HMRlignan™

Technical Description
Name of the plant Picea abies
Part of the plant used Knots wood
Formula C 20 H 22 O 7 (hydroxymatairesinol) + C 2 H 3 KO 2
IUPAC Name 4-[Hydroxy(4-hydroxy-3-methoxyphenyl)methyl]-3-
(4-hydroxy-3-methoxybenzyl)-dihydrofuran-2(3H)-one - potassium acetate adduct
Molecular weight 374.39 (hydroxymatairesinol) g/mol + 98.14 g/mol (AcOK)
Structural Formula
Appearance Off-white crystalline powder
Solubility Soluble in methanol
Identification IR
UV
Assay Hydroxymatairesinol + allo-isomer-potassium acetate
NLT 90 %
Related substances Matairesinol
NMT 7 %
Water content NMT 10 %
Heavy metals NMT 20 ppm
Microbiology Complies with EP
[AcO - K + ]
Storage Preserve in tight container, protected from light, heat and humidity
Bibliografic References
1. Whole grain food intake elevates serum enterolactone.
British Journal of Nutrition (2002), 88, 111–116. David R.
Jacobs Jr., Mark A. Pereira, Katariina Stumpf, Joel J. Pins and
Herman Adlercreutz.
2. Antioxidant and antitumor effects of hydroxymatairesinol
(HM-3000, HMR), a lignan isolated from the knots of spruce.
Eur J Cancer Prev. 2002 Aug;11 Suppl 2:S48-57. Kangas L,
Saarinen N, Mutanen M, Ahotupa M, Hirsinummi R, Unkila M,
Perala M, Soininen P, Laatikainen R, Korte H, Santti R. Hormos
Nutraceutical Ltd, Turku, Finland.
3. Enterolactone inhibits the growth of 7,12-dimethylbenz(a)
anthracene-induced mammary carcinomas in the rat. Mol
Cancer Ther. 2002 Aug;1(10):869-76. Related Articles, Links
Saarinen NM, Huovinen R, Warri A, Makela SI, Valentin-Blasini
L, Sjoholm R, Ammala J, Lehtila R, Eckerman C, Collan YU,
Santti RS.
4. Association between low serum enterolactone and
increased plasma F2-isoprostanes, a measure of lipid
peroxidation. Atherosclerosis. 2002 Feb;160(2):465-9.
Vanharanta M, Voutilainen S, Nurmi T, Kaikkonen J, Roberts
LJ, Morrow JD, Adlercreutz H, Salonen JT.
5. Relationships of urinary phyto-oestrogen excretion to
BMD in postmenopausal women. Clin Endocrinol (Oxf). 2002
Mar;56(3):321-8. Kim MK, Chung BC, Yu VY, Nam JH, Lee HC,
Huh KB, Lim SK.
6. Flaxseed dietary supplement versus hormone replacement
therapy in hypercholesterolemic menopausal womenObstet
Gynecol. 2002 Sep;100(3):495-504. . Lemay A, Dodin S, Kadri
N, Jacques H, Forest JC.
7. Effects of dietary phytoestrogens in postmenopausal
women.. Climacteric. 1998 Jun;1(2):124-9. Dalais FS, Rice
GE, Wahlqvist ML, Grehan M, Murkies AL, Medley G, Ayton R,
Strauss BJ.
8. Dietary flour supplementation decreases post-menopausal
hot flushes: effect of soy and wheat. Maturitas. 1995
Linnea SA
Via Cantonale
CH-6595 Riazzino (TI)
Switzerland
Tel: +41 (0)91 850 5050
Fax: +41 (0)91 850 5070
E-Mail: info@linnea.ch
Web: www.linnea.ch
Apr;21(3):189-95. Murkies AL, Lombard C, Strauss BJ, Wilcox
G, Burger HG, Morton MS.
9. Higher dietary intake of lignans is associated with better
cognitive performance in postmenopausal women. J Nutr.
2005 May;135(5):1190-5. Franco OH, Burger H, Lebrun CE,
Peeters PH, Lamberts SW, Grobbee DE, Van Der Schouw YT.
10. Dietary intake and urinary excretion of lignans in Finnish
men. Br J Nutr. 2010 Mar;103(5):677-85. Epub. 2009. Oct 8.
Nurmi T, Mursu J, Peñalvo JL, Poulsen HE, Voutilainen S.
11. Risk of cardiovascular disease-related and all-cause
death according to serum concentrations of enterolactone:
Kuopio Ischaemic Heart Disease Risk Factor Study. May
12;163(9):1099-104. 2003. Arch Intern Med. Vanharanta M et
al.
12. _Phytoestrogen intake and cardiovascular risk markers
in bangladeshi postmenopausal women. Mymensingh Med
J. 2011 Apr;20(2):219-25. Saleh F, Afnan F, Ara F, Yasmin S,
Nahar K, Khatun F, Ali L.
13. Dietary intake of phytoestrogens is associated with
a favorable metabolic cardiovascular risk profile in
postmenopausal U.S.women: the Framingham study.
J Nutr Feb;132(2):276-82. 2002. de Kleijn MJ et al.
14. Intake of the plant lignans matairesinol, secoisolariciresinol,
pinoresinol, and lariciresinol in relation to vascular inflammation
and endothelial dysfunction in middle age-elderly men and
post-menopausal women living in Northern Italy. Nutr Metab
Cardiovasc Dis. 2010. Jan;20(1):64-71. Epub 2009 Apr 10.
Pellegrini N, Valtueña S, Ardigò D, Brighenti F, Franzini L, Del
Rio D, Scazzina F, Piatti PM, Zavaroni I.
15. Dietary phytoestrogen, serum enterolactone and risk of
prostate cancer: the cancer prostate sweden study (sweden).
Cancer Causes Control. 2006 Mar;17(2):169-80. Hedelin M,
Klint A, Chang ET, Bellocco R, Johansson JE, Andersson SO,
Heinonen SM, Adlercreutz H, Adami HO, Gronberg H, Balter
KA.
HMRlignan
Norway Spruce Lignans

HMR
HMRlignan (Norway Spruce Lignans)
Lignans are a group of phytonutrients widely
distributed in the plant kingdom. Their importance
in health maintenance has been underlined by an
increasingly large pool of scientific knowledge and
epidemiological data, which has identified them
in a wide variety of foods such as unrefined grain
products, seeds (sesame and flax), berries, fruits
and vegetables [1].
Unlike our ancestors’ diet, today’s Western diet
does not include much in terms of lignin-containing
foods, so the amount of lignans available from food
is quite limited. Many researchers suggest that
the decreased intake of foods containing lignan
Source
Linnea HMRlignan is derived from Norway
Spruce knots.
The Norway spruce (Picea abies), which belongs to
the Pinacee family, is a large evergreen coniferous
tree growing to a height of 35–55 m (115-180 ft)
and having a trunk diameter of 1-1.5 m. This
species of spruce is native to Europe and plentiful
in Nordic countries such as Finland, where it is
used extensively in forestry for timber and paper
Activity
Active estrogen-like compounds are obtained
from natural plant compounds locked into the
cellular matrix. As HMRlignan is not in a food
precursors has left women without the ability to
modulate estrogen naturally and, for this reason,
supplementation with a natural concentrated
source is recommended.
Norwegian spruce knots have been found to be rich
in lignans and, in particular, 7-hydroxymatairesinol,
also called HMR [2]. The Norwegian spruce
extract is a new generation of lignan complex that
provides a highly bioavailable supplement and a
more digestible alternative to natural sources. It
carries out the estrogen-like activity that plays an
important role in their reported prophylactic action
against cardiovascular disease and tumours.
production, which has led to a strong national
industrial and academic interest in the study of
wood chemistry.
The source of Linnea raw material is in Europe. In
co-operation with forestry institutions and through
a specific separation process, the knots can be
obtained without any additional impact on the local
environment and with full control of raw material
quality.
matrix, it has a superior bioavailability and proven
pharmacokinetic properties. It is therefore a pure
lignan in the aglycone form (not bound to sugars)
and, upon arrival in a healthy intestinal tract, is
more efficiently transformed into enterolactone [2].
The lignans in the Norway Spruce extract act
like estrogen, stimulating the synthesis and the
circulating levels of sex hormone-binding globulin.
Collectively, through multiple mechanisms of action,
lignans positively influence estrogen balance in
the body, having significant effects during the
climacteric when estrogen levels are in flux. When
estrogen levels decline, lignans may have a weak
estrogen-like effect, mimicking the presence of
Common Applications
Lignan intake increases serum enterolactone,
which is correlated with a decrease in the risk of
coronary heart disease and cardiovascular disease
in middle-aged people.
Like HMR, lignans help to control the severity and
frequency of menopause symptoms and their
presence in the blood and urine of women has
been correlated with a reduced risk of related
chronic diseases [5].
A high intake of lignans in post-menopausal women
leads to a favourable metabolic cardiovascular risk
profile with low breast cancer rates. In fact, breast
Clinical Evidence
Both epidemiological and clinical studies support
the efficacy of dietary lignans in preventing various
estrogen-related diseases/symptoms such as
breast and prostate cancer, menopause symptoms,
cardiovascular diseases, and osteoporosis.
Menopause symptoms
Lignans help to control the menopause by acting on
several symptoms. In a 2002 Canadian study lignans
were shown to improve mild menopausal symptoms
estrogen. When estrogen levels are high, lignans
occupy and block the estrogen receptors, thereby
smoothing both peaks and valleys [3].
As well as being an efficient and direct precursor
of enterolactone, HMRlignan is also a potent
antioxidant as showed by in vitro tests. Finally,
HMRlignan has also been shown to become
incorporated in isolated low-density lipoprotein
fractions, and to protect against copper-induced
LDL oxidation in vitro [2,4].
cancer is a hormone-regulated disease controlled
by estrogens via a complicated series of pathways.
Bone health is also an emerging area where lignans
are being shown to play a positive role. Here too,
estrogens are known to play an important role in
bone maintenance by regulating bone reabsorption.
With regard to human health, the amount of
evidence highlighting the benefits of lignans in
the maintenance of prostate wellbeing is growing
and suggests that enterolactone may have a
direct inhibitory effect on cancer cell growth and
signalling.
and to lower glucose and insulin levels [6].
A significant reduction in the frequency of hot flushes
was observed in two Australian studies [7,8] involving
postmenopausal women (average age 54, range 30-
70 years) suffering at least 14 hot flushes per week.
Menopausal symptom scores as well as hot flushes
were significantly decreased in the groups taking
lignan supplementation.
A recent study conducted by Dutch researchers has
evaluated the influence of dietary phytoestrogen
intake on cognitive function showing that women
consuming higher levels of lignans performed better
in the Mini-Mental State Examination [9].
Bone health
Recent studies have shown a link between lignan
consumption and bone reabsorption reporting
a relationships between urinary phytoestrogen
excretion and bone mineral density (BMD) in
postmenopausal women. Reported results showed
that, in osteoporotic patients, urinary enterolactone
was lower than average and that higher BMD was
correlated with a higher level of urinary enterolactone
[10].
Cardiovascular disease
The Kuopio Ischaemic Heart Disease Risk Factor
Study correlated the daily intake of lignans and serum
enterolactone levels with a reduction in the risk of
coronary heart disease and cardiovascular disease
Toxicity and Safety
As this was a novel lignan source, the researchers
conducted extensive safety testing in accordance
with the rules of pharmaceutical GCP (Good Clinical
Practice).
In a 13-week toxicity study, high systemic exposure to
HMRlignan was tested by dose-related increases
in the total (conjugated and unconjugated) plasma
concentration of 7-HMR and the metabolites ente-
rolactone, 7-hydroxyenterolactone and matairesinol.
Enterolactone appeared to be the main metabolite.
HMRlignan exposure did not significantly affect
clinical signs, ophthalmoscopic findings, neurobeha-
vioural observations or motor activity. The observed
adverse effects of HMRlignan were set at 0.25 % in
food, corresponding to 160 mg/kg body weight/day.
In May 2004, New Dietary Ingredient (NDI) clearance
from the FDA was obtained for the ingredient.
in middle-aged Finns [10,11]. In a more recent study
was revealed an inverse relationship between the total
phytoestrogen and lignan consumption and serum
glucose level with other significant parameters [12].
The higher Matairesinol intake in typical Northern
Italian diet, as well as in a study performed in the U.S.
has assessed the relationship between a high intake
of lignans and a favourable metabolic cardiovascular
risk profile [13,14].
Breast and prostate cancer
Several studies indicate an inverse relationship
between elevated enterolactone levels and the risk of
breast and prostate cancer.
In a 2006 Swedish study, Hedelin et al. investigated
the possibility of phytoestrogens protecting against
prostate cancer and the relationships between
dietary phytoestrogen intake and the risk of prostate
cancer revealing that a high intake of foods rich in
phytoestrogens was correlated with a decrease in the
risk of prostate cancer [15].