Medical Bulletin 29/ May/ 2024 - Video

In a recent study, researchers from Rush University Medical College in Chicago found compelling evidence suggesting that eating late at night, particularly within three hours of bedtime, may significantly increase the risk of developing colorectal cancer.

The study reinforced long-standing advice from experts to avoid late-night meals, especially those high in fats and sugars.

Research has found that eating close to bedtime may disrupt the body's internal clock, or "circadian rhythm." Unlike the central circadian rhythm regulated by the brain's release of melatonin to induce sleep, late-night eating appears to affect the "peripheral circadian rhythm." This peripheral system governs how various parts of the body adjust their functions in response to the transition from day to night. Disruption of this rhythm could potentially contribute to the increased risk of adenoma formation and, subsequently, colorectal cancer.

An adenoma is a small, noncancerous lesion that can potentially turn cancerous over time, with an estimated 5% to 10% undergoing malignant transformation. The risk associated with adenomas varies depending on their size and location within the gastrointestinal tract.

The research team conducted a survey involving 664 individuals undergoing colonoscopy screenings for cancer. Remarkably, 42% of the participants reported being late-night eaters. The findings revealed that this group was 46% more likely to have an adenoma detected during their colonoscopy compared to those who did not eat late at night.

"It is true that eating later at night can disrupt your circadian rhythm. In addition, many of my patients have told me that when they do eat later at night, they don't always make the healthiest food choices. Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs. So, eating late at night can also lead to unwanted weight gain. So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome,” said Amy Bragagnini, spokesperson for The Academy of Nutrition and Dietetics.

The study emphasized the importance of aligning meal times with the body's natural rhythms to maintain overall health and reduce cancer risk. As the evidence continues to grow, the advice to avoid late-night eating becomes even more compelling, offering another reason to heed expert dietary recommendations.

Reference: Digestive Disease Week conference, Washington, DC, May 18-21, 2024; Edena Khoshaba, medical student Rush University Medical College Chicago; Amy Bragagnini, MS, RD, CSO, spokesperson, Academy of Nutrition and Dietetics.

Although scientists still do not know the exact cause of Alzheimer’s disease, most agree that the disease is characterized by the clumping of certain proteins — beta-amyloid and tau — in the brain.

In a study published in the journal GeroScience, scientist examined how the accumulation of large protein clumps in the brain, called insoluble proteins, in general, might accelerate Alzheimer’s disease.

Protein clumping happens when proteins in the brain stick together in the wrong way. In Alzheimer's disease, two types of proteins, beta-amyloid and tau, are involved. Beta-amyloid forms sticky plaques outside brain cells, blocking their communication and causing inflammation. Tau proteins, which normally help support brain cells, form tangles inside the cells, disrupting their function.

These plaques and tangles damage the brain, leading to the memory loss and confusion seen in Alzheimer's disease.

In the study, researchers, using a worm model, discovered that beta-amyloid causes a massive amount of insolubility in other proteins, especially in a subset of proteins researchers called “the core insoluble proteome.”

The insoluble proteins found in the core insoluble proteome have already been linked to other neurodegenerative conditions including Parkinson’s disease and Huntington’s disease, according to the researchers.

Next, researchers wanted to find a way to potentially undo how beta-amyloid makes proteins insoluble. They noticed that many mitochondrial proteins become insoluble as people age and when beta-amyloid is present. So, they thought that improving the quality of mitochondrial proteins might help counteract some of the harmful effects of beta-amyloid.

These findings suggest that beta-amyloid likely causes many proteins, especially those in mitochondria, to become insoluble. This problem with proteins is similar to changes seen in aging.

The discovery that targeting mitochondrial health can mitigate some of these aging effects suggests a potential novel approach to addressing Alzheimer’s disease.

“It has been known for some time that mitochondria can be negatively impacted by [beta-amyloid] but we show that this is likely due to protein insolubility. Luckily, cells possess a way to recycle damaged mitochondria through a process called mitophagy. Our lab and others study a small molecule that boosts mitophagy to rejuvenate mitochondria. We reasoned that using a pharmacological approach to clear away the insoluble proteins from mitochondria could prevent some of the toxic effects of [beta-amyloid] and that’s exactly what we found,” said the study authors.

Reference: Anderton, E., Chamoli, M., Bhaumik, D. et al. Amyloid β accelerates age-related proteome-wide protein insolubility. GeroScience (2024). https://doi.org/10.1007/s11357-024-01169-1

In a study published in the journal Proceedings of the National Academy of Sciences (PNAS), University of Oklahoma researchers investigated a drug’s ability to prevent fat buildup in the liver. This condition often accompanies obesity and can lead to serious fatty liver disease.

The study expands on an earlier finding by Tiangang Li, Ph.D., and a team of researchers at OU Health Harold Hamm Diabetes Center. They discovered that a drug originally designed to fight cancerous tumors can also enhance insulin sensitivity and reduce blood sugar levels. This drug works by stopping the breakdown of a particular protein essential for all cells to react to insulin.

Cancer remains a significant global health challenge, with its prevalence steadily increasing over the years. According to the World Health Organization (WHO), cancer is one of the leading causes of morbidity and mortality worldwide, responsible for an estimated 10 million deaths annually.

In the study, researchers studied mice and removed a gene called Cul 3 from their livers. Normally, this gene is inhibited by the drug to stop the breakdown of a specific protein. By getting rid of the gene, they could see what happens when mice become obese from eating a lot of fatty foods.

The results showed that when the gene was removed, mice on a high-fat diet didn't store fat in their livers, even though they were overweight. Instead, the fat went into their bloodstream and ended up in other tissues like muscles, where it shouldn't be stored. This caused the muscles, which are the body's biggest organ, to respond poorly to insulin, leading to high blood sugar levels in the mice.

“By eliminating the gene, we aggressively prevented fat accumulation in the liver, but this actually worsened insulin resistance in the muscle, which tells us that fat metabolism in these organs is interconnected. These findings suggest that, in addition to lowering liver fat, the simultaneous reduction of obesity and improvement of insulin sensitivity are important for treating fatty liver disease. That’s because these improvements outside the liver are critical for preventing the fat that enters the liver from also building up in other tissues,” said Li.

“The research also illustrates why treating chronic conditions like Type 2 diabetes and fatty liver disease is never simple – an improvement in one area may trigger negative effects in another. Even so, the study was extremely helpful for understanding the process by which fatty liver disease occurs and what the drug is doing in the context of that disease,” said study co-author Jed Friedman, director of OU Health Harold Hamm Diabetes Center and a professor in the OU College of Medicine.

Reference: Gu, Lijie, Li, Tiangang, et al.; Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance; 2024; Proceedings of the National Academy of Sciences; doi:10.1073/pnas.2320934121; https://www.pnas.org/doi/abs/10.1073/pnas.2320934121