Does mercury exposure from fish consumption increase the risk of cardiovascular disease? Probably.  Depends on how much mercury exposure and dietary selenium levels.

In a recent article published by the New England Journal of Medicine, researchers "found no evidence of any clinically relevant adverse effects of mercury exposure on coronary heart disease, stroke, or total cardiovascular disease in U.S. adults and the exposure levels seen in the study (1)." The study was funded by the National Institutes of Health.  Popular press reported the findings as if they apply to everyone.   http://www.medscape.com/viewarticle/739537 ; This is unfortunate.  A careful review of the findings indicates that the cohorts that were studied comprised largely of white, educated U.S. adults.  

During our review of this highly publicized article, we noted that the authors did observe trends toward lower cardiovascular disease risk in women with higher mercury exposures.  We scratched our heads to try to understand how this finding could be found.  We reviewed the publication and found the researchers did a wonderful job of collecting data on the demographic characteristics, risk factors, and lifestyle habits of the 51,529 men and 121,700 women whose toenail clippings had been collected between 1982 and 1987.  They looked at smoking habits, family history of myocardial infarction, hypertension, diabetes, body mass index, alcohol consumption, physical activity levels, dietary intake of fish, protein, cholesterol and whole grains.  Of the men and women who particpated in the study, the researchers identified 3,427 cases who had either died of a heart attack or stroke or developed non-fatal cardiovascular disease and matched them to healthy risk-set-sampled controls according to age, sex, race and smoking status. They analzyed the previously collected and stored toe nail clippings for both mercury and selenium.  The purpose of analyzing the toenail clippings for mercury was to determine whether mercury exposures may have contributed to the risk of developing cardiovascular disease.  The purpose of analyzing the toenail clippings for selenium was to determine whether selenium may have offered protection against mercury toxicity.  Because selenium is thought to provide protection against some forms of mercury exposure, the researchers restricted their analyses to participants with lower selenium toenail concentrations.  Despite lower selenium toenail concentrations, the researchers still found lower cardiac risk with higher mercury exposures in women (1). To explain the trends toward lower cardiovascular risk with higher mercury exposure in women, the researchers stated the "sex difference was probably due to chance."  Here is where it gets dicey.  If the authors had looked at the Se:Hg ratios, as we did, then they may have determined that the sex difference was not at all due to chance but instead due to the fact that the Se:Hg  ratio was higher for the women than the men. This higher Se:Hg ratio in women may explain the lower cardiovascular risk observed with higher mercury exposures in women.

We conducted a thorough analysis of the toenail data provided by Mozaffarian D et al. in their recent article (1) to reveal that with increasing mercury levels and decreasing selenium levels in the worst case scenario, the Se:Hg ratio is still significantly higher for women than men in these cohorts.  The table below provides our analyses of the data gathered by Mozaffarian with our calculations for the Se:Hg ratios: 

Mozaffarian D et al. Toenail Data and FIHRI Calculations of Se:Hg Ratios

A recently published article describes a mercury toxicity model that explains in detail the conditions under which mercury may become toxic (2). One condition may occur when the glutathione (GSH) system is disrupted by excessive mercury levels.  Mercury affects the bioavailability and retention of selenium and interferes with the metabolic processes dependent on selenium in human populations (3).  Glutathione peroxidase is dependent on selenium and a key player in the GSH system.  Low red-cell glutathione peroxidase levels are independently associated with an increased risk of cardiovascular events (4).  Higher mercury exposure levels than those found by Mozaffarian D et al. could indeed contribute to the development of cardiovascular disease, especially in the setting of selenium deficiency. In fact, Mozaffarian D et al. say as much in their conclusion (1). It is important to remember that this study was conducted largely on white, educated U.S. adults.  According to 2010 U.S. Census data, only 73% of Americans are white (5). These findings cannot be generalized to apply to Americans in other ethnic groups that consume far more fish and have greater mercury exposures such as those found in a study published by Dr. Jane Hightower in 2006 (6).  This study is extremely useful however in revealing that in determining the risk of cardiovascular disease that may be associated with excessive mercury exposure, the ratio of Se:Hg levels in toenail clippings may potentially be used as a biomarker.     

This analyses was provided by the following researchers:

Renee Dufault, MAT, Food Ingredient and Health Research Institute

David Wallinga, MD, Institute for Agriculture and Trade Policy

Walter Lukiw, PhD, Department of Neuroscience, LSU Neuroscience Center 

References: 

(1)     Mozaffarian D, Shi P, Morris JS et al. Mercury exposure and risk of cardiovascular disease in U.S. cohorts. N Engl J Med 2011;364:1116-25. http://www.ncbi.nlm.nih.gov/pubmed/21428767 

(2), Dufault R, Schnoll R, Lukiw WJ et al. Mercury exposure, nutritional deficiencies and metabolic disruptions may affect learning in children. Behavioral and Brain Functions 2009;5:44. http://www.behavioralandbrainfunctions.com/content/5/1/44

(3)    Chen C, Yu H, Zhao J et al. The roles of serum selenium and selenoproteins on mercury toxicity in environmental and occupational exposures. Environ Health Perspect 2006;114(2):297-301.

(4)    Blankenberg S, Rupprecht HJ, Bickel C et al. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 2003;349:1605-13.

(5)    U.S.Census Bureau. Overview of race and hispanic origin:2010. http://www.census.gov/prod/cen2010/briefs/c2010br-02.pdf

(6)   Hightower JM, O'Hare A, Hernandez GT. Blood mercury reporting in NHANES:identifying Asian, Pacific Islander, Native American, and multiracial groups. Environmental Health Perspectives. 2006;114(2):173-5.  http://www.medscape.com/viewarticle/524288