Phosphorus, the Magic Bullet For Fat Loss and Against the YoYo-Effect? P. Restores Thermogenesis, Enhances Satiety

This is not the first study to suggest that as little as 12.5% of the suggested upper limit for phosphorus can make a big difference when it comes to weight loss and the ease of weight loss when you battle reduced diet-induced thermogenesis & increased appetite.

I guess those of you who have been reading every SuppVersity article will remember my January article "Phosphorus, an Anti-Obesity Agent? 3x375 mg With Each Meal Strip Almost 4 cm Off Obese Waists in Only 12 Weeks" (re-read it). You liked that one? Well, I guess you will also like the fact that the evidence that there's some use in phosphorus supplements is accumulating.

Recently, scientists from the Lebanese American University in Beirut, Lebanon (Bassil. 2016), have observed that "P supplementation recovers the blunted diet-induced thermogenesis in overweight and obese subjects and enhances their postprandial satiety" (Bassil. 2016).

Phosphates have also been touted as buffer for athletes, but apper less effective than NaHCO3:

The Hazards of Acidosis

Build Bigger Legs W/ Bicarbonate

HIIT it Hard W/ NaCHO3

Creatine + BA = Perfect Match

Bicarb Buffers Creatine

Instant 14% HIIT Boost

Yes, that's right: This means that phosphorus aka "P" supplementation will address two of the main reasons for weight regain aka the YoYo-effect - a diet- / weight-loss-induced reduction in diet-induced thermogenesis and a decrease of the satiety effects of the foods you consume.

Since diet-induced thermogenesis (DIT) is believed to be largely related to ATP production, which is dependent on phosphorus (P) availability, Bassil and Omar speculated that supplementing extra phosphorus to lean and overweight/obese healthy subjects should have beneficial effects on their diet-induced thermogenesis. Accordingly, they measured the latter with or without P in 10 lean and 13 overweight/obese adults in a double-blind randomized cross-over pilot study with a one week washout period that was meant to exclude any possible interference of the previous trial.

Figure 1:  Diet-induced thermogenesis after drinking 75 g glucose solution with and without phosphorus supplementation in lean and obese subjects. (A) Resting metabolic rate at baseline and over 3 h (180 min) after drinking 75 g glucose solution in lean and obese subjects with phosphorus (solid lines) or placebo (dashed lines); (B) Total area under the curve of RMR with phosphorus (solid bars) or placebo (dashed bars) in lean and obese subjects (Bassil. 2016).

The "problem" is that the subjects were healthy, sedentary non-smokers whose body weight had been stable for the past 3 months. As I will elaborate in the bottom line, the significance of the results for reduced-obese individuals, i.e. people who have lost a significant of body weight and are now facing an increased risk of yoyo-ing backup, is limited... but as I said: more about that later.

Correlation between daily dietary P intake and subjects' BMI (Bassil. 2016).

Additional evidence: Phosphorus intakes correlate negatively with BMI -- Next to the previously cited study by Ajoub, et al. (read more), the study at hand does also provide additional evidence that high(er) phosphorus intakes could have an obesity protective effect. After all, the data in the figure to the left clearly indicates that there is a linear, inverse correlation between obesity / BMI (in normal people a good measure of obesity) and the individual's habitual phosphorus intakes. Since fasting serum P is tightly controlled in healthy humans and is not affected by diet, so that the effect of dietary P is only evident post-prandially, this differential DIT response of lean and obese individuals (see Figure 1).

Speaking of explanations... a 2006 study by Mataix, et al. shows that Spaniards who consume more energy than they'd need have an increased risk of suboptimal phosphate intakes. The same goes for people with low education (Mataix. 2006). Both could point to phosphate intakes as a correlate not a cause of reduced obesity risks. Furthermore, we must not forget that US citizens with the highest phosphorus intakes happen to have an increased risk of mortality (Chang. 2014). This association with mortality risk, however, well be unrelated to phosphorus and a simple result of the high amounts of phosphates you will also find in processed foods. In this case, phosphorus would rather be a marker of increased junk food intake, which in turn could be the actual reason for an increase in mortality risk - an increased risk that may, however, eventually be a result of a messed up balance between phosphorus, calcium and magnesium.

I the study at hand, the DIT, as well as the subjects' resting metabolic rate, respiratory quotient, and substrate utilization (ratio of fat and glucose oxidation) were measured after a 10 h overnight fast at fasting and every 30 min for 3 h after subjects drank a standardized glucose solution, with P (500 mg from potassium phosphate, 23% monobasic and 18% dibasic | considering the results of previous studies, it is, by the way, unlikely that the potassium in KP did the trick) or placebo (cellulose) pills.

Figure 2: Subjective appetite scores of lean (gray) and obese (black) subjects, 3 h after drinking 75 g glucose solution with phosphorus (solid bars) or placebo (dashed bars) supplementation (Bassil. 2016).

To assess the subjects' hunger/satiety response, the researchers used the classic validated visual analog scale (VAS) questionnaires we all know from other studies - with quite intriguing results.

• Overweight/obese subjects had a blunted DIT with placebo. 
• P supplementation induced a 23% increase in their DIT area under the curve (p < 0.05).
• The increase in DIT was associated with an increase in carbohydrate oxidation. 
• All subjects, obese or lean had lower appetite following P supplementation.
• The decrease was expressed as a significantly (p = 0.02) lower desire to eat a meal (4.0 ± 0.7 cm) compared with placebo (5.8 ± 0.9 cm). 

At least during/before a diet, the co-consumption of phosphorus with glucose-containing meals could thus, as the scientists point out, be a valid means to recover the blunted diet-induced thermogenesis in overweight and obese subjects and enhances their postprandial satiety.

High phosphorus intakes and/or supplementation accelerated the fat loss in a previous study sign.

So, will this actually prevent the YoYo-effect? That is possible, but nothing the study at hand can prove. Rather than that, it provides new evidence of the usefulness of phosphorus supplements during weight loss interventions. A usefulness that has been previously confirmed by Ajoub, et al. (read more), but does not necessarily mean that the same beneficial effects will be observed in reduced-obese (=formerly obese) individuals whose DIT and appetite response have been shown to be significantly depressed in the post-dieting period. Until this study has been done, we still have the evidence of its usefulness for overweight individuals trying to shed body fat.

Everyone? Well, I guess another two qualifications have to be made: (a) If the effect is, indeed, as the scientists speculate, mediated by ATP, it is not unlikely that the benefits depend on the co-consumption of glucose or rather carbohydrates. Accordingly, low carbers may benefit less, maybe even not at all. And (b) low carbers have another "disadvantage" with respect to phosphorus supplementation: With plenty of the foods you see in the photo at the top-right, their phosphorus intake usually is already very high - increasing it, even more, may thus have no effect irrespective of the glucose intake. Plus: Eventually, you must keep an eye on the balance between phosphorus, calcium, and magnesium. While a healthy kidney helps to balance serum imbalances out, adding another 1,500 mg of phosphorus or 37,5% of the upper intake limit for phosphorus (4g/day) to your diet with the 500mg extra phosphorus you'd take with e.g. three daily meals could increase your long-term calcium and magnesium requirements to a certain degree - a degree that you will probably cover automatically if you get your phosphorus from foods, not supplements, because only the former (e.g. dairy) come packaged with all important co-factors | Comment!

References:

• Bassil, Maya S., and Omar A. Obeid. "Phosphorus Supplementation Recovers the Blunted Diet-Induced Thermogenesis of Overweight and Obese Adults: A Pilot Study." Nutrients 8.12 (2016): 801.
• Chang, Alex R., et al. "High dietary phosphorus intake is associated with all-cause mortality: results from NHANES III." The American journal of clinical nutrition 99.2 (2014): 320-327.
• Mataix, José, et al. "Factors influencing the intake and plasma levels of calcium, phosphorus and magnesium in southern Spain." European journal of nutrition 45.6 (2006): 349-354.

GVT -- Too Much Volume!? Only Trunk / Legs, and Triceps, not Pecs, Biceps or Back Benefit from Doing 10 vs. 5 Sets

Bad news, bros. The biceps suffers when you increase your volume. Your legs, however, need extra hammering.

German Volume Training (GVT), or the "10 sets method", has been used for decades by weightlifters to increase muscle mass. I've used it before and I guess many of you will have tried this allegedly tried and proven method, as well.

"Allegedly proven"? Yes, you read me right. In spite of the fact that it has been around for decades, Amirthalingam et al., the authors of a soon-to-be-published paper in the Journal of Strength & Conditioning Research claim that, "to date, no study has directly examined the training adaptations following GVT" (Amirthalingam. 2016). The purpose of Amirthalingam's latest study was thus to investigate the effect of a modified GVT intervention on muscular hypertrophy and strength.

Looking for more cutting edge exercise and supplementation science?

Vitargo, Red Bull, Creatine & More | ISSN'15 #1

Pump Supps & Synephrine & X | ISSN'15 #2

High Protein, Body Comp & X | ISSN'15 #3

Keto Diet Re- search Update | ISSN'15 #4

The Misquantified Self & More | ISSN'15 #5

BCAA, Cholos-trum, Probiotics & Co | ISSN'15 #6

Nineteen healthy males were randomly assigned to 6 weeks of 10 or 5 sets of 10 repetitions (or as many reps as possible before failing) for specific compound resistance exercises included in a split-routine performed 3 times per week (workout details in Table 1):

Table 1: Overview of the two workout programs (Amirthalingam. 2016).

Mind the fact that, as it is in the original GVT protocol, only the primary movers, the bench press, lat pulldown, leg press, dumbbell lunge, shoulder press and upright row were performed for 10, the auxiliary exercises for 4x10 reps. Before and after the training program, total and regional lean body mass, muscle thickness, and muscle strength were measured by DEXA and ultrasound, as well as standardized strength tests. 

Figure 1: Changes in body composition and body-part specific (individual) gains in percent increase from baseline; the p-values indicate that only the inter-group difference for the trunk mass (green) was stat. sign. (Amirthalingam. 2016).

As you can see in Figure 1, there were significant increases in lean body mass measures across the groups. However, a significantly greater increases in trunk (p = 0.043; ES = -0.21) and arm (p = 0.083; ES = -0.25) lean body mass favored the 5-SET and thus the lower volume group.

Figure 2: Relative changes in muscle thickness and strength (Amirthalingam. 2016).

Similar results were observed for muscular strength, with greater increases in the 5-SET group for bench press (p = 0.014; ES = -0.43) and lat pull-down (p = 0.003; ES = -0.54). That's surprising - at least in view of the results of the latest reviews of the effects training volume on muscle and strength gains - reviews that suggest that volume is the key to your gains.

Advanced Trainees Benefit from Increased Training Volume | more

So, doing only 5 sets it is, then!? Since no increases and even a non-significant decrease was found for the subjects' leg lean body mass, another modification of the program in the form of doing 10 sets only for body parts that benefit (legs, triceps) and only 5 sets for the upper body could be the key to maximal gains... and it could be something to investigate in a future study, which may then provide a less generalizing conclusion than the study at hand: "GVT program is no more effective than performing 5 sets per exercise for increasing muscle hypertrophy and strength. To maximize hypertrophic training effects it is recommended that 4-6 sets per exercise be performed, as it appears gains will plateau beyond this set range and may even regress due to overtraining" (Behringer. 2016) | Comment!

References:

• Amirthalingam, et al. "Effects of a Modified German Volume Training Program on Muscular Hypertrophy and Strength." Journal of Strength & Conditioning Research: Post Acceptance: November 25, 2016 | doi: 10.1519/JSC.0000000000001747.

Meta-Analysis: Could Energy Drinks be All About Taurine? Taurine, not Caffeine Predicts Performance Enhancement

While almost all energy drinks appear to have it, the evidence that taurine adds to the effects of caffeine has hitherto been unconvincing. Does this change with the latest study by a group of researchers from Brazil and Spain?

Energy drinks (ED) are all about caffeine, right? I have to admit. If you had asked me before I've read the latest study from the Londrina State University in Brazil and the Camilo José Cela University in Spain, I would have answered this question in the affirmative. I mean, come on... the strange add-ons the producers mix into their drinks have but one purpose: distinguish drink X from drink Y and, even more importantly, the healthier competition of plain coffee.

The fact that Souza, et al. observed in their latest meta-analysis that "a signifcant association between taurine dosage (mg) and performance (slope = 0.0001; p = 0.04), but not between caffeine dosage (mg) and performance (slope = 0.0009; p = 0.21)," caught my attention.

You can learn more about taurine & other amino acids at the SuppVersity

Taurine Pumps Up Strength & Recovery?

Taurine Improves Insulin + Glucose Metabolism

Taurine ➲ 180% Testosterone Increase

Taurine + BCAA Work Hand in Hand

43% Reduced Performance W/ BCAAs

3g Taurine Boost Glycogen Re-synthesis Sign.

Before we discuss how relevant this result of the authors' meta-regression actually is, it would be prudent to take a brief look at the methodology section of the paper: As you would expect, the scientists performed a systematic review and meta-analysis of published prior to January 2016 disregarding: (1) case reports; (2) review articles; (3) the use of drugs/substances which influ enced the outcome; (4) caffeine use without ED; (5) ED use without caffeine; (6) subjects on energy-restricted diets and/or weight reduction programs; (7) articles with animal models; (8) studies with samples that were ill or had physical limitations for exertion; (9) longitudinal studies.

Eventually N=34 articles that were (1) original; done with healthy adults; (2) reported the caffeine dose in the ED; (3) measured of physical performance pre- and post-intervention; (4) had a placebo group/session; (7) and offered enough data for effect size calculation were included in the scientists' statistical analysis.

Figure 1: Effects on endurance (left) and jumping (right) performance according to meta-analysis (Souza. 2016).

As you can see in Figure 1, the ED ingestion improved both, the subjects' performance in standardized endurance (ES = 0.53; p < 0.001 | Figure 1, left) and jump tests (ES = 0.29; p = 0.01 | Figure 1, right). Likewise beneficial were

• the effects on muscle strength and endurance (ES = 0.49; p < 0.001), and 
• sport-specifc actions (ES = 0.51; p < 0.001; cf. Table 1).

What did not improve, however, are the subjects' sprinting times - well, at least not significantly across the N=17 studies (ES = 0.14; p = 0.06).

Note: This article does not say that caffeine doesn't work! That caffeine works is beyond doubt. What the article does claim, however, is that the results of the meta-analysis, when combined with previous research, suggest that the ratio of caffeine to taurine could explain differences between the efficacy of various drinks (see bottom line for further discussion).

With a borderline significant effect and an increase of 16% in a study by Alford, et al., I would not discount the possibility that EDs would help Usain Bolt, as well.

Table 1: Subgroup analyses of categorical variables (Souza. 2016).

But didn't we want to talk about something else... oh, yes: the role of taurine! I guess some of you are already rolling their eyes. After all, I make no bones about my personal assessment that taurine may indeed be one of the most underrated amino acid supplements on the market (learn more).

Figure 2: Illustration of the subject- and supplement dependent continuous variables and their impact on the effect size indicated by the slope and significance of the results of the meta-regression (Souza. 2016).

So what's the evidence, then? Well with p-value of 0.04, taurine is the only subject / supplement related continuous variable that predicted the performance increase that was observed in the studies. The slope and thus the increase in effect size per unit of taurine in the corresponding meta-regression was however hardly relevant. No wonder, after all, previous studies, as well as the suspected stress-protective as well as anti-protein catabolis mechanisms (Zhang. 2004; HaeMi. 2003) suggest that taurine will have chronic rather than acute effects (cf. Rutherford. 2010); with the studies in this review being acute supplementation studies, these benefits couldn't be recorded, anyways.

Coffee - The Good, The Bad & The Interesting: 2-4 Cups of Coffee for Adiponectin. Roasted Filtered Coffee & High LDL!? The Optimal Caffeine / Taurine Ratios & the Buzz | more!

So, this begs the question: Even if the advantage is small, why could more taurine yield a higher exercise performance? Unfortunately, the authors didn't address this question in detail, but hey, I guess otherwise I would be useless... Now, I cannot tell you for sure what it is and without having access to the full dataset I cannot even confirm my hypothesis, but I still feel reminded of an older article I wrote about the synergy of caffeine and taurine, in which I presented evidence that a 1:10 mix of caffeine to taurine may be the optimal compromise between the jittery energy spike from caffeine and the calming (GABA mediated | Ripps. 2012) effects of taurine.

If we take a look at the continuum of caffeine and taurine intakes in the studies in the meta-analysis at hand, it turns out that - with caffeine dosages ranging from 40 and 325 mg and amount of taurine ranging from 71 to 3105 mg - many of the studies ended up being in that range.

If someone would now correlate the effect sizes and the caffeine:taurine ratio and find that there is a significant relationship between the two, this would provide more evidence that the implications I've formulated based on animal studies in 2013 (read the original article) could inform your supplement and dosing choices, so that 200-400 mg caffeine and 2,000-4,000 mg of taurine make a highly effective stack. As previously pointed out (see red box), this does not imply that caffeine alone wouldn't work, but having it with taurine in the correct ratio may be what makes one energy drink more effective than the other | Comment on Facebook!

References:

• Alford, Chris, Harriet Cox, and Robert Wescott. "The effects of red bull energy drink on human performance and mood." Amino acids 21.2 (2001): 139-150.
• HaeMi, Lee, Paik IlYoung, and Park TaeSun. "Effects of dietary supplementation of taurine, carnitine or glutamine on endurance exercise performance and fatigue parameters in athletes." Korean Journal of Nutrition 36.7 (2003): 711-719.
• Ripps, Harris, and Wen Shen. "Review: taurine: a “very essential” amino acid." (2012).
• Rutherford, Jane A., Lawrence L. Spriet, and Trent Stellingwerff. "The effect of acute taurine ingestion on endurance performance and metabolism in well-trained cyclists." International journal of sport nutrition 20.4 (2010): 322.
• Souza, Diego B., et al. "Acute effects of caffeine-containing energy drinks on physical performance: a systematic review and meta-analysis." European journal of nutrition (2016): 1-15.
• Zhang, M., et al. "Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men." Amino acids 26.2 (2004): 203-207.

Panaxatriol - Ginseng Constituent Has Protein-Anabolic Effects When It's Administered After Resistance Training

Warning: It's too early to stockpile ginseng or ginseng capsules, yet... the independent jury is still out there.

Ginseng is not exactly the agent you will think about when you hear the word "natural anabolic". And in fact, previous studies using whole ginseng or extracts that were usually standardized for ginsenosides shown to help with dementia in athletes were not exactly encouraging.

Against that background, I have to warn you right away (I will repeat my warning in the conclusion) that you should not rush to the next best supermarket or supplement store to get a bag of ginseng roots or pills.

Why's that? Well, you cannot be sure that they contain enough of Panaxatriol, which is the active ginseng saponoid that worked the muscle building magic in the latest sponsored proof-of-concept study from Japan. A rodent study (another reason not to literally buy into the hype, yet), yes, albeit one with results I consider worth reporting... if nothing else, because I expect this agent to be part of yet another kitchen-sink "natural anabolic" supplement in the near future.

In contrast to PT, a high protein intake has been proven to be sign. protein anabolic

Are You Protein Wheysting?

More Protein ≠ Autom. Fat Loss

More Protein ≠ More Satiety

Protein: Food or Supplement?

Protein Timing DOES Matter!

Too Much Whey Pro-Diabetic?

So what do you have to know? Well, it has long been known that the anti-hyperglycemic mechanism of ginseng involves upregulation of Akt signaling and that it owes its nerve-regenerating effects to an upregulation of ERK1/2 signaling. Since these proteins also figure in skeletal muscle protein synthesis, it was only logical for Takamura et al. to assume that "ginseng could increase muscle protein synthesis via the Akt-mTORC1 or ERK1/2-mTORC1" (Takamura. 2016).

Since previous studies suggested that the Panaxatriol saponins are responsible for the effects on Akt and ERK1/2, it was only logical for the Japanese researchers to use isolated panaxatriol saponins, which have an excellent bioavailability, because the interaction with the gastric acid and the enzymes of intestinal bacteria cleaves the branched-chain sugars from the saponins and turns them into active Panaxatriol (PT), in their study. A study on Sprague-Dawley rats, whose legs were divided into control, PT-only, exercise-only, and exercise + PT groups. As the authors explain, "[t]he right legs were subjected to isometric resistance exercise using percutaneous electrical stimulation, while the left legs were used as controls" (Takamura. 2016).

Figure 1: Effects of PT on rpS6 phosphorylation at Ser240/244 0.5 h (A) and 3 h (B) after resistance exercise (Takamura. 2016); Con, control; EX, exercise; PT, panaxatriol; A.U., arbitrary unit

Interestingly enough, the isolated PT was administered only once and after the "workout" at a dose of 0.2 g/kg - 30 mg/kg for a human being (so ~1.8 - 3g of Panaxatriol) and yet it had the effects the scientists had expected: the treatment did not just elevate the Akt and ERK1/2 phosphorylation in the PT treated animals significantly over the exercise-only group, it also triggered highly significant elevations of the downstream controller of muscle protein synthesis, p70S6K, which was significantly increased at both 0.5 h and 3 h after exercise.

Figure 2: Effects of PT on muscle protein synthesis 3 h after resistance exercise. Representative images of western blot analysis with anti-puromycin (Takamura. 2016).

Now you may rightly be arguing that this is all nice, but irrelevant. After all, it's the actual protein synthesis that counts, not the elevation of regulatory proteins. Indeed, you're right, but by the means of the relatively new, but tested SUnSET method (Goodman. 2013), Takamura et al. were able to detect a significant increase in protein synthesis in the rodents that received the PT supplement immediately after their "workout".

The extent of the increase, however, cannot be accurately quantified by this method. Accordingly, we know that the increase in the protein synthesis gauge p70S6K actually triggered increases in protein synthesis, but we don't know if the effect size of this increase was practically relevant.

Yes, you're right, ginseng was also on the list of 20 that may help you stay lean after you lost weight | more.

Beware! Don't buy the next best ginseng supplement! Even though panaxatriol saponins are abundant in ginseng, you can hardly tell how much you had to ingest to arrive at the human equivalent of the effective dose, i.e. 30 mg/kg.

And even if you got the dosage right, you do not know how practically significant and sustainable (maybe that's a one-time thing, or one will become resistant over time) the increase in protein synthesis the authors didn't quantify will actually be. Ah, ... and yes: the fact that this is a sponsored rodent study, obviously doesn't make its results more reliable, either | Comment on Facebook!

References:

• Goodman, Craig A., and Troy A. Hornberger. "Measuring protein synthesis with SUnSET: a valid alternative to traditional techniques?." Exercise and sport sciences reviews 41.2 (2013): 107.
• Takamura, Yusuke, et al. "Panaxatriol derived from ginseng augments resistance exercised–induced protein synthesis via mTORC1 signaling in rat skeletal muscle." Nutrition Research (2016).

DMAA / OxyElitePro - The Good, the Bad and the Downright Ugly - More Powerful (+180% Perf.) Than You'd Think, but ...

Back in the day, when the original Oxy-ELITE Pro was pulled from the market, people paid crazy amounts of money for the bottles that were left on Ebay - a big mistake! Not because it would fry your liver, but rather because it's 'stim' effects will - just as those of other DMAA products - turn against you, w/ chronic use. 

You may (rightly) be asking yourselves, why I am addressing an (albeit famous) supplement that is no longer on the market in 2016 blog post. Well, the answer is simple. I still see people whining about how "awesome" this product was all over the web. People who wish that DMAA and OxyElitePro would come back and people who would be willing to spend at least 5x the original price for the few (long expired) bottles that appear to be traded on the black market.

It's those people I want to advice: Even if you ascribe the liver damage as the result of stupid overdosing and acknowledge that other products appear to be far worse (García-Cortés. 2016 | FFT), don't waste your money on DMAA products, in general, and the original OxyElitePro (OEP), in particular. And here's why...

Unlike the average fat burner, OxyELITE was indeed more than just caffeine:

For Caffeine, Timing Matters! 45 Min or More?

Coffee - The Good, Bad & Interesting

Three Cups of Coffee Keep Insulin At Bay

Caffeine's Effect on Testosterone, Estrogen & SHBG

The Coffee³ Ad- vantage: Fat loss, Appetite & Mood

Caffeine Resis- tance - Does It Even Exist?

The "why"s are based on a recent study from the Department of Physiological Sciences at the University of Espírito Santo (Zovico. 2016) in Brazil. The study was originally conducted to "to evaluate acute and chronic OEP affects, at controlled doses in Wistar rats, on physical performance, metabolic parameters, liver injury markers and oxidative stress markers and mitochondrial biogenesis in skeletal muscle. A study of which you'd guess that it would long have been done in view of the fact that serious adverse effects have been reported after OEP consumption, all over the web.

Figure 1: Photo of the original OxyELITE Pro bottle and supplement facts label (Google Image Search).

In said study, the rats were divided in control, 4.3 mg OEP/kg (1/2 cap in human equivalents, HED), 12.9 mg OEP/kg (~1 cap HED) and 25.8 mg OEP/kg (1.5-2 caps, HED). All groups were submitted to supplementation with OEP for 4 weeks and the experimental protocols were performed 30 min after the first OEP administration (acute response) and 30 min after the last OEP administration at the end of the fourth week (chronic response).

• The Good: OEP simply works -- If you are one of the previously referred to users of the product, you will probably remember your first training "on OEP". How would you describe it? Probably similar to the rodents in Zovico's study, who easily ran 2.6x and 2.8-fold further with the medium, respectively, the high dose of OPE in their blood.

  

  Figure 2: Effects of acute OEP supplementation at different dosages on running distance and time to exhaustion (Zovico. 2016) - based on data that is written out twice in the full-text of the study at hand, but has not been correctly plotted in the figure(s) from the original publication.

  Now, "awesome" would, in fact, be an appropriate word to describe the effects I've plotted for you in Figure 2 (note: the original figure in the study is messed up). In view of the fact that ...

  "[n]o effect was found in other analyses such as spontaneous physical activity, body weight, food and water intake, hepatic toxicity, cardiac oxidative stress and mitochondrial NA amount" (Zovico. 2016),

  ... you will now probably (and rightly so) ask yourselves: "So, what's 'the Bad', then, if it's not liver or heart damage as they both have been reported allegedly as a consequence of the (ab-)use of both, OxyElitePro and DMAA based products, in general?" 
• The Bad: No liver damage, but potentially impaired adaptation to training -- Ok, part of the previously discussed "good news" was that there was no measurable - or, I should say - no sign. changes in AST, ALT and GGT (liver health) and even small beneficial effects on TBARs, i.e. lipid oxidation in the group of rodents that received the medium dose of the supplement (see MDA levels in Figure 3).
  

  

  Figure 3: Oxidative stress measured in MDA per mg or protein (left) and mRNA activity PGC-1A, a primary
  marker of exercise-induced mitochondrial biogenesis (Zovico. 2016).

  On the other hand, the scientists also found a significant, albeit likewise dose-dependent decrease in PGC-1A in the high dose group (the high dose group also saw non-significant decreases in food intake and body weight). With the latter being an important regulator of (exercise-induced) mitochondrial biogenesis, one may speculate that at least part of the exercise-induced adaptational response may be blunted in response to the either DMAA or one of the other supplement ingredients, namely the undisclosed amounts of Bacopa Monnieri, Bauhinia Purpurea, Cirsium Oolygophyllum, or Yohimbe bark extract (cf. Figure 1 | note: we know from previous studies that the 100mg of caffeine can't be the problem).
  
  Since this occurs only with the high dose of the supplement, i.e. 25.8 mg/kg or ~1.5-2 caps for a human being. This effect is bad, but not downright ugly - speaking of which...
• The Ugly: OEP simply stops to work -- If you belong to the group of former OEP users I've previously alluded to and/or have used any other DMAA product more than once or twice, you will probably remember "the Ugly", anyway: After only a few workouts "on OEP" (or any other DMAA) products, the effects began to vanish.
  

  

  Figure 3: Relative endurance performance with acute and chronic (4 wks) supplementation (Zovico. 2016); all data expressed relative to the values of the control group on day 1 (cf. Figure 2).

  And as if that was not bad enough, the stimulant actually began to make you tired - as tired as it made the rodents in the study at hand, whose running performance decreased significantly (by up to 45% in the case of the running distance after high dose consumption) over the course of the 4-week supplementation period compared to the performance of the control group on day one (see Figure 3).
  
  Whether that's related to and/or a consequence of the previously discussed reduction in PGC-alpha expression in the chronically supplemented rodents would have to be investigated in future, studies - it does not seem unlikely, to say the least.

This study raises the question: Can you become caffeine-resistant, too? Learn the answer.

That your liver probably doesn't take a hit doesn't make OEP the hit: I guess that most of you will not even know where to get those expired bottles of OEP I mentioned in the introduction of this article. For those who do and those who contemplate buying one of the many illegal DMAA products you can still order on the Internet, the article at hand should be convincing enough to stay away: I mean, what's the use of a workout booster you can use only once or thrice before it backfires and the formerly ergogenic powder or tablets show their ugly ergolytic (=athletic performance decreasing) face? | Discuss your experience w/ this or other stims?

References:

• García-Cortés, Miren, et al. "Hepatotoxicity by Dietary Supplements: A Tabular Listing and Clinical Characteristics." International journal of molecular sciences 17.4 (2016): 537.
• Zovico, et al. "Effects of controlled doses of Oxyelite Pro on physical performance in rats." Nutrition & Metabolism201613:90 | DOI: 10.1186/s12986-016-0152-4 [ahead of print].