Abstract
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.
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Key Points
In the hull of flaxseed, lignan is present in a linear ester-linked repeated copolymer where SDG is bonded with 3-hydroxy-3-methylglutaric acid (HMG). Studies have shown that HMG can induce dose-dependent hypocholesterolemic effects in animal models, including lowering serum lipids in hyperlipidemic rats similar to SDG. In the gastrointestinal tract, the copolymer undergoes hydrolysis to release both SDG and HMG. Therefore, both compounds might contribute to the hypercholesterolemic effects of whole ground flaxseed.
In this study, the effects of highly enriched SDG with those of SDG polymer on body weight, liver weight, serum lipid parameters, and extent of hepatic lipidosis following daily oral administration to hypercholesterolemic rats was examined. The enriched SDG and SDG polymer have demonstrated hypocholesterolemic effects in rats fed a hypercholesterolemic diet. These hypocholesterolemic and antiatherogenic effects are attributed to the antioxidant properties of SDG, its aglycone, secoisolariciresinol (SECO), and their mammalian lignan metabolites, enterodiol (EDL) and enteroloactone (ENL), and are associated with metabolic syndrome. Although, how these lignans become systematically available when present as an ester-linked polymer is not completely known.
Studies suggest that HMG may not significantly increase the hypocholesterolemic effects of SDG polymer compared to enriched SDG. Together, the similarities in the hypocholesterolemic and pharmacokinetic effects of enriched SDG and SDG polymer suggest that SDG polymer may serve as a more economical alternative for treatment of hypercholesterolemia without the need for SDG enrichment. In conclusion, flaxseed lignans have been investigated as a nutraceutical that can treat and reduce blood cholesterol and liver disease. Although no statistical differences were observed after 23 days’ intervention with either enriched SDG or SDG polymer in hypercholesterolemic rats, lipid-lowering effects were observed following SDG and SDG polymer administration. Both SDG and SDG polymer treatment lowered liver steatosis and NAS scores, suggesting that SDG and SDG polymer can partially attenuate steatosis and hepatocellular injury caused by a high cholesterol diet. The lack of significance between SDG and SDG polymer treatments suggests that SDG polymer may be a suitable substitute for SDG in the treatment of hypercholesterolemia.