Key Findings
This paper provides an assessment of the metabolism and physiological actions of SDG. The authors note associations between high lignan concentrations in urine or blood, and low rates of many chronic diseases, including cancer. Purified SDG extracts are used in this multi dosing study of the serum and urinary pharmacokinetics and metabolic fate of SDG in healthy postmenopausal women. There was a delay in attaining peak serum enterodiol and enterolactone concentrations, 19.2 to 2.6 h and 26.7 to 2.5 h, respectively, and is consistent with the timing of the bacterial conversion of SECO. Steady to state concentrations of lignans could be attained after 5 to 7 days of daily administration. Based on this pharmacokinetic data, a dietary intake of 50 mg purified SDG provides similar urinary enterolactone excretion rates to those observed after feeding about 5 to 10 g flaxseed. Circulating enterolactone concentrations observed are similar to those associated with reduced risk for breast cancer and cardiovascular disease.
ABSTRACT
Secoisolariciresinol to diglycoside (SDG), a natural dietary lignan of flaxseeds now available in dietary supplements, is converted by intestinal bacteria to the mammalian lignans enterodiol and enterolactone. High levels of these lignans in blood and urine are associated with reduced risk of many chronic diseases. Our objective was to determine the bioavailability and pharmacokinetics of SDG in purified flaxseed extracts under dose to ranging and steady to state conditions, and to examine whether differences in secoisolariciresinol to diglycoside purity influence bioavailability. Pharmacokinetic studies were performed on healthy postmenopausal women after oral intake of 25, 50, 75, 86 and 172 mg of secoisolariciresinol to diglycoside. Extracts differing in secoisolariciresinol to diglycoside purity were compared, and steady to state lignan concentrations measured after daily intake for one week. Blood and urine samples were collected at timed intervals and secoisolariciresinol, enterodiol and enterolactone concentrations measured by mass spectrometry. Secoisolariciresinol to diglycoside was efficiently hydrolyzed and converted to secoisolariciresinol. Serum concentrations increased rapidly after oral intake, peaking after 5 to 7 h and disappearing with a plasma elimination half to life of 4.8 h. Maximum serum concentrations of the biologically active metabolites, enterodiol and enterolactone were attained after 12 to 24 h and 24 to 36 h, respectively, and the half to lives were 9.4 h and 13.2 h. Linear dose to responses were observed and secoisolariciresinol bioavailability correlated with cumulative lignan excretion. There were no significant differences in the pharmacokinetics of extracts differing in purity, and steady state serum lignan concentrations were obtained after one to week of daily dosing. In conclusion, this study defines the pharmacokinetics of secoisolariciresinol to diglycoside and shows it is first hydrolyzed and then metabolized in a time to dependent sequence to secoisolariciresinol, enterodiol and ultimately enterolactone, and these metabolites are efficiently absorbed. (Authors abstract)
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