There are over 8,000 polyphenolic compounds in the plant world. (Pandey, Rizvi, 2009) Berries, green tea,
coffee, cocoa, some spices and even red wine all contain polyphenols and have strong
Polyphenols in plants protect them from harmful UV radiation as well as attacks from harmful
Polyphenols are also powerful micronutrients that our bodies use to stay healthy. They have
numerous health beneﬁts that may offer protection from the development of cancers,
cardiovascular disease, osteoporosis, and diabetes. (Pandey, Rizvi, 2009)
While it’s ideally best to get these nutrients through our diet, sometimes an unbalanced diet
prevents us from getting as much as we need.
Polyphenols are grouped in 4 major classes: phenolic acids, ﬂavanoids, stilbenes and lignans.
The Norwegian Spruce Extract of Nordic Sunn is a lignan found in the spruce of Scandinavia.
All polyphenols have various bioavailability which will depend on the type of polyphenol as
well as the colon microﬂora.
A lignan is a polyphenolic compound that occurs naturally in some plants, rye, barley, seeds,
fresh fruits, broccoli, and some berries. In recent years research has shown that a signiﬁcant
amount of lignans are also present in trees, especially the knots of the wood. (Touré, Xu, 2010) (Willför et al., 2003)
It is known that the accumulation of lignans in the core of trees is important for the durability
and longevity of the species. (Mareai, 2011) Lignans’ roles in the longevity of trees may be the key to
their nutritional beneﬁts.
Major plants lignans known are secoisolariciresinol, matairesinol, pinoresinol, sesamin and
hydroxymatairesinol. Similar to isoﬂavanones (most commonly soy beans) lignans are
Isoﬂavanoid and lignans in various foods can be measured via gas chromatography (Adlercreutz, Mazur, 1997), with
soybeans and ﬂaxseed having the highest lignan contents of plants studied.
Many diseases, in particular hormonal related cancers such as breast cancer, have been
observed to be much more prevalent in the West than Asia. There is some evidence that diet
plays a role. Populations consuming more phytoestrogens have been found to have a
reduced risk of breast, colorectal and prostate cancer. In Asia consumption of soybeans (an
isoﬂavone) represent the largest intake of phytoestrogens, while in the Western diet they
come in smaller quantities from lignans in whole grains, seeds and vegetables. (Adlercreutz, Mazur, 1997)
Through the action of bacteria in the digestive system, plant lignans are the precursor to the
major mammalian lignans Enterodial (ED) and Enterolactone (ENL). These mammalian
lignans were ﬁrst discovered in late 1970s and are thought to be responsible for some of the
health beneﬁts of lignans. These mammalian lignans are thought to act as anti-oestrogens
when oestrogen levels are too high, and the other way around when they are too low. (Mareai, 2011)
Norwegian Spruce Extract
Lignans were ﬁrst discovered in trees over 100 years ago. The norwegian spruce extract,
collected from the knotwood of the tree (Picea Abies) is thought to be one of nature’s highest
concentration of lignans available. (Holmbom et al., 2006) (Willför et al., 2003)
Knots in trees have been shown to have 5-10% dry weight of lignans, much higher than
ordinary stemwood, with the Norwegian Spruce containing 6-24% of lignans, this being 50 to
100 times higher than in normal wood. (García-Pérez et al., 2009)
Flaxseed is also known to have the highest concentration of lignans in the plant world,
however Chromatographic analysis of lignans shows that Norwegian Spruce knotwood
extract has between 10 and 20 times more lignans than ﬂaxseed. (Holmbom et al., 2006) (Mareai, 2011)
Norwegian Spruce knotwood lignans are primarily composed of 7-hydroxymatairesinol
(HMR). But is also possesses a large amount of other lignans as well.
Using more recent measurements techniques, it was found that HMR is also the major lignan
source in wheat, oat, barley and bran, but still in much smaller amounts than those found in
Norwegian Spruce. (Holmbom et al., 2007)
Lignans and Metabolism
As seen previously, norwegian spruce knotwood and ﬂaxseed are both major sources of
lignans in nature.
Norwegian Spruce knotwood contains mostly the lignan hydroxymatairesinol (HMR).
Hydroxymatairesinol then gets converted to matairesinol (MAT) through hydrogenolysis and
then mostly into enterolactone (ENL) and some enterodiol (ED) through bacteria in the gut.
(Sjöholm et al., 2003) Norwegian Spruce knotwood also contains secoisolariciresinol (SECO), matairesinol
(MAT) and laciriresinol (LARI). (Holmbom et al., 2006) The chemical structure of HMR is closely related to MAT,
and, therefore provides an efﬁcient precursor of ENL. (Lecchini et al., 2007)
One of the advantages of HMR in Nordic Sunn is that it occurs in its aglycone form (without a
sugar) which some research on other polyphenols and phytoestrogens suggests may
increase its bioavailability. (Remesy et al., 2000) (Lucini et al., 2020)(Heubi et al., 2001)
Flaxseed lignans on the other hand need to go through a multiple step process. Flaxseed
contain a large amount of the lignan precursor secoisolariciresinol diglucoside (SDG). SDG
then gets metabolized in the gut to the lignan secoisolariciresinol (SECO). SECO then gets
broken down by the microﬂora into mostly ED. ED is then partially converted into ENL in the
colon. (Di, 2017)(Eriksen, 2019)
A similar process happens with sesame seeds, also high in lignans. Sesaminol triglucoside
(STG) is the most abundant lignan in sesame seeds and ﬁrst needs to be metabolized to an
aglycone (lignan without sugar). (Kadam et al., 2019) ( et al., 1980)
The lignans are thought to only be effective if they are metabolized, absorbed and reach the
tissues, where they can potentially exert an effect. Some of the health beneﬁts studied seem
to accrue from an increased level of ENL, which HMR converts into directly. (Santti et al., 2000) Research
shows that HMR is quickly absorbed by the body into blood plasma. (Hardy et al., 2013)
Because lignans need to be metabolized in the gut, a healthy gut ﬂora and a high
bioavailability of the lignans are suspected to be both important to achieve the maximum
health beneﬁts. Patients who are taking antibiotics, for example, can have reduced gut ﬂora,
leading to reduced absorption of lignans. Other factors such as sex, BMI and smoking has
also been shown to have an impact on overall ENL levels. (Eriksen, 2019) ( et al., 2017)
One of the big advantages of Nordic Sunn’s Norwegian Spruce extract is its lignans are in
aglycone form. Some research shows that lignans in their aglycone form can be absorbed
more easily and earlier than their glycosated lignan equivalents. (Lucini et al., 2020)
Lignans and Health
Epidemiological studies have proved that lignan-rich diets help reduce risk of various
hormone-dependent cancers, heart disease and osteroporosis. (Mareai, 2011) While Asian populations
get most of the phytoestrogens in their diet from isoﬂavones present in soybeans, Western
populations get most of their phytoestrogens from lignans.
Lignans are ubiquitous in the plant kingdom, albeit in small quantities. Most people consume
some lignans as part of their diet, with vegetarians usually consuming more. The ongoing
EPIC cohort study, following 477,312 men and women in 10 European countries, conﬁrm that
daily lignan intake is 1.5 mg/day on average with a standard deviation of 0.8 mg/day. (González et al., 2014)
Over 40% of lignan intake came from fruits and vegetables. This is consistent with another
cohort study of 637 Dutch men and women where the average intake of lignans was about 1
mg/day. (Milder, 2007)
The typical Western-type diet which has high fat levels can result in altered hormonal levels,
including elevated androgen levels. This diet elevates plasma levels of sex hormones and
decreases the sex hormone binding globulin (SHBG) concentration, increasing the
bioavailability of these steroids. This also results in low levels enterolignans (ENL,ED) and
phytoestrogens. (Adlercreutz, 1990) Lignans could serve to counteract some of the effects of hormonal
imbalance due to high dietary fat intake. (Rowland et al., 2005)
Due to the similarity of the chemical structure of the enterolignans with estradiol, there has
long been the suggestion that these lignans have weak estrogenic/antiestrogenic properties.
The chemical structure of lignans also makes them promising anti-oxidants.
Epidemiological studies point to the beneﬁts of lignans in the diet:
According to the Zutphen cohort study that followed 570 Dutch men between 64 and 84 for
15 years, intake of enterolignans, particularly matairesinol (MAT) was inversely associated with
death due to coronary heart disease, cardiovascular disease, cancer and all cause mortality.
(Kromhout et al., 2006) The fact that MAT stood out as most beneﬁcial is of interest as 7-hydroxymatairesinol
(HMR) is a direct precursor to MAT and both primarily get metabolized to the mammalian
lignan enteralactone. (Kromhout et al., 2006)(Milder, 2007)
The possibility of polyphenols affecting the gut microbiota and, as such, acting as probiotics
has also been explored. (Weber et al., 2020)
The lignans appear unique among the phytoestrogens in their ability to modulate
steroid activity via the aromatase enzymes.Lignans inhibit the activity of human aromatase,
17β-hydroxysteroid dehydrogenase, and 5α-reductase. (Rowland et al., 2005)
In summary, lignans have shown a strong potential to help balance hormones, and act as
powerful anti-oxidant on the body with a variety of beneﬁts.
We live in a world where free radicals can come from many sources and contribute to the
deterioration of health. Sources of free radicals include pollutants, drugs, metal ions,
radiation, and high intakes of polyunsaturated fatty acids, and also strenuous exercise,
mitochondrial dysfunction, and smoking. (Touré, Xu, 2010)
One of the beneﬁts of lignans is thought to be due to antioxidant activity, primarily as an
efﬁcient hydroxyl radical scavengers. (Serraino, Thompson, 1991) Research done on various wood species, and
especially knotwood and bark showed its strong anti-oxidant potential. ( et al., 2006)
Some research shows the mammalian lignan metabolites (enterodiol and enterolactone) may
actually have greater or different activity than the parent lignan. (Thompson et al., 1999)
SECO, ED and ENL were all found to be 4.5 to 5 times more powerful than Vitamin E as a
direct antioxidant. (Touré, Xu, 2010)
HMR, the lignan found in the Norwegian Spruce knotwood, is also known to be a powerful
antioxidant. When comparing to Trolox (the reference for anti-oxidation) HMR ranked higher
than SECO, the major lignan in ﬂaxseed, as an anti-oxidant. (Holmbom et al., 2003)
The behavior of the phytoestrogen lignans depend on the biological levels of estradiol . It is
thought that at normal estradiol levels, the lignans act as estrogen antagonists, but in
postmenopausal women (and thus low estradiol levels) they can act as weak
estrogens. (Mareai, 2011) (Touré, Xu, 2010) This could lead lignans to have both estrogenic and anti-estrogenic
effects and beneﬁts.
In women going through menopause, the hormonal balancing impact of phytoestrogens
have been shown in various studies to help with menopause symptoms such as hot ﬂashes.
(Higdon, Drake, 2004) (Brzezinski, Debi, 1999)
In one study, Japanese women have historically shown low incidence of menopause
symptoms compared to Canadian women. (Lock, 1991) This is presumed to be due to the Japanese
diet being high in phytoestrogens through soybean consumption. In a collaborative studies
phytoestrogens soy and ﬂaxseed both had strong positive effects on hot ﬂashes and vaginal
dryness. (Schenker et al., 1997)
In a study speciﬁcally done using a norwegian spruce extract , researchers found that
supplementation led to a 50% decrease in hot ﬂashes (Hardy et al., 2013), while another study showed the
hormonal balancing effects of HMR supplementation. (Gromova et al., 2020)
There is evidence that steroid production by human fetal adrenal cortical cells is modulated
by estrogen, and thus phytoestrogens could play a hormonal balancing role. Phytoestrogens
have also been studied to their impact on sleep and stress, with possible beneﬁcial impact on
In one study, looking at ENL levels showed an inverse relationship with short sleep and
probability of sleep disorders. This was not the case for END which showed a negative
relationship. (Zhang et al., 2020) It is thought that phytoestrogens may increase DHEA synthesis and
decrease cortisol synthesis by suppressing the activity of the enzyme 21-hydroxylase.(Jaffe et al., 1999)
Epidemiological studies have shown that Asian populations with a higher intake of
phytoetrogens had a lower incidence of various hormonal related cancers than Western
populations. (Adlercreutz, Mazur, 1997) This had led to much research on the beneﬁts of various foods with health
Since the discovery of mammalian lignans in 1980, it has been suspected they had a
beneﬁcial effect on chronic disease. Produced from plant lignans in the gut, they appear to
be anticarcinogenic; lignan metabolites bear a structural similarity to estrogens and can bind
to estrogen receptors and inhibit the growth of estrogen-stimulated breast cancer. In
particular it was found that urinary excretions of breast cancer patients had lower levels of
enterolignans (ED+ENL) as compared to non breast cancer patients. This led to the
hypothesis that enterolignans had a beneﬁcial impact on breast cancer. (Thompson, 1998)(Craig, 1999)
The potential beneﬁcial impact of lignans has been corroborated by several epidemiological
studies. Due to their hormonal balancing effects, it has been suggested that lignan
consumptions could potentially reduce the risk of breast cancer and indeed other hormonal
type cancers (Adlercreutz, Mazur, 1997)(Adlercreutz, 1990)(Adlercreutz, 1995) . In a study of 300 women with early breast cancer, researchers
found a decreased level of mortality risk was associated with higher enterolactone (ENL)
levels. (Boccardo et al., 2012) Another cohort study of 2653 German breast cancer patients found that high
levels of ENL and ED were associated with lower levels of mortality. (Chang-Claude et al., 2011)
As of 2019, there have been 19 epidemiological studies supporting the protective role of
ENL on breast cancer with a minority of studies showing little or no association.(Kadam et al., 2019)
There have also been a number of animal studies pointing to the effectiveness of a high
lignan diet in help reduce breast cancer tumor growth.
A review of in-vitro, animal, observational and clinical studies show that ﬂaxseed or equivalent
lignan supplementation reduce breast cancer and all cause mortality by 33-70% and 40-53%
respectively without reducing the effectiveness of tamoxifen (a breast cancer drug). (Mason, Thompson, 2013)
In recent in-vitro studies it was found that ENL exerts its antimetastatic breast cancer activity
via different pathways. (Kadam et al., 2019)(Mamashli et al., 2016)(Dabrosin et al., 2010)(Liu et al., 2015).
One of the pathways for activity has been postulated that ENL is an aromatase inhibitor and
competes with androstenedione for the enzyme. This would be a beneﬁt as androstenedione
converts to oestrone which may contribute to growth of breast cancer cells. (Adlercreutz, Mazur, 1997)
Lignans and isoﬂavanoids also seem to stimulate sex hormone-binding globulin (SHBG) and
could reduce the biological effect of sex hormones and potentially reduce breast cancer risk.
(Adlercreutz, Mazur, 1997)(Frairia et al., 1996) An increase in SHBG has been seen to lower androgens and the percentages of
free testosterone and free estradiol. This reduces the metabolic clearance rate of the steroids
and, in this way, reduces their biological activity. (Adlercreutz, 1995)
There is also research pointing to the antioxidant impact of lignans to help it protect against
hormone-related diseases. HMR may not need to be converted to mammalian lignans to have
an anticarcinogenic effect. (Santti et al., 2000) (Santti et al., 2001)
In summary, there are several potential anticarcinogenic effects that could be beneﬁcial for
breast health, including; antioxidant effects, enzyme inhibition and/ or stimulation of SHGB
synthesis. (Mareai, 2011)
Because the production of mammalian lignans from plant lignans occur in the colon, it has
been suspected that lignan supplementation might also help reduce the risk of colon cancer.
There’s also research showing that hormones could play a role in this type of disease. (Gruber et al., 2009) (Adlercreutz, Mazur, 1997)
A study looking at 115 colorectal cancer patients showed they had signiﬁcantly lower levels
of serum enterolactone (ENL) levels as compared to a control group (Herzig et al., 2019), while a case cohort
study of over 50,000 Danish participants aged 50-64 where higher levels of ENL were
associated with lower levels of colon cancer (Tjønneland et al., 2010), while another case cohort study in the
Netherlands found higher levels of enterodiol (ED) and ENL were associated with lower
colorectal adenoma risk. (Kampman et al., 2006) In-vitro studies also showed the possible beneﬁt of ENL.(Thompson et al., 1998)
An animal study looking at the impact of Flaxseed and SDG lignans supplementation showed
a 41-53% reduction of colonic aberrant crypts and 48-57% reduction of aberrant crypt loci.
(Thompson, 1998) While in-vitro studies on human cancer colon cells showed that mammalian lignan
enterolactone (ENL) signiﬁcantly reduced the proliferation of such cancer cells. (Thompson et al., 1998) (Tsubura et al., 2005)
Epidemiological and animal studies point to possible beneﬁcial impacts of lignans on colon
Prostate cancer is the second most common cause of cancer among men worldwide. Similar
to what is seen with breast cancer, incidence of prostate cancer is highest in North America
and Europe, with Asian populations showing lower incidence of the disease. (Adlercreutz, Mazur, 1997) (Bray et al., 2012)
Incidence rate and mortality rates are 60 and 17 times higher respectively when comparing
the United States and China . (Rowland et al., 2005)
Prostate Cancer Rates Globally
According to epidemiological studies, as well as in-vitro and in-vivo studies, there is evidence
suggesting that iso-ﬂavanoids and lignans, both phytoestrogens, could be protective against
the proliferation of prostate cancer. (Adlercreutz, Mazur, 1997)(Adlercreutz, 1990)(Hallmans et al., ) ENL was also found to have anti-
proliferative properties on prostate cancer cells. (Rowland et al., 2005) A case-control study conducted in
Scotland found that higher serum ENL concentrations were associated with a lower risk of
prostate cancer. (Prasad, 2004)(Mareai, 2011) In a meta analysis of 11 studies, increased serum concentration of
enterolactone was associated with a signiﬁcant reduced risk of prostate cancer. (He et al., 2015)
In a speciﬁc in-vivo study seeking to examine the effect of 7-hydroxymatairesinol (HMR) on
LNCaP tumours in nude mice, HMR from the Norway Spruce was administered.
Animals in receiving HMR had a reduced tumour take rate, increased percentage of non-
growing tumours, and higher tumour cell apoptotic index, compared to a control group (Mäkela et al., 2005).
It is also been researched that ENL is a inhibitor of the enzyme 5α-reductase, the same
enzyme that is targeted by ﬁnasteride a drug used for benign prostatic hyperplasia.(Adlercreutz, Mazur, 1997) The
inhibition of 5α-reductase could also play a role in inhibiting the conversion of testosterone
to 5a-dihydrotestosterone (DHT). The reduction in DHT concentration has been shown to
modify the risk of prostate cancer and benign hyperplasia. (Adlercreutz, Mazur, 1997)(Santti et al., 2000)
Prostate health is an increasingly important concern for aging men, and lignan
supplementation provides some evidence to be supportive for prostate health.
Diets rich in foods containing lignans (whole grains, nuts, seeds, legumes, fruits, and
vegetables) have been associated with possible reductions in risk of cardiovascular disease.
The anti-oxidant nature of these polyphenols is thought to be the key to their beneﬁts.
Lignans may protect against cardiovascular diseases (CVD) and the metabolic syndrome by
reducing lipid and glucose concentrations, lowering blood pressure, and decreasing
oxidative stress and inﬂammation. (Mareai, 2011)
Five studies using ﬂaxseed lignan supplements indicated beneﬁcial associations with C-
reactive protein, and a meta-analysis that included these studies also suggested lignans have
a lowering effect on plasma total and LDL cholesterol. (McCullough et al., 2010) (Salonen et al., 2003)
In a study on 2684 Finnish men between 1984 and 1989, high ENL plasma levels were
associated with a reduced coronary heart disease and cardiovascular heart disease (Salonen et al., 2003), while
another study of 570 men from the Netherlands, the intake of lignan matairesinol was
inversely associated with mortality due to CHD, CVD, cancer, and all causes. (Kromhout et al., 2006)
A meta-analysis of 8 different studies looking at ENL plasma levels found that increased ENL
levels were associated with a 45% decrease in CVD mortality risk. (Nöthlings et al., 2017)
In the mouse liver, the fat-rich diet inhibited regulators of lysosomal biogenesis and
autophagy pathways such as the master gene TFEB in parallel to an increase in fat
accumulation and the induction of severe steatosis, in line with the observations of Settembre
et al. (Carmine, et al., 2013) who showed that autophagy is required for lipid degradation via the TFEB pathway.
7-HMR and TEP increased TFEB to levels found in the liver of mice on the LFD (10 % fat),
suggesting that the TFEB-regulated pathway may be one of the mechanisms through which
lignan can prevent liver steatosis. Amelioration of liver steatosis was also investigated in vitro
by using the HEPA 1–6 model. (Lorenzo et al., 2018)
The global prevalence of diabetes among adults over 18 years of age rose from 4.7% in 1980
to 8.5% in 2014 and is becoming an increasing problem in today’s world. WHO estimates that
diabetes was the seventh leading cause of death in 2016.(Organization, 2021)
There is growing evidence of beneﬁcial effects of lignans on insulin resistance, glycemic
control and obesity. (Bhathena, Velasquez, 2002)
SDG lignans, for example, have been shown to to be effective in preventing/delaying the
development of type-1 and type-2 diabetes. The hypoglycemic effect of SDG in type-2
diabetes has been suggested to be due to its antioxidant activity. (Mareai, 2011)(Prasad, 2002)
In one in-vivo study, ﬂaxseed lignans prevented diabetes in 75% of the cases in rats treated
with a diabetes promoting chemical. (Westcott et al., 2000) (Prasad, 2000) In a Chinese double-blind randomized
control trial with 73 participants, daily lignan supplementation resulted in improvements in
glycemic control in type 2 diabetic patients. (Lin et al., 2007)
In another in-vivo study using speciﬁcally HMR lignans and norwegian spruce extract, mice
being fed a high-fat diet showed improved glycemic control. Compared to a control, the
subjects fed the extract had signiﬁcantly lower weight, lower insulin resistance, and lower
fasting glucose levels. (Lorenzo et al., 2018)
A growing amount of research is linking diet, inﬂammation and cognition. Similar to other
diseases covered, the Western Diet has been associated with higher incidences of
neurodegenerative diseases.(Battino et al., 2016)
In the past several years, several research works demonstrated that dietary polyphenols could
have beneﬁcial effects in cognitive functions, by acting against oxidative stress and
inﬂammation. Alteration in the homeostasis of gut–brain axis has been associated also to
neurological disorders and neurodegenerative diseases. (Lucini et al., 2020) This has lead to research on
diet, the microbiota-gut-brain axis and its implications in neurological disorders. (Weber et al., 2020)
In terms of general diet, the Mediterranean Diet and Asian Diet have been shown to prevent
a variety of pathologies associated with aging. In fact, it is suggested the polyphenols in these
diets that are associated with the greatest reduction in neurodegeneration. (Weber et al., 2020)
Polyphenols, as antioxidants, act as free radical scavengers, and thereby afford protection
from chronic diseases, such as Alzheimer’s disease and diabetes, in which free radicals play a
major role in the pathogenesis.
There is some evidence that lignans could play a role as an acetylcholinesterase inhibitor,
which is shown to have a neuroprotective effect, as acetylcholinesterase breaks down
acetylcholine, a neurotransmitter. (*) (Lucini et al., 2020) Alzheimer’s patients, for example, have been
found to have low levels of acetylcholine in their brain.
As a further example, ENL was found to attenuate the degeneration of the striatal
dopaminergic terminals in Parkinson’s disease (PD), in the PD rat models (Blandini et al., 2019), while
Polyphenols appear to have a positive effect on the gut microbiome, which may decrease
inﬂammation that contributes to the disease. Therefore, a diet rich in polyphenols may
decrease the symptoms and increase quality of life in PD patients. (Weber et al., 2020)
dietary polyphenolic compounds are potentially able to affect the gut–brain axis
via modulation of the gut microbiota, (Lucini et al., 2020)
Why Nordic Sunn?
Nordic Sunn contains the aglycone lignan 7-hydroxymatairesinol making it more bio-
Nordic Sunn is extracted from an aqueous solution. This has a lesser environmental impact
and provides a product with greater antioxidant potential that other extraction methods. (Mohamadou et al., 2017)
Nordic Sunn uses existing waste currently being discarded by the forestry industry, making it
completely organic and recycled.
World Health Organization. (2021, April 13). Diabetes. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/diabetes.
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Cosentino M, Marino F, Ferrari M, Rasini E, Bombelli R, Luini A, Legnaro M, Delle Canne MG, Luzzani M, Crema F, Paracchini S, Lecchini S. Estrogenic activity of 7-hydroxymatairesinol potassium acetate (HMR/lignan) from Norway spruce (Picea abies) knots and of its active metabolite enterolactone in MCF-7 cells. Pharmacol Res. 2007 Aug;56(2):140-7. doi: 10.1016/j.phrs.2007.05.001. Epub 2007 May 22. PMID: 17572100.
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