by Sol Orwell and Kurtis Frank T-Nation
Creatine? We can hear the comments already.
“I go to T Nation to read about the latest and greatest in building muscle and losing fat, and you want to tell me about creatine? What is this, 1997?”
Hold your water, tough guy. While discussions on creatine might not be burning up the bodybuilding message boards, creatine research has been on fire.
Searching on PubMed (a clearinghouse of almost all scientific studies) yields nearly 200 studies for creatine in 2012, and over 20 for the first month of 2013 alone. So while people like us may not be talking about creatine, researchers are still studying its many benefits – and what they’re finding is very interesting.
In fact, some of this new research could potentially move creatine from being considered a “muscle building” supplement to an important “general well-being” supplement. Imagine that, recommending that your mother take creatine!
Before we get to the new research, let’s address some of the misinformation on exactly what creatine is and what it does.
Creatine is stored in your body as high-energy phosphate groups in the form of phosphocreatine. For those that remember high school biology, your body’s primary source of energy (at the cellular level) is adenosine triphosphate (ATP).
Your body also has adenosine diphosphate (ADP) circulating in its cells. ATP is basically ADP plus a phosphate group. When your body is under stress or doing work (i.e., when you’re lifting weights), it needs immediate energy. Phosphocreatine gives ADP a phosphate group to become ATP, thus giving you energy, fast.
Stated simply, creatine is a stored form of energy that can be accessed quickly by your body.
The beauty of this is that creatine also aids in cellular function. Most of us only think about creatine helping our musculoskeletal cells, but it can also help the cells in your brain, bones, liver, and more!
Is Supplementing a Must?
What if you don’t want to supplement? Is it possible to get enough creatine from your diet? The answer is, yes, it can be done, but it’s not easy. To get to 5 grams of creatine (the recommended daily dosage), you’d need to eat roughly 2 pounds of beef or pig, or 3 pounds of chicken or rabbit.
Herring is arguably the richest dietary source of creatine, but you’d still need to eat 1.5 pounds of it – every single day. And we doubt that even the most creative chef could make a herring smoothie taste good.
It’s even harder for vegetarians. It’s commonly cited that cranberries are a rich source for creatine. The unfortunate reality is that it’s a rich source relative to other plant products. You’d still need to eat 500 pounds of cranberries to get 5 grams of creatine. Good luck with that.
Somewhere along the line, creatine got a bad rep in that it somehow damages your kidneys. The likely cause of this patently false accusation is failing to distinguish between creatine (the supplement) and creatinine, the diagnostic measurement for kidney problems.
If serum creatinine levels are high, your kidneys could be malfunctioning. Creatinine is also the waste product of creatine, and since creatine consumption increases your creatinine levels, this creates a false positive. Over half a dozen studies have been conducted that checked kidney function after creatine consumption – and no problems were found.
There was even a study in which a young man with a single, damaged kidney took creatine for a month, along with almost 3 grams of protein per kilogram of body weight (another widespread myth is “protein damages your kidneys.”)
The end result? No problems whatsoever.
The Latest Research
Now you know (or remember) what creatine does, why it works, that it’s hard to get through your diet, and that it’s safe. So what new benefits has research been finding?
Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressants, and according to their name, they inhibit reuptake of serotonin. Neurons pass molecules known as neurotransmitters from one to another, and reuptake occurs when the neurotransmitters don’t pass through and instead just end up back at the originating neuron. Preventing this from happening encourages signaling of the neurotransmitter to the target neuron.
Although creatine is not inherently an SSRI, a double blind study in which one group was given creatine alongside SSRIs found that creatine supplementation greatly improved the anti-depressive effects of the SSRI medication.
A few other studies have been conducted showing anti-depressive effects of creatine supplementation (mostly in women), but the above trial was the first well-conducted and statistically powerful study to support its anti-depressive effects.
May Help Against Neurological Disease
Several studies conducted on isolated neurons note that toxin-induced death seems to be related to a depletion of cellular energy. Neurons are able to resist being destroyed by toxins as long as they have energy (ATP) and, as discussed earlier, creatine can act as an extra source of ATP, thus enabling neurons with larger creatine storage to last a little bit longer by buffering energy stores.
That means that in some cases, creatine’s buffering effect could potentially save a cell from toxins.
Currently, the cells that are most investigated are those implicated in Parkinson’s Disease – dopamine producing cells in a region of the brain called the Substantia Nigra. That, obviously, could be a big deal.
Exerts Membrane Protective Effects
You might’ve heard creatine bashers say “you gain nothing but water weight,” or that your cells “inflate like little water balloons” while on creatine. While this certainly isn’t all that happens with creatine, creatine does have a fluid retention effect.
Interestingly, the creatine molecule may attach itself to a cell wall. Paired with the increased water retention in a cell, these two mechanisms suggest that creatine may protect cells from membrane damage.
Interestingly, the phenomenon of cell swelling is also linked to anti-cancer effects, although this has yet to be linked to oral creatine intake.
A main concern for people with diabetes (type II) is to reduce their fasting blood glucose, as high levels of blood glucose are associated with the ill effects of diabetes (nerve damage, eye damage, and kidney damage are reliably tied with high glucose and its downstream effects).
Creatine by itself has not yet been shown to reduce fasting blood glucose in diabetics, but similar to its augmentative anti-depressive effects, it appears creatine can augment the effects of exercise on reducing circulating blood glucose. Exercise tends to reduce blood glucose, and creatine seems to make the muscle draw more glucose into it when stimulated by exercise.
It appears to be related to a mechanism called AMPK, and activation of this protein is associated with a cell increasing the rate of uptake for both glucose and fatty acids. AMPK is also the target molecule of anti-diabetic therapies such as Metformin and Berberine, although creatine is much less potent than those two.
Cognitive benefits of creatine, beyond possible neuroprotection, are mostly related to memory formation and retention. These memory-enhancing effects of creatine are actually well established in vegetarians and vegans.
Creatine follows many vitamin-like motifs in the body, and those who don’t eat meat products seem to be in a state of relative deficiency. (As an aside, if you were completely deficient, it would be a genetic disorder that results in mental retardation.) This relative deficiency seems to be a prerequisite for the cognitive enhancing properties of creatine.
I’m not saying that not having creatine makes you dumb, but the studies seem to indicate that an optimal cognitive state requires sufficient creatine intake.
Although creatine doesn’t reliably increase cognition in omnivores, it has been implicated in increasing reaction speed and improving an omnivore’s cognition overall when they were otherwise sleep deprived.
Get On The Creatine Program
The above is but a sample of the research being conducted on creatine. Now well beyond its original fame as an effective muscle builder, creatine seems to help in many facets of healthy living.
Bottom line, creatine works and is safe. Considering how cheap it is, doesn’t it make sense to take it every day?
Alves CR, et al. Creatine-induced glucose uptake in type 2 diabetes: a role for AMPK-a? Amino Acids. (2012)
Andres RH, et al. Effects of creatine treatment on the survival of dopaminergic neurons in cultured fetal ventral mesencephalic tissue. Neuroscience. (2005)
Brustovetsky N, Brustovetsky T, Dubinsky JM. On the mechanisms of neuroprotection by creatine and phosphocreatine. J Neurochem. (2001)
Dahl O. Estimating protein quality of meat products from the content of typical amino-acids and creatine. J Sci Food Agric. (1965)
Genius J, et al. Creatine protects against excitoxicity in an in vitro model of neurodegeneration. PLoS One. (2012)
Groeneveld GJ, et al. Few adverse effects of long-term creatine supplementation in a placebo-controlled trial. Int J Sports Med. (2005)
Gualano B, et al. Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial. Eur J Appl Physiol. (2008)
Gualano B, et al. Effect of short-term high-dose creatine supplementation on measured GFR in a young man with a single kidney. Am J Kidney Dis. (2010)
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Klivenyi P, et al. Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. J Mol Neurosci. (2003)
Lyoo IK, et al. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am J Psychiatry. (2012)
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