Autor: Sławomir Ambroziak
Keywords: capsaicin, nitric oxide, peroxynitrite, arginine, vanilloids, mTOR kinase, TRPV1 vanilloid receptor, overload induced muscle hypertrophy, sarcopenia, cachexia, atrophy.
Although our muscles seem to be a well-known and thoroughly studied tissue, in fact they have a whole bunch of hidden secrets. We still do not know, for example, how to cure most of the muscle diseases and how to prevent muscle atrophy associated with immobilization or denervation. Available in pharmacies popular anabolic drugs that regenerate muscles do not fully meet our expectations in treatment of cachexia and sarcopenia – loss of muscle mass related to age or to some chronic wasting diseases such as cancer, diabetes or AIDS. And because today we know that the proper condition of our muscle tissue is of extreme importance to both slowing down the aging processes of the body and successfully recovering from a variety of serious diseases, therefore scientists are constantly struggling to understand and explain still poorly known mechanisms of muscle development and regeneration.
Although we have known the phenomenon of overload induced muscle hypertrophy empirically for thousands of years (ancient and modern athletes have been basing their training methodology of muscle development on it), the underlying metabolic mechanisms still remain insufficiently explained. Several works of the first decade of this century revealed that a gas hormone – nitric oxide (NO) as well as its oxidation product – peroxynitrite (ONOO) play an important role in this phenomenon, what is described extensively in my book, „Legal Anabolics „. Therefore, a team of Japanese scientists at the National Center of Neurology and Psychiatry, Kodaira, led by Ruegg and Ito, has set itself the goal of clarifying the role of nitric oxide and peroxynitrite in the mechanisms governing the phenomenon of overload-induced muscle hypertrophy, in a study published in January 2013 in Nature Medicine.
The researchers found that nitric oxide is formed as a result of mechanical overload of sarcolemma (cell membrane of muscle fibres). The gas is converted rapidly into peroxynitrite, a sarcoplasmic reticulum stimulant (endoplasmic reticulum, cell element that stores primarily calcium) that tells muscle cells to pump calcium ions to sarcoplasm (muscle fibres cytoplasm). Calcium ions activate mTOR kinase – an enzyme critical for muscle hypertrophy, stimulating muscle protein formation (anabolism) in a strategic phase of this process called translation. Nitric oxide and peroxynitrite occurred to be the key elements in the whole process here because the muscles of the genetically modified mice that lacked nitric oxide synthase (an enzyme producing NO) had not responded to overload stimuli with hypertrophy.
Discovering that the metabolic effects of peroxynitrite activated a cation channel located in the membrane of the endoplasmic reticulum was a great discovery emerging from the work of the Japanese researchers. In 1990s the cation channel was already well-known as so called vanilloid receptor – TRPV1. This receptor primarily provides a sensation of pain. Among the internal (endogenous) factors that activate it the best known are so far endocannabinoids, protons generated as a result of the high acidity in the body as well as thermal radiation; peroxynitrite is another one… Because resistance training leads to environmental acidification and overheating of our muscle cells, these factors may also be involved in the mechanisms standing behind the phenomenon of overload-induced muscle hypertrophy. However, as proven by the Japanese researchers, the most important factor here is peroxynitrite. So far we have discovered a number of external compounds which activate a vanilloid receptor. These are exogenous agonists of TRPV1, of which capsaicin, a substance that gives a pungent taste to several varieties of peppers, is the most common one. Capsaicin is a group of chemical compounds called vanilloids due to their similar structure to the substance giving a pleasant aroma to vanilla pods – vanillin. This is where a name vanilloid receptors, i.e. binding proteins of vanillin structure, originated from. Capsaicin lowers the threshold of TRPV1 sensitivity to thermal stimuli. Normally the channel begins to pump calcium ions at temperature above 40 degrees, but when capsaicin is present – right at 25 degrees. Thus, it opens in normal body temparature conditions that is – as we know – about 37 degrees. (It is possible that peroxynitrite acts through a similar mechanism.) So if capsaicin activates TRPV1 receptor, as well as peroxynitrite, it should also stimulate muscle growth …!
This hypothesis has been also tested by the Japanese researchers … As it turned out, capsaicin fed to mice significantly induced muscle hypertrophy. The animals weren’t even subjected to overloading. Capsaicin alleviated the degree of muscle decay due to immobilization or denervation. In the final conclusions the scientists expressed a belief that TRPV1 receptors may be a new therapeutic target in the treatment of muscle atrophy.
It is worth noting that TRPV1 receptor is a target of more natural nutrients with a sharp flavor – not only capsaicin. These are for example allicin in garlic, piperinein pepper or gingerol in ginger. Since long time hot pepper and ginger or extracts derived from these spices have been used as analgesics and anti-inflammatory remedies (eg in neuralgia or osteoarthritis), and they have recently been gaining more and more popularity in the treatment of obesity and different fat loss programs. Some vanilloids stimulate the release noradrenaline and adrenaline from adrenal glands – lipolytic hormones breaking fat molecules stored in our adipose tissue and increasing our resting metabolic rate that consumes a significant amount of energy. Resting metabolic rate is increased for approximately 10 hours after taking your last serving of capsaicin that allows to burn – with no effort – extra calories.
So finally we see that the use of all these spices in our kitchen or supplements derived from them in a diet of athletes, seniors or people with a tendency to put on weight not only facilitates getting a lean body, but also makes a substantial contribution to muscle development and resistance to injury or to maintaining muscles and joints in a good condition.
You can’t not to mention here that new researches have brought numerous reports of potential anti-cancer properties of capsaicin, other vanilloids and spices ingredients. Reports on capsaicin activity against prostate cancer deserve special attention. This is mainly because androgens such as testosterone and similar to it anabolic-androgenic steroids typically used in a treatment of sarcopenia are suspected of supporting prostate diseases what limits their use in preventing muscle mass deficit in elder men.
Capsaicin is a fat-soluble substance, and all fat-soluble compounds are easily absorbed through the skin. This lets us use popular capsaicin-based ointments that treat aches and pains as a muscle enhancer in the elderly or immobilized who don’t like hot spices or cannot eat them due to gastric problems. You could for example rub such an ointment in a given muscle group once or twice a week, following the periodization of strength training in athletes. Athletes, on the other hand, could rub it in a particular muscle group before each training session aimed at this group’s development.
It should also be noted that the above-mentioned nitric oxide synthase generates NO from amino acid – arginine that is present in protein food. Because nitric oxide dilates blood vessels, this is why athletes fond of arginine supplements usually take it before their workout in order to increase working muscle ischemia. This research gives yet another argument in support of a similar use of capsaicin ointment.
Arginine supplements are becoming more and more popular among the elderly as they act similarly to cardiac nitrates that have been used in cardiology for a long time. Cardiac nitrates release nitric oxide that improves myocardial ischemia as well as contributes to maintaining a high sexual performance (similarly to Viagra) since NO is involved in the mechanism of erection and makes it easier to achieve. And again, we have another argument to justify similar approach – arginine supplements affect positively not only heart failure and sexual prowess, but also the condition of the muscle tissue in the elderly, as demonstrated by, for example, Borsheim study published in Clinical Nutrition in 2008.
