Yang J-H, Lee Y-M, Bae S-G, Jacobs DR, Lee D-H. Associations between organochlorine pesticides and vitamin D deficiency in the US population. PLoS ONE. 2012;7(1):1-5.
Researchers studied 1,275 adults from the 2003–2004 federal National Health and Nutrition Examination Survey for potential association between serum levels of organochlorine pesticides and vitamin D levels.
Serum levels of 13 organochlorine (OC) pesticides were measured and compared with serum levels of 25-(OH) vitamin D. Statistical analysis was carried out using general linear models. Serum concentrations of OC pesticides were ranked into quintiles. Serum 25-(OH)D levels were log transformed due to a right-skewed distribution. General additive models were also used to assess the possibility of a nonlinear spline across the range of OC pesticide concentrations. Numerous demographic and behavioral variables were taken into account.
Among 7 OC pesticides found in >80% of participants, serum p,p’-DDT, p,p’DDE (a storage metabolite of DDT) and ß-hexachlorocyclohexane (a storage metabolite of Lindane) showed significant inverse associations with serum 25-(OH)D (P<0.01). These associations were particularly strong in the top 10% of OC pesticide concentrations, but there was a U-shaped curve in which the highest concentrations of p,p’-DDT were associated with increasing serum concentrations of 25-(OH)D.
Given the Centers for Disease Control and Prevention’s 2000 statement that “virtually all human chronic illness results from the interaction between genetic susceptibility and environmental exposure,”1 the physiologic impact of OC pesticides is clinically significant. DDT and DDE have been linked to diabetes,2 cancer and endocrine disruption,3 neurotoxicity,4 and developmental abnormalities, to mention only a few. Lindane is neurotoxic and probably carcinogenic6 and associated with developmental defects.7 Much clinical literature addresses the impact of OC on these illnesses.
The possible impact of OC on vitamin D levels has not been addressed in humans. Since vitamin D deficiency has also been associated with many diseases,8 diminution of vitamin D levels gives OC pesticides yet another layer of potential toxicity.
The authors’ main focus was the role of vitamin D deficiency in inducing various diseases and assessment of the possible role of OC pesticides in inducing vitamin D deficiency. They did not address the independent toxicities of the OC pesticides they studied.
They speculated that endocrine disruption was the mechanism by which OC pesticides reduced serum 25-(OH) D levels. This ignores a more obvious mechanism: OC pesticides upregulate various cytochromes involved in vitamin D catabolism, particularly CYP 3A4.9,10 Upregulation of those cytochromes would increase the rate of destruction of serum vitamin D, thereby most likely decreasing serum 25-(OH) D levels, independently of endocrine disruption.
Another weakness of the study is the fact that the study assessed serum levels of OC pesticides and vitamin D, and although a final position paper by the World Health Organization has yet to be approved, their draft statement has stated that there may be 100 times higher concentration of OC pesticides in fatty tissues than in serum.11 Hence, it would seem serum levels of OC pesticides do not reflect body burden and therefore may not accurately reflect physiological impact.
They conclude that further investigation might determine whether avoidance of OC pesticides might decrease the risk of vitamin D deficiency-related diseases.
The authors noted other limitations of their study. First, they could not rule out the possibility that low 25-(OH)D levels caused the higher OC serum concentrations, but they were unaware of any studies showing a role for vitamin D in clearance of OC pesticides. There are none, as far as I can determine. Second, they could not correct for sunlight exposure or latitude, which are major variables influencing serum 25-(OH) D levels.
They conclude that further investigation might determine whether avoidance of OC pesticides might decrease the risk of vitamin D deficiency–related diseases. While this is an interesting suggestion and implies that vitamin D deficiencies should especially be looked for in gardeners, golfers, and others commonly exposed to OC pesticides, it ignores the fact that OC pesticides have well-documented toxicity independent of any vitamin D effect and are best avoided for that reason alone.
1. Gene-Environment Interaction Fact Sheet. Washington, DC: Centers for Disease Control, Department of Health and Human Services; August 2000.
2. Turyk M, Anderson H, Knobeloch L, Imm P, Persky V. Organochlorine exposure and incidence of diabetes in a cohort of Great Lakes sport fish consumers. Environ Health Perspect. 2009;117(7):1076-1082.
3. Rogan WJ, Chen A. Health risks and benefits of bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT). Lancet. 2005;366(9487):763–773.
4. Ribas-Fitó N, Torrent M, Carrizo D, et al. In utero exposure to background concentrations of DDT and cognitive functioning among preschoolers. Am J Epidemiol. 2006;164(10):955–962.
5. Weselak M, Arbuckle TE, Foster W. Pesticide exposures and developmental outcomes: the epidemiological evidence. J Toxicol Environ Health B Crit Rev. 2007;10(1-2):41-80.
6. Toxicologic profile for alpha-, beta, gamma- and delta-hexachlorocyclohenxane. Atlanta, GA: Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services. August 2005.
7. Alvarez-Pedrerol M, Ribas-Fitó N, Torrent M, et al. Thyroid disruption at birth due to prenatal exposure to beta-hexachlorocyclohexane. Environ Int. 2008;34(6):737-740.
8. Holick MF . Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281.
9. Medina-Diaz IM, Arteaga-Illan G, Bermudez de Leon M, et al. Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p’-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane. Drug Metab Dispos. 2007;35(1):95-102.
10. Wang Z, Lin YS, Zheng XE, et al. An inducible cytochrome P450 3A4-dependent vitamin D catabolic pathway. Mol Pharmacol. 2012;81(4):498-509.
11. World Health Organization. Draft DDT Health Hazard Assessment. 2008; p. 8