• Norway spruce (Picea abies)
    Norway spruce (Picea abies)
  • Norway spruce (Picea abies)
    Norway spruce (Picea abies)

HMR

HMRlignanTM (NORWAY SPRUCE LIGNANS)

Linnea extracts and manufactures HMR as a botanical ingredient for pharmaceutical purposes.

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 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.

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 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.

Activity

Active estrogen-like compounds are obtained from natural plant compounds locked into the cellular matrix. As HMRlignan™ is not in a food 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 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].

Common Applications and Evidence

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 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.

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 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 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].

Technical Description
Name of the plant Picea abies
Part of the plant used Knots wood
Formula C20H22O7 (hydroxymatairesinol) + C2H3KO2
IUPAC Name 4-[Hydroxy(4-hydroxy-3-methoxyphenyl)methyl]-3- (4-hydroxy-3-methoxybenzyl)-dihydrofuran-2(3H)-one - potassium acetate adduct

Structural Formula
HMRlignan

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 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. 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.