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Received: 12 September 2024
Revised: 12 December 2024
Accepted: 28 January 2025
Published: 30 January 2025
Citation: Stepie ´n, A.E.; Trojniak, J.;
Tabarkiewicz, J. Anti-Oxidant and
Anti-Cancer Properties of Flaxseed.
Int. J. Mol. Sci. 2025,26, 1226.
https://doi.org/10.3390/
ijms26031226
Copyright: © 2025 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
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licenses/by/4.0/).
Review
Anti-Oxidant and Anti-Cancer Properties of Flaxseed
Agnieszka Ewa Stepie ´n 1, Julia Trojniak 2and Jacek Tabarkiewicz 3,*
1
Institute of Health Sciences, Medical College of Rzeszów University, University of Rzeszow, 35-959 Rzeszów,
Poland; agstepien@ur.edu.pl
2Student’s Scientific Club of Immunology, Institute of Medical Sciences, Medical College of Rzeszów
University, University of Rzeszow, 35-959 Rzeszów, Poland; jt117576@stud.ur.edu.pl
3Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszów University,
University of Rzeszow, 35-959 Rzeszów, Poland
*Correspondence: jtabarkiewicz@ur.edu.pl; Tel.: +48-851-68-07
Abstract: Bioactive molecules present in plant products determine their very valuable
health-promoting properties. Among the plants, due to these properties, particular atten-
tion is paid to the seeds of common flax (Linum usitatissimum L.), which have been used
for over 6000 years and are known for their benefits. A review of 117 scientific articles
indexed in PubMed/MEDLINE, ScienceDirect, and Wiley Online Library, published be-
tween 1997 and 2024, was conducted. These seeds are characterized by a high content of
valuable nutrients, such as essential omega-3 fatty acids, including
α
-linolenic acid (ALA),
lignans, isoflavones, phytoestrogens, flavonoids, vitamins, and minerals that influence the
digestive system function and have anti-cancer properties. The presence of these bioactive
compounds in flaxseeds provide anti-cancer properties.
Keywords: flaxseed; linseed; common flax; superfoods; Linum usitatissimum
1. Introduction
Common flax (Linum usitatissimum L.), belonging to the flax family (Linaceae), is one
of the oldest cultivated plants in the world. It is estimated that cultivation in the Middle
East dates back to around 9000 BC [
1
]. Flax is an annual, blue herb that grows in temperate
climates, including Europe, Asia, and North Africa [
2
,
3
]. Each part of the linseed plant
can be used for a range of purposes, including industrial and culinary uses, as well as
animal feed [
4
]. Flax can be cultivated in two forms, depending on the climatic conditions:
oily (Linum usitatissimum L. var. brevimulticaulis Vav.) and fibrous (Linum usitatissimum L.
var. elongatum Vav.) [
2
,
5
]. Furthermore, flax comes in two varieties: brown and golden.
Golden flax thrives in very cold climates, while brown flax thrives in warmer, more humid
climates [
6
]. Common flax produces small flat and oval seeds with pointed tips that range
from golden yellow to reddish brown in color [
3
,
7
]—Figure 1. The seed coat of flaxseed
consists of a true husk (also known as the kernel), a thin endosperm, and two embryos [
8
].
Flaxseed has a crunchy texture and a nutty, slightly spicy taste [3,8].
Flaxseed (linseed) is a traditional ingredient in the human diet. It is widely known
that linseeds have historically been used as a source of fiber and oil. Still, their exceptional
nutritional properties have gained popularity as an important dietary ingredient. More
people are becoming aware of flaxseeds’ health-promoting benefits after being used mostly
for industrial purposes for decades. A number of the nutrients and bioactive compounds
found in linseed benefit human health. Flax components with abundant health-promoting
properties include three types of phenolic compounds, phenolic acids, flavonoids and
lignans, omega-3 fatty acids, dietary fiber, vitamins, and minerals, which is why they are
Int. J. Mol. Sci. 2025,26, 1226 https://doi.org/10.3390/ijms26031226
Int. J. Mol. Sci. 2025,26, 1226 2 of 19
classified as "superfoods" [
3
,
9
]. It is worth noting that flaxseed fiber can support the diges-
tive system’s health by regulating intestinal peristalsis and providing anti-inflammatory
effects [10,11].
Int. J. Mol. Sci. 2024, 25, x FOR PEER REVIEW 2of 21
(a) (b)
Figure 1. Gold flaxseed (linseed) from Linum usitatissimum L. (photographs by J. Trojniak). (a)
Gold flaxseed (linseed) from Linum usitatissimum L. – low magnification, (b) Gold flaxseed (lin-
seed) from Linum usitatissimum L. – higher magnification
Flaxseed (linseed) is a traditional ingredient in the human diet. It is widely known
that linseeds have historically been used as a source of fiber and oil. Still, their exceptional
nutritional properties have gained popularity as an important dietary ingredient. More
people are becoming aware of flaxseedsʹ health-promoting benefits after being used
mostly for industrial purposes for decades. A number of the nutrients and bioactive com-
pounds found in linseed benefit human health. Flax components with abundant health-
promoting properties include three types of phenolic compounds, phenolic acids, flavo-
noids and lignans, omega-3 fay acids, dietary fiber, vitamins, and minerals, which is why
they are classified as ʺsuperfoodsʺ [3,9]. It is worth noting that flaxseed fiber can support
the digestive systemʹs health by regulating intestinal peristalsis and providing anti-in-
flammatory effects [10,11].
Several studies suggest that linseed may be beneficial for heart health due to its anti-
hypertensive, anti-atherosclerotic, and cholesterol-lowering properties [12–14]. Among its
benefits are also the reduction of lipid levels in the blood, anti-diabetic properties, hepa-
toprotective properties, and the prevention of many cardiovascular diseases (CVDs) and
cancers [15–18]—Figure 2. Additionally, some reports mention antipyretic action, analge-
sic effects, reduced symptoms, and improved general functioning, especially in osteoar-
thritis of the knee joint [19,20]. It is also worth mentioning that flaxseed may contribute to
the reduction of inflammatory markers such as CRP and TNF-α [4].
There are documented reports of the positive effects of linseed on human health, in-
cluding tolerance of linseed by people with chronic or genetic diseases, such as cystic fi-
brosis [21]. However, special caution should be taken in some populations [21]. Because
of its estrogenic effect, women and men who are trying to conceive, and especially preg-
nant women, should exercise special caution when taking flaxseed [22]. Additionally, α-
linolenic acid (ALA) present in linseed is associated with improved brain function and is
important for maintaining a healthy nervous system [23].
The benefits of flaxseed have also been established in recent studies, including relief
from perimenopausal symptoms [24]. Its alpha-linolenic acid (ALA) content may protect
against neurological damage and also improve cognitive function in older people [25].
Additionally, flaxseed may reduce inflammatory biomarkers in cardiovascular patients,
offering further benefits to heart health beyond its known cholesterol- and blood pressure-
lowering effects [22].
Figure 1. Gold flaxseed (linseed) from Linum usitatissimum L. (photographs by J. Trojniak). (a) Gold
flaxseed (linseed) from Linum usitatissimum L. – low magnification, (b) Gold flaxseed (linseed) from
Linum usitatissimum L. – higher magnification.
Several studies suggest that linseed may be beneficial for heart health due to its
antihypertensive, anti-atherosclerotic, and cholesterol-lowering properties [
12
–
14
]. Among
its benefits are also the reduction of lipid levels in the blood, anti-diabetic properties,
hepatoprotective properties, and the prevention of many cardiovascular diseases (CVDs)
and cancers [
15
–
18
]—Figure 2. Additionally, some reports mention antipyretic action,
analgesic effects, reduced symptoms, and improved general functioning, especially in
osteoarthritis of the knee joint [
19
,
20
]. It is also worth mentioning that flaxseed may
contribute to the reduction of inflammatory markers such as CRP and TNF-α[4].
Int. J. Mol. Sci. 2024, 25, x FOR PEER REVIEW 3of 21
Figure 2. Selected properties of flaxseed (linseed).
Despite the numerous health and nutritional benefits of flaxseed, it has also been de-
scribed to contain high levels of toxic compounds that can affect the bioavailability of nu-
trients and/or further worsen health problems [26]. When comparing the nutrients and
antinutrients of flaxseed, it can be concluded that the nutrients significantly predominate,
and the level of antinutrients can be significantly minimized by using appropriate meth-
ods of flaxseed processing, such as autoclaving or microwave baking [27,28].
The choice to focus on the anti-oxidant and anti-cancer properties stems from their
crucial significance in the context of research on the prevention of chronic diseases, such
as cancer. Studies indicate that these properties have wide-ranging applications in public
health protection, which justifies their detailed analysis in our work. The oxidative stress
associated with inflammation, especially chronic, is one of the main factors of carcinogen-
esis; what causes those anti-oxidative activities of natural compounds are usually associ-
ated with anti-cancer properties. We chose to summarize the benefits of common flax as
another valuable plant after discussing the benefits of Sambucus Nigra and black garlic,
two other plants that promote health [29,30]. Our study concentrates on compiling scien-
tific reports on the anti-cancer, anti-inflammatory, and anti-oxidant properties, providing
a comprehensive summary of the published literature and highlighting gaps, including
those related to safety and long-term adverse effects, which warrant further investigation.
2. Methodology and Selection Criteria
Our article presents a comprehensive review of literature published between 1997
and 2024, focusing on the anti-oxidant and anti-cancer properties of compounds found in
flaxseed. The analysis was conducted using the following databases: MEDLINE/PubMed,
Wiley Online Library, and ScienceDirect. Our work primarily focused on original research
articles, as well as the collection and synthesis of previous review articles and meta-anal-
yses. The search criteria included keywords such as “flaxseed”, “Linum usitatissimum”,
“antioxidant”, and “anti-cancer”, which were combined in various configurations. A
search in PubMed using the terms ʺflaxseedʺ or ʺLinum usitatissimumʺ yielded a total of
17,420 results. After applying relevant filters, this number was reduced to 102 articles. The
same search strategy was employed in the Wiley Online Library, yielding 118 results, and
in ScienceDirect, yielding 23 results.
Figure 2. Selected properties of flaxseed (linseed).
There are documented reports of the positive effects of linseed on human health,
including tolerance of linseed by people with chronic or genetic diseases, such as cystic
fibrosis [
21
]. However, special caution should be taken in some populations [
21
]. Because
Int. J. Mol. Sci. 2025,26, 1226 3 of 19
of its estrogenic effect, women and men who are trying to conceive, and especially pregnant
women, should exercise special caution when taking flaxseed [
22
]. Additionally,
α
-linolenic
acid (ALA) present in linseed is associated with improved brain function and is important
for maintaining a healthy nervous system [23].
The benefits of flaxseed have also been established in recent studies, including relief
from perimenopausal symptoms [
24
]. Its alpha-linolenic acid (ALA) content may protect
against neurological damage and also improve cognitive function in older people [
25
].
Additionally, flaxseed may reduce inflammatory biomarkers in cardiovascular patients,
offering further benefits to heart health beyond its known cholesterol- and blood pressure-
lowering effects [22].
Despite the numerous health and nutritional benefits of flaxseed, it has also been
described to contain high levels of toxic compounds that can affect the bioavailability of
nutrients and/or further worsen health problems [
26
]. When comparing the nutrients and
antinutrients of flaxseed, it can be concluded that the nutrients significantly predominate,
and the level of antinutrients can be significantly minimized by using appropriate methods
of flaxseed processing, such as autoclaving or microwave baking [27,28].
The choice to focus on the anti-oxidant and anti-cancer properties stems from their
crucial significance in the context of research on the prevention of chronic diseases, such
as cancer. Studies indicate that these properties have wide-ranging applications in public
health protection, which justifies their detailed analysis in our work. The oxidative stress
associated with inflammation, especially chronic, is one of the main factors of carcinogene-
sis; what causes those anti-oxidative activities of natural compounds are usually associated
with anti-cancer properties. We chose to summarize the benefits of common flax as another
valuable plant after discussing the benefits of Sambucus Nigra and black garlic, two other
plants that promote health [
29
,
30
]. Our study concentrates on compiling scientific reports
on the anti-cancer, anti-inflammatory, and anti-oxidant properties, providing a comprehen-
sive summary of the published literature and highlighting gaps, including those related to
safety and long-term adverse effects, which warrant further investigation.
2. Methodology and Selection Criteria
Our article presents a comprehensive review of literature published between 1997
and 2024, focusing on the anti-oxidant and anti-cancer properties of compounds found in
flaxseed. The analysis was conducted using the following databases: MEDLINE/PubMed,
Wiley Online Library, and ScienceDirect. Our work primarily focused on original research
articles, as well as the collection and synthesis of previous review articles and meta-
analyses. The search criteria included keywords such as “flaxseed”, “Linum usitatissimum”,
“antioxidant”, and “anti-cancer”, which were combined in various configurations. A
search in PubMed using the terms “flaxseed” or “Linum usitatissimum” yielded a total of
17,420 results
. After applying relevant filters, this number was reduced to 102 articles. The
same search strategy was employed in the Wiley Online Library, yielding 118 results, and
in ScienceDirect, yielding 23 results.
From the initial pool of 243 articles published between 1997 and 2024, 62 were excluded
following title and abstract screening. A more detailed analysis was performed on the
remaining 181 articles, evaluating their methodology and results. Further analysis in terms
of methodology and results was carried out by reading the full texts of the 181 remaining
articles. Finally, after selecting articles whose subject matter was consistent with our review,
we analyzed 117 scientific papers.
The exclusion criteria included a lack of detailed information on anti-oxidant or anti-
cancer properties, unclear research methods, or data that did not meet scientific reliability
Int. J. Mol. Sci. 2025,26, 1226 4 of 19
standards. Only articles that comprehensively documented the anti-oxidant and anti-cancer
effects of flaxseed were included in the final analysis.
3. Active Ingredients in Flaxseed
The use of phytochemicals to prevent neoplasms is becoming increasingly popular. This in-
hibiting effect of phytochemicals on cancerogenesis is frequently associated with anti-oxidative
properties. Compared to synthetic anti-oxidants, which often come with undesirable side
effects, naturally occurring anti-oxidants are considered a safe alternative [31].
Flaxseed (Linum usitatissimum L.) is a highly nutritious seed containing numerous active
ingredients. There is a wide variation in chemical composition among varieties and growing
conditions. Flaxseed is naturally enriched with
α
-linolenic acids (ALAs), short-chain polyun-
saturated fatty acids (SC-PUFAs), lignans, and dietary fiber and is a cluster of anti-oxidative
and anti-cancer agents and other bioactive compounds [3]—Table 1, Figure 3a–g.
Int. J. Mol. Sci. 2024, 25, x FOR PEER REVIEW 7of 22
(a)
(b) (c)
(d) (e)
(f) (g)
Figure 3. Chemical structures of several of the most important active compounds found in flaxseed
from common flax (Linum usitatissimum L.): (a) α-linolenic acid (ALA); (b) secoisolariciresinol diglu-
coside (SDG); (c) matairesinol (MAT); (d) secoisolariciresinol; (e) laricinesinol; (f) pinoresinol; (g)
chlorogenic acid (CGA).
Researchers have also found that linseed may have an antiviral effect, particularly
against HIV. Several studies have shown that lignans found in linseed can inhibit HIV
virus replication, giving hope for its use in treatment and prevention [54,55].
Figure 3. Chemical structures of several of the most important active compounds found in flaxseed
from common flax (Linum usitatissimum L.): (a)
α
-linolenic acid (ALA); (b) secoisolariciresinol
diglucoside (SDG); (c) matairesinol (MAT); (d) secoisolariciresinol; (e) laricinesinol; (f) pinoresinol;
(g) chlorogenic acid (CGA).
Int. J. Mol. Sci. 2025,26, 1226 5 of 19
Table 1. Active compounds of flaxseed (linseed) from common flax (Linum usitatissimum L.).
Component Contents Unit References
humidity 7.13; 5.39–6.04
[%]
[32–34]
nitrogen 4.01
fat 41; 34/08–40/74
protein 20; 18.9–27.0
ash 3.4; 3.54–4.49
digestive fiber total 28
crude fiber 7.6–11.8
soluble fibers 4.3–8.6; 9 [g/100 g flaxseed]
insoluble fibers 12.8–17.1; 20
fatty acids
α-linolenic acid (ALA) 22.8 [g/100 g flaxseed] [32]
42/97–61/06
58.59 ±0.43;
53.6–57.1
% [33,35,36]
acid linoleic 5.9; [g/100 g flaxseed] [32]
9.18–15.88;
15.50 ±0.21;
14.0–14.4
% [33,35,36]
acid oleic
7.3;
16.33–22.56 [g/100 g flaxseed] [32]
17.27–20.50;
16.67 ±0.23;
18.5–21.0
% [35,36]
acid stearic 1.3 [g/100 g flaxseed] [32]
3.65–5.96;
3.66 ±0.08 % [35,36]
acid palmitic
1.2;
2.1;
4.58–6.42;
[g/100 g flaxseed] [8,32,36]
4.58–6.42;
5.44 ±0.11 [%] [35,36]
acid glutamic 19.6 [g/100 g flaxseed] [32]
acid aspartic 9.3 [g/100 g flaxseed] [32]
saturated (SAFA/SFA)
8.42–12.90;
9.18 ±0.21;
10.0;
9.23-24.01 [%] [33,35–37]
total monounsaturated
(MUFA)
16.37–23.00;
16.69 ±0.24;
16.4–23.5;
18.20–23.53;
22.5
complete unsaturated (PUFA)
52.15–76.94;
74.09 ±0.64;
57.8–74.3
acids phenolic and
lignans
Non-defatted extracts Defatted extracts
[mg/100 g] [32,38,39]
p-hydroxybenzoic acid 1719 6454
chlorogenic acid (CGA) 720–750 1435
ferulic acid 109–161 313
coumaric acid 87 130
gallic acid 28–29 17
vanilla acid 22 42
sinapic acid 18 27
protocatechuic acid 7 7
caffeic acid 4 15
diphyllin 4.2 n.a. 1
secoisolariciresinol
diglucoside (SDG) 1300 n.a.
secoisolariciresinol 156,165 n.a.
lariciresinol 1.7 n.a.
matairesinol (MAT) 3.1 n.a.
pinoresinol 0.8 n.a.
Flavonoids total 35–70 mg/100 g of flaxseed linen [32]
minerals
calcium 170–236
[mg/100 g flaxseed] [3,32]
magnesium 431
phosphorus 370–622
potassium 750–831
sodium 27
zinc 4
iron 2.7–5
manganese 3
Vitamins and dyes
α-Tocopherol 6.26
(µg/g) [40–42]
β-Tocopherol 1/07
γ-Tocopherol 302.0
δ-Tocopherol 2.26
β-Carotenoid 0.52
Xanthophyll 27.1
vitamin C 0.5
g/100 g of flaxseed linen [32]
vitamin B1 0.5
vitamin B2 0.2
vitamin B3 1.2
vitamin B6 0.6
pantothenic acid 0.6
1n.a.—not available.
Int. J. Mol. Sci. 2025,26, 1226 6 of 19
One of the key active ingredients found in linseed are omega-3 fatty acids, including
monounsaturated
α
-linolenic acid (ALA). ALA accounts for approximately 55% of the total
fatty acid content in linseed seeds [
43
]. The body cannot produce this fatty acid on its own and
needs to obtain it from external sources [
44
]. Several studies have shown that omega-3 fatty
acids are especially helpful for cardiovascular health due to their impact on blood cholesterol
levels and their ability to reduce cardiovascular mortality risk [
45
–
47
]. Furthermore, they
regulate metabolic processes and have anti-cancer properties [
45
]. According to studies,
flaxseed consumption has been found to reduce triglycerides as well as improve the blood
lipid profile in people with metabolic disorders [
22
]. As well as being high in protein, linseed
also contains high levels of linoleic acid, which contributes to proper cholesterol levels [
48
,
49
].
Lignans are diphenolic compounds that are formed from the combining of two conif-
erous alcohol residues in the cell wall of higher plants [
50
]. In flaxseeds, the dominant
lignan component is diglucoside secoisolaresinol (SDG), which makes up about 95% of the
lignan content. The remaining 5% are laryresinol, pinoresinol, and matairesinol [
6
]. The
health benefits of flax lignans are thought to be due to their anti-oxidant activity, primarily
as hydroxyl radical scavengers, and their hormone-like activity, in part due to their struc-
tural similarity to 17-
β
-estradiol [
50
]. The behavior of lignans depends on the biological
level of estradiol. With normal estradiol levels, lignans act as estrogen antagonists, but
in postmenopausal women when estrogen levels are low, they may act as weak estro-
gens [
47
]. A combination of bioactive polyphenols and lignans found in linseed, including
the anti-oxidant secoisolariciresinol diglucoside (SDG), as well as its fiber content, benefit
the cardiovascular system [51].
Mammalian lignans enterolactone (EL) and enterodiol are produced by the action
of bacteria in the colon on SDG. Case-control studies have shown a significant inverse
relationship between breast cancer risk and urinary enterolactone levels [52,53].
Researchers have also found that linseed may have an antiviral effect, particularly
against HIV. Several studies have shown that lignans found in linseed can inhibit HIV virus
replication, giving hope for its use in treatment and prevention [54,55].
The orbitides found in flaxseed and flaxseed rhizome are hydrophobic cyclic peptides
that contain eight or nine amino acids without cysteine [
56
]. More than 20 linseed orbitides
have been identified from isolated linseed oil products to date [56].
There is also insoluble fiber in flaxseed, which contributes to the high nutritional value
of the seed. This fiber is necessary for the proper functioning of the digestive system by
maintaining proper intestinal peristalsis. It also provides a feeling of satiety, which may
be especially helpful when losing weight. In some studies, flaxseed fiber has been shown to
prevent digestive disorders such as constipation and even to reduce the risk of colon cancer [
10
].
Besides the active ingredients mentioned above, flaxseed also contains numerous
valuable compounds, including vitamins (A, E, B), minerals (magnesium, iron, zinc), and
flavonoids—Table 1. All of these nutrients play an important role in strengthening the
immune system; improving the skin, hair, and nails; and contributing to the healthy
function of the nervous system.
4. Anti-Oxidant Properties
A cellular inflammatory response is a complex reaction created by both external
and internal factors, and it aims to eliminate the cause of the damage and its negative
effects on cell function. In pathological inflammation, phagocytosis-deficient cells and
those that cannot phagocytose produce an excess of reactive oxygen species (ROS) and
nitrogen species (RNS). These substances spread into the intercellular space, leading to
local oxidative stress and tissue damage [
57
,
58
]. The main pathway of oxidative damage is
hydroxyl-induced lipid peroxidation and hydroxylation of free radicals (OH
·
). As a result of
Int. J. Mol. Sci. 2025,26, 1226 7 of 19
lipid peroxidation, membrane fluidity decreases; membrane leakage increases; membrane
proteins are damaged; and receptors, enzymes, and ion channels are inactivated [
59
].
Excessively active or prolonged inflammation may contribute to the development of various
chronic illnesses [60].
Linseeds contain a large amount of phenolic compounds. It is well known that these
phenolic compounds have anti-cancer as well as anti-oxidant properties. Numerous clinical
studies have demonstrated the anti-inflammatory potential of n-3 polyunsaturated fatty
acids mediated by the decrease in concentrations of inflammatory mediators, such as
prostaglandins E2, leukotriene B4, TNF-α, interleukins, and cytokines [3].
The analysis showed that in overweight people (BMI >30), linseed consumption re-
sulted in a reduction of the levels of TNF
α
, CRP, and hs-CRP compared to the placebo
group. However, no significant differences were observed in other population subgroups.
Additionally, in people with a higher BMI, flaxseed slightly reduced the level of IL-6, al-
though this effect was not significant [
60
]. In rodents, a diet enriched with
α
-linolenic acid,
a component of linseed, reduced oxidative stress and inflammation during myocardial
infarction. The linseed component, n-3 PUFA (ALA), provided heart protection. Flaxseeds
also contain high levels of functional phenolic compounds that may increase the cardiopro-
tective effect [
61
]. Additionally, the linoleic acid metabolite 10-hydroxy-cis-12-octadecenoic
acid (HYA) has been shown to reduce colonic damage in dextran sodium sulfate (DSS)-
induced colitis by modulating inflammatory factors, oxidative state, and colonic microbiota
imbalance. It produces the effect by inhibiting the expression of TNF-
α
and changes in the
expression of intestinal epithelial tight junction (TJ) proteins such as occludin, occludin-1,
and myosin light-chain kinase [62].
The consumption of flaxseed has been shown to reduce insulin resistance, lipid abnor-
malities, atherosclerosis, hypertension, and cardiac arrhythmias, possibly by improving
anti-inflammatory cytokine levels and insulin sensitivity [
63
]. The benefits of linseed oil
on reducing chronic inflammation and reducing CVD risk have also been indicated in
hemodialysis patients, namely, a reduction in CRP and hs-CRP levels and a reduction in
sVCAM-1 levels [45–47]. Furthermore, linseed extract has been reported to reduce TNF-α
levels and alleviate the severity of colitis [47].
By containing compounds such as SDG and ALA, flaxseed affects genes involved
in inflammation control in obese animals. As reported by Mann et al., supplementation
with flaxseed suppresses mild obesity-related inflammation by suppressing Akt2 protein
expression, which reduces the activation of the IKK
β
/NF-
κ
B inflammatory pathway and
the production of pro-inflammatory cytokines [64].
Flaxseed peptides exhibited anti-oxidant properties by scavenging hydroxyl radical
(OH
·
) and inhibiting nitric oxide (NO) production in macrophages [
65
]. Moreover, it was
also observed that linseed extract showed anti-oxidant capacity in the test with stable free
radical molecules (DPPH). The observed effect explains the potential mechanism of the
positive effect of linseed on wound healing. In animal studies, flaxseed products caused
fibrous tissue to be formed and collagen to migrate, indicating that they may be a safe
and effective product for repairing and regenerating the skin [
66
,
67
]. Yu et al. reported
that oral administration of flaxseed SDG reduced skin inflammation and down-regulated
JAK/STAT6 signaling pathways to reduce Th2 immune responses in mice with atopic
dermatitis (AD) [68].
In mice exposed to asbestos, which is a risk factor for cancer, including pleural
mesothelioma, synthetic diglucoside linseed secaisolaricoresinol (SGD) reduced peritonitis
and white blood cell influx. A study showed that SGD inhibited both granulocyte and
macrophage infiltration into the peritoneum [69].
Int. J. Mol. Sci. 2025,26, 1226 8 of 19
Its anti-inflammatory properties are also attributed to its ability to suppress the release
of inflammatory mediators, such as prostaglandins E2, histamine, leukotrienes B4, and
bradykinin. Furthermore, flaxseed oil inhibits the inflammatory process induced by arachi-
donic acid, affecting cyclooxygenase and lipoxygenase, which are involved in arachidonic
acid metabolism [20].
Different results are reported by Aguilar et al. in their experiment; linseed supplemen-
tation had no significant effect on pro-inflammatory biomarkers, including TNF-
α
; IL-1
β
and IL-6; and anti-inflammatory biomarkers, such as IL-10 in overweight perimenopause-
aged women [
70
]. Similar conclusions were reported by Shareghfarid et al., in which
the use of linseed had no significant effect on body weight and inflammatory markers in
overweight and prediabetic adults [
71
]. Another study found that in normal-weight people
following a healthy diet, linseed oil supplementation also did not affect inflammatory
markers and lipid profiles [72].
Biao Y et al. reported that polysaccharides fraction isolated from flaxseed hull and com-
posed of eight kinds of monosaccharides—mannose, rhamnose, galactose, glucose, galac-
tose, xylose, arabinose, and fucose—expressed potent anti-oxidant and anti-inflammatory
properties, probably attributed to its effects on the NO and MAPK pathway [
73
]. Another
possible mechanism of reducing the release of free radicals and inhibiting macrophages
function is modulation from the TLR4/NF-
κ
B/MAPK pathway by flaxseed linusorbs [
74
].
The findings of Huang X. et al. confirmed the anti-oxidant activity of flaxseed polyphe-
nols [
21
]. They also analyzed the phenolic acids and flavonoids content in flaxseeds and
revealed significant differences in polyphenol quantities and types among different flaxseed
varieties, while sinapic acid, ferulic acid, kaempferol, and quercitrin were found to be the
most abundant phenolic compounds. The summary of potential molecular mechanisms of
anti-oxidant and anti-inflammatory effects of flaxseed are summarized in Table 2.
In the majority of the studies, whole flaxseeds or extracts were used, not isolated and
a purified particular compound or combination of compounds; this model reflects dietary
supplementation of flaxseeds. On the other hand, the separate compounds responsible for
particular molecular mechanisms of anti-oxidant activities are poorly identified, which dis-
courages the further use of a single compound in a higher concentration in supplementation
or dietary treatment.
Table 2. The effects of flaxseed in anti-oxidant and anti-inflammatory activity and their potential
mechanism.
Material Type Effect Possible Molecular Mechanism References
In vitro—RAW264.7 cells anti-oxidant and
anti-inflammatory
impact on the NO and MAPK pathways
[73]
In vitro—RAW264.7 cells anti-inflammatory
inhibitory effect on TLR4, inhibition of
transduction of the NF-κB/MAPK
signaling pathway
[74]
Human clinical trial (patients with CF
1
)
anti-inflammatory, decrease in
IsoP and TNFαROS sweeping, Nrf2 path activation [21]
Animal model anti-inflammatory stopping ROS and acting against the
IKKβ/NF-κB signaling pathway [64]
Meta-analysis anti-inflammatory decrease in TNFα, CRP, and hs-CRP [60]
In vitro—RAW 264.7 cells anti-oxidant
regulation of SOD, GSH, and CAT
activity; mitigation of the decline in
intracellular GSH levels; counteraction
of the increase in ROS and MDA levels
[75]
1CF—cystic fibrosis.
Int. J. Mol. Sci. 2025,26, 1226 9 of 19
5. Anti-Cancer Properties
Numerous scientific studies have confirmed that the health-promoting properties
of linseed can support human health. Taking into account flaxseed’s health-promoting
properties, researchers are testing flaxseeds for anti-cancer properties.
There is evidence that linseed proteins may have anti-cancer properties, suggest-
ing they may be used in cancer treatments in the future [
76
]. Additionally, linseed is
characterized by anti-oxidant properties, which may significantly reduce the severity of
cancer-related symptoms due to the association of imbalances in oxidation reactions and
anti-oxidant mechanisms [10].
Flaxseed is also rich in lignans, which are important polyphenols in the context of anti-
cancer effects. Plant substances such as polyphenols are also generally considered to have
anti-inflammatory, antiviral, antibacterial, etc. effects [
77
]. Lignans contained in linseed also
have anti-cancer properties and may be promising chemotherapeutic/chemopreventive
substances [39].
The introduction of linseed orbitides into the body has health potential, especially a
strong anti-cancer effect [
78
]. Flaxseed is considered a superfood for its health properties,
and regular consumption helps regulate cancer-related genes [
79
]. Therefore, linseed can
be a valuable addition to the diet of people who want to help fight or prevent cancer.
Studies have confirmed the anti-cancer effect of substances contained in linseed,
among others, against breast cancer cells, cervical cancer cells, ovarian cancer, colon cancer,
leukemia cells, and melanoma cells [
80
]—Table 3. Studies have also shown that linseed
derivatives, for example, oil linseed, inhibit melanoma metastasis and reduce the growth
of lung cancer, which confirms their protective effect against cancer [
81
]. Very interestingly,
it also turned out that the growth of non-cancerous cells was not inhibited by treatment
with linseed oil, which indicates that linseed and its products preferentially kill malignant
cells, without toxicity to normal cells [80].
The lignans enterodiol and enterolactone are believed to be partially responsible for
inhibiting the growth of human prostate cancer [
3
]. Additionally, flaxseed ligands may
have non-estrogenic effects, including anti-oxidant activity and inhibition of angiogenesis
and cell membrane ATPase [82].
In the study by Sung et al., the anti-cancer effect of linusorb LOB3 ([1–9-N
α
C]-linusorb
B3), a natural peptide found in linseed, has been demonstrated by inducing apoptosis and
inhibiting the motility of cancer cells, especially glioma cells [
83
]. However, it is worth
emphasizing that intravenous infusion of LOB3 may be toxic to humans and may not be
appropriate for the treatment of human breast cancer or melanoma. However, the cream
formulation of LOB3 may have topical use against melanoma and possibly other types of
skin cancers [84].
The anti-proliferative effect of linseed has also been demonstrated in patients with
prostate cancer before surgery. A potential mechanism of action may be down-regulation
of Ki-67 expression [85].
Linseed and its oil reduce the growth of tumors in the later stages of carcinogenesis,
while the mammalian lignan precursor exerts the greatest inhibitory effect on the growth
of new tumors [3].
The role of linseed oil in cancer prevention is attributed to its high level of
α
-linolenic
acid. The fatty acid composition of the tumors revealed a higher incorporation of
α
-linolenic
acid, which in turn resulted in the inhibition of tumor cell growth [
3
].
α
-linolenic acid has
been shown to exert anti-inflammatory effects and has been shown to have anti-proliferative
effects in animal models of premenopausal (high-estrogen) breast cancer [86].
Epidemiological studies indicate that a diet rich in phytoestrogens reduces the risk of
various hormone-dependent cancers, heart disease, and osteoporosis [3].
Int. J. Mol. Sci. 2025,26, 1226 10 of 19
A very interesting relationship was also demonstrated in which linseed oil increased
the effectiveness of trastuzumab (TRAS) in reducing the growth of breast tumors (BT-474)
with HER2 overexpression at high levels of E2 in the circulation [87].
Flaxseed also led to the suppression of target genes, including potent oncogenes,
repressors that target inhibitory cytokine receptors, important growth signaling mediators,
proliferative and anti-apoptotic factors, and steroid receptors that are up-regulated in
cancer, according to Dikshit et al. [
88
]. There was also a change in molecular targets
involved in inflammation, glucose metabolism, and apoptosis, indicating the anti-cancer
and anti-inflammatory effects of linseed in pre-cancerous ovaries [89].
Table 3. The effects of flaxseed in anti-cancer activity and their potential mechanism.
Type of Cancer Cell Line In Vitro/Animal
Model
Active
Compounds Effect Possible Molecular
Mechanism References
breast cancer
HER2(+) BT-474 animal model–mice
Freshly cold-pressed
FSO 1containing 9%
saturated fat, 18%
monounsaturated fat,
14% linoleic acid, and
58% ALA 2
Reduction of tumor
size, increase in
tumor cell apoptosis,
and reduction of
their proliferation
Decreased HER2
signaling through
pathways including
MAPK and the PI3k–Akt
kinase signaling pathway,
decreased expression of
other growth factor
receptors EGFR and
IGFIR
[87]
breast cancer
ER(−)MDA-MB-435 animal model–mice
10% freshly ground
flaxseed, detailed
composition NA 3
Reduction of tumor
growth rate,
inhibition of
metastases
Reducing the expression
of IGF-I and EGFR [82]
melanoma,
breast cancer,
cervical cancer
B16-BL6,
MCF-7,
MDA-MB-231,
MDA-MB-468,
HeLa
in vitro
Flaxseed oil or a
combination of
individual fatty acids:
ALA 2, DHA, EPA,
linoleic acid, oleic acid,
and palmitic acid and the
lignans enterodiol and
EL 4
Inhibiting the
proliferation of
cancer cells and
promoting their
apoptosis
Promoting apoptosis by
activating nuclear
fragmentation, increasing
the activity of caspase-3
and caspase-8
[80]
ovarian cancer primary cancer
animal
model–chickens
(Gallus domesticus)
11 grams of flaxseed per
day, or 6.2 g/kg body
weight, detailed
composition NA 3
Reducing the
incidence and
severity of ovarian
cancer
Reduction of COX-2
levels and PGE2
expression
[89]
ovarian cancer primary cancer
animal
model–chickens
(Gallus domesticus)
11 grams of flaxseed per
day, or 6.2 g/kg body
weight, detailed
composition NA 3
Chemosuppressive
effect, inhibition of
metastases, slowing
down the rate of
tumor growth
Anti-oxidant effect [90]
melanoma,
breast cancer
A375,
Sk-Br-3,
MCF7
in vitro
Linoorbitides: LOB3
(NαC-[Ile-Leu-Val-Pro-
Pro-Phe-Phe-Leu-Ile]),
LOB2
(NαC-[Met-Leu-Ile-Pro-
Pro-Phe-Phe-Val-Ile]),
[MetO]-LOB2 (NαC-
[MetO-Leu-Ile-Pro-Pro-
Phe-Phe-Val-Ile]) and
[MetO]-LOB1
(NαC-[Met-Leu-Val-Phe-
Pro-Leu-Phe-Ile])
Cytotoxicity
towards cancer cells
Cell type specific,
probably hydrophobic
interaction with the cell
membrane, anti-oxidant
potential
[84]
glioma,
breast cancer
human glioma cell
line C6,
U251,
MDA-MB-231
in vitro LOB3
([1–9-NαC]-linusorb B3)
Promoting
apoptosis, inhibiting
cell motility,
preventing
metastasis
Inhibition of SRC and
STAT3 activation,
inhibition of actin
polymerization,
inhibition of Bcl-2 and
Bc1, activation of
caspase-9 and caspase-3
[83]
melanoma B16BL6 animal model–mice
(C57BL/6)
Flaxseed containing 2.93
µmol/g of SDG 5
Reducing the
number,
cross-sectional area,
and volume of
metastatic tumors
NA 3[91]
colon cancer primary cancer
animal
model–Sprague
Dawley rats
SDG
5
-rich extracts (17.57
µg of SDG in 1 mg)
Chemopreventive
effect
Inhibition of CDK4,
reduction of TNF-αand
IL-1βlevels
[92]
Int. J. Mol. Sci. 2025,26, 1226 11 of 19
Table 3. Cont.
Type of Cancer Cell Line In Vitro/Animal
Model
Active
Compounds Effect Possible Molecular
Mechanism References
breast adenocar-
cinoma MCF-7 (HTB-22) in vitro
Flaxseed extract
containing
hexadecanoic acid
methyl ester (9.52%),
methyl stearate
(9.25%),
trans-13-octadecenoic
acid methyl ester
(22.54%),
9,12-octadecadienoic
acid (Z, Z)-methyl
ester (19.02%), 9,12,15-
octadecatrienoic acid
methyl ester (Z, Z, Z)
Inhibiting the
growth of cancer
cells and
inducing
apoptosis
Increase in lipid
peroxidation;
significant increase in
p53 gene expression
and weak increase in
MDM2; increase in
levels of cleaved
caspase 3,
cleaved-PARP, as well
as cleaved caspase 7
[93]
acute myeloid
leukemia
KG-1 and
Monomac-1 acute
myeloid leukemia
cell lines
in vitro
SDG 5, END 6, and
EL 4; EL 4was the
major compound that
showed a
dose-dependent and
time-dependent
anti-proliferative
effect
Antiproliferative
effect, promoting
apoptosis
Up-regulation of Bax
and down-regulation
of Bcl-2, increase in
Bax/Bcl-2 ratio,
overexpression of
lower cytochrome C
molecule, increase in
Caspase 9 activation
[94]
prostate adeno-
carcinoma primary cancer
animal model –
TRAMP and
C57BL/6
transgenic mice
Flaxseed, detailed
composition NA
Inhibiting the
growth and
development of
cancer cells
Ki-67 level reduction [95]
breast adenocar-
cinoma,
hepatocellular
carcinoma,
colon cancer
MCF-7, HepG-2,
HCT-116 in vitro Fs-AuNPs—flaxseed
gold nanoparticles
Non-cytotoxic,
anti-oxidant
effects, induction
of apoptosis of
cancer cells
NA [96]
breast cancer MDA-MB-435
animal model -
athymic nude
mice (Ncr nu/nu)
10% freshly ground
flaxseed and SDG 5
Inhibition of
distant
metastases, little
effect on
locoregional
tumor recurrence
Hormone-dependent
mechanisms,
anti-oxidant,
inhibition inof signal
transduction
pathways modulated
by IGF-I and EGFR
expression
[97]
ovarian adeno-
carcinoma BG1FR animal model –
chickens Whole flaxseed
Reducing
prostaglandin
production,
promoting
apoptosis
through 2-
methoxyestradiol,
reducing the
aggressiveness
and invasiveness
of tumors
Increased CYP1A1
expression, increased
p38 and ERK 1/2
MAPK activation in
the ovary, SMAD 7,
decreased
16-hydroxyestradiol
levels, increased
2-methoxyestradiol
levels
[98]
liver cancer HepG2 in vitro
Non-oxidized
flaxseed orbitides
(CLA and CLB) and
the oxidized flaxseed
orbitides (CLC and
CLK)
Inducing
apoptosis of
cancer cells
Increased protein
levels of Bax/Bcl-2,
Cyto C, caspase-3,
and caspase-8
[78]
1
FSO—flaxseed oil,
2
ALA—
α
-linolenic acid,
3
NA—not available,
4
EL—enterolactone,
5
SDG—
secoisolariciresinol diglycoside, 6END—Enterodiol.
It is also worth mentioning the study by Asselin et al., which showed for the first time
that preventive treatment with linseed, including its components
α
-linolenic acid (ALA)
and diglucoside secoisolaresinol (SDG), significantly alleviated the cardiotoxic side effects
of doxorubicin + trastuzumab in a chronic female
in vivo
model of chemotherapy-induced
cardiomyopathy. Flaxseed prevented adverse left-ventricular remodeling; alleviated my-
Int. J. Mol. Sci. 2025,26, 1226 12 of 19
ofibrillar dysfunction; reduced the degree of inflammation after treatment; and attenuated
the degree of cardiac apoptosis, oxidative stress, and mitochondrial dysfunction [99].
There are a number of factors that contribute to the development of cancer, such as
oxidative stress, inflammation, and cellular malfunction. Research indicates that flaxseed’s
active ingredients, such as lignans and proteins, may have promising properties. In recent
years, researchers have identified lignans in linseed as potential chemotherapeutic and
chemopreventive agents. These compounds may be used to treat cancer and prevent its
occurrence in the future. Cancer cells are inhibited by lignans and undergo apoptosis, a
natural death process, as a result of their presence. One of the lignans present in linseed,
secoisolariciresinol diglucoside (SDG), has been identified as a strong inhibitor of the 5
α
-
reductase enzyme, which in some cases may contribute to the development of prostate
cancer. Additionally, linseed also contains other substances with anti-cancer properties,
such as
α
-linolenic acid and lignin. Also, flaxseeds are rich in fiber, which aids digestion
and reduces the risk of cancer, such as colon cancer, among others.
Combining flaxseed with other drugs has also been proven to produce an anti-cancer
effect. In mice with transplanted colon cancer, combining linseeds with cyclophosphamide
significantly increased the effectiveness of treatment. It appears that linseed could impact
cancer treatment by reducing doses of drugs and thereby limiting toxicity.
Another important property of linseed, although questioned in some studies, is its
ability to reduce inflammation in the body. It is well know that chronic inflammation can
induce cancerogenesis.
The main compound of flaxseed responsible for potential inhibition of inflammation
is
α
-linolenic acid, which is an unsaturated fatty acid. Additionally, it is a precursor to
eicosanoids, which are important mediators of inflammatory processes. Some studies
have shown that consuming linseed may reduce the concentration of pro-inflammatory
cytokines and the activity of factors responsible for the development of inflammation, such
as NF-
κ
B. However, other studies report different results, suggesting that the potential
effects of linseed and its products are not clinically significant and therefore do not work as
anti-inflammatory agents. We suggest that the lack of anti-inflammatory effects of linseed
in some studies could have several reasons: First, due to individual differences, flaxseed
supplementation may vary according to a person’s genetic makeup, health status, age,
diet, and lifestyle [
100
,
101
]. Secondly, an insufficient dose of linseed or its components
could be the cause. To achieve anti-inflammatory effects, a certain amount of flaxseed may
be required, and the doses used by some people may be too low to be effective [
102
,
103
].
As a third factor, poor bioavailability may have been responsible [
104
].
α
-linolenic acid
(ALA) must be converted in the body to more active forms of omega-3 acids, such as
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Despite this, this process is
not equally effective for everyone, especially if omega-3 fatty acids levels are not low [
105
].
Assimilation and absorption are other possible reasons. Ground flaxseeds (or carefully
chewed flaxseeds) can be absorbed by the body more effectively [
106
]. Otherwise, unground
seeds may pass through the digestive system almost unchanged and have no effect. Next,
it is worth considering potential interactions with other dietary ingredients. A diet high
in other fatty acids, especially omega-6, may increase inflammation in the body, even
when consuming flaxseed [
107
]. Inflammation of high intensity could also contribute to
the problem. Compared with the intensity of inflammation in some patients, especially
those with chronic inflammation or autoimmune diseases, flaxseed may have a relatively
weak anti-inflammatory effect. Our last consideration is lignan metabolism. It has been
suggested that the microbiota of the gut may determine the degree of effectiveness of the
lignans in flaxseed [108,109].
Int. J. Mol. Sci. 2025,26, 1226 13 of 19
6. Non-Nutritive Ingredients of Flaxseed
Despite its numerous health benefits, flaxseed also contains bioactive compounds that
can produce harmful health effects, particularly when overconsumed or improperly pro-
cessed. Several potentially harmful components present in flaxseed have been highlighted
in the scientific literature, including cyanogenic glycosides, proteolytic enzyme inhibitors,
and antinutrients such as phytic acid and oxalates [110].
6.1. Cyanogenic Glycosides
One of the bioactive compounds present in flaxseed is cyanogenic glycosides, the most
prominent being linustatin, neolinustatin, and linamarin [
111
]. The average content of
cyanogenic glycosides in flaxseed is around 100–300 mg hydrogen cyanide (HCN) per kilo-
gram of seeds, which limits the recommended daily intake of flaxseed [
112
]. Mature seeds
contain fewer glycosides compared to unripe seeds. In the presence of plant enzymes or
intestinal microflora, these glycosides can be hydrolyzed into toxic hydrogen cyanide (HCN),
which is further metabolized into thiocyanates via intestinal
β
-glycosidase [
3
,
26
]. Studies
indicate that consuming large quantities of unprocessed flaxseed can lead to hydrogen
cyanide poisoning, which may manifest as loss of appetite, lethargy, and neurological
disorders [
39
]. Furthermore, thiocyanates have been reported to inhibit iodine uptake by
the thyroid gland, exacerbating iodine deficiency disorders such as goiter and cretinism
with long-term exposure [
3
]. However, it is worth noting that the toxic effects of hydro-
gen cyanide from flaxseed are relatively rare and primarily occur in cases of excessive
consumption or improper meal preparation.
6.2. Phytic Acid
Phytic acid is another bioactive component of flaxseed that can negatively affect
health. It is well known for its antinutritional properties, as it forms stable complexes with
minerals like calcium, iron, magnesium, and zinc, thus hindering their absorption in the
small intestine [3].
6.3. Proteolytic Enzyme Inhibitors
Flaxseed contains inhibitors of proteolytic enzymes, including trypsin, which can
interfere with protein digestion. These inhibitors block the activity of proteolytic en-
zymes, impeding the breakdown of proteins in the gastrointestinal tract and reducing their
bioavailability. Long-term consumption of large amounts of these inhibitors may contribute
to protein deficiencies, particularly in individuals whose diet is low in other sources of
complete protein [113].
6.4. Effects on Hormonal Balance
Flaxseed also contains lignans, which are phytoestrogens, plant compounds that
mimic the action of estrogens. While flaxseed lignans have been shown to provide health
benefits, such as reducing the risk of hormone-dependent cancers, concerns have been
raised regarding their impact on hormonal balance [
48
]. High lignan intake may lead to
hormonal disruptions, especially in individuals with pre-existing hormonal disorders or
in children during developmental stages. However, these effects are dose-dependent and
vary according to individual sensitivity to phytoestrogens [114].
7. Conclusions
Flaxseed (Linum usitatissimum L.), one of the oldest cultivated plants, has been used for
centuries in traditional medicine. Recent scientific research has increasingly confirmed its
anti-cancer properties, particularly, its effectiveness in preventing hormone-related cancers
Int. J. Mol. Sci. 2025,26, 1226 14 of 19
such as breast and prostate cancer, and its ability to inhibit tumor growth. These effects
are largely attributed to its rich content of omega-3 fatty acids, lignans, and polyphenols,
which help reduce oxidative stress, inflammation, and the risk of chronic diseases.
Flaxseed’s dual role as both a dietary supplement and therapeutic agent makes it a
valuable tool in health promotion and disease prevention. However, the anti-inflammatory
effects of flaxseed have been reported inconsistently, and the lack of a strong anti-
inflammatory response could limit its preventive impact on cancer development. Ad-
ditionally, flaxseed’s health benefits may take time to manifest, and its effects are best
realized when combined with other healthy lifestyle changes, such as a balanced diet and
regular physical activity. Despite its many health benefits, there are some concerns about
flaxseed due to the presence of antinutritional substances like phytic acid and cyanogenic
glycosides, which can be toxic in large amounts. However, proper processing methods can
significantly reduce these compounds, enhancing both the nutritional value and safety of
flaxseed. Further research is needed to refine consumption guidelines, ensuring maximum
benefits while minimizing risks associated with overconsumption or improper use.
Author Contributions: Conceptualization, A.E.S. and J.T. (Jacek Tabarkiewicz); resources, A.E.S.
and J.T. (Julia Trojniak); writing—original draft preparation, A.E.S. and J.T. (Julia Trojniak); writing—
review and editing, A.E.S., J.T. (Julia Trojniak), and J.T. (Jacek Tabarkiewicz); visualization, A.E.S. and
J.T. (Julia Trojniak); supervision, J.T. (Jacek Tabarkiewicz). All authors have read and agreed to the
published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflicts of interest.
Abbreviations
Akt2 ACT Serine/Threonine Kinase 2
ALA α-linolenic acid
Bc1 complex III or ubiquinol cytochrome C oxidoreductase or cytochrome bc1
Bcl-2 B-cell CLL/lymphoma 2
CDK4 cyclin-dependent kinase 4
CF cystic fibrosis
CGA chlorogenic acid
COX-2 cyclooxygenase 2
CRP C-reactive protein
CVD cardiovascular disease
Cyclo C cytochrome C
DHA docosahexaenoic acid
DSS dextran sodium sulfate
EGFR epidermal growth factor receptor
EL enterolactone
EPA eicosapentaenoic acid
HER2(+) HER2-positive breast cancer
Hs-CRP highly sensitive C-reactive protein
HYA 10-hydroxy-cis-12-octadecenoic acid
IGF-I insulin like growth factor 1
IGFIR insulin like growth factor 1 receptor
IKKβIκB Kinase β
Int. J. Mol. Sci. 2025,26, 1226 15 of 19
IL-1βinterleukin 1β
IL-6 interleukin 6
IL-10 interleukin 10
LOB3 [1–9-N αC]-linusorb B3
MAPK mitogen-activated protein kinases
MAT matairesinol
NF-κB the nuclear factor kappa B
PGE2 prostaglandin E2
PI3k-Akt the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)
SDG diglucoside secoisolaresinol
SRC proto-oncogene tyrosine-protein kinase Sr
STAT3 signal transducers and activators of transcription 3
sVCAM-1 circulating vascular cell adhesion molecule-1
TNF-αtumor necrosis factor α
TRAS trastuzumab
References
1.
Li, Y.; Chen, J.; Li, X.; Jiang, H.; Guo, D.; Xie, F.; Zhang, Z.; Xie, L. Adaptive Response and Transcriptomic Analysis of Flax (Linum
usitatissimum L.) Seedlings to Salt Stress. Genes 2022,13, 1904. [CrossRef] [PubMed]
2. Rymar, E. Własciwo´sci Prozdrowotne Lnu (Linum ussitatissimum L.). Herbalism 2021,3, 92–111. [CrossRef]
3.
Kajla, P.; Sharma, A.; Sood, D.R. Flaxseed—A Potential Functional Food Source. J. Food Sci. Technol. 2015,52, 1857–1871. [CrossRef] [PubMed]
4.
Sarfraz, H.; Ahmad, I.Z. A systematic review on the pharmacological potential of Linum usitatissimum L.: A significant nutraceuti-
cal plant. J. Herb. Med. 2023,42, 100755. [CrossRef]
5.
Popis, E.; Ratusz, K.; Przybysz, M.A.; Krygier, K.; Konarska, M.; Sakowska, A. World and Polish Production of Linseed and
Linseed Oil. Sci. J. Wars. Univ. Life Sci. SGGW Probl. World Agric. 2015,15, 106–116.
6.
Calado, A.; Neves, P.M.; Santos, T.; Ravasco, P. The Effect of Flaxseed in Breast Cancer: A Literature Review. Front. Nutr. 2018,5,
4. [CrossRef] [PubMed]
7.
Singh, K.K.; Mridula, D.; Rehal, J.; Barnwal, P. Flaxseed: A Potential Source of Food, Feed and Fiber. Crit. Rev. Food Sci. Nutr.
2011,51, 210–222. [CrossRef] [PubMed]
8. Bernacchia, R.; Preti, R.; Vinci, G. Chemical Composition and Health Benefits of Flaxseed. Austin J. Nutr. Food Sci. 2014,2, 1045.
9.
Jarošová, M.; Lorenc, F.; Bedrní ˇcek, J.; Petrášková, E.; Bjelková, M.; Bártová, V.; Jarošová, E.; Zdráhal, Z.; Kyselka, J.; Smetana, P.;
et al. Comparison of Yield Characteristics, Chemical Composition, Lignans Content and Antioxidant Potential of Experimentally
Grown Six Linseed (Linum usitatissimum L.) Cultivars. Plant Foods Hum. Nutr. 2024,79, 159–165. [CrossRef] [PubMed]
10. Nowak, W.; Jeziorek, M. The Role of Flaxseed in Improving Human Health. Healthcare 2023,11, 395. [CrossRef]
11.
Guan, Z.-W.; Yu, E.-Z.; Feng, Q. Soluble Dietary Fiber, One of the Most Important Nutrients for the Gut Microbiota. Molecules
2021,26, 6802. [CrossRef]
12.
Caligiuri, S.P.; Aukema, H.M.; Ravandi, A.; Guzman, R.; Dibrov, E.; Pierce, G.N. Flaxseed consumption reduces blood pressure
in patients with hypertension by altering circulating oxylipins via an
α
-linolenic acid-induced inhibition of soluble epoxide
hydrolase. Hypertension 2014,64, 53–59. [CrossRef] [PubMed]
13.
Skoczy´nska, A.H.; Gluza, E.; Wojakowska, A.; Turczyn, B.; Skoczy ´nska, M. Linseed oil increases HDL3 cholesterol and decreases
blood pressure in patients diagnosed with mild hypercholesterolaemia. Kardiol. Pol. 2018,76, 1242–1250. [CrossRef] [PubMed]
14.
Prasad, K. Hypocholesterolemic and antiatherosclerotic effect of flax lignan complex isolated from flaxseed. Atherosclerosis 2005,
179, 269–275. [CrossRef] [PubMed]
15.
Prasad, K. Importance of Flaxseed and Its Components in the Management of Hypertension. Int. J. Angiol. 2019,28, 153–160. [CrossRef]
16.
Noreen, S.; Tufail, T.; Ul Ain, H.B.; Awuchi, C.G. Pharmacological, Nutraceutical, and Nutritional Properties of Flaxseed (Linum
usitatissimum): An Insight into Its Functionality and Disease Mitigation. Food Sci. Nutr. 2023,11, 6820–6829. [CrossRef]
17.
Ebrahimi, B.; Nazmara, Z.; Hassanzadeh, N.; Yarahmadi, A.; Ghaffari, N.; Hassani, F.; Liaghat, A.; Noori, L.; Hassanzadeh, G.
Biomedical Features of Flaxseed against Different Pathologic Situations: A Narrative Review. Iran. J. Basic Med. Sci. 2021,24, 551.
18.
Berzou, S.; Labbaci, F.Z.; Guenzet, A.; Dida-Taleb, N.; Mir, H.; Krouf, D. Oil-Extracted from Flaxseeds Protects against Endothelial
Dysfunction and Oxidative Stress by Modulating Nitric Oxide, Thiols Contents and Improving Redox Status in Ouabain-Induced
Hypertensive Rats. Nutr. Clin. Métab. 2024,38, 120–1258. [CrossRef]
19.
Mosavat, S.H.; Masoudi, N.; Hajimehdipoor, H.; Emami Meybodi, M.K.; Niktabe, Z.; Tabarrai, M.; Ghorat, F.; Khodadoost, M.
Efficacy of Topical Linum usitatissimum L. (Flaxseed) Oil in Knee Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled
Clinical Trial. Complement. Ther. Clin. Pract. 2018,31, 302–307. [CrossRef]
Int. J. Mol. Sci. 2025,26, 1226 16 of 19
20.
Kaithwas, G.; Mukherjee, A.; Chaurasia, A.K.; Majumdar, D.K. Anti-inflammatory, analgesic and antipyretic activities of Linum
usitatissimum L. (flaxseed/linseed) fixed oil. Indian J. Exp. Biol. 2011,49, 932–938.
21.
Turowski, J.B.; Pietrofesa, R.A.; Lawson, J.A.; Christofidou-Solomidou, M.; Hadjiliadis, D. Flaxseed Modulates Inflammatory and
Oxidative Stress Biomarkers in Cystic Fibrosis: A Pilot Study. BMC Complement. Altern. Med. 2015,15, 148. [CrossRef]
22.
Sabet, H.R.; Ahmadi, M.; Akrami, M.; Motamed, M.; Keshavarzian, O.; Abdollahi, M.; Rezaei, M.; Akbari, H. Effects of Flaxseed
Supplementation on Weight Loss, Lipid Profiles, Glucose, and High-Sensitivity C-Reactive Protein in Patients with Coronary Artery
Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clin. Cardiol. 2024,47, e24211. [CrossRef]
23.
De Barros Mucci, D.; Fernandes, F.S.; dos Santos Souza, A.; de Carvalho Sardinha, F.L.; Soares-Mota, M.; Tavares do Carmo,
M.d.G. Flaxseed Mitigates Brain Mass Loss, Improving Motor Hyperactivity and Spatial Memory, in a Rodent Model of Neonatal
Hypoxic-Ischemic Encephalopathy. Prostaglandins Leukot. Essent. Fat. Acids 2015,97, 13–19. [CrossRef] [PubMed]
24.
Shrivastava, R.; Bhattacharya, S.; Verma, N.; Mehdi, A.A.; Pandey, A.; Ansari, J.A. Effects of Flaxseed on Perimenopausal
Symptoms: Findings from a Single-Blind, Randomized, Placebo-Controlled Study. Cureus 2024,16, e68534. [CrossRef] [PubMed]
25.
Ogawa, T.; Sawane, K.; Ookoshi, K.; Kawashima, R. Supplementation with Flaxseed Oil Rich in Alpha-Linolenic Acid Improves
Verbal Fluency in Healthy Older Adults. Nutrients 2023,15, 1499. [CrossRef]
26.
Mueed, A.; Shibli, S.; Jahangir, M.; Jabbar, S.; Deng, Z. A comprehensive review of flaxseed (Linum usitatissimum L.): Health-
affecting compounds, mechanism of toxicity, detoxification, anticancer and potential risk. Crit. Rev. Food Sci. Nutr. 2023,63,
11081–11104. [CrossRef]
27.
Kauser, S.; Hussain, A.; Ashraf, S.; Fatima, G.; Javaria, S.; Abideen, Z.U.; Kabir, K.; Yaqub, S.; Akram, S.; Shehzad, A.; et al.
Flaxseed (Linum usitatissimum); phytochemistry, pharmacological characteristics and functional food applications. Food Chem.
Adv. 2024,4, 100573. [CrossRef]
28.
Olombrada, E.; Mesias, M.; Morales, F.J. Risk/benefits of the use of chia, quinoa, sesame and flax seeds in bakery products. An
update review. Food Rev. Int. 2024,40, 1047–1068. [CrossRef]
29.
St˛epie´n, A.E.; Trojniak, J.; Tabarkiewicz, J. Health-Promoting Properties: Anti-Inflammatory and Anticancer Properties of
Sambucus nigra L. Flowers and Fruits. Molecules 2023,28, 6235. [CrossRef]
30.
St˛epie ´n, A.E.; Trojniak, J.; Tabarkiewicz, J. Anti-Cancer and Anti-Inflammatory Properties of Black Garlic. Int. J. Mol. Sci. 2024,25,
1801. [CrossRef] [PubMed]
31.
El Omari, N.; Menyiy, N.E.; Zengin, G.; Goh, B.H.; Gallo, M.; Montesano, D.; Naviglio, D.; Bouyahya, A. Anticancer and
Anti-Inflammatory Effects of Tomentosin: Cellular and Molecular Mechanisms. Separations 2021,8, 207. [CrossRef]
32.
Rahimlou, M.; Hejazi, J. Perspective Chapter: Flaxseed (Linumusitatissimum L.)—Chemical Structure and Health-Related Functions.
In Lignin—Chemistry, Structure, and Application; IntechOpen: London, UK, 2023; pp. 1–16.
33.
ˇ
Colovic, D.; Berenji, J.; Levart, A.; Levic, J.; Salobir, J.; Pezo, L.; ˇ
Colovic, R. Nutritional Characteristics of Seeds of Eighteen Linseed
(Linum humille Mill.) cultivars from Serbia. Zemdirbyste 2016,103, 175–182. [CrossRef]
34.
Shim, Y.Y.; Gui, B.; Arnison, P.G.; Wang, Y.; Reaney, M.J.T. Flaxseed (Linum Usitatissimum L.) Bioactive Compounds and Peptide
Nomenclature: A Review. Trends Food Sci. Technol. 2014,38, 5–20. [CrossRef]
35.
Affes, M.; Fakhfakh, J.; Ayadi, M.; Allouche, N. Characterization of Linum usitatissimum L. Used in Tunisia as Food Crop. Food
Meas. 2017,11, 781–791. [CrossRef]
36.
Yang, J.; Wen, C.; Duan, Y.; Deng, Q.; Peng, D.; Zhang, H.; Ma, H. The Composition, Extraction, Analysis, Bioactivities,
Bioavailability and Applications in Food System of Flaxseed (Linum usitatissimum L.) Oil: A Review. Trends Food Sci. Technol. 2021,
118, 252–260. [CrossRef]
37.
Bayrak, A.; Kiralan, M.; Ipek, A.; Arslan, N.; Cosge, B.; Khawar, K.M. Fatty Acid Compositions of Linseed (Linum usitatissimum
L.) Genotypes of Different Origin Cultivated in Turkey. Biotechnol. Biotechnol. Equip. 2010,24, 1836–1842. [CrossRef]
38.
El-Beltagi, H.S.; Salama, Z.; El-Hariri, D.M. Evaluation of Fatty Acids Profile and the Content of Some Secondary Metabolites in
Seeds of Different Flax Cultivars (Linum usitatissimum L.). Gen. Appl. Plant Physiol. 2007,33, 187–202.
39.
Bekhit, A.E.D.A.; Shavandi, A.; Jodjaja, T.; Birch, J.; Teh, S.; Mohamed Ahmed, I.A.; Al-Juhaimi, F.Y.; Saeedi, P.; Bekhit, A.A.
Flaxseed: Composition, Detoxification, Utilization, and Opportunities. Biocatal. Agric. Biotechnol. 2018,13, 129–152. [CrossRef]
40.
Kiczorowska, B.; Samoli´nska, W.; Andrejko, D.; Kiczorowski, P.; Antoszkiewicz, Z.; Zaj ˛ac, M.; Winiarska-Mieczan, A.; B ˛akowski,
M. Comparative Analysis of Selected Bioactive Components (Fatty Acids, Tocopherols, Xanthophyll, Lycopene, Phenols) and
Basic Nutrients in Raw and Thermally Processed Camelina, Sunflower, and Flax Seeds (Camelina sativa L. Crantz, Helianthus L.,
and Linum L.). J. Food Sci. Technol. 2019,56, 4296–4310. [CrossRef]
41.
Guo, X.; Wu, Y.; Xiang, N.; Gao, F.; Qiu, C. Effect of Ultrasonic Pretreatment on the Biosynthesis of Tocopherols, Tocotrienols and
Carotenoids in Flax Sprouts (Linum usitatissimum L.). J. Nat. Fibers 2022,19, 9904–9913. [CrossRef]
42.
Mueed, A.; Deng, Z.; Korma, S.A.; Shibli, S.; Jahangir, M. Anticancer Potential of Flaxseed Lignans, Their Metabolites and
Synthetic Counterparts in Relation with Molecular Targets: Current Challenges and Future Perspectives. Food Funct. 2022,14,
2286–2303. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2025,26, 1226 17 of 19
43.
Mc Cullough, R.S.; Edel, A.L.; Bassett, C.M.C.; Lavallée, R.K.; Dibrov, E.; Blackwood, D.P.; Ander, B.P.; Pierce, G.N. The Alpha
Linolenic Acid Content of Flaxseed Is Associated with an Induction of Adipose Leptin Expression. Lipids 2011,46, 1043–1052.
[CrossRef] [PubMed]
44.
Pandohee, J. Alpha-Linolenic Acid. In Nutraceuticals and Health Care; Academic Press: Cambridge, MA, USA, 2021; pp. 279–288. [CrossRef]
45.
Lemos, J.R.N.; de Alencastro, M.G.; Konrath, A.V.; Cargnin, M.; Manfro, R.C. Flaxseed Oil Supplementation Decreases C-Reactive
Protein Levels in Chronic Hemodialysis Patients. Nutr. Res. 2012,32, 921–927. [CrossRef]
46.
Mirfatahi, M.; Tabibi, H.; Nasrollahi, A.; Hedayati, M.; Taghizadeh, M. Effect of Flaxseed Oil on Serum Systemic and Vascular
Inflammation Markers and Oxidative Stress in Hemodialysis Patients: A Randomized Controlled Trial. Int. Urol. Nephrol. 2016,
48, 1335–1341. [CrossRef] [PubMed]
47.
Morshedzadeh, N.; Rahimlou, M.; Shahrokh, S.; Karimi, S.; Mirmiran, P.; Zali, M.R. The Effects of Flaxseed Supplementation
on Metabolic Syndrome Parameters, Insulin Resistance and Inflammation in Ulcerative Colitis Patients: An Open-Labeled
Randomized Controlled Trial. Phytother. Res. 2021,35, 3781–3791. [CrossRef]
48.
Al-Madhagy, S.; Ashmawy, N.S.; Mamdouh, A.; Eldahshan, O.A.; Farag, M.A. A Comprehensive Review of the Health Benefits of
Flaxseed Oil in Relation to Its Chemical Composition and Comparison with Other Omega-3-Rich Oils. Eur. J. Med. Res. 2023,28,
240. [CrossRef]
49.
Pan, A.; Yu, D.; Demark-Wahnefried, W.; Franco, O.H.; Lin, X. Meta-Analysis of the Effects of Flaxseed Interventions on Blood
Lipids. Am. J. Clin. Nutr. 2009,90, 288–297. [CrossRef]
50.
Touré, A.; Xueming, X. Flaxseed Lignans: Source, Biosynthesis, Metabolism, Antioxidant Activity, Bio-Active Components, and
Health Benefits. Compr. Rev. Food Sci. Food Saf. 2010,9, 261–269. [CrossRef] [PubMed]
51.
Parikh, M.; Netticadan, T.; Pierce, G.N. Flaxseed: Its Bioactive Components and Their Cardiovascular Benefits. Am. J. Physiol.
Heart Circ. Physiol. 2018,314, 146–159. [CrossRef]
52.
Pietinen, P.; Stumpf, K.; Männistö, S.; Kataja, V.; Uusitupa, M.; Adlercreutz, H. Serum Enterolactone and Risk of Breast Cancer: A
Case-Control Study in Eastern Finland. Cancer Epidemiol. Biomark. Prev. 2001,10, 339–344.
53.
Ingram, D.; Sanders, K.; Kolybaba, M.; Lopez, D. Case-Control Study of Phyto-Oestrogens and Breast Cancer. Lancet 1997,350,
990–994. [CrossRef]
54.
Xu, X.Y.; Wang, D.Y.; Li, Y.P.; Deyrup, S.T.; Zhang, H.J. Plant-Derived Lignans as Potential Antiviral Agents: A Systematic Review.
Phytochem. Rev. 2022,21, 239–289. [CrossRef] [PubMed]
55.
Schröder, H.C.; Merz, H.; Steffen, R.; Müller, W.E.G.; Sarin, P.S.; Trumm, S.; Schulz, J.; Eich, E. Differential
in vitro
Anti-HIV
Activity of Natural Lignans. Z. Naturforschung Sect. C J. Biosci. 1990,45, 1215–1221. [CrossRef] [PubMed]
56.
Burnett, P.G.G.; Young, L.W.; Olivia, C.M.; Jadhav, P.D.; Okinyo-Owiti, D.P.; Reaney, M.J.T. Novel Flax Orbitide Derived from
Genetic Deletion. BMC Plant Biol. 2018,18, 90. [CrossRef] [PubMed]
57.
Chera, E.I.; Pop, T.I.; Pop, R.M.; Pârvu, M.; Uifălean, A.; Cătoi, F.A.; Cecan, A.D.; Mîrza, C.M.; Achima
s
,
-Cadariu, P.; Pârvu, A.E.
Flaxseed Ethanol Extract Effect in Acute Experimental Inflammation. Medicina 2022,58, 582. [CrossRef] [PubMed]
58.
Biswas, S.K. Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? Oxid. Med.
Cell Longev. 2016,2016, 5698931. [CrossRef] [PubMed]
59. Tiwari, A.K. The Antioxidant Paradox. Pharmacogn. Mag. 2019,15, 173–175. [CrossRef]
60.
Rahimlou, M.; Jahromi, N.B.; Hasanyani, N.; Ahmadi, A.R. Effects of Flaxseed Interventions on Circulating Inflammatory
Biomarkers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv. Nutr. 2019,10, 1108–1119. [CrossRef]
61.
Leung, K.S.; Galano, J.M.; Oger, C.; Durand, T.; Lee, J.C.Y. Enrichment of Alpha-Linolenic Acid in Rodent Diet Reduced Oxidative
Stress and Inflammation during Myocardial Infarction. Free Radic. Biol. Med. 2021,162, 53–64. [CrossRef]
62.
Sahoo, D.K.; Heilmann, R.M.; Paital, B.; Patel, A.; Yadav, V.K.; Wong, D.; Jergens, A.E. Oxidative Stress, Hormones, and Effects of Natural
Antioxidants on Intestinal Inflammation in Inflammatory Bowel Disease. Front. Endocrinol. 2023,14, 1217165. [CrossRef] [PubMed]
63.
Abdelkarem, H.M.; Fadda, L.H. Flaxseed and Quercetin Improve Anti-Inflammatory Cytokine Level and Insulin Sensitivity in
Animal Model of Metabolic Syndrome, the Fructose-Fed Rats. Arab. J. Chem. 2017,10, S3015–S3020. [CrossRef]
64.
Mann, M.; Rhee, Y. Flaxseed Effects on Inflammation Regulatory Gene Expressions in an Obese Animal Model. Plant Foods Hum.
Nutr. 2021,76, 292–296. [CrossRef]
65.
Udenigwe, C.C.; Lu, Y.L.; Han, C.H.; Hou, W.C.; Aluko, R.E. Flaxseed Protein-Derived Peptide Fractions: Antioxidant Properties and
Inhibition of Lipopolysaccharide-Induced Nitric Oxide Production in Murine Macrophages. Food Chem. 2009,116, 277–284. [CrossRef]
66.
Draganescu, D.; Ibanescu, C.; Tamba, B.I.; Andritoiu, C.V.; Dodi, G.; Popa, M.I. Flaxseed Lignan Wound Healing Formulation:
Characterization and in Vivo Therapeutic Evaluation. Int. J. Biol. Macromol. 2015,72, 614–623. [CrossRef] [PubMed]
67.
Soleimani, Z.; Hashemdokht, F.; Bahmani, F.; Taghizadeh, M.; Memarzadeh, M.R.; Asemi, Z. Clinical and Metabolic Response
to Flaxseed Oil Omega-3 Fatty Acids Supplementation in Patients with Diabetic Foot Ulcer: A Randomized, Double-Blind,
Placebo-Controlled Trial. J. Diabetes Complicat. 2017,31, 1394–1400. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2025,26, 1226 18 of 19
68.
Yu, L.; Xu, Q.; Wang, P.; Luo, J.; Zheng, Z.; Zhou, J.; Zhang, L.; Sun, L.; Zuo, D. Secoisolariciresinol Diglucoside-Derived
Metabolite, Enterolactone, Attenuates Atopic Dermatitis by Suppressing Th2 Immune Response. Int. Immunopharmacol. 2022,111,
109039. [CrossRef] [PubMed]
69.
Christofidou-Solomidou, M.; Pietrofesa, R.A.; Park, K.; Albelda, S.M.; Serve, K.M.; Keil, D.E.; Pfau, J.C. Synthetic Secoisolari-
ciresinol Diglucoside (LGM2605) Inhibits Libby Amphibole Fiber-Induced Acute Inflammation in Mice. Toxicol. Appl. Pharmacol.
2019,375, 81–93. [CrossRef]
70.
Aguilar, C.M.; Sant’Ana, C.T.; Costa, A.G.V.; Silva, P.I.; Costa, N.M.B. Comparative Effects of Brown and Golden Flaxseeds on
Body Composition, Inflammation and Bone Remodelling Biomarkers in Perimenopausal Overweight Women. J. Funct. Foods
2017,33, 166–175. [CrossRef]
71.
Shareghfarid, E.; Nadjarzadeh, A.; Heidarzadeh-Esfahani, N.; Azamian, Y.; Hajiahmadi, S. The Effect of Flaxseed Oil Supplemen-
tation on Body Composition and Inflammation Indices in Overweight Adults with Pre-Diabetes. Nutr. Metab. Insights 2022,15,
11786388221090083. [CrossRef]
72.
Kontogianni, M.D.; Vlassopoulos, A.; Gatzieva, A.; Farmaki, A.E.; Katsiougiannis, S.; Panagiotakos, D.B.; Kalogeropoulos, N.;
Skopouli, F.N. Flaxseed Oil Does Not Affect Inflammatory Markers and Lipid Profile Compared to Olive Oil, in Young, Healthy,
Normal Weight Adults. Metabolism 2013,62, 686–693. [CrossRef] [PubMed]
73.
Biao, Y.; Jiannan, H.; Yaolan, C.; Shujie, C.; Dechun, H.; Julian Mcclements, D.; Chongjiang, C. Identification and characterization
of antioxidant and immune-stimulatory polysaccharides in flaxseed hull. Food Chem. 2020,315, 126266. [CrossRef] [PubMed]
74.
Li, J.; Chen, J.; Huang, P.; Cai, Z.; Zhang, N.; Wang, Y.; Li, Y. The Anti-Inflammatory Mechanism of Flaxseed Linusorbs on
Lipopolysaccharide-Induced RAW 264.7 Macrophages by Modulating TLR4/NF-
κ
B/MAPK Pathway. Foods 2023,12, 2398.
[CrossRef] [PubMed]
75.
Huang, X.; Wang, N.; Ma, Y.; Liu, X.; Guo, H.; Song, L.; Zhao, Q.; Hai, D.; Cheng, Y.; Bai, G.; et al. Flaxseed polyphenols: Effects of
varieties on its composition and antioxidant capacity. Food Chem. X 2024,23, 101597. [CrossRef] [PubMed]
76.
Merkher, Y.; Kontareva, E.; Alexandrova, A.; Javaraiah, R.; Pustovalova, M.; Leonov, S. Anti-Cancer Properties of Flaxseed
Proteome. Proteomes 2023,11, 37. [CrossRef] [PubMed]
77.
De Silva, S.F.; Alcorn, J. Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry,
Pharmacokinetics, and Molecular Targets. Pharmaceuticals 2019,12, 68. [CrossRef] [PubMed]
78.
Peng, C.; Li, J.; Zhao, A.; Yu, S.; Zheng, L.; Deng, Z.Y. Non-Oxidized and Oxidized Flaxseed Orbitides Differently Induce HepG2 Cell
Apoptosis: Involvement of Cellular Uptake and Membrane Death Receptor DR4. J. Sci. Food Agric. 2024,104, 4296–4308. [CrossRef]
79.
Shim, Y.Y.; Tse, T.J.; Saini, A.R.K.; Kim, Y.J.; Reaney, M.J.T. Uptake of Flaxseed Dietary Linusorbs Modulates Regulatory Genes
Including Induction of Heat Shock Proteins and Apoptosis. Foods 2022,11, 3761. [CrossRef]
80.
Buckner, A.L.; Buckner, C.A.; Montaut, S.; Lafrenie, R.M. Treatment with Flaxseed Oil Induces Apoptosis in Cultured Malignant
Cells. Heliyon 2019,5, e02251. [CrossRef]
81.
Han, J.; Lu, S.S.; Wang, Z.J.; Li, Y.L. Flax Seed Oil Inhibits Metastatic Melanoma and Reduces Lung Tumor Formation in Mice.
JBUON 2015,20, 1546–1552.
82.
Chen, J.; Mark Stavro, P.; Thompson, L.U. Dietary Flaxseed Inhibits Human Breast Cancer Growth and Metastasis and Downregulates
Expression of Insulin-like Growth Factor and Epidermal Growth Factor Receptor. Nutr. Cancer 2002,43, 187–192. [CrossRef]
83.
Yoon Sung, N.; Jeong, D.; Young Shim, Y.; Ahmed Ratan, Z.; Jang, Y.-J.; T Reaney, M.J.; Lee, S.; Lee, B.-H.; Kim, J.-H.; Yi, Y.-S.; et al.
The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization,
and Suppression of Src Activity in Glioblastoma Cells. Molecules 2020,25, 5881. [CrossRef] [PubMed]
84.
Okinyo-Owiti, D.P.; Dong, Q.; Ling, B.; Jadhav, P.D.; Bauer, R.; Maley, J.M.; Reaney, M.J.T.; Yang, J.; Sammynaiken, R. Evaluating
the Cytotoxicity of Flaxseed Orbitides for Potential Cancer Treatment. Toxicol. Rep. 2015,2, 1014–1018. [CrossRef] [PubMed]
85.
Demark-Wahnefried, W.; Polascik, T.J.; George, S.L.; Switzer, B.R.; Madden, J.F.; Ruffin IV, M.T.; Snyder, D.C.; Owzar, K.; Hars, V.;
Albala, D.M.; et al. Flaxseed Supplementation (Not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men
Presurgery. Cancer Epidemiol. Biomark. Prev. 2008,17, 3577–3587. [CrossRef]
86.
Flower, G.; Fritz, H.; Balneaves, L.G.; Verma, S.; Skidmore, B.; Fernandes, R.; Kennedy, D.; Cooley, K.; Wong, R.; Sagar, S.; et al.
Flax and Breast Cancer: A Systematic Review. Integr. Cancer Ther. 2014,13, 181–192. [CrossRef]
87.
Mason, J.K.; Fu, M.; Chen, J.; Thompson, L.U. Flaxseed Oil Enhances the Effectiveness of Trastuzumab in Reducing the Growth of
HER2-Overexpressing Human Breast Tumors (BT-474). J. Nutr. Biochem. 2015,26, 16–23. [CrossRef]
88.
Dikshit, A.; Gao, C.; Small, C.; Hales, K.; Hales, D.B. Flaxseed and Its Components Differentially Affect Estrogen Targets in
Pre-Neoplastic Hen Ovaries. J. Steroid Biochem. Mol. Biol. 2016,159, 73–85. [CrossRef]
89.
Eilati, E.; Bahr, J.M.; Hales, D.B. Long Term Consumption of Flaxseed Enriched Diet Decreased Ovarian Cancer Incidence and
Prostaglandin E2 in Hens. Gynecol. Oncol. 2013,130, 620–628. [CrossRef]
90.
Ansenberger, K.; Richards, C.; Zhuge, Y.; Barua, A.; Bahr, J.M.; Luborsky, J.L.; Hales, D.B. Decreased Severity of Ovarian Cancer
and Increased Survival in Hens Fed a Flaxseed-Enriched Diet for 1 Year. Gynecol. Oncol. 2010,117, 341–347. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2025,26, 1226 19 of 19
91.
Yan, L.; Yee, J.A.; Li, D.; McGuire, M.H.; Thompson, L.U. Dietary Flaxseed Supplementation and Experimental Metastasis of
Melanoma Cells in Mice. Cancer Lett. 1998,124, 181–186. [CrossRef] [PubMed]
92.
Shah, N.R.; Patel, B.M. Secoisolariciresinol Diglucoside Rich Extract of L. usitatissimum Prevents Diabetic Colon Cancer through
Inhibition of CDK4. Biomed. Pharmacother. 2016,83, 733–739. [CrossRef]
93.
Hu, T.; Linghu, K.; Huang, S.; Battino, M.; Georgiev, M.I.; Zengin, G.; Li, D.; Deng, Y.; Wang, Y.T.; Cao, H. Flaxseed Extract Induces
Apoptosis in Human Breast Cancer MCF-7 Cells. Food Chem. Toxicol. 2019,127, 188–196. [CrossRef] [PubMed]
94.
Tannous, S.; Haykal, T.; Dhaini, J.; Hodroj, M.H.; Rizk, S. The Anti-Cancer Effect of Flaxseed Lignan Derivatives on Different
Acute Myeloid Leukemia Cancer Cells. Biomed. Pharmacother. 2020,132, 110884. [CrossRef]
95.
Lin, X.; Gingrich, J.R.; Bao, W.; Li, J.; Haroon, Z.A.; Demark-Wahnefried, W. Effect of Flaxseed Supplementation on Prostatic
Carcinoma in Transgenic Mice. Urology 2002,60, 919–924. [CrossRef]
96.
Al-Radadi, N.S. Green Biosynthesis of Flaxseed Gold Nanoparticles (Au-NPs) as Potent Anti-Cancer Agent Against Breast Cancer
Cells. J. Saudi Chem. Soc. 2021,25, 101243. [CrossRef]
97.
Chen, J.; Wang, L.; Thompson, L.U. Flaxseed and Its Components Reduce Metastasis after Surgical Excision of Solid Human
Breast Tumor in Nude Mice. Cancer Lett. 2006,234, 168–175. [CrossRef] [PubMed]
98.
Dikshit, A.; Hales, K.; Hales, D.B. Whole Flaxseed Diet Alters Estrogen Metabolism to Promote 2-Methoxtestradiol-Induced
Apoptosis in Hen Ovarian Cancer. J. Nutr. Biochem. 2017,42, 117–125. [CrossRef]
99.
Asselin, C.Y.; Lam, A.; Cheung, D.Y.C.; Eekhoudt, C.R.; Zhu, A.; Mittal, I.; Mayba, A.; Solati, Z.; Edel, A.; Alejandro Austria, J.;
et al. The Cardioprotective Role of Flaxseed in the Prevention of Doxorubicin- and Trastuzumab-Mediated Cardiotoxicity in
C57BL/6 Mice. J. Nutr. 2020,150, 2353–2363. [CrossRef] [PubMed]
100.
Burdge, G.C.; Calder, P.C.
α
-Linolenic Acid Metabolism in Adult Humans: The Effects of Gender and Age on Conversion to
Longer-Chain Polyunsaturated Fatty Acids. Eur. J. Lipid Sci. Technol. 2005,107, 426–439. [CrossRef]
101.
Patenaude, A.; Rodriguez-Leyva, D.; Edel, A.L.; Dibrov, E.; Dupasquier, C.M.C.; Austria, J.A.; Richard, M.N.; Chahine, M.N.;
Malcolmson, L.J.; Pierce, G.N. Bioavailability of
α
-Linolenic Acid from Flaxseed Diets as a Function of the Age of the Subject. Eur.
J. Clin. Nutr. 2009,63, 1123–1129. [CrossRef]
102.
Edel, A.L.; Patenaude, A.F.; Richard, M.N.; Dibrov, E.; Austria, J.A.; Aukema, H.M.; Pierce, G.N.; Aliani, M. The Effect of Flaxseed
Dose on Circulating Concentrations of Alpha-Linolenic Acid and Secoisolariciresinol Diglucoside Derived Enterolignans in
Young, Healthy Adults. Eur. J. Nutr. 2016,55, 651–663. [CrossRef]
103.
Li, L.; Li, H.; Gao, Y.; Vafaei, S.; Zhang, X.; Yang, M. Effect of Flaxseed Supplementation on Blood Pressure: A Systematic Review,
and Dose-Response Meta-Analysis of Randomized Clinical Trials. Food Funct. 2023,14, 675–690. [CrossRef] [PubMed]
104.
Clavel, T.; Doré, J.; Blaut, M. Bioavailability of Lignans in Human Subjects. Nutr. Res. Rev. 2006,19, 187–196. [CrossRef] [PubMed]
105.
Brenna, J.T.; Salem, N.; Sinclair, A.J.; Cunnane, S.C.
α
-Linolenic Acid Supplementation and Conversion to n-3 Long-Chain
Polyunsaturated Fatty Acids in Humans. Prostaglandins Leukot. Essent. Fat. Acids 2009,80, 85–91. [CrossRef] [PubMed]
106.
Austria, J.A.; Richard, M.N.; Chahine, M.N.; Edel, A.L.; Dupasquier, C.M.C.; Pierce, G.N.; Malcolmson, L.J. Bioavailability of
Alpha-Linolenic Acid in Subjects after Ingestion of Three Different Forms of Flaxseed. J. Am. Coll. Nutr. 2008,27, 214–221. [CrossRef]
107.
Calder, P.C. N
−
3 Polyunsaturated Fatty Acids, Inflammation, and Inflammatory Diseases. Am. J. Clin. Nutr. 2006,83, 1505S–1519S.
[CrossRef]
108.
Clavel, T.; Henderson, G.; Engst, W.; Doré, J.; Blaut, M. Phylogeny of Human Intestinal Bacteria That Activate the Dietary Lignan
Secoisolariciresinol Diglucoside. FEMS Microbiol. Ecol. 2006,55, 471–478. [CrossRef] [PubMed]
109.
Clavel, T.; Lippman, R.; Gavini, F.; Doré, J.; Blaut, M. Clostridium saccharogumia Sp. Nov. and Lactonifactor longoviformis Gen.
Nov., Sp. Nov., Two Novel Human Faecal Bacteria Involved in the Conversion of the Dietary Phytoestrogen Secoisolariciresinol
Diglucoside. Syst. Appl. Microbiol. 2007,30, 16–26. [CrossRef]
110.
Pramanik, J.; Kumar, A.; Prajapati, B. A review on flaxseeds: Nutritional profile, health benefits, value added products, and
toxicity. eFood 2023,4, e114. [CrossRef]
111.
Huang, C.; Tse, T.J.; Purdy, S.K.; Chicilo, F.; Shen, J.; Meda, V.; Reaney, M.J.T. Depletion of cyanogenic glycosides in whole flaxseed
via Lactobacillaceae fermentation. Food Chem. 2023,403, 134441. [CrossRef]
112.
Roozegar, M.H.; Shahedi, M.; Keramet, J.; Hamdami, N.; Roshanak, S. Effect of coated and uncoated ground flaxseed addition on
rheological, physical and sensory properties of Taftoon bread. J. Food Sci. Technol. 2015,52, 5102–5110. [CrossRef] [PubMed]
113.
Cardoso Carraro, J.C.; Dantas, M.I.D.S.; Espeschit, A.C.R.; Martino, H.S.D.; Ribeiro, S.M.R. Flaxseed and human health: Reviewing
benefits and adverse effects. Food Rev. Int. 2012,28, 203–230. [CrossRef]
114.
Imran, S.; Munir, S.; Altemimi, A.B.; Fatima, I.; Rabail, R.; Batool, I.; Khalid, N.; Abdi, G.; Shabbir, M.A.; Aadil, R.M. Therapeutic
implications of flaxseed peptides and bioactive components against various diseases. J. Funct. Foods 2024,119, 106324. [CrossRef]
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