Judith L. Balk

Nutrient Involvement in Preeclampsia

Preeclampsia is a pregnancy-specific condition that increases maternal and infant mortality and morbidity. It is diagnosed by new-onset increased blood pressure and proteinuria during gestation; for many years these markers were the sole targets for study. More recently, increased attention to the multisystemic nature of the syndrome with involvement of almost all organs, activation of coagulation and increased sensitivity to pressor agents has expanded understanding of the disorder. The epidemiology of preeclampsia, being more common in poor women, long ago suggested that nutrients might be involved in the disorder. Numerous conflicting hypotheses were advanced but the testing of these hypotheses has either been done poorly or not at all. Review of the available data indicates very few studies that provide useful insights. In many studies the syndrome is poorly defined and in most studies nutritional data (questionnaires or biomarkers) are obtained on women with the clinical syndrome. In overtly preeclamptic women it is impossible to decipher cause from effect. Nonetheless, current concepts of the genesis of preeclampsia that include endothelial dysfunction, inflammatory activation, oxidative stress and predisposing maternal factors provide targets for well-designed nutritional investigation. In this review the current concepts of the pathogenesis of preeclampsia are reviewed and available data are assessed in light of these concepts. Targets for nutritional investigation based on the current knowledge of pathophysiology are suggested.

A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium.

Objective: This study was designed to assess endometrial histology in postmenopausal women not taking hormone replacement therapy, to evaluate side effects and efficacy of phytoestrogens in treating menopause-associated symptoms, and to determine whether 6 months of phytoestrogen supplementation altered endometrial histology. Methods: We performed a prospective, double-blinded, randomized, placebo-controlled trial comparing the effects of 6 months of dietary phytoestrogen supplemtation versus placebo in postmenopausal women. Baseline endometrial biopsies were performed and, if adequate, nonhyperplastic, noncancerous, and non-ovulatory, subjects were randomly assigned to receive daily placebo or soy cereal supplementation for 6 months. Study subjects completed baseline and weekly dietary, symptom, and side effect logs. Repeat endometrial biopsies were obtained at 6 months. Results: Subjects were recruited from January 1998 through June 2000. Twenty-seven subjects were randomized, and 19 completed the study. One (3.7%) baseline endometrial sample was weakly proliferative. All other baseline and final biopsies were consistent with atrophic, inactive endometrium. The maximum risk of endometrial stimulation with phytoestrogens is 35%. Hot flushes, night sweats, and vaginal dryness were significantly less severe at the final week of the study compared with baseline in the placebo group. Insomnia was more common in the treated group. There were no other statistically significant differences in symptoms or side effects. Conclusion: Phytoestrogens did not cause stimulation of the endometrium. Insomnia was more frequent over the 6-month study in the soy group, whereas hot flushes, night sweats, and vaginal dryness improved from baseline in the placebo group but not in the soy group.

Melatonin osteoporosis prevention study (MOPS): a randomized, double-blind, placebo-controlled study examining the effects of melatonin on bone health and quality of life in perimenopausal women

Abstract:  The purpose of this double‐blind study was to assess the effects of nightly melatonin supplementation on bone health and quality of life in perimenopausal women. A total of 18 women (ages 45–54) were randomized to receive melatonin (3 mg, p.o., n = 13) or placebo (n = 5) nightly for 6 months. Bone density was measured by calcaneal ultrasound. Bone turnover marker (osteocalcin, OC for bone formation and NTX for bone resorption) levels were measured bimonthly in serum. Participants completed Menopause‐Specific Quality of Life‐Intervention (MENQOL) and Pittsburgh Sleep Quality Index (PSQI) questionnaires before and after treatment. Subjects also kept daily diaries recording menstrual cycling, well‐being, and sleep patterns. The results from this study showed no significant change (6‐month‐baseline) in bone density, NTX, or OC between groups; however, the ratio of NTX:OC trended downward over time toward a ratio of 1:1 in the melatonin group. Melatonin had no effect on vasomotor, psychosocial, or sexual MENQOL domain scores; however, it did improve physical domain scores compared to placebo (mean change melatonin: −0.6 versus placebo: 0.1, P < 0.05). Menstrual cycling was reduced in women taking melatonin (mean cycles melatonin: 4.3 versus placebo: 6.5, P < 0.05), and days between cycles were longer (mean days melatonin: 51.2 versus placebo: 24.1, P < 0.05). No differences in duration of menses occurred between groups. The overall PSQI score and average number of hours slept were similar between groups. These findings show that melatonin supplementation was well tolerated, improved physical symptoms associated with perimenopause, and may restore imbalances in bone remodeling to prevent bone loss. Further investigation is warranted.

The relationship between perceived stress, acupuncture, and pregnancy rates among IVF patients: A pilot study

UNLABELLED The aim of this paper was to determine the effect of acupuncture on perceived stress levels in women on the day of embryo transfer (ET), and to determine if perceived stress levels at embryo transfer correlated with pregnancy rates. The study was an observational, prospective, cohort study based at the University IVF center. PATIENT(S) 57 infertile patients undergoing IVF or IVF/ICSI. INTERVENTIONS(S) Patients were undergoing Embryo Transfer with or without acupuncture as part of their standard clinical care. MAIN OUTCOME MEASURE(S) Perceive Stress Scale scores, pregnancy rates. RESULT(S) women who received this acupuncture regimen achieved pregnancy 64.7%, whereas those without acupuncture achieved pregnancy 42.5%. When stratified by donor recipient status, only non-donor recipients potentially had an improvement with acupuncture (35.5% without acupuncture vs. 55.6% with acupuncture). Those who received this acupuncture regimen had lower stress scores both pre-ET and post-ET compared to those who did not. Those with decreased their perceived stress scores compared to baseline had higher pregnancy rates than those who did not demonstrate this decrease, regardless of acupuncture status. CONCLUSIONS(S) The acupuncture regimen was associated with less stress both before and after embryo transfer, and it possibly improved pregnancy rates. Lower perceived stress at the time of embryo transfer may play a role in an improved pregnancy rate.

Effect of Sahaja yoga meditation on quality of life, anxiety, and blood pressure control.

OBJECTIVE The present study investigates the effect of Sahaja yoga meditation on quality of life, anxiety, and blood pressure control. DESIGN The prospective observational cohort study enrolled two study groups: those receiving treatment from the International Sahaja Yoga Research and Health Center (meditation group) and those receiving treatment from the Mahatma Gandhi Mission Hospital (control group). Researchers measured quality of life, anxiety, and blood pressure before and after treatment. RESULTS Sixty-seven (67) participants in the meditation group and 62 participants in the control group completed the study. The two groups were comparable in demographic and clinical characteristics. At baseline, the meditation group had higher quality of life (p<0.001) than controls but similar anxiety level (p=0.74) to controls. Within-group pre- versus post-treatment comparisons showed significant improvement in quality of life, anxiety, and blood pressure in the meditation group (p<0.001), while in controls, quality of life deteriorated and there was no improvement in blood pressure. The improvement in quality of life, anxiety reduction, and blood pressure control was greater in the meditation group. The beneficial effect of meditation remained significant after adjusting for confounders. CONCLUSIONS Meditation treatment was associated with significant improvements in quality of life, anxiety reduction, and blood pressure control.

Prophylactic bilateral oophorectomy or removal of remaining ovary at the time of hysterectomy in the United States, 1979-2004

OBJECTIVE The purpose of this study was to describe national rates and trends of prophylactic bilateral oophorectomy or remaining oophorectomy (BO/RO) at hysterectomy in women without specific gynecologic disease. STUDY DESIGN Data from the National Hospital Discharge Survey were analyzed for 1979-2004. Hysterectomies were divided into 2 groups: (1) hysterectomy with BO/RO and (2) hysterectomy alone (> or =1 ovary remaining). Age-adjusted rates (AARs) were calculated with 2000 US census data. RESULTS Approximately 3,686,000 hysterectomies with BO/RO were performed from 1979-2004. AARs of hysterectomy with BO/RO decreased during this period; the AARs in women > or =50 years old increased. The number of hysterectomies alone was 5,461,100, and AARs of hysterectomy alone decreased significantly from 2.9 per 1000 women in from 1979-1981 to 1.1 per 1000 women in 2001 (P < .001). The proportion of women who underwent hysterectomy with BO/RO increased from 29% in 1979 to 45% in 2004. CONCLUSION Although AARs of prophylactic BO/RO decreased from 1979-2004, the actual proportion of BO/RO at hysterectomy increased.

Efficacy and safety of vaginal estriol and progesterone in postmenopausal women with atrophic vaginitis

Objective: The aim of this study was to assess the efficacy and safety of intravaginal estriol and progesterone on atrophic vaginitis in postmenopausal women. Methods: Under a physician-sponsored Investigational New Drug application, 19 healthy postmenopausal women with atrophic vaginitis received vaginal suppositories containing estriol (1 mg) and progesterone (30 mg). The participants were instructed to insert one suppository intravaginally once daily for 2 weeks and thrice weekly for a total of 6 months. Vaginal pH, Vaginal Maturation Index, urinalysis, self-reported vaginal dryness, menopausal quality of life, and serum estriol and progesterone levels were measured at enrollment and after 3 and 6 months of suppository use. Endometrial biopsies were obtained at enrollment and at 6 months. After 2 weeks of therapy, six participants had serum estriol and progesterone measured. Results: The Vaginal Maturation Index, vaginal pH, and vaginal dryness rating improved significantly at 3 and 6 months compared with baseline. Menopausal quality of life scores improved significantly in all domains, with the sexual subscale showing the most improvement. There were no cases of endometrial hyperplasia after 6 months of suppository use. Serum preinsertion estriol at week 2 and months 3 and 6 were similar to baseline levels. Serum preinsertion progesterone increased but returned to baseline preinsertion levels at month 6, and preinsertion levels were significantly less at month 6 compared with month 3. Conclusions: Intravaginal administration of a combination estriol and progesterone agent to women with atrophic vaginitis may represent a safe and effective alternative to systemic hormone replacement, although this study was not adequate to provide proof of efficacy given that it was uncontrolled.

The effects of glucosamine sulfate on intervertebral disc annulus fibrosus cells in vitro.

BACKGROUND CONTEXT Glucosamine has gained widespread use among patients, despite inconclusive efficacy data. Inconsistency in the clinical literature may be related to lack of understanding of the effects of glucosamine on the intervertebral disc, and therefore, improper patient selection. PURPOSE The goal of our study was to investigate the effects of glucosamine on intervertebral disc cells in vitro under the physiological conditions of inflammation and mechanical loading. STUDY DESIGN Controlled in vitro laboratory setting. METHODS Intervertebral disc cells isolated from the rabbit annulus fibrosus were exposed to glucosamine sulfate in the presence and absence of interleukin-1β and tensile strain. Outcome measures included gene expression, measurement of total glycosaminoglycans, new proteoglycan synthesis, prostaglandin E2 production, and matrix metalloproteinase activity. The study was funded by NIH/NCCAM, and the authors have no conflicts of interest. RESULTS Under conditions of inflammatory stimulation alone, glucosamine demonstrated a dose-dependent effect in decreasing inflammatory and catabolic mediators and increasing anabolic genes. However, under conditions of mechanical stimulation, although inflammatory gene expression was decreased, PGE2 was not. In addition, matrix metalloproteinase-3 gene expression was increased and aggrecan expression decreased, both of which would have a detrimental effect on matrix homeostasis. Consistent with this, measurement of total glycosaminoglycans and new proteoglycan synthesis demonstrated detrimental effects of glucosamine under all conditions tested. CONCLUSIONS These results may in part help to explain the conflicting reports of efficacy, as there is biological plausibility for a therapeutic effect under conditions of predominate inflammation but not under conditions where mechanical loading is present or in which matrix synthesis is needed.

Glucosamine supplementation demonstrates a negative effect on intervertebral disc matrix in an animal model of disc degeneration.

Study Design. Laboratory based controlled in vivo study. Objective. To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration. Summary of Background Data. Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A Centers for Disease Control report from 2009 reported that many patients are using glucosamine supplementation for low back pain, without significant evidence to support its use. Because disc degeneration is a major contributor of low back pain, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. Methods. Eighteen skeletally mature New Zealand White rabbits were divided into 4 groups: control, annular puncture, glucosamine, and annular puncture + glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107 mg/d (weight based equivalent to human 1500 mg/d). Annular puncture surgery involved puncturing the annulus fibrosus of 3 lumbar discs with a 16-gauge needle to induce degeneration. Serial magnetic resonance images were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan content, relative gene expression measured by real time polymerase chain reaction, and histological analyses. Results. The magnetic resonance imaging index and nucleus pulposus area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and glycosaminoglycan content. Gene expression was consistent with a detrimental effect on matrix. Conclusion. These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, magnetic resonance imaging, histology, and total proteoglycan is antianabolic. This raises concern about this commonly used supplement, and future research is needed to establish the clinical relevance of these findings.

Using Yoga to Promote Bone Health and Reduce Fracture Risk in the Geriatric Population

In this article, we review the literature on the applicability of Hatha Yoga for bone health in a geriatric population. We also describe our recent pilot study assessing the effects of Hatha Yoga on bone turnover markers, and we discuss the logistics and feasibility of yoga in our study population, which comprised sedentary osteopenic women. We discuss the practical lessons learned from our pilot study. Yoga has the potential to decrease fracture risk in a geriatric population via several mechanisms, including improving balance, reducing fall risk and fear of falls, improving functioning, reducing hyperkyphosis, and improving bone turnover.