Association between Equol Production Status and Nonalcoholic Steatohepatitis

Abstract

Equol is a metabolite of daidzein, a major soybean isoflavone with estrogenic and antioxidant activities. As the production of equol depends on the presence of certain members of the intestinal microflora, not all individuals can produce equol. We examined the relationship between NASH histological features and equol production. In an animal model, obese OLETF rats were intraperitoneally injected with a porcine serum to augment liver fibrogenesis. Equol-rich soy product, SE5-OH was orally administered during the experimental period. Treatment with SE5-OH markedly attenuated the development of liver fibrosis and expression of alpha-smooth muscle actin. In clinical research, 38 NAFLD patients (13 men and 25 women) were included. The degree of fibrosis and ballooning in equol-nonproducers was significantly higher than in equol-producers in women. The percentage of nonproducers with NAFLD activity score (NAS) ≥ 5 was significantly higher than that of producers. None of the histological features were significantly different between nonproducers and producers in men. Decision tree analysis identified predictors for NAS ≥ 5 in women. The status of equol production was the strongest predictor, followed by fasting glucose. Since equol can be noninvasively detected in urine, it can be applied as a screening tool for the progression of NASH in women.

Association between equol and non‐alcoholic fatty liver disease in Japanese women in their 50s and 60s

“…Three studies previously reported the association between equol production and NAFLD 14,18,19 . Two studies did not find a significant association between equol and NAFLD 18,19 .…”

Factors Influencing Skin Aging and the Important Role of Estrogens and Selective Estrogen Receptor Modulators (SERMs)

“… 89 In fact, like 17β-estradiol, phytoestrogens have been shown to decrease nonalcoholic fatty liver disease, 97 which was associated in one study with equol production status. 98 From in vitro and clinical studies, equol has similar actions to 17β-estradiol by stimulating collagen, elastin and TIMP expression, while inhibiting elastase and MMPs. 10 , 13 , 91 , 99 …”

“…89 In fact, like 17β-estradiol, phytoestrogens have been shown to decrease nonalcoholic fatty liver disease, 97 which was associated in one study with equol production status. 98 From in vitro and clinical studies, equol has similar actions to 17β-estradiol by stimulating collagen, elastin and TIMP expression, while inhibiting elastase and MMPs. 10,13,91,99 For example, in a randomized, single-center 12-week clinical study women that applied a topical equol treatment twice per day displayed significant increases (across eight skin parameters) over baseline values (Figure 5).…”

Hypolipidemic Effects of Soy Protein and Isoflavones in the Prevention of Non-Alcoholic Fatty Liver Disease- A Review

“…Akahane et al [ 50 ] recently reported that progression of NAFLD and NASH was strongly associated with the production of equol. A clinical study conducted in 38 NAFLD patients (13 men and 25 women) showed that the degree of hepatic fibrosis and ballooning was markedly higher in the equol non-producers than in the producers in women.…”

“…However, these associations were not observed in men. Limitations of the study include small sample size, a single-center study, unknown exact amounts of soy products consumed, liver fibrosis assessed by less ideal method, and inconclusive causal relationship [ 50 ]. The sex-dependent effect of equol may be attributed to the difference in the endogenous estrogen levels, abundance of hepatic estrogen receptor (ER) [ 51 ] and responsiveness to equol between males and females.…”