Category Archives: Women’s Health

Science and health of special interest to women.

Sleeping position associated with late pregnancy stillbirth

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A research paper recently published in the British Medical Journal reports a strong association between sleep practices and stillbirth late in pregnancy. The authors set out to…

“…determine whether snoring, sleep position, and other sleep practices in pregnant women are associated with risk of late stillbirth.”

The compared date for 155 women with a singleton stillbirth after 28 weeks of pregnancy (and without congenital abnormality) with 310 women with pregnancies and gestation matched to those in which stillbirth occurred as controls. They examined maternal snoring, daytime sleepiness, and sleep position at the time of going to sleep and on waking. Their data were striking for the association with sleep position in particular:

“No relation was found between snoring or daytime sleepiness and risk of late stillbirth. However, women who slept on their back or on their right side on the previous night…were more likely to experience a late stillbirth compared with women who slept on their left side… Women who got up to go to the toilet once or less on the last night were more likely to experience a late stillbirth compared with women who got up more frequently. Women who regularly slept during the day in the previous month were also more likely to experience a late stillbirth than those who did not.”

Sleeping on the back or right side conferred a 250% increase of stillbirth late in pregnancy than sleeping on the right side. The results for sleep position and frequency of rising for the toilet during the night make sense considering the vascular dynamics. Daytime sleepiness is frequently associated with decreased oxygenation due to apneas or hypopneas during the night. The authors’ conclusion is a call to action to prevent the devastating heartbreak of late pregnancy stillbirth by better advice based on more science:

“This is the first study to report maternal sleep related practices as risk factors for stillbirth, and these findings require urgent confirmation in further studies.”

Meanwhile, it seems prudent to prefer a right side sleeping position while awaiting further confirmation. Also, clinicians, pregnant patients and their partners should be alert to signs of sleep disordered breathing.

Green tea polyphenols protect against sunburn and improve skin quality

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Skin protection strategies during sun-drenched activities while minimizing vitamin D attenuating sunscreens can include green tea polyphenols according to a study recently published in The Journal of Nutrition. The authors first observe:

“Dietary constituents including polyphenols and carotenoids contribute to endogenous photoprotection and modulate skin characteristics related to structure and function of the tissue. Animal and in-vitro studies indicate that green tea polyphenols affect skin properties.”

They performed a 12-wk, double-blind, placebo-controlled study during which 60 female volunteers consumed either a beverage with green tea polyphenols or a control drink. During the study they measured skin photoprotection, structure, and function at baseline, 6 weeks and 12 weeks.  Their data showed  impressive benefits:

“Following exposure of the skin areas to 1.25 minimal erythemal dose of radiation from a solar simulator, UV-induced erythema decreased significantly in the intervention group by 16 and 25% after 6 and 12 wk, respectively. Skin structural characteristics that were positively affected included elasticity, roughness, scaling, density, and water homeostasis.”

Additionally…

“Intake of the green tea polyphenol beverage for 12 wk increased blood flow and oxygen delivery to the skin. Likewise, in a separate, randomized, double-blind, single-dose (0.5, 1.0, and 2.0 g) study of green tea polyphenols, blood flow was maximized at 30 min after ingestion.”

The green tea polyphenol beverage used in the study provided a dose of 1402 mg total catechins per day. Because the average 6 ounce cup of green tea contains between 50 and 100 mg of catechins and can vary widely depending on the tea and other factors, taking green tea polyphenols in a reliable supplemental form is more practical than attempting to drink  fifteen or more cups of tea. There is no good reason why the authors’ conclusion does not also apply to men:

“In summary, green tea polyphenols delivered in a beverage were shown to protect skin against harmful UV radiation and helped to improve overall skin quality of women.”

While generally safe, because there is some evidence that green tea catechins may enhance the Th2 (humoral) immune response, clinicians should bear this in mind and individuals receiving treatment for Th2-dominant autoimmune disorders should discuss the use of green polyphenols with their provider.

The highest amounts of calcium intake increase the risk of fracture

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Patients are often surprised to learn that osteoporosis is not a calcium deficiency disorder but rather a failure to maintain the microarchitecture of the bone of which the protein matrix is a critical component. Moreover, earlier posts on magnesium and calcium have document the pro-inflammatory potential of calcium supplementation. Now fascinating research just published in the British Medical Journal offers evidence that calcium above the lowest quintile does not improve the risk of fracture of any type, while the highest levels actually increase the risk of fracture. The authors set out to…

“……investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis.”

They note that confusion regarding the issue of calcium requirements has been…

“…reflected by the wide range of daily calcium recommendations for individuals older than 50 years: at present 700 mg in the UK, 800 mg in Scandinavia, 1200 mg in the United States, and 1300 mg in Australia and New Zealand.”

The authors investigated 61,433 women born between 1914 and 1948 for 19 years for correlations between dietary intake of calcium and fractures of any type, hip fractures, and osteoporosis. They took into consideration vitamin D consumption, hormonal status, and other pertinent biological and lifestyle factors including physical activity. Perhaps not surprisingly in light of other evidence that has emerged recently about calcium, their data challenges the conventional wisdom:

“These findings show an association between a low habitual dietary calcium intake (lowest quintile) and an increased risk of fractures and of osteoporosis. Above this base level, we observed only minor differences in risk. The rate of hip fracture was even increased in those with high dietary calcium intakes.“

In others, amounts higher than the lowest level of calcium intake adequate to avoid gross insufficiency and compromised bone micoarchitecture there were not only no significant benefits, the highest levels of intake increased fracture risk. The authors comment:

“The present results may reflect a situation when a moderate intake of calcium* combined with adequate intake of other micronutrients is sufficient to meet the structural and functional demands of the skeleton. High levels of intake did not further decrease the rate of fracture, and might even increase the rate of hip fractures…Moreover, use of supplemental calcium has been associated with higher rates of hip fracture both in a cohort study and in randomised controlled trials…Furthermore, high calcium doses slow bone turnover and also reduce the number of active bone remodelling sites. This situation can lead to a delay of bone repair caused by fatigue, and thus increase the risk of fractures independent of bone mineral density.”

*Their data indicate that a total dietary intake of 700 mg of calcium per day is sufficient to prevent fracture and osteoporosis. The authors conclude:

“Incremental increases in calcium intake above the level corresponding to the first quintile of our female population were not associated with a further reduction of osteoporotic fracture rate.”

Considering that chronic inflammation can be a primary factor in causing loss of the protein ‘scaffolding’ of bone responsible for strength, resilience, and the matrix to which minerals attach, these findings invoke recollection of the recent evidence that calcium supplementation can increase the inflammation of  cardiovascular disease. In case you missed it, a recent research paper published in the British Medical Journal follows up on earlier reports of this association. The authors’ intent was…

“To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women’s Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk.”

The examined the data from a randomised, placebo controlled trial of calcium alone or with vitamin D in 36,282 postmenopausal women over seven years for myocardial infarction, coronary revascularisation, death from coronary heart disease, and stroke. The data told an interesting story:

“In the WHI CaD Study there was an interaction between personal use of calcium supplements and allocated calcium and vitamin D for cardiovascular events…Calcium or calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.24 (1.07 to 1.45), P=0.004) and the composite of myocardial infarction or stroke (1.15 (1.03 to 1.27), P=0.009).”

Clinicians and patients need to appreciate that inflammation, a fundamental causal factor in both osteoporosis and cardiovascular disease, can be made worse by calcium supplements. The authors conclude:

“Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.“

 

Should women undergoing treatment for breast cancer take antioxidant supplements?

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An important study just published in Cancer Epidemiology, Biomarkers & Prevention adds to the  evidence that supplementation can be helpful rather than an impediment to oxidizing therapies. The authors set out to address a concern that has persisted in the face of mounting evidence to the contrary:

“Antioxidants may protect normal cells from the oxidative damage that occurs during radiotherapy and certain chemotherapy regimens; however, the same mechanism could protect tumor cells and potentially reduce effectiveness of cancer treatments. We evaluated the association of vitamin supplement use in the first 6 months after breast cancer diagnosis and during cancer treatment with total mortality and recurrence.”

They evaluated 4,877 women diagnosed with invasive breast cancer in Shanghai, China, between March 2002 and April 2006 for the correlation between supplement use and breast cancer total mortality and recurrence. Women were interviewed approximately 6 months after diagnosis and followed up by interviews and records. What did the data show?

“Vitamin use shortly after breast cancer diagnosis was associated with reduced mortality and recurrence risk, adjusted for multiple lifestyle factors, sociodemographics, and known clinical prognostic factors. Women who used antioxidants (vitamin E, vitamin C, multivitamins) had 18% reduced mortality risk and 22% reduced recurrence risk. “

Interestingly, in this study…

“The inverse association was found regardless of whether vitamin use was concurrent or nonconcurrent with chemotherapy, but was present only among patients who did not receive radiotherapy.”

The data were sufficient for the authors to conclude:

“Vitamin supplement use in the first 6 months after breast cancer diagnosis may be associated with reduced risk of mortality and recurrence…Our results do not support the current recommendation that breast cancer patients should avoid use of vitamin supplements.”

The autoimmune aspect of preterm labor

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A paper just published in PLoS ONE (Public Library of Science) presents findings that expand our understanding of the inflammatory aspect of preterm labor.  The authors state:

“Preterm parturition is characterized by innate immune activation and increased proinflammatory cytokine levels. This well established association leads us to hypothesize that preterm delivery is also associated with neonatal T lymphocyte activation and maturation.”

For our lay readership, innate immune activation refers to the cell-mediated ‘first phase’ Th1 immune response versus the ‘second phase’ Th2 antibody aspect mediated by T lymphocyte activation. The authors obtained cord blood samples following normal and preterm deliveries, and deliveries complicated by clinical chorioamnionitis (inflammation of the fetal membranes). What did they find?

“Infants born following preterm delivery demonstrated enhanced CD4+ T lymphocyte activation… Neonates delivered following clinical chorioamnionitis also demonstrated increased T cell activation. Preterm neonates had an increased frequency of CD45RO+ T cells.”

Autoimmune cross-reactions to environmental stimuli fuels a wide range of disorders. Consider the role of gluten sensitivity in a variety of female reproductive disorders. The authors conclude:

“Preterm parturition is associated with neonatal CD4+ T cell activation, and an increased frequency of CD45RO+ T cells. These findings support the concept that activation of the fetal adaptive immune system in utero is closely associated with preterm labor.“

The obvious practical implication is that screening for preterm labor can be accomplished by testing for antibodies to the fetal membranes. In positive cases rational therapy can be applied on a functional basis to address the underlying causes of immune overactivation.

Better have a backup if you use cranberry for urinary tract infections

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There is an abundance of anecdotal evidence for the effectiveness of cranberry products in the treatment or prevention of urinary tract infections, but a randomized placebo-controlled trial just published in the journal Clinical Infectious Diseases indicates that there should be an alternative therapy available for backup. The authors note:

“A number of observational studies and a few small or open randomized clinical trials suggest that the American cranberry may decrease incidence of recurring urinary tract infection (UTI).”

Their double-blind, placebo-controlled trial examined the effects of cranberry on risk of recurring UTI among 319 college women who presented with an acute UTI confirmed by a positive urine culture. They were followed up until a second UTI or for 6 months, whichever came first. The data amounted to a disappointing result:

“Overall, the recurrence rate was 16.9%, and the distribution of the recurrences was similar between study groups, with the active cranberry group presenting a slightly higher recurrence rate (20.0% vs 14.0%). The presence of urinary symptoms at 3 days, 1–2 weeks, and at ≥1 month was similar between study groups, with overall no marked differences.”

Although it is recognized that cranberry juice contains compounds that decrease the adherence of uropathogens—decrease the ability of bacteria to attach to urinary tract tissue—and there have been some positive reports, the authors’ conclusion should be borne in mind:

“Among otherwise healthy college women with an acute UTI, those drinking 8 oz of 27% cranberry juice twice daily did not experience a decrease in the 6-month incidence of a second UTI, compared with those drinking a placebo.”

A paper published years ago in the The Journal of Urology sheds light on why we have a negative trial like this that contradicts other studies and anecdotal reports. The authors investigated the properties of d-mannose, another ‘natural’ agent used to treat urinary tract infections by reducing bacterial adherence:

“The effect of D-mannose on adherence of 73 Escherichia coli strains to vaginal and buccal epithelial cells from women with recurrent urinary tract infections…was tested. Urinary, vaginal or anal isolates from women with such infections were used.”

They found that there was a significant difference depending on the strain of bacteria:

“Of the strains 66 (90 per cent) demonstrated adherence to epithelial cells. D-mannose inhibited completely the adherence of 25 strains (42 per cent) that adhered to vaginal cells and inhibited an additional 11 strains (18 per cent) by at least 50 per cent. Similar results were obtained with buccal cells.”

This highlights the obvious clinical fact: when treating an infection, the effectiveness of any kind of antimicrobial intervention will vary according to the strain (not just the species) of the pathogen. Sensitivity should be determined beforehand whenever possible; otherwise have a backup.

Magnesium and sudden cardiac death in women

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More evidence for the importance of magnesium in cardiovascular disease in general and sudden cardiac death in particular is offered in a paper recently published in The American Journal of Clinical Nutrition. The authors state:

“Magnesium has antiarrhythmic properties in cellular and experimental models; however, its relation to sudden cardiac death (SCD) risk is unclear…We prospectively examined the association between magnesium, as measured in diet and plasma, and risk of SCD.”

They examined magnesium intake for 88,375 women participating in the Nurses’ Health Study along with other nutrients and lifestyle factors for 26 years. During this time 505 cases of sudden or arrhythmic death were documented. Within this group they correlated plasma magnesium for 99 SCD cases and 291 controls who were matched for relevant variables such as age, smoking, and other elements of cardiovascular disease. What did their data show?

“After multivariable adjustment for confounders and potential intermediaries, the relative risk of SCD was significantly lower in women in the highest quartile compared with those in the lowest quartile of dietary and plasma magnesium. The linear inverse relation with SCD was strongest for plasma magnesium, in which each 0.25-mg/dL increment in plasma magnesium was associated with a 41% lower risk of SCD.”

In other words, the women with the highest levels of plasma and dietary magnesium had a significantly lower risk for sudden cardiac death. The association was particularly strong for plasma magnesium (our functional reference range for plasma magnesium is 2.0-2.5 mg/dL). The authors conclude:

“In this prospective cohort of women, higher plasma concentrations and dietary magnesium intakes were associated with lower risks of SCD. If the observed association is causal, interventions directed at increasing dietary or plasma magnesium might lower the risk of SCD.”

This data was generated within the Nurses’ Health Study, but there is no reason to assume that the practical implications don’t apply to men. You can easily see earlier reports on magnesium and cardiovascular disease by typing ‘magnesium’ in the search box. Clinicians and interested laypersons will further appreciate a forthcoming post on the association of intracellular magnesium and glutathione recycling, a critical process in the regulation of inflammation and nitric oxide production.

Body fat distribution, insulin and breast cancer

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A report just published in the Journal of the National Cancer Institute adds more evidence to the importance of insulin regulation in ER (estrogen receptor) negative breast cancer. The authors first note a conundrum in breast cancer epidemiology:

“Body mass index is inversely associated with risk of premenopausal breast cancer, but the underlying mechanisms for this association are poorly understood. Abdominal adiposity is associated with metabolic and hormonal changes, many of which have been associated with the risk of premenopausal breast cancer.”

They investigated the association between body fat distribution, hip circumference, and waist to hip ratio, and the incidence of premenopausal breast cancer in the Nurses’ Health Study II:

“During 426 164 person-years of follow-up from 1993 to 2005, 620 cases of breast cancer were diagnosed among 45 799 women. Hormone receptor status information was available for 84% of the breast cancers.”

When they looked at the group as a whole, no statistically significant associations were found. However…

“…each of the three body fat distribution measures was statistically significantly associated with greater incidence of estrogen receptor (ER)–negative breast cancer.”

The risk for ER-negative breast cancer was increased by 275% for waist circumference, 240% for hip circumference, and 195% for waist to hip ratio (comparing the highest to the lowest quintile). The authors state:

“These findings may suggest that an insulin-related pathway of abdominal adiposity is involved in the etiology of premenopausal breast cancer.“

The implication is that factors associated with increased abdominal adiposity influence the development of breast cancer through estrogen independent pathways, specifically the influence of excess levels of insulin on tumor growth that also promote the accumulation of fat around the waist. As experienced clinicians know, tumors often have mixed cell types. The role of insulin as a tumor promoter should never overlooked in case management, with careful attention to the regulation of blood sugar and insulin.

Caffeine consumption during pregnancy is not associated with pre-term birth

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The notion that caffeine consumption during pregnancy is a risk factor for pre-term birth does not hold up in an extensive meta-analysis published in the American Journal of Clinical Nutrition. The authors state:

“The effect of caffeine intake during pregnancy on the risk of preterm delivery has been studied for the past 3 decades with inconsistent results…We performed a meta-analysis examining the association between caffeine consumption during pregnancy and risk of preterm birth.”

They identified 15 cohort and 7 case-control studies that met inclusion criteria among MEDLINE and EMBASE articles published between 1966 and July 2010. What did the data show?

“The combined odds ratios (ORs) obtained by using fixed-effects models for cohort studies were 1.11, 1.10, and 1.08 for risk of preterm birth comparing the highest with the lowest level of caffeine intake (or no intake)during the first, second, and third trimesters, respectively. Results for the case-control studies yielded no associations for the first, second, or third trimesters.”

In other words, as they state in their conclusion, no statistically significant risk from caffeine consumption emerged from the data:

“In this meta-analysis, we observed no important association between caffeine intake during pregnancy and the risk of preterm birth for cohort and case-control studies.”

Even with a family history of breast cancer breast healthy behavior pays off

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Whatever the genetic disposition for breast cancer, epigenetic influences—conduct and environmental factors that modify gene expression—are often decisive. A study just published in the journal Breast Cancer Research offers further evidence that those with a family history of breast cancer can act effectively to reduce the risk:

“A family history of later-onset breast cancer (FHLBC) may suggest multi-factorial inheritance of breast cancer risk, including unhealthy lifestyle behaviors that may be shared within families. We assessed whether adherence to lifestyle behaviors recommended for breast cancer prevention–including maintaining a healthful body weight, being physically active and limiting alcohol intake–modifies breast cancer risk attributed to FHLBC in postmenopausal women.”

The authors analyzed breast cancer outcomes in relationship to lifestyle and risk factors collected by questionnaire of 85,644 postmenopausal women into the Women’s Health Initiative Observational Study.

“The rate of invasive breast cancer among women with an FHLBC who participated in all three behaviors was 5.94 per 1,000 woman-years, compared with 6.97 per 1,000 woman-years among women who participated in none of the behaviors. The rate among women with no FHLBC who participated in all three behavioral conditions was 3.51 per 1,000 woman-years compared to 4.67 per 1,000 woman-years for those who participated in none.”

The data showed benefit for women both with and without a family history of breast cancer as they state in their conclusion:

“Participating in breast healthy behaviors was beneficial to postmenopausal women and the degree of this benefit was the same for women with and without an FHLBC.“

And we have evidence to suggest that if breast healthy behaviors were to include such important factors and blood sugar and insulin management, healthy hormone regulation, metabolic and other components of the functional medicine approach the outcomes would further improve.