Scientists have long known that physical ailments can also affect the brain. Problems such as obesity, high blood pressure and insulin resistance put a strain on the metabolism and cardiovascular system. Over time, this stress can accelerate cognitive decline and increase the risk of Alzheimer’s disease. Researchers at Arizona State University, in collaboration with partners from several institutions, now report that these effects may occur much earlier than expected. In young adults with obesity, the team identified biological markers associated with inflammation, liver stress and early brain cell damage. These small but measurable changes are similar to patterns seen in older adults with cognitive impairment.
The study revealed another important finding. Many of the young adults had unusually low blood levels of choline, a nutrient that is essential for liver health, regulating inflammation and protecting long-term brain function. “This research adds to the growing evidence that choline is a valuable marker of metabolic and brain dysfunction – and underscores the importance of adequate daily intake, as it is essential for human health,” says Ramon Velazquez. “Several new reports published this month link reduced blood choline levels to behavioral changes, including anxiety and memory impairment, as well as broader metabolic disorders.” Velazquez is leading the study as part of ASU’s Banner Neurodegenerative Disease Research Center, working with colleagues at ASU’s School of Life Sciences, Banner Sun Health Research Institute and the Mayo Clinic, AZ. The results were published in Aging and Disease.
Early Effects of Obesity on the Brain
Although it is well known that obesity increases the risk of chronic diseases such as heart disease and type 2 diabetes, this study suggests that its impact on the brain may develop much earlier. The researchers measured elevated levels of pro-inflammatory proteins and enzymes that indicate stress on the liver. They also found increased levels of neurofilament light chain (NfL), a protein that is released when neurons are damaged. NfL was associated with low blood choline levels in these young adults, although behavioral changes are not normally expected at this age.
NfL has been shown to be an important early warning signal for neurodegeneration. It is found in elevated levels in people with mild cognitive impairment and Alzheimer’s disease. The observation of these markers in young adults is significant and suggests that obesity may have measurable effects on the brain long before symptoms appear. The findings support the notion that inflammation, metabolic stress and early neuronal changes may be linked in ways that begin much earlier in life than previously thought.
The Influence of Choline on Brain Health and Metabolism
A key aspect of the study concerns choline, a nutrient that is essential for cell membrane structure, inflammation control, liver function and the production of acetylcholine, a neurotransmitter important for memory. Choline is particularly important for the structure of cell membranes, as it is a component of phospholipids that surround and stabilize every cell in the body. Choline also fulfills a central function in the nervous system: it serves as a precursor for the neurotransmitter acetylcholine, which is necessary for memory, learning processes, muscle movements and the regulation of the cardiovascular system. In addition, choline is crucial for fat metabolism and liver health, as it supports the transport of fat from the liver and can thus prevent fatty liver. It also plays a particularly important role during pregnancy because it supports the brain development of the unborn child.
The body can only produce small amounts of this nutrient itself, so it must also be taken in through the diet. Rich food sources include eggs, poultry, fish, beans and cruciferous vegetables such as broccoli, cauliflower and Brussels sprouts. Participants with obesity had significantly lower blood choline levels, and these reductions corresponded with greater signs of inflammation, insulin resistance, elevated liver enzyme levels and NfL. The researchers also observed that the women in the study had lower choline levels than the men, which is a noteworthy finding since women are more likely to suffer from cognitive aging and Alzheimer’s disease. National dietary surveys show that many Americans, especially teens and young adults, are not meeting the recommended choline intake.
The problem of inadequate choline intake affects Europe in a similar way. Studies show that the average choline intake in many European countries is also below the recommended levels. Since choline supports the brain and liver, a long-term deficiency can increase susceptibility to metabolic stress and increase the effects of obesity on the brain. “Most people are not aware that they are not consuming enough choline,” said Wendy Winslow, first author of the study. “Including choline-rich foods in the diet can reduce inflammation and support both the body and the brain as we age.”
Nutrient Considerations for New Weight Loss Drugs
Modern weight loss medications have revolutionized the treatment of obesity by effectively helping to reduce weight and improve metabolic and cardiovascular health. However, the appetite suppressant effect of GLP-1 drugs significantly reduces food intake. This can lead to an inadequate intake of choline and other important nutrients. The authors point out that further studies are needed to investigate whether the combination of GLP-1 therapies with adequate dietary choline intake can help maintain metabolic resilience and overall health.
The study involved 30 adults between the ages of 20 and 39, made up of equal numbers of overweight and normal weight individuals. Each participant provided a fasting blood sample. Samples were analyzed for circulating choline, inflammatory cytokines, insulin, glucose, liver enzymes, additional metabolic parameters and NfL. Comparisons between groups revealed consistent patterns: lower choline levels, greater inflammation, metabolic stress and evidence of neuronal damage in young adults with obesity. To understand how these findings relate to brain aging, the team compared their results with data from older adults who had been diagnosed with mild cognitive impairment or Alzheimer’s disease.
The same combination of low choline levels and high NfL was found in both young and older adults. This suggests that biological changes associated with Alzheimer’s may begin many years before the onset of symptoms, particularly in people suffering from metabolic stress or obesity.
Research Paves the Way for New Strategies to Protect Brain Health
Overall, the study shows a strong link between obesity, inflammation, choline levels and early neuronal stress. This combination could explain why metabolic disorders increase the likelihood of cognitive decline later in life. Although the study does not establish a causal link, it identifies a group of biomarkers that are very similar to those found in older adults with cognitive impairment. The results are also consistent with previous studies in rodents showing that insufficient choline intake in mice can lead to obesity, metabolic problems and increased pathogenesis of Alzheimer’s disease.
“Our results suggest that in young adults, good metabolic health and adequate choline intake contribute to neuronal health, laying the foundation for healthy aging,” says Jessica Judd, co-author of the study. Further research will investigate how early metabolic stress can influence the long-term risk of neurodegenerative diseases, with the ultimate aim of developing new strategies to protect brain health across the lifespan.
Other Nutrients that Can Have a Positive Effect on the Brain
Omega-3 fatty acids: Omega-3 fatty acids have long been shown to contribute to good heart health and now also play a role in cognitive health. A study in mice found that omega-3 polyunsaturated fatty acid supplementation led to better object recognition memory, spatial and localization memory (consciously retrievable memories such as facts and knowledge) and better retention of negative responses. Foods rich in omega-3 fatty acids include salmon, flaxseed oil and chia seeds.
Phosphatidylserine and phosphatidic acid: Research has shown that a combination of phosphatidylserine and phosphatidic acid can improve memory, mood and cognitive function in older people.
Walnuts: A diet supplemented with walnuts may have a positive effect on reducing the risk, delaying the onset or slowing the progression of Alzheimer’s disease in mice.
Citicoline: Citicoline is a natural substance found in the body’s cells that contributes to the development of brain tissue, regulating memory and cognitive function, improving communication between neurons and protecting neural structures from free radical damage. Clinical studies have shown that citicoline supplements can help maintain normal cognitive function in old age and protect the brain from free radical damage.
Cocoa flavanols: Cocoa flavanols have been linked to improved circulation and heart health, and preliminary research also suggests a possible link to improved memory. For example, cocoa flavanols have been shown to improve the function of a specific part of the brain called the dentate gyrus, which is associated with age-related memory.
Magnesium: Magnesium supplements are often recommended for people who have suffered a severe concussion. Foods rich in magnesium include avocados, soybeans, bananas and dark chocolate.
Blueberries: Blueberries are known for their antioxidant and anti-inflammatory properties as they are high in anthocyanins, a flavonoid that enhances the health-promoting properties of foods. Moderate consumption of blueberries may provide neurocognitive benefits such as improved neuronal signaling in the brain centers.