The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers

Setchell, Kenneth D.R.; Zhao, Xueheng; Jha, Pinky; Heubi, James E.; Brown, Nesbitt D.

doi:10.3945/ajcn.2009.27981

Cited by 82 publications

(75 citation statements)

References 56 publications

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“…The reservoir forming properties of equol in the epidermis may be due to its lipophilic characteristics where its octanol-water partition coefficient is 3.20, which is higher than other polyphenolic molecules (Rothwell et al, 2005). Additionally, intestinal absorption data support this proposition where equol (either as the R-or S-isomer) has the highest absorption levels (80-85%) compared to other isoflavonoids, such as genistein (at 15-20%) or daidzein (at 30-40%) (Setchell et al, 2009;Setchell & Clerici, 2010). Drug-delivery studies have shown the more stable isomer is R-equol versus S-equol (Alvira et al, 2008) and in vitro culture data suggest that the R-isomer accounts for the chemoprotective effects of equol rather than the S-isomer in breast and prostate cancer cells (Magee et al, 2006).…”

Section: Discussionsupporting

confidence: 66%

“…Further research has revealed that equol concentrations in low-soy consuming US populations reflect equol intakes from mammalian (cow) milk sources (Frankenfeld, 2011;Hoikkala et al, 2007;Mustonen et al, 2009) that can be as high as 1.5 mg/kg in cow's milk (Höjer et al, 2012). Notably, the metabolism of Rand S-equol in humans appears to be similar (Setchell et al, 2005(Setchell et al, , 2009. Therefore, humans are exposed to this polyphenolic compound from different plant and food sources regardless of age, gender, or geographical location with scientific data to support a consumption/exposure record that appears to be safe (Frankenfeld, 2011;Lephart, 2013a).…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin

Lephart¹

2013

Pharmaceutical Biology

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Context: Equol is a polyphenolic/isoflavonoid molecule that can be expressed as isomers. However, the characteristics of the equol isomers on dermal gene/protein expression and human skin percutaneous absorption remain unknown. Objective: Perform a comprehensive investigation on equol as: R-equol, racemic equol or Sequol to determine their differential expression of skin-related genes, quantify collagen expression and determine percutaneous absorption in human skin. Methods: Quantified: (i) gene expression/mRNA levels via gene array technology using human skin equivalents with equol exposure at 1.2% in qPCR experiments, (ii) in vitro collagen expression in human fibroblasts, and (iii) percutaneous absorption by Franz cell techniques. Results: In the qPCR studies, only three genes displayed the greatest significant expression by S-equol, whereas 16 genes displayed the greatest significant levels (either stimulation or inhibition) by R-equol and/or racemic equol, such as extracellular matrix proteins (i.e., collagen and elastin), nerve growth factor, aging genes [FOS, 100 A8 and A9 calcium-binding proteins, 5a-reductase type 1, and matrix metalloproteinases (1, 3, and 9)], and inflammatory genes (e.g., interleukin-1 alpha, interleukin-6, and cyclooxygenase-1). Collagen type I expression in fibroblasts was greater with racemic versus S-equol treatment at 1 and 10 nM. Percutaneous absorption demonstrated high sequestering in keratinocytes with subsequent accumulation/ release over time. Discussion and conclusion: Overall, these results illustrate the significant differences in mirrorimage molecules or isomers of equol where R-equol and/or racemic equol are better molecules for skin gene expression compared to S-equol and the percutaneous absorption of equol represents a unique epidermal reservoir delivery mechanism.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin

Lephart¹

2013

Pharmaceutical Biology

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“…40,41 Overall, apparent bioavailability of these isoflavones are similar. Nonetheless, the rates of absorption of the isoflavones daidzein and genistein as glycosides are distinctly different from those of daidzein and genistein in their aglycone form and this has recently been suggested to be an important difference that could influence the ultimate efficacy of isoflavones.…”

Section: Bioavailability and Pharmacokineticsmentioning

confidence: 86%

The role of soy isoflavones in menopausal health

et al. 2011

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Several areas for further research have been identified on soy and midlife women. More clinical studies are needed that compare outcomes among women whose intestinal bacteria have the ability to convert daidzein to equol (equol producers) with those that lack that ability (equol nonproducers) in order to determine if equol producers derive greater benefits from soy supplementation. Larger studies are needed in younger postmenopausal women, and more research is needed to understand the modes of use of soy isoflavone supplements in women. The interrelations of other dietary components on soy isoflavones consumed as a part of diet or by supplement on equol production also require further study, as do potential interactions with prescription and over-the-counter medications. And finally, greater standardization and documentation of clinical trial data of soy are needed.

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“…Maximum plasma S-equol concentrations occur between 1 and 3 hours after oral administration and it is cleared from plasma with a half-life of 7 to 10 hours. 23,29,32,33 Consequently, over 80% of S-equol is excreted in the urine within 24 hours after administration. 23,32,33 Based on these pharmacokinetics to achieve sustained steady-state serum concentrations, a twice-daily dose, rather than a once-daily dose of S-equol is considered optimal.…”

Section: General Backgroundmentioning

confidence: 99%

S-equol: A Potential Nonhormonal Agent for Menopause-Related Symptom Relief

Utian

Jones

Setchell

2015

Journal of Women's Health

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Many women suffering from vasomotor symptoms (VMS) are now seeking nonpharmaceutical treatments for symptom relief. Recently, S-equol, an intestinal bacterial metabolite of the soybean isoflavone daidzein has received attention for its ability to alleviate VMS and provide other important health benefits to menopausal women. S-equol is found in very few foods and only in traces. About 50% of Asians and 25% of non-Asians host the intestinal bacteria that convert daidzein into S-equol. Clinical trials that evaluated the efficacy of an S-equol-containing product found that VMS were alleviated but these trials were limited in scope and primarily involved Japanese women for whom hot flashes are a minor complaint. The only trial in the United States evaluating hot flashes found symptoms were significantly reduced by S-equol, but the study lacked a placebo group, although it did include a positive control. The daily dose of S-equol used in most trials was 10 mg, and because the half-life of S-equol is 7-10 hours, to maximize efficacy, it was taken twice daily. Subanalysis of epidemiologic studies suggests that equol producers are more likely to benefit from soyfood consumption than nonproducers with respect to both cardiovascular disease and osteoporosis, although the data are inconsistent. The limited safety data for S-equol do not suggest cause for concern, especially with regard to its effects on breast and endometrial tissue. Further studies are needed before definitive conclusions of its effectiveness for VMS can be made, but the preliminary evidence warrants clinicians discussing the potential of S-equol for the alleviation of VMS with patients.

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The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers

Abstract: The high bioavailability of both diastereoisomers contrasts with previous findings for the soy isoflavones daidzein and genistein, both of which have relatively poor bioavailability, and suggests that low doses of equol taken twice daily may be sufficient to achieve biological effects.

Cited by 82 publications

References 56 publications

Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin

Protective effects of equol and their polyphenolic isomers against dermal aging: Microarray/protein evidence with clinical implications and unique delivery into human skin

The role of soy isoflavones in menopausal health

S-equol: A Potential Nonhormonal Agent for Menopause-Related Symptom Relief

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