Joel Evans, MD discusses various studies focused on pesticide exposure, obesity and dementia, B-vitamins, and pregnancy.

by Joel M. Evans, MD

Pesticide Exposure and Risk of Parkinson’s Disease: A Family-Based Case-Control Study

BMC Neurol. 2008 Mar 28;8(1):6

Hancock DB, Martin ER, Mayhew GM, Stajich JM, Jewett R, Stacy MA, Scott BL, Vance JM, Scott WK

Background: Pesticides and correlated lifestyle factors (e.g., exposure to well-water and farming) are repeatedly reported risk factors for Parkinson’s disease (PD), but few family-based studies have examined these relationships.

Methods: Using 319 cases and 296 relative and other controls, associations of direct pesticide application, well-water consumption, and farming residences/occupations with PD were examined using generalized estimating equations while controlling for age-at-examination, sex, cigarette smoking, and caffeine consumption.

Results: Overall, individuals with PD were significantly more likely to report direct pesticide application than their unaffected relatives (odds ratio=1.61; 95% confidence interval, 1.13-2.29). Frequency, duration, and cumulative exposure were also significantly associated with PD in a dose-response pattern (p<0.013). Associations of direct pesticide application did not vary by sex but were modified by family history of PD, as significant associations were restricted to individuals with no family history. When classifying pesticides by functional type, both insecticides and herbicides were found to significantly increase risk of PD. Two specific insecticide classes, organochlorines and organophosphorus compounds, were significantly associated with PD. Consuming well-water and living/working on a farm were not associated with PD.

Conclusions: These data corroborate positive associations of broadly defined pesticide exposure with PD in families, particularly for sporadic PD. These data also implicate a few specific classes of pesticides in PD and thus emphasize the need to consider a more narrow definition of pesticides in future studies.

Comment: This study is important because it looks closely at the link between pesticide exposure and Parkinson’s disease (PD) in families while controlling for family history. This is important to study because many practitioners associate the link between PD and pesticides to be true only for a subgroup of the population with abnormalities (SNP’s) in particular detoxification genes. What this study showed is that people with any exposure to pesticides (defined by any application, even with protective gear) and no family history (to eliminate the possibility of genetic influence) had an increased risk of PD up to 1.6 fold. The greater the exposure, the greater the incidence PD, but minimal exposure was still associated with a statistically significant increase in PD. The important point of this study is that pesticide application is risky even with protective gear, and holistic practitioners must get a detailed history of pesticide exposure and application (even in childhood) from all patients, especially those with neurologic disease, cancer and other chronic diseases or symptom complexes.

Central Obesity and Increased Risk of Dementia More Than Three Decades Later

Neurology, first published online before publication on March 26, 2008 as doi:10.1212/01.wnl.0000306313.89165.ef

R. A. Whitmer PhD*, D. R. Gustafson PhD, E. Barrett-Connor MD, M. N. Haan DrPH, E. P. Gunderson PhD, and K. Yaffe MD

Background: Numerous reports show that a centralized distribution of adiposity is a more dangerous risk factor for cardiovascular disease and diabetes than total body obesity. No studies have evaluated whether the same pattern exists with dementia. The objective was to evaluate the association between midlife central obesity and risk of dementia three decades later.

Methods: A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, January 1, 1994, to June 16, 2006. Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted.

Results: A total of 1,049 participants (15.9%) were diagnosed with dementia. Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33–3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58–2.35). Those with high SAD (>25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98–3.81) vs those with low SAD (<25 cm) and normal BMI (18.5–24.9 kg/m2), whereas those both obese (BMI >30 kg/m2) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI, 2.85–4.55).

Conclusions: Central obesity in midlife increases risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled.

Comment: This is study describes yet another consequence of the obesity epidemic: dementia. A long term longitudinal analysis (average of 36 years) of over 6,500 middle aged men and women conclusively demonstrated that an increase in central obesity is associated with an increase in dementia in later life. This is independent of Body Mass Index (BMI), showing that increased abdominal obesity increased dementia risk even in the presence of a normal BMI.  This finding is important for many reasons. First, as we study the consequences of the obesity epidemic, this is the first study to look at the impact on dementia. Second, the importance of measuring abdominal fat, which is representative of visceral adipose tissue (VAT), rather than BMI is again emphasized.  Finally, though the authors state that the mechanisms need to be elucidated, there is enough science documenting the metabolically active nature of visceral adipose tissue (VAT) and the functional imbalances of Alzheimer’s disease (AD) to feel comfortable about the mechanisms. As just one example, most holistic practitioners are aware of the well documented pro-inflammatory nature of VAT and the link between inflammation and AD. Thus, this article provides another example of the effect of obesity to disruption to normal bodily function.

B-Vitamins Reduce Plasma Levels of Beta Amyloid

Neurobiol Aging, 2008; 29(2): 303-5

Flicker L, Martins RN, Thomas J, Acres J, Taddei K, Vasikaran SD, Norman P, Jamrozik K, Almeida OP

Elevated plasma homocysteine (tHcy) is a risk factor for Alzheimer’s disease (AD), and thus B vitamins may have a role in the prevention of AD. The objective of this study was to determine if tHcy lowering vitamins decrease the circulating levels of A-beta protein 1-40 (A beta 40). We randomized 299 older men to treatment with 2mg of folate, plus 25mg of B6 and 400 microg of B12, or placebo. After 2 years of treatment the mean (S.E.) increase of A beta 40 was 7.0 pg/ml (8.4) in the vitamin group (4.9%), and 26.8 pg/ml (7.7) (18.5%) in the placebo group. We conclude that B vitamins may decrease the plasma level of A beta 40 and have a role in the prevention of AD.

Comment: I chose this study as a complement to the previous one to show that there are additional relationships in the functional medicine web that relate to dementia. We are all aware of the well described relationship of elevated homocysteine, an indicator of reduced methylation capacity, to AD. Here the authors designed a study to test the hypothesis that treating older men with a group of vitamins known to lower homocysteine (folate, B6, and B12) for two years can reduce the amount of the normal age related increase in a substance (A-beta protein 1-40) that is a constituent of the amyloid plaques found in the brains of AD patients. What they found is that the vitamin regimen decreased the increase of A-beta 40 by almost 66%, a significant decrease. This study gives additional support to the importance of B vitamins in the prevention of AD, which is important to remember in light of the previous study on the connection of central obesity and dementia.

Omega-3 Fatty Acids for Major Depressive Disorder During Pregnancy: Results From a Randomized, Double-Blind, Placebo-Controlled Trial

J Clin Psychiatry March 18, 2008: e1-e8; pii: ej07m03646

Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC, Pariante CM

From the Department of Psychiatry and Mind-Body Interface Research Centre (Drs. Su and C-L Huang) and the Department of Obstetrics and Gynecology (Dr. Chiu), China Medical University Hospital, Taichung, Taiwan; the School of Nutrition and Health Sciences (Drs. Su and S-Y Huang) and the School of Health Care Administration (Drs. K-C Huang and Chang), Taipei Medical University, Taipei, Taiwan; and the Institute of Psychiatry, King’s College London, United Kingdom (Drs. Su and Pariante and Ms. Chang).

Background: Perinatal depression is common, and treatment remains challenging. Depression has been reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs). A profound decrease of omega-3 PUFAs in the mother during pregnancy is associated with the higher demand of fetal development and might precipitate the occurrence of depression. In this study, we examined the efficacy of omega-3 PUFA monotherapy for the treatment of depression during pregnancy.

Method: From June 2004 to June 2006, we conducted an 8-week, double-blind, placebo-controlled trial comparing omega-3 PUFAs (3.4 g/d) with placebo in pregnant women with major depressive disorder (DSM-IV criteria). No psychotropic agent was given 1 month prior to or during the study period. The Hamilton Rating Scale for Depression (HAM-D) was scored every other week as the primary measurement of efficacy, while the Edinburgh Postnatal Depression Scale (EPDS) and Beck Depression Inventory (BDI) were secondary measures.

Results: Thirty-six subjects were randomly assigned to either omega-3 PUFAs or placebo, and 33 among them were evaluated in more than 2 visits. A total of 24 subjects completed the study. As compared to the placebo group, subjects in the omega-3 group had significantly lower HAM-D scores at weeks 6 (p = .001) and 8 (p = .019), a significantly higher response rate (62% vs. 27%, p = .03), and a higher remission rate, although the latter did not reach statistical significance (38% vs. 18%, p = .28). At the study end point, subjects in the omega-3 group also had significantly lower depressive symptom ratings on the EPDS and BDI. The omega-3 PUFAs were well tolerated and there were no adverse effects on the subjects and newborns.

Conclusions: Omega-3 PUFAs may have therapeutic benefits in depression during pregnancy. In regard to the safety issue and psychotherapeutic effect, as well as health promotion to mothers and their newborns, it is worthy to conduct replication studies in a larger sample with a broad regimen of omega-3 PUFAs in pregnant women with depression.

Trial Registration: Identifier: NCT00618865.

Comment: Clinicians that care for women of childbearing age are frequently asked about their opinion on antidepressants. The time honored philosophy that medication during preconception and pregnancy should be used only when necessary and only when the benefits outweigh the risks, combined with recent studies documenting the issues associated with neonatal health (respiratory and behavioral problems) in infants whose mothers took antidepressants during pregnancy, creates a dilemma for the clinician in managing the patient with diagnosed depression or depressive symptoms. This study helps practitioners looking for a safe and effective alternative to antidepressants by showing that omega 3 essential fatty acids may have therapeutic benefits in pregnancy. There is much literature on omega 3’s, pregnancy and depression with mixed reports of efficacy. It is nice to see this study documenting a high response rate, lending literature support for the clinical practice of using omega 3’s as a closely monitored intervention in this group of patients.

Additional articles from Joel M. Evans, M.D.:

Joel M. Evans, M.D. is an Assistant Clinical Professor of Obstetrics, Gynecology and Women’s Health at Albert Einstein College of Medicine. He is also the author of The Whole Pregnancy Handbook (Gotham 2005).