Allergic responses to common foods could significantly increase risk of heart disease, cardiovascular death
Antibodies to allergens such as dairy, peanuts may up risk even for people without obvious food allergies, surprising new research reveals
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UVA HEALTH'S JEFFREY WILSON, MD, PHD, AND COLLABORATORS HAVE DISCOVERED AN IMPORTANT AND PREVIOUSLY UNAPPRECIATED CAUSE OF HEART DISEASE: SENSITIVITY TO COMMON FOOD ALLERGENS SUCH AS DAIRY AND PEANUTS. THIS CAN AFFECT BOTH PEOPLE WITH FOOD ALLERGIES AND THOSE WITH NO SYMPTOMS.
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CREDIT: UVA HEALTH
Sensitivity to common food allergens such as dairy and peanuts could be an important and previously unappreciated cause of heart disease, new research suggests – and the increased risk for cardiovascular death includes people without obvious food allergies.
That increased risk could be comparable to – or exceed – the risks posed by smoking, as well as diabetes and rheumatoid arthritis, the researchers report.
UVA Health scientists and their collaborators looked at thousands of adults over time and found that people who produced antibodies in response to dairy and other foods were at elevated risk of cardiovascular-related death. This was true even when traditional risk factors for heart disease, such as smoking, high blood pressure and diabetes, were taken into account. The strongest link was for cow’s milk, but other allergens such as peanut and shrimp were also significant.
The troubling finding represents the first time that “IgE” antibodies to common foods have been linked to increased risk of cardiovascular mortality, the researchers report. The findings do not conclusively prove that food antibodies are causing the increased risk, but the work builds on prior studies connecting allergic inflammation and heart disease.
Approximately 15% of adults produce IgE antibodies in response to cow’s milk, peanuts and other foods. While these antibodies cause some people to have severe food allergies, many adults who make these antibodies have no obvious food allergy. The new research found that the strongest link with cardiovascular death was in people who had the antibodies but continued to consume the food regularly – suggesting they didn’t have a severe food allergy.
“What we looked at here was the presence of IgE antibodies to food that were detected in blood samples,” said researcher Jeffrey Wilson, M.D., Ph.D., an allergy and immunology expert at the University of Virginia School of Medicine. “We don’t think most of these subjects actually had overt food allergy, thus our story is more about an otherwise silent immune response to food. While these responses may not be strong enough to cause acute allergic reactions to food, they might nonetheless cause inflammation and over time lead to problems like heart disease.”
Unexpected Food Allergy Findings
The researchers were inspired to investigate the possibility that common food allergies could be harming the heart after members of the UVA team previously linked an unusual form of food allergy spread by ticks to heart disease. That allergy, first identified by UVA’s Thomas Platts-Mills, M.D., Ph.D., is transmitted by the bite of the lone star tick, found throughout much of the country.
The allergy – commonly if inaccurately called the “red meat allergy” – sensitizes people to a particular sugar, alpha-gal, found in mammalian meat. The symptomatic form of the allergy, known as “alpha-gal syndrome,” can cause hives, upset stomach and breathing difficulties – even potentially deadly anaphylaxis – three to eight hours after affected people eat beef or pork. (Poultry and fish don’t contain the sugar, so they don’t trigger a reaction.)
To see if other food allergies could be affecting the heart, a team including Wilson, Platts-Mills and collaborators from UVA, as well as Corinne Keet, M.D., Ph.D., of the University of North Carolina, reviewed data collected from 5,374 participants in the National Health and Examination Survey (NHANES) and the Wake Forest site of the Multi-Ethnic Study of Atherosclerosis (MESA). Of those people, 285 had died from cardiovascular causes.
Among the NHANES participants, IgE antibodies to at least one food was associated with a significantly higher risk of cardiovascular death, the researchers found. This was particularly true for people sensitive to milk, a finding that held true among the MESA participants as well. Additional analysis also identified peanut and shrimp sensitization as significant risk factors for cardiovascular death in those individuals who routinely ate them.
“We previously noted a link between allergic antibodies to the alpha-gal red meat allergen and heart disease,” Wilson explained. “That finding has been supported by a larger study in Australia, but the current paper suggests that a link between allergic antibodies to food allergens and heart disease is not limited to alpha-gal. In some ways, this is a surprising finding. On the other hand, we are not aware that anyone has looked before.”
Allergies and the Heart
While this is the first time that allergic antibodies to common foods have been linked to cardiovascular mortality, other allergic conditions – such as asthma and the itchy rash known as eczema or atopic dermatitis – previously have been identified as risk factors for cardiovascular disease.
The researchers speculate that allergic antibodies to food may be affecting the heart by leading to the activation of specialized cells, called mast cells. Mast cells in the skin and gut are known to contribute to classic allergic reactions, but they are also found in the cardiac blood vessels and heart tissue. Persistent activation of mast cells could drive inflammation, contributing to harmful plaque buildup that can cause heart attacks or other heart damage, the researchers believe.
The scientists underscore, however, that this is not yet certain. It’s possible that other genetic or environmental factors could be at play. It’s even possible that cardiovascular disease could increase the risk for food sensitization – meaning that heart disease could up your risk for food allergies, rather than the other way round – though the new results suggest this is unlikely.
The researchers are calling for further studies to better understand the implications of their finding before recommending any changes in how doctors treat or manage food allergies.
“This work raises the possibility that in the future a blood test could help provide personalized information about a heart-healthy diet,” Wilson said. “Though before that could be recommended, we still have a lot of work to do understand these findings.”
Findings Published
The researchers have published their findings in the leading allergy journal, the Journal of Allergy and Clinical Immunology. The research team consisted of Keet, Emily McGowan, David Jacobs, Wendy Post, Nathan Richards,
Lisa Workman, Platts-Mills, Ani Manichaikul and Wilson. Wilson and Platts-Mills have received support from Thermo-Fisher/Phadia; a full list of the authors’ disclosures is included in the paper.
The research was supported by the National Institutes of Health’s National Institute of Allergy and Infectious Disease, grants 5U01AI125290, R37-AI20565 and R21AI151497; and by an AAAAI Foundation Faculty Development Award. A list of the financial backers of the MESA trial is available in the paper.
To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.
JOURNAL
Journal of Allergy and Clinical Immunology
ARTICLE PUBLICATION DATE
9-Nov-2023
Antibodies to cow’s milk linked to increased risk of cardiovascular death
Analyses led by Corinne Keet, MD, PhD, at the University of North Carolina School of Medicine, of two longitudinal studies reveal how an increased level of an antibody called immunoglobin (IgE) to cow’s milk is associated to cardiovascular-related death
IMAGE:
CORINNE KEET, MD, PHD, PEDIATRIC ALLERGY AND IMMUNOLOGY PROFESSOR IN THE UNC DEPARTMENT OF PEDIATRICS
view moreCREDIT: UNC SCHOOL OF MEDICINE
Sensitivity to common food allergens such as cow’s milk and peanuts could be an important and previously unappreciated cause of heart disease, new research suggests – and the increased risk for cardiovascular death includes people without obvious food allergies.
In a paper published in The Journal of Allergy and Clinical Immunology that describes analyses led by Corinne Keet, M.D., Ph.D., pediatric allergy and immunology professor in the UNC Department of Pediatrics of two longitudinal studies, the authors show that the people who produced IgE antibodies to cow’s milk and other foods were at significantly increased risk of cardiovascular mortality. This was true even when traditional risk factors for heart disease, such as smoking, high blood pressure, and diabetes were accounted for. The strongest link was for cow’s milk, but IgE to other allergens such as peanut and shrimp were also significant among those who eat the foods.
This troubling finding represents the first time that IgE antibodies to common foods have been linked to increased risk of cardiovascular mortality, the researchers report. The findings do not conclusively prove that food antibodies are causing the increased risk, but the work builds on previous studies connecting allergic inflammation and heart disease.
“People who had an antibody called IgE to foods that they regularly eat seemed to be at increased risk for dying from heart disease,” said Keet, who is the corresponding author of the paper. “We were surprised by these findings because it is very common to have IgE to foods (about 15% of American adults have IgE to common food allergens), and most people don't have any symptoms when they eat the food. As allergists, our thinking has been that it is not important if people have IgE to foods, as long as they don't have symptoms when they eat the food,” she said.
Funded by the National Institute of Allergy and Infectious Disease and an AAAAI Faculty Development Award to her collaborator Jeff Wilson at the University of Virginia, this research used two methods to examine the association between IgE sensitization to foods and cardiovascular mortality. Data from 4,414 adults who participated in The National Health and Examination Survey (NHANES) and 960 participants in the Wake Forest site of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort were used. Participants were enrolled in MESA from 2000-2002 and followed for up to 19 years. Participants were enrolled in NHANES from 2005 to 2006 and data on mortality up to 14 years were tracked. Total and specific IgE was measured to cow’s milk, egg, peanut, shrimp, and a panel of aeroallergens for the NHANES group. IgE to cow’s milk, alpha-gal, peanut, dust mite and timothy grass were measured in the MESA group. In NHANES, 229 cardiovascular deaths were recorded and 960 deaths from MESA were also reported. Milk sensitization was particularly associated in both NHANES & MESA. Researchers also discovered that food sensitization to shrimp and peanut were both additional risk factors for heart disease.
It is also important to note that associations in the findings related to food sensitization rather than clinical allergy. Although researchers did not have access to information about clinical food allergy in either cohort, they expect that individuals who report regularly eating a food allergen on food frequency questionnaires were not showing symptoms of a food allergy. Thus, the findings that showed how associations were strengthened when researchers excluded those who avoided the food suggest that these findings were most relevant to those who have not been diagnosed with food allergy. Keet says the results raise questions about whether these apparently non-allergic individuals may have long-term consequences from consuming foods to which they are sensitized.
The study states that aside from two recent reports linking IgE to the unusual carbohydrate allergen alpha-gal to coronary artery disease, cardiovascular disease had not previously been identified as a long-term complication of food sensitization. However, there is now substantial evidence for the importance of allergic-type immune pathways in normal cardiac physiology and heart disease. Because discovering the link between milk sensitization with cardiovascular mortality is new, Keet says there’s more to explore as far as the relevance of food sensitization and diet in cardiovascular disease development.
“More research needs to be done about how sensitization to common food allergens is related to cardiovascular disease,” she said. “While this study provides good evidence of an association between sensitization to these allergens and death from cardiovascular disease, there is much work to be done to understand if this is a causal relationship.”
Media contact: Brittany T. Phillips, Communications Specialist, UNC Health | UNC School of Medicine
JOURNAL
Journal of Allergy and Clinical Immunology
METHOD OF RESEARCH
Observational study
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Antibodies to Cow’s Milk Linked to Increased Risk of Cardiovascular Death
ARTICLE PUBLICATION DATE
9-Nov-2023
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