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UPDATE: Dark Side of Creatine – The Science Behind the Truth

 

I apologize for my late response to these posts. I was on a long trip overseas. Regardless, I’d like to put the record straight regarding this topic.  (Read my first creatine post here)

  1. Creatine phosphate has been reported to inhibit AMPK activity (Ponticos M, Lu QL, Morgan JE, Hardie DG, Partridge TA, and Carling D. Dual regulation of the AMP-activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle. EMBO J 17: 1688 –1699, 1998. Rafaeloff-Phail R, Ding L, Conner L, Yeh WK, McClure D, Guo H, Emerson K, and Brooks H. Biochemical regulation of mammalian AMP-activated protein kinase activity by NAD and NADH. J Biol Chem 279: 52934 –52939, 2004.). In fact, AMPK and creatine phosphate (PCR) antagonizes each other. Just to explain my opinion, here are some background facts.AMPK (mammalian AMP-activated protein kinase) is a kinase enzyme that plays a major role in response to stress, particularly energy stress such as during exercise or fasting. When activated, AMPK initiates changes in cellular metabolism enabling working muscles to better meet energy challenge. These metabolic responses include:
    • Increased glucose transport
    • Increased fatty acid oxidation
    • Increased mitochondrial biogenesis (which makes skeletal muscle more durable when encountering energy challenge such as during intense or prolonged physical drill).

    The point is: AMPK was found to be negatively regulated by the cellular ratio of phosphocreatine/creatine. The higher this ratio is, the more inactivated AMPK becomes. Hence, the higher the level of creatine phosphate is (all creatine supplements increase cellular levels of creatine phosphate), the more inhibited AMPK will be.

  2. Phosphocreatine is formed by phosphorylation of creatine via the enzyme creatine kinase (CK). This process serves as an important energy reservoir for ATP production. Phosphocreatine is a carrier of phosphate energy (ATP) which inhibits AMPK.Whereas AMPK is activated by increased cellular level of AMP (a metabolic byproduct of energy depletion) such as during intense exercise; it is inhibited by high levels of ATP (and low levels of cellular AMP) such as after feeding.Similarly, AMPK is inhibited by high cellular levels of phosphocreatine over low levels of creatine (such as after creatine supplementation) and rapidly activated by lower levels of phosphocreatine such as during exercise without creatine supplements.All this might seem complicated but the principle behind is simple:Energy depletion activates AMPK, increases fat burning, increases energy utilization and increases mitochondrial biogenesis whereas energy loading (creatine supplementation; carb-loading) causes the opposite – inhibition of AMPK and related effects.One more note, creatine phosphate seems to indirectly inhibit NAD, a key deacetylate enzyme that plays a critical role in the regulation of mitochondrial homeostasis, energy utilization and resistance to aging.
  3. Creatine supplementation can help increase muscle mass and improve strength performance. But so do other performance enhancing substances such as steroids, growth hormone and pro-hormones. Being performance enhancing (and anabolic) does NOT make creatine healthy.
  4. Creatine supplements have shown to benefit clinical cases such as creatine insufficiency, certain neurologic dysfunctions and muscle dystrophy.Similarly there are thousands of other substances out there – drugs and medications in particular – with proven scientific records of benefiting clinical cases involving metabolic disorders or diseases. For instance, antibiotics are still highly effective against infection; but this does not justify the use of antibiotics by healthy individuals. Certainly not on a daily basis.
  5. All creatine supplements are synthetic and therefore unnatural. It is my view that all synthetic supplements should be avoided. Growing body of evidence from aging research indicates that the human body hasn’t evolved for synthetic nutrients. In spite of the impressive research behind creatine’s anabolic and strength enhancing properties, it is yet a drug-like substance which leads me to the next issue.
  6. Side effects – Though denied by the industry and overlooked by those creatine users who deliberately choose to ignore this part, creatine does cause side effects. These include water retention (edema), undesirable weight gain, potential muscle injury, loss of capacity to self-produce creatine, gastrointestinal disorders, anterior leg compartment syndrome, dehydration, cramping, and kidney and liver damage. And though arguable, there is yet the concern that long-term effects of creatine supplements remain unknown.
  7. Energy loading substance. Not only that creatine is an energy loading substance that increases cellular ATP regeneration and thus inhibits AMPK, it is generally recommended to “load” creatine with carbohydrates. Studies have shown that adding 93g carbs to 5g creatine increases muscle creatine by 60%. Lower carbs servings with creatine were not as effective at promoting muscle creatine retention. Given the recommendation for a loading phase of 20g creatine per day. You can calculate how much carbs (typically dextrose) one needs to shove in in order to get maximum creatine retention. So here again, though creatine and carb loading can help boost performance, the excessive carb loading (particularly from dextrose) has a detrimental effect on insulin and overall health.If you’re using creatine to enhance performance or build muscle, you need to ask yourself what is more important – your performance and muscle size or your health. Pumping and loading energy is certainly effective in achieving athletic scores, but have no doubt, it also lowers your resistance to disease and aging.

In Conclusion

Creatine is indeed one of the most researched supplements with proven record of increasing muscle mass and strength gain; it is also one of the biggest money makers in the sport nutrition industry. Nevertheless, creatine is a synthetic substance with a drug-like impact involving potential side effects and risks.

Criticizing creatine might be politically incorrect these days, but I believe that that’s exactly what makes this issue particularly important – expressing true opinion about products which are treated as the “sacred cows” by mainstream fitness and the industry. I’ve always been expressing my opinion regardless to how popular they are.

Fifteen years ago, my concept of intermittent fasting and skipping meals were considered dietary heresy. Today IF is one of the most popular approaches to dieting and every diet guru tries to jump on that wagon.

There is an evolutionary process to controversial ideas. Opinions that were initially raising great resistance and anger have been proven later as factually true and thus respected accordingly. I was ahead of time when I came with the concept of intermittent fasting as a practical diet and perhaps I’m ahead of time with this issue now.

Final Note: Creatine manufacturers insist that creatine is safe. But how safe is it? The industry tries to “wash out” the evidence of side effects. I remember how aspartame was considered “safe” twenty years ago, when it was used as a popular sweetener in all sorts of sport nutrition products. I also remember how fructose was popularized as a safe sugar that does not raise insulin. It is now known that none of these are safe. Would creatine be a similar case? Only time will tell…

References


Poortmans JR, Francaux M: Adverse effects of creatine supplementation: fact or fiction? Sports Med 2000, 30:155-170.

Pritchard NR, Kalra PA: Renal dysfunction accompanying oral creatine supplements. Lancet 1998, 351:1252-1253.

La creatine dangereuse? L’Equipe10. 1998, April 10

Koshy KM, Giswold E, Scheenberger EE: Interstitial nephritis in a patient taking creatine. N Engl J Med 1999, 340:814-5.

Thorsteinsdottir B, Grande JP, Garovic VD: Acute renal failure in a young weight lifter taking multiple food supplements including creatine monohydrate. J Renal Nutr 2006, 16(4):341-345.

Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR: Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol 1997, 76:566-567.

Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux M: Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Med Sci Sports Exerc 2005, 37:1717-1720.

Schilling BK, Stone MH, Utter A, Kearney JT, Johnson M, Coglianese R, Smith L, O’Bryant HS, Fry AC, Starks M, Keith R, Stone ME: Creatine supplementation and health variables: a retrospective study.
Med Sci Sports Exerc 2001, 33:183-188.

About Ori Hofmekler — founder of Defense Nutrition and author of The Warrior Diet, is a nutritional and fitness expert. Follow him on Twitter, Facebook and Google+.

2 Comments

  1. Avatar for Ori Hofmekler
    Dan Paisley-
    November 28, 2014 at 6:42 pm

    Wow, better stop eating meat seeing as people get the majority of their daily intake from that and it is synthesised in the body exactly the same way… Surprising someone selling organic supplements saying “synthetic” hmm or non organic is evil.

    Won’t even get into the Aspartame issue, you must have PKU and can’t consume Phenylalanine? Considering Aspartame get’s broken down into constituents, methanol, aspartic acid and phenylalanine above, which you consume more of in your every day diet from meat, fruit and green leafy veg.

    Must be why all them millions of people drinking protein shakes, diet drinks among other things are all passing out in the street and getting fatal diseases… oh wait there not.

    Not saying it’s good for you, just protecting people from fear mongering black and white conspiracy, *******

    Be realistic at least.

  2. Avatar for Ori Hofmekler
    Dan Paisley-
    November 28, 2014 at 6:43 pm

    Wow, better stop eating meat seeing as people get the majority of their daily intake from that and it is utilised in the body exactly the same way… Surprising someone selling organic supplements saying “synthetic” hmm or non organic is evil.

    Won’t even get into the Aspartame issue, you must have PKU and can’t consume Phenylalanine? Considering Aspartame get’s broken down into constituents, methanol, aspartic acid and phenylalanine above, which you consume more of in your every day diet from meat, fruit and green leafy veg.

    Must be why all them millions of people drinking protein shakes, diet drinks among other things are all passing out in the street and getting fatal diseases… oh wait there not.

    Not saying it’s good for you, just protecting people from fear mongering black and white conspiracy, *******

    Be realistic at least.

    How long before this is deleted, got a feeling it's that type of site, conversation not allowed that contradicts your view?