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according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
FROM MOVEMENT DISORDERS