Aromatase inhibitors

There are some things bodybuilders don't like. These include small muscles, 5 guys standing around a machine taking 30 minutes to do a set, people who drop their weights loudly, and people who leave all the weight plates in the gym 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.

Estrogen and its disadvantages

Estrogen 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 - even though they have some estrogenic activity - do not have a steroid form. There are three primary types of estrogen that occur naturally in the body: Estrone (E1), Estradiol (E2), and Estriol (E3). Estradiol (E2) is considered the most potent of these three estrogens and is also the estrogen that has the strongest estrogenic activity.

As has already been mentioned, both men and women require estrogen for a number of bodily functions, which include blood clotting and the regulation of cholesterol levels. However, estrogen's most important role 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. Because of 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 estrogen produced comes from the ovaries. However, estrogen 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 abundant testosterone in the body, more estrogen is produced by the aromatase enzyme. Therefore, anyone who aims to increase their testosterone levels either through natural or non-natural means runs the risk of increasing their estrogen 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 estrogen levels.

Aromatase inhibitors

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

Zinc

Zinc is an important mineral that is often praised for its ability to support healthy testosterone levels. Zinc is often found in conjunction with magnesium and vitamin B6 in the popular ZMA supplements that are used to increase testosterone levels. While studies have yet to conclusively show that zinc supplementation can actually increase testosterone levels, it has been clearly proven that adequate amounts of this mineral are necessary for the maintenance of natural testosterone levels in two ways. The first pathway is the maintenance of testicular activity, as zinc deficiency is associated with hypogonadism - reduced function of the testes, which are responsible for testosterone production. The second way is based on a reduction in the activity of the aromatase enzyme.

Studies conducted with animals have shown that zinc deficiency resulted 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 seeds and also produced by other plants in the presence of pathogenic threats such as bacteria or fungi - has enjoyed a decade of increasing interest in the sports science community 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 levels (2). Other studies have been able to show that resveratrol supplementation resulted in increased testosterone concentrations (3), most likely due to resveratrol's action as an aromatase inhibitor. Resveratrol is also used to promote weight loss and for 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 may cause side effects. Currently, there are no definitive dosage recommendations for the use of resveratrol as an antiestrogen agent.

Lignans

Lignans are compounds found in plants such as safflower and flaxseed that are thought to have potent antiestrogen activity. There are a large number of studies that have investigated the use of lignans to treat and possibly prevent breast cancer, ovarian cancer, and cervical cancer, all cancers that are promoted by high estrogen activity.

When lignans are supplied in the diet, they are converted in the body into enterodiol and enterolactones, both of which themselves dock onto the estrogen receptors and can cause estrogen activity there, but this activity is very, very weak. This allows these metabolites of lignans to compete with estrogen for estrogen receptors, resulting in reduced body-wide estrogen activity. Although lignans may not reduce estrogen levels, they can reduce the effects of estrogen.

Studies on the potential weak estrogenic effect or an antiestrogenic 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 consumption of lignans in the form of flaxseed may help with cardiovascular disease. Currently, there are no current dosage recommendations for the use of lignans as an antiestrogen 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 Phenehtyl Ester (CAPE) is an organic compound commonly found in plants and is also a component of propolis from beehives. It has previously been shown that this compound can help with acute inflammation, but science has only recently begun to study CAPE for its anticancer effects. In fact, one study was able to show that CAPE may be a potential selective estrogen receptor modulator or SERM (5). SERMs are certain compounds 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, such as those needed for bone growth. At the moment, there are no dosage recommendations or conclusive studies on the antiestrogen activity of CAPE.

Ptersostilbene

Pterostilbene is an organic compound similar to resveratrol found in blueberries. Pterostilbene is said to increase the bioavailability of resveratrol due to its chemical structure. Over the past several years, pterostilbene has been extensively studied for its use in a wide range of applications including 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 by itself has any effect on the levels or activity of estrogen.

Ellagic Acid (Ellagic Acid) & Ellagitannins

Ellagic acid is an antioxidant found in many fruits and vegetables including pomegranates, blackberries, craneberries, pecans and walnuts. Ellagic acid can be readily converted into other antioxidants known as ellagitannins. Few studies have been conducted with these compounds, but they are already beginning to show that they appear to have antiviral and blood pressure-lowering abilities. One study (7) examined 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. Currently, there is 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, craneberries, rosemary, thyme, and in high concentrations in apple peels. 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 with mice also found that Ursolic Acid supplementation was able to reduce fat mass and blood glucose levels in a fasting state. In another study (9), ursolic acid isolated from the yerba mate plant was investigated and a mild aromatase inhibitory effect was observed. The studies currently conducted are quite promising regarding the aromatase inhibitory and anabolic properties of Ursolic Acid, but it is too early to make a specific dosage recommendation.

Red Clover & Genistein

Red Clover is a wild plant that has been traditionally used for a wide range of applications including reducing inflammation and treating respiratory problems. 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 exhibits some aromatase inhibitory activity (10). Interestingly, biochanin A can also be readily converted to 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 may act as an aromatase inhibitor, problems with increased estrogen activity may occur when biochanin A is converted to genistein. Therefore, further research is needed before it is known conclusively whether Red Clover should be used in antiestrogen formulas.

Alpha-Naphthoflavone

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

White Button Mushrooms (Mushroom)

The common mushroom or the white button mushroom is one of the most common edible mushrooms. This mushroom can be found in practically every supermarket. Early studies were able to show that extracts from these mushrooms may have potent 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 dosing recommendations.

Ingredients without end

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

Conclusion

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

• Zinc
• Resveratrol
• Ellagitannins
• Ursolic Acid
• Alpha-Naphthoflavones
• Agaricus Bisporus (White Button Mushroom 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 31st May 2012.
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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.
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