Isoflavones

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  • The accepted definition of osteoporosis.
  • Speaker’s Notes There are an estimated 4-6 million postmenopausal women with low bone mass or osteoporosis in the Indian. female population. Based on guesstimates, 54% of the women aged 50-64 are estimated to have low bone mass or osteoporosis (defined by T-score –1.0 SDs or lower). These statistics worsen as women age. Up to 86% of women 65 and over have low bone mass or osteoporosis.
  • Speaker’s Notes There are an estimated 4-6 million postmenopausal women with low bone mass or osteoporosis in the Indian. female population. Based on guesstimates, 54% of the women aged 50-64 are estimated to have low bone mass or osteoporosis (defined by T-score –1.0 SDs or lower). These statistics worsen as women age. Up to 86% of women 65 and over have low bone mass or osteoporosis.
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  • Speaker’s Notes The National Academy of Sciences Guidelines of 1997 emphasized the need for adequate calcium through diet or supplementation in excess of 1200 mg daily for postmenopausal women. Extra doses of vitamin D are particularly important for the institutionalized elderly. Weight-bearing exercise has been shown to maintain or increase bone mineral density in pre- and postmenopausal women. There are a variety of fall-prevention techniques that are beyond the scope of this presentation.
  • Speaker’s Notes The National Academy of Sciences Guidelines of 1997 emphasized the need for adequate calcium through diet or supplementation in excess of 1200 mg daily for postmenopausal women. Extra doses of vitamin D are particularly important for the institutionalized elderly. Weight-bearing exercise has been shown to maintain or increase bone mineral density in pre- and postmenopausal women. There are a variety of fall-prevention techniques that are beyond the scope of this presentation.
  • Speaker’s Notes The National Academy of Sciences Guidelines of 1997 emphasized the need for adequate calcium through diet or supplementation in excess of 1200 mg daily for postmenopausal women. Extra doses of vitamin D are particularly important for the institutionalized elderly. Weight-bearing exercise has been shown to maintain or increase bone mineral density in pre- and postmenopausal women. There are a variety of fall-prevention techniques that are beyond the scope of this presentation.
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  • Speaker’s Notes There is a hierarchy of research evidence to be evaluated in judging outcomes of any kind. It’s important to make a value judgment based on the individual patient. For example, research dictates that a 62-year-old postmenopausal woman with a BMD T-score of –3.5 should be treated, but if she has terminal breast cancer, clinical judgment advises us to the contrary.
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  • The idea that certain foods can be a boon to health is nothing new. Even generations ago, people knew the benefits of eating their vegetables or munching an apple a day to keep the doctor at bay. But in recent years, the food industry has promoted functional foods. Although functional foods remain undefined under current US food regulation, functional foods are generally understood to be foods that provide a specific health benefit above and beyond their inherent nutritional value. Consumers seem to prefer the term functional foods over terms such as nutraceutical or designer foods. Some such foods come naturally packed with healthful compounds, with whole foods such as fruits and vegetables representing the simplest example of a functional food; in other cases manufacturers add certain ingredients to make foods functional, such as cereal with added folic acid. Our supermarkets are full of functional foods, but the increasing number of products claiming specific health benefits is making the grocery store look more and more like a pharmacy. Unlike a drug, though, functional foods are available without a prescription, and often without much guidance on how they should be used. It’s unlikely that anyone drinking calcium-fortified juice will get too much calcium, and we know a lot about how that key ingredient works. But with some of the more questionable products, juices fortified with the herb echinacea, for example, no one yet knows what level of intake is safe or how the substance might interact with other medications. Currently, the Food & Drug Administration and the Federal Trade Commission is responsible for regulating functional foods.
  • The idea that certain foods can be a boon to health is nothing new. Even generations ago, people knew the benefits of eating their vegetables or munching an apple a day to keep the doctor at bay. But in recent years, the food industry has promoted functional foods. Although functional foods remain undefined under current US food regulation, functional foods are generally understood to be foods that provide a specific health benefit above and beyond their inherent nutritional value. Consumers seem to prefer the term functional foods over terms such as nutraceutical or designer foods. Some such foods come naturally packed with healthful compounds, with whole foods such as fruits and vegetables representing the simplest example of a functional food; in other cases manufacturers add certain ingredients to make foods functional, such as cereal with added folic acid. Our supermarkets are full of functional foods, but the increasing number of products claiming specific health benefits is making the grocery store look more and more like a pharmacy. Unlike a drug, though, functional foods are available without a prescription, and often without much guidance on how they should be used. It’s unlikely that anyone drinking calcium-fortified juice will get too much calcium, and we know a lot about how that key ingredient works. But with some of the more questionable products, juices fortified with the herb echinacea, for example, no one yet knows what level of intake is safe or how the substance might interact with other medications. Currently, the Food & Drug Administration and the Federal Trade Commission is responsible for regulating functional foods.
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  • Speaker’s Notes Benefits of raloxifene include improved bone mass, no breast tenderness, bleeding, or spotting and the potential for reduced risk of breast cancer. Raloxifene does not relieve vasomotor symptoms: Hot flashes are often the reason patients come in for treatment. Raloxifene may increase hot flashes. Decreases low-density lipoproteins but does not increase high-density lipoproteins.
  • Soybeans and other legumes are best known as an excellent source of protein. They are also rich in calcium, iron, zinc, vitamin E, several of the B-vitamins and fiber. They are low in saturated fat, but rich in omega-3 fatty acids. 25 grams of soy protein per day may reduce the risk of heart disease. The phytoestrogens or isoflavones may reduce menopause symptoms such as hot flashes. Saponins may lower LDL cholesterol and contain anti-cancer enzymes. Tofu takes up the flavor of what it’s cooked with, but many individuals are opposed to its mouth feel. Try grinding up a third of a package of tofu to add to any combination dish. You’ll add high quality protein, more calcium if it’s fermented using calcium, reduce the fat content of the dish AND give you the added of disease fighting phytonutrients.
  • Soybeans and other legumes are best known as an excellent source of protein. They are also rich in calcium, iron, zinc, vitamin E, several of the B-vitamins and fiber. They are low in saturated fat, but rich in omega-3 fatty acids. 25 grams of soy protein per day may reduce the risk of heart disease. The phytoestrogens or isoflavones may reduce menopause symptoms such as hot flashes. Saponins may lower LDL cholesterol and contain anti-cancer enzymes. Tofu takes up the flavor of what it’s cooked with, but many individuals are opposed to its mouth feel. Try grinding up a third of a package of tofu to add to any combination dish. You’ll add high quality protein, more calcium if it’s fermented using calcium, reduce the fat content of the dish AND give you the added of disease fighting phytonutrients.
  • Soybeans and other legumes are best known as an excellent source of protein. They are also rich in calcium, iron, zinc, vitamin E, several of the B-vitamins and fiber. They are low in saturated fat, but rich in omega-3 fatty acids. 25 grams of soy protein per day may reduce the risk of heart disease. The phytoestrogens or isoflavones may reduce menopause symptoms such as hot flashes. Saponins may lower LDL cholesterol and contain anti-cancer enzymes. Tofu takes up the flavor of what it’s cooked with, but many individuals are opposed to its mouth feel. Try grinding up a third of a package of tofu to add to any combination dish. You’ll add high quality protein, more calcium if it’s fermented using calcium, reduce the fat content of the dish AND give you the added of disease fighting phytonutrients.
  • Soybeans and other legumes are best known as an excellent source of protein. They are also rich in calcium, iron, zinc, vitamin E, several of the B-vitamins and fiber. They are low in saturated fat, but rich in omega-3 fatty acids. 25 grams of soy protein per day may reduce the risk of heart disease. The phytoestrogens or isoflavones may reduce menopause symptoms such as hot flashes. Saponins may lower LDL cholesterol and contain anti-cancer enzymes. Tofu takes up the flavor of what it’s cooked with, but many individuals are opposed to its mouth feel. Try grinding up a third of a package of tofu to add to any combination dish. You’ll add high quality protein, more calcium if it’s fermented using calcium, reduce the fat content of the dish AND give you the added of disease fighting phytonutrients.
  • Isoflavones

    1. 1. Menopause Management Options in the New millenium The Natural, Safe and Proactive Approach
    2. 2. Mrs. Deshpande Age: 45 Years Mrs. Mistry Age: 52 years
    3. 3. Mrs. Mukherjee Age: 61 years Mrs. Khan Age: 73 years
    4. 4. One Link Is Common Between All of Them ……
    5. 5. The Common Link Between All of Them Is …… <ul><li>Menopause </li></ul>And its complications
    6. 6. What is Menopause? <ul><li>It is the transition between a woman’s childbearing years and non-childbearing years </li></ul><ul><li>It is the last stage of a gradual biological process that actually begins during the mid-thirties. </li></ul><ul><li>It occurs between 45 and 55 years when menses stops </li></ul>
    7. 7. Changes Taking Place With Menopause Menopause Physical <ul><li>Irregular periods </li></ul><ul><li>Hot flushes </li></ul><ul><li>Night sweats </li></ul><ul><li>Palpitations </li></ul><ul><li>Sexual changes </li></ul><ul><li>Skin & hair </li></ul><ul><li>Joint pains </li></ul><ul><li>Urinary symptoms </li></ul><ul><li>Weight gain </li></ul><ul><li>Headache </li></ul>Psychological <ul><li>Depression </li></ul><ul><li>Irritability </li></ul><ul><li>Tiredness / poor sleep </li></ul><ul><li>Anxiety </li></ul><ul><li>Loss of libido </li></ul><ul><li>Weepiness </li></ul><ul><li>Forgetfulness & </li></ul><ul><li>Loss of concentration </li></ul>
    8. 8. Menopause and its implications Long term consequences Menopausal symptoms such as hot flushes Short term consequences Menopause Drastic fall in serum oestrogen levels from 50 – 600 units (picograms per ml) to 5 – 10 units Osteoporosis  Risk of CAD Vaginal Atrophy  Risk of dementia Oestrogen deficiency
    9. 9. Long Term Menopausal Effects <ul><li>Atrophy of vagina/ urethra </li></ul><ul><li>Osteoporosis </li></ul><ul><li>Cardiovascular disease </li></ul><ul><li>The average life expectancy for women has increased </li></ul><ul><li>Any woman 60-years-old or more is expected to live at least one-third of her life after menopause. </li></ul>
    10. 10. Total Cholesterol Levels After Menopause Maturitas 12(1990)321-331. Months Percent -24 6 -18 -12 -6 0 Menopause 90 100 110
    11. 11. LDL Cholesterol Levels After Menopause Percent -24 6 -18 -12 -6 0 Menopause Maturitas 12(1990)321-331. Months 90 100 110
    12. 12. Triglyceride Levels After Menopause Percent - 24 6 -18 -12 -6 0 Menopause Maturitas 12(1990)321-331 . Months 90 100 110
    13. 13. HDL Cholesterol Levels After Menopause Percent -24 6 -18 -12 -6 0 Menopause Maturitas 12(1990)321-331. Months 90 100 110
    14. 14. Most Important Problem of Menopause Osteoporosis Late complaints Silent disease Old age attribution
    15. 15. Postmenopausal Osteoporosis: What Happens?
    16. 16. Postmenopausal Osteoporosis: What Actually Occurs? <ul><li>Thus, due to this increased skeletal porosity, there is an increase in fragility with sites like spine, wrist and hip being more susceptible to fracture. </li></ul><ul><li>Presents usually with Kyphosis / chronic back pain; </li></ul>Reduced bone mass and Micro-architectural deterioration modulated by a disturbed bone remodelling sequence .  Increased bone resorption Increased bone porosity in the trabecular bone (larger marrow spaces) with decreased mineralisation Thinning of cortical bone and decreased quantity of matrix
    17. 17. Age and Bone Mineral Density [BMD] <ul><li>Peak BMD achieved by 25 to 30 years of age; </li></ul><ul><li>After 30, bone loss occurs @ 0.5% to 1% yearly; </li></ul><ul><li>Accelerated rate of bone loss in women, especially during the first 5 years after menopause, due to  oestrogen </li></ul><ul><li>Male Bone mass = approximately 30 % higher than in females </li></ul>
    18. 18. Menopause and Bone Mass Density [BMD] Elder women have 1/2 BMD of that in their 20s Age (yrs) 50 100 ----- Trabecular ----- Compact 30 40 80 Bone Mass density % MENOPAUSE
    19. 19. Osteoporosis Estimations DEXA (Dual Energy X-ray Absorptiometry) Quantitative computerized tomography Quantitative Ultrasonography T-score indicates the number of standard deviation below or above the average peak bone mass in young adults CONCLUSION - Expensive and not very common
    20. 20. Management of Osteoporosis <ul><li>Traditional </li></ul><ul><li>Calcium (1200 – 1500 mg/day in divided doses) </li></ul><ul><li>Vitamin D 400 IU / day * [*600 IU/day for patients over age 70] </li></ul><ul><li>Phosphorus, magnesium </li></ul><ul><li>Weight-bearing exercise </li></ul>Yates AA, et al. J Am Diet Assoc . 1998;9:699-706., NIH Consensus Conference. JAMA 1994; 272: 1942-8. <ul><li>Newer options </li></ul><ul><li>Hormone replacement therapy (HRT) </li></ul><ul><li>SERMs </li></ul><ul><ul><li>Isoflavones </li></ul></ul><ul><ul><li>Raloxifene </li></ul></ul><ul><li>Bisphosphonates </li></ul><ul><ul><li>Alendronate </li></ul></ul><ul><ul><li>Risedronate </li></ul></ul><ul><li>Calcitonin </li></ul>
    21. 21. <ul><li>Traditional </li></ul><ul><li>Calcium (1200 – 1500 mg/day in divided doses) </li></ul><ul><li>Vitamin D 400 IU / day * [ *600 IU/day for patients over age 70] </li></ul><ul><li>Phosphorus, magnesium </li></ul><ul><li>Fall-prevention techniques & exercise </li></ul>Management of Osteoporosis <ul><li>Newer options </li></ul><ul><li>Hormone replacement therapy (HRT) </li></ul><ul><li>SERMs </li></ul><ul><ul><li>Isoflavones </li></ul></ul><ul><ul><li>Raloxifene </li></ul></ul><ul><li>Bisphosphonates </li></ul><ul><ul><li>Alendronate </li></ul></ul><ul><ul><li>Risedronate </li></ul></ul><ul><li>Calcitonin </li></ul>Yates AA, et al. J Am Diet Assoc . 1998;9:699-706., NIH Consensus Conference. JAMA 1994; 272: 1942-8.
    22. 22. Options for Menopause Management SERMs HRT TIBOLONE ISOFLAVONES MENOPAUSE
    23. 23. Hormone Replacement Therapy ERT or HRT = Therapy with either Estrogen alone or combined with a progestin. To strengthen bones To reduce the Risk of heart disease To help control other Menopausal Symptoms such as hot flushes, sweats, disturbed sleep
    24. 24. Estrogen and Coronary Artery Disease Reduces LDL levels by their action on the liver Increases triglyceride levels Estrogen influences CAD
    25. 25. Estrogen Effect on Bone remodelling Estrogen effect:  bone resorption &  bone formation by Direct inhibition of osteoclasts Direct stimulation of osteoblasts Indirect effect by altering local humoral mediators
    26. 26. Consequences of Hormone Replacement Therapy C onsequence = women may also subject themselves to the harmful effects of estrogen  risk of cancer of uterus / breast  risk of DVT and Gallstone formation  Triglyceride levels. Unusual DUB, headaches, nausea, fluid retention, swollen breasts, weight gain Short term side effects Long term side effects
    27. 27. The problem and a possible solution! <ul><li>Because of the possibility of dangerous side-effects, medical opinion is still divided about the use of HRT in post-menopausal women </li></ul>The option available, is to use ….. … . drugs with the desired oestrogen-like effects but without the dangerous side-effects
    28. 28. The possible solution! <ul><li>Drugs called SERMs like Raloxifene and Tamoxifene are available to function as oestrogen without fear of dangerous side effects </li></ul>The problem is their side effect profile like DVT and hot flushes. The option narrows down to drugs that function like SERMs without their side effect profile
    29. 29. Such Drugs Are Available Today PHYTOESTROGENS The Next Frontier In Nutrition
    30. 30. <ul><li>A group of plant chemicals that elicit an estrogen-like response b y virtue of their chemical structure. </li></ul><ul><li>They are capable of binding to estrogen receptors, where, they seem to exert either estrogenic [agonistic action] or antiestrogenic effects [antagonistic action] . </li></ul>What Are phytoestrogens? J Clin Endocrinol Metab 2002 Dec;87(12):5539-44
    31. 31. Hence, phytoestrogens may be described as natural SERMs or natural selective estrogen receptor modulators, since they have both actions – agonistic and antagonistic
    32. 32. Why are phytoestrogens getting to be very popular? <ul><li>Multiple Target System Effects …With all the Benefits of oestrogen replacement but no Risks / Side effects! </li></ul>Phytoestrogens Uterus Breast Lipids Brain Bone
    33. 33. Sources of Phytoestrogens Most food Phytoestrogens isoflavonoids lignans coumestans More than 300 foods have been shown to contain phytoestrogens (Kurzer and Xu, 1997) . found in beans of legume family with soyabeans as major dietary source found in high fiber foods such as cereal brans and flaxseeds various beans such as split peas, long beans, alfalfa and clover sprouts
    34. 34. Types of phytoestrogens Phytoestrogens Isoflavonoids Lignans Others Isoflavones Coumestans Genistein (~60%) Daidzein (~25%) Glycetein (~15%)
    35. 35. What Are Isoflavones? <ul><li>By virtue of their chemical structure, isoflavones are effective phytoestrogens. </li></ul><ul><li>Isoflavone bioavailablity is complex and is influenced widely by source with subsequent variations in metabolic impact. </li></ul>Amongst all available phytoestrogens, the soya isoflavones are found to be the most effective
    36. 36. Isoflavones in Soya Isoflavone R1 R2 Daidzein H H Genistein H OH Glycetein OCH 3 H The principal isoflavones in soya are usually found in the form of glycosides, which after ingestion are hydrolyzed in the large intestine by the action of bacteria to release isoflavones. O O H O R 2 O H R 1
    37. 37. Isoflavones in Other Foods Formononetin Biochanin A Coumestrol Isoflavones are also found in chickpeas, clover & alfalfa sprouts and are of other types -
    38. 38. Comparative estrogen Activity of Phytoestrogens <ul><li>The current interest in isoflavones has been generated by their potential hormonal effects and is a result of epidemiological studies, primarily from Japan where soya consumption is high </li></ul>
    39. 39. ISOFLAVONES <ul><li>TIME MAGAZINE, July 17, 2000 Vol. 156 No. 3 </li></ul>The Sales of supplements that contain soya isoflavones, a form of phytoestrogen, tripled from 1998 to 1999.
    40. 40. Genistein – the isoflavone That Has Been Extensively Studied! <ul><li>Genistein is the most studied of the isoflavones. </li></ul><ul><li>At some places, it appears to mimic estrogen by stimulating estrogen receptors even though its potency is weak - estimated to be 1/400th to 1/1000th of estradiol. </li></ul><ul><li>At other places, by binding to receptors, genistein blocks the ability of the far more potent estradiol to activate the receptor. </li></ul>
    41. 41. Isoflavones – Selective Estrogen Receptor Modulator Activities Oestrogen Agonist Oestrogen Antagonist Beta receptors - Bone, Liver, Brain Alpha receptors - Breast, Uterus
    42. 42. MENOPAUSE Short term side Effects like flushing Osteoporosis Decrease in Cardioprotection Alzheimer’s disease  estrogen level Isoflavones Isoflavones
    43. 43. Isoflavones: pharmacokinetics <ul><li>Ingested isoflavones are usually present as aglycones or glycosides [with glucose] </li></ul><ul><li>9.3 and 9.0 h, respectively - </li></ul><ul><li>Bioavailability higher </li></ul><ul><li>Extensive tissue distribution </li></ul><ul><li>Higher Cmax </li></ul>ß-glycosides 5.2 and 6.6 h Aglycones - genistein & daidzein ( t max )
    44. 44. Isoflavones: metabolism <ul><li>Ingested isoflavones are absorbed and biotransformed by intestinal microflora; </li></ul><ul><li>They, then, undergo enterohepatic recycling to reach circulating concentrations that exceed by several orders of magnitude the amounts of endogenous estrogens. </li></ul><ul><li>These phytoestrogens and their metabolites exert many potent hormonal and nonhormonal activities that may explain the biological effects of phytoestrogens. </li></ul>
    45. 45. Isoflavones: safety A double-blind placebo-controlled study of 34 premenopausal women found that 1 year's use of isoflavones upto a dose of 100 mg per day had no effect on any of the hormones involved with the menstrual cycle. The effects of an isoflavone intervention on the reproductive cycle of premenopausal women. Presented at: European Conference on Nutrition & Cancer; June 21–24, 2001; Lyon, France.
    46. 46. Isoflavones: Effects on hormones Results suggest that a soya diet with low levels of isoflavones and low energy intake from protein can reduce circulating ovarian steroids without altering gonadotropins. J Clin Endocrinol Metab 2001 Jul;86(7):3045-52
    47. 47. Isoflavones: Hot flushes No soya-related changes observed on Vaginal cytology Endometrial thickness Uterine artery pulsatility index <ul><li>Severity of hot flushes assessed in a 6 week study by means of the Greene climacteric scale </li></ul><ul><li>Reduction in the mean number of hot flushes per week was observed in participants who were receiving the standardized soya extract. </li></ul><ul><li>Menopause 2000 Mar-Apr 7: 2, 105-11 </li></ul>metabolic & hormonal parameters
    48. 48. Isoflavones: Hot Flushes A double-blind placebo-controlled study was done in 104 women for vasomotor symptoms of menopause Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soya supplementation on hot flushes. Obstet Gynecol. 1998;91:6–11 ACOG's position is that short-term (less than 2 years) intake of soy and isoflavones may be helpful in treating vasomotor symptoms
    49. 49. Isoflavones: Cardiovascular Risk Factors <ul><li>There is convincing evidence that isoflavones have beneficial effects on cardiovascular disease risk factors. </li></ul><ul><li>Curr Opin Lipidol 2001 Aug;12(4):433-7. </li></ul>Isoflavones Reduce cholesterol Prevent CAD <ul><ul><li>Results of various studies support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older women </li></ul></ul><ul><ul><li>Arterioscler Thromb Vasc Biol 2002 Aug 1;22(8):1316-22 </li></ul></ul>
    50. 50. Isoflavones: + Soya Protein on Total Cholesterol * P<0.05 vs day 0 ISP (+) : soy protein containing isoflavones (33mg) ISP (–) : soy protein deficient in isoflavones (3.2mg) * * lowers total cholesterol by about 9%, Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soya protein intake on serum lipids. N Engl J Med . 1995;333:276–282.
    51. 51. Isoflavones: + Soya Protein on LDL-cholesterol * P<0.05 vs day 0 ISP (+) : soy protein containing isoflavones (33mg) ISP (–) : soy protein deficient in isoflavones (3.2mg) * * <ul><li>12.9 decrease </li></ul><ul><li>possibly due to </li></ul><ul><li>Enhancement of bile acid secretion; and </li></ul><ul><li>Reduced cholesterol metabolism. </li></ul>
    52. 52. Isoflavones: + Soya Protein on Lipids <ul><li>In a study, as compared with values measured during the control diet: </li></ul><ul><ul><li>The plasma LDL cholesterol concentration was 6.5% lower ( P < 0.02) during the high-isoflavone diet; </li></ul></ul><ul><ul><li>The ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the high- and low -isoflavone diets, respectively ( P < 0.02). </li></ul></ul>American Journal of Clinical Nutrition, Vol. 73, No. 2, 225-231, February 2001
    53. 53. Isoflavones: + Soya Protein on LDL Oxidation <ul><li>The isoflavones, genistein and daidzein, and equol (a daidzein metabolite produced by intestinal microflora) are antioxidants in vitro; equol is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation. </li></ul><ul><li>In a study, conducted to verify this activity, it was conclusively evident that: </li></ul><ul><ul><li>Consumption of isoflavones reduced lipid peroxidation in vivo and increased the resistance of LDL to oxidation. </li></ul></ul><ul><ul><li>This antioxidant action may be significant with regard to risk of atherosclerosis, cardiovascular disease in general, and cancer. </li></ul></ul>American Journal of Clinical Nutrition, Vol. 72, No. 2, 395-400, August 2000
    54. 54. Isoflavones: CAD Baillieres Clin Endocrinol Metab 1998 Dec 12:4 589-604 J. Nutr. 125: 624S-630S, 1995 preventing the oxidation of lipoprotein particles preventing cell adhesion altering growth factor activity inhibiting progression of athero-sclerosis Isoflavones prevent CAD by the following proposed mechanisms
    55. 55. Isoflavones: CAD <ul><li>According to the Nutrition Committee of the American Heart Association (AHA) there is increasing evidence that consumption of soya protein in place of animal protein can lower blood cholesterol levels and may provide other cardiovascular benefits. </li></ul>Circulation, November 14, 2000 ACOG's position is that long-term intake of soy and isoflavones may improve blood cholesterol levels
    56. 56. Isoflavones: Blood pressure J Clin Endocrinol Metab 2001 Jul;86(7):3053-60 105 postmenopausal women), received either soya protein isolate (40 g soya protein, 118 mg isoflavones) or casein for 3 months. soya group, as compared with casein, showed a significant fall in BP.
    57. 57. Isoflavones: Cancer Isoflavone activities on breast and Uterus Induce apoptosis Inhibit differentiation in cancer cells Inhibit cell proliferation Acta Pol Pharm 2000 Mar-Apr 57:2 135-55
    58. 58. Isoflavones: Cancer <ul><li>Isoflavone intake may exert cancer-preventive effects by decreasing estrogen synthesis and altering metabolism away from genotoxic metabolites toward inactive metabolites. Cancer Epidemiol Biomarkers Prev 1998 Dec 7:12, 1101-8 </li></ul><ul><li>Soya isoflavones increase the metabolism of endogenous estrogens to the protective 2-hydroxylated estrogens in women, thus lowering 17beta-estradiol levels and the long-term risk for breast cancer. Cancer Res 2000 Mar 1 60:5, 1299-305 </li></ul>
    59. 59. Isoflavones: in Obesity & Diabetes <ul><li>Evidence is emerging that phytoestrogens play a beneficial role in obesity and diabetes. </li></ul><ul><li>Nutritional intervention studies suggest that isoflavones favorably alter insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile. </li></ul>Diabetes Care 2002 Oct;25(10):1709-14, Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes by Jayagopal V et al, Department of Medicine, University of Hull, U.K Am J Clin Nutr 2002 Dec;76(6):1191-201
    60. 60. Isoflavones: in Migraine <ul><ul><li>30% of women afflicted with migraine have menstrually associated attacks, often refractory to treatment. </li></ul></ul><ul><ul><li>Evidence suggests estrogen and progestin fluctuations may influence menstrual migraine. </li></ul></ul><ul><ul><li>Isoflavones have demonstrated estrogenic effects in some tissues, but without stimulation of the endometrium, suggesting decreased risk in long-term use. </li></ul></ul><ul><ul><li>Biomed Pharmacother 2002 Aug;56(6):283-8, Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine, Burke BE, et al, Research Service, Department of Veterans Affairs Medical Center, Boise, ID 83702, USA. </li></ul></ul>
    61. 61. Isoflavones: in Migraine <ul><ul><li>In a study, 49 patients were randomized to compare placebo treatment with soya isoflavones for 24 weeks. </li></ul></ul><ul><ul><li>Average frequency of menstrually associated migraine attacks during weeks 9-24 was reduced from 10.3 +/- 2.4 (mean +/- s.e.m.) in placebo treated patients to 4.7 +/- 1.8 in patients treated with the isoflavones. </li></ul></ul><ul><ul><li>Biomed Pharmacother 2002 Aug;56(6):283-8, Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine, Burke BE, et al, Research Service, Department of Veterans Affairs Medical Center, Boise, ID 83702, USA. </li></ul></ul>
    62. 62. Isoflavones: Breast cancer <ul><li>Research has shown both protective and stimulatory effects of soya and soya isoflavones on breast cancer, based on – </li></ul><ul><ul><li>Epidemiologic, </li></ul></ul><ul><ul><li>In vitro, and </li></ul></ul><ul><ul><li>In vivo studies. </li></ul></ul><ul><li>2 case-control studies show support for soya consumption in reducing breast cancer risk in premenopausal women. </li></ul>Menopause 2000 Jul-Aug;7(4):215-29, The role of isoflavone consensus opinion of The North American Menopause Society.
    63. 63. Isoflavones: BMD J Am Coll Nutr 2002 Dec;21(6):560-3 <ul><ul><li>Urinary isoflavone excretion in the isoflavone-administered group was significantly increased at weeks 3 and 10, but urinary excretion of bone resorption markers was reduced significantly in the isoflavone-administered group, while the placebo group did not show any significant reduction. </li></ul></ul>Conclusions <ul><ul><li>The collection of 24-hour urine and the measurement of bone stiffness were performed at 0 and 10 weeks. Urinary excretion of isoflavones and bone resorption markers were analyzed.. </li></ul></ul>Endpoint 40 healthy postmenopausal females were randomized in double-blind manner to receive 40 mg. / day 6 months of oral quinapril 40 mg or placebo once daily for 10 weeks. Study To verify whether isoflavones really help in bone resoprtion. Objective
    64. 64. Isoflavones: BMD <ul><li>A preliminary study involving perimenopausal women for 6 months showed that the higher dose of isoflavones was associated with a significant increase in bone mineral density (BMD) at the lumbar spine site. </li></ul>American Journal of Clinical Nutrition, Vol. 72, No. 3, 844-852, September 2000
    65. 65. Isoflavones: Reasons for Variations <ul><li>The clinical effectiveness of soya protein in cardiovascular, bone and menopausal health may be a function of the ability to biotransform soya isoflavones like daidzein to the more potent estrogenic isoflavone, equol. </li></ul><ul><li>The failure to distinguish those subjects who are &quot;equol-producers&quot; from &quot;nonequol producers&quot; in previous clinical studies could plausibly explain the variance in reported data on the health benefits of soya. </li></ul>J Nutr 2002 Dec;132(12):3577-84
    66. 66. Soya Protein and Isoflavone Content Harv Mens Health Watch 2002 Oct;7(3):1-3 Food Portion Approximate Soya Protein Content (mg) Approximate Isofavone Content (mg) Boiled soyabeans 1 cup 20 47 Soya flour 1/2 cup 25 50 Soya milk 8 oz 4–10 0–50 Soya nuts, roasted 2 table spoons 8 40 Soya sauce 1 table spoon less than 1 less than 1 Texturized soya protein 4 oz 11–16 30–40 Tofu 4 oz 5–13 30–40
    67. 67. Isoflavones and bone ADMINISTERED ISOFLAVONES Oestrogen receptor on Osteoblast occupied production of interleukins No activation of osteoclasts Resorption is blocked Correction of osteoporosis More bone production than loss and proper mineral deposition occurs
    68. 68. Isoflavones: Comparison with ERT / HRT Yes Nil Breast pain, tenderness Increased Reduced Risk of endometrial cancer Relieved Relieved Vasomotor symptoms Yes [50 – 80%] Nil Vaginal bleeding Possibly increased Reduced Risk of breast cancer Yes Nil Bloating, weight gain No Yes Action on cholesterol Yes Yes Prevention of osteoporosis ERT / HRT Isoflavones
    69. 69. Isoflavones: Compared with Raloxifene <ul><li>Raloxifene as a substitute for HRT has limitations due to the absence of effects on the vasomotor symptoms of menopause </li></ul><ul><li>Raloxifene cannot be given to pre or peri-menopausal women because of the side effect profile of DVT, flushing, etc.. </li></ul>
    70. 70. Isoflavones: Compared With Tibolone <ul><li>Tibolone is an expensive proposition in comparison to isoflavones in soya and that, too, can be given only in the postmenopausal phase. </li></ul><ul><li>Isoflavones help to reduce menopausal symptoms as well as enhance quality of life with their multi-target approach. </li></ul>
    71. 71. Isoflavones: Benefits <ul><li>Reduces menopausal symptoms. </li></ul><ul><li>Prevents and treats postmenopausal osteoporosis; </li></ul><ul><li>Reduces risk of breast cancer and uterine [endometrial] cancer. </li></ul><ul><li>Provides beneficial effect on lipids and reduces cardiovascular risk factors to protect against CAD. </li></ul>Lowers cholesterol Builds bone mass Protects against cancer Prevents Alzheimer’s disease
    72. 72. Isoflavones: Latest Health Claims <ul><li>Soya protein enriched with isoflavones has a LDL-cholesterol lowering effect in persons in the high-risk range. - Am J Clin Nutr, 2001;73:667-80). </li></ul><ul><li>Data presented on June 22, 2001, at ENDO 2001, the 83rd annual meeting of The Endocrine Society, demonstrated that phytoestrogens may benefit the health and bones of postmenopausal women. </li></ul>
    73. 73. Isoflavones: Latest Health Claims <ul><li>Soya may help protect against the onset of Alzheimer's disease, especially in postmenopausal women, according to research presented April 3, 2001, at the 221st national meeting of the American Chemical Society. </li></ul><ul><li>An increase in dietary soya consumption may help protect postmenopausal women from developing cancer, according to researchers . </li></ul>Cancer Epidemiology Biomarker & Prevention2000;9(8): 781-6
    74. 74. Isoflavones - Candidates Premenopausal women as a proactive approach to prevent menopausal complications; Perimenopausal women showing visceral, vasomotor & psychological menopause manifestations Postmenopausal women. Postmenopausal women Perimenopausal women Premenopausal women
    75. 75. Isoflavones: Candidates <ul><li>Women who have undergone hysterectomy or surgical oophorectomy or who cannot tolerate HRT or where HRT is contra-indicated - </li></ul><ul><ul><li>Vaginal bleeding </li></ul></ul><ul><ul><li>Breast pain and tenderness </li></ul></ul><ul><ul><li>Bloating and weight gain </li></ul></ul><ul><ul><li>Suspicion of breast / endometrial cancer </li></ul></ul><ul><ul><li>Uncontrolled hypertension / Migraine </li></ul></ul><ul><ul><li>Fibroids and Endometriosis </li></ul></ul>
    76. 76. Isoflavones: Dosage <ul><li>Soya sauce and soya bean oil contain almost no isoflavones. </li></ul><ul><li>There is some evidence that amounts of 40-80 mg/day of isoflavones are needed for effects on arterial compliance, and for antioxidant effect on lipids, as little as 10 mg/day may be effective. </li></ul><ul><li>Most studies on hot flushes have used isoflavone amounts of 40-80 mg/day, and these amounts may benefit vasomotor symptoms. </li></ul>
    77. 77. Isoflavones: Current Status <ul><li>Approved </li></ul><ul><li>Endorsed </li></ul><ul><li>accepted </li></ul>
    78. 78. Phytoestrogens and ACC <ul><li>A new study published in the May 2000 issue of the Journal of the American College of Cardiology finds that phytoestrogens (natural chemicals found in many plants) provide women with many of the same benefits as hormone replacement therapy (HRT) without increasing the risk of breast or uterine cancers. </li></ul>
    79. 79. What Is The Right Approach? <ul><li>A blend of traditional and modern methods is the ideal approach to the management of postmenopausal osteoporosis! </li></ul><ul><li>THIS IS POSSIBLE, IF CARE IS TAKEN … </li></ul><ul><li>To provide calcium and other essentials for bone building and postmenopausal health </li></ul><ul><li>To provide HRT with desired estrogen-like effects but without the dangerous side-effects </li></ul>
    80. 80. What Is The Ideal Composition? <ul><li>Isoflavones </li></ul><ul><li>Calcium </li></ul><ul><li>Vitamin D </li></ul><ul><li>Magnesium </li></ul><ul><li>Phosphorus </li></ul>THIS IS POSSIBLE AND TAKEN CARE OF WITH …
    81. 81. Thank You

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