![Page 1: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/1.jpg)
LIGNANSOptimizing Women’s Health
Donald Brown, ND, Managing Director, Natural Product Research Consultants • www.nprcdb.com
![Page 2: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/2.jpg)
1. PremenopausalBreast HealthUterine Fibroid Prevention
3. PostmenopausalBreast HealthCardiovascular HealthCognitive FunctionColon Health
Lignans: Health Benefits in theDifferent Phases of a Woman’s Life
2. MenopauseHot FlashesBreast Health
![Page 3: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/3.jpg)
Lignans: A Definition
• Lignans are one of three main groups of plant compounds classifiedas phytoestrogens. The other two are isoflavonoids and coumestans.All three groups are characterized by diphenolic rings, making them structurally similar to endogenous estrogen.
• The predominant plant lignans of dietary importance are matairesinol, hydroxymatairesinol (HMR), secoisolariciresinol, and pinoresinol.
• These are converted in the gut to the mammalian lignans, enterolactone (ENL) and enterodiol (EDL).
![Page 4: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/4.jpg)
Lignans: Dietary andSupplement Sources
SECO Secoisolariciresinol (mg/100g)
MAT Matairesinol (mg/100g)
Note
Flaxseed 180 1 SECO as glycoside
Sesame seed trace 0.2
Rye, Wheat, Oat, Barley
0.05 – 0.1 0 – 0.1 New data has found HMR to be the predominant lignan in grains
Cranberry Strawberry
0.5 – 1 trace
Soy (different varieties)
0.01 – 0.05 trace
7-HMR (dietary supplement
80,000
![Page 5: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/5.jpg)
Hydroxymatairesinol (HMR)A Micronutrient Common in Foods
• 24 plant lignans were analyzed by HPLC-MS/MS in bran extracts of 16 cereal species, four nut species, and in sesame seeds and linseeds.
• HMR was found to be the dominant lignan in wheat, triticale, barley, corn, amaranth, millet, and oat bran (primarily found in the bran portion of grains)
J Agric Food Chem 2007;55:1337– 46.
![Page 6: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/6.jpg)
Hydroxymatairesinol (HMR)A Micronutrient Common in Foods, cont.
• Charts such as the previous were based on older extraction methods which were likely to destroy the HMR in the grains. • Scandinavian studies associating
increased intake of lignans with health benefits in women and men are most likely due to increased intake of dietary sources such as rye bread, whole meal breads, and wheat and wheat bran as opposed to flax.
![Page 7: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/7.jpg)
Dietary and SupplementLignan Conversion
Secoisolariciresinol Matairesinol Hydroxymatairesinol
![Page 8: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/8.jpg)
Dietary and SupplementLignan Conversion
Secoisolariciresinol Matairesinol Hydroxymatairesinol
GUT MICROFLORA
ENTERODIOL ENTEROLACTONE
![Page 9: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/9.jpg)
Dietary and SupplementLignan Conversion
ENTEROLACTONE
![Page 10: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/10.jpg)
Enterolactone
• ENL is the primary circulating mammalian lignan and is used as the primary biomarker for plant lignan intake.
• Humans vary considerably in their ability to metabolize plant lignans due to:- Differences in intestinal transit time- Gut microflora composition- The use of antibiotics
![Page 11: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/11.jpg)
EnterolactoneMechanisms of Action
• Hormonal- 2OHE/16OHE ratio- Sex hormone binding globulin- Aromatase
• Antioxidant• Anti-inflammatory • Anti-Proliferative/Pro-Apoptoic
![Page 12: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/12.jpg)
HMR AND ENLClinical Study
![Page 13: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/13.jpg)
7-HMRClinical Study in Menopausal Women
• Title: The effect of 7-HMR on mammalian lignan and estrogen metabolite levels in menopausal women: A randomized, double-blind, single-dummy, parallel group, pilot study.
• Study Design: 8-week controlled study in 20 menopausal women (diagnosis of natural or surgical menopause for at least one year; age 50-75 years; BMI ≥25 and ≥35 kg/m2). Study comparing two doses of 7-HMR (25 mg/day and 50 mg/day).
Poster Presentation, Scripps Integrative Medicine 5th Annual Natural Supplements Conference,January 17-20, 2008.
![Page 14: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/14.jpg)
7-HMRPharmacokinetic Data
• Prior to randomization, 12 women were selected for a pharmacokinetic study to determine serum levels of 7-HMR and ENL after a single dose (25 mg) of 7-HMR.
• Blood was drawn at baseline (time 0) and then at ½, 1, 2, 4, 8, 12,
24, 48, and 72 hours following the 7-HMR dose.
• Data is available for 11 women (one subject was non-compliant)
![Page 15: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/15.jpg)
Mean 7-HMR Levels
* p = 0.003
** p = 0.0001
3000
2000
1000
00 0.5 1 2 3 4 5 6 7 8 9 10 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
**
**
*
Time (hours)
nmol
/l se
rum
![Page 16: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/16.jpg)
Mean Serum ENL Levels
*
Time (hours)
nmol
/l se
rum
* p = 0.018
** p = 0.029
* **
![Page 17: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/17.jpg)
ENL Levels Over 72 Hrs
Time (hours)
nmol
/l se
rum
* p = 0.059
** p = 0.018
*** p = 0.029
* **
***
![Page 18: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/18.jpg)
7-HMR8-Week Pilot Study
• Following a 1-week washout phase (lignan-poor diet), women had a baseline blood draw for HMR, ENL, Baseline hot flash diaries were collected as well (see results in hot flash section of presentation).
• Women were randomized to one of two doses of 7-HMR – 25 mg or 50 mg per day. The mean age of the 25 mg group was 53.9 years and 55.9 years for the 50 mg group.
• At visits 2 (week 4) and visit 3 (week 8), blood draw for HMR and ENL repeated and hot flash diaries collected.
![Page 19: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/19.jpg)
7-HMRENL Levels – 4 and 8 weeks (25 mg)
25 mg
* p = 0.02
** p = 0.03
123456789
T0 T4 T8
***
nmol
/l se
rum
![Page 20: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/20.jpg)
2
4
6
8
10
12
T0 T4 T8
* *
7-HMRMean ENL Levels – 4 and 8 weeks (50 mg)
50 mg
* p = 0.01
nmol
/l se
rum
![Page 21: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/21.jpg)
CARDIOVASCULAR HEALTH
![Page 22: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/22.jpg)
• Serum ENL has been shown to decrease Plasma F - isoprostane (a measure of lipid peroxidation) Atherosclerosis 2002;160:465–9.
• Serum ENL levels are inversely correlated with risk of coronary heart disease-related and cardiovascular-disease-related mortality in males. Arch Intern Med 2003;163:1099–1104.
2
Enterolactone Cardiovascular Health
![Page 23: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/23.jpg)
• National Health and Nutrition Examination Survey (NHANES 1994-2004) examined lignan intake in 1,492 U.S. adults (males and females) and urinary excretion of enterolactone and enterodiol.
• Higher urinary concentrations of enterolactone, and to a lesser extent enterodiol, were associated with higher levels of HDL-cholesterol and lower levels of triglycerides.
Enterolactone Cardiovascular Health
![Page 24: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/24.jpg)
BREAST HEALTH
![Page 25: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/25.jpg)
Dietary Lignans/ENL Breast Cancer Risk
• Several, but not all epidemiological studies have reported reduced risk of breast cancer associated with increased intake of dietary lignans and/or higher plasma levels of ENL.
• A case control study of premenopausal women found that overall risk of breast cancer was inversely correlated with plasma ENL.
• Another found the same in both pre- andpost-menopausal women.1. British J Cancer 2009;100:1492-8.2. Eur J Cancer Prev 2006;15:225-32.3. Cancer Epidemiol Biomarkers Prev 2001;10:339-44.
1
2
3
![Page 26: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/26.jpg)
Dietary Lignans/ENL Breast Cancer Risk
-
• Increased plasma ENL was associated with a significant decreased risk of ER breast cancer in both pre- and postmenopausal women.
• Higher dietary lignan intake and serum levelsof ENL were associated with a reduced risk of ER and PR breast cancer in postmenopausal women.
1. Breast Cancer Res Treatment 2006;99:309-11.2. Cancer Epidemiol Biomarkers Prev 2004;13:2084-9.3. J Natl Cancer Inst 2007;99:457-86.
1 2
3
-
+
![Page 27: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/27.jpg)
• Increased intake of dietary lignans was associated with:
- An approximately 40-50% decreased odd of having breast cancer in both pre- and postmenopausal women
- Significantly reduced odds of having an invasive tumor (especially premenopausal women)
- Decreased risk of ER breast cancer and HER2 in premenopausal women
- Decreased risk of ER breast cancer on postmenopausal women
- Among premenopausal women, the highest tertile of total lignan intake had greatly reduced odds of having triple negative tumors compared to those in the lowest tertile
J Nutr 2012;142:91-8.
-
-
+
Dietary Lignans/ENL Breast Cancer Risk
![Page 28: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/28.jpg)
HOT FLASHES
![Page 29: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/29.jpg)
• In an open-label, pilot study, flaxseed (40 g/day) was found to decrease mean hot flash scores after 6 weeks of ingestion in women with moderate to severe menopausal symptoms.
• 57% reduction in hot flashes but 50% of women experienced GI symptoms and 6 (21%) withdrew from the study.
J Society Integrative Med 2007;5:106-12.
Lignans (flaxseed) Hot Flashes
![Page 30: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/30.jpg)
7-HMR Pilot Study-Hot Flash Data
• Following a 1-week washout phase (lignan-poor diet), women had a baseline blood draw for HMR, ENL, Baseline hot flash diaries were collected as well (see results in hot flash section of presentation).
• Women were randomized to one of two doses of 7-HMR – 25 mg or 50 mg per day. The mean age of the 25 mg group was 53.9 years and 55.9 years for the 50 mg group.
• At visits 2 (week 4) and visit 3 (week 8), blood draw for HMR and ENL repeated and hot flash diaries collected.
Poster Presentation, Scripps Integrative Medicine 5th Annual Natural Supplements Conference, January 17-20, 2008.
![Page 31: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/31.jpg)
7-HMR Hot Flashes
• At baseline, both groups had a similar mean number of hot flashes per day (4.3)
• In the 25 mg group, the change in mean number of hot flashes was not significant at week 4, but was reduced to 3.7 by week 8 (p = 0.01)
• In the 50 mg group, the change in hot flashes from baseline were reduced to 2.7 per day at week 4 (37.2%; p = 0.04) and 2.0 per day at week 8 (53.5%; p = 0.01)
• Between groups comparison found a significant advantage for the 50 mg group at both week 4 (p = 0.003) and at week 8 (p = 0.007)
![Page 32: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/32.jpg)
HMRlignan™ (50mg)Hot Flash Reduction
*
Number of treatment weeks
Mea
n nu
mbe
r of
hot
fla
shes
.51.01.52.02.53.03.54.04.55.0
0 4 8
*p=0.04 **p=0.01
* *
![Page 33: · PDF fileLignans: A Definition ¥ Lignans are one of three main groups of plant compounds classified as phytoestrogens. The other two are isoflavonoids and coumestans](https://reader034.vdocument.in/reader034/viewer/2022042620/5a79d56a7f8b9ae67b8c611d/html5/thumbnails/33.jpg)
End