Flax Lignan Complex Research Articles

Flaxseed and Its Components in Treatment of Hyperlipidemia and Cardiovascular Disease.

This paper describes the effects of flaxseed and its components (flax oil, secoisolariciresinoldiglucoside[SDG], flax lignan complex [FLC], and flax fibers] on serum lipids (total cholesterol [TC], low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]) in animals and humans. Ordinary flaxseed reduces TG, TC, LDL-C, and TC/HDL-C levels in a dose-dependent manner in animals. In humans, it reduces serum lipids in hypercholesterolemicpatients but has no effects in normocholesterolemicpatients. Flax oil has variable effects on serum lipids in normo- and hypercholesterolemic animals. Flax oil treatment, with a dosage containing greater than 25 g/day of α-linolenic acid, reduces serum lipids in humans. Although FLC reduces serum lipids and raises serum HDL-C in animals, its effects on serum lipids in humans are small and variable. Flax fibers exert small effects on serum lipids in humans. Crop Development Centre (CDC)-flaxseed, which contains low concentrations of α-linolenic acid, has significant lipid lowering effects in animals. Pure SDG has potent hypolipidemic effects and raises HDL-C. In conclusion, flaxseed and pure SDG have significant lipid-lowering effects in animals and humans, while other components of flaxseed have small and variable effects.

Importance of Flaxseed and its Components in the Management of Hypertension.

This review paper describes the effects of flaxseed and its components (flax oil, secoisolariciresinol diglucoside [SDG], flax lignan complex [FLC], and flaxseed protein hydrolysate [FPH]) on blood pressure (BP) in Sprague Dawley rats (SDR), spontaneously hypertensive rats (SHR), and humans. Flaxseed, flax oil, and FLC had variable effects on BP in humans, while SDG and FPH significantly reduced the BP in SDR and SHR. The effect of SDG was dose-dependent and long lasting. The lowering of BP is mediated through inhibition of soluble epoxide by α -linolenic acid in flax oil, stimulation of guanylate cyclase and inhibition of angiotensin converting enzyme (ACE) by SDG, and inhibition of renin and ACE activity by FPH. Flaxseed, flax oil, and FLC have variable effects on BP (none, slight, and significant). They are effective in lowering BP in individuals with hypertension and metabolic syndrome but ineffective in healthy individuals' ineffectiveness of flaxseed and its compounds in lowering BP may be due to their low doses, long interval of dosing, short duration of consumption, and patient status. In conclusion, the data at present suggest that flaxseed, flax oil, and FLC cannot serve as therapeutic agents for the treatment of hypertension. However, they can be used as an adjunct in the treatment of hypertension. A clinical trial should be conducted of these agents with higher doses which would be given twice daily for long duration. Pure SDG and FPS may serve as therapeutic agents for the treatment of hypertension but they have not been tried in humans.

Flaxseed and Diabetes.

Flaxseed contains 32% to 45% of its mass as oil of which 51% to 55% is α-linolenic acid. Flax lignan complex and secoisolariciresinol diglucoside (SDG) have been isolated from flaxseed. Flaxseed and its components have antioxidant, hypolipidemic and hypoglycemic effects. These are mostly due to the SDG content. Oxidative stress has been implicated in both type 1 and type 2 diabetes. Flaxseed, flaxseed oil and flax lignan complex have not been investigated as to whether they reduce the incidence of diabetes and/or delay the development of diabetes. However, their effects on serum glucose have been studied. Flaxseed and flax lignan complex improve glycemic control. Animal models of type I diabetes involving streptozotocin administration or utilizing Bio-Breed diabetic (BBdp) prone rats are associated with oxidative stress. SDG treatment reduced the incidence of diabetes using serum glucose levels by 75% in the streptozotocin model of diabetes and by 72% in the BBdp rat model of diabetes. These reductions in development of diabetes were associated with decreases in oxidative stress measured by serum and pancreatic malondialdehyde (MDA). SDG delays the development of diabetes in Zucker diabetic fatty (ZDF) rat model of type 2 diabetes and this effect was associated with a reduction in serum MDA and glycated haemoglobin A1C. The data suggest that SDG may have a great potential for reducing the incidence of type 1 diabetes and delaying the development of type 2 diabetes in humans.

Prevention and treatment of atherosclerosis with flaxseed-derived compound secoisolariciresinol diglucoside.

Atherosclerosis is the primary cause of coronary artery disease, heart attack, strokes, and peripheral vascular disease. Alternative/complimentary medicines, although are unacceptable by medical community, may be of great help in suppression, slowing of progression and regression of atherosclerosis. Numerous natural products are in use for therapy in spite of lack of evidence. This paper discusses the basic mechanism of atherosclerosis, risk factors for atherosclerosis, and prevention, slowing of progression and regression of atherosclerosis with flaxseed-derived secoisolariciresinol diglucoside (SDG). SDG content of flaxseed varies from 6mg/g to 18 mg/g. Flaxseed is the richest source of SDG. SDG possesses antioxidant, antihypertensive, antidiabetic, hypolipidemic, anti-inflammatory and antiatherogenic activities. SDG content of some commonly used food has been described. SDG in very low dose (15 mg/ kg) suppressed the development of hypercholesterolemic atherosclerosis by 73 % and this effect was associated with reduction in serum total cholesterol, LDL-C, and oxidative stress, and an increase in the levels HDL-C. A summary of the effects of flaxseed and its components on hypercholesterolemic atherosclerosis has been provided. Reduction in hypercholesterolemic atherosclerosis by flaxseed, CDC-flaxseed, flaxseed oil, flax lignan complex and SDG are 46 %, 69 %, 0 %, 34 % and 73 % respectively in dietary cholesterol -induced rabbit model of atherosclerosis. SDG slows the progression of atherosclerosis in animal model. Long-term use of SDG regresses hypercholesterolemic atherosclerosis. It is interesting that regular diet following high cholesterol diet accelerates in this animal model of atherosclerosis. In conclusion SDG suppresses, slow the progression and regresses the atherosclerosis. It could serve as an alternative medicine for the prevention, slowing of progression and regression of atherosclerosis and hence for the treatment of coronary artery disease, stroke and peripheral arterial vascular diseases.

Natural Products in Regression and Slowing of Progression of Atherosclerosis

Many natural products, including vitamin E, garlic, purpurogallin, flaxseed and its components [secoisolariciresinol diglucoside (SDG) and flax lignan complex (FLC)] and resveratrol have been reported to suppress hypercholesterolemic atherosclerosis. It is known that all of the drugs that suppress the development of atherosclerosis do not regress and/or slow the progression of atherosclerosis. To be of potential benefit in patients with established atherosclerosis, a drug should produce regression and/or slow the progression of atherosclerosis. In this review, the effects of vitamin E, SDG and FLC in the regression and slowing of progression of hypercholesterolemic atherosclerosis and their mechanisms have been described. The effectiveness of vitamin E in patients with established coronary disease is very controversial. However, in experimental animal controlled studies, vitamin E does not regress or slow the progression of hypercholesterolemic atherosclerosis. The mechanisms of the ineffectiveness of vitamin E in regression and slowing of progression of atherosclerosis have been discussed. SDG is effective in slowing the progression of atherosclerosis and partially effective in regression of hypercholesterolemic atherosclerosis. These effects are associated with reduction in oxidative stress. FLC does not regress hypercholesterolemic atherosclerosis but slows the progression of hypercholesterolemic atherosclerosis. Slowing of progression is associated with reduction on oxidative stress. In conclusion, vitamin E does not regress or slow the progression of established atherosclerosis. SDG slows the progression and regresses established atherosclerosis. FLC does not regress but slows the progression of established atherosclerosis.

Flaxseed and Cardiovascular Health

Flaxseed and its components may improve cardiovascular health because of their numerous attributes. Flaxseed contains 35% of its mass as oil, of which 55% is alpha-linolenic acid (ALA). Flax meal, which is devoid of oil, contains the lignan secoisolariciresinol diglucoside (SDG). Flaxseed, flaxseed with very low ALA, flaxseed oil, flax lignan complex (FLC), and SDG reduce the development of hypercholesterolemic atherosclerosis by 46%, 69%, 0%, 73%, and 34%, respectively, in the rabbit model. FLC and SDG slow the progression of atherosclerosis but have no effect in regression of atherosclerosis. Suppression of atherosclerosis by flaxseed is the result of its lignan content and not the result of ALA content. Suppression of atherosclerosis is associated with lowering of serum lipids and antioxidant activity. Effects of flaxseed on serum lipids in experimental animals are variable from no change to slight reduction. Flaxseed oil does not affect serum lipids, except for a slight reduction in serum triglycerides. Lignan in general reduces serum total cholesterol and low-density lipoprotein cholesterol and raises serum high-density lipoprotein cholesterol. SDG and its metabolites have antioxidant activity. Flaxseed and flaxseed oil do not have antioxidant activity except they suppress oxygen radical production by white blood cells. Flaxseed oil/ALA has variable effects on inflammatory mediators/markers (interleukin [IL]-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, interferon-gamma, C-reactive protein, and serum amyloid A). Doses of ALA less than 14 g/d do not affect inflammatory mediators/markers, but 14 g/d or greater reduce inflammatory mediators/markers. Flaxseed oil decreases soluble vascular cell adhesion molecule-1 but has no effect on soluble intracellular adhesion molecule-1, soluble E-selectin, and monocyte colony-stimulating factor. Flaxseed has variable effects on IL-6, high-sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1. FLC reduces plasma levels of C-reactive protein but has no effects on IL-6, tumor necrosis factor-alpha, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, or monocyte chemoattractant protein. Flaxseed has a very small hypotensive effect, but flaxseed oil does not lower blood pressure. However, SDG is a very potent hypotensive agent. Flaxseed oil decreases platelet aggregation and increases platelet activating inhibitor-1 and bleeding time. Flaxseed and FLC have no effect on the hemopoietic system. SDG is a potent angiogenic and antiapoptotic agent that may have a role in cardioprotection in ischemic heart disease. In conclusion, flaxseed, FLC, and SDG, but not flaxseed oil, suppress atherosclerosis, and FLC and SDG slow progression of atherosclerosis but have no effect on regression. Flaxseed oil suppresses oxygen radical production by white blood cells, prolongs bleeding time, and in higher doses suppresses serum levels of inflammatory mediators and does not lower serum lipids.

Flax Lignan Complex Slows Down the Progression of Atherosclerosis in Hyperlipidemic Rabbits

Flax lignan complex suppresses the development of hypercholesterolemic atherosclerosis. However, it is not known whether flax lignan complex would slow down the progression of hypercholesterolemic atherosclerosis. This study was carried out to determine whether flax lignan complex slows down the progression of already developed atherosclerosis, and whether this effect is associated with reductions in serum lipids and oxidative stress. The studies were conducted in 4 groups of rabbits: group I, regular diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (4 months); group IV, 0.25% cholesterol diet (2 months) followed by 0.25% cholesterol diet plus flax lignan complex (2 months). Serum lipids and oxidative stress parameters (malondialdehyde, antioxidant reserve, white blood cell chemiluminescence) were measured before and at monthly intervals thereafter on their respective diets. Aortas were removed at the end of the protocol for assessment of atherosclerosis and oxidative stress. Atherosclerosis in group II was associated with hyperlipidemia and increased oxidative stress. Significant areas of the aortic intimal surfaces from group II (37.76% + 7.96%), group III (76.6% + 9.04%), and group IV (52.95% + 10.29%) were covered with atherosclerotic plaques. Group IV rabbits had 40% more atherosclerotic lesions than group II but 31% fewer lesions than group III. The flax lignan complex-induced reduction in the progression of atherosclerosis was associated with reductions in oxidative stress. In conclusion, flax lignan complex was effective in slowing down the progression of atherosclerosis by 31%, and this effect was associated with a reduction in oxidative stress.

Serum biochemical changes in rabbits on a regular diet with and without flax lignan complex following a high-cholesterol diet

Flax lignan complex (FLC) isolated from flaxseed suppresses development of hypercholesterolemic atherosclerosis. It does not produce regression of atherosclerosis, but prevents its regular diet-induced acceleration following a high-cholesterol diet. It is not known if replacement of a high-cholesterol diet with a regular diet has deleterious effects on body organs. To determine if short-term use of a high-cholesterol diet, and a regular diet with or without FLC following the high-cholesterol diet, have any adverse effects on serum electrolytes, glucose and enzymes related to the liver, kidneys, skeletal muscle and intestines. Blood samples were collected from the rabbits before and at various intervals during the high-cholesterol diet, and while on the regular diet with or without FLC, following the high-cholesterol diet. Measurements of serum total cholesterol, glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), albumin, creatinine, electrolytes (sodium [Na], potassium [K], chloride [Cl]) and carbon dioxide (CO(2)) were taken. The high-cholesterol diet produced hypercholesterolemia, which was associated with reductions in serum glucose and no significant changes in serum Na, K, Cl, CO(2), ALT, ALP, AST, GGT, albumin or creatinine. Regular diet with or without FLC, following the high-cholesterol diet, reduced serum total cholesterol and glucose, increased serum Na, Cl and creatinine, but produced no significant alterations in serum K, CO(2), ALT, AST, GGT or albumin. FLC reduced serum ALP, but regular diet produced no significant change. Short-term use of a high-cholesterol diet, or a regular diet with or without FLC following the high-cholesterol diet, does not produce deleterious effects in the liver, kidneys, skeletal muscle, intestine or bone, as shown by changes in serum electrolytes, glucose and enzymes.

A Study on Regression of Hypercholesterolemic Atherosclerosis in Rabbits by Flax Lignan Complex

Flax lignan complex (FLC) isolated from flaxseed suppresses the development of hypercholesterolemic atherosclerosis. The objectives of this study were to investigate if FLC produces regression of atherosclerosis and if regression is associated with reductions in serum lipids and oxidative stress. The studies were conducted in 4 groups of rabbits: group I, control diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (2 months) followed by regular diet (4 months); and group IV, 0.25% cholesterol diet (2 months) followed by regular diet and FLC (4 months). Serum lipids and oxidative stress parameters were measured before and at various intervals thereafter on their respective diets. The aortas were removed at the end of the protocol for assessment of atherosclerotic plaques and oxidative parameters. Atherosclerosis in group II was associated with hyperlipidemia and increased oxidative stress. Atherosclerotic changes were accelerated in group III, and this was associated with reductions in serum lipids and oxidative stress. Atherosclerotic lesions in group IV were similar to group II, but significantly smaller than those in group III, and were associated with reductions in serum lipids and oxidative stress similar to that in group III. These results indicate that FLC does not produce regression but prevents the acceleration of atherosclerosis due to the removal of cholesterol in the diet. These effects of FLC are not associated with reductions in serum lipids and oxidative stress.

Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed

Hypercholesterolemia, low HDL-C and oxygen radicals have been implicated in the development of atherosclerosis. Lignan complex isolated from flaxseed contains secoisolariciresinol diglucoside (SDG), 3-hydroxy-3methylglutaric acid (HMGA) and cinnamic acids. SDG and cinnamic acids are antioxidants, and HMGA is a hypocholesterolemic agent. Antioxidants are known to reduce hypercholesterolemic atherosclerosis. The objectives of this study were to determine if lignan complex reduces (i) serum cholesterol, (ii) oxidative stress, and (iii) atherosclerosis in hypercholesterolemic rabbits. Rabbits were assigned to four groups: Group I, control; Group II, lignan complex control (lignan complex, 40 mg/kg body weight daily orally); Group III, 0.5% cholesterol; Group IV, 0.5% cholesterol diet + lignan complex, (40 mg/kg body weight daily orally). Blood samples were collected before (time 0) and after 1 and 2 months of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and serum malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for measurement of atherosclerotic plaques, MDA and aortic tissue chemiluminescence (Aortic CL), a marker of antioxidant reserve. Rabbits in Group III developed atherosclerosis (50.84 ± 6.23% of the intimal surface of the aorta was covered with atherosclerotic changes) which was associated with an increase in the serum TG, TC, LDL-C, HDL-C, MDA and aortic MDA and antioxidant reserve. Lignan complex reduced the development of atherosclerosis by 34.37% and this was associated with a decrease in serum TC by 20%, LDL-C by 14%, TC/HDL-C by 34%, serum MDA by 35% and aortic MDA by 58%. Serum HDL-C was elevated by 30% in hypercholesterolemic rabbits and by 25% in normocholesterolemic rabbits with lignan complex. Lignan complex did not affect the TC and LDL-C and serum MDA in the normocholesterolemic rabbits. However, it increased the aortic MDA in the normocholesterolemic rabbits. These results suggest that lignan complex isolated from flaxseed reduced the extent of hypercholesterolemic atherosclerosis and this effect was associated with marked decreases in oxidative stress, serum total cholesterol, LDL-C and risk ratio, and elevation of serum HDL-C. Lignan complex may, therefore, be beneficial in preventing atherosclerosis, and reducing risk factors for coronary artery disease and stroke.