Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men
Introduction
Metabolic syndrome which is characterized by visceral obesity, dyslipidemia, hyperglycemia, and hypertension has been gradually increasing over the last few decades and has become a major public health challenge worldwide [1]. Various therapies have been developed to treat metabolic syndrome [2]. However, diet is an important factor that influences the array of underlying condition and should be considered during patient treatment.
Flaxseeds are one of the richest sources of plant lignans [3], [4]. The lignan secoisolariciresinol diglucoside (SDG) is present in greater quantity in the seed coat than in other tissues of the seed [5]. In humans and other animals, ingested SDG is converted by bacteria in the colon to the biologically active lignans enterodiol (END) and enterolactone (ENL) [3], [6], [7]. These SDG metabolites possess antioxidant activity and have been shown to protect humans against hormone-dependent cancers, such as breast and prostate cancers [8], [9], [10]. In addition, the intake of SDG has been shown to effectively inhibit the development of type 1 and 2 diabetes [11], [12].
Recent studies have shown that oral administration of flaxseed and flaxseed-derived lignan reduces blood total and low-density lipoprotein (LDL) cholesterol levels in postmenopausal women and hypercholesterolemic individuals [13], [14], [15]. The doses of SDG and flaxseed used in these studies were 200 to 600 mg/d and 30 to 50 g/d, respectively. In addition to lignan extracts, flaxseeds contain a water-soluble fiber known as mucilage [16]. Viscous fibers, such as mucilage, can gel and swell in the intestine, which can lead to intestinal obstruction and discomfort [17]. Therefore, these doses are higher than those that can be reasonably consumed by moderately hypercholesterolemic or healthy subjects. Recent studies have also shown that fatty liver diseases, namely non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are linked to metabolic syndrome and cardiovascular disease (CVD) [18], [19], [20]. We have previously demonstrated that administration of SDG to mice attenuates high-fat, diet-induced liver fat accumulation, hypercholesterolemia [21].
Given results from these studies, we hypothesized that a low dose of SDG (20 mg or 100 mg), compared to the higher levels of SDG used in previous human research, would decrease the cholesterol levels in moderately hypercholesterolemic men. Moreover, we hypothesized that oral administration of SDG would decrease the level of liver disease risk factors induced by hypercholesterolemia in humans, but not rodents. Specifically, our objective was to investigate the effects of 20 mg and 100 mg SDG intake (that can be practically ingested on a daily basis) on hypercholesterolemia and liver disease risk factors in moderately hypercholesterolemic men for 12 weeks.
Section snippets
Subjects
A total of 30 moderately hypercholesterolemic men between 21 and 57 years of age were recruited for this study between January and May of 2009. The subjects were required to have a fasting total cholesterol level of 4.65 to 6.21 mmol/L (180-240 mg/mL) at the beginning of the study. Subjects who were taking cholesterol-lowering pharmaceutical agents or who had ingested flaxseed supplements (flax oil, flax lignan, or flax fiber) within the past 3 months were excluded from the study. None of the
Baseline characteristics of the subjects
All of the subjects (n = 30) completed the study, but we excluded 6 subjects from the final analysis. Of these 6 subjects, 2 subjects from the 100-mg SDG group and 1 from the placebo group admitted following unhealthy eating habits. In addition, 2 subjects from the 20-mg SDG group and 1 from the placebo group did not regularly consume the test capsules (for >3 days in a row or for 10 days total). Therefore, data pertaining to only 8 individuals from each group were analyzed. The baseline
Discussion
In the present study, we determined the effects of daily intake of flaxseed lignan (SDG) capsules during 12 weeks on hypercholesterolemia and liver disease risk factors in moderately hypercholesterolemic men. We showed that intake of 100 mg of SDG for 12 weeks results in a significant decrease in the ratio of LDL/HDL cholesterol, which is an important predictor of the risk of CVD in moderately hypercholesterolemic men. Although differences were not statistically significant, the changes in
Acknowledgment
The authors thank Medical Informatics Co, Ltd and Syowa Medical Science Co, Ltd for supporting this study.
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