Tuesday, April 29, 2025

Receiving a booster vaccine in the same arm as your first dose can generate a more effective immune response more quickly

 Sydney scientists have revealed why receiving a booster vaccine in the same arm as your first dose can generate a more effective immune response more quickly. The study, led by the Garvan Institute of Medical Research and the Kirby Institute at UNSW Sydney and published in the journal Cell, offers new insight that could help improve future vaccination strategies.

The researchers found that when a vaccine is administered, specialised immune cells called macrophages became ‘primed’ inside lymph nodes. These macrophages then direct the positioning of memory B cells to more effectively respond to the booster when given in the same arm.

The findings, made in mice and validated in human participants, provide evidence to refine vaccination approaches and offer a promising new approach for enhancing vaccine effectiveness.

“This is a fundamental discovery in how the immune system organises itself to respond better to external threats – nature has come up with this brilliant system and we're just now beginning to understand it,” says Professor Tri Phan, Director of the Precision Immunology Program at Garvan and co-senior author.

Scientia Professor Anthony Kelleher, Director of the Kirby Institute and co-senior author says: “A unique and elegant aspect of this study is the team’s ability to understand the rapid generation of effective vaccine responses. We did this by dissecting the complex biology in mice and then showed similar findings in humans. All this was done at the site of the generation of the vaccine response, the lymph node.”

How vaccination site matters

Immunisation introduces a harmless version of a pathogen, known as a vaccine antigen, into the body, which is filtered through lymph nodes – immune ‘training camps’ that train the body to fight off the real pathogen. The researchers previously discovered that memory B cells, which are crucial for generating antibody responses when infections return, linger in the lymph node closest to the injection site.

Using state-of-the-art intravital imaging at Garvan, the team discovered that memory B cells migrate to the outer layer of the local lymph node, where they interact closely with the macrophages that reside there. When a booster was given in the same location, these ‘primed’ macrophages – already on alert – efficiently captured the antigen and activated the memory B cells to make high quality antibodies.

“Macrophages are known to gobble up pathogens and clear away dead cells, but our research suggests the ones in the lymph nodes closest to the injection site also play a central role in orchestrating an effective vaccine response the next time around. So location does matter,” says Dr Rama Dhenni, the study’s co-first author, who undertook the research as part of his Scientia PhD program at Garvan.

Clinical study validates findings

To determine the relevance of the animal results to human vaccines, the team at the Kirby Institute conducted a clinical study with 30 volunteers receiving the Pfizer-BioNTech COVID-19 mRNA vaccine. Twenty participants received their booster dose in the same arm as their first dose, while 10 had their second shot in the opposite arm.

“Those who received both doses in the same arm produced neutralising antibodies against SARS-CoV-2 significantly faster – within the first week after the second dose,” says Ms Alexandra Carey-Hoppé, co-first author and PhD student from the Kirby Institute.

“These antibodies from the same arm group, were also more effective against variants like Delta and Omicron. By four weeks, both groups had similar antibody levels, but that early protection could be crucial during an outbreak,” says Dr Mee Ling Munier, co-senior author and Vaccine Immunogenomics group leader at the Kirby Institute.

“If you've had your COVID jabs in different arms, don’t worry – our research shows that over time the difference in protection diminishes. But during a pandemic, those first weeks of protection could make an enormous difference at a population level. The same-arm strategy could help achieve herd immunity faster – particularly important for rapidly mutating viruses where speed of response matters.”

Looking ahead

Beyond the potential to refine vaccination guidelines, the findings offer a promising avenue for enhancing the effectiveness of vaccines.

“If we can understand how to replicate or enhance the interactions between memory B cells and these macrophages, we may be able to design next-generation vaccines that require fewer boosters,” says Professor Phan.

Friday, April 25, 2025

Even light exercise could help slow cognitive decline in people at risk of Alzheimer’s

 


In a landmark clinical trial of physical exercise in older adults with mild memory loss, people who exercised at low or moderate-high intensity showed less cognitive decline when compared to those receiving usual care

Peer-Reviewed Publication

University of California - San Diego

Aladdin Shadyab 

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Aladdin Shadyab, Ph.D., is an associate professor at the UC San Diego Herbert Wertheim School of Public Health and Human Longevity Science and the Department of Medicine at UC San Diego School of Medicine.

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Credit: Kyle Dykes/UC San Diego Health Sciences

Researchers at University of California San Diego and Wake Forest University have found that both low and moderate-high intensity exercise could be valuable tools in the fight against Alzheimer’s. The new research, published as two papers in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, describes the results of the EXERT study (Exercise in Adults with Mild Memory Problems), a multi-site clinical trial of lower or moderate-high intensity exercise in sedentary older adults with amnestic mild cognitive impairment, a major risk factor for Alzheimer’s dementia. The researchers also compared their results to an existing dataset of comparable individuals who only received usual care, such as regular check-ups with health care providers and medication management.

The researchers found:

  • In EXERT participants, cognitive function remained stable over 12 months in both low and moderate-high intensity exercise groups.
  • Both forms of exercise were associated with significantly less cognitive decline over 12 months when compared to individuals who were not involved in the exercise study.
  • Both EXERT exercise groups tended to show less brain volume loss over 12 months, including in the prefrontal cortex.  

Individuals with amnestic mild cognitive impairment, a condition characterized by memory complaints and objective memory decline, are at high risk of developing Alzheimer’s dementia, with approximately 16% of people with this condition progressing to Alzheimer’s each year.

“This is a critical time to intervene in this population, because they don’t have dementia yet, but are at a very high risk,” said Aladdin Shadyab, Ph.D., M.P.H., lead author of one of the new papers and associate professor at the UC San Diego Herbert Wertheim School of Public Health and Human Longevity Science and School of Medicine. “Together, these findings show us that even low intensity exercise may slow cognitive decline in at-risk older adults.”

While previous studies have suggested that exercise may be beneficial for cognitive health, the evidence has been mixed, and large, well-designed studies are needed to fully understand the potential benefits of exercise for older adults with mild cognitive impairment. The EXERT study, coordinated by the Alzheimer’s Disease Cooperative Study (ADCS) at UC San Diego, in partnership with Wake Forest University School of Medicine, fills this gap.

“EXERT was one of the first large clinical trials of exercise that partnered with the YMCA and its trainers to bring the intervention closer to home for research participants,” said Howard Feldman, M.D., ADCS director. “This approach brings us one step closer to its implementation in the community.”

The ADCS was formed in 1991 under a cooperative agreement between the National Institute on Aging and UC San Diego and is one of the key initiatives for Alzheimer’s research supported by the federal government, addressing treatments for both cognitive and behavioral symptoms of Alzheimer’s.

“There’s an urgent need to identify effective and feasible ways to prevent and treat Alzheimer’s dementia, and UC San Diego has been a leader in this field for many years,” added Feldman, who is also a professor in the Department of Neurosciences at UC San Diego School of Medicine.

EXERT included nearly 300 sedentary older adults with mild cognitive impairment who were randomly assigned to either moderate-high intensity aerobic training or lower-intensity stretching, balance and range of motion activities. Participants completed their assigned exercise 3-4 times per week for 12 months under the supervision of a YMCA trainer, and the study also included regular assessments of cognitive function and brain volume.

“EXERT is a landmark study because it’s the largest rigorous trial of exercise ever conducted in adults with mild cognitive impairment,” said Laura Baker, Ph.D., principal investigator of the EXERT study and professor of gerontology and geriatric medicine at Wake Forest University School of Medicine. “Exercise has well-documented benefits to nearly every aspect of human health, but we’re still unlocking the full potential of exercise as medicine for older adults with memory problems.

Though the researchers expected to see further cognitive decline in EXERT participants, they actually found that cognitive function remained stable for both exercise groups over the course of the study. This suggests that both lower and higher intensity exercise could slow cognitive decline. Another possible explanation for the results is that participating in research itself, regardless of the treatment, may offer protection against cognitive decline due to the intellectual and social stimulation involved.

Overall, the findings of both studies taken together suggest that exercise may be a promising, safe, and feasible strategy to promote brain health and prevent continued cognitive decline for older adults with mild cognitive impairment.

“While there’s still a lot to learn, these findings show that regular intensity exercise, even at low intensity, could go a long way toward helping older adults slow or delay cognitive decline, and this is promising news for those who are at high risk for dementia,” added Shadyab.

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Link to the main EXERT findings: https://doi.org/10.1002/alz.14586

Exercise boosts brain health - 2nd study

 

 — even when energy is low

Mizzou researchers find that exercise improves brain health, even when ketone production in the liver is impaired

Peer-Reviewed Publication

University of Missouri-Columbia

Mizzou researchers 

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Mizzou researchers

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Credit: Ben Stewart with University of Missouri

COLUMBIA, Mo. -- We know exercise is good for our body, but what about our brains? A new study from the University of Missouri suggests that exercise plays a crucial role in keeping our minds sharp, even when one of the brain’s key energy sources isn’t available.

The study, led by Mizzou researchers Taylor Kelty and R. Scott Rector, offers fresh insight into brain health and suggests that exercise could play a bigger role in preventing cognitive decline than previously thought.

With the number of Americans expected to develop Alzheimer’s disease more than doubling by 2060, this research raises an intriguing possibility: Could regular physical activity be the key to preserving memory and cognitive performance as we age?

When the body runs low on its usual fuel — glucose — the liver makes ketones, an alternative energy source that helps power the brain. These molecules support cognitive memory, learning and overall brain health. But what happens when the liver can’t produce enough of them? Can exercise help compensate for this ketone deficiency?

Kelty and Rector, the director of the Roy Blunt NextGen Precision Health building, were determined to find out.

In the study, the researchers looked at what happens when ketone production is limited in the liver. As expected, the result was a noticeable decline in brain function and memory. But then, something remarkable happened: Exercise still managed to help reverse some of the cognitive decline, even with the ketone production impaired.

“Going into the study, we thought that with fewer ketones and the cognitive impairments that causes, exercise may not be able to overcome that impairment,” Kelty, a postdoctoral fellow in Rector’s lab, said. “But it seems like exercise is so powerful that there are other mechanisms going on in the brain that allow it circumvent those impairments and still receive the benefits from exercise.”

Rector, who is also a professor in the School of Medicine, emphasized the complexity of exercise’s effects.

“This study highlights how exercise benefits the body in a multitude of ways, even when we don’t fully understand all the molecular mechanisms involved,” Rector said. “Even when we remove a single pathway, exercise is doing so many other things that it can help mitigate those deficiencies.”

The findings are especially promising for people with liver conditions that prevent the body from making ketones.

Kelty pointed out that the emerging field of liver-brain research is beginning to show that individuals with severe liver dysfunction have a higher risk of developing dementia.

“If ketone production in the liver is disrupted, it could be a potential cause of cognitive decline, ultimately leading to conditions like dementia,” Kelty said.

Ideally, this research helps raise awareness about the importance of ketone production on brain health and the impact exercise can have on staying mentally sharp.

“There’s so much we’re still uncovering, and with all the state-of-the-art resources and interdisciplinary collaborations at Mizzou, it’s exciting to think about where this research might take us next,” Kelty said. “Exercise could be a key piece of the puzzle in preserving brain health as we age.”

With more than two decades at Mizzou, Rector said he’s proud to be part of a community that makes research like this possible.  

“The support we’ve received from Mizzou, the Division of Research, Innovation and Impact, and the NextGen Precision Health initiative has been incredible,” Rector said. “We hope our work will ultimately help a lot of people in the future.”

 “Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise” was published in The Journal of Physiology.  This work was funded by the National Institutes of Health (NIH) and is a part of the NIH Molecular Transducers of Physical Activity Consortium (MoTrPAC), a national research consortium designed to discover the molecular mechanisms of how physical activity improves health and prevents disease. 

Cinnamon could affect drug metabolism in the body

 


Researchers study how cinnamon interacts with prescription medications

Peer-Reviewed Publication

University of Mississippi

Cinnamon Herb-Drug Interactions 

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A bit of cinnamon in your coffee won't hurt, but ask your doctor before using cinnamon supplements while taking prescription medications, researchers at the National Center for Natural Products Research advise. A recent study suggests that compounds in cinnamon can reduce the effect of some drugs.

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Credit: Graphic by Stefanie Goodwiller/University Marketing and Communications

OXFORD, Miss. – Cinnamon is one of the oldest and most commonly used spices in the world, but a new study from the National Center for Natural Products Research indicates a compound in it could interfere with some prescription medications.  

In a recent study published in Food Chemistry: Molecular Sciences, researchers at the University of Mississippi center found that cinnamaldehyde – a primary component of cinnamon – activates receptors that control the metabolic clearance of medication from the body, meaning consuming large amounts of cinnamon could reduce the effects of drugs. 

“Health concerns could arise if excessive amounts of supplements are consumed without the knowledge of health care provider or prescriber of the medications,” said Shabana Khan, a principal scientist in the center. “Overconsumption of supplements could lead to a rapid clearance of the prescription medicine from the body, and that could result in making the medicine less effective.” 

Aside from its culinary uses, cinnamon has a long history of being used in traditional medicine and can help manage blood sugar and heart health and reduce inflammation. But how the product actually functions in the body remains unclear. 

Sprinkling cinnamon on your morning coffee is unlikely to cause an issue, but using highly concentrated cinnamon as a dietary supplement might. 

“Despite its vast uses, very few reports were available to describe the fate of its major component – cinnamaldehyde,” Khan said. “Understanding its bioaccessibility, metabolism and interaction with xenobiotic receptors was important to evaluate how excess intake of cinnamon would affect the prescription drugs if taken at the same time.” 

Not all cinnamon is equal. Cinnamon oil – which is commonly used topically as an antifungal or antibacterial and as a flavoring agent in food and drinks – presents almost no risk of herb-drug interactions, said Amar Chittiboyina, the center's associate director.  

But cinnamon bark – especially Cassia cinnamon, a cheaper variety of cinnamon that originates in southern China – contains high levels of coumarin, a blood thinner, compared to other cinnamon varieties. Ground Cassia cinnamon bark is what is normally found in grocery stores.  

Wednesday, April 23, 2025

Oral hormone therapy may improve biomarkers of cardiovascular health

 Deciding whether to start hormone therapy during the menopause transition, the life phase that’s the bookend to puberty and when a woman’s menstrual cycle stops, is a hotly debated topic. While hormone therapy, or replacing the hormones that were previously produced by the body with synthetic medication, is recommended to manage bothersome symptoms like hot flashes and night sweats, Matthew Nudy, assistant professor of medicine at the Penn State College of Medicine, said there’s confusion about the long-term effects of hormone therapy, especially on cardiovascular health.

However, long-term use of estrogen-based hormone therapies may have beneficial effects on heart health, according to a new study, led by Nudy. A multi-institutional team analyzed data from hormone therapy clinical trials that were part of the Women’s Health Initiative (WHI) — a long-term national study focused on menopausal women — and found that estrogen-based hormone therapy improved biomarkers associated with cardiovascular health over time. In particular, the study suggests that hormone therapy may lower levels of lipoprotein(a), a genetic risk factor associated with a higher risk of heart attack and stroke.

Their findings were published in the journal Obstetrics & Gynecology. The study adds to the understanding of the complex interaction between hormone therapy and heart health, providing additional guidance to patients and doctors, according to Nudy.

“The pendulum has been swinging back and forth as to whether hormone therapy is safe for menopausal women, especially from a cardiovascular disease perspective,” Nudy said. “More recently, we’re recognizing that hormone therapy is safe in younger menopausal women within 10 years of menopause onset, who are generally healthy and who have no known cardiovascular disease.”

Hot flashes and night sweats are symptoms commonly associated with menopause but the hormonal changes that accompany this phase of life usher in another major shift — an increased risk of cardiovascular disease. The decline in the hormone estrogen can lead to changes in cholesterol, blood pressure and plaque buildup in blood vessels, which increase the risk of heart attack and stroke.

The research team was interested in understanding the long-term effect of hormone therapy on cardiovascular biomarkers, which hasn’t been evaluated over an extended period of time. Prior research in the field primarily looked at short-term effects.

Here, the team analyzed biomarkers associated with cardiovascular health over a six-year period from a subset of women who had participated in an oral hormone therapy clinical trial that was part of the WHI. Participants were randomly assigned to one of two groups — an estrogen-only group and an estrogen plus progesterone group — were between the ages of 50 and 79 when they were assigned to a group and were post-menopausal. They provided blood samples at baseline and at one-, three- and six-years. In total, they analyzed samples from 2,696 women, approximately 10% of the total trial participants.

The research team found that hormone therapy had a beneficial effect on most biomarkers in both the estrogen-only and the estrogen-plus-progesterone groups over time. Levels of LDL cholesterol, the so-called “bad” cholesterol, were reduced by approximately 11% while total cholesterol and insulin resistance decreased in both groups. HDL cholesterol, the so-called “good” cholesterol, increased by 13% and 7% for the estrogen-only and estrogen-and-progesterone groups, respectively.

However, triglycerides and coagulation factors, proteins in the blood that help form blood clots, increased.

More surprising to the research team, they said, levels of lipoprotein(a), a type of cholesterol molecule, decreased 15% and 20% in the estrogen-only and the estrogen-plus-progesterone groups, respectively. Unlike other types of cholesterol, which can be influenced by lifestyle and health factors such as diet and smoking, concentrations of lipoprotein(a) are thought to be determined primarily by genetics, Nudy explained. Patients with a high lipoprotein(a) concentration have an increased risk of heart attack and stroke, especially at a younger age. There’s also an increased risk of aortic stenosis, where calcium builds up on a heart valve.

“As a cardiologist, this finding is the most interesting aspect of this research,” Nudy said. “Currently, there are no medications approved by the Food and Drug Administration (FDA) to lower lipoprotein(a). Here, we essentially found that oral hormone therapy significantly reduced lipoprotein(a) concentrations over the long-term.”

When the research team examined the findings by self-reported racial and ethnic group, they found that the decrease in lipoprotein(a) concentration was more pronounced among participants with American Indian or Alaska Native ancestry or Asian or Pacific Islander ancestry — by 41% and 38%, respectively. Nudy said it isn’t clear why the reductions were steeper among these groups, but the team said they hope to investigate it further in future research studies.

Nudy noted that the estrogen therapy the women received in the clinical trial was conjugated equine estrogens, a commonly prescribed form of oral estrogen therapy. Before being absorbed by the body, oral hormone therapy is processed in the liver, through a process called first pass metabolism. That process could increase inflammatory markers, which may explain the rise in triglycerides and coagulation factors.

“There are now other common formulations of estrogen hormone therapy like transdermal estrogen, which is administered through the skin,” Nudy said. “Newer studies have found that transdermal estrogen doesn’t increase triglycerides, coagulation factors or inflammatory markers.”

For those considering menopause hormone therapy, Nudy recommended undergoing a cardiovascular disease risk assessment, even if the person hasn’t had a previous heart attack or stroke or hasn’t been diagnosed with cardiovascular disease. It will give health care providers more information when considering the best option to treat menopause symptoms.

“Currently, hormone therapy is not FDA-approved to reduce the risk of coronary artery disease or stroke,” Nudy said. 

Adolescents who sleep longer perform better at cognitive tasks

 

Adolescents who sleep for longer – and from an earlier bedtime – than their peers tend to have improved brain function and perform better at cognitive tests, researchers from the UK and China have shown.

But the study of adolescents in the US also showed that even those with better sleeping habits were not reaching the amount of sleep recommended for their age group.

Sleep plays an important role in helping our bodies function. It is thought that while we are asleep, toxins that have built up in our brains are cleared out, and brain connections are consolidated and pruned, enhancing memory, learning, and problem-solving skills. Sleep has also been shown to boost our immune systems and improve our mental health.

During adolescence, our sleep patterns change. We tend to start going to bed later and sleeping less, which affects our body clocks. All of this coincides with a period of important development in our brain function and cognitive development. The American Academy of Sleep Medicine says that the ideal amount of sleep during this period is between eight- and 10-hours’ sleep.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge said: “Regularly getting a good night’s sleep is important in helping us function properly, but while we know a lot about sleep in adulthood and later life, we know surprisingly little about sleep in adolescence, even though this is a crucial time in our development. How long do young people sleep for, for example, and what impact does this have on their brain function and cognitive performance?”

Studies looking at how much sleep adolescents get usually rely on self-reporting, which can be inaccurate. To get around this, a team led by researchers at Fudan University, Shanghai, and the University of Cambridge turned to data from the Adolescent Brain Cognitive Development (ABCD) Study, the largest long-term study of brain development and child health in the United States.

As part of the ABCD Study, more than 3,200 adolescents aged 11-12 years old had been given FitBits, allowing the researchers to look at objective data on their sleep patterns and to compare it against brain scans and results from cognitive tests. The team double-checked their results against two additional groups of 13-14 years old, totalling around 1,190 participants. The results are published today in Cell Reports.

The team found that the adolescents could be divided broadly into one of three groups:

Group One, accounting for around 39% of participants, slept an average (mean) of 7 hours 10 mins. They tended to go to bed and fall asleep the latest and wake up the earliest.

Group Two, accounting for 24% of participants, slept an average of 7 hours 21 mins. They had average levels across all sleep characteristics.

Group Three, accounting for 37% of participants, slept an average of 7 hours 25 mins. They tended to go to bed and fall asleep the earliest and had lower heart rates during sleep.

Although the researchers found no significant differences in school achievement between the groups, when it came to cognitive tests looking at aspects such as vocabulary, reading, problem solving and focus, Group Three performed better than Group Two, which in turn performed better than Group One.

Group Three also had the largest brain volume and best brain functions, with Group One the smallest volume and poorest brain functions.

Professor Sahakian said: “Even though the differences in the amount of sleep that each group got was relatively small, at just over a quarter-of-an-hour between the best and worst sleepers, we could still see differences in brain structure and activity and in how well they did at tasks. This drives home to us just how important it is to have a good night’s sleep at this important time in life.”

First author Dr Qing Ma from Fudan University said: “Although our study can’t answer conclusively whether young people have better brain function and perform better at tests because they sleep better, there are a number of studies that would support this idea. For example, research has shown the benefits of sleep on memory, especially on memory consolidation, which is important for learning.”

The researchers also assessed the participants’ heart rates, finding that Group Three had the lowest heart rates across the sleep states and Group One the highest. Lower heart rates are usually a sign of better health, whereas higher rates often accompany poor sleep quality like restless sleep, frequent awakenings and excessive daytime sleepiness.

Because the ABCD Study is a longitudinal study – that is, one that follows its participants over time – the team was able to show that the differences in sleep patterns, brain structure and function, and cognitive performance, tended be present two years before and two years after the snapshot that they looked at.

Senior author Dr Wei Cheng from Fudan University added: “Given the importance of sleep, we now need to look at why some children go to bed later and sleep less than others. Is it because of playing videogames or smartphones, for example, or is just that their body clocks do not tell them it’s time to sleep until later?”

The research was supported by the National Key R&D Program of China, National Natural Science Foundation of China, National Postdoctoral Foundation of China and Shanghai Postdoctoral Excellence Program. The ABCD Study is supported by the National Institutes of Health.

Reference

Ma, Q et al. Neural correlates of device-based sleep characteristics in adolescents. Cell Reports; 22 Apr 2025; DOI: 10.1016/j.celrep.2025.115565

Walnut consumption curbs inflammation and colon cancer risk

 

There are new findings out about the benefits of eating walnuts. Results from a UConn School of Medicine clinical trial on the cover of the April edition of the journal Cancer Prevention Research show walnuts improve systemic inflammation while also reducing colon cancer risk.

Why walnuts?
Ellagitannins, plant-derived polyphenol compounds found in walnuts, are shown to be metabolized exclusively by the gut microbiome into a wide range of anti-inflammatory molecules called urolithins. These urolithins are associated with very potent anti-inflammatory properties and may even inhibit cancer.

“Ellagitannins in the walnut are importantly providing the anti-inflammatory and anti-cancer properties that we’re seeing in patients in our clinical trial research, particularly the gut’s conversion of ellagitannins to a potent anti-inflammatory agent, urolithin A,” reports Daniel W. Rosenberg, Ph.D. and his multidisciplinary team of researchers at the UConn School of Medicine.

Rosenberg serves as the HealthNet Chair in Cancer Biology and is an Investigator in the Center for Molecular Oncology. He has studied walnut properties for more than a decade and has researched the connection between walnut consumption and its anti-inflammatory properties.

The UConn research team’s clinical trial findings show that high levels of urolithin A formation by the gut microbiome from walnut consumption has a positive impact on reducing inflammatory markers across blood, urine, and fecal samples, and may even positively affect the immune cells within colon polyps.

For the clinical trial, patients between the ages of 40 to 65 years and at an elevated risk for colon cancer, were referred for the study from the Division of Gastroenterology at UConn Health, the University of Connecticut’s academic medical center. Each of the 39 enrolled study participants were screened by the clinical research team at UConn John Dempsey Hospital and asked to complete an NIH Food Frequency Questionnaire for analysis by Ock Chun Ph.D., a nutritional epidemiologist in the College of Agriculture, Health and Natural Resources at UConn Storrs. Patients were asked to avoid all ellagitannin-containing foods and beverages for a week to set their urolithin levels at or close to zero before they began consuming ellagitannin-rich walnuts as part of their closely monitored diet. At the end of the three-week study, all participants received a high-definition colonoscopy performed by Drs. John Birk and Haleh Vaziri.

Among the key findings, the researchers found that elevated urolithin A levels in the urine of patients correlated with the serum levels of peptide YY, an interesting protein that has been associated with inhibition of colorectal cancer. Reduced levels of several inflammation markers present in the blood were also found, especially in obese patients that had the greatest capacity to form urolithins by their gut microbiome.

Rosenberg also used high-dimensional spatial imaging technology that allowed UConn researchers to develop a detailed view of the direct cellular interactions present inside colon polyps that were removed during colonoscopy at the end of the walnut study. This cutting-edge advanced imaging technology revealed that patients with high levels of urolithin A formation following walnut consumption was directly associated with reduced levels of several important proteins that are often present in polyps, showing for the first time how walnut ingestion may directly enhance colon health.

The research team also discovered that the protein vimentin, often associated with more advanced forms of colon cancer, was greatly reduced inside polyp tissues obtained from patients who had also formed the highest levels of urolithin A by their gut microbiome.

These important new research findings build upon the earlier work of Dr. Masako Nakanishi, an assistant professor in the Rosenberg Lab, who showed in several earlier publications that walnuts had beneficial and anti-cancer effects in the colons of cancer-prone mice, key findings that prompted the current clinical trial.

“Urolithin A has a very positive influence on inflammation and maybe even cancer prevention,” says Rosenberg. “Our study proves that dietary supplementation with walnuts can boost the general population’s urolithin levels in those people with the right microbiome, while significantly reducing several inflammatory markers, especially in obese patients.”

Rosenberg concludes, “Our study provides strong rationale for dietary inclusion of walnut ellagitannins for cancer prevention. Nutrients from walnuts can contribute to reduced cancer risk. There are many potential benefits one can get from eating walnuts, with so little downside risk, that just grabbing a handful every day is really something that you can easily do for your long-term health benefit.”

This research is supported by generous awards from the American Institute for Cancer Research, the California Walnut Commission, and the National Cancer Institute.