Fit Kids = Smart Kids, Creatine & Muscle Repair, Epigenetic Transfer From one Leg to Another. Plus: Fat Effects of Anti-Psychotics, Larger Muscle = Greater CNS Impact, Rhodiola a Natural Opiate, Hawthorn for More & Thicker Hair

It's never too early for your first push-up ;-)

"10" is this week's SuppVersity figure of the week. Ten as in "ten push-ups" which is the mean number of push-ups the 12 year-old boys and girls from the Coe study you can read about in one of the items of today's news mash-up aka "On Short Notice". I am honestly not yet sure what to make of it, it's not as bad as what I had expected based on a couple of observations I have made as of late, but it still goes to show you that you cannot take the most fundamental feats of physical fitness for granted, when it comes to pre-/peri-pubertal kids in today's sedentary society.

Now, while I am still trying to make up my mind I would suggest we take a look at the actual outcomes of the study. The 10 push-ups were after all only part of the subject characteristics and not the reason Coe et al. actually conducted their study.

Fit Kids are smart kids - Strength and cardio both matter!

You can hardly start your career as a physical culturist too early, there are simply way too many benefits from giving your body the nutrients and the exercise it needs and therefore it is actually not surprising that conclusion of a recently published paper in the Journal of Sports Medicine and Physical Fitness reads:

"Students with the highest fitness level performed better on standardized tests and students with the lowest fitness level performed lower in class grades" (Coe. 2013)

Interestingly enough, this effect was associated with both cardiorespiratory fitness and strength, which brings us back to yesterday's news about the PGC-1 alpha isoforms (read the comments as well) and the detailed follow up I just decided to post on the whole matter, tomorrow.

Figure 1: Spearman rank correlations and achievements cores in terms of grades (0:min, 80:max), test scores (% of max) and combined (% of mean of all kids; data based on Coe. 2013)

Since this is the first study of its kind to investigate all five established parameters of health-related fitness (HFR), it should also be mentioned that body composition, flexibility and muscular endurance did not show the same statistically significant correlations the scientists observed for cardiorespiratory endurance and muscle strength in the kids (52% boy, 48% girls; all from the same age group ~12 years). Now, it would be nice if the people who design the curricula would keep that in mind, when they add junk after junk to the syllabus and regard sports and being active as an unnecessary diversion from the constant intellectual drills.

Creatine can do much, but it can't accelerate skeletal muscle repair after a workout 

The results of a recent study from the Department of Kinesiology and Physical Education at the Wilfrid Laurier University in Canada (McKinnon. 2013) , in the course of which  a total of 27 male (n = 15) and female (n = 12) participants between the ages of 18-24 completed an experimental training protocol with either

• 2x creatine monohydrate (20g) and a carbohydrate supplement (20g) in order to blend consistency and taste (CREA),
• 2x 40 g of maltodextrin only in 500mL of water (MALTO), or
• no supplementation at all (control)  

The supplement was consumed over a 5-day period (check out the "Pharmacokinetics of Creatine" posts and you will learn that this dosage regimen is an unnecessary overkill - even if you insist on "loading") after which the participants participated in a baseline strength test that was followed by a muscle-damaging protocol that consisted of maximal force eccentric contractions:

Suggested read: "Creatine a Proven Non-Anabolic Agent: It's the Increase in Training Intensity that Will Give You the Hypertrophic Edge (read full story)

"Subjects performed 60 maximal eccentric contractions that were divided into 6 sets of 10 repetitions, with a 45 second rest period between repetitions.  The velocity of eccentric contractions was varied between sets (2 at 75°/sec, 2 at 90°/sec, and 2 at 120°/sec). This protocol has been used in previous studies and has been shown to be an effective means of inducing skeletal muscle damage (Cooke et al., 2009). The researchers also provided verbal encouragement to the subjects to help maintain maximal effort throughout the protocol." (McKinnon. 2013)

After adequate rest, the first of 5 post-tests was conducted. The results (figure 2) clearly show that despite the overall greater force recovery in the creatine group, the relative rebound after an allegedly higher drop was seen in the MALTO group while it was minimal in the no-supplement group.

Figure 2: Force recovery and muscle soreness at 0h, 24h, 48h, 72h, 96h in the control, maltodextrin and creatine groups subsequent to a 5-day suppelemtation regimen (nothing,  2x 20g crea + 2x20g malto, or 2x40g malto (McKinnon. 2013)

Overall the scientists are yet still right, when they say that "creatine supplementation failed to significantly influence indices elbow flexor muscle damage or rate of muscle recovery following eccentric muscle contractions." After all, there were no statistically significant differences between either the muscle force loss and rate of recovery or muscle soreness (small figure in figure 2) between the groups - and it is unlikely that this would change after the initial 96h of recovery.

Additional suggested reads:

• DHEA Blunts Muscle Damage During 5 Days of Combined Endurance, Strength and HIIT Training in Young Men (read more)
• Speed Up Your Regeneration and Propel Your Gains by Taking a HOT Bath Bath 2-Days Before Arduous Workouts (read more)
• Overtraining, Inflammation, Insufficient Repair: Scientists Shed Some More Light on the Counterproductive Triad of Ups & Downs in Testosterone, IL-6, IL-10, COX II & Co (read more)

Ah, I almost forget to mention, you see that the mean isometric peak torque is not even back up to 100% after 96h, right? Remember that whenever you decide that it would be a good idea to do "yet another set of forced reps". It is possible that the seasoned strength training veteran you are, you recover faster than the subjects in the study at hand who had not trained for at least 4 months, but it stands out of question that eccentric forced reps will increase the time you need to regenerate, let alone to see what we are all striving for, i.e. super-compensation effects (see suggested links on the right for more on "doing too much" and faster recuperation after workouts).

Working out one leg changes genes in the other leg as well 

The progress research in the area of epigenetics, i.e. the changes of gene methylation and thus activity in response to nutrition, exercise and other variables you can easily control is actually amazing. With the recent publication of a study into what you may call epi-genetic cross-reactivity further contributing to our insights into the relations of the local and system epigenetic effects of exercise and their respective metabolic downstream effect (Catoire. 2013).

Figure 3: Graphical summary of the study design and selected results (Catoire. 2013)

As you can see in my graphical mini-summary of the study design (top) and outcomes (middle + bottom) in figure 3 there was a whole lot going on... and that despite the fact that I did already spare you a complete page with font 10 lists of genes that changed (you do have the numbers, I guess that shall suffice) and paired them in groups. What's funny is that, when it's all said and done, this does yet again tie in to yesterday's news on PGC-1 alpha 4 - how? Well, let's hear (or read), what the scientists have to say in the discussion of their results:

"Many of the observed exercise-induced changes in gene expression are likely part of an acute stress response related to disturbances in homeostasis elicited by exercise. The most highly induced genes in the exercising leg were all members of the NR4A family, a subgroup of orphan receptors within the nuclear receptor superfamily. NR4A1 and NR4A3 have been reported to be upregulated shortly after acute exercise and during recovery in rat, pig, and human [24], and this upregulation likely occurs locally by contractile stimuli. This finding was confirmed by our study in which we observed an upregulation of NR4As in the exercising, but not in the non-exercising leg. NR4A transcription factors are also known to be induced by adrenaline and noradrenaline. Circulating adrenalin and noradrenalin levels were increased in our study but must exert only a minor effect as NR4As were exclusively induced in the exercising leg,. [...] NR4A1 and 3 are thought to play a key role in regulating energy metabolism and early adaptation. [...] The results may imply that NR4A family might play an important role in the regulation of metabolic responses after exercise." (Catoire. 2013)

The study at hand does thus add yet another puzzle piece to the image of the crossroads of the endocrine (from one tissue to the other) and intracrine (in this case in the exercised muscle) effects of energy and metabolic changes on the one hand and muscular contraction and local stress, on the other hand. As closely interwoven as they are, we are now - thanks to the novel gene essays - able to see through the complex network, understand what exercise does to our physiology and can then, in the next step, come up with ways to modulate these effects for our own benefit.

It is clear that this is not going to be easy and the presence of two "mutants" among the 12 relatively old  study participants (52 year; "old" only for studies like this, of course!) suggests that any cookie cuter solutions are probably about to fail. I mean, if you have got two guys out of twelve where the overall magnitude of gene expression changes in the exercising and non-exercising leg were very similar, it is more than likely that you would see these and other anomalies very frequently; and each of them would have to be considered if you wanted to design he optimal workout (nutrition and supplementation) regimen for an individual (good news for personal trainers, if you know what you are doing, no sciency compendium is ever going to replace you ;-)

In rehab, doctors and therapists use the neurological stimulation a stiff leg receives, when you move the other while looking into a mirror that fools you into believing that the stiff leg would be moving as well.

In that it does not even really matter, whether the observed anomalies were actually due to genetic differences or, as the scientists suspect simply the result of unconsciously performed isometric contractions in of the non-exercising leg. The ensuing neuronal activation could have brought about similar effects as they are observed (and intended) during mirror therapy (see image on the right), where an involuntary neural stimulation of the muscles in a stiff leg occurs, when the mirror fools you into believing that you actually just moved your stiff leg, or other body part, when it was in fact only the counter-lateral limb that moved (note: one of the latest reviews of the literature says about its efficacy in stroke rehab would facilitate the recovery of "motor function, activities of daily living and pain" and could be recommended "at least as an adjunct to normal rehabilitation for patients after stroke"; cf. Thieme. 2013).

With the effects of neural stimulation, which has already been shown to induce gene expression changes via increased calcium concentrations in the skeletal muscle as well as via other mechanisms (Long. 2007; Kanzleiter. 2009; Chin. 2010, we do thus have a third player in the epigenetic / protein regulatory exercise orchestrate that does now consist of a metabolic, a contractile / stress mediated and a neuronal component. As far as skeletal muscle hypertrophy is concerned, the local expression does still appear to be the major determinant of adaptation and thus growth - to train your left leg only expecting that the other will grow due to "bystander effects" is therefore almost as hilarious as skipping leg day with the lame excuse that your legs would grow from training your biceps ;-)

On ultra short notice

With that I'll call it a day as far as the detailed posts are concerned and invite you to come back tomorrow, when I am going to pick up on this discussion in a detailed post on the Roa study on PGC-1 alpha 4, muscle growth, myofiber composition, strength development, workouts and the whole megillah. For the time being here is a bunch of unsorted other things I considered newsworthy:

• Anti-psychotics increase lipid synthesis by depressing it!? What sounds totally counterintuitive, is actually the main message of an editorial to the latest issue of the Journal of Lipid Research, in which Skreede, Steen & Ferno argue that a paper by Canfrán-Duque et al. clearly suggests that the obesity and hypercholesterolemic effects of 2nd generation anti-psychotics such as clozapine, risperidone, and ziprasidone are brought about by the counter-regulatory upregulation of cellular lipogenesis in response to their suppressive effect on cholesterol synthesis. (Skreede. 2013)
• The greater the muscle group you work, the larger the impact on the central nervous system will be (Rossmann. 2013) -- In the end everybody will know that intuitive, back and leg days are the hardest and most taxing to the whole system. Based on a trial involving eight young men who performed exhaustive large (cycling – BIKE) and small (knee extensor – KE) muscle mass dynamic exercises at 85% of the modality-specific maximal workload, scientists from Salt Lake City did now provide further experimental evidence that supports the notion that the CNS tolerates a greater magnitude of peripheral fatigue and likely a greater intramuscular metabolic disturbance when the pertinent afferent signaling comes from small vs. large muscle groups . 
• Rhodiola Rosea turns out to be an opiate (Lee. 2013).-- In a recent study scientists from the Chi-Mei Medical Center in Yong Kang, Tainan City, Taiwan were able to show that the popular but questionable (as far as the significance of its effects are concerned) adaptogen rhodiala decreased the systolic blood pressure of spontaneously hypertensive rats. Intriguingly the effect was blunted by the administration of the selective opioid μ-receptor antagonist, cyprodime, but not by naloxonazine, an antagonist specific to opioid μ1-receptor, which suggests that a direct effect on the opiate receptor. Moreover, the level of mood enhancing and relaxing beta-endorphins rose in both wild type and hypertensive rodents (with the effect being more pronounced in the latter)
• Chinese hawthorn for the hair, not the heart (Shin. 2013) -- I guess if you hear hawthorn or Crataegus you will probably think of its purported beneficial effects on heart health. Now if the results from a recent rodent study are applicable to humans, as well, you will soon have to establish a novel neuronal connection between (Chinese) hawthorn and your scalp, or rather the hair on your scalp . With its beneficial effects on the initiation of the anagen phase in mice in teloge and the ensuing increase in skin color, thickness of the hair shafts, and density (number and size) of the hair. Oral C. pinnatifida extract (at a human equivalent dose of ~320mg/day) could soon be all the rage among men and women who fear for their superb head of hair.

I think this is enough for today. There is a life beyond the SuppVersity not for you, of course, but for me - so while you head over to the SuppVersity facebook page for even more news, I am going to enjoy Saturday night ;-)

References:

• Canfrán-Duque, A., M. Casado, Ó. Pastor, J. Sánchez-Wandelmer, G. Peña, M. Lerma, P. Mariscal, P. Bracher, M. Lasunción, and R. Busto. Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro. J Lipid Res. 2013 [in press]
• Catoire M, Mensink M, Boekschoten MV, Hangelbroek R, Müller M, et al.  Pronounced Effects of Acute Endurance Exercise on Gene Expression in Resting and Exercising Human Skeletal Muscle. PLoS ONE 7. 2013; 11: e51066.
• Chin ER. Intracellular Ca2+ signaling in skeletal muscle: decoding a complex message. Exerc Sport Sci Rev. 2010 Apr;38(2):76-85. 
• Coe DP, Pivarnik JM, Womack CJ, Reeves MJ, Malina RM. Health-related fitness and academic achievement in middle school students. J Sports Med Phys Fitness. 2013 Dec;52(6):654-60. 
• Kanzleiter T, Wilks D, Preston E, Ye J, Frangioudakis G, Cooney GJ. Regulation of the nuclear hormone receptor nur77 in muscle: influence of exercise-activated pathways in vitro and obesity in vivo. Biochim Biophys Acta. 2009 Aug;1792(8):777-82. 
• Lee WJ, Chung HH, Cheng YZ, Lin HJ, Cheng JT. Rhodiola-Water Extract Induces β-endorphin Secretion to Lower Blood Pressure in Spontaneously Hypertensive Rats. Phytother Res. 2013 Nov 28.
• Long YC, Glund S, Garcia-Roves PM, Zierath JR. Calcineurin regulates skeletal muscle metabolism via coordinated changes in gene expression. J Biol Chem. 2007 Jan 19;282(3):1607-14.
• Rossman MJ, Venturelli M, McDaniel J, Amann M, Richardson RS. Muscle mass and peripheral fatigue: a potential role for afferent feedback? Acta Physiol (Oxf). 2013 Dec;206(4):242-50. 
• Shin HS, Lee JM, Park SY, Yang JE, Kim JH, Yi TH. Hair Growth Activity of Crataegus pinnatifida on C57BL/6 Mouse Model. Phytother Res. 2013 Nov 12.
• Skrede J, Steen VM, Ferno J. Antipsychotic-induced increase in lipid biosynthesis: activation through inhibition? Journal of Lipid Research. December 7, 2013 [Epub ahead of print] 
• Thieme H, Mehrholz J, Pohl M, Behrens J, Dohle C. Mirror therapy for improving motor function after stroke. Cochrane Database Syst Rev. 2013 Mar 14;3:CD008449.

Low Vitamin D & Insulin Resistance; Ghrelin Response to Overfeeding; Glutamine for the Elderly; 5g/Day Creatine for Women; MSM for GH Activity in Bone; Curcumin for Burns

Vitamin D research hyper-inflation - unfortunately few of the papers will ever be printed, otherwise we could at least use them to heat our homes, in case the price for oil gas and other fossil energy keep rising ;-)

The SuppVersity Figure of the Week is "1614"! That's the number of studies with the exact phrase "vitamin D" in their title that have been published in the past 9 months and 14 days of the year 2013 (more than five papers per day!). Compared to 1,453 papers in the year 2011 and 1,169 papers in 2010. Projected onto the rest of the year that's going to be a +40% increase in mostly redundant papers! I mean, let's be honest, we have not made any significant scientific progress in the area of vitamin D research over the past months: We have still no idea where the associations end and the causations begin and are more or less clueless as to why vitamin D supplementation simply does not yield any of the beneficial results it is supposed to.

And as if that was not already bad enough, due to the advent of an infinite number of second-class online journals that made the vitamin D paper hyperinflation only possible, most of these papers will never be printed. Otherwise I'd suggest we put them to some good use and burn them like the woman in the image on the right was burning paper money during the days of monetary hyperinflation, over here in Germany in the years 1922 - 1923 ;-)

Vitamin D and insulin resistance 

Having low levels does only make a difference, if you are obese. That's the result of the most recent analysis of data from the MONICA10 cohort consisting of 2656 participants (men and women aged 41–71 years) who participated in a 10-year follow-up examination during 1993–1994 as part of a population-wide survey in Denmark (cf. figure 1; data adjusted for sex, season of blood collection, history of CVD, family history of diabetes, physical activity during leisure time, healthy food index, fish intake, supplement use, smoking status, alcohol intake and educational level):

Figure 1: Risk of incident diabetes associated with serum 25(OH)D and waist circumference categorized as normal, overweight and obese (data based on Husmemoen. 2013).

"Low serum 25(OH)D was associated independently with incident diabetes. The inverse association was only found in overweight-obese and not in normal weight individuals, suggesting that obesity may modify the effect of vitamin D status on the risk of diabetes." (Husmemoen. 2013)

These results stand in line with previous research you've read about here at the SuppVersity suggesting that rather than the absolute 25-OHD levels, which are indicative of your "vitamin D reserves", an obesity induced disruption in the management / metabolism of the "sunshine vitamin" appears to be the real culprit that's behind the associations (not causations!) between low vitamin D levels and the metabolic syndrome.

That this problem can't be solved by simply adding more vitamin D to the equation stands to reason and would also explain why the few controlled vitamin D3 supplementation trials in non (morbidly) obese, highly vitamin D deficient individuals that exist did not bring about any of the metabolic benefits the researchers had expected.

Supplemental glutamine prevents non-sarcopenic age-induced weight loss 

We usually think of being overweight, when we talk of "weight problems". For older people it is yet often rather the opposite. Many are losing weight and start to literally wither away. And while glutamine does not help with the muscular aspect (strength training and at least 20g of EAA-rich proteins with every meal), it could at least help with making the most of the food you eat and the supps you take.

While the mechanism is not yet fully elucidated, the results of a recent study by Meynial-Denis et al. clearly suggest that the provision of supplemental glutamine effectively prevents the loss of body weight. A possible mechanism my be related to its concomitant (or upstream?) effects on the integrity and function of the enterocytes in the gut lining of the very old rats the researchers used as a model (Meynial-Denis. 2013).

Therefore I am not convinced that the researchers hypothesis that these effects are brought about by

1. the ameliorative effects of glutamine on the age-induced CO(2)/glutamate ratio, and
2. the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis,

fully explain the observed effects. And even if they are, the additional (maybe in that case downstream) improvement of nutrient absorption subsequent to the conservation or restoration of a healthy/-ier gut lining can hardly be underestimated. After all, it is becoming increasingly clear that much of the age-induced loss of body weight is at least promoted, if not causally related to the decreased absorption of various essential nutrients.

Unexpected ghrelin response during 7-day overfeeding experiment in obese subjects

"Confusing" would in fact be a better term to describe the surprising finding that 7-days on a diet containing 70% more energy than the 68 healthy young, normalweight, overweight and obese men usually consumed did not reduce, but increase the amount of the acylated form of ghrelin (often touted as the "active" = hunger promoting form of ghrelin), in the blood of the study participants (Wadden. 2013). Moreover, ...

• there was no significant difference in fasting acylated ghrelin between normal weight, overweight, and obese men at baseline and
• the amount of acylated ghrelin was negatively correlated with weight and BMI for normal weight and with BMI in overweight men.

Yet while ghrelin also correlated with the changes in body weight and BMI the study participants experienced in the course of the one-week intervention. It was negative (which is obviously what you should expect) only in he normal- and overweight subjects. In the obses study participants, on the other hand, the correlation was positive, i.e. more weight gain = more ghrelin.

Illustration of the global obesity epidemic (WHO. 2005). The study at hand makes it pretty clear that a pathological dysregulation of energy intake is at least part of the problem.

In other words: While there were no differences at baseline an increase in acetylated ghrelin was associated with lower body weights and weight loss in normal- and overweight subjects, while the obese (=pathologically overweight subjects) showed increases in acetylated ghrelin, when they gained weight.

If we stick to the fundamental hyptothesis that ghrelin is in fact a "hunger hormone" and the acylation, i.e. the addition of an acyl functional group to the basic molecule, works like an "on switch" that activates the appetite increasing effects of ghrelin, this means nothing else than overeating and gaining weight makes obese men hungrier. This finding provides further evidence for the hypothesis that the natural regulation of food intake is not simply impaired, but totally out of whack in obese individuals.

MSM turns out to be a local GH booster and bone builder 

MSM? That's the stuff in the joint supplements, right? Correct! Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities that is a longstanding standard ingredient in joint supplements (next to glucosamine sulfate and chondroitin sulfate - you notice the sulf... ah, pattern here, right?).

I guess you knew all that already, but I would be surprised if you had also been aware of the fact that MSM exerts direct anabolic effects on the bone by increasing the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and mesenchymal stem cells.

"MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. [...] Furthermore, MSM increased ALP activity and the mineralization of MSCs." (Joung. 2013)

Unfortunately, in vitro studies like these don't provide any information on appropriate dosages, but a study that was published in August 2013 reports that dosages up to 10-fold higher than the dose equivalent of the 300-400mg/day, which are at the upper end of the spectrum of the dosage recommendations of currently available MSM supplements, lead to "dose dependent" decrease in the degeneration of the cartilage in the knee joints in a mouse model of osteoarthritis (Ezaki. 2013). The hilariously high dose of 30-40g (100x the recommended amount), on the other hand, led to significant losses of body, liver, and spleen weight.

So, even with an acute fracture you better keep your MSM intake within reasonable limits - specifically, because we do not even know if oral methylsulfonylmethane will help with either bone-healing or bone strength in humans, at all.

If muscle is metabolic currency, creatine is the cash machine

"Ehhh! This will make me hold water? No thanks I already got enough of that! And muscle, not thanks..." Shut up! Muscle is metabolic currency and gaining muscle and strength is equally beneficial for the health of men and women, alike.

Against that background you may want to print the results from a recently published paper by Andreo Fernando Aguiar from the North University of Paranay and his colleagues and put the print out somewhere where all, not just the older ladies at your gym will see that taking 5g of creatine /day helped eighteen healthy ladies in their best years (64.9±5.0 years) to

If looking gorgeous and being strong & healthy is your goal, creatine is your supplement of choice, ladies...and gents! Changes in body fat percentage and muscle mass in response to 12-week strength training expressed relative pre value in control group (calculated based on Aguiar. 2013)

• train at a more than 2-fold higher volume,
• make 5.1, 3.9, and 8.8% greater progresss in bench press, leg extension, and biceps curl performance
• gain 3.2% more fat-free mass and 2.8% more muscle mass, and
• be more efficient in performing submaximal-strength

...than the nine women in the placebo group (Aguiar. 2013). With a somewhat higher overall training volume and maybe three instead of just 2 sets of 10-15 reps of

• vertical bench press, lat pulldown, 
• biceps curl, triceps pushdown, 
• knee extension, leg curls, 
• seated calf raises, and abdominal crunches

three times per week and a reduced carbohydrate intake (carbs down by 20% to 45% and protein up by 20% to 40% of the total energy intake) I am pretty sure the ladies in the creatine group would also have been able to turn the hitherto non-significant 2% reduction in total body fat into a significant one.

"Strong is the new sexy" and creatine can help you to get there!

About time to pull the emergency break strength train eat and take creatine?!

In a way it's unfortunate that the ability to promote weight loss is an almost necessary prerequisite for an ergogenic to  be attractive to women. If you can't answer the question "Will it make me lose weight... ah, I mean fat?" with a definitive "Yes, ma'am!", they won't buy it. That said, even with the current training and dietary regimen, the women in the creatine group dropped 1.6% total body fat and, due to the increase in lean mass, decreased their body fat percentage by -2.8%, while the ladies in the control group gained 1.2% body fat (total), so that their body fat percentage effectively did not change at all (+0.4%). Stronger, leaner and healthier! What more can you ask for in a dietary supplement?

Topical curcumin improves wound healing (plus tips how to prepare it)

In view of its profound anti-inflammatory effects it is actually not straight forward that curcumin would improve wound healing - at least not in the early, inflammatory phase of the process. Accordingly the researcher from the Department of Dermatology at the Faculty of Medicine of the Namik Kemal University in Tekirdag, Turkey, divided their burned rodents into 3x2 groups who were scheduled to be anesthetized on day 4 (A), day 6 (B) or day 8 (C) after after they had been burned with an aluminum branding iron that had been placed without pressure for 30s on the back of the rats (Kulac. 2013).

Histopathological scores for inflammatory cells, collagen, deposition, angiogenesis, granulation tissue formation, and epithelialization in each group (based on Kulac. 2013); group A (4th day post burn), group B (8th day post burn), group C (12th day post burn)

The rats in the three treatment groups who had received 200 µl of curcumin at a concentration of 100 mg/kg body weight, topically, once daily, showed increased wound healing during all the critical steps of tissue regeneration, i.e. inflammation, collagen deposition, angiogenesis, development of granulation tissue, and the repair of epithelium.

Interestingly, the inflammatory cell infiltration was significantly increased in curcumin groups and that regardless of when the tissue samples were analyzed. Collagen deposition, angiogenesis and granulation tissue formation were likewise higher in curcumin compared to the placebo group, with the earliest squamous epithelial re-epithelialization being observed on the 4th in treatment subgroup (figure 2, Group A).

Self-made curcumin band-aids / pastes

And in case you don't want to waste money or support Johnson and Johnson by buying the tumeric laced bandages they apparently sell in India, here are two ways to prepare a bandage and a tumeric paste that will probably help with sorts of inflammatory skin conditions (Hinkle. 2013):

In India people use tumeric + honey facial masks; also to treat acne, by the way.

• tumeric wrap / band-aid: Combine one teaspoon of dried turmeric powder with two teaspoons of either dried or fresh ginger. Spread the mixture over a cloth, then wrap around the affected area and seal it with a plastic bandage.
• tumeric paste for burns: Combine one teaspoon of turmeric powder with one teaspoon of aloe vera gel and apply it directly to the burned / inflamed part of your skin (make sure not to apply it directly onto open wounds, though!)

Be careful, though! Tumeric is also a powerful dye that's not easy to wash off again. So whatever towel you may be using as a wrap may therefore be ruined and in case the paste gets in contact with your shiny new white shirt, hot pants or whatever those are likely to be ruined, as well.

---

Have you ever listened to the to the SuppVersity Science Round Up on Super Human Radio? If not, check out the podcasts

That's it for today, folks. I am not sure whether you feel this is sad or good, but I hope for you, and in a way me and the SuppVersity, that it is the latter, because it may well be that I will increase the frequency of these On Short Notice. In that I will be trying to get even further away from the lengthy items from last week and make them actually short, again ;-)

A pros pos short, those who like these news updates, may also enjoy the weekly SuppVersity Science Round Up that airs live every Thursday at 12.30 or 1.00PM EST, And if you can't tune in live, you can simply have google show you the links to the podcasts of the latest shows.


References:

• Aguiar AF, Januário RS, Junior RP, Gerage AM, Pina FL, do Nascimento MA, Padovani CR, Cyrino ES. Long-term creatine supplementation improves muscular performance during resistance training in older women. Eur J Appl Physiol. 2013 Oct 7.
• Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y. Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. J Bone Miner Metab. 2013 Aug 10.
• Hinkle, Lynette. Homemade Remedies With Turmeric. eHow.com - Herbs & Botanicals for Health J-Z. < http://www.ehow.com/way_5402326_homemade-remedies-turmeric.html > retrieved on Oct 13, 2013.
• Husemoen LL, Skaaby T, Thuesen BH, Jørgensen T, Fenger RV, Linneberg A. Serum 25(OH)D and incident type 2 diabetes: a cohort study. Eur J Clin Nutr. 2013 Oct 3. doi: 10.1038/ejcn.2013.134. 
• Joung YH, Lim EJ, Darvin P, Chung SC, Jang JW, et al. MSM Enhances GH Signaling via the Jak2/STAT5b Pathway in Osteoblast-Like Cells and Osteoblast Differentiation through the Activation of STAT5b in MSCs. PLoS ONE. 2013; 7(10): e47477.
• Kulac M, Aktas C, Tulubas F, Uygur R, Kanter M, Erboga M, Ceber M, Topcu B, Ozen OA. The effects of topical treatment with curcumin on burn wound healing in rats. J Mol Histol. 2013 Oct 2.
• Meynial-Denis D, Bielicki G, Beaufrère AM, Mignon M, Patureau Mirand P, Renou JP. Glutamate and CO(2) production from glutamine in incubated enterocytes of adult and very old rats. J Nutr Biochem. 2013 Aug 13.
• Wadden D, Cahill F, Amini P, Randell E, Vasdev S, Yi Y, Zhang W, Sun G. Serum acylated ghrelin concentrations in response to short-term overfeeding in normal weight, overweight, and obese men. PLoS One. 2013;7(9):e45748.

Are Elevated Iron and Uric Acid Levels Too Much of a Price to Pay for a Creatine-Induced 11% Performance Increase?

Video 1 (GSSI): Notre Dame's Michael Floyd goes all out on the Wingate test (click to watch)

I guess you could say that these are the "classic days", here at the SuppVersity, contrary to my previous post on choline, which is - judged by the few people who still use it today, an "old school supplement" (cf. "Choline: Stronger, Faster, Leaner & More Muscular, or Just Another Dumb-and-Barbell Story?") - yesterday's post on caffeine highlighted the efficacy of a potent ergogenic aid and metabolic activator, with the effects of which most of us are so familiar that we are alway tempted to turn to useless crap like raspberry ketones, when what we are already doing is not only tried and proven, but based on respectable scientific data even more effective than the latest "innovation" from the snake oil industry. And let's be honest, haven't we all been tempted by one or another "new creatine", as well?

+11% peak performance in one week, solely from 5x4g of creatine per day!

A a matter of fact, creatine monhydrate does in fact share the same fate of being proven, but "boring" staple supplement and although that alone should be incentive enough to address the unquestionably outstanding +11% in anaerobic peak performance, +5% in continuous anaerobic performance and a +6% increase in total workload in a classic wingate anaerobic performance test speak, Barros et al. observed in a group of trained male subjects in response to a 7-day creatine loading protocol (20g creatine monohydrate, in 5 doses spread across the day, not glucose / sugar added; cf. Barros. 2013) After all, my gut tells me that the contemporary changes in the concentration of iron in the blood of the subjects in the the creatine arm of the study could revoke the mainstream-media fearmongerish hoopla over the purported dangers of the #1 natural ergogenic.

Figure 1: Basal iron, FRAP, malondialdehyde (MDA) and uric acid levels before and after 7-day supplementation with 5x4g of creatine monohydrate per day (based on Barros. 2013)

I mean, there is no debating, the level of iron in the blood of the creatine supplemented undergraduate students (age, 23.1 ± 5.8 years; height, 175.4 ± 2.3 cm; weight, 81.1 ± 9.3 kg) all of whom had been avid trainees for at least 6 months did increase by no less than 94.3%, while the subjects in the placebo group experienced a -21% reduction of these highly reactive molecules (Just as an aside, the decline in serum iron in the placebo group and the significant difference in baseline levels between the random groups, alone, render any implications at least questionable; I mean, wouldn't you expect the serum parameters to stay the same, when you do nothing extraordinary, aside from popping some sugar pills?).

Figure 2: Changes in wingate anaerobic performance (left) and exercise induced changes iron, FRAP, malondialdehyde (MDA) levels during the wingate test at the end of the supplementation period (based on Barros. 2013)

In conjunction with the likewise highly significant increase in uric acid levels, conventional (blogosphere-)wisdom, which constantly ignores the antioxidative nature of uric acid, which acts as efficient antioxidant and chelating agent for iron ions (Karlsson. 1997), limits the oxidation of polyunsaturated fatty acid in the erythrocyte membrane and prevents hemolysis (= the rupture of red blood cells) in vitro (Einsele. 1987), would suggest that taking creatine takes a close second to fructose on the list of the villains of the bad, bad "neolithic" century.

How dangerous is the creatine induced increase in iron?

Image 1 (Paramount Pictures): I guess, it must have been creatine monohydrate, then, that turned Robert Downey Jr. into Ironman ;-)

Now, despite the as of late publicly propagated concerns about increased iron levels and their potential causative role in the etiology of insulin resistance and diabesity (obesity + diabetes), recent scientific evidence suggests that "high iron", such as all previous scapegoats people like to hold liable, just to make sure not to admit that it is the sickening combination of laziness, convenience and unsound dietary advice that is at the heart of the current obesity epidemic.

Huang et al., for example, did observe a direct effect of iron overload on diabetes risk - the latter was however a result of hereditary hemochromatosis (a genetic defect in iron metabolism) in their 2011 rodent trial (Huang. 2011). Results from two more recent studies by Silva et al. also indicate that the metabolic disturbances lead to differential expressions of the proteins involved in the metabolism of iron and thus substantiate the associative (and not causative) nature of the relation between high iron / ferritin and the metabolic syndrome (Silva. 2011; Silva. 2013).

Iron not causative? So why does phlebotomy help, then? If you read my post on the recently published data from the first controlled human trial that investigated the effects of phlebotomy on markers of blood glucose management, you will be aware that the measures they took, e.g. the HOMA-IR, are not really appropriate to assess the effects of this particular treatment (cf. "Phlebotomy: Can You Bleed Yourself Healthy and Lean?"). Furthermore, it is only logical that the removal of some of this "highly inflammable stuff" from an inflamed body will provide health benefits, even if the latter was totally benign for someone who has a lot less inflammation going on.

What is even more important, though, is that the difference between exercise-induced increases in serum iron and diet and diabesity-related increases in the storage form of iron, ferritin, in the liver. This is particularly true in view of the fact that our understanding of the former, i.e. the exercise induced release of iron into the blood stream is more than limited (Roberts. 1989; Smith. 1994). What we do see in the Barros study, however, is that the overall effect of creatine is rather anti- than pro-oxidative, since the increase in overall antioxidative capacity (as indicated by the changes in the iron-specific FRAP essay; cf. figure 1) did not just...

• negate the potential negative effects of increased basal iron levels (see lowered baseline MDA levels post supplementation in figure 1), it also 
• countered the exercise-induced lipid oxidation during the 2nd wingate test (as indicated by lower MDA levels; cf. figure 2). 

Eventually, the scientists say, the increase in antioxidant activity that is brought about by the ingestion of 20g/day creatine irrespective of whether you exercise or not could actually yield "general health benefits" (Barrios. 2013); and I would like to add that evidence for Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, recovery from ischemia and, guess what, diabetes already exists (Tarnopolsky. 2000;"Creatine Ameliorates Type II Diabetes")! Certainly not bad for one of those bodybuilding supplements, "anabolics" or "gateway drugs", as creatine is often mislabeled , when a 100% clueless "journalist" tries to get the attention of his editor-in-chief, wouldn't you agree?

Suggested readings (some also mentioned in the text):

• The Pharmacology of Creatine (Part 1 and Part 2) 
• Supercharging Creatine With Baking Soda (click here to read)
• 5g/day Creatine for Type II Diabetics? (click here to read)
• All posts tagged with "creatine" (click here to read)
• Phlebotomy: Can You Bleed Yourself Healthy and Lean? (click here to read)

References:

1. Barros MP, Ganini D, Lorenço-Lima L, Soares CO, Pereira B, Bechara EJ, Silveira LR, Curi R, Souza-Junior TP. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test. J Int Soc Sports Nutr. 2013 Jun 12;9(1):25. 
2. Huang J, Jones D, Luo B, Sanderson M, Soto J, Abel ED, Cooksey RC, McClain DA. Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes. 2011 Jan;60(1):80-7.
3. Orozco MN, Solomons NW, Schümann K, Friel JK. Response of urinary biomarkers of systemic oxidation to oral iron supplementation in healthy men. Food Nutr Bull. 2013 Mar;33(1):53-62. 
4. Roberts D, Smith DJ. Effects of high-intensity exercise on serum iron and α1-antitrypsin in trained and untrained men. Clin Sports Med 1989, 1:63–71.
5. Silva M, Bonomo Lde F, Oliveira Rde P, Geraldo de Lima W, Silva ME, Pedrosa ML. Effects of the interaction of diabetes and iron supplementation on hepatic and pancreatic tissues, oxidative stress markers, and liver peroxisome proliferator-activated receptor-α expression. J Clin Biochem Nutr. 2011 Sep;49(2):102-8.
6. Silva M, de Brito Magalhães CL, de Paula Oliveira R, Silva ME, Pedrosa ML. Differential expression of iron metabolism proteins in diabetic and diabetic iron-supplemented rat liver. J Biochem Mol Toxicol. 2013 Mar;26(3):123-9. 
7. Smith DJ, Roberts D. Effects of high volume and/or intense exercise on selected blood chemistry parameters. Clin Biochem 1994, 27:435–440.
8. Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Curr Opin Clin Nutr Metab Care. 2000 Nov;3(6):497-502.

Adelfo Cerame - R2WC: My Pre-Contest Supplement & Diet Regimen. Plus: Dr. Andro @ Quantum Physiques Radio

Image 1: That's what I call a Quantum Physique ;-)

I want to use Adelfo's blogpost today for a brief announcement, which is not exactly related to our common friend and soon to be pro wheelchair bodybuilder. Some of you will probably already have seen the link on the SuppVersity facebook page, the rest of you can just click here if you are not already fed up reading my stuff and believe you can handle another dose of "Dr. Andro" in podcast format ;-) I have been on Brian Cunningham's Quantum Physiques Radio show and despite the fact that this is no typo (the name of the show is Quantum Physiques), we have actually covered everything from Adam and Eve (=Paleo) to Einstein and his unwillingness to accept the strange behavior of quantum objects... I had a lot of fun and I guess at least some of you will enjoy listening to the show, as well!

Ah... I almost forgot: Don't take all the flattering things Brian says too literally. If anyone here deserves praise it's Adelfo, who is - judged by the latest pics I saw - right on his way to his pro-card; and with that I successfully got myself out of the limelight and pass the bar to someone who has his "Quantum Physique", already ;-)

My dear friends and followers, here at the SuppVersity!

It’s less than 10 days left, until your (hopefully) favorite wheelchair bodybuilder *lol* will be off to another competition! Time for me to look back and time for you to get some valuable insights into my diet and supplement regimen. I will try to make it as concise as possible and provide you with a brief rundown of what I have been doing for the past six weeks, which, as you will soon see was not much different from what I have found works best for me in the course of the past months already. And other than minor tweaks and adjustments, which can oftentimes really make a huge difference, you certainly won't start fixing something that ain't broken in the first place. Right? So let's see what we've got then:

Shameless plug! Just in case anyone of you is interested in joining me as a Myotropics Physique Nutrition sponsored athlete and/or fitness model, I suggest you head over to our Facebook site, like us and join the Myotropics Physique Nutrition Photo Contest.

The grand prize (male & female winners!) is a trip to Vegas + professional photo shoot and of course the opportunity to represent the company in the future. For the unlikely case that you don't have enough friends and family to vote for you, there are a lot of other things that make it well worth to participate in the contest!

Contest prep supplement staples:

1. Thermogenic/ fat burner:
   
   Dosing: 1 serving upon waking during my fasting hours
   
   Notes: I don’t use fat burners all throughout my prep; I incorporate them, when I’m about 4-6 weeks out to help pick things up. Don't expect them to actively burn fat, though. It is more a means to keep your overall energy levels and metabolism up, as well as to shift your metabolism further into the "fat burning" zone in order to preserve precious muscle and liver glycogen.
    
2. DAA/ D-aspartic acid
   
   Dosing: Mid-morning during my fasting hours - 1 serving 3g
   
   Notes: Those of you who have been following my posts here at the SuppVersity from the very beginning will remember that I did a test run for Purus Labs’ D-Pol in the course of my last prep, and really liked this supp; I am not sure if it's just in my head, but I felt that it did help me to maintain and slightly increase my strength even while dieting, so I figured "why not use it again" - and until now I did not regret that decision.
    
3. VPX Friction + baking soda + taurine
   
   Dosing: I take these pre-workout - 1 serving of Friction, 1tsp. baking soda and 5g of taurine
   
   Notes: I usually don’t take pre-workout supplements during the off-season, because I feel like I get enough energy from my foods, when I am dieting, though, I enjoy the little extra boost they give me and the taurine and baking soda help me endure and recover from longer workouts
    
4. BCAA’s + Creatine monohydrate
   
   Dosing: Intra-workout - 25g BCAA (bulk powder), 5g creatine monohydrate (bulk powder)
   
   Notes: This is a supplement combination that I do year round, and sometimes I’ll add baking soda to it if I feel like or have the taste for it. The reason I take the creatine intra-workout at the moment is that my current preworkout already contains creatine, by spacing it out somewhat I try to maximize absorption (if the idea of not taking all your creatine at once is news to you, check out Adel's post "The Pharmacology of Creatine")
    
5. Melatonin (regular, not time released)
   
   Dosing: 30mg before bed, when I notice that my sleep gets worse or I am having trouble falling asleep
    
6. Protein shake
   
   Dosing: 40g = 1 serving of Physique 2.0
   
   Notes: Before being sponsored by Myotropics, I used just supplement with a regular fast digesting whey, in view of the more sustained protein influx from the total milk proteins, I did yet switch to a full serving of Physique 2.0, which has the added bonus of  having 15g of ThermiCarb (a patented form of WM HDP) per serving (I also have a prototype of our new product, which is just the carbohydrate fraction of Physique 2.0, I use post-workout, see detailed plan below). I  add in another tbsp. of raw honey for some faster carbs and am good to go.

I guess, some of you may now be disappointed, as I suppose you expected to see a much longer list full of exotic items you could waste your money on, but let's be honest, we all know that supplements ain't game changers and if you revise my plan you will see that sticking to the tried and proven trio of creatine, protein and some free form amino acids, complemented by one or two things you personally like (in my case these were a pre-workout product and the DAA), is all it really takes, when you got your exercise and nutrition regimen dialed in to the T.

Bodybuilding nutrition made simple: A Food-based meal planning template

This takes us right to the next and - at least in my humble opinion - way more important part of contest dieting: The diet itself! Or rather the foods and macronutrient ratios you are aiming for. I obviously eat other foods, as well, but the following selection represents the cornerstones of my contest prep diet, you can pick an puzzle them together as you like or introduce your own favorite foods; having a "stock" of items to turn to does make planning your diet much easier and less stressful - keep that in mind before you discard the notion of having "standard foods" you combine in different ways for whatever reason

• Protein sources:
  
  

  

  Image 2: This is what a typical rest day protein and fat meal would look like ;-)

  Pork loin: center cut/ tenderloin/ sirloin I’ve ditched the chicken breast and switched over to lean pork cuts. If you choose the right cuts and quality of pork, the macronutrient profile of a lean cut of pork is just the same as a piece of chicken breast. Lean pork cuts are also a lot tastier in my  opinion and less pricy.
  
  Game Meats: Elk/ antelope/ dear/ bison/ wild boar At my local farmers market they sell frozen packaged game meats – I like wild gamey meats, because they have a distinctive taste to them that I enjoy, plus they’re grass- fed, and the fat content is a lot lower, and, again, almost as close to chicken breast in macronutrient content.
  
  Whole cage free eggs: Whole eggs are one of my favorite protein sources to choose from for my non-training day/rest day meals; on these days my fat intake is a bit higher, conversely the carbohydrate intake is reduced and the yolks provide me with all the healthy fats and fat soluble nutrients I need.
  
  Tilapia/ canned tuna These are foods I incorporate into my regimen towards the end of my prep; for some reason I’ve always done it this way. I just find these two foods convenient and efficient for me to prepare and they fit nicely into the macronutrient ratios I am aiming for in the final 2-3 weeks of my prep.

• Carbohydrate sources:
  
  

  

  Image 3: Yeah, folks! That's Pineapple on the plate in the background ! And no, I am not afraid that there is fructose in it!

  Starches - Tubers such as, sweet potatoes/ yams/ organic russets/ colored potatoes
  I like tubers as my main source for starchy carbs because I can eat more of it and it fills and satisfies me; basically I can have larger servings from tubers with my given macronutrient numbers for carbohydrates compared to other carbohydrate sources, such as rice, which I do yet eat on occasion
  
  Vegetables - cucumbers/ zucchini/ carrots/ kale/ sweet mini peppers Not only do they taste good raw and by themselves, but they’re cheap, and you can buy a weeks worth for around $10
  
  Fruits: Pineapples/ papayas / bananas (earlier in the prep) Other than their awesome health benefits, these fruits satisfy my sweet tooth. 
  
  Honey (raw)  Another carbohydrate dense food that I like to use after my workouts to speed up glycogen replenishment

• Fat sources:
  
  Virgin coconut oil I take a tbsp. with almost every meal
  
  Sour cream/ heavy whipping cream/ real cheeses I use these 3 fat sources to add to or if I have any more room for my fat macros.

Putting it all together - no blueprint, just an example

To finally give you a general idea of what all that looks like in practice, I have compiled the following overview of my nutrition and supplementation regimen on an exemplary day in my life during contest prep:  

5-6am: I wake and take my fat burner  - I’m trying OxyElite Pro this prep, and it’s just as good as meltdown, the product I used during my last prep 7-8am: Cardio - 15-20 minute HIIT cardio/ 20 minute swim, or  45-60 minute of low intensity cardio (walking the dog) 9 or 10am: D-aspartic acid one serving (3g) 3pm: Breaking fast w/  pre-workout meal - 2 tilapia fillets/ or 2 cans of tuna - cucumbers & carrots - 1 tbsp.  RAW coconut oil 3:45pm: Pre-workout supplements - VPX Friction - 1 tsp baking soda - 5g taurine

4:30-6:30pm: Training + Intra-workout  - 25g BCAA’s - 5g creatine monohydrate Immediately post-workout:   - Physique 2.0 - 1 serving - ThermiCarb - 1 serving - 1 tbsp. RAW honey 7:30-8:00pm: PWO meal - 2 tilapia fillets - sweet potato - fruits & veggies 10:30pm: Last meal  - Pork tenderloin - veggies - 1 tbsp. coconut oil 11pm: 30mg melatonin (if I feel, I need it)

Modifications on non-training days: On my non-training days, I’m not on any supplements other than my fat burner; my meals on my rest days consists of whole eggs, wild game meats, fruits and vegetables and 1 tbsp. of coconut oil with every meal.Meal#1 ground antelope + fruits + veggies + coconut oil… I guess you get the notion ;-)

Does Creatine Blunt Fat Loss? A Recent Study Supports Long-Standing Suspicions, But What Are the Implications?

Better  lean than strong? Why not both?

Anyone remember the allegedly not very popular post on the "anti-creatine" β-Guanidinopropionic Acid (GPA) and it's ability to increase AMPK, decreases blood glucose & insulin, induce weight loss without dieting, increase skeletal muscle oxidative capacity and delay the development of mammary cancer (read up on the news)? I thought so...

Even I had was just about to forget about it, when I stumbled upon a recently published Brazilian study which found that the "real" - not the anti-creatine - does in fact what you would expect from the "evil twin" of GPA: It blunts the exercise induced fat loss in highly trained amateur athletes (Manjarrez-Montes de Oca. 2013).

"What!? Creatine makes me fat?"

Now, before you start freaking out, let me say this: There are also studies which suggest that creatine supplementation does the exact opposite, i.e. that it can (combined with an intense exercise protocol) decrease body fat level (van Loon. 2003; Volek. 2004). If you dig deeper, you will yet find that most studies actually don't report any changes in the ratio of fat to total body mass most of you know as "body fat percentage" (Kreider. 1998; Volek. 1999; Becque. 2000).

Whatever the results of the individual experiments may be, in the end only studies like the one done by Jeff Volek et al. at the University of Connecticut or the study at hand, i.e. studies in the course of which the scientists actually measure/d the total amount of lean and fat mass can provide an adequate idea of what exactly supplemental creatine can do for our physiques. If the data includes only body fat percentages, maybe even measured with bio-impedance (→ yesterday's Facebook news on "losing" 1.4% of body fat in a single session), this does not suffice to say, whether the absolute amount of body fat changed. Or in other words, whether any observed increase / decrease in body fat (%) was simply a result of the fact that the ratio of lean to total body mass increased faster than the rate of fat to total body mass, wile the subjects abs still disappeared under a nasty layer of blubber.

Figure 1: Changes in body mass, bone free lean mass, fat mass and body fat percentage (left), as well as individual "fat gain" response to creatine supplementation in the 14 subjects (Manjarrez-Montes de Oca. 2013).

The study at hand is in fact a perfect example for the way body fat  levels alone can fool you. A brief glance at the data in figure 1 confirms that. While the body fat percentage says that the 12 non-smoking, non-vegetarian, red and black belt male recreational taekwandoo players must effectively have lost weight in the creatine phase of this, the total fat mass reveals that adding 50mg/kg creatine to their sports drink (30 g of sucrose, artificial flavor, 500ml) lead to an increase, the addition of the same amount of maltodextrin to a decrease in DEXA measured total body fat.

If it were not for the results of of 2002 paper by Huso, I guess, I would just tell you to simply forget about the hoopla and discard the notion that creatine would have any effect on body fat levels, at all (Huso. 2002). Huso et al. had investigated the influence of creatine supplementation (20 g/day for 4 days, then 2 g/day for 17 days) on substrate utilization during rest using a double-blind crossover design. To this ends the researchers recruited 10 active men who participated in a 12 wk resistance training protocol (3x /week full body resistance training; 3 sets, 10 reps) involving a placebo and a creatine trial that were separated by a 4-wk washout.

Figure 2: Changes in body composition (body mass, body fat and fat free mass) and 1RM strength on the bench press and leg press in the 12-week double-blind randomized cross over trial by Huso et al. (Huso. 2002)

Very similar to Manjarrez-Montes de Oca et al. in the study at hand,  Huso et al. observed a significant decrease in fat mass (-2.4kg) in the placebo trial, while there were no significant changes in either of the two parameters, when the subjects were "on creatine".

So how come that creatine does even have the ability to inhibit fat loss?

Just like the identical change in lean mass (in fact, only the strength increase speaks in favor of the creatine loading + maintenance regimen) the inhibition of the fat loss in the trial of the Huso study was actually only a "side finding". Originally, Huso et al. had set out to elucidate, whether the "anecdotal evidence of weight gain, including a lack of fat loss, in persons taking creatine" (Huso. 2002) could be brought about by creatine induced increases / decreases of the respiratory exchange ratio (RER = the ratio of carbohydrates to fats that are oxidized during a workout). And while the scientists state in their abstract that the "[c]hanges in substrate oxidation" they observed "may influence the inhibition of fat mass loss associated with creatine after weight training" (Huso. 2002), it is at least in my humble opinion not very likely that the small statistically only borderline significant shift from fat to carbohydrate oxidation (+/- 9%, respectively) alone can actually explain the >2kg difference in total fat mass loss. Still, this is exactly what Manjarrez-Montes de Oca et al. feel would be the most likely explanation for the observations they made 11 years later, as well:

I wonder if Usain Bolt consumes creatine supplements. Or is he on GPA, click here to learn what would be more likely.

"It has been suggested that the increase in carbohydrate utilization induced by Cr may be due to an activation of the enzyme phosphofructokinase, which produce an increase in glucose utilization, with elevation of malonyl-CoA and inhibition of carnitine palmitoyltransferase 1 (CPT1) system, which transports fatty acids into the mitochondria for oxidation (Huso. 2002).

If fatty acids are not transported into the mitochondria of skeletal muscle cells to be oxidized, they could be expected to be maintained in blood as triglycerides; and then stored in the adipose tissue.

We observed a higher concentration of triglycerides after Cr supplementation, and also found that subjects after Cr treatment gained fat mass whereas after placebo treatment fat was lost. Therefore, both findings could imply that fatty acid mitochondrial uptake has been inhibited by Cr ingestion, altering the normal fat loss produced by TKD training."

What you should keep in mind though, is that the dietary intake was not controlled for (what if increased glucose oxidation simply made the subjects hungrier?). In calorically restricted scenario the results could thus have been very different, so that it is overall not very likely that creatine would ruin your dieting efforts. Moreover, there is some, allegedly not very conclusive evidence that the addition of a reasonable amount of creatine to your diet could actually help you spare muscle tissue. The fact that the placebo-specific increase in protein oxidation from 11.6% to 15.3% was just as absent in the creatine group as the fat loss, is however hardly a convincing, let alone bullet-proof argument in favor of creatine as a dieting aid. After all the protein oxidation in the creatine group remained stable on the same high levels of roughly 15%.

---

Bottom line: I don't feel that the evidence "against" taking reasonable amounts of creatine (2-3g per day) is conclusive enough to panic and give up on the possible beneficial effects on lean mass (Nissen. 2003; Poortmans. 2010). Still, if you really have good reason to believe that creatine may blunt your fat loss (it's not impossible, take a look at the "high responders" in figure 1, right), I don't see why you could not give it a try and simply stop taking your creatine for a months or so. If after an initial flattening effect you don't see any other changes in your physique you are at least sure that you don't belong to the unlucky few, for whom creatine monohydrate (not one of the sugar-laden combi products!) could maybe and due to whatever interaction of genes, diet and whatever other confounding factors, forestall fat loss.

References:

• Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc. 2000 Mar;32(3):654-8.
• Huso ME, Hampl JS, Johnston CS, Swan PD. Creatine supplementation influences substrate utilization at rest. J Appl Physiol. 2002 Dec;93(6):2018-22.
• Kreider RB, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinardy J, Cantler E, Almada AL. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc. 1998 Jan;30(1):73-82.
• Manjarrez-Montes de Oca R, Farfán-González F, Camarillo-Romero S, Tlatempa-Sotelo P, Francisco-Argüelles, Kormanowski A, González-Gallego J, Alvear-Ordenes I. Effects of creatine supplementation in taekwondo practitioners. Nutr Hosp. 2013;28(2):391-399.
• Meglasson MD, Wilson JM, Yu JH, Robinson DD, Wyse BM, de Souza CJ. Antihyperglycemic action of guanidinoalkanoic acids: 3-guanidinopropionic acid ameliorates hyperglycemia in diabetic KKAy and C57BL6Job/ob mice and increases glucose disappearance in rhesus monkeys. J Pharmacol Exp Ther. 1993 Sep;266(3):1454-62.
• 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.
• Poortmans JR, Rawson ES, Burke LM, Stear SJ, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 11. Br J Sports Med. 2010 Aug;44(10):765-6.
• van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clin Sci (Lond). 2003 Feb;104(2):153-62.
• Volek JS, Duncan ND, Mazzetti SA, Staron RS, Putukian M, Gómez AL, Pearson DR, Fink WJ, Kraemer WJ. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Med Sci Sports Exerc. 1999 Aug;31(8):1147-56.
• Volek JS, Ratamess NA, Rubin MR, Gómez AL, French DN, McGuigan MM, Scheett TP, Sharman MJ, Häkkinen K, Kraemer WJ. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. 2004 May;91(5-6):628-37.

Anti-Creatine β-Guanidinopropionic Acid (GPA) Increases AMPK, Decreases Blood Glucose & Insulin, Induces Weight loss Without Dieting, Increases Oxidative Capacity and Can Even Delay the Development of Mammary Cancer! BUT...

While he may be so fast that he is almost out of the focus, when the photographer finally released the shutter, Usain Bolt, the fasted man on earth actually doesn't look as if his fiber type composition was highly type II dominant, does he? 

While the relation may be distant, you will soon see that today's blogpost is somewhat related to Saturday's news item about the ability of high dose nicotinic acid to shift the muscle fiber type composition from a towards the oxidative side of things. After all, there is hardly anything that is more "glycolytic" (I am using the word here in a very broad sense) than the use of the intramuscular phosphocreatine stores to squeeze out another rep or explode out of the starting block and sprint towards the finish line in less than 10 seconds.

Ah, yes those phosphocreatine stores, they are great and creatine is the staple supplement for anyone looking to improve his glycolytic performance. But hey, wait a minute: Shouldn't that actually mean that taking creatine would be a bad thing for an ironman (not the one from the cinema, but the Hawaiian ;-)?

GPA - Supplemental creatine unloading for edurance athletes!?

Well, the answer to the question "Is creatine bad for endurance athletes" is, as long as you stick to reasonable doses "No! It isn't.". It neither helps nor hinders endurance performance and a "real" Ironman could probably even get away with one of those sugar-laden "cell-volumizers" without doing much harm. His body is would just burn through the carbs without any of them ending up as additional ballast on his hips. That said, previous studies by Vanakoski et al. or Chwalbiñska-Moneta clearly show that performance detriments are not an issue and in the latter of the two studies, the creatine supplement did even improve the "endurance (expressed by the individual lactate threshold) and anaerobic performance, independent of the effect of intensive endurance training" so that the highly trained rowers who participated in the study at hand would in fact have had an edge at the end of the race and may - if they would have otherwise been on par with the competition - probably have won the race (Vanakoski. 1998; Chwalbiñska-Moneta. 2003).

Surprise: Anyone of you who has ever taken NO Xplode 2.0 (new or old formula) has already been supplementing with GPA - both the original and the "advanced strength" formula contain an undisclosed amount of GPA. Apropos, if you are interested in the differences between the two, check out my previous article on the matter - I guess I don't give away too much, when I tell you that they are few and far between.

There is however a significant difference between not supplementing with creatine and relying on your own body's ability to produce the "meat amino acid" ("creatine" is derived from the greek word for meat) from L-arginine, glycine, and L-methionine and using a "supplement", or rather, another amino acid that does actually hamper its recycling and thus availability by the creatine kinase enzyme. β-guanidinopropionic acid (bGPA, simply GPA or N-(aminoiminomethyl)-beta-alanine), an amino acid with a similar molecular structure as creatine, is such a molecule. GPA reduces the flux through the CK reaction, by reducing cellular creatine uptake and will thus effectively have similar effect as the genetic ablation of the CK enzyme, which does - probably to your surprise - not just hamper the viability of respective mouse mutants, but will also (and here we are getting back to the effects of nicotinic acid) improved their muscular endurance and lead to a shift from type II to type I fiber predominance (Van Deursen 1993; Ventura-Clapier 2004; Vaarmann, 2008).

In short, when you use 5g of creatine as a means to "load" your PCr stores, the administration of GPA will have an "unloading" effect. This effect has in fact been studies in a number of previous studies. The effects and potential side effects of GPA are yet unclear and that despite the notwithstanding that it is freely available on the market and *surprise* you may well have been taking very small quantities of it in the past (maybe even still are), since NO Xplode 2.0 is by no means the only supplement that contains small (and obviously undisclosed) amounts of GPA in its kitchen sink ... ah, I mean "proprietary blend" (see "Ask Dr. Andro: Are There NO Changes in the New N.O.-Xplode 2.0 Advanced Strength Formula?", read full article). Reason enough for Inge Oudman, Joseph F. Clark and Lizzy M. Brewster from the Academic Medical Center in Amsterdam (Netherlands) and the University of Cincinnati to conduct a systematic review to assess the effect of this substance on the mammalian energy metabolism (Oudman. 2013).

So what did the scientists find? Is GPA the "next creatine" we've been waiting for?  ;-)

The primary outcome of the review was the effect of GPA on energy metabolism, function, and morphology of tissues "with high and fluctuating energy demands" (Oudman. 2013) - this includes the obvious,...

• skeletal muscle, where it reduces creatine, phosphocreatine, total creatine, and ATP by 66.1%, 79.7%, 86.7% , and 38.8%, blunted the total creatine kinase activity (-28.6%), but increased the intra-mitochondrial creatine recycling (CK activity) by 200%, reduced the activity of glycolytic enzymes (phosphorylase -38.8%, lactate dehydrogenase -16.2%), increased AMPK expression by 45% and AMPK mRNA by 20%, promoted GLUT-4 expression (+45% in slow-, +33% in fast twitch fibers) and subsequently doubled muscle glycogen content, while decreasing blood glucose (-5%) and insulin levels (-27% in non-diabetic animals), improved endurance during non-/light weight bearing exercises and hampered it during heavier exercise, doubled mitochondrial DNA (evidence for the shift towards an oxidative muscle type), and decreased total and relative muscle weight by 19% and 10% respectively;
• heart muscle, where similar decreases in creatine, phosphocreatine, total creatine, and ATP occurred and GPA decreased the survival rates after myocardial infarction by ~50%

but also the vascular musculature, where no significant effects were observed, in the central nervous system and the brain, where GPA reduced the creatine concentration (brain), doubled the adenylate kinase and succinate dehydrogenase activity (both are involved in energy reallocation), increased the risk of seizures, but showed potentially protective effects against neurodegenerative diseases.  Furthermore the scientists report that GPA reduced creatine uptake in the kidney, reduced the body temperature and increased the amount of BAT (+3.4%, in rodents!). And last, but certainly not least, GPA delayed the development of mammary gland tumors in a rodent model (cf. Chira. 1995; Metzner. 2009)

To summarize...

It looks like a marathon supplement, but it's not even sure that endurance athletes would benefit from taking GPA. In the off.season it could "intensify" the training, but before a race it appears to be rather counter-indicated (photo trainerjosh.com).

Overall the review confirms the notion that the administration of GPA leads to marked reductions in creatine, phosphocreatine, and ATP concentrations and reduces cytosolic, while increasing mitochondrial CK activity in skeletal muscle. These observations stand in line with a shift from a glycolitic to a mitochondrial oxidative metabolism that is facilitated / goes hand in hand with

• a shift from type II to type I fiber predominance,
• increased glucose tolerance, and
• reduced skeletal muscle and body weight

which do not incidentally remind us of the adaptive responses to endurance exercise. It goes without saying that mainstream science is psyched about the "reduced body weight with unchanged food intake" of which the Oudman et al. argue that it "may be related to the fiber type shift, as an association between type II fiber predominance and body weight was previously reported".

Other, per se unquestionably more favorable confounding factors are the increased cellular fatty acid transporter protein concentration, fatty acid oxidative capacity and the compensatory increase in AMPK expression that is actually a response to the perceived energy (ATP) deficiency that develops in response to the administration of GPA (click here to learn more about AMPK's role in fatty acid oxidation and glucose metabolism). So, as paradox as it may sound: Despite its negative effects on the use of glucose as a substrate GPA could actually improve, not deteriorate glucose metabolism via an AMPK mediated "metformin-esque" effect on GLUT-4 expression.

---

Way too many trainees tend to forget the true meaning of "supplement". Supplements are something that "supplement" something else. In the case of creatine supplementation the latter supplements your efforts in the gym and won't (and this has recently been confirmed) build muscle on its own.

So what's the verdict then? Now, all that does certainly sound pretty cool, well - at least for a cut - so would it be better to avoid creatine for leaner muscle gains and use GPA, whenever you are cutting? The first of these bottom-line questions is easy to answer: No! Studies have repeatedly shown that creatine supplementation does not only increase the mass gains, it also improves the ratio of lean to fat mass more than resistance training alone (as long as you the baseline diets are identical).

What about GPA as a diet tool, then? While it certainly would appear that taking (hitherto by the way unknown) amounts of GPA could help you lose weight, it is unlikely that this weight loss will make you look the way, you want to look. I mean if you have to lose weight at all costs, because your health depends on it, GPA could provide a viable AMPK promoter that may help you achieve just that.

Especially strength athletes, sprinters and the like, as well as anyone wanting to look / perform like one of these athletes should yet resort to the tried and proven dietary tweaks to get rid of the extra weight. And there is actually no reason not to continue taking a regular maintenance dose of 3g of creatine during the cut,also in view of the fact that the "beneficial" effects of GPA supplementation are actually brought about by blocking one out of two energy sources - much like keto dieting, by the way, but that's a topic for another blogpost ;-)

Related read: "Ask Dr. Andro: The Pharmacokinetics of Creatine"- Part I & Part II

References:

• Chwalbiñska-Moneta J. Effect of creatine supplementation on aerobic performance and anaerobic capacity in elite rowers in the course of endurance training. Int J Sport Nutr Exerc Metab. 2003 Jun;13(2):173-83.
• Metzner L, Dorn M, Markwardt F, Brandsch M. The orally active antihyperglycemic drug beta-guanidinopropionic acid is transported by the human proton-coupled amino acid transporter hPAT1. Mol Pharm. 2009; 6: 1006– 1011.
• Ohira Y, Inoue N. Effects of creatine and beta-guanidinopropionic acid on the growth of Ehrlich ascites tumor cells: i.p. injection and culture study. Biochim Biophys Acta. 1995; 1243:367–372.
• Oudman I, Clark JF, Brewster LM. The Effect of the Creatine Analogue Beta-guanidinopropionic Acid on Energy Metabolism: A Systematic Review. PLoS One. 2013;8(1):e52879.
• Vaarmann A, Fortin D, Veksler V, Momken I, Ventura-Clapier R. Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice. Biochim Biophys Acta. 2008; 1777: 39–47.
• Vanakoski J, Kosunen V, Meririnne E, Seppälä T. Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations. Int J Clin Pharmacol Ther. 1998 May;36(5):258-62.
• Van Deursen J, Heerschap A, Oerlemans F, Ruitenbeek W, Jap P. Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity. Cell. 1993; 74: 621–631
• Ventura-Clapier R, Kaasik A, Veksler V. Structural and functional adaptations of striated muscles to CK deficiency. Mol Cell Biochem 2004; 256–257: 29–41.