naturopathydigest.com -- Critical Research

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Critical Research

This is the first installment of what will be a regular feature in Naturopathy Digest. Each month, we will print abstracts from studies published in the top peer-reviewed journals; each abstract will include the complete citation and an online link to the journal. Whenever possible, this link directs you to a page where you can order the full text of the study, if desired.

Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite.

Michael Platten, Peggy P. Ho, Sawsan Youssef, et al.

Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (T_H1) cytokines. N-(3,4,-Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating T_H1-mediated autoimmune diseases such as MS.

Source: Science, Nov. 4, 2005:310(5749):850-55.

The risk of lymphoma development in autoimmune diseases: a meta-analysis.

Elias Zintzaras, PhD; Michael Voulgarelis, MD, PhD; Haralampos M. Moutsopoulos, MD, FACP, FRCP

Background: The risk of development of non-Hodgkins lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren syndrome (pSS) to the risk of NHL development.

Methods: We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sjögren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis.

Results: The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P<.01; I²>70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively.

Conclusions: Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.

Source: Archives of Internal Medicine, Nov. 14, 2005;165(20):2337-2344.

Nutrition and depression: implications for improving mental health among childbearing-aged women.

Lisa M. Bodnar and Katherine L. Wisner

Adequate nutrition is needed for countless aspects of brain functioning. Poor diet quality, ubiquitous in the United States, may be a modifiable risk factor for depression. The objective was to review and synthesize the current knowledge of the role of nutrition in depression, and address implications for childbearing-aged women. Poor omega-3 fatty acid status increases the risk of depression. Fish oil and folic acid supplements each have been used to treat depression successfully. Folate deficiency reduces the response to antidepressants. Deficiencies of folate, vitamin B₁₂, iron, zinc, and selenium tend to be more common among depressed than nondepressed persons. Dietary antioxidants have not been studied rigorously in relation to depression. Childbearing-aged women are particularly vulnerable to the adverse effects of poor nutrition on mood because pregnancy and lactation are major nutritional stressors to the body. The depletion of nutrient reserves throughout pregnancy and a lack of recovery postpartum may increase a woman's risk of depression. Prospective research studies are needed to clarify the role of nutrition in the pathophysiology of depression among childbearing-aged women. Greater attention to nutritional factors in mental health is warranted given that nutrition interventions can be inexpensive, safe, easy to administer, and generally acceptable to patients.

Source: Biological Psychiatry, Nov. 1, 2005;58(9):679-85.

Prescription of teratogenic medications in United States ambulatory practices.

Eleanor Bimla Schwarz, MD, MS; Judith Maselli, MSPH; Mary Norton, MD; and Ralph Gonzales, MD, MSPH

Purpose: The purpose of this study was to identify the potentially teratogenic medications most frequently prescribed to women of childbearing age and the specialty of physicians who provide ambulatory care to women who use such medications. In addition, we evaluated rates of contraceptive counseling to explore awareness of the risks associated with teratogenic medication use.

Subjects and methods: The prescription of teratogenic medications and provision of contraceptive counseling on 12,681 visits made by nonpregnant women, 14 to 44 years of age, to 1,880 physicians in U.S. ambulatory practice (National Ambulatory Medical Care Survey) between 1998 and 2000 was analyzed.

Results: Use of a potentially teratogenic, class D or X, medication by a woman of childbearing age is documented on 1 of every 13 visits made to U.S. ambulatory practices. These include anxiolytics (4.1 million annual prescriptions), anticonvulsant medications (1.4 million annual prescriptions), antibiotics like doxycycline (1.4 million annual prescriptions), and statins (0.8 million annual prescriptions). Isotretinoin accounts for less than 5% of potentially teratogenic prescriptions (0.5 million annual prescriptions). Internists and family/general practitioners provide ambulatory care to 45% of women prescribed potentially teratogenic medications, psychiatrists provide ambulatory care to 20% of women prescribed potentially teratogenic medications, and dermatologists provide ambulatory care to 20% of women prescribed potentially teratogenic medications. Contraceptive counseling was provided on less than 20% of visits that documented use of a potential teratogen by a woman of childbearing age. Women using low-risk (class A or B) drugs received contraceptive counseling as frequently as women using potential teratogens (P = .24).

Conclusion: Potentially teratogenic medications are prescribed to millions of women of childbearing age each year. Physician awareness of the teratogenic risk associated with class D or X medications seems low.

Source: The American Journal of Medicine November 2005;118(11):1240-49.

Avoiding milk is associated with a reduced risk of insulin resistance and the metabolic syndrome: findings from the British Women's Heart and Health Study.

D. A. Lawlor, S. Ebrahim, N. Timpson and G. Davey Smith

Objective: To examine the association of milk consumption with insulin resistance and the metabolic syndrome.

Methods: The association was examined in 4,024 British women ages 60-79 who were randomly selected from primary care centers in 23 towns.

Results: Women who never drank milk had lower homeostasis model assessment insulin resistance (HOMA) scores, triglyceride concentrations and body mass indices, and higher high-density lipoprotein (HDL)-cholesterol concentrations, than those who drank milk. The age-adjusted odds ratio for the metabolic syndrome comparing non-milk drinkers with drinkers was 0.55 (0.33, 0.94), which did not attenuate with adjustment for potential confounders. Diabetes was less common in non-milk drinkers.

Conclusion: Individuals who do not drink milk may be protected against insulin resistance and the metabolic syndrome. However, randomized controlled trials are required to establish whether milk avoidance is causally associated with these outcomes.

Source: Diabetic Medicine June 2005;22(6):808-11.

Milk, milk products and lactose intake and ovarian cancer risk: a meta-analysis of epidemiological studies.

Susanna C. Larsson , Nicola Orsini, Alicja Wolk. Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden

It has been proposed, on the basis of animal models and ecological studies, that consumption or metabolism of dairy sugar may increase the risk of ovarian cancer. Case-control and cohort studies of the association between lactose and dairy food consumption and ovarian cancer risk, however, have yielded varied findings. We summarized the available literature on this topic using a meta-analytic approach. Random-effects models were used to estimate the summary relative risks. A linear regression analysis of the natural logarithm of the RR was carried out to assess a possible dose-response relationship between lactose intake and ovarian cancer risk. Eighteen case-control and 3 prospective cohort studies were eligible for inclusion in the meta-analysis. The findings of case-control studies were heterogeneous, and, except for whole milk summary relative risk for highest vs. lowest category = 1.27, 95% confidence interval [CI] = 0.97-1.68), do not provide evidence of positive associations between dairy food and lactose intakes with risk of ovarian cancer. In contrast, the 3 cohort studies are consistent and show significant positive associations between intakes of total dairy foods, low-fat milk, and lactose and risk of ovarian cancer. The summary relative risk for a daily increase of 10 g in lactose intake (the approximate amount in 1 glass of milk) was 1.13 (95% CI = 1.05-1.22) for cohort studies. In conclusion, prospective cohort studies, but not case-control studies, support the hypothesis that high intakes of dairy foods and lactose may increase the risk of ovarian cancer.

Source: International Journal of Cancer, Jan. 15, 2005;118(2):431-41.

Significant spinal injury resulting from low-level accelerations: a case series of roller coaster injuries.

Michael D. Freeman, PhD, DC, MPH; Arthur C. Croft, DC, MPH, MS; Clarence N. Nicodemus, PhD; Christopher J. Centeno, MD; Whitney L. Elkins, MPH

Objectives: To describe a cohort of significantly injured roller coaster riders and the likely levels of acceleration at which the injuries occurred, and to compare these data with contemporary efforts to define a lower limit of acceleration below which no significant spinal injury is likely to occur.

Design: A retrospective case series of roller coaster ride-induced significant spinal injuries.

Setting: Injury incident records and emergency medical service records for the Rattler roller coaster in San Antonio, Texas, were evaluated for a 19-month period in 1992 and 1993. Medical records for the more significant injuries were also reviewed and the specific injuries were tabulated, along with the demographics of the cohort.

Participants: There were 932,000 riders of the Rattler roller coaster, estimated to represent between 300,000 and 600,000 individual riders.

Main Outcome Measures: Injury incident reports and medical record review.

Results: It is estimated that there were a total of 656 neck and back injuries during the study period, and 39 were considered significant by the study inclusion criteria. Seventy-two percent (28/39) of the injured subjects sustained a cervical disk injury; 71% of these injuries were at C5-6 (15 disk herniations, 5 symptomatic disk bulges) and 54% were at C6-7 (11 disk herniations, 4 symptomatic disk bulges). In the lumbar spine, the most frequent injury was a symptomatic disk bulge (20% of the cohort), followed by vertebral body compression fracture (18%), and L4-5 or L5-S1 disk herniation (13%). Accelerometry testing of passengers and train cars indicated a peak of 4.5 to 5g of vertical or axial acceleration and 1.5g of lateral acceleration over approximately 100ms (0.1s) on both.

Conclusions: The results of this study suggest that there is no established minimum threshold of significant spine injury. The greatest explanation for injury from traumatic loading of the spine is individual susceptibility to injury, an unpredictable variable.

Source: Archives of Physical Medicine and Rehabilitation November 2005;86(11):2126-2130.

Magnesium intake in relation to risk of colorectal cancer in women.

Susanna C. Larsson, MSc; Leif Bergkvist, MD, PhD; Alicja Wolk, DMSc

Context: Animal studies have suggested that dietary magnesium may play a role in the prevention of colorectal cancer, but data in humans are lacking.

Objective: To evaluate the hypothesis that a high magnesium intake reduces the risk of colorectal cancer in women.

Design, setting and participants: The Swedish Mammography Cohort, a population-based prospective cohort of 61,433 women ages 40 to 75 years without previous diagnosis of cancer at baseline from 1987 to 1990.

Main outcome measure: Incident invasive colorectal cancer.

Results: During a mean of 14.8 years (911,042 person-years) of follow-up, 805 incident colorectal cancer cases were diagnosed. After adjustment for potential confounders, we observed an inverse association of magnesium intake with the risk of colorectal cancer (P for trend = .006). Compared with women in the lowest quintile of magnesium intake, the multivariate rate ratio (RR) was 0.59 (95% confidence interval [CI], 0.40-0.87) for those in the highest quintile. The inverse association was observed for both colon (RR, 0.66; 95% CI, 0.41-1.07) and rectal cancer (RR, 0.45; 95% CI, 0.22-0.89).

Conclusion: This population-based prospective study suggests that a high magnesium intake may reduce the occurrence of colorectal cancer in women.

Source: Journal of the American Medical Association, Jan. 5, 2005;293(1):86-89.

Magnesium intake and reduced risk of colon cancer in a prospective study of women.

Aaron R. Folsom and Ching-Ping Hong. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota.

A recent prospective study among Swedish women suggested an inverse association of dietary magnesium intake with incidence of colorectal cancer. The authors assessed this association in a cohort of 35,196 Iowa women initially free of cancer and ages 55-69 years in 1986. Intakes of magnesium and other nutrients were assessed by food frequency questionnaire at baseline. Over 17 years of follow-up through 2002, 1,112 women developed colorectal cancer. After adjustment for age, energy, other nutrients, and risk factors for colorectal cancer, the hazard ratios of colorectal cancer across quintiles of magnesium intake were 1.00, 0.96, 0.83, 0.87, and 0.80 (95% confidence interval: 0.62, 1.03; p_trend = 0.06). The association was largely absent for rectal cancer, but for colon cancer, the hazard ratios were 1.00, 1.00, 0.88, 0.85, and 0.77 (95% confidence interval: 0.58, 1.03; p_trend = 0.04). These findings offer further evidence that a diet high in magnesium may reduce the occurrence of colon cancer among women. If replicated by other observational studies, a clinical trial would be needed to determine whether it is magnesium, specifically, and not other aspects of the contributing foods, that may offer benefit.

Source: American Journal of Epidemiology. Epub ahead of print, Nov. 30, 3005.

The effect of body mass index on global brain volume in middle-aged adults: a cross sectional study.

Michael A. Ward, Cynthia M. Carlsson, Mehul A. Trivedi, Mark A. Sager, and Sterling C. Johnson

Background: Obesity causes or exacerbates a host of medical conditions, including cardiovascular, pulmonary, and endocrine diseases. Recently, obesity in elderly women was associated with greater risk of dementia, white matter ischemic changes, and greater brain atrophy. The purpose of this study was to determine whether body type affects global brain volume, a marker of atrophy, in middle-aged men and women.

Methods: T1-weighted 3D volumetric magnetic resonance imaging was used to assess global brain volume for 114 individuals 40 to 66 years of age (average=54.2 years; standard deviation=6.6 years; 43 men and 71 women). Total cerebrospinal fluid and brain volumes were obtained with an automated tissue segmentation algorithm. A regression model was used to determine the effect of age, body mass index (BMI), and other cardiovascular risk factors on brain volume and cognition.

Results: Age and BMI were each associated with decreased brain volume. BMI did not predict cognition in this sample; however, elevated diastolic blood pressure was associated with poorer episodic learning performance.

Conclusions: These findings suggest that middle-aged obese adults may already be experiencing differentially greater brain atrophy, and may potentially be at greater risk for future cognitive decline.

Source: BMC Neurology 2005;5:23.