Flaxseed- A Shield against Diseases?

We have progressed in the modern world making our lives comfortable with the help of industrialisation, urbanisation, and globalisation, social and economic developments. These plethoras of events have led to rapid alterations in diets and lifestyles like inappropriate diet, poor quality of nutrition, lack of physical activity and much other behaviour known to be detrimental to health. Thus, large population of people have poor health because of the increased incidences of diseases like obesity, metabolic syndrome, diabetes, cardiovascular diseases, polycystic ovarian disease, allergies of different sorts and some types of cancers. Living a healthy life is a challenge for all of us in the modern day world as we are always being threatened by several degenerate lifestyle diseases. Indigenous populations tradionally used natural products to treat a broad range of diseases and ailments [1,2].


Introduction
We have progressed in the modern world making our lives comfortable with the help of industrialisation, urbanisation, and globalisation, social and economic developments. These plethoras of events have led to rapid alterations in diets and lifestyles like inappropriate diet, poor quality of nutrition, lack of physical activity and much other behaviour known to be detrimental to health. Thus, large population of people have poor health because of the increased incidences of diseases like obesity, metabolic syndrome, diabetes, cardiovascular diseases, polycystic ovarian disease, allergies of different sorts and some types of cancers. Living a healthy life is a challenge for all of us in the modern day world as we are always being threatened by several degenerate lifestyle diseases. Indigenous populations tradionally used natural products to treat a broad range of diseases and ailments [1,2].
In recent times, many drug discovery experiments have natural products as their main component and because of their chemical diversity have led the researchers to study plant materials in hope of finding their medicinal properties [3,4]. Our quest for wellness and increasing awareness regarding the role of proper diet has made us search for foods that can work like medicine. The answer to this query is 'Functional foods' or 'neutriceuticals' which are basically foods or dietary compounds which not only provide basic nutrition but may also provide a health benefit .i.e., they give a health punch in addition to their traditional nutrient content [5]. Flaxseed is being labelled as a functional food because of its nutritional composition which has positive effects on disease prevention providing health beneficial components [6]. Canada is the major exporter of flaxseed and flaxseed products, approximately 80% of the global trade [8]. An analysis of brown Canadian flax averaged 41% fat, 20% protein, 28% total dietary fibre, 7.7% moisture and 4% Ash which is the mineral residue left after samples are burned [10,11]. Of all the lipids in flaxseed 53% are a-linolenic acid (ALA), 17% linoleic acid (LA), 19% oleic acid, 3% steric acid and 5% palmitic acid and provides an excellent n-6:n-3 fatty acid ratio of approximately 0.3:1 [12]. The three components of flaxseed which are generally associated with improved cardiovascular health are [13]: The omega-3 polyunsaturated a-linolenic acid (ALA, 20% of dry weight), b.
Researchers are trying to find if omega-3 fatty acid: ALA present in flaxseed, which is one of its richest source [14] may help in protecting against certain infections and in treating diseases like ulcers, migraine headaches, eating disorders, attention deficit/hyperactivity disorders, emphysema, psoriasis, preterm labour, glaucoma, Lyme's disease, lupus and panic attacks [15]. Many studies [16][17][18][19] done over a period of time have gathered data from large populations and reported that ALA levels are inversely correlated with primary cardiovascular events. Omega-3 fatty acids because of their biological effects have become useful in managing chronic conditions such as type-2 diabetes, kidney disease, hypertension, rheumatoid arthritis, stroke, Alzheimer disease, alcoholism and certain types of cancers [20]. After ingestion, ALA is metabolically converted into omega-3 fatty acids, eicosapentaenoic acid (EPA) and decosahexanoic acid (DHA) [15] and multiple clinical trials have demonstrated that the long chain polyunsaturated fatty acids (PUFA), EPA and DHA can reduce the risk of cardiac death [21][22][23]. Fish is one of the sources of ALA but due to limited intake of fish worldwide, plant based PUFA: ALA may be an important alternative source and can be obtained from different types of nuts, seeds and seed oils, mainly flaxseed, walnut, canola oil and soybean oil [15]. Flaxseed is one of the most important oilseed crop because we can almost use plant's every part commercially [8,9].
Dupasquier et al. [24] demonstrated that dietary flaxseed can inhibit atherosclerosis by decreasing the levels of circulating cholesterol and also via its anti-proliferative and anti-inflammatory actions at the cellular level [24]. Increased cardiovascular disease, obesity, diabetes, neurodegenerative declines and cancers are linked with chronic inflammation and oxidative stress [25]. High omega 6/omega 3 ratio in diet has found to promote the pathogenesis of many chronic diseases and increased dietary intake of linoleic acid, an omega-6 fatty acid leads to oxidation of low density lipoproteins (LDL), platelet aggregation and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phospholipids. Omega-3 fatty acids exert strong anti-inflammatory effects by suppressing interleukin 1b, tumour necrosis factor-a and interleukin-6 while omega-6 fatty acids are pro-inflammatory [26,27]. Calguiri et al. [28] in their study on patients of peripheral arterial disease, using 30g of milled flaxseed/day for 6 months reported significant decrease in blood pressure, both systolic as well as diastolic and suggested that this might have occurred via soluble epoxide hydrolase inhibition by ALA of flaxseed, which altered oxylipin concentration.
Flaxseed also has bioactive compound lignin [29,30], the main lignan precursor being secoisosolariciresinol diglucoside (SDG) [31], after ingestion this plant SDG is converted to mammalian lignans by bacteria in the human colon [32]. SDG first undergoes hydrolysis to plant lignan secoisolariciresinol (SECO) which is further converted to enterolignans: enterodiol (ED) and enterolactone (EL), then these metabolites (phytoesterogens) are absorbed and exert their health benefits [33,34]. Thompson et al. [35] in their study on breast cancer patients found that daily intake of 25g of flaxseed significantly decreased cell proliferation, increased apoptosis and affect cell signalling by reducing c-erbB2(HER2) expression and proposed that may be lignans by competing with oestradiol for binding to oestradiol receptors act as anti-oestrogens. The mammalian lignan enterolactone has shown to decrease endogenous oestrogen synthesis by inhibiting aromatase activity [35,36]. Szewczyk et al. [37] used the compounds from the extracts of roots, leaves and stems of flax on the human breast cancer cell lines MCF7 (estrogen receptor positive) and BT20 (estrogen receptor negative) for their phytoestrogenic properties and suggested the role of plant extract for prevention of hormone sensitive carcinoma as they observed significant inhibition of cell vitality and proliferation in the MCF7 cell line.
In a study by Farzana et al. [38] on patients of polycystic ovarian disease(PCOS), supplementation with flaxseed powder, led to significant decrease in ovarian volume, number of follicles and improvement in frequency of menstrual cycles, reasoning it to be due to flaxseed causing reduction in testosterone, circulating oestrogen, luteinising hormone, insulin levels and increased follicle stimulating hormone contributing to follicular maturation and the anti-inflammatory actions to the reduction in ovarian volume. A diet of crushed 40g of flaxseeds was compared with the hormonal therapy for alleviating the menopausal symptoms; it was found to have the same effects but also decreased the glucose and insulin levels [39].
A variety of in-vitro and in-vivo studies have reported that the flaxseed lignan and its mammalian metabolites induce protective effects on many chronic diet related disease through variable mechanisms including phytoestrogenic and antioxidant effects [40][41][42]. Another study concluded that flaxseed plant lignans SDG and SECO are effective against oxidative stress as they exert strong antioxidant effects [33]. The fibre content of flaxseeds is twice that of high fibre beans and varies between 22% to 26% in the form of soluble (mainly mucilage gums) and insoluble (cellulose and lignins) dietary fibres in proportion varying between 20:80 and 40:60 [33,43,44]. It was found that flaxseed dietary fibres have a role in regulating the body weight by suppressing hunger and nutrient absorption, as the gel formed by them when mixed with water delays gastric emptying and decreases blood glucose level [34,45]. It also lowers cholesterol, as the gel surrounds it and doesn't let it to be absorbed and favours its faecal excretion34. Thakur et al. [46] advised the use of flaxseed mucilage in combination with other mucilage providing added benefits for controlling Type 2 Diabetes Mellitus because when they used flaxseed mucilage to reduce the clinical symptoms of diabetes mellitus associated with lipidaemia there was decrease in fasting blood sugar, total cholesterol and LDL. In their study Kristensen et al. [45] found that both flax drink and flax bread reduced plasma total cholesterol, LDL, and increased fat excretion, so they opinioned that viscous flaxseed dietary fibres may be useful for lowering blood cholesterol and potentially play a role in energy balance.
When 55 hypercholesterolemic subjects were given 300/60mg/d of dietary SDG from flaxseed extract for 8 weeks, it significantly decreased total cholesterol, LDL-cholesterol and glucose concentrations in a dose dependent manner [47]. Flaxseed supplementation in postmenopausal women reduced serum total cholesterol, LDL cholesterol, triglycerides, apolipoproteinA-1 and apolipoprotein B concentrations the known risk factors of coronary heart disease [48]. Ingestion of flaxseed in hypertensive individuals produced significant reduction in blood pressure: both systolic and diastolic, with circulating a-linolenic acid levels correlating with systolic and diastolic blood pressures and lignan levels with changes in diastolic blood pressure [49]. Cassani et al. [50] found improvement in the blood levels of total cholesterol, LDL, uric acid, and adiponectin associated with weight loss, decreased systolic blood pressure and also reduction in inflammatory markers: C-reactive proteins (CRP) and tumour necrosis factor-F-) and were in favour of adding flaxseed to a weight loss diet as an important tool to reduce the inflammatory markers CRP and TNF-a. Flaxseed intake decreased fasting glucose with increased insulin sensitivity in overweight or obese individuals with pre-diabetes but with no significant effect on fructosamine, CRP, adiponectin and Interleukin-6(IL-6) [51].
Flax is low in carbohydrates (sugars and starches) so can be advised to persons' with specific diseases as it provides only 1g/100g contributing very little to total carbohydrate intake [34]. If we compare the amino acid pattern of flax protein with that of soybean which is considered as one of the most nutritious of the plant protein it is the same [52] and is rich in essential amino acids that are required for protein synthesis that have their role in maintenance and repair of cells, tissues and organs [34]. Calmodulin is a co-factor involved in the production of nitric oxide responsible for several neurodegenerative diseases and flaxseed protein hydrolysate induces a change in calmodulin's secondary and tertiary structures [53]. It also inhibits angiotensin converting enzyme thus reducing angiotensin a vasoconstrictor which causes an increase in blood pressure [54]. Protein in flaxseed meal was observed to be more effective in reducing proteinuria and renal histologic abnormalities than soyprotein [55].
It has been found that 30g portion of the flaxseed constitutes 7% to 30% of the Recommended Dietary Allowances (RDA) for calcium, magnesium and phosphorous [11]. When its potassium content is compared with the recommended sources such as banana, its high [56] and high potassium intake has seen to be inversely associated with stroke incidences, platelet aggregation [57].

Conclusion and Recommendation
Modernisation along with making our lives comfortable has pushed us into a web of modern diseases like obesity, metabolic syndrome, diabetes, cardiovascular diseases, polycystic ovarian disease, allergies of different sorts and some type of cancers. Recent scientific research works have suggested that adding a functional food as a dietary modification can be one of the lifestyle modifications and play an important role in preventing and protecting us against these chronic diseases. Insight into multiple in-vitro and in-vivo research studies and data on flaxseed give us strong indication that flaxseed is one of the richest source of a-linoleinic acid and lignan in addition to being rich in dietary fibre. Flaxseed as one of the functional foods can act as protective shield to combat this variety of diseases. It being a good source of ALA can easily replace the fish and other marine sources of ALA whose use is limited worldwide. People should be educated about the health benefits of flaxseed and encouraged to incorporate it in their diet as a supplement in different forms.