Sldge’s BodyBlog

Yohimbine is the primary alkaloid found in the Pausinystalia yohimbe tree. It is available OTC and via prescription as a dietary supplement and as treatment for erectile dysfunction respectively. For the latter, it seems to work mostly via vasodilation of the periphery, which basically means it improves blood flow to your Dong Johnson. For the former, it works by antagonizing the alpha-2 adrenergic receptor.

To briefly explain the adrenergic system so this makes a little more sense to you, consider two receptor types: Alpha and Beta. Of these there are five subtypes: Alpha-1 and 2; and Beta-1, 2 and 3. The alpha receptors have further subsets to that (A, B and C) but that is a little too deep for the sake of this. These receptors are activated endogenously by epinephrine (EPI) and norepinephrine (NOR) with differing potencies. The simplest way to think of it is that at rest, EPI/NOR typically activate the alpha receptors. This alters signal transduction pathways, such as reducing cyclical AMP (cAMP) concentrations, inhibiting neurotransmission, relaxing smooth muscles (hence the vasodilation explained above) and generally putting the dampers on fat loss. When called for, such as during exercise, fear, or use of stimulant drugs, EPI/NOR concentrations increase and exceed a certain threshold. This switches their affinities to the beta receptors which ramps up cAMP, increases lipolysis (breakdown of fat from stores into the bloodstream), increases neurotransmission and generally increases calorie expenditure/metabolic rate. It is this that has been the basis of the stimulant fat burner for many years now.

As an alpha-2 antagonist, yohimbine prevents EPI/NOR from binding, and thus prevents the metabolic slowdown that comes with it. However yohimbine is not selective for this receptor like some available synthetic drugs. In fact, it has a bit of a shotgun effect, spraying many receptors at once, including (antagonizing) serotonin and dopamine receptors. This could be why some people do not respond well to oral yohimbine, specifically those that suffer bad anxiety from it. This effect can be worsened by the addition of a strong stimulant or synthetic beta-2 adrenergic agonists, like ephedrine or Clenbuterol. This is a silly move by some who think they are “hardcore” enough to mix the two, resulting in a significantly elevated heart rate and very high blood pressure. And in reference to silly moves, this segues nicely into the basis of this article…

Before discussing the specific case, I want to put this into perspective for all you good readers. The recommended dose for yohimbine is generally 0.2mg/kg of bodyweight, and it is also widely suggested that you start low and build up to this dose. This means that a 180lb man would eventually build-up to about 16mg per day, preferably split into smaller doses. So consider my amazement when the Journal of Clinical Toxicology throws up a new article discussing a case file of a 37 year old bodybuilder who ended up in  the hospital exhibiting malaise, vomiting, loss of consciousness, and repeated seizures after ingesting yohimbine. He scored a 3 on the <meta content="Word.Document" name="ProgId" /><meta content="Microsoft Word 12" name="Generator" /><meta content="Microsoft Word 12" name="Originator" />

<style> </style>http://www.unc.edu/~rowlett/units/scales/glasgow.htm” target=”_blank”>Glasgow Coma Scale (which basically means comatose) and required electrical breathing apparatus. His blood pressure reading was 259/107, putting him in stage 2 hypertension, which would have been stage 4 had they not consolidated stages 3 and 4 into stage 2 recently. And in order to put the final vital sign into perspective, the normal resting heart rate for an adult is in the 60-90 beats per minute region. His heart rate was140 BPM, which is essentially like him going at 75% of his maximum heart rate on the treadmill, all while lying on a hospital bed in a state of arrest.

Did I mention that the guy took 5 grams?

His Darwin award is in the post.

Source: Giampreti A, Lonati D, Locatelli C, Rocchi L, Campailla MT. Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol (Phila). 2009 Jul 30.

As a researcher I am constantly on the lookout for new and exciting compounds whether they increase muscle, reduce fat or enhance performance. Those that do the latter are known as “ergogenics.” For athletes and sportsmen, these can make all the difference not only during competition, but as an aid during training/practice. This article does not discuss any of the new and novel things I come across as they are saved for product formulation (gotta make a living somehow), but it does discuss a potential new twist for an old friend. The article title has already given away that I am referring to coenzyme Q10. This seems to be the new thing right now, especially with the new forms available with (apparent) better oral bioavailability such as Ubiquinol and Idebenone.

Research into CoQ10 has always been a little sketchy with regards to younger, healthy individuals. It could be one of those things that only really benefits the elderly (or those with heart problems) as studies rarely used healthy participants. But recently a new study was published in the Journal of Strength & Conditioning Research that piqued my interest as the researchers (Gökbel, H et al) investigated the effects of CoQ10 on performance during repeated bouts of supramaximal exercise in sedentary men. For the laymen among you, supramaximal is any type of exercise that demands anaerobic respiration because energy-demands far exceed that which can be produced via oxidative metabolism. And you can read sedentary as god-damn lazy. What they found was that CoQ10 did not differ from placebo with regards to fatigue (which decreased with each rep for both groups), but the CoQ10 group did note a higher mean power but not peak power. This basically means that they weren’t able to increase their power generation on later reps, but were able to keep power generation higher (than placebo) across all reps. This study was done using 100mg of CoQ10 over two eight-week periods, but an older study I’d now like to make note of that used 300mg per day for four weeks may elucidate a potential mechanism for the Ergogenic effect.

The researchers in this study (Linnane AW et al) weren’t investigating CoQ10 as an ergogenic, but rather its influence on protein expression and muscle fiber composition. Their study found that those using CoQ10 displayed less type I fibers and more type IIb fibers. Type I fibers are known as “slow twitch” fibers as they have a higher oxidative capacity (lots of mitochondria helps) so are ideal for endurance type activity. Type IIb fibers are known as “fast twitch” fibers, and for good reason too – they contract rapidly, preferring the glycolytic pathway of respiration, allowing them to generate a ****-ton of power. These are the fibers typically recruited for weightlifting and also have the highest capacity for growth. They concluded that CoQ10 has this effect by acting as a “gene regulator”. Thus, it is possible that taking CoQ10 regularly may help you maintain strength across all/most sets during a workout. Dosage seems to be 100-300mg daily, or whatever dose that equates to in the Ubiquinol/Idebenone form.

Sources:

Gökbel, Hakk; Gül, Ibrahim; Belviranl, Muaz; Okudan, Nilsel. The Effects Of Coenzyme Q10 Supplementation on Performance During Repeated Bouts of Supramaximal Exercise in Sedentary Men. The Journal of Strength & Conditioning Research: 28 July 2009.

Linnane AW, Kopsidas G, Zhang C, Yarovaya N, Kovalenko S, Papakostopoulos P, Eastwood H, Graves S, Richardson M. Cellular redox activity of coenzyme Q10: effect of CoQ10 supplementation on human skeletal muscle. Free Radic Res. 2002 Apr;36(4):445-53.

 

In the grand scheme of things, this article is nothing revolutionary – quite the opposite in fact as it may seem quite obvious. Oxygen deprivation (hypoxia) is generally bad for the whole ‘living’ concept, so you’d expect it would not be all that fantastic for muscle growth. And yet the way we train as bodybuilders and as powerlifters involves an oxygen-absent metabolic pathway called anaerobic respiration. Obviously we can’t train and live anaerobically indefinitely because we haven’t evolved that way, but for short bursts of time we can, and the eventual outcome is growth. The real interest in this article in how the cell caters for these periods of hypoxia and whether we can take advantage of it to benefit training.

 

Scientists have identified a gene called DNA-damage-inducible transcript 4, which is also known (and more easily remembered) as REDD1. It is REDD1’s job to suppress energy-costly metabolic processes during cellular stress in order to prevent the cell exceeding its limits. Growth and replication are considered costly when the life of the cell is at stake. It does this by inhibiting the mammalian target of rapamycin, which you may be more familiar with when I give its acronym, mTOR. If you didn’t already know, mTOR is the regulator of cell proliferation and protein synthesis. Out of interest, its not just hypoxia that activates REDD1 – glucocorticoids (such as cortisol) do also, explaining one of the (if not the) ways in which they are really not super-duper for muscle growth. The REDD1 gene excites scientists because they are looking into ways of inducing cell death in specific cells, such as tumor and cancer cells, without harming the existing healthy cells. As bodybuilders, all we want to know is how to get bigger and stronger, right? The removal of REDD1 is quite rapid once oxygen levels normalize, controlled by the ubiquitin-proteasome pathway. This allows the cell to deal with periods of stress really quite brilliantly.

 

And now onto some questions for which I currently have no answers; namely, is hypoxia training a bad idea or does it help prep us for the periods of low oxygen during training? The cell can deal with short periods of low oxygen very well, and we can still cause muscle growth despite it. There is equipment available to buy for this very purpose, limiting the amount of breath you can take in, not to mention the practice of some UFC athletes who tape their nostrils closed and breathe through a snorkel. And some athletes have been training at altitude for competition for decades. Is it worth it? No idea, but any feedback based on your experiences is most welcome.

 

Source: Katiyar S, Liu E, Knutzen CA, Lang ES, Lombardo CR, Sankar S, Toth JI, Petroski MD, Ronai Z, Chiang GG. REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1 ubiquitin ligase. EMBO Rep. 2009 Aug;10(8):866-72.

Prolylcarboxypeptidase (PRCP) has been known of for decades now, but very recent research into it has shed light on its involvement in the adipostat. PRCP is an enzyme that works by removing something called the C-terminus from the end of an amino acid chain. In layman’s, all amino acids begin with an N-terminus (i.e. an amine group that contains a nitrogen atom, hence the ‘N’) and end with a C-terminus (i.e. a carboxyl group). A chain of amino acids is formed by connecting the N-terminus of one amino acid to the C-terminus of the next, thus giving rise to polypeptides (typically short amino acid chains) and proteins (long amino acid chains). If this is still not clear, think of PRCP as an enzyme that chops the end off a protein, thereby changing its properties and what it can do.PRCP has so far been found to be involved in regulating blood pressure, but now research coming out of the Yale School of Medicine has connected it with the peptide hormone alpha-melanocyte-stimulating hormone (aMSH). aMSH is heavily involved in the production and release of melanin, a pigment that gives rise to skin color. In fact, two synthetic analogs of aMSH have been developed, one of which is Melanotan which is being sold on the black market quite a lot lately and is the reason that some bodybuilders in your gym look like they’ve been dipped in wood stain. The other has given rise to Bremelanotide, a drug for treating sexual dysfunction that was abandoned last year due to health concerns.

aMSH is also a powerful appetite suppressant hormone in the brain, however the researchers found that its activity is short-lived due to rapid deactivation. While the full picture has yet to be decoded, they did discover that PRCP was responsible for altering the structure of aMSH (by cleaving the C-terminus) rendering it no longer neuroactive. To further investigate this, they inhibited PRCP in mice and discovered that it reduced food intake across the board, even in obese mice. They also found that mice bred deficient in the PRCP gene were naturally leaner despite high calorie intakes. Both groups had higher levels of aMSH in the brain (specifically, the hypothalamus, which is generally considered the food control center of the body) compared to the control group. This research will surely kick off a new avenue of research with regards to helping the obese control their appetites.

Source: Wallingford N, Perroud B, Gao Q, Coppola A, Gyengesi E, Liu ZW, Gao XB, Diament A, Haus KA, Shariat-Madar Z, Mahdi F, Wardlaw SL, Schmaier AH, Warden CH, Diano S. Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents. J Clin Invest. 2009 Jul 20.

Ketotifen is an anti-histamine available in two forms: eye drops to treat conjunctivitis, and oral tablet for asthma control. It is also well-known in the bodybuilding community as a means of up-regulating beta-2 adrenergic receptors that have been down-regulated from the use of potent beta-2 receptor agonists like clenbuterol. Beta-2 agonists can be highly lipolytic and are often used during periods of dieting down. By inhibiting the desensitizing effect on the receptors, the user can take advantage of the fat loss effects of the agonists for longer periods of time. Ketotifen’s anti-histamine effect is via mast cell stabilization. Mast cells are found in many tissues, storing histamine for their involvement in the allergic response. A mast cell stabilizer (such as ketotifen) basically stabilizes the cell (no real surprise there given their name) and prevents histamine release. This is how it helps asthmatics.

Mast cells are also heavily involved in defence against infection, facilitating healing in damaged tissue and promoting blood flow. Researchers at Harvard have recently found that under certain conditions mast cells build up to levels well beyond that required, becoming very unstable and causing inflammation. They also found a ton of them in obese and diabetic human fat tissue – much more than found in normal human fat tissue. To investigate, the researchers fattened up some mice to obese proportions and split them into four groups – control, healthy diet, mast cell stabilizer, or a combination of a healthy diet and mast cell stabilizer. While the mast cell stabilizer group improved significantly, the combination group basically recovered 100%. Not content, the researchers tried to fatten up some mast cell-deficient mice with no success.

This was a rodent study and there is no evidence that this effect will occur in humans, so it’s not something I can recommend, but the prospect is exciting for sure. Next up for the researchers is to take this new investigation to primates - then we will know a lot more.

Source: Liu J, Divoux A, Sun J, Zhang J, Clément K, Glickman JN, Sukhova GK, Wolters PJ, Du J, Gorgun CZ, Doria A, Libby P, Blumberg RS, Kahn BB, Hotamisligil GS, Shi GP. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med. 2009 Jul 26.

Stretching is the act of elongation of skeletal muscles, typically done to improve the elasticity of the muscle. It is often done before (and/or after) physical exercise as part of a “warm-up” to promote blood flow for muscle cushioning, or “cool-down” in order to help flush harmful toxins from the muscle. The latter of which is firmly believed to help reduce the soreness felt after training (sometimes occurring days after training, known as delayed onset muscle soreness or DOMS). Researchers from Norway, Australia and the UK wanted to see whether stretching before and after exercise help reduce soreness and reduce the chance of injury. Using the internet, over two thousand people participated, split into two groups – stretch and non-stretch – and gave feedback online over twelve weeks. What they found was that stretching did not seem to prevent injury, but did seem to reduce what they call “bothersome soreness” of the legs, buttocks and back. The study is hardly definitive, as feedback was subjective (albeit against a control group), and variables were plentiful. Additionally, many people find a good stretch before and after training mentally reassuring, and there are even some camps who believe that stretching after a workout helps make muscle fascia more malleable and willing to grow. There is even some speculation that stretched fascia is what allows the “muscle memory” phenomena to occur. There is, however, no scientific evidence in support of fascia stretching and increased muscle growth.

Source: Jamtvedt G, Herbert RD, Flottorp S, Odgaard-Jensen J, Håvelsrud K, Barratt A, Mathieu E, Burls A, Oxman AD. A pragmatic randomised trial of stretching before and after physical activity to prevent injury and soreness. Br J Sports Med. 2009 Jun 11.

Naringenin is a flavonoid found in citrus fruits, particularly in grapefruit. It inhibits at least one enzyme of the Cytochrome P450 system, thereby diminishing the body’s ability to break down drugs and toxins. It is for this reason that some fat burners include naringenin or other CYP 450 inhibitors in order to potentiate the stim-effect of the product. A recent study into the flavonoid investigated its effects on metabolic syndrome with some very favorable results. It was found that the majority of metabolic disturbances were corrected; cholesterol was lowered, fatty acid oxidation increased, glucose metabolism returned to normal and insulin resistance improved. This was performed in the rat model so research is still in the early stage, but what has really excited the scientists is that these effects have come about independently of calorie intake. This suggests that there is some sort of genetic reprogramming occurring. The team are planning further research.

Source: Mulvihill EE, Allister EM, Sutherland BG, Telford DE, Sawyez CG, Edwards JY, Markle JM, Hegele RA, Huff MW. Naringenin prevents dyslipidemia, apoB overproduction and hyperinsulinemia in LDL-receptor null mice with diet-induced insulin resistance. Diabetes. 2009 Jul 10.

Vinegar is made by fermenting alcohol in various ways to produce all the different varieties available. It has long been part of traditional medicine used for anything ranging from soothing minor burns, to easing arthritis to promoting restful sleep. While this may come as little surprise to those already in the know about the wealth of benefits vinegar has to offer, scientists in Japan have found it to be an excellent tool for controlling blood sugar levels, reducing blood pressure and preventing fat accumulation. Naturally bodybuilder’s are more concerned with glucose management and fat prevention, so these are the two main topics I’ll stick to.

The key component in vinegar is acetic acid. It makes up around 5% of the composition of typical vinegars, although some pickling vinegars can be up to 15-20%. The acetic acid upon ingestion, supplies an acetyl group which can then combine with Coenzyme A (CoA) to form acetyl-CoA which is central to the metabolism of carbohydrates and fat as part of the Krebs cycle. This also raises the production of adenosine monophosphate (AMP) in the liver, unbalancing the AMP:ATP (adenosine triphosphate – the energy “currency” of every cell) ratio and activating an enzyme called AMP-activated protein kinase (AMPk). AMPk has been referred to as the metabolic “master switch”, controlling many genes involved in glucose metabolism and lipogenesis, causing them to down regulate and thus prevent body fat accumulation.

Acetic acid can also increase the oxidation of fatty acids in the liver (i.e. reduce fat, not just prevent its accrual) by inhibiting the use of glucose as a fuel (a process called glycolysis). This occurs because acetic acid has a pH-buffering effect on the cell. Under homeostatic conditions, natural concentrations of acetic acid are usually kept quite low in order to avoid disrupting the control of the cellular pH. This metabolic regulation takes place because chief control of glycolysis is provided by the enzyme phosphofructokinase (PFK) which is extensively pH sensitive. Acidifying (lowering) pH acts to inhibit the actions of PFK, thereby promoting glycogen storage (if it cannot be used for fuel, it gets stored,). Incidentally, this can be a plus for bodybuilder’s in itself as it enhances glycogen synthesis and repletion in muscle tissue.

The researchers plan to perform further clinical studies into the effects of vinegar on fat mass as well as investigate the effect of acetic acid on fatty oxidative activation in other organs, particularly skeletal muscle. I especially look forward to the latter and will report back as soon as the data is published.

Source: Kondo T, Kishi M, Fushimi T, Kaga T. Acetic acid upregulates the expression of genes for fatty acid oxidation enzymes in liver to suppress body fat accumulation. J Agric Food Chem. 2009 Jul 8;57(13):5982-6.

Let’s not kid ourselves, losing weight, providing we aren’t referring to single-digit competition-ready levels of body fat, is not all that difficult. Providing the dieter sticks to their regime of eating less than they metabolically require for prolonged periods of time they will lose fat. Of course most folk in this day and age find even that to be too much hard work, but that is a different topic entirely. For the sake of this piece we will focus only on those who can lose the weight but find that the real challenge comes in keeping the weight off. This occurs because the brain appears to employ several biomarkers that keep tabs on your current metabolic condition (levels of body fat and energy flux), which once rise due to higher energy demands as you get fatter, do not seem to want to go back down to where they were. Thus, when you get fat and then manage to get lean again, your brain just isn’t happy and wants to be fat again. Exact reasons for this are still not firmly established, although evolutionary thought suggests it is a survival technique - the brain is essentially convinced that there is a famine and that the person is starving. Plainly put, the sudden and gross availability of food for humankind transpired much faster than humankind had to evolve to it. But the brain is fine with this – absolutely ecstatic probably, as it means starvation is no longer an issue for those with access to it.

Anyhow, these “raised” biomarkers leave major energy gaps, caused by the person having the appetite they had at a higher weight and the brain thinking that it requires the same amount of calories, along with a reduced level of energy expenditure. For a lot of dieters, the result of this is what has been called “yo-yo dieting”, where they will shed weight and then put it right back on, in a perpetual cycle. The latest research from the University of Colorado believe they have found the solution: exercise. I expect that a lot of readers will have stopped reading at this point, and some may have not even opened this article after reading the title since it all seems so obvious, but there appears to a little more to it than the fact that regular exercise burns calories.

After fattening up their pet rats to obese levels, they then dieted them down with a low-calorie diet. They split them into two groups, allowing one to exercise frequently while the other group did a whole lot of nothing. Both groups were given the freedom to eat however much they wanted, whenever they wanted it. While both groups regained weight, the exercising group regained much less and was eventually able to defend its lower body weight. The researchers found that the regular exercise not only burned calories, but also reduced their drive to eat, making body weight maintenance much simpler. The exercising group had lower body fat and biomarkers that overestimated the levels of body fat, almost convincing the brain that all is well. This reinforces the point that to be healthy and look good requires a complete lifestyle change, not a temporary alteration.

Source: Maclean PS, Higgins JA, Wyatt HR, Melanson EL, Johnson GC, Jackman MR, Giles ED, Brown IE, Hill JO. Regular Exercise Attenuates the Metabolic Drive to Regain Weight After Long Term Weight Loss. Am J Physiol Regul Integr Comp Physiol. 2009 Jul 8.

Research into post-exercise massage is hit and miss at the best of times. There are often claims that it will increase circulation, aid in the removal of toxins from the muscle tissue, and decrease inflammation. However recent research seems to indicate otherwise. Scientists from Queen’s University in Canada state that the exact opposite occurs – blood flow is impeded, thus impairing lactic acid removal. However, the study design did conduct the massage immediately after activity, so a smarter idea may be to leave a buffer zone of a few hours before getting a massage.

 

Source: Victoria Wiltshire, Veronica Poitras, Melissa Pak, Terence Hong, Jay Rayner, Michael E. Tschakovsky. Massage Impairs Rather Than Enhances Lactic Acid Removal From Muscle After Strenuous Exercise. Queen’s University, Kingston, ON, Canada.