Vitamin E has been considered to be an anabolic factor since ‘the beginning of time’. In addition to vitamin B12, also known as dibenocoside, it was another micro-nutrient substance used passionately by all athletes to support the development of muscle mass and strength.

Despite the enormous popularity of vitamin E in athletes’ nutrition, until recently we did not know much about the mechanisms of its action in muscle tissue and its usefulness in supporting strength efforts. Although we know much more today, many questions remain unanswered….

vitamin e

The birth of a legend

The legend of ‘anabolic vitamin E’ was born almost at the time of its discovery. In 1922, two scientists, Evans and Bishop, attempted to establish the relationship between diet and animal reproduction. They developed a special diet for this purpose, balancing sugars, fats, proteins, minerals and all the vitamins known at the time – A, B, C and D – and fed it to rats. As it turned out, the animals fed in this way did not produce offspring. Only the addition of whole wheat grains or embryos (especially the latter) to the feed had a positive effect on fertilisation and on the course and delivery of pregnancies. Evans therefore came up with a hypothesis about the existence of a new, previously unknown vitamin, essential for reproduction. Shortly afterwards, this infertility-prevention factor was identified and marked with the next letter of the alphabet – E, as well as a synonym – tocopherol – for the Greek words tokos – ‘progeny’ and phero – ‘carry’.

(Today we know that the activity of vitamin E shows many different, similar compounds – 4 tocopherols, 4 tocotrienols and a certain number of their various derivatives.)

Detailed research has brought further revelations – avitaminosis E (deficiency disease) leads to changes in the pituitary gland and inhibition of gonadotropin production (hormones that support sexual gland functions), and consequently – in females – to fetal resorption, while in males – to irreversible damage to the testicles. Let us remind you that in the 1920s it was already well known that testicles are the production site of one of the strongest anabolic hormones – testosterone….

But it’s not over yet… Further research has shown that avitaminosis E has fatal consequences for muscle tissue. In case of a deep deficiency of tocopherol, skeletal muscles lose their dynamic abilities, become paralysed and disappear. The production of acetylcholine and rich energy phosphates – adenosine triphosphate (ATP) and phosphocreatine – is inhibited, while creatine escapes from muscle tissue and leaves the body with urine. There is a rapid, unproductive burning and loss of glucose reserves, fibrils and muscle cell cytoplasm disappear and muscle cells are saturated with calcium and cholesterol.

In 1940, Bicknell made his first attempts to treat dystrophy with vitamin E, a progressive muscular atrophy, and a year later he was joined by Stone. This procedure was also extended to another muscle disease – myasthenia. The results seemed to be quite encouraging; it was possible to stop the escape of creatine, achieve a certain increase in muscle contraction strength and achieve a moderate improvement in the existential comfort of patients.

Infants and children suffering from disease syndromes with muscle weakness also responded well to vitamin E treatment – they could hold their heads straight, sit down and learn to walk, which proved impossible before the therapy.

At the same time, in 1942, one of the renowned pharmacological journals published a publication of Adamstone’s research proving that vitamin E increases the power of testosterone.

Later it was reported that the administration of sex hormones increases the body’s demand for vitamin E… With the increase in the level of these compounds in the body, there was a parallel decrease in the value of tocopherol in the bloodstream, which indicated an increased use of tocopherol by various organs and tissues.

Subsequent observations even indicated a similar activity of tocopherol in muscle tissue to testosterone – both in case of deficiency of the first and second factor, muscle weakness and creatine escape occurred; both administration of one and the other, alleviated these symptoms and led to improvement of muscle condition. It is not only about the effect of vitamin E through the pituitary gland and gonadotropin, because similar results were obtained in castrated males, unable to respond, with increased testosterone production, on the increase in the level of pituitary gonadotropins.

It was also found that similar relations between tocopherol and estradiol – a female sex hormone from the group of estrogens – occur in muscle tissue… Both the first and the second factor develop the uterus muscle. Today, however, we know that estrogens have a similar, growth-enhancing effect on both the uterine and skeletal muscles.

The activity of tocopherol imitating the action of sex hormones is also visible in many other health aspects, to the extent that it has been tried (with good results) as an alternative to hormone replacement therapy, in the course of menopause (menopause and menopause) or after surgical castration. Administration of vitamin E in these cases prevented e.g. hot flashes, increased libido, increased frequency and quality of erection. (Sypniewski’s Manual of Pharmacology, 1954, discusses tocopherol in the group of sex hormones.) According to the literature review, we will find supporters of a similar approach so far…

It is also worth mentioning the results of research on bioavailability, which proved that vitamin E ingested is accumulated to the greatest extent, in the muscle tissue. This seemed to mean that vitamin E is the most important for the development of this tissue.

In the light of such a set of reports, can it surprise us that vitamin E quickly gained an anabolic agent among athletes of nymphs…?

Legend VS reality

Scientific research, carried out on athletes and people with heavy physical work, initially produced quite encouraging results. It was quite clear that vitamin E can support the development of exercise skills.

However, in the 1970s, these works were pointed out to serious methodological errors: first of all – lack of placebo control. And in the experiences of the following decades, conducted after the 70’s, it was only – worse and worse….

Scientific studies on the influence of vitamin E supplementation on the development of endurance efforts did not show statistically significant differences between ‘tocopherol’ and placebo groups. The exception was only one situation – training at high altitude.

On the other hand, surprisingly little research was done on the influence of vitamin E on the effectiveness of resistance (strength) training. Here, some results seemed to indicate some benefits of tocopherol supplementation. Although small effects, in the form of strength and muscle mass improvement, were found to be statistically unreplaceable, it turned out that vitamin E limits muscle breakdown (catabolism), associated with severe strength training, and reduces the resulting muscle soreness. The best results were obtained in the case of elderly people, exercising gymnastics and recreation. Tocopherol may contribute to muscle development in some way – as an anti-catabolic.

Nobody, however, thought (this is my comment) to confront the results obtained over vitamin E supplementation in high endurance training with the information from the 1950s, concerning the positive influence of exercises at altitudes, on the development of muscle mass.

Good news for strengthlifters also recently came from the ‘plot’ of molecular biology: tocopherol stimulated synthesis and increased the level of tropomiosine – the protein of muscle fibres responsible for the initiation of their contraction.

But the less successful news in the meantime was also… Excess tocopherol stopped muscle cell growth. It also led, which had not been observed before, to hypervitaminosis (disease from excess), which manifested itself – among other things – in muscle fatigue and weakness. Paradoxically, however, this problem mainly concerned the elderly, who used vitamin E to stop the loss of muscle tissue. It is interesting that diametrically different results were obtained with regard to old people exercising and not exercising gymnasium….

A certain, defined vitamin E status remains absolutely essential to maintain proper testosterone production. However, it turns out that ‘more’ does not mean ‘better’ in this case. It was observed that the level of testosterone in the bloodstream correlates inversely with the level of vitamin E – the more vitamin E, the less testosterone and vice versa. This could be explained in two ways… Either testosterone depletes vitamin E reserves (as we already know) or vitamin E lowers testosterone levels. Unfortunately, the truth turned out to be painful – both mechanisms have their part in this phenomenon. As it has been recently established, the excess of vitamin E limits testosterone production.


In some circumstances, tocopherol stimulates the development of muscle tissue, in others it inhibits the development of muscle tissue. Do the latest scientific reports explain to us the reasons for this state of affairs…?

In the publications from 10 years ago we could read only about one mechanism of vitamin E action – antioxidant activity. And although this mechanism was known almost at the very beginning of our work on tocopherol, we could not point to any other mechanism until the end of the last century. Only the newest tools of molecular biology made a breakthrough in inquiring the truth about vitamin E – the same as in the case of a whole mass of other bioactive molecules.

However, let us stop for a moment at the antioxidant activity, which for nearly 80 years was associated with all the effects of vitamin E….

Antioxidants are compounds with the ability to eliminate free oxygen radicals – very reactive biological molecules, blamed for numerous health and metabolic perturbations. Although we know a huge amount of antioxidant compounds, those with vitamin E activity have a certain, unique property – an exceptionally strong ability to penetrate biological membranes. It is important because free radicals oxidize lipid components of these membranes (mainly – unsaturated fatty acids), which increases their permeability – and thus interferes with cellular functions. However, compounds with vitamin E activity stabilize membranes, interrupting the process of lipid oxidation.

Based on this mechanism – in fact – it is possible to explain many aspects of physiological activity of vitamin E. Take, for example, its influence on the pituitary gland and gonadotropins….

The work of the pituitary gland is regulated by a different anatomical structure of the brain – the hypothalamus. For example, the hypothalamus produces gonadoliberin – a superior hormone that stimulates the pituitary gland to release gonadotropins. The hypothalamus, through the so-called arched nucleus, is connected with the blood-brain barrier, which transfers various substances circulating in the bloodstream to the hypothalamus. Among the penetrating substances we can also find sexual hormones – e.g. testosterone and estradiol, which inhibit the release of gonadoliberine and gonadotropins. And when fewer gonadotropins reach the gonadal glands (e.g. testicles), the testicles produce less testosterone. This is the so-called negative feedback mechanism, in which testosterone – via the hypothalamus and pituitary gland – regulates its own production level, which serves to maintain optimal hormone levels in the body. However, when the lipids of the blood-brain barrier membranes become excessively oxidized – many more sex hormones will go to the hypothalamus and pituitary gland, and the production and release of gonadoliberine and gonadotropins will be completely stopped. Gonadotropins will cease to affect the testes – these glands will disappear and testosterone production will be inhibited. And less testosterone is the weaker muscles – you know! This can happen in the case of vitamin E deficiency, when there is no proper protection against oxidation of lipid components of membranes.

Changes in cell membranes, made by free radicals, also lead to the destruction of membrane receptors, responsible for the reaction of cells to many hormones, such as the mentioned gonadotropins or various growth factors, maintaining the status of tissues of the sexual glands. Free radicals also damage the mitochondria membranes and receptors located there (we will discuss this below), which is important because testicular cell mitochondria are strategically synthesized by testosterone. For example, free radicals have been shown to reduce tissue response to gonadotropins by blocking the production of secondary signal transmitter (cAMP) and to inhibit the synthesis of sex hormones at one of the early stages of this process – the production of their precursor – progesterone. Thus, we can see that free radicals disturb testosterone production also at the level of the testicles themselves, as well as disturb the vital functions of these glands, especially in the case of deep vitamin E deficiency. Again: less testosterone – weaker muscles!

But muscles can also weaken here for another reason… When the components of mitochondria and reticulum membranes get too oxidized, huge portions of calcium ions are released into the muscle cell light, stored in these cellular organelles, activating catabolic enzymes and initiating destructive processes. And this may be the most important mechanism, leading to muscle atrophy as a result of avitaminosis E.

But only a few years ago we learned a deeper truth about free radicals – these molecules also have a friendly face. If we talk about the development of muscles, free radicals that arise during training activate the so-called transcription factors, stimulating genes to produce muscle proteins, thanks to which muscles gain strength and increase their mass. So they work here similarly to anabolic hormones, which will be discussed below. Thus, it is oversupplied

vitamine e

Vitamins – hormones

But let us now go beyond oxidation and see what new science has found on other mechanisms of vitamin E action….

Hormones work primarily in a way similar to free radicals: they activate transcription factors (either directly or through special enzymes called kinzes) that stimulate our genes to produce proteins. Since these are both structural and enzymatic proteins, as well as signal, regulatory and transport proteins, the body responds actively to the action of hormones – whether it is the growth of organs and tissues, or the intensification of various life processes.

However, vitamins are most often accompanied by enzymes (coenzymes, coenzymes), catalyzing chemical reactions that take place inside the body. However, we know the exceptions – such as vitamins such as A or D, which work in exactly the same way as hormones. According to the current state of knowledge – the group of ‘vitamins-hormones’ probably includes also vitamin E; this also activates some transcription factors – both via kinase and directly….

Vitamin E stimulates e.g. kinase PI3K – the same kinase through which such strong anabolic hormones as insulin or IGF act. At the same time, however, unfortunately, it deactivates another one – PKC – which, as has been observed, is responsible for the inhibitory effect of excess tocopherol on the growth of muscle cells.

Tocopherol has a direct effect on transcription factors such as: pregnant X receptors (PXR), peroxysome proliferator receptors (PPAR) and orphan receptors (OR). And as we now know, at least one group of these transcription factors – PPAR – is involved in the production of muscle proteins and is responsible for the development of muscle mass.

The products of tocopherol metabolism in the body, called quinones, activate two extremely important transcription factors – NF-kB and AP-1, which stimulate genes to produce more than 300 muscle proteins. Therefore, it is possible that this is the reason why these compounds proved to be much more effective than tocopherol in the treatment of muscle diseases.

Another tocopherol conversion product – 2,2,5,7,8-pentamethyl-6-chromanol (PMCol – pentamethylchromanol) – is even more interesting; this compound reacts with androgen receptors – exactly the same transcription factors through which it acts on testosterone muscles. However, probably the tocopherol itself (or any of its derivatives), using an unknown mechanism, inhibits production and reduces the number of androgen receptors, but only in prostate cancer cells. Interestingly, this phenomenon does not occur in healthy cells of the body. Interestingly enough, in prostate cancer cells, pentamethylchromanol blocks androgen receptors, inhibiting protein synthesis and inhibiting tumor mass gain, which was not observed in healthy body cells. Therefore, there is a justified suspicion that it shows the activity of a selective androgen receptor modulator (SARM), i.e. such a compound, which in some tissues (pituitary, prostate) acts as an antagonist – an opponent, while in others (bones, muscles) – as an agonist – an ally of testosterone. (Such seemingly paradoxical SARM activity is possible because different tissues have different sets of so-called transcription coregulators, which join androgen receptors together with testosterone.) This suspicion is also confirmed by the high similarity of pentamethylchromanol with the two new SARM drugs still in clinical trials. It looks as if the structure and activity of pentamethylchromanol inspired biochemists to synthesize these compounds. It is also worth noting that some side effects associated with the use of SARM and overdose of vitamin E are identical; it is a visual disturbance.

In the light of these observations it is easier to understand some, sometimes contradictory effects of vitamin E….

We already know that testosterone reaches the hypothalamus and pituitary gland, where it finally blocks (alone or through its stronger metabolite – DHT) gonadotropin secretion. There is no doubt that testosterone exerts this effect via androgen receptors. However, if these receptors are purposely blocked by pentamethylchromanol from vitamin E, the binding of testosterone to the receptors will be low and the inhibition of gonadotropin secretion will be low. However, in the absence of vitamin E in the body, androgen receptors of hypothalamus or pituitary glands are not properly blocked, which leads to excessive testosterone activity and serious perturbations in these anatomical structures – and consequently – strong inhibition of gonadotropin production and release. Thus, we find an excellent explanation for the protective role of vitamin E in relation to the pituitary gland and testicles, because gonadotropins – as we know – maintain the status quo of the tissues of these gonads and stimulate it to produce testosterone.
It is rare for a compound to be a full antagonist of a hormone. He is more often called a partial agonist. It looks like it blocks the receptors of a given hormone, but at the same time it shows a certain, minimal activity. It is suspected that pentamethylchromanol may be a partial agonist of the hypothalamic and pituitary androgen receptor, with very low testosterone activity (androgenic activity). Therefore, when the body has an optimal amount of this compound – the phenomena described above take place. However, when we have to deal with its strong excess – pentamethylchromanol, through its minimal androgenic activity, compensates for the quality – quantity – and inhibits the release of gonadoropins, just like testosterone. And here is a possible reason why hypervitaminosis E reduces testosterone levels.
If we actually consider pentamethylchromanol to be a SARM compound, we come to the conclusion that it must also behave as a partial agonist with regard to androgenic muscle tissue receptors, but with a much stronger androgenic activity. This in turn explains to us why, in the event of a testosterone deficiency, vitamin E can partially replace it. However, let us not forget that pentamethylchromanol is only a partial agonist, i.e. an androgen with low testosterone activity. When it occurs in the muscles, in optimal amounts, it binds only free androgen receptors, not occupied by testosterone, which increases the production of muscle proteins. However, when pentamethylchromanol levels significantly exceed the optimum, this compound blocks strong testosterone access to all androgen receptors, and when acting much less on gene transcription, it limits the potential for protein production and relatively weakens muscles.

And how do you explain the interaction between vitamin E and testosterone…?
Partial agonists often bind the receptor not in the place designated for a given hormone, but in the position characteristic of the above mentioned coregulators. This ultimately results in the fact that their presence facilitates the binding of the hormone with the receptor and strengthens the activity by transcription of the resulting complex. Therefore, compounds with similar characteristics are sometimes called ‘hormonal allergens’. For example, estradiol is a testosterone allergen. Therefore, in order for testosterone to show adequate anabolic potential, it must remain in our body, in relation to estradiol – as 80:1. There are many indications that the second known testosterone allergen is pentamethylchromanol, but – so far – its proper proportion to the sensitized hormone has not been established. And this finding is important because an allergen – when it is not in the right proportion to its proper hormone – can act as its antagonist. Since this is the case with oestradiol (at least in some tissues), it should be suspected that pentamethylchromanol is also present. This again explains why hypervitaminosis E can weaken the muscles.

Finally, I left another phenomenon – vitamin E is an inhibitor (bloker) of enzymes (phospholipases and cyclooxygenases) producing tissue hormones from the group of prostanoids, mediators of pain and inflammation. So it works here similarly to aspirin, ibuprofen or other similar anti-inflammatory and analgesic agents. Due to this, it probably endures the muscle soreness. However, as prostanoids are also hormones involved in the development of muscle tissue (some stimulate and some inhibit this process), so there is no silence about the sense of using similar drugs to support strength training. It seems that the latest research has finally solved this problem… It results from them that analgesics, although they inhibit anabolism of proteins in the first phase after application, in the long term of their administration they facilitate the development of muscle strength and mass. So here we have another mechanism, through which a reasonable supplementation of vitamin E promotes the formation of form in strength disciplines.


The conclusion of all this is that vitamin E belongs to the group of measures for which Mother Nature has designated the so-called ‘therapeutic window’. This means that the excess of vitamin E and its deficiency will be equally unfavourable (in this case – for the development of muscles). Unfortunately, there are no clear guidelines in the literature that would make it possible to determine the optimum of vitamin E intake.

It seems, however, that the optimal dose for people training with weights oscillates around 100 mg per day.

Those athletes who use testosterone or its derivatives – anabolic-androgenic steroids – for sports preparation cycles may think about larger portions. First of all, because, as we know, the administration of sex hormones increases the body’s need for vitamin E. That is the first thing! Secondly, vitamin E (what was mentioned and should be remembered) shows synergy with testosterone, strengthening its action. And thirdly, it can reduce the risk of adverse effects of testosterone and steroids, such as: hypothalamic-pituitary-gonadal axis blockade, testicular atrophy or prostate hypertrophy.

In this case, vitamin E supplementation with a dose of about 200 mg can be considered.

And last but not least, another very important point…!
Vitamin E supports the development of the muscles only when it is administered in conjunction with the full complex of vitamins from the B group. Otherwise, it works on the contrary – destructively on the muscles. And although this phenomenon was observed already in the 1940s, so far no logical explanation has been found for it. (Probably nobody has researched it later…)
It is equally important to carry out tocopherol supplementation in strength sports together with a vitamin B complex or a strong mineral-vitamin preparation intended for athletes, containing appropriately high doses of these vitamin E protectors.