Milk intake in midlife was associated with substantia nigra neuron loss, as measured at autopsy, in individuals unaffected by Parkinson disease (PD), data from the Honolulu-Asia Aging Study (HAAS) indicated.
Whether contamination of milk with organochlorine pesticides such as heptachlor epoxide (found at excessively high levels in the milk supply in Hawaii in the early 1980s) has a role in substantia nigra neurodegeneration warrants further study, Robert D. Abbott, PhD, and colleagues reported online in Neurology.
Abbott is with Shiga University of Medical Science in Otsu, Japan, and the Pacific Health Research and Education Institute in Honolulu.
"While past reports [including HAAS] have found an association between dairy products, including milk intake, and higher PD risk, current findings suggest that the relationship can begin with early nigral neurodegeneration prior to the onset of clinical PD, and may involve a link with heptachlor epoxide," said the investigators. "Although generalizability to women and other ethnicities is difficult to confirm, the link is reasonable for Hawaii, where contamination of the milk supply with heptachlor epoxide is well-documented."
Neuron density in the ventrolateral, ventromedial, and dorsolateral quadrants of the substantia nigra was 41.5% lower for those who consumed more than 16 ounces of milk per day than it was for those who consumed less (95% CI 22.7%–55.7%, p<0.001), the study showed. In decedents who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p=0.017). For those who were ever smokers, an association between milk intake and neuron density was absent, said the investigators.
This finding coincides with a previous report by Abbott and colleagues on clinical PD in which the presence of significant interaction between milk intake and pack-years of cigarette smoking was absent. Reanalysis of that data showed that milk intake of more than 16 ounces per day continued to be strongly associated with an increased risk of PD, but only in nonsmokers, said Abbott and colleagues.
"While this is an important omission, it adds support for a neuroprotective effect of cigarette smoking against factors that would otherwise be associated with an increased risk of PD," wrote the authors. "Its role in the current study and in other studies involving environmental exposures and preclinical features of PD warrants consideration."
This study makes heptachlor contamination a plausible culprit for higher PD risk among frequent milk drinkers in HAAS, Honglei Chen, MD, PhD, and Karen Marder, MD, MPH, said in an accompanying editorial. However, they emphasized, the findings need to be taken in context.
"This study may not offer a good explanation for the association of milk or dairy consumption and PD in other cohorts," they emphasized.
Chen and Marder also expressed concern about the fact that accelerated neuron loss was observed only in a relatively small sample size of 12 nonsmokers who drank more than two cups of milk per day. On the other hand, in nonsmokers who drank less than two cups of milk per day, minimal or no neuron loss was observed. "Therefore, the possibility of chance association cannot be excluded," they said.
In addition, milk consumption was only assessed once, at enrollment. "We have to assume that this measurement represented participants' dietary habits over time," said Chen and Marder. "Further, it is unclear whether milk consumption is related to incidental Lewy bodies or prodromal symptoms, such as the sense of smell, among individuals without clinical PD."
Finally, the study did not demonstrate that brain heptachlor came from milk and not other sources, they pointed out. (Abbott and colleagues acknowledged they lacked evidence that the actual milk consumed by study decedents was in fact contaminated with heptachlor epoxide.)
Despite these issues, the study has demonstrated the value of epidemiologic studies to explore potential causal mechanisms underlying PD, and underscores the importance of environmental data collection, concluded Chen and Marder.