The Functional Nutrients of Flaxseed and Their Effect on Human Health: A Review

Introduction: Humans have consumed flaxseed (Linum usitatissimum) since the earliest times. It has been used as ready-to-eat breakfast cereals, breakfast drinks, salad dressings, porridge, and as beverages. To date, flaxseed is recognized as a functional food in the world’s food market because of its health benefits besides the basic nutrition. Objectives: To review the functional nutrients of flaxseed with their respective health benefits. Methods: Electronic search of Pub Med, Health Inter Network Access to Research Initiative (HINARI), and Google Scholar databases was conducted. Outcomes of interest were the functional nutrients of flaxseed and potential health benefits mainly; antioxidant, free radical scavenging, anticarcinogenic, and anti-hypercolesterolemic. Findings: Majority of the articles reviewed showed that flaxseed contains essential nutrients and non-nutrients such as alpha linolenic acid (ALA), lignans known as secoisolariciresinol diglucoside (SDG), and crude fiber that have important health benefits to humans. Conclusions: Eating flaxseed meal in different forms may have beneficial effect in preventing or reducing various forms of cancer, cardiovascular disease, hypertension, diabetes, constipation, diverticular disease and others. Further studies about the Recommended Daily Intake (RDI) and more in vivo studies to ascertain the health benefits of flaxseed nutrients are recommended. Review Article Ayelign and Alemu; EJNFS, 6(2): 83-92, 2016; Article no.EJNFS.2016.012 84


INTRODUCTION
Flaxseed (Linum usitatisimum) also known as linseed is an ancient crop with a long history of cultivation [1]. It was used for medical purposes in ancient Egypt and Greece, mainly to relieve abdominal pains. Currently, it is cultivated in more than 50 countries, the majority of them in the northern hemisphere. Canada is the main flaxseed producer, followed by China, United States, India and Ethiopia [2]. Its percentage of production by the aforementioned countries in 2004 was 26%, 24%, 14%, 11% and 4% respectively [3]. Ethiopia is the fifth largest producer worldwide and flaxseed is the second oil crop next to Niger seed (Guizotia abyssinica) [4].
Flaxseed has been used as food for centuries in Asia, Europe, and Africa. Some uses of flaxseed for human consumption include ready-to-eat breakfast cereals, breakfast drinks, salad dressings, biscuits, crackers, soups, and cakes. Flaxseed flour is used commercially to make bread in the United States [3]. In Ethiopia, flaxseed is used for food; the seeds are usually roasted, ground, mixed with spices and water, and served with Injera and breads. It is also consumed in the forms of porridge, and beverage called chillika. Limited amounts are also pressed locally for its edible oil [4].
To date, flaxseed is becoming popular as a functional food in the world's food market. Functional foods are inventive and potential products, which can provide health benefits in addition to the basic nutrition [5]. Flaxseed fits this depiction, because it is rich in ALA, phytochemical known as lignan, and crude fiber. Due to their anti-hypercolesterolemic, anticarcinogenic and glucose metabolism controlling effects, these nutrients may prevent or reduce the risk of various chronic diseases like cancer, diabetes, arteriosclerosis, hypertension and others [1,6,7].
The aforementioned chronic diseases have been increased from time to time and affect the majority of our people both in developing and developed countries. Incorporating flaxseed to our daily meal is very important in combating or reducing those chronic diseases. Hence, this review (or manuscript) is essential to provide a complete picture of flaxseed functional nutrients with their health benefits and it is also used as basis for future research.

METHODS
Published results from experimental studies that describe the functional nutrients of flaxseed and having health benefit outcomes were all included to this literature based analysis. Electronic search of Pub Med, Health Inter Network Access to Research Initiative (HINARI), and Google Scholar data bases up to 2014 was conducted. Search was done in key words: "Flaxseed", "Functional food", "Omega-3 fatty acids", "Lignan", and "Crude fiber". Thirty seven full version articles written in English were used.

The Nutritional Profile of Flaxseed
Understanding the nutritional profile of flaxseed helps in recognizing its value in a healthy diet [8]. Flaxseed is a rich source of the ALA, phenolic compound known as lignans and crude fiber. Flaxseed also contains a high content of protein. However, the nutritional composition of flaxseed varies considerably between varieties and environmental conditions. It can also vary on seed processing and method of analysis [8].

Poly Unsaturated Fatty Acids
Flaxseed is rich in polyunsaturated fatty acids (PUFA's), particularly ALA, lower amounts of linoleic acid (LA), and oleic acid. Flaxseed oil has a very high ALA content, six times richer than most fish oils. Fifteen (15 g) of flaxseed oil provides 8 g of ALA, which is converted in the body to Eicosa Pentaenoic Acid (EPA) and then Docosa Hexaenoic Acid (DHA) at efficiency of 5-10% and 2-5%, respectively [9].
In flaxseed, 39 g/100 g of dry matter is oil. Cotyledons are the tissue in which oil is mainly stored, containing ALA, LA and oleic acids. Flaxseed oil is mainly found as triacylglycerol (98%) with lower contents of phospholipids (0.9%) and free fatty acids (0.1%) [10]. Oil extraction yield and fatty acid content vary slightly between authors, and both depend on oil extraction technology [11]. However, ALA is the major fatty acid found in flaxseed oil [12]. Table  1, shows the fatty acid profile for flaxseed oil.

Health Benefits
PUFA's are important for all systems of the body to function properly. Fatty acids from flaxseed oil has been gaining popularity in the health food market because of its reported health benefits and disease preventive properties on coronary heart disease, some kinds of cancer and neurological and hormonal disorders [13].
Certain population studies have shown that a diet rich in ω-3 fatty acids, particularly EPA and DHA found in fish oil or metabolized product of ALA can help to prevent heart disease. In the body, ALA can be converted in to EPA and DHA at a rate of nearly 7 -10 % with the help of enlongase and desaturase enzymes (Fig. 1). EPA and DHA are highly unsaturated fatty acids that play vital roles in fetal development, cardiovascular function, and Alzheimer's disease [14]. Omega-3 fatty acids (ALA, EPA and DHA) have been found to play a role in atherosclerosis and peripheral arterial disease. It is thought that both EPA and DHA improve plaque stability, decrease endothelial activation, and improve vascular permeability, thereby decreasing the chance of experiencing a cardiovascular event [15].
A study by Rodriguez-Leyva et al. reported that, flaxseed ALA has the most potent antihypertensive effects on hypertensive patients [16]. A review article by Caligiuri et al. also reported that, flaxseed is an alternative or complementary strategy for patients who cannot control their blood pressure with medication, or for those who cannot afford to medication, or for those who prefer a dietary approach [17].
Consumption of flaxseed oil has significant effect on slowing bleeding time thereby reducing the risk of myocardial infarction. A randomised controlled study by Oomah and Sitter reported that, consumption of flaxseed oil significantly increased the ALA, EPA and DHA content in red blood cells and in all tissues except brain [18].
Flaxseed has been reported to lower human serum total cholesterol and hepatic fat deposition in both lean and obese rats, and it has also been shown to suppress hypercholesterolemic atherosclerosis. Daleprane JB et al. reported that a diet supplemented with 25% flaxseed was able to improve the lipid profile, body mass, and vasodilator responses of healthy rats [19].
Lilian Thompson's research group at the University of Toronto studied the effects of flaxseed on cancer. In one study, they added the flaxseeds lignan fraction, or the oil to the diet of mice who had previously been administered a chemical carcinogen to induce cancer. All three treatments reduced the established tumor load [20]. More recently Thompson's research group studied mice that were injected with human breast cancer cells. After the injection the mice were fed a basal diet (lab mouse chow) for 8 weeks while the tumors grew. Then one group continued the basal diet and another was fed a 10% flaxseed diet. The flaxseed reduced the tumor growth rate and reduced metastasis by 45% [21].
Epidemiological studies by Sacco and Ward also reported that higher intakes of ALA from flaxseed may support bone health in aging men and women. However, further investigation is needed to determine whether and how flaxseed and its components affect skeletal health during aging [22]. So the Regulation addresses the health benefits of the major components of flaxseed oil, ALA, in relation to brain and neurological development, molecule precursors regulating cell functions, maintenance of normal cardiac function, nutrient tasks and interactions, maintenance of normal blood pressure, and enhancement of mood. For flax, ALA, EU health related claims are depicted in Table 2. In contrast to the potential health benefits, all health claims in EU are not authorised because of non-compliance with the Regulation: on the basis of the scientific evidence assessed, this claimed effect for this food has not been substantiated.
A lignan is a phytoestrogen [25], and it is a diphenolic compound found in most fiber-rich plants, like grains (wheat, barley, and oats); legumes (beans, lentils, and soybeans); and vegetables (garlic, asparagus, broccoli, and carrots) [1]. However, SDG is the major lignans found in plants. Flaxseed is the richest source of SDG, having 7 mg/g. This is 75 to 800 times more SDG than any other foods. Variety, location, and crop year are factors that affect the concentration of flaxseed lignans. Whole seed and ground flaxseed typically contain between 0.7% and 1.9% SDG respectively [1].
The biological activity of lignans is related to their bioactivation in to mammalian lignin (or enterolignan) called enterolactone (ENL) and enterodiol (END) [1,26]. The conversion of lignans in to enterolignans (or its bioavailability) is depending on the presence of gastrointestinal microbiota. Deglucosylation, demethylenation, ring cleavage, demethylation, dehydroxylation and oxidation are the necessary chemical processes required to convert lignans to enterolignan [27].
In the GI tract, the sugar moiety of SDG is hydrolysed with the help of bacteria and release SECO. This is followed by dehydroxylation and demethylation by the colonic microflora to give the mammalian lignan END (Fig. 2)

Health Benefits
The SDG and its metabolites; END & ENL, have been reported to exert protective effects against diet-related chronic diseases through a variety of mechanisms including antioxidant and free radical scavenging activities [31].
Epidemiological evidence indicates that ENL and END may be protective against certain chronic diseases, although discrepancies are observed between "in vivo" and "in vitro" experiments. Thus "in vitro" results often do not match the findings of "in vivo" studies, this could be explained by the low bioavailability of lignans. Furthermore, END and ENL could display antioxidant, oestrogenic and/or anti-oestrogenic activities in addition to the aforementioned health benefits. However, to date, there is no report on recommended daily or minimum daily intake of lignans for disease prevention [27].

Crude Fiber
Flaxseed contains both soluble and insoluble fiber, which is about 28% of the dry weight of flaxseeds [8].

Health Benefits
Traditionally humans have been used flaxseed for the prevention of constipation. Recently, researches indicated that flaxseed fiber has an effect on blood glucose metabolism and hyperlipidemia. The insoluble flaxseed fiber, due to its water binding ability, increases the intestinal bulk which is helpful in the treatment of constipation, irritable bowel syndrome and diverticular disease. While, SFG delays gastric emptying, improves glycemic control, prevents constipation and reduces serum cholesterol [34].

Constipation and crude fiber
Flaxseed mucilage is multi-branched hydrophilic substances, forming viscous solutions that delay gastric emptying and nutrient absorption from the small intestine. That's why; it improves glycemic control in diabetes, and assuages constipation [34].

Serum lipids and crude fiber
Flaxseed mucilage binds bile acids in the intestine to increase the excretion of cholesterol in faeces; hence it decreases blood total cholesterol. Kristensen M et al. reported that consumption of dietary fibers (5 gm) from flaxseeds daily for one week considerably increased fecal excretion of fat and reduced total and LDL-cholesterol markedly [35].
Kristensen M et al. also reported that, giving 5 g of flaxseed gum per day for three months in type 2 diabetics reduced total and LDL cholesterol by 10 and 16% respectively [35]. The probable mechanism of action is through an intrusion with bile acid metabolism. Flaxseed mucilage can hinder micelle formation and thus diminish lipid uptake and inhibit re-uptake of bile acids. Flaxseed mucilage reduces serum cholesterol by causing hepatic synthesis of bile acids which diverts cholesterol away from lipoprotein synthesis in the liver [36].

Cardiovascular diseases and crude fiber
Crude fibers have the tendency to lower blood cholesterol, thus it may shield against coronary heart disease, decreasing hypertension and normalizing blood glucose levels occurring after a meal [37].

Crude fiber and colorectal cancer
A study by Bingham SH et al. showed that total dietary fiber consumption is inversely associated with colorectal cancer risk. Hence, they conclude that doubling of total fiber intake from foods could reduce the risk of colorectal cancer by 40 %. The possible explanation is that, different types of cell walls adsorb a range of carcinogens to different extents. Especially lignin, an important component in flaxseed cell walls, is good adsorbers [38].

CONCLUSION
Due to the presence of functional nutrients; ALA, phytochemicals such as lignans (especially SDG), and crude fiber in flaxseed; flaxseed has additional health benefits beyond the basic nutrition. As a result, it is marked as functional food in different parts of the world. Due to their antioxidant, free radical scavenging, antihypercolesterolemic, and glucose metabolism controlling effects, the aforementioned nutrients may combat or reduce the risk of various important diseases such as cancer, diabetes, hypertension, cardiovascular disease, coronary heart disease, constipation, irritable bowel syndrome, diverticular disease and others.
Although, further studies about the minimum recommended daily intake for all population groups and more in vivo studies are required to ascertain the health benefits of flaxseed nutrients.