A Review on Flax Seed: A Legume for Longevity

Abstract

Flax seed, tiny packs of nutrients supply a wealth of health benefits. Dietary flaxseed has an amazing use in a different health conditions. Research evidences on the properties of dietary flaxseed have wide spread information. It has been found that the tiny, edible seeds of the flax plant, have gained superfood status because of its therapeutic values in preventing the diseases. From the past few years, there is growing evidences that the people have become more health conscious. Many trials have been conducted with the upgraded standards of control available in order to provide consistent information on its significance to the general community. The purpose of this review is to provide a comprehensive summary of the research that have reinforced the growth of flaxseed as a commodity with importance in the health and medicine fields. Flaxseed is emerging as a vital functional food element because of its rich contents of α- linolenic acid (ALA, omega-3 fatty acid), lignans, and fiber. Flax lignans have potential health benefits such as in reduction of cardiovascular disease, cancer, atherosclerosis, diabetes, arthritis, osteoporosis, autoimmune and neurological disorders. The role of the Flax protein in the prevention and treatment of heart disease and in supporting the immune system has been proven. The present review focuses on the evidences of the potential health benefits of flaxseed through human and animals. Its role in enhancing the longevity by alleviating the common health challenges like hypertension, cancer and diabetes.

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*Corresponding author: E-mail: kinjalpatel54@gmail.com;
Journal of Pharmaceutical Research International
33(39A): 107-122, 2021; Article no.JPRI.71488
ISSN: 2456-9119
(Past name: British Journal of Pharmaceutical Research, Past ISSN: 2231-2919,
NLM ID: 101631759)
A Review on Flax Seed: A Legume for Longevity
Kinjal P. Patel
1*
, Shivkant Patel
1
, Dillip Kumar Dash
1
,
Ramachandran Balaraman
1
and Rajesh A. Maheshwari
1
1
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Waghodia,
Vadodara-391760, Gujarat, India.
Authors’ contributions
This work was carried out in collaboration among all authors. All authors read and approved the final
manuscript.
Article Information
DOI: 10.9734/JPRI/2021/v33i39A32148
Editor(s):
(1) Dr. Juan Carlos Troiano, University of Buenos Aires, Argentina.
Reviewers:
(1) Dusan Surdilovic, Gulf Medical University, UAE.
(2) Mohammad Daud Ali, Mohammed Al-Mana College for Medical Sciences, Saudi Arabia.
Complete Peer review History:
https://www.sdiarticle4.com/review-history/71488
Received 20 May 2021
Accepted 26 July 2021
Published 29 July 2021
ABSTRACT
Flax seed, tiny packs of nutrients supply a wealth of health benefits. Dietary flaxseed has an
amazing use in a different health conditions. Research evidences on the properties of dietary
flaxseed have wide spread information. It has been found that the tiny, edible seeds of the flax
plant, have gained superfood status because of its therapeutic values in preventing the diseases.
From the past few years, there is growing evidences that the people have become more health
conscious. Many trials have been conducted with the upgraded standards of control available in
order to provide consistent information on its significance to the general community. The purpose of
this review is to provide a comprehensive summary of the research that have reinforced the growth
of flaxseed as a commodity with importance in the health and medicine fields. Flaxseed is
emerging as a vital functional food element because of its rich contents of α- linolenic acid (ALA,
omega-3 fatty acid), lignans, and fiber. Flax lignans have potential health benefits such as in
reduction of cardiovascular disease, cancer, atherosclerosis, diabetes, arthritis, osteoporosis,
autoimmune and neurological disorders. The role of the Flax protein in the prevention and
treatment of heart disease and in supporting the immune system has been proven. The present
review focuses on the evidences of the potential health benefits of flaxseed through human and
animals. Its role in enhancing the longevity by alleviating the common health challenges like
hypertension, cancer and diabetes.
Review Article

Patel et al.; JPRI, 33(39A): 107-122, 2021; Article no.JPRI.71488
108
Keywords: Flax seed; lignans; α- linolenic acid; cardiovascular disease; atherosclerosis; diabetes;
cancer; arthritis.
ABBREVIATIONS
ALA: α- linolenic acid; B.C: before Christ; A.D: Anno Domini; pH: Power of hydronium; FS: Flax seed;
PUFAs: Poly Unsaturated Fatty Acids; EPA: eicosapentaenoic acid ; DHA: docosahexaenoic acid; LA:
linoleic acid; EL: enterolactone; ED: enterodiol; SECO: secoisolariciresinol; p-CA P-coumaric; FA:
ferulic acid; SDG: secoisolariciresinol diglucoside; HTN: Hypertension; JNC-7: Joint National
Committee 7; ACE: angiotensin-converting enzyme; CHD: Coronary Heart Disease; CAM:
complementary and/or alternative medicine; LOBs: Linoorbitides; p-AKT: protein kinase B, p-JNK: c-
Jun N-terminal kinase; p ERK extracellular signal-regulated kinase; MAPK: mitogen-activated protein
kinase; CRC: colorectal cancer; BMI: Body mass index; CFA: Complete Freund's adjuvant; PGE
2
:
Prostaglandin E
2
; LTB
4
:
leukotriene B
4
; WC: Waist circumference; TNF: Tumor necrosis factor; IL:
Inter leukin; COPD: chronic obstructive pulmonary disease; SOD: superoxide dismutase; CAT:
catalase; GSH: glutathione peroxidase; MDA: Malondialdehyde; NO: Nitrous oxide.
1. INTRODUCTION
In this modern period, one of the major obstacles
that current living faces is excellent health, as
individuals are suffering from a variety of
degenerative lifestyle disorders. Foods that can
act as medicine have sparked attention as
people become more sensible of the importance
of diet and their desire for wellness. With rapid
changes in lifestyle and a growing awareness of
the negative consequences of excessive
consumption, the scientists and health
professionals are exploring the plant products.
The focus has switched from chemical-based
therapy to natural-based therapy in the
management of ailments. The focus is on
extracting the functional dietary components of
plants and seeds that were found in ancient
nature [1]. In recent years, as empirical evidence
on their safety and usefulness has become
increasingly available, herbal (plant) treatments
have aroused the curiosity of researchers. As a
result, new terminology for herbal medicines is
emerging in the scientific community, such as
phytotherapy, phytomedicine, phytoneering, and
nutraceuticals. Flaxseed has been used in both
nutrition and medicine. Flaxseeds have a wide
range of nutritional properties that are
encouraging health professionals and
nutritionists to use them in the development of
functional meals and the selection of a healthy
diet [2].
Flax seed has been used from ancient
civilizations and cultures. According to
archaeological evidence, flax seeds have been
used from the time of Nefertiti in Egypt. Flax, also
known in India as "Tisi" or "Alsi," was utilised to
supplement the food of the hardworking villagers.
Flaxseed is an key oilseed crop for industrial,
food, feed, and fibre production [3]. Almost every
portion of the flaxseed plant is commercially
useful, whether raw or processed. The stem
produces high-quality fibre that is both strong
and long-lasting. Linum usitatissimum Linn is the
scientific name for flax. Katan (Linum
usitatissimum Linn.) is an annual or biennial herb
in the Linaceae family that grows to be
approximately 2 feet tall. It likely was first grown
in Egypt but has been cultivated all around the
world. The flax plant can be woven into linen, its
fibers are two to three times as strong as cotton!
[4-7].
This blue-flowered crop is greatly adaptable. The
fact that different portions of the plant have
unique economic purposes demonstrates the
value of L. usitatissimum as a multipurpose crop.
Brown flaxseeds and golden (or yellow)
flaxseeds are the two most common types (Fig.
1). Both have a comparable nutritional profile and
the same quantity of short-chain-3 fatty acids.
Whole flaxseed, ground flaxseed, flaxseed oil,
and partially defatted flaxseed meal are the four
most frequent types of flaxseed for human
consumption. Flax "milk" is a brand-new product
on the market. Flax milk is a great alternative to
dairy milk because it is cholesterol-free and
lactose-free. It's suitable for anyone with soy,
gluten or nut allergies, and it is better than
almond milk in the health benefits features [5].
Oil is extracted from flaxseeds to produce
flaxseed oil. To extract the liquid from flaxseed, it
is ground and then pressed with an oil press.
Even though flaxseed oil has a high
concentration of ALA, some of the other nutrients
contained in ground flaxseed may not make it
into the oil version after processing. Small, nutty,
and crunchy seeds have recently garnered
superfood notoriety, they are one of the oldest

crops, having been farmed since the dawn of
civilization.
Fig. 1. Brown flaxseed
Flaxseeds are obtainable in two forms: whole or
ground. Both kinds have their own set of
advantages [5]. As flaxseeds can be tough to
chew, grinding them before eating ,can help to
improve its digestion. Pre-
ground flaxseed have
a lower shelf life than who
le flaxseeds. Flaxseed
is a plant-
based food that is high in fibre,
antioxidants, and omega-
3 fatty acids. Some
refer to it as "functional food," indicating that it
can be consumed to improve one's health.
Furthermore, flaxseed has been described as
havin
g a “nice nutty fragrance and aroma”,
making it potentially suitable for use in a variety
of meals [4]. Flaxseed has been successfully
included into snack bars, muffins, bagels, bread,
buns, tea biscuits, cinnamon rolls, and pasta in
tests,Volume of flaxse
ed in the diet can affect the
flavour of food. Before baking, flaxseed was
incorporated into foods for human consumption
at concentrations of 5–
28% of total components
(by weight). Intake of daily flaxseed can be as
high as 40 to 50 g [6-10].
2. HISTORY
Ayurveda is a very old and still alive tradition that
is widely practised in India, Sri Lanka, and
different nations and has a decent philosophical
and experimental foundation. Flaxseed oil is said
to help with mental and physical endurance by
combating f
atigue and slowing down the ageing
process. Hippocrates, the father of medicine,
advised flax for the alleviation of abdominal pains
around 650 B.C., around the same time
Theophrastus suggested flax mucilage as a
cough remedy. Hildegard von Bingen, in the
century A.D., utilised flax meal in hot compresses
to cure both exterior and internal diseases [3,11].
Patel et al.; JPRI, 33(39A): 107-122, 2021
; Article no.
109
crops, having been farmed since the dawn of
[8]
Flaxseeds are obtainable in two forms: whole or
ground. Both kinds have their own set of
advantages [5]. As flaxseeds can be tough to
chew, grinding them before eating ,can help to
ground flaxseed have
le flaxseeds. Flaxseed
based food that is high in fibre,
3 fatty acids. Some
refer to it as "functional food," indicating that it
can be consumed to improve one's health.
Furthermore, flaxseed has been described as
g a “nice nutty fragrance and aroma”,
making it potentially suitable for use in a variety
of meals [4]. Flaxseed has been successfully
included into snack bars, muffins, bagels, bread,
buns, tea biscuits, cinnamon rolls, and pasta in
ed in the diet can affect the
flavour of food. Before baking, flaxseed was
incorporated into foods for human consumption
28% of total components
(by weight). Intake of daily flaxseed can be as
Ayurveda is a very old and still alive tradition that
is widely practised in India, Sri Lanka, and
different nations and has a decent philosophical
and experimental foundation. Flaxseed oil is said
to help with mental and physical endurance by
atigue and slowing down the ageing
process. Hippocrates, the father of medicine,
advised flax for the alleviation of abdominal pains
around 650 B.C., around the same time
Theophrastus suggested flax mucilage as a
cough remedy. Hildegard von Bingen, in the
15th
century A.D., utilised flax meal in hot compresses
to cure both exterior and internal diseases [3,11].
3. PLANT MORPHOLOGY
The plant's root is made up of absorbent tissue
that allows it to store all of the water obtained by
the fine rootlets that protrude in all directions and
at various depths. Flax fibres are discovered
inside the plant as individually separated
filaments of
various lengths that vary depending
on the leaf’s height on the stem of the plant. The
yield of flax straw and fibres is maximum in the
yellow maturity stage. Individual flax fibres are
isolated in the plant, yet they are organised in
bundles that are ent
irely and firmly enclosed by
the holding tissue. Stem bends in all directions,
the smooth glossy surfaces let them to
effortlessly slide on one other [12,13,14].
4. BIO-
CHEMICAL CONSTITUENT OF
FLAX SEED
4.1 Fiber
Whole FS (flax seed) has a whole fibre c
roughly 28%. Insoluble fibres in FS include
cellulose, hemicellulose, and lignans, while
soluble fibres in the form of mucilage gums make
up about a third of the fibre [5,15,16]. Because
mucilage is found mostly in the epidermis of the
seed coat,
removing the seed coat removes a
large portion of the soluble fibre in FS.
Commercially available fibre supplements
produced from FS currently include both soluble
and insoluble fibres [17].
Flax is low in carbohydrates (sugars and
starches), providing
only 1 gram (g) per 100 g.
Flaxseed polysaccharideis composed of two
major fractions: 3/4
th
of a neutral arabinoxylan
and 1/4
th
of an acidic rhamnogalacturonan. The
arabinoxylan is composed primarily of xylose,
arabinose, and galactose and the L
D-galactose, D-
galacturonic and L
are the part of rhamnogalacturonan.Significant
variations has been observed in monosaccharide
composition, carbohydrate yield and quality
among accessions from the different part of
world collection of flaxseed [17].
4.2 Protein
Flaxseed grain and paste contain roughly 21%
and 34% protein, respectively. Genetic and
environmental variables can affect the protein
level in flaxseed. Seeds grown in cool areas
have a more oil and a low protein content.
Flaxseed ha
s two main storage proteins: a salt
; Article no.
JPRI.71488
The plant's root is made up of absorbent tissue
that allows it to store all of the water obtained by
the fine rootlets that protrude in all directions and
at various depths. Flax fibres are discovered
inside the plant as individually separated
various lengths that vary depending
on the leaf’s height on the stem of the plant. The
yield of flax straw and fibres is maximum in the
yellow maturity stage. Individual flax fibres are
isolated in the plant, yet they are organised in
irely and firmly enclosed by
the holding tissue. Stem bends in all directions,
the smooth glossy surfaces let them to
effortlessly slide on one other [12,13,14].
CHEMICAL CONSTITUENT OF
Whole FS (flax seed) has a whole fibre c
ontent of
roughly 28%. Insoluble fibres in FS include
cellulose, hemicellulose, and lignans, while
soluble fibres in the form of mucilage gums make
up about a third of the fibre [5,15,16]. Because
mucilage is found mostly in the epidermis of the
removing the seed coat removes a
large portion of the soluble fibre in FS.
Commercially available fibre supplements
produced from FS currently include both soluble
Flax is low in carbohydrates (sugars and
only 1 gram (g) per 100 g.
Flaxseed polysaccharideis composed of two
of a neutral arabinoxylan
of an acidic rhamnogalacturonan. The
arabinoxylan is composed primarily of xylose,
arabinose, and galactose and the L
-rhamnose,
galacturonic and L
-fructose acid
are the part of rhamnogalacturonan.Significant
variations has been observed in monosaccharide
composition, carbohydrate yield and quality
among accessions from the different part of
Flaxseed grain and paste contain roughly 21%
and 34% protein, respectively. Genetic and
environmental variables can affect the protein
level in flaxseed. Seeds grown in cool areas
have a more oil and a low protein content.
s two main storage proteins: a salt

Patel et al.; JPRI, 33(39A): 107-122, 2021; Article no.JPRI.71488
110
soluble component with a high molecular weight
(11-12S; globulin; 18.6% nitrogen) and a water
soluble basic component with a low molecular
weight (1.6- 2S; albumin; 17.7% nitrogen).They
contain all essential amino acids except lysine,
making them a protein source that is
incomplete[18].
4.3 Fatty Acid
The fatty acid profile of FS is PUFAs>
monounsaturated fatty acids > few saturated
fatty acids [5]. ALA is an n3 polyunsaturated fatty
acid (PUFA) and is one of two essential fatty
acids required in the human diet [19]. In human,
the conversion rate of ALA to long chain PUFAs
like EPA and DHA is low [19]. However, this
conversion may be up controlled under certain
conditions [20]. ALA has a higher affinity for Δ6-
desaturase than the other essential fatty acid,
linoleic acid (LA), but because the Westernized
diets contain much higher levels of LA than ALA,
ALA is often metabolized to longer chain n3
PUFAs at much lower rates than omega-6 (n6)
PUFAs are converted [14]. This indicates that an
improvement in n6 to n3 ratio in the diet could
increase conversion rates of ALA to DHA and
EPA. FS contains relatively high levels of both
essential fatty acids, ALA and LA [5].
4.4 Lignans
Polyphenolic substances found in fiber-rich plant
products called lignans. In comparison to other
plants, FS contains 75–100 times more lignans
[21]. In defatted FS flour and whole FS, SDG
concentration can range from 11.7–24.1 mg/g
and 6.1–13.3 mg/g, respectively [21,22]. The
abdominal micro flora in the colon converts SDG
into the mammalian lignans enterolactone (EL)
and enterodiol (ED) after consuming FS. The
consortium END-49, which includes Clostridium
saccharogumia, Eggerthella lenta, Blautia
producta, and Lactonifact or longoviformis, has
been identified as the bacteria strains involved in
the transformation of SDG to EL or ED [23,24]. In
humans, the lignans are acted upon by the
gastrointestinal microflora to release EL and ED
through secoisolariciresinol (SECO). P-coumaric
(p-CA) and ferulic acid (FA) are the other
reported phenolic compounds from FS.
Cellulose: It is a Plant cell walls' primary
structural material.
Mucilage Gums: Flax mucilage is made up of
three different types of arabinoxylan, each of
which forms big aggregates in solution and
contributes to the gel characteristics of the
product [5].
4.5 Vitamins and Minerals
Flax has an abundance vitamin E, mostly in the
form of gamma tocopherol. Flax tocopherol
content is affected by the cultivar, seed maturity,
growing region, growth conditions, and extraction
process. Flax includes a modest quantity of
vitamin K in the form of phylloquinone, which is
an vital component of the blood clotting
mechanism. In flax seed, P, Mg, K, Na, Fe, Cu,
Mn, and Zn are reported [25].
4.6 Anti-nutritional Factors
In flax seed, there are trace levels of cyanogenic
glycosides and linamarin. Vitamin B
6
deficiency
is caused by linatin [26]. Flaxseed depressed
vitamin E levels in rats only when fed at very high
levels [27]. Another anti-nutrient found in
flaxseed is phytic acid, which varies from 23 to
33 g per kg of flaxseed meal. Calcium, zinc,
magnesium, copper, and iron are all inhibited by
phytic acid. It's a powerful chelator that forms
protein and mineral-phytic acid complexes,
lowering their bioavailability [28,29,30].
4.7 Storage
Due to high content of alpha linolenic acid (ALA),
it is prone to oxidation. The oxidation and
eventual rancidity will result in affect the flavours
and a musty scent, both of which will be rejected
in taste tests. So, proper storage condition is
required.
Regardless of how you get your ground
flaxseeds keep them in an airtight container in
the refrigerator. If using glass, choose tinted
glass to reduce the amount of light that the
ground flaxseeds are exposed to. Flaxseeds are
substantially more susceptible to oxidation and
spoiling after processed. They may usually be
stored safely for 6 to 16 weeks. If stored in an
airtight container in a dark, cool, dry location,
whole flaxseeds can last 6-12 months. Flaxseed
oil is especially perishable and should always be
purchased in opaque bottles that have been kept
refrigerated [31].
5. THERAPEUTIC USES
5.1 Hypertension
One of the primary causes of global illness
burden is hypertension. [32] Hypertension is the

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111
leading cause of death worldwide. Hypertension
(HTN) is well-defined as a blood pressure of
140/90 mmHg or higher, according to the Joint
National Committee 7 (JNC-7) guidelines. A
research for cost-effective medication for
treatment of hypertension is going on [32,33].
Flaxseed and its components may prove to be an
effective treatment for hypertension, either alone
or in conjunction with other commercially
available medications. The advantages of using
flax seed and its components include their
inexpensive cost and lack of adverse effects.
Consumption of flaxseeds is a simple strategy to
lower blood pressure. Previous clinical research
suggests that patients who consumed flaxseeds
on a daily basis for more than 12 weeks had their
blood pressure under control. Potassium, which
is found in seeds, is helpful in reducing blood
pressure by reducing tension in blood vessel wall
[33-35].
SDG (precursors of enterolignran), fibres and oil
are the important constituents in flaxseed.
Prasad looked explored the effects of several
intravenous dosages of SDG (3, 5, 10, 15, 20, 20
mg/kg) on the arterial pressures of anaesthetized
Sprague Dawley rats. He found that 10 mg/kg
resulted in a 32, 36, and 33 percent reduction in
systolic, diastolic, and mean arterial pressures
after 4 hours; 15 mg/kg resulted in a 15, 24, and
22 percent reduction; and 20 mg/kg resulted in a
20, 33, and 29 percent reduction. Hypotension is
induced by SDG through angiotensin-converting
enzyme suppression.Through ACE inhibition and
guanylate cyclase activity, pure SDG, which is
extracted from flaxseed, significantly lowers
systolic, diastolic, and mean arterial pressures in
a dose-dependent manner [36,37]. The drop in
BP caused by flaxseed protein hydrolysate is
mediated by a decrease in oxylipins caused by
the suppression of soluble epoxide hydrolase
activity by -linolenic acid. Some oxylipins have
been shown to cause vasoconstriction [38,39].
As a result, lowering oxylipin levels lowers blood
pressure. According to the findings, flaxseed and
flax oil could be utilised as an additional therapy
for hypertension [40]. Pure SDG may be useful
as a treatment medication for hypertension due
to its great and long-lasting pharmacological
effect on blood pressure. The hypotensive effects
of flaxseed are attributed to a-linolenic acid's
suppression of soluble epoxide hydrolase
activity, activation of guanylate cyclase and
inhibition of ACE by SDG.High concentration of
vitamin E also reported in flaxseed, which
enhances sodium excretion in the urine, which
may support in the reduction of blood pressure
[41]. Ineffectiveness of flaxseed and its
constituents' may be accredited to a low dose, a
long interval between doses and a short time of
ingestion, as well as patient status [42].
6. LIPID LOWERING EFFECT
The human diet has shifted from unrefined whole
grains and green vegetables to refined grains
with low fibre content and more animal items
since the industrial revolution. Whole flaxseed
has been demonstrated in certain research to
decrease serum cholesterol levels in animals and
people both. Biochemical measures in rats, mice,
and rabbits showed favourable reactions,
demonstrating flaxseed's hypocholesterolemic
activity, which was connected to a higher lipid
content in the faeces [43-50]. Many in vivo
studies have observed ,the different flax seed
dosages modify the lipid profiles differently.
Dawley rats were fed 10%, 20%, or 30% raw or
heated flaxseed in the basal diet for 30 days. In
the study conclusion, flaxseed was observed to
considerably lower total cholesterol and boost
high density lipoprotein cholesterol in blood [51].
The high levels of ALA, lignans, and fibre in
flaxseed may contribute to improved lipid profile.
As a result, increasing the amount of flaxseed in
one's diet improves the blood lipid profile-
improving effect of flaxseed. Both fibre and
lignans bind to bile acids, amphipathic molecules
generated from cholesterol in the liver, and
transport them out of the body through the
digestive tract. Flaxseed also includes
phytosterols, which have a structure similar to
cholesterol and hence inhibit cholesterol
absorption in the intestines. Another mechanism
of flax seed is that it interrupts cholesterol
circulation in the enterohepatic system [52-54].
Increased bile acid synthesis is the main
cholesterol-lowering mechanisms of flaxseed and
another component, besides its oil, contributes to
its hypocholesterolemic property [55,56]. Lignans
are estrogen like components which also have
antioxidant activity in reducing the oxidative
damage in many diseases like heart disease,
cancer and diabetes [57-59]. Flax seeds contain
fiber, lignans and phytoestrogens, which
decrease the levels of 7 alpha-hydroxylase and
acyl-CoA cholesterol transferase. Incorporating
30 g of roasted flax seed in daily diet found the
positive modification of lipid profile. In the Seven
Countries Study, CHD (coronary heart disease)
was reduced with increased consumption of ALA.
At the end of 4 years’s Lyon diet clinical trial,
data concluded the consumption of flax seed

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112
condensed number of CHD patient and total
deaths by 50%–70% [51].
7. CANCER
7.1 Breast Cancer
Breast cancer is a disease that affects the cells
of the breasts. Breast cancer can affect both in
men and women, however it is more common in
women. Cancer awareness and research funding
have aided in the advancement of breast cancer
diagnosis and treatment. Clinical evidence
suggests that flax seed has antitumor properties
against several cancers [60,61–63], making it a
CAM (complementary and/or alternative
medicine) candidate for human cancer treatment
Linoorbitides (LOBs) are a class of cyclic
cyclopeptide compounds found in flaxseed that
have a cell-type specific and concentration
dependent cytotoxic action on human breast
cancer Sk-Br-3 and MCF7 cell lines, as well as
melanoma A375 cells. LOBs' anti-oxidative
activity could be a key factor in their cytotoxic
effects on cancer cells. After 24 hours of
exposure at 400 ug/mL, cytotoxicity of LOB3,
LOB2, [MetO]-LOB2, and [MetO]-LOB1 against
Sk-Br-3 cells was 75 percent, 41 percent, 36
percent, and 28 percent, respectively.
Lignans have a unique phenolic structure and
are found in small amounts in many foods, but in
considerable quantities in flaxseed. Dietary
ingestion of the flaxseed lignan,
(secoisolariciresinol diglucoside (SDG)),
consequences in glucosidic cleavage in the
gastrointestinal tract to yield secoisolariciresinol
(SECO), which is further converted to the
mammalian lignans, enterodiol (ED) and
enterolactone (ENL), with the help of intestinal
microflora [64-67].
According to the data, ENL is the most bioactive
lignan. Non steroidal phytoestrogens that have a
chemical structure similar to mammalian
estrogens and induce estrogen-like actions in
animals include flaxseed lignans. (Fig. 2)
Enterolactone and enterodiol bind to oestrogen
receptors, causing cell growth to alter. A link was
discovered between a higher level of EL and a
lower incidence of breast cancer in
postmenopausal women. Lignans operate as
weak estrogen in postmenopausal women, while
oestrogen antagonists in women with normal
oestrogen levels [68,69]. When Flax oil was
combined with trastuzumab for epidermal growth
factor receptor 2 positive breast cancer, the anti-
tumour effects of trastuzumab were increased,
and the trastuzumab concentrations required to
eradicate tumours in athymic mice were
suggested to be reduced [70]. Flaxseed and its
bioactive components anti-tumour actions
include a suppression of the phosphorylation of
p-AKT, p-ERK and p-JNK kinases, resulting in a
slowing of the MAPK pathway [71], inhibition of
CDK4 down regulation of multiple miRNAs,
decreased expression of mRNAs for Bcl2, cell
cycle proteins, ER alpha and beta and
epidermal and insulin-like growth factor receptors
[71,72].
Fig. 2. Different types of flax seed lignans and metabolism of SDG (Secoisolariciresinol
diglucoside) [68]

Patel et al.; JPRI, 33(39A): 107-122, 2021; Article no.JPRI.71488
113
Clinical evidence suggests that combining
metformin with flax seed lignans, ENL, improved
metformin cytotoxicity in MDA-MB-231 cells in a
concentration-dependent manner by inhibiting
fatty acid synthase (FASN). Flax or lignan
fraction were fed to mice groups for two weeks
before and after the injection of melanoma cells.
When compared to the control, the flax therapy
(at 2.5, 5, or 10% of diet intake) reduced the
number of tumours by 32, 54, and 63 percent,
respectively. The SDG, provided in doses
comparable to 2.5, 5, or 10% flax seed, also
reduced tumour number, from 62 tumours per
mouse in the control group to 38, 36, and 29
tumours per mouse in the SDG groups,
respectively [70-74].
7.2 Colon Cancer
CRC (colorectal cancer) is a form of cancer that
starts in the large intestine and spreads
throughout the body (colon). The colon is a big
intestinal section. In comparison to adults, older
people are more likely to get colon cancer.
Modifiable and non-modifiable risk variables are
separated. Non changeable factors include
ethnicity, age, and a family history of colorectal
polyps, cancer, or inflammatory bowel disease.
Modifiable factors include BMI (Body mass
index), physical inactivity, alcohol consumption,
and a diet high in red meats [75-77].
Increased dietary fibre intake, shortened transit
time, and increased stool bulking have all been
linked to CRC prevention. Increased ALA, as well
as an improvement in the n6 to n3 ratio, improve
gut health by lowering inflammatory and
oxidative stress indicators, as well as inhibiting
cell proliferation and promoting apoptosis. The
bioactive components of FS (lignans, fibre, and
ALA) have been linked to cell cycle disruption
and a lower the risk of colon cancer. Various
colon cancer cell lines were used to examine the
cellular processes of FS lignans. Treatment of
SW480 cells (human colon adenocarcinoma
cells) with ED alone or in conjunction with EL
resulted in a decrease in cell number, induction
of S-phase cell cycle arrest, and elevated cyclin.
A dose-dependent rise in the number of
apoptotic cells (0–40 mg/L). In CaCo
2
cells
human colon adenocarcinoma cells, EL and ED
at varied doses (50–150 M) were found to reduce
cell growth and promote apoptosis [78,79].
8. RHEUMATOID ARTHRITIS
Rheumatoid arthritis is an autoimmune illness
that causes chronic inflammation [80]. Effective
novel anti-arthritic drugs are currently being
researched. CFA (Complete Freund's adjuvant)-
induced arthritis was significantly protected by L.
usitatissimum fixed oil in a dose-dependent
manner. CFA also causes a delayed
hypersensitivity reaction, which is significantly
reduced by flax seed. Alpha linolenic acid (ALA),
a component of L. usitatissimum fixed oil, has a
dual inhibitory effect on arachidonate
metabolism, resulting in reduced PGE
2
and LTB
4
synthesis via inhibition of the cyclooxygenase
and lipoxygenase pathways of arachidonic acid
metabolism, as well as lower vascular
permeability. Fixed oil revealed a dose-
dependent protection compared to the swelling
observed in the synovial cavity after turpentine oil
administration. Between days 2 and 10 following
formaldehyde administration. L. usitatissimum
fixed oil (3 ml/kg) significantly reduced the
arthritic score compared to control. On day 10,
the anti-arthritic activity of L usitatissimum fixed
oil (3 ml/kg) was superior to that of the standard
drug aspirin (i.e. 70% inhibition). On the 14th
day, L. usitatissimum fixed oil significantly
reduced paw diameter in a dose-dependent
manner, with percentage protection of 21.5, 75.3,
and 91.7 percent, respectively, at dose levels of
1, 2, and 3 ml/kg. Reduced vascular permeability
generated by the oil could potentially help with
anti-arthritic properties. The fixed oil of L.
usitatissimum, which contains 57.38 percent
ALA, has been proven to be beneficial in
inflammatory joint treatment [81,82].
9. OBESITY
Obesity is a common and preventable disease of
public health, importance in all age groups and in
both developed and developing countries. The
increasing prevalence of obesity places a huge
burden on health care use and cost. Weight loss
is linked to numerous health and financial
advantages. Dietary therapy, physical activity,
and lifestyle changes are all effective weight loss
strategies [82].
The main findings show that following the
intervention, those who consumed flaxseed
products had lower body weight, BMI and WC
(Waist circumference) than controls. However,
subgroup analyses revealed that body
composition indices were reduced with whole
flaxseed consumption only, in trials lasting ≥12
weeks, and among participants with BMI ≥ 27 kg
per m
2
[83]. SDG may also help to regulate
adiponectin levels and may help to prevent or
reduce obesity by increasing fat oxidation in the

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114
skeletal muscle. Dietary fibre, particularly soluble
fibre, has been demonstrated to have anti-
obesity properties and to help people lose weight
[84]. Dietary fibre may help to promote weight
loss by delaying stomach emptying, producing
feelings of fullness by absorbing significant
amounts of water [85], and/or increasing the
concentration of short chain fatty acids, which
induce satiety through a variety of pathways [86]
(Fig. 2). When flax seed is mixed with water, it
also acts as a gel. This gel delays stomach
emptying, which may help to reduce blood
glucose levels. Furthermore, dietary fibre can
increase viscosity and inhibit bile acid re-uptake,
lowering micelle production and lipid uptake
[87-89].
10. DIABETES
Diabetes is an ailment in which blood glucose,
also recognized as blood sugar, is abnormally
high. Blood glucose is the main energy source,
which arises from the food you consume.
Pancreas secrets the hormone, Insulin which
aids glucose absorption into cells for use as
energy currency. Flaxseed has recently gained a
lot of attention for its potential health benefits in a
variety of metabolic illnesses, such as diabetes.
Insulin resistance and the pathophysiology of
many metabolic disorders associated with type 2
diabetes are influenced by fat accumulation,
particularly abdominal obesity and visceral fat
[90,91]. According to a clinical investigation data,
flaxseed enriched yoghurt can help type 2
diabetic people better manage their diabetes.
The flaxseed component secoisolariciresinol
diglucoside (SDG), which is the major flaxseed
lignin, has been shown to help glycemic
management. In Zucker diabetic rats, pure SDG
is likewise beneficial at delaying the onset of
diabetes [92]. The hypoglycemic impact of SDG
in type-2 diabetes is attributed to reduction of the
Phosphoenol pyruvate carboxyl kinase enzyme,
which is a major enzyme involved in glucose
production in the liver and also a rate limiting
enzyme in the glyconeogenetic pathway [93,94].
Data from the Research supported the
pharmacological effect of insoluble fiber, slows
down the release of sugar into the blood and
reduces blood sugar level. Supplementation of
10 g of flaxseed powder with diet for type 2
diabetics patients for duration of 30 days,at the
end of study, data concluded the reduced fasting
blood glucose and glycated haemoglobin by by
19.7 % and 15.6 % respectively [95]. It could be
because flaxseed has a lower glycemic
carbohydrate level and a higher dietary fibre
content. According to findings from a diabetic
female clinical trial, supplementation of flaxseed
powder in 15 and 20 g/day over a period of two
months reduced postprandial blood glucose
levels by 7.9% and 19.1%, respectively [96].
Another study on 25 diabetic participants
supplemented flaxseed powder in bread form for
90 days and observed a substantial drop in blood
glucose levels supported the favourable effect of
flax seed in diabetes. In humans and animals,
ALA from flaxseed oil has been related to
enhanced insulin sensitivity. In instance, an 8-
week research in 16 obese persons found an
increase in insulin sensitivity after they received
a daily oral dose of ALA in supplement form
[92].
Fig. 3. Effect of flax seed in gastrointestinal tract [4]

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11. RESPIRATORY DISEASES
Flaxseed appears to have a positive effect in
mice, according to an in vivo study. When mice
were given flaxseed for a long time, they were
protected from bacterial colonisation of the lungs
by Streptococcus pneumonia and had less
histopathological involvement of lung tissue. The
levels of pro-inflammatory (TNF- and IL-1) and
anti-inflammatory (IL-10) cytokines are also
altered by flaxseed [97]. Flex seed fatty acids
and lignans have been demonstrated to have
anti-inflammatory and antioxidant properties in
Acute Lung Injury [98]. In vivo and in vitro studies
strongly supported flaxseed's beneficial role in
asthma and allergic disease prevention.
In vivo and in vitro studies firmly confirmed
flaxseed's beneficial effect in asthma and allergy
disease prevention. The discovery of fatty acid
bioactive metabolites produced by lipoxygenase
and cyclo-oxygenase has revealed some
molecular processes [99,100] Rv and PD are two
newly found lipid mediators produced by the
oxidation of n-3 fatty acids (EPA and DHA), and
they've been linked to inflammatory treatment.
Reduced inflammation reduces asthma
symptoms and has a bronchodilator effect [101].
A randomised controlled clinical trial was
conducted on 60 COPD patients. In the test
group, a Pharmacopeial Unani formulation called
“Lauq Katan” (Linctus of Linum usitatissimum
mucilage) was given three times a day in a dose
of 10 gm, and in the control group, Theophylline
200 mg was given three times a day for six
weeks. The test medicine Lauq Katan was found
to have a substantial effect in the management of
COPD based on spirometer measures FEV1 and
FEV1/FVC [102].
12. ANTI OXIDANT
Oxidative stress is caused by an imbalance
between the synthesis of oxidant chemicals and
the antioxidant defence mechanism. Antioxidant
enzymes such as superoxide dismutase (SOD),
catalase (CAT), and glutathione peroxidase
(GSH-Px) are important regulators of the
oxidant/antioxidant equilibrium. Flaxseed is
abundant in -linolenic, and oleic acids, all of
which play important roles in maintaining cell
membrane integrity [103-105] .Clostridia sp,
which is found in the colon, converts
secoisolariciresinol diglucoside, which contains
plant lignin, into enterodiol and enterolactone.
Other minor lignins found in flaxseed include
matairesinol, isolariciresinol, and pinoresinol.
Acids have antioxidant capabilities due to their
free radical scavenging activities [106].During
lipid peroxidation, certain compounds are
formed. The detection of these products in
biological systems may provide useful
information about the severity of free radical-
induced cell damage. Malondialdehyde (MDA)
and nitric oxide are the most often used
indicators for this purpose (NO). Changes in
antioxidant enzyme activity in biological systems
can also be used to estimate the level of
oxidative stress [107-109].
Cadmium is used to induce oxidative stress in
rats. Cadmium was administered to rats for 30
days, and the effects on a range of organs and
erythrocytes were assessed using oxidative
stress markers. As a result, specific conclusions
on the therapeutic and protective uses of this
chemical in cadmium overdose have been
reached. This is corroborated by the fact that
levels of MDA and NO, both of which are
oxidative stress markers, have decreased, while
antioxidant enzyme activity have near to the
control group levels. As a result, it existed that,
flaxseed oil might be utilised as a supportive
treatment in conjunction with cadmium
intoxication [107].
13. OTHER PHARMACOLOGICAL
EFFECTS
 Flaxseed lignans in the diet helped mice to
recover after being exposed to radiation. A
similar outcome was discovered in
humans. While compared with control
group, there were lower levels of
inflammation, injury, oxidative damage,
and fibrosis, as well as a higher survival
rate [110].
 When platelets aggregate at the site of
injury, the clotting mechanism begins.
Flaxseed, like other omega-3 fatty acids,
makes platelets less "sticky," preventing
them from forming huge clots and
interfering with the clotting process, as well
as acting as a blood thinner [111].
 The astringent qualities of flaxseed raw oil
in several fungicidal lotions are also
suggested by data. Raw oil is said to
provide moderate insect repelling effects
[112].
 During pregnancy and early childhood
,When flax seed consumed, due to
presence of high levels of long chain
polyunsaturated fatty acids ,it revealed as
immunomodulatory agent [113,114].

Patel et al.; JPRI, 33(39A): 107-122, 2021; Article no.JPRI.71488
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 Flaxseed constituents such as alpha
linolenic acid,and the omega-3 fat found in
promotes bone health by helping to
prevent excessive bone turnover [2,115].
 As stated by Ayurveda, flaxseed has
properties like Madhura (balances the skin
pH), Picchaila (lubricous) Balya (improves
elasticity of the skin), Grahi (as
moisturizer), Tvagdoshahrit (removes skin
blemishes), Vranahrit (wound healing) and
useful in Vata (skin) disorders including
dryness, undernourishment, lack of glow
[2,116].
 Serotonin (sleep hormone) levels in the
blood is enhanced by flax seed due to its
high content of omega-fatty acids and
tryptophan. Magnesium works by relaxing
the nervous system and muscles, as well
as preventing night terrors, both of which
are effective in the treatment of anxiety,
stress, and depression. As a result, flax
seed can be included in the daily diet of
insomniacs [117].
 When pregnant woman diet fed with
flaxseed, benefits reported like decreased
the depressive symptoms and
neuroprotection during experimental
neonatal hypoxic-ischemic encephalopathy
by lessening brain mass loss together with
improvements in motor hyperactivity and
spatial memory [118,119]
 Flaxseed is used to treat persistent cough
and asthma, according to some scientific
evidence. Ayurveda is a very old and still
alive tradition that is widely practised in
India, Sri Lanka, and other nations with a
good philosophical and experimental
foundation. In 650 B.C Scientist
theophrastus recommended the use of flax
mucilage as a cough remedy. The omega -
3 fatty acid which is seen flaxseed may
beneficial for avoiding and treating
hardening of the arteries. So, it may help to
fight against covid 19 as an immune
booster [2,120].
14. POSSIBLE SIDE EFFECTS
 Raw flaxseed contains toxins, so one
should limit consumption, though the toxins
are killed when the seeds are roasted
or cooked.
 Higher doses of flaxseeds may cause side
effects like diarrhoea, nausea, stomach
pain, flatulence, bloating.
 Most experts recommend you consume no
more than 5 table spoon full
of flaxseed a day. All that fiber is good for
digestive system - but only if it should eat
with plenty of water. Otherwise,
it can backfire and make constipation
worse.
 Flaxseed may interfere with hormonal level
during pregnancy.
 Flaxseed oil may inhibit the clotting of your
blood, so avoid taking it for a few weeks
after the surgery [2].
15. CONCLUSION
In light of the information provided above, it is
evident that flaxseeds are rich in linolenic acid
and lignans. It is also an excellent source of
soluble fiber, antioxidants and high-quality
protein. Since its journey from being a medicine
in ancient time to being superfood nowadays, it
has become an increasingly popular source.
Clinical trials have shown that flaxseed’s
constituents offer disease prevention and
therapeutic benefits, which has led to
the development of new branded healthy and
functional foods using flaxseeds and oil.
Researcher concluded that flaxseed lignans and
omega-3 fatty acids are effective in reducing the
risks associated with heart disease, cancer
(breast and colon,) and other human health
diseases such diabetes, obesity and rheumatoid
arthritis. So, flaxseed can be used a dietary
supplement in whole or ground forms. As a
result, flaxseeds and flaxseed oil may be
preferred ingredients in functional foods and
nutraceuticals in future.
DISCLAIMER
The products used for this research are
commonly and predominantly use products in our
area of research and country. There is absolutely
no conflict of interest between the authors and
producers of the products because we do not
intend to use these products as an avenue for
any litigation but for the advancement of
knowledge. Also, the research was not funded by
the producing company rather it was funded by
personal efforts of the authors.
CONSENT
It is not applicable.
ETHICAL APPROVAL
It is not applicable.

Patel et al.; JPRI, 33(39A): 107-122, 2021; Article no.JPRI.71488
117
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
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