Biomedical Base
Harvard Clinical Nutrition Research Center
Biomedical Base
Women's Health
Following are the primary investigators of this theme and a brief discussion of their work.
Joann Manson
Dr. Manson joins the HCNRC renewal as a new Investigator. She became aware of the Center as a participant in our annual symposium on Nutrition and Women’s Health in 2004 (APPENDIX E2). As Director of the Corners Center for Women’s Health and Gender Biology and Chief of the Division of Preventative Medicine at the Brigham and Women’s Hospital, Dr. Manson brings a new theme to the HCNRC renewal application. She and other new Investigators (Drs. Buring, Blumberg, Mantzoros and Gordon) along with former Investigators (Drs. Field and Herzog) make up a strong group investigating nutrition and women’s health. A brief summary of Dr. Manson’s activities is as follows. The Women’s Health Initiative (WHI) is a national multicenter randomized clinical trial that includes a dietary intervention component. The diet modification trial is testing the role of low-fat intake (<20% calories from fat) and increased intake of fruits, vegetables, and whole grains in preventing development of breast cancer, colorectal cancer, and cardiovascular disease over an average of 8-9 years of follow-up. Participants are postmenopausal women aged 50-59 years at baseline. The diet trial results are expected to be published in October or November 2005.
Julie Buring
Dr. Buring joins the HCNRC renewal as a new Investigator. She is Professor of Medicine at Harvard Medical School, Deputy Director of the Division of Preventive Medicine in the Department of Medicine at Brigham and Women’s Hospital, and Director of Research at the Harvard Medical School Osher Institute, Division for Research and Education in Complementary and Integrative Medical Therapies. Dr. Buring is also Professor of Epidemiology at both the Harvard and Boston University Schools of Public Health. Her research focuses on the epidemiology of chronic disease, primarily cardiovascular disease and cancer, and especially among women. She is involved in a number of large-scale clinical trials or observational cohort studies of the prevention of these diseases. She was Principal Investigator of the just completed Women’s Health Study, a large-scale randomized trial of the benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer, conducted among 40,000 female health professionals, and is Principal Investigator of the extended follow-up of the participants. In addition, Dr. Buring is Co-Principal Investigator of the Women’s Antioxidant Cardiovascular Study (evaluating the benefits of antioxidant therapy among 8,000 women with a history of cardiovascular disease), the Physicians’ Health Study II (a randomized trial of vitamins E, C, beta-carotene and a multivitamin currently ongoing among 15,000 male physicians), and the Brigham and Women’s Hospital Vanguard Center of the Women’s Health Initiative, which is evaluating low-fat diet, postmenopausal hormones, and calcium/vitamin E supplementation among 70,000 women nationwide.
Jeffrey Blumberg
Dr. Blumberg joins the HCRNC renewal as a new Investigator. As Associate Director of the USDA Nutrition Center on Aging at Tufts, he adds an additional link between the two Centers. His research is as follows. The generation of reactive oxygen and nitrogen species during cellular metabolism is affected by environmental factors, including diet and physical activity, and appears to play a critical role in the aging process. High dietary intakes of antioxidants are associated with better maintenance of physiologic function and a lower prevalence of many degenerative conditions in older adults. He works to understand how antioxidants reduce oxidative stress and impacts on the pathogenesis of chronic disease and translates this information into opportunities for health promotion and medical nutrition in an aging population. Dr. Blumberg also examines biomarkers of oxidative stress as they are used to define dietary antioxidants and apply them to the examination of flavonoids, a class of polyphenolic phytochemicals. Their research focuses on the potential role of flavonoids in diet by studying their bioavailability, metabolism, antioxidant activity, and interactions with other dietary antioxidants. By providing quantitative data on biomarkers of oxidative stress as measures of dietary antioxidant requirements, his research may help substantiate and improve the scientific basis for the Dietary Guidelines for Americans and help provide a basis for Dietary Reference Intakes for flavonoids, particularly with regard to the needs of older adults. Further, his research on flavonoids is providing new information useful for the selection and production of plant cultivars rich in those compounds found to be most bioavailable and bioactive.
Catherine Gordon
Dr. Gordon joins the HCNRC renewal as a new Investigator after receiving a P/F award as an Associate Investigator in the previous funding period. The P/F award was instrumental in her RO1 funding. She now directs the Children’s Hospital Bone Health Center. The focus of her research group is the effect of nutrition on bone. Examples of ongoing protocols are: risk factors associated with vitamin D deficiency in infants and toddlers (a follow-up study to a protocol recently completed in adolescents); anorexia nervosa, inflammatory bowel disease and cystic fibrosis as models of malnutrition’s effects on bone; and studies examining factors that influence the acquisition of peak bone mass. In all of these protocols, her group is interested in genotypes that predict both bone density and skeletal responses to specific interventions. She is also exploring new technologies to evaluate bone density, including quantitative ultrasound and hip structural analysis of dual energy x-ray absorptiometry bone density measurements. She works closely with Drs. Goodman, Field, Miller, Klibanski, Grinspoon and Holick. She uses the Mass Spectrometry Core and Biostatistics Program.
Christos Mantzoros
Dr. Mantzoros joins the HCNRC renewal as a new Investigator. His junior faculty member, Dr. Jean Chan, was awarded a P/F grant in 2004. There is evidence that the abnormalities in the reproductive and other neuroendocrine axes associated with hypothalamic amenorrhea (HA) are related to negative energy balance. Levels of leptin, an adipocyte-secreted hormone that circulates at levels corresponding to fat mass and provides a signal of energy availability to the central nervous system, are low in HA. Leptin replacement in leptin-deficient animals and humans results in normalization of reproductive and other neuroendocrine defects in these models. In a recent “proof-of-concept” pilot study published in The New England Journal of Medicine and funded in part by the HCNRC Pilot Feasibility Program, Dr. Mantzoros and Chan have demonstrated that administration of replacement-dose recombinant human leptin (r-metHuLeptin) to women with hypothalamic amenorrhea and low leptin levels resulted in ovulatory menstrual cycles, follicular growth, and improvement of reproductive, thyroid, and IGF hormones as well as bone formation markers (APPENDIX C1 – representative reprints). They plan to conduct a randomized, double-blind, placebo-controlled, r-metHuLeptin administration study, which will part of a 2006 HCNRC Pilot Feasibility application, to test the hypothesis that low leptin levels contribute to the etiology of amenorrhea, infertility, and bone loss observed in these women. The primary endpoint will be assessment of bone mineral density, and secondary outcomes will include hormone and bone marker levels, evidence of ovulatory menstrual cycles, immunologic function, body composition, resting metabolic rate, and overall sense of well-being, appetite, and food intake.
Dr. Herzog continues as an Investigator in the HCNRC renewal. He is an international authority on anorexia nervosa. He works closely with several investigators and associate investigators to determine the consequences of malnutrition and the absence of estrogen and insulin-like growth factors on nutritional health. He helps coordinate a multicenter study on osteoporosis in women with eating disorders.
William Christen
Dr. Christen joins the HCNRC renewal as a new Investigator. He was attracted to the Center by the P/F program in which he was funded in 2004-2005 as a Type III applicant. His primary interest is in epidemiologic evidence for antioxidant supplements in women’s health, particularly in age-related macular degeneration. His has extensively NIH support to study chronic disease in the Nurses’ Health Study and the Physician’s Health Study.
Biographical sketch forthcoming.