Cinnamon is one of the oldest and most commonly used spices in the world – but a new study from the University of Mississippi indicates a compound in it could interfere with some prescription medications.
In a recent study published in Food Chemistry: Molecular Sciences, the researchers 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 natural products centre. “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 flavouring 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.
“In contrast, true cinnamon from Sri Lanka carries a lower risk due to its reduced coumarin content,” he said. “Coumarin’s anticoagulant properties can be hazardous for individuals on blood thinners.”
More research is needed to fully understand the role that cinnamon plays in the body and what potential herb-drug interactions may occur, said Bill Gurley, a principal scientist in the Ole Miss center and co-author of the study.
“We know there’s a potential for cinnamaldehyde to activate these receptors that can pose a risk for drug interactions,” he said. “That’s what could happen, but we won’t know exactly what will happen until we do a clinical study.”
Until those studies are complete, the researchers recommend anyone interested in using cinnamon as a dietary supplement to check with their doctor first.
“People who suffer from chronic diseases – like hypertension, diabetes, cancer, arthritis, asthma, obesity, HIV, AIDS or depression – should be cautious when using cinnamon or any other supplements,” Khan said. “Our best advice is to talk to a health care provider before using any supplements along with the prescription medicine.
“By definition, supplements are not meant to treat, cure or mitigate any disease.”
Even vegans who get enough total protein may fall short for some essential amino acids
In New Zealand study, 3 in 4 vegans ate sufficient protein, but half didn’t meet daily lysine and leucine requirements
In a new study of people with long-term vegan diets, most ate an adequate amount of total daily protein, but a significant proportion did not meet required levels of the amino acids lysine and leucine. Bi Xue Patricia Soh and colleagues at Massey University, New Zealand, present these findings in the open-access journal PLOS One on April 16, 2025.
Proteins are made up of various molecular “building blocks” known as amino acids. While the human body can synthesise most of the amino acids we need to live, we completely rely on the food we eat to provide the nine “indispensable amino acids” we cannot make ourselves. Typically, plant-based foods have more varied levels of indispensable amino acids that the body can use, as compared to animal-sourced foods, so they are of particular concern in vegan diets.
However, most prior research on protein in vegan diets has not considered specific amino acids nor the digestibility of different foods, which accounts for the fact that not all of what we eat, including amino acids, is fully utilised by the body.
To help deepen understanding of amino acid intake in vegan diets, Soh and colleagues analysed detailed, four-day food diaries kept by 193 long-term vegans living in New Zealand. They used information from the United States Department of Agriculture and the New Zealand FoodFiles database to calculate participants’ intake of different amino acids from the different foods they ate.
The analysis showed that about three quarters of participants met daily total protein requirements. Accounting for body weight, intake of all indispensable amino acids also met requirements.
However, when considering digestibility, only about half of the participants met daily requirements for lysine and leucine levels, making them the most limiting indispensable amino acids in the study. Among the food types consumed by participants, legumes and pulses were the biggest contributors to overall protein and lysine intake.
These findings underscore that meeting total daily protein requirements does not necessarily mean meeting indispensable amino acid requirements. On the basis of their findings, the researchers call for future research to explore how intake of leucine and lysine could be boosted for vegans in a nutritionally balanced manner.
The authors add: “Vegan diets are the most restrictive form of plant-based eating, relying entirely on plant sources for all nutrients. Achieving high protein quality on a vegan diet requires more than just consuming enough protein – it also depends on the right balance and variety of plant foods to supply all the amino acids in the quantities that our body needs. Prolonged deficiencies in these essential nutrients can negatively affect overall protein balance, muscle maintenance and other physiological functions, especially in more vulnerable populations.”
“In our study, lysine and leucine were the most commonly under-consumed amino acids in our vegan cohort and fall below the daily requirements needed by our body. This is because many plant foods generally contain lower quantities of these amino acids that can be absorbed and utilised by the body. However, the inclusion of legumes, nuts and seeds emerged as valuable plant sources – not only to support overall protein intake but also to specifically increase lysine and leucine quantities in a vegan diet.”
A new study from Mass General Brigham suggests that eating only during the daytime could help people avoid the health risks associated with shift work. Results are published in Nature Communications.
“Our prior research has shown that circadian misalignment – the mistiming of our behavioral cycle relative to our internal body clock – increases cardiovascular risk factors,” said senior author Frank A.J.L. Scheer, PhD, a professor of Medicine at Brigham and Women’s Hospital. “We wanted to understand what can be done to lower this risk, and our new research suggests food timing could be that target.”
Animal studies have shown that aligning food timing with the internal body clock could mitigate the health risks of staying awake during the typical rest time, which prompted Scheer and his colleagues to test this concept in humans.
For the study, researchers enlisted 20 healthy young participants to a two-week in-patient study at the Brigham and Women’s Center for Clinical Investigation. They had no access to windows, watches, or electronics that would clue their body clocks into the time. The effect of circadian misalignment could be determined by comparing how their body functions changed from before to after simulated night work.
Study participants followed a “constant routine protocol,” a controlled laboratory setup that can tease apart the effects of circadian rhythms from those of the environment and behaviours (eg, sleep/wake, light/dark patterns). During this protocol, participants stayed awake for 32 hours in a dimly lit environment, maintaining constant body posture and eating identical snacks every hour. After that, they participated in simulated night work and were assigned to either eating during the nighttime (as most night workers do) or only during the daytime. Finally, participants followed another constant routine protocol to test the aftereffects of the simulated night work. Importantly, both groups had an identical schedule of naps, and, thus, any differences between the groups were not due to differences in sleep schedule.
The investigators examined the aftereffects of the food timing on participants’ cardiovascular risk factors and how these changed after the simulated night work. Researchers measured various cardiovascular risk factors, including autonomic nervous system markers, plasminogen activator inhibitor-1 (which increases the risk of blood clots), and blood pressure.
Remarkably, these cardiovascular risk factors increased after simulated night work compared to the baseline in the participants who were scheduled to eat during the day and night. However, the risk factors stayed the same in the study participants who only ate during the daytime, even though how much and what they ate was not different between the groups—only when they ate.
Limitations of the study include that the sample size was small, although of a typical size for such highly controlled and intensive randomised controlled trials. Moreover, because the study lasted two weeks, it may not reflect the chronic risks of nighttime versus daytime eating.
A strength is that the study participants’ sleep, eating, light exposure, body posture, and activity schedule were so tightly controlled.
“Our study controlled for every factor that you could imagine that could affect the results, so we can say that it’s the food timing effect that is driving these changes in the cardiovascular risk factors,” said Sarah Chellappa, MD, MPH, PhD, an associate professor at the University of Southampton, and lead author for the paper.
While further research is necessary to show the long-term health effects of daytime versus nighttime eating, Scheer and Chellappa said the results are “promising” and suggest that people could improve their health by adjusting food timing. They add that avoiding or limiting eating during nighttime hours may benefit night workers, those who experience insomnia or sleep-wake disorders, individuals with variable sleep/wake cycles, and people who travel frequently across time zones.
Researchers from the University of Missouri have discovered that kaempferol, a natural antioxidant found in certain fruits and vegetables, such as kale, berries and endives, may support nerve cell health and holds promise as a potential treatment for ALS. Photo: Pixabay CC0
A natural compound found in everyday fruits and vegetables may hold the key to protecting nerve cells — and it’s showing promise as a potential treatment for ALS and dementia, according to new research from the University of Missouri.
“It’s exciting to discover a naturally occurring compound that may help people suffering from ALS or dementia,” Smita Saxena, a professor of physical medicine and rehabilitation at the School of Medicine and lead author of the study, said. “We found this compound had a strong impact in terms of maintaining motor and muscle function and reducing muscle atrophy.”
The study, which appears in Acta Neurologica, discovered that kaempferol, a natural antioxidant found in certain fruits and vegetables, such as kale, berries and endives, may support nerve cell health and holds promise as a potential treatment for ALS.
In lab-grown nerve cells from ALS patients, the compound helped the cells produce more energy and eased stress in the protein-processing center of the cell called the endoplasmic reticulum. Additionally, the compound improved overall cell function and slowed nerve cell damage. Researchers found that kaempferol worked by targeting a crucial pathway that helps control energy production and protein management — two functions that are disrupted in individuals with ALS.
“I believe this is one of the first compounds capable of targeting both the endoplasmic reticulum and mitochondria simultaneously,” Saxena said. “By interacting with both of these components within nerve cells, it has the potential to elicit a powerful neuroprotective effect.”
The challenge
The catch? The body doesn’t absorb kaempferol easily, and it could take a large amount to see real benefits in humans. For instance, an individual with ALS would need to consume at least 4.5kg of kale in a day to obtain a beneficial dose.
“Our bodies don’t absorb kaempferol very well from the vegetables we eat,” Saxena said. “Because of this, only a small amount reaches our tissues, limiting how effective it can be. We need to find ways to increase the dose of kaempferol or modify it so it’s absorbed into the bloodstream more easily.”
Another hurdle is getting the compound into the brain. The blood-brain barrier — a tightly locked layer of cells that blocks harmful substances — also makes it harder for larger molecules like kaempferol to pass through.
What’s next?
Despite its challenges, kaempferol remains a promising candidate for treating ALS, especially since it works even after symptoms start. It also shows potential for other neurodegenerative diseases including Alzheimer’s and Parkinson’s.
To make the compound easier for the body to absorb, Saxena’s team at the Roy Blunt NextGen Precision Health building is exploring ways to boost its uptake by neurons. One promising approach involves packaging lipid-based nanoparticles — tiny spherical particles made of fats that are commonly used in drug delivery.
“The idea is to encapsulate kaempferol within lipid-based nanoparticles that are easily absorbed by the neurons,” Saxena said. “This would target kaempferol to neurons to greatly increase its beneficial effect.”
The team is currently generating the nanoparticles with hopes of testing them by the end of the year.
Emerging evidence suggests that lycopene—a natural plant extract—may have antidepressant properties. New research in Food Science & Nutrition reveals the mechanisms behind its antidepressant effects.
Lycopene is a carotenoid, related to beta-carotene and gives some vegetables and fruits (eg, tomatoes, grapefruit) a red colour. Lycopene is a powerful antioxidant that might help protect cells from damage.
In mice with depressive-like behaviours, brain analyses revealed impairments in the hippocampus. Lycopene treatment lessened these impairments and reversed the animals’ depressive-like traits.
Lycopene treatment boosted the expression of brain-derived neurotrophic factor (BDNF), a protein with roles in many aspects of brain function. Experiments indicated that a signalling pathway involving BDNF (called the BDNF-TrkB pathway, which helps regulate learning, memory, and communication between neurons) is inhibited in mice with depression, and that lycopene treatment alleviates this inhibition.
The study “offers an effective avenue for the development of novel antidepressant therapies,” the authors wrote. “We plan to conduct further verification in future studies and include multiple brain regions in our research.”
The pleasure we get from eating junk food — the dopamine rush from crunching down on salty, greasy chips and a luscious burger — is often blamed as the cause of overeating and rising obesity rates in our society. But a new study suggests that pleasure in eating, even eating junk food, is key for maintaining a healthy weight in a society that abounds with cheap, high-fat food.
Paradoxically, anecdotal evidence suggests that people with obesity may take less pleasure in eating than those of normal weight. Brain scans of obese individuals show reduced activity in pleasure-related brain regions when presented with food, a pattern also observed in animal studies.
Now, University of California, Berkeley, researchers have identified a possible underlying cause of this phenomenon — a decline in neurotensin, a brain peptide that interacts with the dopamine network — and a potential strategy to restore pleasure in eating in a way that helps reduce overall consumption.
The study, published in Nature, reveals an unsuspected brain mechanism that explains why a chronic high-fat diet can reduce the desire for high-fat, sugary foods, even when these foods remain easily accessible. The researchers propose that this lack of desire in obese individuals is due to a loss of pleasure in eating caused by long-term consumption of high-calorie foods. Losing this pleasure may actually contribute to the progression of obesity.
“A natural inclination toward junk food is not inherently bad — but losing it could further exacerbate obesity,” said Stephan Lammel, a UC Berkeley professor in the Department of Neuroscience and a member of the Helen Wills Neuroscience Institute.
The researchers found that this effect is driven by a reduction in neurotensin in a specific brain region that connects to the dopamine network. Importantly, they demonstrate that restoring neurotensin levels — either through dietary changes or genetic manipulations that enhance neurotensin production — can reinstate the pleasure in eating and promote weight loss.
“A high-fat diet changes the brain, leading to lower neurotensin levels, which in turn alters how we eat and respond to these foods,” Lammel said. “We found a way to restore the desire for high-calorie foods, which may actually help with weight management.”
While findings in mice don’t always translate directly to humans, this discovery could open new avenues for addressing obesity by restoring food-related pleasure and breaking unhealthy eating patterns.
“Imagine eating an amazing dessert at a great restaurant in Paris — you experience a burst of dopamine and happiness,” said Neta Gazit Shimoni, a UC Berkeley postdoctoral fellow. “We found that this same feeling occurs in mice on a normal diet, but is missing in those on a high-fat diet. They may keep eating out of habit or boredom, rather than genuine enjoyment.”
Gazit Shimoni and former UC Berkeley graduate student Amanda Tose are co-first authors, and Lammel is senior author of the study, which will be published March 26 in the journal Nature.
Solving a long-standing puzzle in obesity research
For decades, doctors and researchers have struggled to understand and treat obesity, as countless fad diets and eating regimens have failed to produce long-term results. The recent success of GLP-1 agonists like Ozempic, which curb appetite by increasing feelings of fullness, stands out among many failed approaches.
Lammel studies brain circuits, particularly the dopamine network, which plays a crucial role in reward and motivation. Dopamine is often associated with pleasure, reinforcing our desire to seek rewarding experiences, such as consuming high-calorie foods.
While raising mice on a high-fat diet, Gazit Shimoni noticed a striking paradox: While in their home cages, these mice strongly preferred high-fat chow, which contained 60% fat, over normal chow with only 4% fat, leading them to gain excessive weight. However, when they were taken out of their home cages and given free access to high-calorie treats such as butter, peanut butter, jelly or chocolate, they showed much less desire to indulge than normal-diet mice, which immediately ate everything they were offered.
“If you give a normal, regular-diet mouse the chance, they will immediately eat these foods,” Gazit Shimoni said. “We only see this paradoxical attenuation of feeding motivation happening in mice on a high-fat diet.”
She discovered that this effect had been reported in past studies, but no one had followed up to find out why, and how the effect connects to the obesity phenotype observed in these mice.
To investigate this phenomenon, Lammel and his team used optogenetics, a technique that allows scientists to control brain circuits with light. They found that in normal-diet mice, stimulating a brain circuit that connects to the dopamine network increased their desire to eat high-calorie foods, but in obese mice, the same stimulation had no effect, suggesting that something must have changed.
The reason, they discovered, was that neurotensin was reduced so much in obese mice that it prevented dopamine from triggering the usual pleasure response to high-calorie foods.
“Neurotensin is this missing link,” Lammel said. “Normally, it enhances dopamine activity to drive reward and motivation. But in high-fat diet mice, neurotensin is downregulated, and they lose the strong desire to consume high-calorie foods — even when easily available.”
The researchers then tested ways to restore neurotensin levels. When obese mice were switched back to a normal diet for two weeks, their neurotensin levels returned to normal, dopamine function was restored, and they regained interest in high-calorie foods.
When neurotensin levels were artificially restored using a genetic approach, the mice not only lost weight, but also showed reduced anxiety and improved mobility. Their feeding behaviour also normalised, with increased motivation for high-calorie foods and a simultaneous reduction of their total food consumption in their home cages.
“Bringing back neurotensin seems to be very, very critical for preventing the loss of desire to consume high-calorie foods,” Lammel said. “It doesn’t make you immune to getting obese again, but it would help to control eating behaviour, to bring it back to normal.”
Toward more precise treatments for obesity
Although directly administering neurotensin could theoretically restore feeding motivation in obese individuals, neurotensin acts on many brain areas, raising the risk of unwanted side effects. To overcome this, the researchers used gene sequencing, a technique that allowed them to identify specific genes and molecular pathways that regulate neurotensin function in obese mice.
This discovery provides crucial molecular targets for future obesity treatments, paving the way for more precise therapies that could selectively enhance neurotensin function without broad systemic effects.
“We now have the full genetic profile of these neurons and how they change with high-fat diets,” Lammel said. “The next step is to explore pathways upstream and downstream of neurotensin to find precise therapeutic targets.”
Lammel and Gazit Shimoni plan to expand their research to explore neurotensin’s role beyond obesity, investigating its involvement in diabetes and eating disorders.
“The bigger question is whether these systems interact across different conditions,” Gazit Shimoni said. “How does starvation affect dopamine circuits? What happens in eating disorders? These are the questions we’re looking at next.”
It is well known that consuming sugary drinks increases the risk of diabetes, but the mechanism behind this relationship is unclear. Now, in a paper published in the Cell Press journal Cell Metabolism, researchers show that metabolites produced by gut microbes might play a role.
In a long-term cohort of US Hispanic/Latino adults, the researchers identified differences in the gut microbiota and blood metabolites of individuals with a high intake of sugar-sweetened beverages. The altered metabolite profile seen in sugary beverage drinkers was associated with a higher risk of developing diabetes in the subsequent 10 years. Since some of these metabolites are produced by gut microbes, this suggests that the microbiome might mediate the association between sugary beverages and diabetes.
“Our study suggests a potential mechanism to explain why sugar-sweetened beverages are bad for your metabolism,” says senior author Qibin Qi, an epidemiologist at Albert Einstein College of Medicine. “Although our findings are observational, they provide insights for potential diabetes prevention or management strategies using the gut microbiome.”
Sugar-sweetened beverages are the main source of added sugar in the diets of US adults – in 2017 and 2018, US adults consumed an average of 34.8g of added sugar each day from sugary beverages such as soda and sweetened fruit juice. Compared to added sugars in solid foods, added sugar in beverages “might be more easily absorbed, and they have a really high energy density because they’re just sugar and water,” says Qi.
Previous studies in Europe and China have shown that sugar-sweetened beverages alter gut microbiome composition, but this is the first study to investigate whether this microbial change impacts host metabolism and diabetes risk. It’s also the first study to investigate the issue in US-based Hispanic/Latino population — a group that experiences high rates of diabetes and is known to consume high volumes of sugar-sweetened beverages.
The team used data from the ongoing Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large-scale cohort study with data from over 16 000 participants living in San Diego, Chicago, Miami, and the Bronx. At an initial visit, participants were asked to recall their diet from the past 24 hours and had blood drawn to characterise their serum metabolites. The researchers collected faecal samples and characterized the gut microbiomes of a subset of the participants (n = 3035) at a follow-up visit and used these data to identify association between sugar-sweetened beverage intake, gut microbiome composition, and serum metabolites.
They found that high sugary beverage intake, defined as two or more sugary beverages per day, was associated with changes in the abundance of nine species of bacteria. Four of these species are known to produce short-chain fatty acids: molecules that are produced when bacteria digest fibre and that are known to positively impact glucose metabolism. In general, bacterial species that were positively associated with sugary beverage intake correlated with worse metabolic traits. Interestingly, these bacteria were not associated with sugar ingested from non-beverage sources.
The researchers also found associations between sugary beverage consumption and 56 serum metabolites, including several metabolites that are produced by gut microbiota or are derivatives of gut-microbiota-produced metabolites. These sugar-associated metabolites were associated with worse metabolic traits, including higher levels of fasting blood glucose and insulin, higher BMIs and waist-to-hip ratios, and lower levels of high-density lipoprotein cholesterol (“good” cholesterol). Notably, individuals with higher levels of these metabolites had a higher likelihood of developing diabetes in the 10 years following their initial visit.
“We found that several microbiota-related metabolites are associated with the risk of diabetes,” says Qi. “In other words, these metabolites may predict future diabetes.”
Because gut microbiome samples were only collected from a subset of the participants, the researchers had an insufficient sample size to determine whether any species of gut microbes were directly associated with diabetes risk, but this is something they plan to study further.
“In the future, we want to test whether the bacteria and metabolites can mediate or at least partially mediate the association between sugar-sweetened beverages and risk of diabetes,” says Qi.
The team plans to validate their findings in other populations and to extend their analysis to investigate whether microbial metabolites are involved in other chronic health issues linked to sugar consumption, such as cardiovascular disease.
Epidemiologists in the School of Public Health conducted a meta-analysis to assess whether red wine protects against cancer, comparing the cancer risks of red wine vs. white wine. It is published in the journal Nutrients.
Alcohol – specifically, the ethanol in alcoholic beverages – metabolises into compounds that damage DNA and proteins, contributing to cancer risk. In 2020, excessive alcohol consumption was linked to more than 740 000 cancer cases worldwide, accounting for 4.1% of all cases.
Despite the classification of alcoholic beverages as Group 1 carcinogens, meaning they are carcinogenic to humans, a common perception is that not all alcoholic beverages are alike. Red wine, in particular, is often considered a healthier choice, and its consumption is on the rise. The popularity of red wine may stem from the widespread belief that its high resveratrol content, an antioxidant with anti-inflammatory properties, offers protective effects against cancer.
Researchers from the Brown University School of Public Health have conducted a study that scours “the vast and often contradictory literature on the carcinogenicity of red and white wine” to assess whether this assumption holds up, and to compare the cancer risks associated with wine type.
“In an effort to better understand the potential impact of wine consumption on cancer risk, we conducted a comprehensive meta-analysis to assess whether red wine is truly a healthier choice than white wine,” said Eunyoung Cho, co-lead author of the study and associate professor of epidemiology and of dermatology at Brown. “Our analysis included as many published epidemiological studies as possible that separately explored the relationship between red and white wine consumption and cancer risk.”
Analyzing 42 observational studies (20 cohort and 22 case-control) involving nearly 96,000 participants, Cho and her team found no overall increased cancer risk from wine consumption, regardless of type. However, they also found no clear evidence that red wine mitigates cancer risk.
Paradoxically, when focusing on cohort studies that follow participants over a long period of time, researchers found that white wine is associated with a 22% increased risk of skin cancer compared to red wine intake.
“The results of our meta-analysis revealed no significant difference in cancer risk between red and white wine overall,” Cho said. “However, we did observe a distinction when it came to skin cancer risk. Specifically, the consumption of white wine, but not red wine, was associated with an increased risk of skin cancer.”
The reasons for this are indeterminate. Researchers suggest that heavy consumption of wine may correlate to high-risk behaviors, such as indoor tanning and inadequate sunscreen use. However, it is unclear why white wine, in particular, is the culprit.
In an additional twist, the study also found a stronger association between white wine intake and increased overall cancer risk among women. This finding warrants further investigations into potential underlying mechanisms.
The meta-analysis, the first study of its kind, challenges the belief that red wine is healthier than white. It also points to the need for further study into the association between white wine consumption and cancer risk, particularly in women.
Some fast food offerings, such as cheeseburgers, contain more than 60% of calories from fat. Photo by Jonathan Borba
Just a few days of eating a diet high in saturated fat could be enough to cause memory problems and related brain inflammation in older adults, a new study in rats suggests.
In the study, published in Immunity & Aging, researchers fed separate groups of young and old rats the high-fat diet for three days or for three months to compare how quickly changes happen in the brain versus the rest of the body when eating an unhealthy diet.
As expected based on previous diabetes and obesity research, eating fatty foods for three months led to metabolic problems, gut inflammation and dramatic shifts in gut bacteria in all rats compared to those that ate normal chow, while just three days of high fat caused no major metabolic or gut changes.
When it came to changes in the brain, however, researchers found that only older rats – whether they were on the high-fat diet for three months or only three days – performed poorly on memory tests and showed negative inflammatory changes in the brain.
The results dispel the idea that diet-related inflammation in the aging brain is driven by obesity, said senior study author Ruth Barrientos, an investigator in the Institute for Behavioral Medicine Research at The Ohio State University. Most research on the effects of fatty and processed foods on the brain has focused on obesity, yet the impact of unhealthy eating, independent of obesity, remains largely unexplored.
“Unhealthy diets and obesity are linked, but they are not inseparable. We’re really looking for the effects of the diet directly on the brain. And we showed that within three days, long before obesity sets in, tremendous neuroinflammatory shifts are occurring,” said Barrientos, also an associate professor of psychiatry and behavioural health and neuroscience in Ohio State’s College of Medicine.
“Changes in the body in all animals are happening more slowly and aren’t actually necessary to cause the memory impairments and changes in the brain. We never would have known that brain inflammation is the primary cause of high-fat diet-induced memory impairments without comparing the two timelines.”
Years of research in Barrientos’ lab has suggested that aging brings on long-term “priming” of the brain’s inflammatory profile coupled with a loss of brain-cell reserve to bounce back, and that an unhealthy diet can make matters worse for the brain in older adults.
Fat constitutes 60% of calories in the high-fat diet used in the study, which could equate to a range of common fast-food options: For example, nutrition data shows that fat makes up about 60% of calories in a McDonald’s double smoky BLT quarter pounder with cheese or a Burger King double whopper with cheese.
After the animals were on high-fat diets for three days or three months, researchers ran tests assessing two types of memory problems common in older people with dementia that are based in separate regions of the brain: contextual memory mediated by the hippocampus (the primary memory center of the brain), and cued-fear memory that originates in the amygdala (the fear and danger center of the brain).
Compared to control animals eating chow and young rats on the high-fat diet, aged rats showed behaviors indicating both types of memory were impaired after only three days of fatty food – and the behaviors persisted as they continued on the high-fat diet for three months.
Researchers also saw changes in levels of a range of proteins called cytokines in the brains of aged rats after three days of fatty food, which signaled a dysregulated inflammatory response. Three months after being on the high-fat diet, some of the cytokine levels had shifted but remained dysregulated, and the cognitive problems persisted in behavior tests.
“A departure from baseline inflammatory markers is a negative response and has been shown to impair learning and memory functions,” Barrientos said.
Compared to rats eating normal chow, young and old animals gained more weight and showed signs of metabolic dysfunction – poor insulin and blood sugar control, inflammatory proteins in fat (adipose) tissue, and gut microbiome alterations – after three months on the high-fat diet. Young rats’ memory and behavior and brain tissue remained unaffected by the fatty food.
“These diets lead to obesity-related changes in both young and old animals, yet young animals appear more resilient to the high-fat diet’s effects on memory. We think it is likely due to their ability to activate compensatory anti-inflammatory responses, which the aged animals lack,” Barrientos said.
“Also, with glucose, insulin and adipose inflammation all increased in both young and old animals, there’s no way to distinguish what is causing memory impairment in only old animals if you look only at what’s happening in the body. It’s what is happening in the brain that’s important for the memory response.”
It’s common knowledge that sugar causes cavities, but new research provides evidence that – depending on your genetic makeup – starches could also be a contributing factor.
The study, published in Microorganisms, explores the response of the oral microbiome to starch, finding that the number of copies of a particular gene, AMY1, in combination with starch, alters the complex composition of bacteria that play a role in oral health.
“Most people have been warned that if you eat a bunch of sugar, make sure you brush your teeth,” said Angela Poole, senior author and assistant professor of molecular nutrition in the College of Agriculture and Life Sciences and the College of Human Ecology. “The takeaway finding here is that depending on your AMY1 copy number, you may want to be just as vigilant about brushing your teeth after eating those digestible starches.”
Researchers, including first author Dorothy Superdock, PhD ’23, collected saliva samples from 31 subjects with a range of AMY1 copy numbers – copies of the AMY1 gene in the DNA – and added starch to the cultured samples, or biofilms, to see how the bacterial makeup changed. They found that, in general, the diversity of bacteria decreased when starch was added. For those samples with high numbers of AMY1, the starch significantly reduced the proportions of two bacteria, Atopobium and Veillonella, while Streptococcus appeared to increase.
All three bacteria are associated with tooth decay or gum disease, Poole said.
“Some increased and some decreased, so it’s not so straightforward as saying, ‘The whole thing is good or bad,’” Poole said. “It’s an interaction, but it looks like the AMY1 copy number, as well as which species are present in people’s mouths when they eat starch, is affecting the risk for developing these diseases.”
AMY1 codes for the salivary amylase enzyme, which helps break down starch in the mouth. Previous studies have associated AMY1 with cavities and periodontal disease. Poole, in prior studies, found that a high AMY1 copy number is associated with higher levels of the species Porphyromonas endodontalis, which is strongly associated with periodontitis and gum disease.
But how the salivary amylase enzyme interacts with its main substrate, starch, to alter the oral microbiome and increase disease risk was unclear.
“That’s what we wanted to know in this experiment,” Poole said. “What’s going on in the mouth if someone eats starch, and is the answer different if their copy number is high or if it’s low? What we found was that there are other bacteria involved in these processes and that the changes depended on AMY1.”
The researchers also found evidence that the oral microbiome has co-evolved in response to increasing copies of AMY1, which is found in higher numbers in populations where there’s a long history of agriculture and starch consumption. In the pool of 31 samples, taken locally in Ithaca, the AMY1 number ranged from two to 20 copies.
“The populations that historically had greater access to starch tend to have more copies,” Poole said, “which makes sense from a practical standpoint, because it would have given you a survival advantage when food is scarce, to be able to break down those starches more efficiently.”
In saliva samples with a high AMY1 copy number, the researchers saw increased populations of bacteria, like Streptococcus, that feed off the starch’s sugars.
“If someone has a high copy number, they break down starch efficiently, and bacteria that like those sugars are going to grow more in that person’s mouth,” Poole said. “So you can have species behave differently based on the different substrates. It’s pretty incredible – how we adapt and these microbes turn around and adapt, too.”
