Herbal / Medical Blogs
The calcium and cardiovascular disease risk connection - Is it true??
A study of 1,471 post menopausal women in New Zealand with a mean age of 74 were randomized to receive 1 gm of calcium citrate or placebo daily for 5 years. The occurrence of sudden death, heart attacks, stroke and transient ischemic attacks were reported by either the women or their family members. A twofold increase in MIs was seen among women in the calcium group compared with the placebo group. When accumulating the total of heart attacks, strokes or sudden deaths, the incidence was 1.47 times higher in the calcium group than in the placebo group as well. However, when the investigators incorporated national health database results for unreported cardiovascular events, the increase in the incidence in heart attacks was not statistically significant.
Bolland M, Barber P, Doughty R, et al. Vascular events in healthy older women receiving calcium supplementation: Randomised controlled trial. BMJ 2008;Feb 2; 336:262-266
[Click here to download fulltext PDF from BMJ]
Commentary: It is interesting and important to point out that the Women’s Health Initiative ( Circulation 2007;115:846) showed no statistically significant increase in cardiovascular events in postmenopausal women receiving calcium supplements and another study showed a non-significant but yet a trend in increased risk for ischemic heart disease. (Arch Intern Med 2006;166:869). These three studies all point to the fact that there is no definite statement or conclusion that can be made regarding calcium and cardiovascular events. That said, I am concerned that the importance of calcium supplementation in postmenopausal women, especially younger postmenopausal women, is very overplayed. And, most individuals do not estimate their dietary calcium sources, and then use a pill to supplement in addition to dietary sources to meet a total of 1,200mg-1,500 mg per day. Rather, they often take 1,000 mg to 1,500 mg per day, in addition to their dietary sources. A result of this misinterpretation of calcium guidelines might be excessive calcium and depletion of other nutrients such as copper, silicon and magnesium, all of which have cardioprotective benefits. In addition, these total daily calcium guidelines turn out to be most important to young girls and postmenopausal women 65 and older. These are the times in life when lack of bone architecture/density growth (young girls) and bone loss (elderly women) is most crucial in the prevention of osteoporosis and risk for fractures. For women in their 30’s, 40’s, 50’s and early 60’s, our bones seem to do just fine with average dietary intake.
Fatigue in Women
Fatigue is one of those experiences we all have had, at one time or another - either from too much work, too little sleep, stress, recovering from a trip, during a cold/flu, or what have you. This is not the kind of fatigue that really plagues some of us. Chronic fatigue syndrome or being persistently fatigued from a chronic and/or serious illness (ex/ hypothyroid, diabetes, hypoglycemia, depression, cancer) are the most debilitating kinds of fatigue. In between these short term bouts from relatively minor problems, and the more daily fatigue from something more serious, lies the episodic or recurring fatigue that can happen in relationship to different cycles and phases of a woman’s life - premenstrual, pregnancy and perimenopause.
Pregnancy is demanding in it’s own unique way: hormonal changes, increased nutritional demands, changes in sleep and eating patterns. Regular exercise, good healthy eating habits, a prenatal supplement, regular sleep, and moderating one’s work load, are usually enough to maintain energy throughout the pregnancy. Some women may become anemic during pregnancy and simple tests can detect this followed by simple nutrients as supplementation. At times, other health problems emerge during the pregnancy that can cause fatigue such as hypothyroid and diabetes. With good prenatal care, these can be detected and treated appropriately.
The cycles or phases of hormonal change such as the monthly premenstrual time, and the perimenopause transition can challenge what is called our stress adaptation mechanisms. There are three phases to this stress response which are regulated in large part, by our adrenal glands. The initial phase is the alarm reaction, or fight-or-flight response. This is triggered by reactions in the brain that cause the pituitary gland to produce a hormone, which causes the adrenals to secrete adrenaline as well as other stress related hormones. The alarm phase is usually very short lived. The next phase is the resistance reaction, which allows us to continue to deal with stress, after the fight-or-flight response has worn off. Hormones such as cortisol and other corticosteroids secreted by the adrenal cortex are in motion here and responsible for the resistance reaction. These hormones stimulate the conversion of protein to energy so that we have adequate fuel, after our glucose reservoirs have been used. The resistance reaction provides the energy and stabilizes our circulation under times of stress, as well as enabling us to deal with the emotional aspects of stress, fight infections and continue to perform our tasks. If the stress insult is prolonged and the resistance reaction is extended beyond our body’s capabilities to maintain balance, we become at risk for significant health care problems and end up in the final stage of general adaptation syndrome— exhaustion. In the exhaustion phase, our adrenal glands
have become depleted of hormones called glucocorticoids, and our body has a loss of potassium. In this phase, the body’s cells and tissues do not receive enough glucose or other nutrients to function properly.
As the exhaustion phase continues, our cells and organs in general feel the tremendous demand, and our metabolism is extremely challenged. Now we enter what we might call cellular fatigue and literally, our cells don’t get enough fuel to drive their function. This stress to our system takes a toll and nutritional status declines and disease status increases.
Premenstrual syndrome and perimenopause are their own kind of stress on the system. During these times, many women find their threshold of tolerating stress decreases. The complicated interaction of our hormones and our brain chemistry challenges our stress adaptation mechanisms, and fatigue can result. These fluctuating levels, both decreases and increases, in hormones such as estrogen, progesterone, cortisol and thyroid, interact with brain neurotransmitters such as serotonin, dopamine, GABA, and others, that affect our emotional and physical responses to life, to stressors in our environment, to insults, and even to infections.
Different circumstances call for different approaches, and if persistent fatigue is something that plagues you, it is important to consult with a licensed health care practitioner to determine the cause. A good medical history, physical exam, and selected laboratory tests can determine if the cause is low thyroid, anemia, an infectious agent, low or high blood sugar, or a serious illness. Licensed alternative practitioners will also have tools and perspectives to consider food sensitivities, toxicities, neurotransmitter imbalances, hormonal status and something we call adrenal fatigue syndrome.
A condition alternative medicine often calls “adrenal fatigue”, is a unique contribution to understanding a sometimes elusive problem such as fatigue.
Adrenal gland function and its production of hormones are vital performance tasks in our response to stress and our larger responses in our general adaptation syndrome. Nutritional and herbal support for a person who displays symptoms of intense or prolonged stress, and/or a fatiguing of the ability to adapt to the stress, can play a critical role in supporting our adrenal glands to adapt. An abnormal adrenal response, whether it is deficient or excessive hormone release, can be in large part addressed with key nutrients such as pantothene, B6, zinc, magnesium and vitamin C. These nutrients play a critical role in the optimal function of the adrenal glad and in the manufacture of adrenal hormones. Levels of these nutrients can be diminished during times of stress. Urinary excretion of vitamin C is increased during stress. Pantothene is also important during times of high stress or in individuals with adrenal fatigue. A deficiency of pantothenic acid results in fatigue, headaches, insomnia and more. Notable botanicals can also support adrenal function and enhance resistance to stress such as Siberian and Panax ginseng. These ginsengs are referred to as general tonics or adaptogens. Both Chinese and Siberian ginseng can be used to restore vitality in individuals who are chronically fatigued or who have decreased mental and physical performance and/or stamina. These ginseng species have been shown to act as tonics and anti-stress agents, enhancing the ability to cope with both physical and emotional stressors., , Individuals who take ginseng often report an increase in vitality, well being, increased mood, competence at work, mental and physical performance and reduced feelings of stress and anxiety. Rhodiola is well known amongst the Eastern Europeans for its ability to enhance energy, stamina and endurance. rhodiola appears to increase the chemicals that provide energy to the muscle of the heart and to prevent the depletion of adrenal hormones induced by acute stress.
Ashwagandha is also a significant adaptogen providing adrenal and immune support, , for increasing resistance to environmental stressors and as a general tonic. Ashwagandha contains several important active constituents including withanolides. Its mechanisms of action include pain relief, antioxidant effects, reducing inflammation, stimulating thyroid function, as well as respiratory and immune function. Some researchers have claimed that ashwagandha as an antistressor effect. It appears that it may suppress stress induced increases in dopamine receptors in the brain.
Astragalus has been used historically for strengthening and regulating the immune system, as a tonic, antioxidant, anti-inflammatory, antibacterial antiviral and to protect the liver. A lengthy list for sure. Although there is insufficient evidence to support the effectiveness of all of these uses, there is preliminary research that it is positive in some areas. Astragalus extracts seem to be able to restore or improve immune function in immune deficient cases. It may be able to restore suppressed T-cell function in cancer patients.7 Abnormal liver enzyme tests have improved in people chronic hepatitis when taking Astragalus. Astragalus is also thought to increase cardiac output and may be beneficial in individuals with congestive heart failure and compromised blood flow to the heart muscle. 8
We’re all familiar with our favorite spaghetti sauce that contains basil, but we may not know that this same plant, also known as Holy basil is a rich source of vitamin C, calcium, magnesium, potassium and iron. Holy basil has been gaining some attention due to experimental studies in humans on blood glucose. Elevated glucose levels were lowered by 21 mg/dl and lowering glucose after a meal, was also a positive effect of the basil. Many individuals with adrenal dysfunction, have increased glucose levels due to the increased cortisol as a result of stress.
Shisandra is plant most familiar to those who use Chinese herbs. In traditional Chinese medicine, schisandra is used for many common problems, including physical fatigue. Schisandra is used for improving immune function, recovery after surgery, increasing physical performance and endurance, and for increasing resistance to disease and stress. Schisandra is also possibly effective for improving concentration. It is thought that the variety of lignans found in the fruit, are the active constituents in schisandra.
Maca, or Peruvian Ginseng, may be one of the most important plants having a diverse effect on the female reproductive system. Traditionally, it has been used for chronic fatigue syndrome, enhancing energy, stamina and overall energy. In the female reproductive system, its use for enhancing fertility, regulating the menstrual cycle, treating common menopause symptoms and to increase libido has been familiar to the traditional peoples of Peru and elsewhere, for many a generation. Studies soon to be published, will be able to document some of its specific effects for menopausal women.
This type of herbal/nutritional support is especially helpful for those who have been determined to have adrenal fatigue. Symptoms such as fatigue, low vitality, low libido, depression, anxiety, poor memory, low stamina, and difficulty handling the premenstrual phase and the perimenopausal transition are key indications of adrenal fatigue.
Some women who have premenstrual fatigue or perimenopausal fatigue, may need additional hormonal support as well. This may include actually using hormones as medicines, but also may involve improving the metabolisim of our hormones. These considerations can best be addressed utilizing a comprehensive approach with a licensed naturopathic physician who has both the alternative medicine perspective, as well as the ability to prescribe various hormones such as progesterone, estrogen, testosterone, cortisol and thyroid.
The best approach to fatigue is to find out the cause. Don’t just ignore your fatigue and “gut it out” and don’t make assumptions about the cause of your fatigue. With good health care team approach utilizing your insights, your reading and natural foods store resources, a naturopathic physician, and possibly medical doctor or other allied practitioners, you can be more assured of understanding the cause and therefore the best solutions.
References
- Farnsworth N, et al. Siberian Ginseng: Current status as an adaptogen. Economic Medicinal Plant Research 1985;1: 156-215.
- Hikino H. Traditional remedies and modern assessment: The ase of Ginseng. In R.O.B. Wijeskera, ed. The Medicinal Plant Industry (Boca Raton, FL: CRC Press, 1991), 149-166.
- Shibata S, et al. Chemistry and Pharmacology of Panax. Econ Med Plant Research 1985;1:217-284.
- Hallstrom C, Fulder S, Carruthers. Effect of Ginseng on the performance of nurses on night duty. Comp Med East and West 1982;6:277-282.
- Maslova L, Kondrat’ev B, Maslov L, Lishmanov I. The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Eksp Klin Farmakol 1994;57:61-63. (Article in Russian).
- Upton R, ed. Ashwagandha root (Withania somnifera): Analytical, quality control, and therapeutic monograph. American Herbal Pharmacopoeia 2000;April: 1-25.
- Sun Y, Hersh E, Talpaz M, et al. Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs. Cancer 1983;52(1): 70-3.
- Upton R, Ed. Astragalus Root: analytical, quality control, and therapeutic monograph. Santa Cruz, CA: Am Herbal pharmacopoeia; 1999; 1-25.
- Agrawal P, Rai V, Singh R. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus. Int J Clin Pharmacol Ther. 1996;34(9): 406-409.
- Upton R, ed. Schisandra Berry: Analytical, Quality and Control, and Therapeutic Monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999; 1-25.
Soy as a prevention strategy for Osteoporosis
The potential for soy protein or soy isoflavones to alter bone metabolism and bone loss is currently contradictory and inconclusive. Our two best measurements are bone density testing with DXA (an xray test) measures or bone metabolism markers. The lack of agreement in the literature is thought to be related to variations in study design using different soy products, (ie soy protein isolate, whole soy foods, or extracted soy isoflavones), different populations with sometimes perimenopausal women, other times early or even late postmenopause, and then of course different durations and dosage and bone marker assessments. All these different approaches make it very difficult to determine the effectiveness of soy, and therefore difficult to make clinical judgments.
Soybeans contain a class of compounds called phytoestrogens, comprising mostly genistein, daidzein and glycitein, all of which have a biochemical structure similar to 17 beta estradiol. The binding of isoflavones to estrogen receptors is preferential for the estrogen receptor beta and thus indicates that soy isoflavones act as selective estrogen modulators. Daidzein is similar in shape to a drug called Ipriflavone which is used in Europe to treat osteoporosis. In the U.S., Ipriflavone is available as a nutritional supplement.
Bone mineral density (BMD) is the gold standard for determining fracture risk due to nontraumatic events. Bone turnover is an independent predictor of fracture risk.
While the effects of soy on bone metabolism has been inconsistent, many positive studies do exist that suggest a role for soy in slowing bone turnover and bone density in women. Soy appears to have a pro estrogen effect on bone in some experimental evaluations. The bone density of ovariectomized rats was evaluated in which soy replaced casein in the diet, compared to another group that received estrogen. The addition of soy inhibited bone loss, although not to the same extent as was achieved with the estrogen treatment. Another study of ovariectomized rats also reported a positive effect of the soy phytoestrogen genistein in maintaining bone. These authors also reported that genistein suppresses the bone losing cells (osteoclasts), both in the test tube and in vivo. Arjmandi also did a double-blind, randomized, controlled trial using 40g of soy protein containing isoflavones over 3 months in postmenopausal women. Bone resorption was decreased, when compared to milk protein.
Several human studies have provided further insight and comfort in the possible role of soy in our bone health. A study conducted at the University of Illinois found that menopausal women had an increase in mineral levels and density in their lumbar spines after taking 55-90 mg of isoflavones for six months. The placebo group showed the lowest bone density and the greatest bone loss, while the estrogen group showed the highest bone density and the slowest bone loss. What was surprising was that the soybean diet was effective in preventing bone loss in the fourth lumbar vertebra and, although less so, in the right hip as well. Soybean seems to have more of an effect on trabecular bone (more predominant in the spine) than on cortical bone (more predominant in the hip). The soy did not show as great an ability in preventing bone loss as the estrogen group, but the positive effect it showed is encouraging.
A study of the relation of soy isoflavone intake and bone mineral density was conducted within the Study of Women’s Health Across the Nation, a US cohort study of women aged 42-52 years. For African-American and Caucasian women, average intakes of genistein was too low to pursue analyses. For Chinese women, no association between genistein and bone mineral density was found. Pre-menopausal, but not peri-menopausal, Japanese women whose intakes were greater had a higher bone density of the spine and femoral neck. Mean spinal bone density of those women in the highest group was 7.7% greater than that of women in the lowest group. Bone density of the femoral neck was 12% greater in the highest intake group versus the lowest.
Other positive studies on soy and bone density also give some credence to the role of soy and bone health. In a study estimating the daily intakes of soy isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption, high consumption of soy products was associated with increased bone mass.
A very recent analysis of nine studies further increases our optimism about using soy to inhibit bone resorption. Nine studies with a total of 432 menopausal women were evaluated for meta-analysis. Amount of soy intake varied amongst the nine studies from 37 mg of isoflavones per day to 118 mg of isoflavones per day. Testing for urinary peptides (deoxypyridinoline) of bone turnover demonstrated that when all nine study results are combined, those who consumed isoflavones had a decrease in these biomarkers of -2.08 nmol/mmol when compared to those who did not consume isoflavones. In five of the studies, isolated soy protein was used, as a group, there was no significant effect on urinary deoxypyridinoline. In the current analysis, significant reduction in urinary deoxypyridinoline did not occur in those studies with isoflavones of less than 90 mg/day. In a review of the research in 2003, the author concluded that 90mg of isoflavones per day is required to achieve benefits on bone health.
In contrast to the positive studies, several clinical trials using a variety of soy protein isolate formulations found no clinically important effects of soy on bone metabolism and bone turnover markers. Further inconsistent research can be seen with several clinical trials using soy protein or isoflavones demonstrating a positive effect on BMD, while others have not had positive findings.
I mentioned variations in dosing, duration, soy formulations used, and different study populations as possible reasons for inconsistent results on the effects of soy isoflavones on bone turnover and bone density. But, another significant consideration may be due to how the isoflavones are metabolized in the gut. In the recent study mentioned about analyzing nine studies 10 the significant effects on urinary peptides occurred in Asian women but not Caucasian women. This may be due to the conversion of isoflavones into its active metabolite equol in intestinal flora, and that only one-third of Caucasian women can metabolize isoflavones into equol, whereas more than half of Asian women possess this ability.
Soy isoflavones may also have more of an effect in post-menopausal women than in pre or perimenopausal women. In one study, 53.3 mg of isoflavones per day was associated with an increase in bone density in postmenopausal women, but not pre-menopausal women.
An area of soy foods that may be overlooked, is the amount of calcium in some soy foods. A diet that includes greater amounts of soy products can account for a meaningful amount of calcium, and some soy foods can offer as much or more calcium than a serving of dairy products.
With the inconsistent research, it is difficult to draw confident conclusions about the role of soy in bone health. My clinical advice is to increase soy foods as part of a regular diet in prevention strategies for all pre, peri and postmenopausal women. For all women who have significant risk factors for osteoporosis, I would in addition, recommend soy supplementation so that their total daily soy isoflavone intake would deliver approximately 90 mg of soy isoflavones per day. For treatment of peri and postmenopausal women who already have osteoporosis, I would not consider soy an adequate treatment alone. In addition to the 90 mg per day of soy isoflavones and typical supplementation including calcium, vitamin D and other potential nutrients (K, boron, magnesium, manganese, and more), dietary and exercise advice, for these women who already have osteoporosis, I am in favor of proven conventional therapies to reduce fracture risk.
References
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- Setchell K. Soy isoflavones-benefits and risk from nature’s selective estrogen receptor modulators (SERMS). J Am Coll Nutr 2001; 20: 354S-362S.
- Garnero P, Hausherr E, Chapuy M, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 1996; 11:1531-1538.
- Arjmandi B, Alekel L, Hollis B, Amin D, Stacwicz-Sapuntzakis M, Guo , Kukreja S. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 1996;126:161-167.
- Blair H, Jordan S, Peterson T, Barnes S. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J cell Biochem. 1996;61:629-637.
- Arjmandi B, Khalil D, Smith B, et al. Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. J Clin Endocrinol Metab 2003; 88: 1048-1054.
- Erdman J, Stillman R, Lee K, Potter S. Short-term effects of soybean isoflavones on bone in postmenopausal women. Program and Abstract Book, Second International symposium on the Role of Soy in Preventing and Treating Chronic Disease. Brussels, Belgium, 1996.
- Greendale G, FitzGerald G, Huang M, et al. Dietary soy isoflavones and bone mineral density: Results from the study of women’s health across the nation. Amer J Epidemiology 2002;155(8):746-754.
- Somekawa Y, Chiguchi M, Ishibashi T, Takeshi A. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 2001;97:109-115.
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- Branca F. Dietary phyto-oestrogens and bone health. Proc Nutr Soc 2003; 62: 877-887.
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- Dalais F, Ebeling P, Kotsopoulos D, McGrath B, Teede H. The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol 2003; 58:704-709.
- Potter S, Baum J, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998; 68:1375S-1379S.
- Alekel D, Germain A, Peterson C, et al. Isoflavone-rich soy protein attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000; 72:844-852.
- Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo controlled study. J Bone Miner Res 2002; 17:1904-1912.
- Chen Y, Ho S, Lam S, Ho S, Woo J. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88:4740-4747.
- Lydeking-Olsen E, Beck-Jensen J, Setchell K, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss: a 2 year randomized, placebo-controlled trial. Eur J Nutr 2004;43:246-257.
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- Kreijkamp-Kaspers S, Kok L, et al. Effects of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. JAMA 2004; 292:65-74.
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