Aromatase inhibitors

There are some things that bodybuilders don't like. These include small muscles, 5 guys standing around a machine taking 30 minutes to do a set, people dropping their weights loudly and people leaving all the gym's weight plates on the machine or barbell after their set. And then there's the estrogen. Even though we all need a certain amount of estrogen to function properly in our daily lives, higher estrogen levels can be a hindrance if you're serious about building muscle. Of course, you can do it with high estrogen levels, but it won't be easy.

Oestrogen and its disadvantages

Oestrogen is the primary female sex hormone and is a steroid in its natural form. There are also synthetically produced and naturally occurring estrogens, such as plant sterols, which, although they have some estrogenic activity, are not steroidal in form. There are three primary types of oestrogen that occur naturally in the body: Oestrone (E1), oestradiol (E2) and oestriol (E3). Oestradiol (E2) is considered the most potent of these three oestrogens and is also the oestrogen with the strongest oestrogen activity.

As mentioned above, both men and women need oestrogen for a number of bodily functions, including blood clotting and the regulation of cholesterol levels. However, the most important role of estrogen is its ability to promote the development of female characteristics, which include breast enlargement and changes in body fat distribution and total body fat percentage. Due to its effects on the ratio of fat to lean muscle mass, estrogen is not conducive to significant muscle growth or hypertrophy.

Aromatase & Testosterone

Estrogen can be produced in the body in different ways. In women, most of the oestrogen produced comes from the ovaries. However, oestrogen can also be produced by the liver, fat cells and adrenal glands in both men and women. Another pathway by which estrogen can be produced is through the action of aromatase, an enzyme also known as estrogen synthase. This particular enzyme in the body converts androgens such as testosterone into estrogens such as estradiol. This means that when there is plenty of testosterone in the body, more oestrogen is produced by the aromatase enzyme. Therefore, anyone aiming to increase their testosterone levels, either through natural or non-natural means, runs the risk of increasing their oestrogen levels at the same time. This is the reason why aromatase inhibitors are often used at the same time to counteract such an increase in oestrogen levels.

Aromatase inhibitors

Aromatase inhib itors are synthetic or natural substances that help to reduce the activity of the aromatase enzyme and thereby reduce the degree to which testosterone is converted into oestradiol. Aromatase inhibitors are also important in certain cancers, such as breast cancer and ovarian cancer, as increased estrogen levels help the cancer cells in these cancers to multiply. Aromatase inhibitors are often used by men to prevent or treat gynecomastia - a common problem with massively elevated testosterone levels or increased aromatase activity. There are many clinical aromatase inhibitors, including the well-known lentarone. In addition to these pharmaceutical agents, there are also a number of naturally occurring substances that have some anti-oestrogenic activity, some of which affect the aromatase enzyme. The following sections briefly describe some substances and ingredients that may exhibit anti-oestrogen activity.

Zinc

Zinc is an important mineral that is often praised for its ability to support healthy testosterone levels. Zinc is often found in combination with magnesium and vitamin B6 in popular ZMA supplements, which are used to increase testosterone levels. While studies have not yet conclusively shown that zinc supplementation can actually increase testosterone levels, it has been clearly demonstrated that sufficient amounts of this mineral are necessary for maintaining natural testosterone levels in two ways. The first way is to maintain testicular activity, as zinc deficiency is associated with hypogonadism - reduced function of the testes, which are responsible for testosterone production. The second pathway is based on a reduction in the activity of the aromatase enzyme.

Animal studies have shown that zinc deficiency results in increased estradiol levels due to increased aromatase enzyme activity (1). There are no current dosage recommendations for the use of zinc as an aromatase inhibitor, but it is important to consume at least 15 mg of zinc per day in the form of food or supplements, not exceeding 40 mg of zinc per day.

Resveratrol

Resveratrol - a plant compound found in grape skins and grape seeds and also produced by other plants in the presence of pathogenic threats such as bacteria or fungi - has enjoyed increasing interest in the sports science community for a decade due to its potential performance-enhancing benefits. One of these benefits is the inhibition of the aromatase enzyme, which occurs at both the enzyme and genetic level (2). Other studies have been able to show that resveratrol supplementation resulted in increased testosterone levels (3), most likely due to resveratrol's action as an aromatase inhibitor. Resveratrol is also used to promote weight loss and due to its ability to increase nitric oxide production. In terms of dosage, 150 mg of resveratrol per day has been shown to be effective in promoting fat metabolism, although dosages of 2.5 grams per day can cause side effects. There are currently no conclusive dosage recommendations for the use of resveratrol as an anti-oestrogen agent.

Lignans

Lignans are compounds found in plants such as safflower or linseed and are thought to have potent anti-oestrogen activity. There are a large number of studies that have investigated the use of lignans for the treatment and possibly prevention of breast cancer, ovarian cancer and cervical cancer - all cancers that are promoted by high oestrogen activity.

When lignans are consumed in the diet, they are converted in the body into enterodiol and enterolactones, both of which can dock to the oestrogen receptors and induce oestrogen activity, albeit at a very, very low level. As a result, these metabolic products of lignans can compete with oestrogen for the oestrogen receptors, which results in reduced body-wide oestrogen activity. Although lignans may not reduce estrogen levels, they may reduce the effects of estrogen.

Studies on the potential weak estrogen effect or anti-estrogen effect of lignans are currently at an early stage and further research is needed to make conclusive statements on this topic (4). However, there is strong evidence that the consumption of lignans in the form of flaxseed can help with cardiovascular disease. There are currently no current dosage recommendations for the use of lignans as an anti-oestrogen agent. However, it has been shown that 30 to 50 grams of flaxseed can help lower LDL cholesterol levels.

Caffeic acid phenethyl ester (caffeic acid phenethyl ester)

Caffeic acid phenethyl ester (CAPE) is an organic compound commonly found in plants and is also a component of propolis from beehives. This compound has previously been shown to help with acute inflammation, but science has only recently begun to investigate CAPE for its anti-cancer effects. In fact, one study was able to show that CAPE could be a potential selective estrogen receptor modulator or SERM (5). SERMs are certain compounds that are commonly used to treat a number of cancers associated with high estrogen levels. They are used for this purpose because they act selectively in cancer-prone tissues but do not affect other important estrogen receptors that are needed for bone growth, for example. There are currently no dosage recommendations or conclusive studies on the anti-oestrogen activity of CAPE.

Pterostilbene

Pterostilbene is an organic compound similar to resveratrol and is found in blueberries. Pterostilbene is said to increase the bioavailability of resveratrol due to its chemical structure. In recent years, pterostilbene has been studied extensively for its use in a wide range of applications including the treatment of high cholesterol, diabetes and even cancer. One study was able to show that this compound can increase the effect of a selective estrogen receptor modulator (SERM) (6). However, there is no evidence that pterostilbene on its own has any effect on estrogen levels or activity.

Ellagic acid (ellagic acid) & ellagitannins

Ellagic acid is an antioxidant found in many fruits and vegetables including pomegranates, blackberries, cranberries, pecans and walnuts. Ellagic acid can easily be converted into other antioxidants known as ellagitannins. Few studies have been conducted on these compounds, but it is already beginning to emerge that they appear to have antiviral and blood pressure lowering capabilities. One study (7) investigated the effect of ellagitannins from pomegranates on breast cancer cells in vitro and found that ellagitannins may have antiaromatase activity. This was mainly based on the compound urolithin, which is formed during the digestion of ellagitannins. There is currently no dosage recommendation for ellagitannins and no conclusive study results for the use of ellagic acid or ellagitannins as aromatase inhibitors.

Ursolic Acid

Ursolic acid is an organic compound found in basil, cranberries, rosemary, thyme and in high concentrations in apple peel. One study (8) found that ursolic acid could help prevent muscle breakdown and improve muscle growth by enhancing insulin/IGF-1 signaling. This study conducted on mice also found that ursolic acid supplementation was able to reduce fat mass and blood glucose levels in the fasting state. In another study (9), ursolic acid isolated from the yerba mate plant was examined and a slight aromatase-inhibiting effect was observed. The studies currently available are quite promising with regard to the aromatase-inhibiting and anabolic properties of ursolic acid, but it is still too early to recommend a specific dosage.

Red Clover & Genistein

Red Clover is a wild plant that has traditionally been used for a wide range of applications including reducing inflammation and treating respiratory conditions. The extract of this plant is also a commonly used ingredient in natural supplements for the treatment of benign prostatic hyperplasia. Red Clover contains a chemical compound known as biochanin A, which shows some aromatase inhibitory activity (10). Interestingly, biochanin A can also be easily converted into another compound known as genistein. Genistein, another natural compound, can increase the growth of breast cancer cells (11). As an isoflavone, genistein may act similarly to estrogen. While biochanin A can act as an aromatase inhibitor, there may be problems with increased estrogen activity when biochanin A is converted to genistein. Further research is therefore required before it is clear whether Red Clover should be used in anti-oestrogen formulations.

Alpha-naphthoflavone

Alpha-naphthoflavone is a synthetic compound that has been shown in early studies to have potent aromatase inhibitory activity (12, 13). However, there is a lack of human studies, which is why no real dosage recommendation is available.

White Button Mushrooms (Champignon)

The common button mushroom or white button mushroom is one of the most widespread edible mushrooms. This mushroom can be found in practically every supermarket. Early studies were able to show that extracts from these mushrooms can have strong aromatase inhibitory activity (14, 15). However, as with many other ingredients, the lack of further follow-up studies means that there are currently no conclusive dosage recommendations.

Ingredients without end

These are just some of the most common ingredients found in natural anti-oestrogen or aromatase inhibitor supplements today. There are also many other ingredients with anti-oestrogen and aromatase inhibiting effects. There is currently no consensus as to which of these ingredients is better or best. Ingredients with anti-oestrogenic activity reduce the degree to which oestrogen can exert its effect without reducing the oestrogen levels themselves, while aromatase-inhibiting ingredients reduce the conversion of testosterone into oestrogen. Aromatase inhibitors may be the better choice here, as they essentially allow higher testosterone levels to be maintained.

Conclusion

Oestrogen is a hormone that is absolutely essential for the body to function optimally. However, higher estrogen levels can often mean that the road to bigger muscles and greater muscle mass is a little longer. If you're using testosterone booster supplements or want to make the most of your testosterone levels, you should definitely consider using an aromatase inhibitor or anti-estrogen supplement. When opting for such a supplement, the following are the top 6 ingredients you want to see on the ingredient list:

• Zinc
• resveratrol
• Ellagitannins
• Ursolic Acid
• Alpha-Naphthoflavones
• Agaricus Bisporus (White Button Muschroom Extract)

References:

1. Om AS, Chung KW. 'Dietary zinc deficiency alters 5 alpha-reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver.' J Nutr. 1996 Apr;126(4):842-8.
2. Wang Y, Lee KW, Chan FL, Chen S, Leung LK. 'The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells.' Toxicol Sci. 2006 Jul;92(1):71-7. epub 2006 Apr 11.
3. Shin S, Jeon JH, Park D, Jang MJ, Choi JH, Choi BH, Joo SS, Nahm SS, Kim JC, Kim YB (January 2008). "trans-Resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo". Arch. Pharm. Res. 31 (1): 83-7.
4. Linus Pauling Institute - Micronutrient Research For Optimum Health - Lignans - http://lpi.oregonstate.edu/infocenter/phytochemicals/lignans/ - Last Accessed May 31, 2012.
5. Jung BI, Kim MS, Kim HA, Kim D, Yang J, Her S, Song YS. 'Caffeic acid phenethyl ester, a component of beehive propolis, is a novel selective estrogen receptor modulator.' Phytother Res. 2010 Feb;24(2):295-300.
6. Mannal P, McDonald D, McFadden D. 'Pterostilbene and tamoxifen show an additive effect against breast cancer in vitro.' Am J Surg. 2010 Nov;200(5):577-80.
7. Adams LS, Zhang Y, Seeram NP, Heber D, Chen S. 'Pomegranate ellagitannin-derived compounds exhibit antiproliferative and antiaromatase activity in breast cancer cells in vitro.' Cancer Prev Res (Phila). 2010 Jan;3(1):108-13.
8. Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM. 'mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass.' Cell Metab. 2011 Jun 8;13(6):627-38.
9. Gnoatto SC, Dassonville-Klimpt A, Da Nascimento S, Galéra P, Boumediene K, Gosmann G, Sonnet P, Moslemi S. 'Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition.' Eur J Med Chem. 2008 Sep;43(9):1865-77. Epub 2007 Dec 7.
10. Khan SI, Zhao J, Khan IA, Walker LA, Dasmahapatra AK. 'Potential utility of natural products as regulators of breast cancer-associated aromatase promoters.' Reprod Biol Endocrinol. 2011 Jun 21;9:91.
11. van Duursen MB, Nijmeijer SM, de Morree ES, de Jong PC, van den Berg M. 'Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model.' Toxicology. 2011 Nov 18;289(2-3):67-73. epub 2011 Aug 10.
12. Campbell, Deborah R.; Kurzer, Mindy S. (1993). "Flavonoid inhibition of aromatase enzyme activity in human preadipocytes". Journal of Steroid Biochemistry and Molecular Biology 46 (3): 381-388.
13. Kellis JT Jr, Vickery LE (1984). "Inhibition of human estrogen synthetase (aromatase) by flavones". Science 225 (4666): 1032-1034.
14. Grube BJ, Eng ET, Kao YC, Kwon A, Chen S. 'White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation.' J Nutr. 2001 Dec;131(12):3288-93.
15. Chen S, Oh SR, Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D. 'Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus).' Cancer Res. 2006 Dec 15;66(24):12026