madman
Super Moderator
Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies
Abstract
Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. Several studies and case-reports describing feminizing effects including lowering testosterone levels and raising estrogen levels in men have been published. For this reason, the clinical data were meta-analyzed to determine whether soy or isoflavone intake affects total testosterone (TT), free testosterone (FT), estradiol (E2 ), estrone (E1 ), and sex hormone-binding globulin (SHBG). PubMed and CAB Abstracts databases were searched between 2010 and April 2020, with the use of controlled vocabulary specific to the databases. Peer-reviewed studies published in English were selected if (1) adult men consumed soyfoods, soy protein, or isoflavone extracts (from soy or red clover) and [2] circulating TT, FT, SHBG, E2, or E1 was assessed. Data were extracted by two independent reviewers. With one exception, studies included in a 2010 meta-analysis were included in the current analysis. A total of 41 studies were included in the analyses. TT and FT levels were measured in 1753 and 752 men, respectively; E2 and E1 levels were measured in 1000 and 239 men, respectively, and SHBG were measured in 967 men. Regardless of the statistical model, no significant effects of soy protein or isoflavone intake on any of the outcomes measured were found. Sub-analysis of the data according to isoflavone dose and study duration also showed no effect. This updated and expanded meta-analysis indicates that regardless of dose and study duration, neither soy protein nor isoflavone exposure affects TT, FT, E2 or E1 levels in men.
1. Introduction
For centuries foods made from soybeans, such as tofu and miso, have played an important role in the diets of many Asian countries [1, 2]. Much more recently, soyfoods have become popular in many non-Asian countries because of their purported nutritional and health benefits and the increased interest in plant-based diets and plant protein [3-7]. In addition to the traditional Asian soyfoods, soy protein can be incorporated into the diet via supplementation with and/or by consuming foods containing soy protein ingredients, namely soy flour, soy protein concentrate (SPC) and soy protein isolate (SPI). On a moisture-free basis, these products are approximately 50, 65, and 90% protein, respectively [8].
Much of the soy-related health research published over the past 3 decades has taken place because, among commonly consumed foods, the soybean is a uniquely rich source of isoflavones [9, 10]. Mean isoflavone intake in Japan among older adults ranges from approximately 30 to 50 mg/d [11, 12] whereas per capita isoflavone intake in the United States [13] and Europe [14] is <3 mg/d. The three isoflavones, genistein, daidzein, and glycitein and their respective glycosides, comprise approximately 50, 40, and 10% of the total soybean isoflavones content, respectively [15]. Each gram of soy protein in traditional soyfoods is associated with approximately 3.5 mg isoflavones (expressed as the aglycone equivalent weight) [11]. In contrast, much of the isoflavone content is lost in the production of SPI and SPC, although the degree of loss depends upon the method of manufacture [15, 16]. Isoflavone values in this manuscript refer to the aglycone equivalent weight.
Isoflavones have a chemical structure similar to the hormone estrogen which allows them to bind to both estrogen receptors (ER) – ER and ER [17, 18], and to exert estrogen-like effects under certain experimental conditions. For this reason, they are commonly classified as phytoestrogens. Circulating levels of isoflavones in response to the ingestion of approximately two servings of traditional soyfoods are three orders of magnitude higher than estrogen [19]. However, isoflavones differ from estrogen at the molecular level in that they preferentially bind to and activate ERβ in comparison to ERα whereas estrogen has equal affinity for both receptors [20-23]. This difference in binding preference is important because the two ERs have different tissue distributions and, when activated, can exert different and sometimes opposite physiological effects [24, 25]. The preference of isoflavones for ERβ is the primary reason that isoflavones are seen as capable of having tissue-selective effects and the reason they are often classified as selective estrogen receptor modulators (SERMs) [26-29]. [30].
Isoflavones have been rigorously investigated over the past 30 years for a number of potential health benefits in both men and women [31-37]. However, isoflavones are not without controversy as there is concern that isoflavones feminize men. This concern, which coincided with the rising apprehension that environmental estrogens play a role in the declining sperm count occurring among men worldwide.[38-40], has some support from animal studies [41, 42].
*To our knowledge, the current meta-analysis is the first to examine the effects of soy intake and isoflavone exposure on estrogen levels in men.
In conclusion, extensive clinical data published over the past two decades shows that in men neither soy nor isoflavone intake, even when exposure occurs for an extended period of time and exceeds typical Japanese intake, affects levels of total testosterone, free testosterone, estradiol or estrone.
Abstract
Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. Several studies and case-reports describing feminizing effects including lowering testosterone levels and raising estrogen levels in men have been published. For this reason, the clinical data were meta-analyzed to determine whether soy or isoflavone intake affects total testosterone (TT), free testosterone (FT), estradiol (E2 ), estrone (E1 ), and sex hormone-binding globulin (SHBG). PubMed and CAB Abstracts databases were searched between 2010 and April 2020, with the use of controlled vocabulary specific to the databases. Peer-reviewed studies published in English were selected if (1) adult men consumed soyfoods, soy protein, or isoflavone extracts (from soy or red clover) and [2] circulating TT, FT, SHBG, E2, or E1 was assessed. Data were extracted by two independent reviewers. With one exception, studies included in a 2010 meta-analysis were included in the current analysis. A total of 41 studies were included in the analyses. TT and FT levels were measured in 1753 and 752 men, respectively; E2 and E1 levels were measured in 1000 and 239 men, respectively, and SHBG were measured in 967 men. Regardless of the statistical model, no significant effects of soy protein or isoflavone intake on any of the outcomes measured were found. Sub-analysis of the data according to isoflavone dose and study duration also showed no effect. This updated and expanded meta-analysis indicates that regardless of dose and study duration, neither soy protein nor isoflavone exposure affects TT, FT, E2 or E1 levels in men.
1. Introduction
For centuries foods made from soybeans, such as tofu and miso, have played an important role in the diets of many Asian countries [1, 2]. Much more recently, soyfoods have become popular in many non-Asian countries because of their purported nutritional and health benefits and the increased interest in plant-based diets and plant protein [3-7]. In addition to the traditional Asian soyfoods, soy protein can be incorporated into the diet via supplementation with and/or by consuming foods containing soy protein ingredients, namely soy flour, soy protein concentrate (SPC) and soy protein isolate (SPI). On a moisture-free basis, these products are approximately 50, 65, and 90% protein, respectively [8].
Much of the soy-related health research published over the past 3 decades has taken place because, among commonly consumed foods, the soybean is a uniquely rich source of isoflavones [9, 10]. Mean isoflavone intake in Japan among older adults ranges from approximately 30 to 50 mg/d [11, 12] whereas per capita isoflavone intake in the United States [13] and Europe [14] is <3 mg/d. The three isoflavones, genistein, daidzein, and glycitein and their respective glycosides, comprise approximately 50, 40, and 10% of the total soybean isoflavones content, respectively [15]. Each gram of soy protein in traditional soyfoods is associated with approximately 3.5 mg isoflavones (expressed as the aglycone equivalent weight) [11]. In contrast, much of the isoflavone content is lost in the production of SPI and SPC, although the degree of loss depends upon the method of manufacture [15, 16]. Isoflavone values in this manuscript refer to the aglycone equivalent weight.
Isoflavones have a chemical structure similar to the hormone estrogen which allows them to bind to both estrogen receptors (ER) – ER and ER [17, 18], and to exert estrogen-like effects under certain experimental conditions. For this reason, they are commonly classified as phytoestrogens. Circulating levels of isoflavones in response to the ingestion of approximately two servings of traditional soyfoods are three orders of magnitude higher than estrogen [19]. However, isoflavones differ from estrogen at the molecular level in that they preferentially bind to and activate ERβ in comparison to ERα whereas estrogen has equal affinity for both receptors [20-23]. This difference in binding preference is important because the two ERs have different tissue distributions and, when activated, can exert different and sometimes opposite physiological effects [24, 25]. The preference of isoflavones for ERβ is the primary reason that isoflavones are seen as capable of having tissue-selective effects and the reason they are often classified as selective estrogen receptor modulators (SERMs) [26-29]. [30].
Isoflavones have been rigorously investigated over the past 30 years for a number of potential health benefits in both men and women [31-37]. However, isoflavones are not without controversy as there is concern that isoflavones feminize men. This concern, which coincided with the rising apprehension that environmental estrogens play a role in the declining sperm count occurring among men worldwide.[38-40], has some support from animal studies [41, 42].
*To our knowledge, the current meta-analysis is the first to examine the effects of soy intake and isoflavone exposure on estrogen levels in men.
In conclusion, extensive clinical data published over the past two decades shows that in men neither soy nor isoflavone intake, even when exposure occurs for an extended period of time and exceeds typical Japanese intake, affects levels of total testosterone, free testosterone, estradiol or estrone.
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