The findings are based on data from more than 7,000 adults between the ages of 40-65 who are part of the GCAT | Genomes for Life cohort, led by the Germans Trias i Pujol Research Institute (IGTP). In 2018, participants provided details about their height, weight, meal timing, lifestyle habits, and socioeconomic background through questionnaires.

Five years later, in 2023, more than 3,000 of these individuals returned for follow-up assessments. Researchers recorded updated measurements and collected new survey data, allowing them to track changes and identify patterns over time.

Early Eating and Longer Fasting Linked to Lower BMI

“Our results, in line with other recent studies, suggest that extending the overnight fast could help maintain a healthy weight if accompanied by an early dinner and an early breakfast. We think this may be because eating earlier in the day is more in line with circadian rhythms and allows for better calorie burning and appetite regulation, which can help maintain a healthy weight. However, it is too soon to draw definitive conclusions, so recommendations will have to wait for more robust evidence,” explains Luciana Pons-Muzzo, researcher at ISGlobal at the time of the study and currently at IESE Business School.

Gender Differences and Lifestyle Patterns

When researchers compared results by gender, they found notable differences. Women generally had lower BMI, followed the Mediterranean diet more closely, and were less likely to drink alcohol. At the same time, they reported poorer mental health and were more often responsible for household or family supervision.

Using a method called ‘cluster analysis’, the team grouped participants with similar characteristics. One small group of men stood out. These individuals typically ate their first meal after 14:00 and fasted for about 17 hours. Compared to others, they were more likely to smoke and drink alcohol, less physically active, and less likely to follow the Mediterranean diet. They also tended to have lower levels of education and higher rates of unemployment. Researchers did not observe a similar pattern among women.

Intermittent Fasting and Breakfast Skipping

“There are different ways of practising what is known as ‘intermittent fasting’ and our study relates to one of them, which is overnight fasting. What we observed in a subgroup of men who do intermittent fasting by skipping breakfast is that this practice has no effect on body weight. Other intervention studies in participants with obesity have shown that this tactic is no more effective than reducing calorie intake in reducing body weight in the long term,” says Camille Lassale, ISGlobal researcher and senior co-author of the study.

Chrononutrition and the Body’s Internal Clock

“Our research is part of an emerging field of research known as ‘chrononutrition’, which focuses not only on analysing what we eat, but also the times of day and the number of times we eat,” says Anna Palomar-Cros, researcher at ISGlobal at the time of the study and currently at IDIAP Jordi Gol. “At the basis of this research is the knowledge that unusual food intake patterns can conflict with the circadian system, the set of internal clocks that regulate the cycles of night and day and the physiological processes that must accompany them,” she adds.

Earlier Meals Linked to Broader Health Benefits

This study builds on earlier ISGlobal research in chrononutrition. Previous findings have shown that eating dinner and breakfast earlier in the day is associated with a lower risk of cardiovascular disease and type 2 diabetes, reinforcing the idea that meal timing plays a meaningful role in long-term health.

That is exactly what happened during a University of Colorado Boulder field study in an agricultural region of Oklahoma. The team was using advanced instruments to study how tiny airborne particles form and evolve. Instead, they uncovered something surprising: the first airborne detection of Medium Chain Chlorinated Paraffins (MCCPs), a type of toxic organic pollutant, in the Western Hemisphere. The findings were published in ACS Environmental Au.

“It’s very exciting as a scientist to find something unexpected like this that we weren’t looking for,” said Daniel Katz, CU Boulder chemistry PhD student and lead author of the study. “We’re starting to learn more about this toxic, organic pollutant that we know is out there, and which we need to understand better.”

What Are MCCPs and Why They Matter

MCCPs are now being evaluated for possible regulation under the Stockholm Convention, an international agreement aimed at protecting human health from persistent and widespread chemicals. Although these pollutants have previously been detected in places like Antarctica and Asia, scientists had struggled to measure them in the air over the Western Hemisphere until this study.

These chemicals are commonly used in industrial processes, including metalworking fluids and the production of PVC and textiles. They frequently appear in wastewater and can end up in biosolid fertilizer, also called sewage sludge, which is produced during wastewater treatment. The researchers believe the MCCPs they detected in Oklahoma likely originated from nearby fields where this type of fertilizer had been applied.

“When sewage sludges are spread across the fields, those toxic compounds could be released into the air,” Katz said. “We can’t show directly that that’s happening, but we think it’s a reasonable way that they could be winding up in the air. Sewage sludge fertilizers have been shown to release similar compounds.”

A Possible Side Effect of Regulation

MCCPs are closely related to Short Chain Chlorinated Paraffins (SCCPs), which are already regulated under the Stockholm Convention and by the U.S. Environmental Protection Agency since 2009. Those earlier regulations followed evidence that SCCPs can travel long distances, persist in the environment, and pose risks to human health.

However, researchers suspect that limiting SCCPs may have led industries to substitute them with MCCPs, increasing the presence of these related chemicals.

“We always have these unintended consequences of regulation, where you regulate something, and then there’s still a need for the products that those were in,” said Ellie Browne, CU Boulder chemistry professor, CIRES Fellow, and co-author of the study. “So they get replaced by something.”

How Scientists Tracked the Chemicals

The discovery came from continuous air monitoring at the Oklahoma site. The team used a nitrate chemical ionization mass spectrometer, a sensitive instrument that can identify specific compounds in the air. Measurements were collected around the clock for a full month.

As Katz analyzed the data, he identified unusual isotopic patterns that did not match known compounds. After further investigation, those patterns were linked to chlorinated paraffins associated with MCCPs.

Links to “Forever Chemicals” and Future Research

Katz noted that MCCPs share similarities with PFAS, a group of chemicals often called “forever chemicals” because they break down very slowly in the environment. Concerns about PFAS contamination in soil recently led the Oklahoma Senate to ban biosolid fertilizer.

Now that scientists have confirmed how to detect MCCPs in the air, the next step is to track how their levels change over time. Researchers want to understand how concentrations vary across seasons and what effects these chemicals may have once they are airborne.

“We identified them, but we still don’t know exactly what they do when they are in the atmosphere, and they need to be investigated further,” Katz said. “I think it’s important that we continue to have governmental agencies that are capable of evaluating the science and regulating these chemicals as necessary for public health and safety.”

At the center of the discovery is a carbene, a form of carbon with just six valence electrons. Under normal conditions, carbon atoms are most stable with eight electrons. With only six, carbenes are highly unstable and react almost instantly with their surroundings. In water, they typically break down right away.

For decades, scientists believed that vitamin B1, also known as thiamine, might briefly form a carbene-like structure inside cells to help drive essential biochemical reactions. However, because of the molecule’s extreme instability, no one had been able to directly observe it in such conditions.

First Stable Carbene Observed in Water

Researchers have now succeeded in creating a carbene that remains stable in water. Not only did they generate it, they also isolated it, sealed it in a tube, and observed it staying intact for months. The findings are detailed in a study published in Science Advances.

“This is the first time anyone has been able to observe a stable carbene in water,” said Vincent Lavallo, a professor of chemistry at UC Riverside and corresponding author of the paper. “People thought this was a crazy idea. But it turns out, Breslow was right.”

A 1958 Hypothesis Finally Confirmed

Lavallo is referring to Ronald Breslow, a Columbia University chemist who proposed in 1958 that vitamin B1 could transform into a carbene to enable key biochemical reactions. While the idea was influential, it remained unproven because carbenes were known to be too unstable, especially in water, to capture or study.

To overcome this challenge, Lavallo’s team developed a protective molecular structure that surrounds the carbene. He describes it as “a suit of armor,” designed to shield the reactive center from water and other nearby molecules. With this protection, the carbene becomes stable enough for detailed analysis using nuclear magnetic resonance spectroscopy and x-ray crystallography, offering clear evidence that such molecules can exist in water.

“We were making these reactive molecules to explore their chemistry, not chasing a historical theory,” said first author Varun Raviprolu, who completed the research as a graduate student at UCR and is now a postdoctoral researcher at UCLA. “But it turns out our work ended up confirming exactly what Breslow proposed all those years ago.”

Toward Greener Chemistry and Drug Production

The implications go beyond solving a scientific mystery. Carbenes are widely used as “ligands,” or supporting components in metal-based catalysts that help drive chemical reactions. These catalysts play a major role in producing pharmaceuticals, fuels, and other materials. However, many of these processes depend on toxic organic solvents.

By stabilizing carbenes in water, the researchers may have opened the door to safer and more environmentally friendly chemical production.

“Water is the ideal solvent — it’s abundant, non-toxic, and environmentally friendly,” Raviprolu said. “If we can get these powerful catalysts to work in water, that’s a big step toward greener chemistry.”

Closer to Mimicking Chemistry in Living Cells

The ability to create and maintain reactive intermediate molecules in water also brings scientists closer to replicating the chemistry that naturally occurs inside living cells, which are mostly composed of water.

“There are other reactive intermediates we’ve never been able to isolate, just like this one,” Lavallo said. “Using protective strategies like ours, we may finally be able to see them, and learn from them.”

A Milestone Years in the Making

For Lavallo, who has spent two decades working with carbenes, the achievement carries both scientific and personal significance.

“Just 30 years ago, people thought these molecules couldn’t even be made,” he said. “Now we can bottle them in water. What Breslow said all those years ago — he was right.”

Raviprolu sees the breakthrough as a broader lesson about persistence in science.

“Something that seems impossible today might be possible tomorrow, if we continue to invest in science,” he said.

According to the researchers, smell-related problems arise when immune cells in the brain, known as “microglia,” begin removing connections between two important regions: the olfactory bulb and the locus coeruleus. The olfactory bulb, located in the forebrain, processes signals from scent receptors in the nose. The locus coeruleus, found in the brainstem, helps regulate this process through long nerve fibers that extend to the olfactory bulb.

“The locus coeruleus regulates a variety physiological mechanisms. These include, for example, cerebral blood flow, sleep-wake cycles, and sensory processing. The latter applies, in particular, also to the sense of smell,” says Dr. Lars Paeger, a scientist at DZNE and LMU. “Our study suggests that in early Alzheimer’s disease, changes occur in the nerve fibers linking the locus coeruleus to the olfactory bulb. These alterations signal to the microglia that affected fibers are defective or superfluous. Consequently, the microglia break them down.”

Alterations in the membrane

The team, led by Dr. Lars Paeger and co-author Prof. Dr. Jochen Herms, identified specific changes in the membranes of these nerve fibers. They found that phosphatidylserine, a fatty molecule normally located on the inside of a neuron’s membrane, had shifted to the outer surface.

“Presence of phosphatidylserine at the outer site of the cell membrane is known to be an “eat-me” signal for microglia. In the olfactory bulb, this is usually associated with a process called synaptic pruning, which serves to remove unnecessary or dysfunctional neuronal connections,” explains Paeger. “In our situation, we assume that the shift in membrane composition is triggered by hyperactivity of the affected neurons due to Alzheimer’s disease. That is, these neurons exhibit abnormal firing.”

Evidence From Animal Models, Human Tissue, and Brain Scans

The conclusions are supported by multiple lines of evidence. The researchers studied mice that show Alzheimer’s-like features, examined brain tissue from deceased patients, and analyzed positron emission tomography (PET) scans from individuals with Alzheimer’s or mild cognitive impairment.

“Smell issues in Alzheimer’s disease and damage to the associated nerves have been discussed for some time. However, the causes were unclear until yet. Now, our findings point to an immunological mechanism as cause for such dysfunctions — and, in particular, that such events already arise in the early stages of Alzheimer’s disease,” says Joachim Herms, a research group leader at DZNE and LMU as well as a member of the Munich-based “SyNergy” Cluster of Excellence.

Implications for Early Diagnosis and Treatment

So-called amyloid-beta antibodies have recently become available for the treatment of Alzheimer’s. For these therapies to work effectively, they must be given early in the disease process. This is where the new findings could make a difference.

“Our findings could pave the way for the early identification of patients at risk of developing Alzheimer’s, enabling them to undergo comprehensive testing to confirm the diagnosis before cognitive problems arise. This would allow earlier intervention with amyloid-beta antibodies, increasing the probability of a positive response,” says Herms.

A recent review published in Science China Life Sciences by Professor Yan-Jiang Wang and colleagues explores why progress has been limited. The researchers argue that focusing on a single cause has not worked because Alzheimer’s is far more complex. It arises from the combined effects of amyloid-beta (Aβ) buildup, Tau protein tangles, genetic risk factors, aging-related changes, and broader health conditions. Because of this complexity, they suggest that future treatments must take a more comprehensive and coordinated approach.

Alzheimer’s Disease Involves Multiple Interconnected Factors

The review highlights several key areas that are reshaping how scientists understand Alzheimer’s.

Beyond Amyloid-Beta (Aβ)

Amyloid-beta has long been a central target in Alzheimer’s research, but treatments aimed only at this protein have produced limited results. Scientists are now paying closer attention to Tau hyperphosphorylation, a process that leads to the formation of neurofibrillary tangles and the loss of brain cells. Addressing both Aβ and Tau may be necessary to slow disease progression more effectively.

Genetic Risk and Emerging Gene Therapies

Genetics play a major role in determining Alzheimer’s risk. While APOE ε4 remains the most widely recognized genetic factor, researchers are identifying additional variants linked to specific populations. Advances in genome editing (CRISPR/Cas9) are also being explored as potential one-time treatments that could modify disease risk at its source.

Aging and Whole-Body Health Shape Alzheimer’s Progression

Aging as a Central Driver

Aging is the strongest risk factor for Alzheimer’s and involves a range of biological changes. These include declining mitochondrial function, the buildup of damaged cells, and increased DNA damage. The review points to “senolytic” therapies, which aim to remove aging glial cells, as a possible way to improve brain health and slow decline.

Systemic Health and the Gut-Brain Connection

Alzheimer’s is also influenced by conditions that affect the entire body. Issues such as insulin resistance, high blood pressure, and imbalances in gut bacteria can worsen disease processes. Researchers are investigating whether existing diabetes medications and therapies targeting the gut-brain axis could help reduce these effects.

Toward Integrated and Multi-Target Alzheimer’s Therapies

The authors emphasize the need to move away from “reductionist” thinking and toward “integrated strategies.” This shift involves developing treatments that target multiple aspects of the disease at once. It also includes using advanced laboratory models, such as human iPSC-derived organoids, to test new therapies more effectively. In addition, precision medicine approaches based on early biomarkers like plasma pTau217 could allow doctors to identify and treat Alzheimer’s earlier and more accurately.

“Success in defeating Alzheimer’s hinges on interdisciplinary collaboration and holistic innovation,” the authors conclude. Their findings outline a path forward, suggesting that with the right combination of strategies, Alzheimer’s could eventually become a manageable or even preventable condition rather than an inevitable decline.

“We were surprised to find that zeaxanthin, already known for its role in eye health, has a completely new function in boosting anti-tumor immunity,” said Jing Chen, PhD, Janet Davison Rowley Distinguished Service Professor of Medicine and senior author of the study. “Our study show that a simple dietary nutrient could complement and strengthen advanced cancer treatments like immunotherapy.”

How Zeaxanthin Activates Cancer-Fighting T Cells

The research builds on years of work from Chen’s lab exploring how nutrients shape immune responses. By analyzing a large library of nutrients found in blood, the team identified zeaxanthin as a compound that directly enhances the performance of CD8+ T cells. These immune cells play a central role in identifying and destroying cancer cells.

CD8+ T cells rely on a structure called the T-cell receptor (TCR) to detect abnormal cells. The researchers found that zeaxanthin helps stabilize the formation of this receptor complex when T cells encounter cancer. This leads to stronger internal signaling, which increases T-cell activation, boosts cytokine production, and improves the cells’ ability to kill tumors.

Boosting the Power of Immunotherapy

In mouse studies, adding zeaxanthin to the diet slowed tumor growth. The effect became even more pronounced when combined with immune checkpoint inhibitors – a type of immunotherapy that has transformed cancer treatment in recent years. Together, the combination produced stronger anti-tumor responses than immunotherapy alone.

The team also tested human T cells that had been engineered to target specific cancer markers. In laboratory experiments, zeaxanthin enhanced these cells’ ability to destroy melanoma, multiple myeloma, and glioblastoma cells.

“Our data show that zeaxanthin improves both natural and engineered T-cell responses, which suggests high translational potential for patients undergoing immunotherapies,” Chen said.

A Safe, Accessible Nutrient With Broad Potential

Zeaxanthin is already widely used as an over-the-counter supplement for eye health. It is naturally present in foods such as orange peppers, spinach, and kale. Because it is inexpensive, easy to obtain, and well tolerated, researchers believe it could be quickly tested as a complementary approach to cancer treatment.

The findings also highlight the broader importance of diet in immune health. In earlier work, Chen’s team identified trans-vaccenic acid (TVA), a fatty acid found in dairy and meat, as another compound that enhances T-cell function through a different pathway. Together, these discoveries suggest that nutrients from both plant and animal sources may work in complementary ways to support the immune system.

What Comes Next for Zeaxanthin in Cancer Care

While the results are promising, the researchers stress that the work is still in its early stages. Most of the evidence so far comes from laboratory experiments and animal models. Clinical trials will be needed to determine whether zeaxanthin can improve outcomes for people with cancer.

“Our findings open a new field of nutritional immunology that looks at how specific dietary components interact with the immune system at the molecular level,” Chen said. “With more research, we may discover natural compounds that make today’s cancer therapies more effective and accessible.”

The study, “Zeaxanthin augments CD8+ effector T cell function and immunotherapy efficacy,” was supported by grants from the National Institutes of Health, the Ludwig Center at the University of Chicago, and the Harborview Foundation Gift Fund.

Additional authors include Freya Zhang, Jiacheng Li, Rukang Zhang, Jiayi Tu, Zhicheng Xie, Takemasa Tsuji, Hardik Shah, Matthew Ross, Ruitu Lyu, Junko Matsuzaki, Anna Tabor, Kelly Xue, Chunzhao Yin, Hamed R. Youshanlouei, Syed Shah, Michael W. Drazer, Yu-Ying He, Marc Bissonnette, Jun Huang, Chuan He, Kunle Odunsi, and Hao Fan from the University of Chicago; Fatima Choudhry from DePaul University, Chicago; Yuancheng Li and Hui Mao from Emory University School of Medicine, Atlanta; Lei Dong from University of Texas Southwestern Medical Center, Dallas; and Rui Su from Beckman Research Institute, City of Hope, Duarte, CA.