2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and
Company Inc. 1998.
3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine.
Institute of Applied Complementary Medicine Inc. 1997.
1. Heptinstall S, et.al., Parthenolide Content and Bioactivity of Feverfew (Tanaceum Parthenuim (L.) Schultz-Bip), Estimation of
Commercial and Authenticated Feverfew Products, J Pharm Pharmacol 44, 1992, 391-395.
2. Heptinstall S, et.al., Extracts of Feverfew Inhibits Granule Secretion in Blood Platelets and Polymorphonuclear Leukocytes, Lancet 1,
1985, 1971-1074.
3. Johnson ES, et.al., Efficacy of Feverfew as Prophylactic Treatment of Migraine, Br Med J 291, 1985, 569-573.
4. Murphy JJ, Heptistall S, and Mitchell JRA, Randomized Double-blind Placebo-controlled Trial of Feverfew in Migraine Prevention,
Lancet ii, 1988, 189-192.
5. Pattrick M, et.al., Feverfew in Rheumatoid Arthritis: A Double-blind, Placebo-controlled study, Ann Rheum Dis 48, 1989, 547-549.
6. Murray MT, The Healing Power of Herbs (2nd edition), Prima Publishing, 1995.
7. De Weerdt CJ, Bootsma HRP, Hendricks H. Herbal medicines in migraine prevention. Randomized double-blind, placebo-controlled
crossover trial of a feverfew preparation. Phytomedicine. 1996; 3: 225-230.
8. Dietary Supplement Information Bureau. www.content.intramedicine.com: Feverfew
9. Palevitch D, Earon G, Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: a double-blind
placebo-controlled study. Phytother Res. 1997; 11: 508-511.
10. Pittler MH, Vogler BK, Ernst E. Feverfew for preventing migraine ( Cochrane Review). Cochrane Database Syst Rev. 2000; (3):
CDOO2286.
11. Healthnotes, Inc.2001. www.healthnotes.com: Feverfew.
12. Newall C, Anderson LA, Phillpson JD. Herbal Medicines: A Guide for Health-Care Professionals. London, England: Pharmaceutical
Press; 1996: 120.
13. McNeill JR. Interactions between herbal and conventional medicines. Can J CME. 1999; 11 (12): 97-110.
14. Groenewegen WA, et al. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human
platelet activity in-vitro. J Pharm Pharmacol. 1990; 42 (8): 553-57.
15. Biggs MJ, et al. Platelet aggregation in patients using feverfew for migraine. Lancet. 1982; 2 (8301): 776.
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Meschino Health Comprehensive Guide to Herbs
Flaxseed and Flaxseed Powder
General Features
Flaxseeds are a rich source of secoisolariciresinol diglycoside (SLD) and other mammalian lignan precursors.
Flaxseed contains 800-times more of these mammalian lignan precursors than is found in any other food (i.e. beans,
nuts). The presence of SLD and related lignan precursors as well as its rich alpha-linolenic acid (omega-3 fat) content
makes Flaxseed a very unique dietary supplement providing a broad range of health-promotion effects. The
consumption of Flaxseed or processed Flaxseed (i.e. muffin or bread) has been shown to significantly raise blood
levels of the mammalian lignans enterolactone and enterodiol in a dose-dependent manner. Enterolactone and
enterodiol are produced in the colon by the action of bacteria on SLD.1,4 Both enterolactone and enterodiol act as
phytoestrogens and can thus, bind to estrogen receptors on breast (and other reproductive tissues) cells and inhibit
certain enzymes (i.e., aromatase enzyme in adipose tissue, also known as estrogen synthase) 2
These, and other synergistic effects have made Flaxseed a target for breast cancer research. Other Flaxseed
attributes have stimulated research to examine its potential benefits in the prevention of cardiovascular disease,
cancer (i.e. breast, prostate, colon), osteoporosis and the management of menopausal symptoms. 3,4
Principle Active Constituents
a. Mammalian Lignan Precursors
In particular: Secoisolariciresinol and matairesinol. These are converted into the mammalian lignans, enterolactone
and enterodiol by colonic bacteria. Enterolactone and enterodiol are phytoestrogens and exhibit other functions
(i.e. antioxidants).
b. Alpha-Linolenic Acid (an Omega-3 fat)
The amount of alpha-linolenic acid in Flaxseed Powder is far less than in flaxseed oil (see flaxseed oil, alpha-
linolenic acid), which is more likely to provide more significant health-promotion effects related to Omega-3 fat
consumption (e.g., anti-inflammatory effects)
c. Fiber
Soluble and insoluble fiber 4,5,6
Clinical Application and Mechanism of Action
1. Cancer Prevention and Support
Experimental Evidence - Enterolactone and enterodiol have been shown to exhibit the following anti-cancer
functions on an experimental basis:
• Compete with estradiol for nuclear binding estrogen binding sites in rat uteri
• Inhibit growth of estrogen-sensitive breast cancer cell lines
• Inhibit angiogenesis of cancer cells
• Inhibit aromatase enzyme, reducing the synthesis of estrone hormone in adipose tissue
• Decrease aberrant crypt and foci in rat colonic epithelium
• Inhibit epithelial cell proliferation in rat mammary gland
• Decrease tumor size in promotion stage of breast cancer in animal studies 5
• Reduced colon cancer development with concurrent intake of Flaxseed in carcinogen-induced colon cancer
experiments with rats 4
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•
Provide antioxidant protection 7
•
Lifetime exposure and gestational exposure to Flaxseed lignans induces cancer prevention structural
changes to mammary glands and endocrine changes consistent with a reduced risk of breast cancer
development in animals 12
•
Induce cancer cell differentiation
•
Inhibition of tyrosine kinase and DNA topoisomerase – two key enzymes that determine the rate of cell
division 8
•
Anti-mitotic effect 4
•
Reduction of plasma insulin-like growth factor-1 levels (IGF-1) in rats. Higher IGF-1 blood levels is associated
with an increased risk of breast cancer in some human studies 9
•
Reduction of pulmonary metastasis of melanoma cells and inhibit the growth of metastasic tumors that formed
in the lungs of mice 10
Human Evidence - Enterolactone and enterodiol have been shown to exhibit the following anti-cancer
functions in human studies:
•
Antiproliferative effect on the breast, similar to that of other selective estrogen receptor modulators, such as
tamoxifen and raloxifen 11
•
Stimulate production of sex hormone-binding globulin (SHBG), decreasing levels of free unbound sex
hormones 12
•
Decrease the synthesis of 16-alpha hydroxyestrone and increase the synthesis of 2 hydroxyestrone. 13 A
higher 2 hydroxyestrone to 16-alpha hydroxyestrone ratio (urinary metabolites) has been shown to be related
to a decreased risk of breast cancer in women. This is a suggested “chemoprotective effect”. 14
•
Breast cancer patients excrete very low levels of lignans compared with non breast cancer subjects 4
•
Vegetarian women are known to have a lower incidence of breast cancer and exhibit higher blood levels of
mammalian lignans 15
•
Improvement in cystic mastalgia, a potentially precancerous condition in women 16
•
Increased or longer luteal phase, increased progesterone to estradiol ratios during the luteal phase, fewer
anovulatory cycles, and a decreased tendency to ovarian dysfunction; all of which are linked to a reduced risk
of breast cancer in women 4
2. Cyclical Mastalgia
In a double blind placebo-controlled study by Plu-Bureau et al, they demonstrated that patients ingesting the
flaxseed muffin (25gm Flaxseed ) reported a significant improvement in breast pain reduction compared to the
placebo group, during the three consecutive menstrual cycle duration of the trial. Results were attributed to the
antiestrogen effects of Flaxseed lignans. 16
3. Cholesterol Lowering and Other Effects on Reducing Cardiovascular Disease
Animal studies originally suggested that Flaxseed intake had a hypocholesterolemic effect, that is due to its soluble
fiber concentration, not to its alpha-linolenic acid content.16
In human trials including men and postmenopausal women with high blood cholesterol levels, Flaxseed Powder or
Flaxseed supplementation in various forms has been shown to reduce total cholesterol (approximately 7-10
percent), reduce LDL-cholesterol (approximately 15 percent), reduce lipoprotein (a) (Lp(a)) concentrations by
approximately 7 percent. Lp(a) is emerging as an important risk factor for cardiovascular disease as it increases
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clotting behaviour of platelets, cholesterol deposition in the artery wall and it oxidizes LDL-cholesterol, making it
very atherogenic.
Flaxseed supplementation is the only dietary factor shown to reduce Lp(a) to date.
Estrogen replacement therapy reduces Lp(a) levels, but cholesterol lowering drugs (i.e. statin drugs) do not
17,18,19
Flaxseed lignans inhibit the cholesterol-7-alpha hydroxylase and acyl CoA cholesterol transferase enzymes,
involved in cholesterol synthesis, thus reducing total cholesterol. 24
1. Chronic Renal Failure and Renal Disease In Lupus
Animal and human studies indicate that a diet rich in soy based protein and isoflavones, and/or Flaxseed lignans
retard the development and progression of chronic renal disease. The protective effect is considered to be due to
effects on cell growth and proliferation, extracellular matrix synthesis, reduced oxidative stress and inflammation
reduction 20
In humans (and animals) Flaxseed supplementation has demonstrated renoprotective effects in human lupus
nephritis, with significant delay in the onset of proteinuria, and preservation of the glomerular filtration rate (GFR)
and renal size
5. Bone Density and Menopausal Symptom Support
Preliminary evidence in women suggests that the phytoestrogen influence of enterolactone and enterodiol (from
Flaxseed supplementation) has a positive effect on bone density and menopausal symptoms (i.e. hot flashes) 11
6. Prostate Cancer Protective Effect
Flaxseed lignans interfere with steroid metabolism and bioavailablity in a fashion that is linked to reduced prostate
cancer risk. They also inhibit enzymes such as tyrosine kinase and topoisomerase, which initiate the cellular
proliferation rate. Epidemiological studies link the above endocrine and molecular events with up to an 80 percent
reduction in risk of prostate cancer 22
7. Constipation
Human studies reveal that Flaxseed supplementation improves laxation 5 It appears that Flaxseed intake
increases fecal excretion of bile acids, increasing laxation and reducing the conversion of bile acids to cholesterol in
the liver; thereby lowering blood cholesterol 23,5
Dosage Ranges
1. General Health and Cholesterol Lowering: 25–50 gms of ground flaxseeds per day (unground seeds are
significantly less bioavailable in regards to their lignan precursors content) 1, 13,14,17,18,19
2. Cyclical Mastalgia: 25 gm per day of ground Flaxseed Powder1,13,14,16
3. Female Menopausal Support: 25-50 gm per day of ground Flaxseed Powder13,14
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Meschino Health Comprehensive Guide to Herbs
Adverse Side Effects and Toxicity
Ground Flaxseed is extremely non-toxic. It is well tolerated according to human trails with no significant side effects,
other than the occasional report of mild abdominal discomfort 5,16,23,24
Drug-Nutrient Interactions
There are no well-known drug-nutrient interactions for ground Flaxseed , Flaxseed Powder or Flaxseed -containing
products 1,16,25
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and
mineral supplements. All other supplements or dose alterations may pose a threat to the developing fetus and there is
generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other
than a prenatal supplement. Any supplementation practices beyond a prenatal supplement should involve the
cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)
References: Pregnancy and Lactation
i. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
ii.
Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company Inc. 1998.
iii.
The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
iv.
Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary
Medicine Inc. 1997.
v.
Nesbitt PD et al. Human metabolism of mammalian lignan precursors in raw and processed flaxseed. Am J Clin Nutr 1995;69(3):549-55
vi.
Huthcins AM et al. Flaxseed influences urinary lignan excretion in a dose-dependent manner in postmenopausal women. Cancer
Epidemiol Biomarkers Prev 2000;9(10):1113-8
vii.
Tham DM et al. Clinical Review 97 : Potential health benefits of dietary phytoestrogens : a review of the clinical, epidemiological, and
mechanistic evidence. J Clin Endocrinol Metab 1998;83(7):2223-35
viii.
Zeigler J. Just the Flax, Ma’am: Researchers Testing Linseed. J Natl Cancer Instit 1994;86(23):1746-8
ix.
Cunnane SC et al. Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr 1995;61(1):62-8
x.
Prasad K et al. Reduction in hypercholesterolemia atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid. Atherosclerosis
1998;136(2):367-75
xi.
Kitts DD et al. Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol
and enterolactone. Mol Cell Biochem 1999;202(1-2):91-100
xii.
Kurzer MS et al. Dietary Phytoestrogens. Annu Rev Nutr 1997;17:353-81
xiii.
Richard SE et al. Plasma insulin-like growth factor-1 levels in rats are reduced by dietary supplementation of flaxseed or lignan
secoisolariciresinol diglycoside. Cancer Lett (Ireland) 2000;161(1):47-55
xiv.
Li D et al. Dietary supplementation with secolariciresinol diglycoside (SDG) reduce experimental metastasis of melanoma cells in mice.
Cancer Lett 1999;142(1):91-96
xv.
Brzzinski A, Debi A. Phytoestrogens: the natural selective estrogen receptor modulators? Eur J Obstet Gynecol Reprod Biol
1999;85(1):47-51
xvi.
Tou JC, Thompson LU. Exposure to flaxseed or its lignan component during different developmental stages influences rat mammary
gland structures. Carcinogenesis 1999;20(9):1831-5
xvii.
Haggans CJ et al. Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. Nutr Cancer
1999;33(2):188-95
xviii.
Haggns CJ et al. The effect of flaxseed and wheat bran consumption on urinary estrogen metabolism in premenopausal women. Cancer
Epidemiol Biomarkers Prev 2000;9(7):719-25
xix.
Thompson LU et al. Antitumorigenic effect of mammalian lignan precursor from flaxseed. Nutr Cancer 1996;26:159-65
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Meschino Health Comprehensive Guide to Herbs
xx.
Gross PE et al. Effect of dietary flaxseed in women with cyclical mastalgia. Program and abstract of the 23rd Annual San Antonio Breast
Cancer Symposium. Dec 6-9 2000; San Antonio Texas. Abstract 153. Breast Cancer Res Treat. 2000;64:49
xxi.
Arjmandi BH et al. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein (a) concentrations in postmenopausal
women. Nutr Res 1998;18:1203-14
xxii.
Jenkins DJA et al. Health aspects of partially defatted flaxseed, including effects on serum lipis, oxidative measures, and ex vivo
androgen and progestin activity : a controlled cross over trial. Am J Clin Nutr 1999;69(3):395-402
xxiii.
Flaxseed Lowers Cholesterol. Nutr Science News 1998;3(11):575
xxiv.
Velasquez M et al. Dietary Phytoestrogens : A possible role in renal disease prtection. Am J Kidney Dis 2001;37(5):1056-68
xxv.
Clark WF et al. A novel treatment for lupus nephritis : lignan precursor derived from flaxseed. Lupus 2000;9(6):429-36
xxvi.
Denis L et al. Diet and its preventive role in prostate disease. Eur Urol 1999;35(5-6):377-87
xxvii.
Chen WJL et al. Hypocholesterolemic effects of soluble fibers. In Kritchevsky D, Yahouny GD, eds. Dietary Fiber: basic and clinical
aspects. New York: Plenum Press, 1986:275-89
xxviii.
Sanghui A et al. Inhibition of rat liver cholesterol 7-alha hydroxylase and acyl CoA : cholesterol acyl transferase activities by enterodiol
an enterolactone. In Kritchevsky D, ed. Proceedings of the Symposium on Drugs Affecting Lipid Metabolism. New York: Plenum Press,
1984:311-322
xxix.
Healthnotes Online. Healthnotes Inc. 2000. www.healthnotes.com: Flaxseed
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Meschino Health Comprehensive Guide to Herbs
Garlic (Allium sativum)
General Features
Garlic is a member of the lily family and is a perennial plant composed of individual cloves enclosed in a white skin. It
has been cultivated for more than 5,000 years in the Middle East and is an important part of Chinese Traditional
Medicine. Within the bulb are contained its medicinal ingredients. These sulfur-containing active constituents have
been shown to provide a multitude of health benefits, from preventing the common cold to reducing cancer risk.
However, the available scientific evidence indicates that Garlic’s most established health benefit is related to the
prevention of cardiovascular disease. 1,40,41
Principle Active Constituents
The active constituents in Garlic are a mixture of sulfur-containing compounds, many of which are derived from allicin.
These include:
Diallyl sulfide
Diallyl trisulfide
Methyl allyl trisulfide
Methyl allyl disulfide
S-allyl cysteine (SAC)
Ajoene 1
Clinical Application and Mechanism of Action
1. Cancer Prevention Studies
Laboratory studies involving chemically induced cancers in animals suggest that Garlic compounds may inhibit
certain cancers, such as breast, colon, skin, uterine, esophageal and lung cancer.
Mechanisms:
Modification of Phase I and Phase II liver detoxification enzymes by diallyl sulfide. Diallyl sulfide
has been shown to speed up the detoxification of various carcinogens by increasing the Phase I and
Phase II detoxification enzyme systems in the liver and intestinal cells
Increased glutathione concentrations and increased activity of the glutathione-S-transferase enzyme
by allyl methyl trisulfide and processed Garlic. Glutathione is a vital intracellular antioxidant and is
also directly involved with the detoxification of many hazardous biochemical agents.
Inhibits the initiation and promotion phases of carcinogenesis induced by 7, 12-dimethyl-benz(a)-
anthracene (DMBA).
Inhibits synthesis of N-nitroso compounds in human studies (5 grams of fresh crushed Garlic has
been shown to block N-nitrosoproline formation). Many nitrosamine products are classified as
carcinogens and thus, Garlic may act to help prevent cancer by limiting their formation and
concentration levels in various tissues. Consistent with this finding is the fact that Garlic
consumption is associated with decreased risk of esophageal, stomach, and colon cancer in human
observational studies (epidemiological evidence).
Enhances DNA repair enzyme activity.
Inhibits tumor proliferation
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Meschino Health Comprehensive Guide to Herbs
1. The quantity of S-allyl cysteine (SAC) present in various Garlic preparations has been shown to correlate with
the ability of these preparations to inhibit in-vivo formation of DNA adducts resulting from DMBA treatment.
Other nutrients enhance the protective effects of Garlic in cancer studies. These nutrients include selenium and
vitamin A.
The pungent odor of Garlic is caused mainly by allicin. Allinase enzyme within Garlic converts alliin into allicin upon
damage or crushing of Garlic cells. The crushing process brings allinase enzyme into contact with alliin allowing this
reaction to occur. Thus, S-allyl-L-cysteine sulphoxide (alliin) decomposes into the reactive intermediate allyl sulphenic
acid, two molecules of which spontaneously condense to form diallyl thiosulphin