduce cholesterol by up to 15% and it has been used to correct certain inborn errors of metabolism, such as in people born without the enzyme(s) responsible for making creatine.
Some studies have found that creatine may increase growth hormone production.
What is creatine?
Creatine is formed in the human body from the amino acids methionine, glycine and arginine. The average person’s body contains approximately 120 grams of creatine stored as creatine phosphate. Certain foods such as beef, herring and salmon, are fairly high in creatine.
However, a person would have to eat pounds of these foods daily to equal what can be obtained in one teaspoon of powdered creatine.
Creatine is directly related to adenosine triphosphate (ATP). ATP is formed in the powerhouses of the cell, the mitochondria. ATP is often referred to as the “universal energy molecule” used by every cell in our bodies. An increase in oxidative stress coupled with a cell’s inability to produce essential energy molecules such as ATP, is a hallmark of the aging cell and is found in many disease states.
Key factors in maintaining health are the ability to: (a) prevent mitochondrial damage to DNA caused by reactive oxygen species (ROS) and (b) prevent the decline in ATP synthesis, which reduces whole body ATP levels. It would appear that maintaining antioxidant status (in particular intra-cellular glutathione) and ATP levels are essential in fighting the aging process.
It is interesting to note that many of the most promising anti-aging nutrients such as CoQ10, NAD, acetyl-l-carnitine and lipoic acid are all taken to maintain the ability of the mitochondria to produce high energy compounds such as ATP and reduce oxidative stress.
The ability of a cell to do work is directly related to its ATP status and the health of the mitochondria. Heart tissue, neurons in the brain and other highly active tissues are very sensitive to this system. Even small changes in ATP can have profound effects on the tissues’ ability to function properly.
Of all the nutritional supplements available to us currently, creatine appears to be the most effective for maintaining or raising ATP levels.
How does creatine work?
In a nutshell, creatine works to help generate energy. When ATP loses a phosphate molecule and becomes adenosine diphosphate (ADP), it must be converted back to ATP to produce energy. Creatine is stored in the human body as creatine phosphate (CP) also called phosphocreatine.
When ATP is depleted, it can be recharged by CP. That is, CP donates a phosphate molecule to the ADP, making it ATP again. An increased pool of CP means faster and greater recharging of ATP, which means more work can be performed.
This is why creatine has been so successful for athletes. For short-duration explosive sports, such as sprinting, weight lifting and other anaerobic endeavors, ATP is the energy system used.
To date, research has shown that ingesting creatine can increase the total body pool of CP which leads to greater generation of energy for anaerobic forms of exercise, such as weight training and sprinting. Other effects of creatine may be increases in protein synthesis and increased cell hydration.
Creatine has had spotty results in affecting performance in endurance sports such as swimming, rowing and long distance running, with some studies showing no positive effects on performance in endurance athletes.
Whether or not the failure of creatine to improve performance in endurance athletes was due to the nature of the sport or the design of the studies is still being debated.
Creatine can be found in the form of creatine monohydrate, creatine citrate, creatine phosphate, creatine-magnesium chelate and even liquid versions.
However, the vast majority of research to date showing creatine to have positive effects on pathologies, muscle mass and performance used the monohydrate form. Creatine monohydrate is over 90% absorbable. What follows is a review of some of the more interesting and promising research studies with creatine.
Creatine and neuromuscular diseases
One of the most promising areas of research with creatine is its effect on neuromuscular diseases such as MD. One study looked at the safety and efficacy of creatine monohydrate in various types of muscular dystrophies using a double blind, crossover trial.
Thirty-six patients (12 patients with facioscapulohumeral dystrophy, 10 patients with Becker dystrophy, eight patients with Duchenne dystrophy and six patients with sarcoglycan-deficient limb girdle muscular dystrophy) were randomized to receive creatine or placebo for eight weeks.
The researchers found there was a “mild but significant improvement” in muscle strength in all groups. The study also found a general improvement in the patients’ daily-life activities as demonstrated by improved scores in the Medical Research Council scales and the Neuromuscular Symptom scale. Creatine was well tolerated throughout the study period, according to the researchers.1
Another group of researchers fed creatine monohydrate to people with neuromuscular disease at 10 grams per day for five days, then reduced the dose to 5 grams per day for five days.
The first study used 81 people and was followed by a single-blinded study of 21 people.
In both studies, body weight, handgrip, dorsiflexion and knee extensor strength were measured before and after treatment. The researchers found “Creatine administration increased all measured indices in both studies.” Short-term creatine monohydrate increased high-intensity strength significantly in patients with neuromuscular disease.2
There have also been many clinical observations by physicians that creatine improves the strength, functionality and symptomology of people with various diseases of the neuromuscular system.
Creatine and neurological protection/brain injury
If there is one place creatine really shines, it’s in protecting the brain from various forms of neurological injury and stress. A growing number of studies have found that creatine can protect the brain from neurotoxic agents, certain forms of injury and other insults.
Several in vitro studies found that neurons exposed to either glutamate or beta-amyloid (both highly toxic to neurons and involved in various neurological diseases) were protected when exposed to creatine.3 The researchers hypothesized that “? cells supplemented with the precursor creatine make more phosphocreatine (PCr) and create larger energy reserves with consequent neuroprotection against stressors.”
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 the tip of the iceberg showing creatine may have therapeutic uses for a wide range of neurological disease as well as injuries to the brain.
One researcher who has looked at the effects of creatine commented, “This food supplement may provide clues to the 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, the researchers looked at:
1) Ejection fraction of the heart (blood present in the ventricle at the end of diastole and expelled during the contraction of the heart)
2) 1-legged knee extensor (which tests strength)
3) Exercise performance on the 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, the ejection fraction at rest and during the exercise phase did not increase.
However, the biopsies revealed a considerable increase in tissue levels of creatine and creatine phosphate in the patients getting the supplemental creatine. More importantly, patients getting the 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, the 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 the effects of creatine supplementation on endurance and muscle metabolism in people with congestive heart failure.11 In particular the 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 the 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 the placebo group.
This shows that creatine supplementation in chronic heart failure augments skeletal muscle endurance and attenuates the abnormal skeletal muscle metabolic response to exercise.
It is important to note that the 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.
Conclusion
Creatine is quickly becoming one of the 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 the 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 the next big find in anti-aging nutrients.
Although the doses used in some studies were quite high, recent studies suggest lower doses are just as effective for increasing the overall creatine phosphate pool in the body.
Two to three grams per day appears adequate for healthy people to increase their tissue levels of creatine phosphate. People with the aforementioned pathologies may benefit from higher intakes, in the 5-to-10 grams per day range.
About the Author
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Regular readers of my work have come to expect articles about the power of whey proteins to potentaily fight cancer and improve immunity among its many benefits. The ability of whey to fight cancer, improve glutathione levels and immunity, is well documented.
Additional research suggests possible medical uses for whey that are quite unexpected and different from whey’s traditional role as an immune booster and anti cancer functional food. For example, whey may be able to reduce stress and lower cortisol and increase brain serotonin levels, improve liver function in those suffering from certain forms of hepatitis, reduce blood pressure, as well as other amazing recent discoveries, such as whey’s possible effects on weight loss, which is the focus of this article.
What is whey?
When we talk about whey we are actually referring to a complex milk-based ingredient made up of protein, lactose, fat and minerals. Protein is the best-known component of whey and is made up of many smaller protein subfractions such as: Beta-lactoglobulin, alpha-lactalbumin, immunoglobulins (IgGs), glycomacropeptides, bovine serum albumin (BSA) and minor peptides such as lactoperoxidases, lysozyme and lactoferrin.
Each of the subfractions found in whey has its own unique biological properties. Modern filtering technology has improved dramatically in the past decade, allowing companies to separate some of the highly bioactive peptides - such as lactoferrin and lactoperoxidase - from whey.
Some of these subfractions are only found in very minute amounts in cow’s milk, normally at less than one percent (e.g., lactoferrin, lactoperoxidase, etc.)
The medicinal properties of whey have been known for centuries. For example, an expression from Florence, Italy. Circa 1650, was “Chi vuol viver sano e lesto beve scotta e cena presto” which translates into English as “If you want to live a healthy and active life, drink whey and dine early.”
Another expression from Italy regarding the benefits of whey (circa 1777) was “Allevato con la scotta il dottore e in bancarotta.” Which translates into English “If everyone were raised on whey, doctors would be bankrupt.”
Is whey a weight loss functional food?
A few years ago, I might have said no. Now I am not so sure. Although there was a smattering of studies suggesting whey had certain properties that might assist with weight loss, a number of recent studies appear to further support the use of whey as a possible weight loss supplement. Most interesting - at least to nerds like me - the effect appears to be not by a single mechanism, but several. This article will briefly explore a few possible pathways by which whey may assist the dieter.
“I’m hungry!”
Human hunger and appetite are regulated by a phenomenally complicated set of overlapping feedback networks, involving a long list of hormones, psychological factors as well as physiological factors, all of which are still being elucidated. It’s a very intensive area of research right now, with various pharmaceutical companies looking for that “magic bullet” weight loss breakthrough they can bring to market.
One hormone getting attention by researchers looking for possible solutions to obesity is cholecystokinin (CCK). Several decades ago, researchers found CCK largely responsible for the feeling of fullness or satiety experienced after a meal and partially controls appetite, at least in the short term.
Cholecystokinin (CCK) is a small peptide with multiple functions in both the central nervous system and the periphery (via CCK-B and CCK-A receptors respectively). Along with other hormones, such as pancreatic glucagon, bombesin, glucagon-like peptide-1, amide (GLP-1), oxyntomodulin, peptide YY (PYY) and pancreatic polypeptide (PP)., CCK is released by ingested food from the gastrointestinal tract and mediates satiety after meals.
Such a list would not be complete without at least making mention of what many researchers consider the “master hormones” in this milieu, which is insulin and leptin. If that’s not confusing enough, release of these hormones depends on the concentration and composition of the nutrients ingested.
That is, the type of nutrients (i.e., fat, protein, and carbohydrates) eaten, the amount of each eaten, and composition of the meal, all effect which hormones are released and in what amounts… Needless to say, it’s a topic that gets real complicated real fast and the exact roles of all the variables is far from fully understood at this time, though huge strides have been made recently.
Whey’s effects on food intake.
This (finally!) brings us to whey protein. Whey may have some unique effects on food intake via its effects on CCK and other pathways. Many studies have shown that protein is the most satiating macro-nutrient. However, it also appears all proteins may not be created equal in this respect.
For example, two studies using human volunteers compared whey vs. casein (another milk based protein) on appetite, CCK, and other hormones (Hall WL, Millward DJ, Long SJ, Morgan LM.Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr. 2003 Feb;89(2):239-48).
The first study found that energy intake from a buffet meal ad libitum was significantly less 90 minutes after a liquid meal containing whey, compared with an equivalent amount of casein given 90 minutes before the volunteers were allowed to eat all they wanted (ad libitum) at the buffet. In the second study, the same whey preload led to a plasma CCK increase of 60 % ( in addition to large increases in glucagon-like peptide [GLP]-1 and glucose-dependent insulinotropic polypeptide) following the whey preload compared with the casein.
Translated, taking whey before people were allowed to eat all they wanted (ad libitum) at a buffet showed a decrease in the amount of calories they ate as well as substantial increases in CCK compared to casein. Subjectively, it was found there was greater satiety followed the whey meal also.
The researchers concluded “These results implicate post-absorptive increases in plasma amino acids together with both CCK and GLP-1 as potential mediators of the increased satiety response to whey and emphasize the importance of considering the impact of protein type on the appetite response to a mixed meal.” Several animal studies also find whey appears to have a pronounced effect on CCK and or satiety over other protein sources.
It should be noted however that not all studies have found the effect of whey vs. other protein sources on food intake (Bowen J, Noakes M, Clifton P, Jenkins A, Batterham M.Acute effect of dietary proteins on appetite, energy intake and glycemic response in overweight men. Asia Pac J Clin Nutr. 2004;13(Suppl):S64.).
It should also be noted that although studies find protein to be the most satiating of the macro-nutrients, certain protein sources (e.g. egg whites) may actually increase appetite (Anderson GH, Tecimer SN, Shah D, Zafar TA. Protein source, quantity, and time of consumption determine the effect of proteins on short-term food intake in young men. J Nutr. 2004 Nov;134(11):3011-5.), so protein sources appear worth considering when looking to maximize weight loss and suppress appetite.
How whey achieves this effect is not fully understood, but research suggests it’s due to whey’s high glycomacropeptide and alpha-lactalbumin content, as well as its high solubility compared to other proteins, and perhaps it’s high percentage of branch chain amino acids (BCAA’s).
Whey’s effects on bodyfat, insulin sensitivity, and fat burning… .
So we have some studies suggesting whey may have some unique effects on hormones involved in satiety and or may reduce energy (calorie) intake of subsequent meals, but do we have studies showing direct effects of whey vs. other proteins on weight loss? In animals at least, whey has looked like a promising supplement for weight loss.
Although higher protein diets have been found to improve insulin sensitivity, and may be superior for weight loss (with some debate!) then higher carbohydrate lower protein diets, it’s unclear if all proteins have the same effects.
One study compared whey to beef (Damien P. Belobrajdic,, Graeme H. McIntosh, and Julie A. Owens. A High-Whey-Protein Diet Reduces Body Weight Gain and Alters Insulin Sensitivity Relative to Red Meat in Wistar Rats. J. Nutr. 134:1454-1458, June 2004) and found whey reduced body weight and tissue lipid levels and increased insulin sensitivity compared to red meat.
Rats were fed a high-fat diet for nine weeks, then switched to a diet containing either whey or beef for an additional six weeks. As has generally been found in other studies, the move to a high dietary protein reduced energy intake (due to the known satiating effects of protein compared to carbs or fat), as well as reductions in visceral and subcutaneous bodyfat.
However, the rats getting the whey, there was a 40% reduction in plasma insulin concentrations and increased insulin sensitivity compared to the red meat. Not surprisingly, the researchers concluded “These findings support the conclusions that a high-protein diet reduces energy intake and adiposity and that whey protein is more effective than red meat in reducing body weight gain and increasing insulin sensitivity.”
Other studies suggest taking whey before a workout is superior for preserving/gaining lean body mass (LBM) and maintaining fat burning (beta oxidation) during exercise over other foods taken prior to a workout. The study called “A preexercise lactalbumin-enriched whey protein meal preserves lipid oxidation and decreases adiposity in rats” (Am J Physiol Endocrinol Metab 283: E565-E572, 2002.) came to some very interesting conclusions.
One thing we have known a long time is the composition of the pre-exercise meal will affect substrate utilization during exercise and thus might affect long-term changes in body weight and composition. That is, depending on what you eat before you workout can dictate what you use for energy (i.e. carbs, fats, and or proteins) which alters what you burn (oxidize) for energy.
The researchers took groups of rats and made the poor buggers exercise two hours daily for over five weeks (talk about over training!), either in the fasted state or one hour after they ingested a meal enriched with a simple sugar (glucose), whole milk protein or whey protein.
The results were quite telling. Compared with fasting (no food), the glucose meal increased glucose oxidation and decreased lipid oxidation during and after exercise. Translated, they burned sugar over body fat for their energy source. In contrast, the whole milk protein and whey meals preserved lipid oxidation and increased protein oxidation. Translated, fat burning was maintained and they also used protein as a fuel source.
Not surprisingly, the whey meal increased protein oxidation more than the whole milk protein meal, most likely due to the fact that whey is considered a “fast” protein that is absorbed rapidly due to it’s high solubility.
As one would expect, by the end of the five weeks, body weight was greater in the glucose, whole milk protein and whey fed rats than in the fasted ones. No shock there. Here is where it gets interesting: In the group getting the glucose or the whole milk protein, the increase in weight was from bodyfat, but in the whey fed group, the increase in weight was from an increase in muscle mass and a decrease in bodyfat!
Only the rats getting the whey before their workout increased muscle mass and decreased their bodyfat. The researchers theorized this was due to whey’s ability to rapidly deliver amino acids during exercise. Is this the next big find in sports nutrition or those simply looking to preserve muscle mass loss due to aging?
Hard to say at this time being it was done in rats, but if it turns out to be true in humans (and there is no reason people can’t try it now) it would indeed be a breakthrough in the quest to add muscle and lose fat.
About the Author
More from sports nutrition expert and industry author Will Brink: Online Articles: http://www.brinkzone.com/onlinearticles.html Muscle Building: http://www.musclebuildingguide.com/ Diet Supplements: http://www.dietsupplementsreview.com/
