Dr. Ron’s Research Review – April 10, 2013

© 2013

This week’s research review focuses on Saw palmetto (Serenoa repens) and aromatase.

Is saw palmetto is an aromatase inhibitor?

Possibly; at high doses.

A recent study with 42 healthy males showed that Serenoa extract with astaxanthin (Alphastat, Mytosterone) at 800 and 2000 mg/day increased testosterone and decreased DHT. Estradiol declined only at the high dose. (Angwafor and Anderson 2008)

Serenoa, however, is not listed in the recent review by Balunas, "Natural compounds with aromatase inhibitory activity." (Balunas and Kinghorn 2010)

Drsata 2002 is cited by supplement companies, however, the article is in Czech, and states the following. (Drsata 2002)

"Non-steroidal 5 alpha-reductase inhibitors (e.g. polyunsaturated fatty acids) are effective components of several phytopharmaceuticals. They receive attention due to their complexity and low hazards. Extracts of Serenoa repens seeds (Permixon, Capistan in the Czech Republic), of Pygeum africanum, of Urtica radicis roots (Urtica, Urtiron) or catequine structures from the green tea belong to this group. "

"Inhibition of the "aromatase" complex, which catalyzes transformation of androgens to estrogens, may contribute to the complexity of phytotherapeutic effects."

Dr. Ron


Articles

An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males

            (Angwafor and Anderson 2008) Download

BACKGROUND: Maintaining endogenous testosterone (T) levels as men age may slow the symptoms of sarcopenia, andropause and decline in physical performance. Drugs inhibiting the enzyme 5alpha-reductase (5AR) produce increased blood levels of T and decreased levels of dihydrotestosterone (DHT). However, symptoms of gynecomastia have been reported due to the aromatase (AER) enzyme converting excess T to estradiol (ES). The carotenoid astaxanthin (AX) from Haematococcus pluvialis, Saw Palmetto berry lipid extract (SPLE) from Serenoa repens and the precise combination of these dietary supplements, Alphastat(R) (Mytosterone(trade mark)), have been reported to have inhibitory effects on both 5AR and AER in-vitro. Concomitant regulation of both enzymes in-vivo would cause DHT and ES blood levels to decrease and T levels to increase. The purpose of this clinical study was to determine if patented Alphastat(R) (Mytosterone(trade mark)) could produce these effects in a dose dependent manner. METHODS: To investigate this clinically, 42 healthy males ages 37 to 70 years were divided into two groups of twenty-one and dosed with either 800 mg/day or 2000 mg/day of Alphastat(R) (Mytosterone(trade mark)) for fourteen days. Blood samples were collected on days 0, 3, 7 and 14 and assayed for T, DHT and ES. Body weight and blood pressure data were collected prior to blood collection. One-way, repeated measures analysis of variance (ANOVA-RM) was performed at a significance level of alpha = 0.05 to determine differences from baseline within each group. Two-way analysis of variance (ANOVA-2) was performed after baseline subtraction, at a significance level of alpha = 0.05 to determine differences between dose groups. Results are expressed as means +/- SEM. RESULTS: ANOVA-RM showed significant within group increases in serum total T and significant decreases in serum DHT from baseline in both dose groups at a significance level of alpha = 0.05. Significant decreases in serum ES are reported for the 2000 mg/day dose group and not the 800 mg/day dose group. Significant within group effects were confirmed using ANOVA-2 analyses after baseline subtraction. ANOVA-2 analyses also showed no significant difference between dose groups with regard to the increase of T or the decrease of DHT. It did show a significant dose dependant decrease in serum ES levels. CONCLUSION: Both dose groups showed significant (p = 0.05) increases in T and decreases in DHT within three days of treatment with Alphastat(R) (Mytosterone(trade mark)). Between group statistical analysis showed no significant (p = 0.05) difference, indicating the effect was not dose dependent and that 800 mg/per day is equally effective as 2000 mg/day for increasing T and lowering DHT. Blood levels of ES however, decreased significantly (p = 0.05) in the 2000 mg/day dose group but not in the 800 mg/day dose group indicating a dose dependant decrease in E levels.

Natural compounds with aromatase inhibitory activity: an update

            (Balunas and Kinghorn 2010) Download

Several synthetic aromatase inhibitors are currently in clinical use for the treatment of postmenopausal women with hormone-receptor positive breast cancer. However, these treatments may lead to untoward side effects and so the search for new aromatase inhibitors continues, especially those for which the activity is promoter-specific, targeting the breast-specific promoters I.3 and II. Recently, numerous natural compounds have been found to inhibit aromatase in noncellular, cellular, and IN VIVO studies. These investigations, covering the last two years, as well as additional studies that have focused on the evaluation of natural compounds as promoter-specific aromatase inhibitors or as aromatase inducers, are described in this review.

 

[Enzyme inhibition in the drug therapy of benign prostatic hyperplasia]

         (Drsata 2002) Not available

Enzyme inhibition belongs to common mechanisms of drug action and enzymes of hormone metabolism belong to targets in the treatment of benign prostatic hyperplasia. Transformation of testosterone to 5 alpha-dihydrotestosterone is catalyzed by cholestenone-5 alpha-reductase (EC 1.3.1.22, 5 alpha-reductase). Different effects of dihydrotestosterone and testosterone represent a rational basis for pharmacotherapy by 5 alpha-reductase inhibition. The enzyme is active in the prostate and other organs and tissues, with different distribution of at least two 5 alpha-reductase isoenzymes. Beside this, progesterone-5 alpha-reductase (EC 1.3.1.30) as another enzyme with 5 alpha-reductase activity is present in human tissues including the prostate. The existence of several 5 alpha-reductase activities gives bright possibilities of 5 alpha-reductase inhibition. Basic 5 alpha-reductase inhibitors are synthetic steroid (e.g. finasteride--Proscar). Various mechanisms of their effect (classical reversible competitive inhibition, mechanism-based "suicide" inhibitors, tightly bound irreversible inhibitors...) represent different pharmacokinetic patterns, too. Non-steroidal 5 alpha-reductase inhibitors (e.g. polyunsaturated fatty acids) are effective components of several phytopharmaceuticals. They receive attention due to their complexity and low hazards. Extracts of Serenoa repens seeds (Permixon, Capistan in the Czech Republic), of Pygeum africanum, of Urtica radicis roots (Urtica, Urtiron) or catequine structures from the green tea belong to this group. Beside androgens, participation of estrogens in the origin and development of benign prostatic hyperplasia is probable. Inhibition of the "aromatase" complex, which catalyzes transformation of androgens to estrogens, may contribute to the complexity of phytotherapeutic effects.

References

Angwafor, F., 3rd and M. L. Anderson (2008). "An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males." J Int Soc Sports Nutr 5: 12 PMID: 18700016

Balunas, M. J. and A. D. Kinghorn (2010). "Natural compounds with aromatase inhibitory activity: an update." Planta Med 76(11): 1087-93 PMID: 20635310

Drsata, J. (2002). "[Enzyme inhibition in the drug therapy of benign prostatic hyperplasia]." Cas Lek Cesk 141(20): 630-5 PMID: 12515038