Researchers discovered a connection between methylmalonic acid (a sign that your cells aren’t making energy properly) and neurofilament light chains (a marker of brain cell damage). Using data from over 2,000 Americans, scientists found that people with higher levels of methylmalonic acid also had higher levels of brain damage markers. This relationship was especially strong in people with diabetes or low vitamin B12 levels. While this is an interesting finding, more research is needed to understand if fixing the energy problem would actually prevent brain damage.

The Quick Take

  • What they studied: Whether a blood marker showing that cells aren’t producing energy well (methylmalonic acid) is connected to another blood marker showing brain cell damage (neurofilament light chains)
  • Who participated: 2,070 Americans from a national health survey, with an average age of 47 years old, representing a mix of different ages, backgrounds, and health conditions
  • Key finding: People with higher methylmalonic acid levels had higher brain damage markers. The connection was especially strong in people with diabetes or low vitamin B12, where the link was much more pronounced
  • What it means for you: This suggests that problems with how your cells make energy might be connected to brain cell damage, but this is early research. It doesn’t prove that one causes the other, and more studies are needed before doctors would change how they treat patients

The Research Details

This was a cross-sectional study, which is like taking a snapshot of a large group of people at one point in time. Researchers looked at data from the National Health and Nutrition Examination Survey (NHANES) from 2013-2014, which regularly collects health information from thousands of Americans. They measured two things in people’s blood: methylmalonic acid (which shows how well cells are making energy) and neurofilament light chains (which shows if brain cells are being damaged). Then they used statistical tools to see if these two measurements were connected to each other.

The researchers used a method called multiple linear regression, which helps them understand the relationship between two things while accounting for other factors that might affect the results. They also looked at whether the relationship was straight or curved, and they checked if the connection was stronger in certain groups of people, like those with diabetes or vitamin B12 deficiency.

This type of study is useful for finding connections between health markers, but it can’t prove that one thing causes another. It’s like noticing that people who carry umbrellas are wet—it doesn’t mean the umbrella made them wet; they both might be connected to rain.

Understanding connections between cell energy problems and brain damage is important because it might help doctors identify people at risk for brain problems earlier. If scientists can prove that fixing energy problems prevents brain damage, it could lead to new treatments. This study is a first step in that direction.

This study has some strengths: it included a large, diverse group of Americans, and the researchers carefully adjusted their analysis to account for other factors that might affect the results. However, because it’s a snapshot in time (cross-sectional), we can’t know if the energy problem came before the brain damage or if they developed together. The study also relied on blood tests, which are good but don’t tell us everything about what’s happening in the brain. More research following people over time would be needed to confirm these findings.

What the Results Show

The main finding was that for every small increase in methylmalonic acid (a marker of cell energy problems), there was a measurable increase in brain damage markers. Specifically, when methylmalonic acid went up by 1 unit, brain damage markers went up by about 3 units. People with the highest levels of methylmalonic acid had about 5 units more brain damage markers compared to those with the lowest levels.

Interestingly, the relationship wasn’t perfectly straight—it had a turning point. Below a certain threshold (5.51 units of methylmalonic acid), the connection was weaker. But above that point, the connection became much stronger, with brain damage markers jumping up significantly. This suggests that once methylmalonic acid reaches a certain level, the risk of brain cell damage increases more dramatically.

The connection was especially strong in two groups: people with diabetes and people with low vitamin B12 levels. In these groups, the relationship between energy problems and brain damage markers was much more pronounced than in the general population. This suggests that these conditions might make the brain more vulnerable to damage from energy problems.

The study found that the relationship between energy problems and brain damage was consistent across different age groups and sexes, though it was stronger in people with existing health conditions. The fact that vitamin B12 status affected the strength of the relationship is interesting because vitamin B12 is important for both energy production and nerve health.

This is one of the first studies to directly examine the connection between methylmalonic acid (energy problems) and neurofilament light chains (brain damage markers) in a large population. Previous research has shown that both of these markers are important in various brain diseases, but the connection between them hadn’t been well studied. This research adds to our understanding of how cell energy problems might contribute to brain damage.

This study has several important limitations. First, because it’s a snapshot in time, we can’t tell if energy problems cause brain damage or if they happen together for other reasons. Second, the study only measured these markers once in each person’s blood, so we don’t know how they change over time. Third, while the study included many people, the effect sizes were relatively small, meaning the practical importance isn’t yet clear. Finally, the study can’t explain why the relationship exists or what the exact mechanism is—it only shows that the two things are connected.

The Bottom Line

Based on this research alone, there are no specific new treatments or lifestyle changes to recommend. However, if you have diabetes or low vitamin B12 levels, maintaining good control of these conditions and ensuring adequate B12 intake may be important for overall brain health. This is a moderate-confidence finding that needs confirmation with additional research before it changes medical practice.

People with diabetes, those with vitamin B12 deficiency, and anyone concerned about brain health should be aware of this research. However, this is early-stage research, and it shouldn’t change current medical treatment. People with neurological concerns should continue following their doctor’s advice. This research is most relevant to scientists and doctors working on brain health and metabolism.

This is basic research aimed at understanding disease mechanisms, not a treatment study. Even if future research confirms these findings, it would likely take several years of additional studies before any new treatments based on this work would be available to patients.

Want to Apply This Research?

  • Track vitamin B12 intake (through diet or supplements) and monitor any neurological symptoms like tingling, numbness, or memory changes. Record these weekly to identify patterns over time.
  • If you have diabetes or low B12 levels, use the app to remind you to take B12 supplements if prescribed, eat B12-rich foods (like meat, fish, eggs, or fortified cereals), and maintain stable blood sugar through consistent meals and activity.
  • Set up monthly check-ins to log energy levels, cognitive function (memory, focus), and any neurological symptoms. Share this data with your healthcare provider to help them monitor your brain health over time, especially if you have risk factors like diabetes.

This research describes an association between two blood markers and does not prove that one causes the other. This is early-stage research that has not yet led to new clinical recommendations. If you have concerns about brain health, neurological symptoms, or vitamin B12 deficiency, please consult with your healthcare provider. Do not make changes to your medical treatment based on this study alone. Anyone considering B12 supplementation or other interventions should discuss this with their doctor first, especially if they take medications or have existing health conditions.