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Polyphenols

“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.”

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 antioxidant properties.

Polyphenols in plants protect them from harmful UV radiation as well as attacks from harmful pathogens.

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.

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Lignans

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 phytoestrogens.

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.

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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)

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Source (Di, 2017)

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.

Powerful Antioxidant

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)

Menopausal Symptoms

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)

Stress

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 both.

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)

Breast Health

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 protective properties.

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)

Colon Health

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 health.

Prostate Health

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

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Source (Bray et al., 2012)

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.

Cardiovascular 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)

Obesity

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)

Glycemic Support

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)

Brain Health

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- available.

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.

Bibliography

World Health Organization. (2021, April 13). Diabetes. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/diabetes.

Udani JK, Brown DJ, Tan MO, Hardy M. Pharmacokinetics and bioavailability of plant lignan 7-hydroxymatairesinol and effects on serum enterolactone and clinical symptoms in postmenopausal women: a single-blinded, parallel, dose-comparison study. J Am Coll Nutr. 2013;32(6):428-35. doi: 10.1080/07315724.2013.849578. PMID: 24606716; PMCID: PMC3877914.

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.

Mali AV, Padhye SB, Anant S, Hegde MV, Kadam SS. Anticancer and antimetastatic potential of enterolactone: Clinical, preclinical and mechanistic perspectives. Eur J Pharmacol. 2019 Jun 5;852:107-124. doi: 10.1016/j.ejphar.2019.02.022. Epub 2019 Feb 14. PMID: 30771348; PMCID: PMC6938675.

Saarinen NM, Wärri A, Mäkelä SI, Eckerman C, Reunanen M, Ahotupa M, Salmi SM, Franke AA, Kangas L, Santti R. Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies). Nutr Cancer. 2000;36(2):207-16. doi: 10.1207/S15327914NC3602_10. PMID: 10890032.

Saarinen NM, Huovinen R, Wärri A, Mäkelä SI, Valentín-Blasini L, Needham L, Eckerman C, Collan YU, Santti R. Uptake and metabolism of hydroxymatairesinol in relation to its anticarcinogenicity in DMBA-induced rat mammary carcinoma model. Nutr Cancer. 2001;41(1-2):82-90. doi: 10.1080/01635581.2001.9680616. PMID: 12094633.

Bylund A, Saarinen N, Zhang JX, Bergh A, Widmark A, Johansson A, Lundin E, Adlercreutz H, Hallmans G, Stattin P, Mäkela S. Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo. Exp Biol Med (Maywood). 2005 Mar;230(3):217-23. doi: 10.1177/153537020523000308. PMID: 15734725.

McCann MJ, Gill CI, McGlynn H, Rowland IR. Role of mammalian lignans in the prevention and treatment of prostate cancer. Nutr Cancer. 2005;52(1):1-14. doi: 10.1207/s15327914nc5201_1. PMID: 16090998.

Biasiotto G, Zanella I, Predolini F, Archetti I, Cadei M, Monti E, Luzzani M, Pacchetti B, Mozzoni P, Andreoli R, De Palma G, Serana F, Smeds A, Di Lorenzo D. 7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6 mice on a high-fat diet. Br J Nutr. 2018 Oct;120(7):751-762. doi: 10.1017/S0007114518001824. Epub 2018 Aug 14. PMID: 30105962.

Bigdeli B, Goliaei B, Masoudi-Khoram N, Jooyan N, Nikoofar A, Rouhani M, Haghparast A, Mamashli F. Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis. Toxicol Appl Pharmacol. 2016 Dec 15;313:180-194. doi: 10.1016/j.taap.2016.10.021. Epub 2016 Oct 28. PMID: 27984132.

Danbara N, Yuri T, Tsujita-Kyutoku M, Tsukamoto R, Uehara N, Tsubura A. Enterolactone induces apoptosis and inhibits growth of Colo 201 human colon cancer cells both in vitro and in vivo. Anticancer Res. 2005 May-Jun;25(3B):2269-76. PMID: 16158974.

Zamora-Ros R, Sacerdote C, Ricceri F, Weiderpass E, Roswall N, Buckland G, St-Jules DE, Overvad K, Kyrø C, Fagherazzi G, Kvaskoff M, Severi G, Chang-Claude J, Kaaks R, Nöthlings U, Trichopoulou A, Naska A, Trichopoulos D, Palli D, Grioni S, Mattiello A, Tumino R, Gram IT, Engeset D, Huerta JM, Molina-Montes E, Argüelles M, Amiano P, Ardanaz E, Ericson U, Lindkvist B, Nilsson LM, Kiemeney LA, Ros M, Bueno-de-Mesquita HB, Peeters PH, Khaw KT, Wareham NJ, Knaze V, Romieu I, Scalbert A, Brennan P, Wark P, Vineis P, Riboli E, González CA. Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Cancer. 2014 Oct 28;111(9):1870-80. doi: 10.1038/bjc.2014.459. Epub 2014 Aug 14. PMID: 25121955; PMCID: PMC4453722.

Settembre, C., De Cegli, R., Mansueto, G., Saha, P. K., Vetrini, F., Visvikis, O., Huynh, T., Carissimo, A., Palmer, D., Klisch, T. J., Wollenberg, A. C., Di Bernardo, D., Chan, L., Irazoqui, J. E., & Ballabio, A. (2013). TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nature cell biology, 15(6), 647–658. https://doi.org/10.1038/ncb2718

Ferreira, Ana & Morais, Eduarda & Leite, Ana & Mohamadou, Aminou & Holmbom, Bjarne & Holmbom, Thomas & Neves, Bruno & Freire, Mara & Silvestre, Armando. (2017). Enhanced Extraction and Biological Activity of 7-hydroxymatairesinol obtained from Norway spruce knots using Aqueous Solutions of Ionic Liquids. Green Chem.. 19. 10.1039/C7GC01091E.

Pietarinen, S.P., Willför, S.M., Ahotupa, M.O. et al. Knotwood and bark extracts: strong antioxidants from waste materials. J Wood Sci 52, 436–444 (2006). https://doi.org/10.1007/s10086-005-0780-1

Holmbom, B., Eckerman, C., Eklund, P. et al. Knots in trees – A new rich source of lignans. Phytochemistry Reviews 2, 331–340 (2003). https://doi.org/10.1023/B:PHYT.0000045493.95074.a8

Rubashkina, A. N., Lapochkina, N. P., Torshin, I. Y., & Gromova, O. A. (2020). The role of 7-hydroxymatairezinol in modulation of estrogen metabolism and therapy for mastopathy. Gynecology, 22(4), 43-48. doi: 10.26442/20795696.2020.4.200183

Giuliano C, Siani F, Mus L, Ghezzi C, Cerri S, Pacchetti B, Bigogno C, Blandini F. Neuroprotective effects of lignan 7-hydroxymatairesinol (HMR/lignan) in a rodent model of Parkinson's disease. Nutrition. 2020 Jan;69:110494. doi: 10.1016/j.nut.2019.04.006. Epub 2019 Apr 25. PMID: 31586482.

Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab. 1998 Dec;12(4):691-705. doi: 10.1016/s0950-351x(98)80011-6. PMID: 10384820.

Buck K, Zaineddin AK, Vrieling A, Heinz J, Linseisen J, Flesch-Janys D, Chang-Claude J. Estimated enterolignans, lignan-rich foods, and fibre in relation to survival after postmenopausal breast cancer. Br J Cancer. 2011 Oct 11;105(8):1151-7. doi: 10.1038/bjc.2011.374. Epub 2011 Sep 13. PMID: 21915130; PMCID: PMC3208499.

Vanharanta M, Voutilainen S, Rissanen TH, Adlercreutz H, Salonen JT. Risk of Cardiovascular Disease–Related and All-Cause Death According to Serum Concentrations of Enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study. Arch Intern Med. 2003;163(9):1099–1104. doi:10.1001/archinte.163.9.1099.

Willför SM, Smeds AI, Holmbom BR. Chromatographic analysis of lignans. J Chromatogr A. 2006 Apr 21;1112(1-2):64-77. doi: 10.1016/j.chroma.2005.11.054. Epub 2005 Dec 13. PMID: 16356507.

Eriksen, Anne Kirstine (2019). The role of whole grains and lignans in lifestyle diseases. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880 ; 2019:25 ISBN 978-91-7760-368-9 eISBN 978-91-7760-369-6[Doctoral thesis]

Di Y.: Flaxseed lignan supplementation as possible adjuvant therapy for prostate and breast cancer, Ph.D. Thesis, University of Saskatchewan, Saskatoon, SK, Canada, 2017

Smeds AI, Eklund PC, Sjöholm RE, Willför SM, Nishibe S, Deyama T, Holmbom BR. Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts. J Agric Food Chem. 2007 Feb 21;55(4):1337-46. doi: 10.1021/jf0629134. Epub 2007 Jan 30. PMID: 17261017.

Stevanovic, Tatjana & Diouf, Niokhor & García-Pérez, Martha. (2009). Bioactive Polyphenols from Healthy Diets and Forest Biomass. Current Nutrition & Food Science. 5. 264-295. 10.2174/157340109790218067.

Eklund P, Lindholm A, Mikkola JP, Smeds A, Lehtilä R, Sjöholm R. Synthesis of (-)-matairesinol, (-)-enterolactone, and (-)-enterodiol from the natural lignan hydroxymatairesinol. Org Lett. 2003 Feb 20;5(4):491-3. doi: 10.1021/ol0273598. PMID: 12583751.

Mareai, Sadiq. (2011). Secoisolariciresinol Diglucoside: A potent multifarious bioactive phytoestrogen of flaxseed. 2.

Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2(5):270-278. doi:10.4161/oxim.2.5.9498

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997 Apr;29(2):95-120. doi: 10.3109/07853899709113696. PMID: 9187225.

Setchell, K., Lawson, A., Mitchell, F. et al. Lignans in man and in animal species. Nature 287, 740–742 (1980). https://doi.org/10.1038/287740a0

Rienks, J., Barbaresko, J., & Nöthlings, U. (2017). Association of Polyphenol Biomarkers with Cardiovascular Disease and Mortality Risk: A Systematic Review and Meta-Analysis of Observational Studies. Nutrients, 9(4), 415. doi:10.3390/nu9040415

Pan A, Sun J, Chen Y, Ye X, Li H, Yu Z, Wang Y, Gu W, Zhang X, Chen X, Demark-Wahnefried W, Liu Y, Lin X. Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PLoS One. 2007 Nov 7;2(11):e1148. doi: 10.1371/journal.pone.0001148. PMID: 17987126; PMCID: PMC2048577.

Lock M. Contested meanings of the menopause. Lancet. 1991 May 25;337(8752):1270-2. doi: 10.1016/0140-6736(91)92931-q. PMID: 1674073.

Brzezinski, Amnon; Adlercreutz, Herman‡; Shaoul, Roger; Rosier, Ariel*; Shmueli, Avigail†; Tanos, Vasilus; Schenker, Joseph G. Short-term Effects of Phytoestrogen-rich Diet on Postmenopausal Women, Menopause: Volume 4 - Issue 2 - p 89-94

Brzezinski, Amnon; Adlercreutz, Herman; Shaoul, Roger; Rosier, Ariel; Shmueli, Avigail†; Tanos, Vasilus; Schenker, Joseph G. Short-term Effects of Phytoestrogen-rich Diet on Postmenopausal Women, Menopause: Volume 4 - Issue 2 - p 89-94

Adlercreutz H. Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest Suppl. 1990;201:3-23. PMID: 2173856.

Adlercreutz H. Phytoestrogens: epidemiology and a possible role in cancer protection. Environ Health Perspect. 1995 Oct;103 Suppl 7(Suppl 7):103-12. doi: 10.1289/ehp.95103s7103. PMID: 8593855; PMCID: PMC1518863.

MasonJulie K and ThompsonLilian U. Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer?. Applied Physiology, Nutrition, and Metabolism. 39(6): 663-678. https://doi.org/10.1139/apnm-2013-0420

Sung MK, Lautens M, Thompson LU. Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res. 1998 May-Jun;18(3A):1405-8. PMID: 9673348.

Tuomisto A, Nørskov NP, Sirniö P, Väyrynen JP, Mutt SJ, Klintrup K, Mäkelä J, Bach Knudsen KE, Mäkinen MJ, Herzig KH. Serum enterolactone concentrations are low in colon but not in rectal cancer patients. Sci Rep. 2019 Aug 1;9(1):11209. doi: 10.1038/s41598-019-47622-6. PMID: 31371751; PMCID: PMC6671944.

Johnsen NF, Olsen A, Thomsen BL, Christensen J, Egeberg R, Bach Knudsen KE, Loft S, Overvad K, Tjønneland A. Plasma enterolactone and risk of colon and rectal cancer in a case-cohort study of Danish men and women. Cancer Causes Control. 2010 Jan;21(1):153-62. doi: 10.1007/s10552-009-9445-5. Epub 2009 Oct 21. PMID: 19844797.

Guglielmini P, Rubagotti A, Boccardo F. Serum enterolactone levels and mortality outcome in women with early breast cancer: a retrospective cohort study. Breast Cancer Res Treat. 2012 Apr;132(2):661-8. doi: 10.1007/s10549-011-1881-8. Epub 2011 Nov 18. PMID: 22094938.

Center MM, Jemal A, Lortet-Tieulent J, Ward E, Ferlay J, Brawley O, Bray F. International variation in prostate cancer incidence and mortality rates. Eur Urol. 2012 Jun;61(6):1079-92. doi: 10.1016/j.eururo.2012.02.054. Epub 2012 Mar 8. PMID: 22424666.

He J, Wang S, Zhou M, Yu W, Zhang Y, He X. Phytoestrogens and risk of prostate cancer: a meta-analysis of observational studies. World J Surg Oncol. 2015 Jul 31;13:231. doi: 10.1186/s12957-015-0648-9. PMID: 26228387; PMCID: PMC4521376.

Milder, I. (2007). Lignan intake in the Netherlands and its relation with mortality.

Senizza A, Rocchetti G, Mosele JI, Patrone V, Callegari ML, Morelli L, Lucini L. Lignans and Gut Microbiota: An Interplay Revealing Potential Health Implications. Molecules. 2020 Dec 3;25(23):5709. doi: 10.3390/molecules25235709. PMID: 33287261; PMCID: PMC7731202.

Toure, A., & Xue-ming, X. (2010). Flaxseed Lignans: Source, Biosynthesis, Metabolism, Antioxidant Activity, Bio-Active Components, and Health Benefits. Comprehensive reviews in food science and food safety, 9 3, 261-269 .

Rowland, I., Gibson, G., Heinken, A. et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr 57, 1–24 (2018). https://doi.org/10.1007/s00394-017-1445-8

Julia Peterson, Johanna Dwyer, Herman Adlercreutz, Augustin Scalbert, Paul Jacques, Marjorie L McCullough, Dietary lignans: physiology and potential for cardiovascular disease risk reduction, Nutrition Reviews, Volume 68, Issue 10, 1 October 2010, Pages 571–603, https://doi.org/10.1111/j.1753-4887.2010.00319.x

Saarinen NM, Tuominen J, Pylkkänen L, Santti R. Assessment of information to substantiate a health claim on the prevention of prostate cancer by lignans. Nutrients. 2010 Feb;2(2):99-115. doi: 10.3390/nu2020099. Epub 2010 Jan 28. PMID: 22254011; PMCID: PMC3257165.

Sun J, Jiang H, Wang W, Dong X, Zhang D. Associations of Urinary Phytoestrogen Concentrations with Sleep Disorders and Sleep Duration among Adults. Nutrients. 2020 Jul 16;12(7):2103. doi: 10.3390/nu12072103. PMID: 32708566; PMCID: PMC7400948.

Winston J Craig, Health-promoting properties of common herbs, The American Journal of Clinical Nutrition, Volume 70, Issue 3, September 1999, Pages 491s–499s, https://doi.org/10.1093/ajcn/70.3.491s

Serraino M, Thompson LU. The effect of flaxseed supplementation on early risk markers for mammary carcinogenesis. Cancer Lett. 1991 Nov;60(2):135-42. doi: 10.1016/0304-3835(91)90220-c. PMID: 1657368.

Morand C, Manach C, Crespy V, Remesy C. Respective bioavailability of quercetin aglycone and its glycosides in a rat model. Biofactors. 2000;12(1-4):169-74. doi: 10.1002/biof.5520120127. PMID: 11216481.

Higdon J.,Drake VJ (2004). Lignans. Linus Pauling Institute. https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/lignans.

Brzezinski A, Debi A. Phytoestrogens: the "natural" selective estrogen receptor modulators? Eur J Obstet Gynecol Reprod Biol. 1999 Jul;85(1):47-51. doi: 10.1016/s0301-2115(98)00281-4. PMID: 10428321.

Kitts DD, Yuan YV, Wijewickreme AN, Thompson LU. Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol Cell Biochem. 1999 Dec;202(1-2):91-100. doi: 10.1023/a:1007022329660. PMID: 10705999.

Prasad K, Mantha SV, Muir AD, Westcott ND. Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism. Mol Cell Biochem. 2000 Mar;206(1-2):141-9. doi: 10.1023/a:1007018030524. PMID: 10839204.

Willför SM, Ahotupa MO, Hemming JE, Reunanen MH, Eklund PC, Sjöholm RE, Eckerman CS, Pohjamo SP, Holmbom BR. Antioxidant activity of knotwood extractives and phenolic compounds of selected tree species. J Agric Food Chem. 2003 Dec 17;51(26):7600-6. doi: 10.1021/jf030445h. PMID: 14664514.

Aryal S, Skinner T, Bridges B, Weber JT. The Pathology of Parkinson's Disease and Potential Benefit of Dietary Polyphenols. Molecules. 2020 Sep 24;25(19):4382. doi: 10.3390/molecules25194382. PMID: 32987656; PMCID: PMC7582699.

Fortunati N, Fissore F, Fazzari A, Becchis M, Comba A, Catalano MG, Berta L, Frairia R. Sex steroid binding protein exerts a negative control on estradiol action in MCF-7 cells (human breast cancer) through cyclic adenosine 3',5'-monophosphate and protein kinase A. Endocrinology. 1996 Feb;137(2):686-92. doi: 10.1210/endo.137.2.8593818. PMID: 8593818.

Rennert G, Rennert HS, Pinchev M, Lavie O, Gruber SB. Use of hormone replacement therapy and the risk of colorectal cancer. J Clin Oncol. 2009 Sep 20;27(27):4542-7. doi: 10.1200/JCO.2009.22.0764. Epub 2009 Aug 24. PMID: 19704062; PMCID: PMC2754905.

Bylund A, Zhang JX, Bergh A, Damber JE, Widmark A, Johansson A, Adlercreutz H, Aman P, Shepherd MJ, Hallmans G. Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice. Prostate. 2000 Mar 1;42(4):304-14. doi: 10.1002/(sici)1097-0045(20000301)42:4<304::aid-pros8>3.0.co;2-z. PMID: 10679760.

Prasad K. Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG). Mol Cell Biochem. 2000 Jun;209(1-2):89-96. doi: 10.1023/a:1007079802459. PMID: 10942205.

Prasad, Kailash. (2004). Antihypertensive Activity of Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed: Role of Guanylate Cyclase. International Journal of Angiology. 13. 7-14. 10.1007/s00547-004-1060-4.

Prasad, K. Suppression of phosphoenolpyruvate carboxykinase gene expression by secoisolariciresinol diglucoside (SDG), a new antidiabetic agent. International Journal of Angiology 11, 107–109 (2002). https://doi.org/10.1007/BF01616377

Kuijsten A, Arts IC, Hollman PC, van't Veer P, Kampman E. Plasma enterolignans are associated with lower colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev. 2006 Jun;15(6):1132-6. doi: 10.1158/1055-9965.EPI-05-0991. PMID: 16775171.

Pistollato F, Sumalla Cano S, Elio I, Masias Vergara M, Giampieri F, Battino M. Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease. Adv Nutr. 2016 Jul 15;7(4):679-89. doi: 10.3945/an.115.011775. PMID: 27422503; PMCID: PMC4942871.

Saarinen NM, Abrahamsson A, Dabrosin C. Estrogen-induced angiogenic factors derived from stromal and cancer cells are differently regulated by enterolactone and genistein in human breast cancer in vivo. Int J Cancer. 2010 Aug 1;127(3):737-45. doi: 10.1002/ijc.25052. PMID: 19924815.

Xiong XY, Hu XJ, Li Y, Liu CM. Inhibitory Effects of Enterolactone on Growth and Metastasis in Human Breast Cancer. Nutr Cancer. 2015;67(8):1324-32. doi: 10.1080/01635581.2015.1082113. Epub 2015 Oct 16. PMID: 26473769.

Bhathena SJ, Velasquez MT. Beneficial role of dietary phytoestrogens in obesity and diabetes. Am J Clin Nutr. 2002 Dec;76(6):1191-201. doi: 10.1093/ajcn/76.6.1191. PMID: 12450882.

Bhathena SJ, Velasquez MT. Beneficial role of dietary phytoestrogens in obesity and diabetes. Am J Clin Nutr. 2002 Dec;76(6):1191-201. doi: 10.1093/ajcn/76.6.1191. PMID: 12450882.

Setchell KD, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, Brashear WT, Kirschner AS, Cassidy A, Heubi JE. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr. 2001 Apr;131(4 Suppl):1362S-75S. doi: 10.1093/jn/131.4.1362S. PMID: 11285356.

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