Pharmacokinetics of Enterolignans in Healthy Men and Women Consuming a Single Dose of Secoisolariciresinol Diglucoside

Abstract

High concentrations of enterolignans in plasma are associated with a lower risk of acute coronary events. However, little is known about the absorption and excretion of enterolignans. The pharmacokinetic parameters and urinary excretion of enterodiol and enterolactone were evaluated after consumption of their purified plant precursor, secoisolariciresinol diglucoside (SDG). Twelve healthy volunteers ingested a single dose of purified SDG (1.31 micromol/kg body wt). Enterolignans appeared in plasma 8-10 h after ingestion of the purified SDG. Enterodiol reached its maximum plasma concentration 14.8 +/- 5.1 h (mean +/- SD) after ingestion of SDG, whereas enterolactone reached its maximum 19.7 +/- 6.2 h after ingestion. The mean elimination half-life of enterodiol (4.4 +/- 1.3 h) was shorter than that of enterolactone (12.6 +/- 5.6 h). The mean area under the curve of enterolactone (1762 +/- 1117 nmol/L . h) was twice as large as that of enterodiol (966 +/- 639 nmol/L . h). The mean residence time for enterodiol was 20.6 +/- 5.9 h and that for enterolactone was 35.8 +/- 10.6 h. Within 3 d, up to 40% of the ingested SDG was excreted as enterolignans via urine, with the majority (58%) as enterolactone. In conclusion, a substantial part of enterolignans becomes available in the blood circulation and is subsequently excreted. The measured mean residence times and elimination half-lives indicate that enterolignans accumulate in plasma when consumed 2-3 times a day and reach steady state. Therefore, plasma enterolignan concentrations are expected to be good biomarkers of dietary lignan exposure and can be used to evaluate the effects of lignans.

Plasma Enterolignans Are Associated with Lower Colorectal Adenoma Risk

“…The concentration of enterolignans in plasma is not dependent on memory, and takes into account metabolism by the colonic flora and bioavailability as well. Enterolignans will accumulate in plasma when consumed twice or thrice a day (39). Thus, steady state plasma concentrations of enterodiol and enterolactone are likely to be achieved because plant lignans are present in many foods and beverages.…”

Interindividual differences in phytochemical metabolism and disposition

“…The efficiency of conversion of plant lignan precursors to END and ENL in 24-h incubations with human fecal inocula varied greatly depending on the compound and ranged from 0 to 100%. Studies have reported that urinary excretion of ENL is very low or nonexistent in some study participants challenged with SDG [9,35,36]; these results suggest that there may a subpopulation of individuals that lacks the bacteria or appropriate intestinal environment necessary for oxidation of END to ENL.…”

“…Circulating concentrations of phytochemicals, such as psoralens, lignans, and the flavonoids naringenin and hesperitin, can vary widely among individuals even in the context of controlled feeding studies [8][9][10]. The process of phytochemical disposition, like that of disposition of drugs and other xenobiotics, involves absorption, metabolism, distribution, and excretion, and each of these parts may contribute to pharmacokinetic variability (Figure 1) [11].…”

A Comparison Between Lignans from Creosote Bush and Flaxseed and Their Potential to Inhibit Cytochrome P450 Enzyme Activity

“…A Lineweaver-Burke plot gave parallel lines, a pattern consistent with uncompetitive inhibition (not shown). SDG (and SECO) is often referred to as the precursor for the enterolignans, ED and EL (Thompson et al, 1991;Borriello et al, 1985a;Kuijsten et al, 2005;Axelson et al, 1982c;Bambagiotti-Alberti et al, 1994). Much of the putative health benefits of flaxseed lignans are ascribed to the enterolignan forms, although definitive data for such assertions is lacking.…”