Availability of bioactive flax lignan from foods and supplements.

Hyperlipidemia, high levels of blood lipids including cholesterol and triglycerides, is a major risk factor for cardiovascular disease. Traditional treatments of hyperlipidemia often include lifestyle changes and pharmacotherapy. Recently, flaxseed has been approved as a nutrient that lowers blood lipids. Several metabolites of flaxseed lignan secoisolariciresinol diglucoside (SDG), have been identified that reduce blood lipids. SDG is present in flaxseed hull as an ester-linked copolymer with 3-hydroxy-3-methylglutaric acid (HMGA). However, purification processes involved in hydrolysis of the copolymer and enriching SDG are often expensive. The natural copolymer of SDG with HMGA (SDG polymer) is a source of bioactive compounds useful in prophylaxis of hypercholesterolemia. After consumption of the lignan copolymer, SDG and HMGA are released in the stomach and small intestines. SDG is metabolized to secoisolariciresinol, enterolactone and enterodiol, the bioactive forms of mammalian lignans. These metabolites are then distributed throughout the body where they accumulate in the liver, kidney, skin, other tissues, and organs. Successively, these metabolites reduce blood lipids including cholesterol, triglycerides, low density lipoprotein cholesterol, and lipid peroxidation products. In this review, the metabolism and efficacies of flaxseed-derived enriched SDG and SDG polymer will be discussed.

Hypocholesterolemic Efficacy of Secoisolariciresinol Diglucoside and Its Polymer in Rat.

Hypercholesterolemia is a risk factor for cardiovascular disease. Conventional treatment methods include lifestyle changes and pharmaceutical interventions, but recently Health Canada approved a health claim for whole ground flaxseed as an alternative treatment for hypercholesterolemia. The literature suggests flaxseed lignans are responsible for the cholesterol-reducing effects of flaxseed. In this study, 96.1% secoisolariciresinol diglucoside (SDG) and a 50% SDG enriched polymer (SDG polymer) were investigated as treatments for hypercholesterolemia in rats. Wistar female rats were fed a 1% high-cholesterol diet for a one-week acclimatization prior to a 23-day intervention with enriched SDG or SDG polymer. A reduction in body weight normalized liver weight was observed in rats treated with enriched SDG when compared to the controls. Both enriched SDG (96.1%) and SDG polymer reduced serum triacylglycerol (19% and 15%, respectively) and increased high-density lipoprotein cholesterol (15% and 24%, respectively). Histopathologic analyses revealed lipid-lowering effects of either enriched SDG or SDG polymer along with lower steatosis scores and nonalcoholic fatty liver disease activity. Furthermore, the lack of statistical significance between SDG and SDG polymer treatment groups suggests that SDG polymer may be a potential alternative to enriched SDG for hypercholesterolemia with similar efficacy but lower cost.

Oral Pharmacokinetics of Enriched Secoisolariciresinol Diglucoside and Its Polymer in Rats.

Secoisolariciresinol diglucoside (SDG) is the principal lignan of flaxseed and precursor of its aglycone, secoisolariciresinol (SECO), and the mammalian lignans enterolactone (EL) and enterodiol (ED), the putative bioactive forms of oral administration of SDG. SDG is present in the seed hull as an ester-linked polymer. Although extraction and purification of SDG monomer is costly, the use of naturally occurring SDG in polymer form may offer a more economical approach for delivery of this precursor. The extent of SDG release from the polymer and subsequent bioavailability of SDG metabolites are unknown. To understand the relative bioavailability of SDG polymer, this study examined the comparative bioavailability of enriched SDG and SDG polymer in rats after a single oral SDG equivalent dose (40 mg/kg). A validated LC-MS/MS method quantified SDG and its metabolites in rat plasma following serial blood collections. SDG remained undetectable in rat plasma samples. Unconjugated SECO was detected in plasma after 0.25 h. Unconjugated ED was observed after 8 h (3.4 ± 3.3 ng/mL) and 12 h (6.2 ± 3.3 ng/mL) for enriched SDG and SDG polymer, respectively. Total (conjugated and unconjugated) ED and EL resulting from enriched SDG and SDG polymer reached similar maximal concentrations between 11 and 12 h and demonstrated similar total body exposures (AUC values). These data suggest a similar pharmacokinetic profile between the enriched and polymer form of SDG, providing support for the use of SDG polymer as a more economical precursor for SECO, ED, and EL in applications of chronic disease management.