Metabolic Mind: How Metabolites Affect the Brain
We all know that one mom who is super health-conscious; the one who only cooks with non-GMO, farm raised, organic produce and is obsessed with Instagram food trends. If you haven’t met one yet, you should come over and have dinner at my house.
My mom is what society would call a health-nut. Even though she’s a full time mom, she spends a lot of time learning about how what we eat affects our overall wellbeing. I, the budding scientist in the family, love to question her rationale for why eating more kale is going to suddenly have a positive effect on my anxiety and depression. She’s always telling me, “you are what you eat!”
Until I started studying metabolomics, I didn’t realize what a profound impact what we eat has on the way our body functions, and even our mind works. Sorry, Mom, maybe I should’ve listened to you about what goes in my salads after all …
What is Metabolomics?
Metabolomics is the study of the human metabolome, and the human metabolome is the collection of all of the products (aka metabolites) of chemical reactions happening within the human body.
Woah. Those were some big words. Basically, metabolomics is the study of EVERY SINGLE CHEMICAL REACTION IN YOUR BODY! All of them! From the reactions that cause your muscle fibers to grow, to the ones that cause your brain to stay awake while you read this article.
Specifically, I’ve been looking into primary metabolites, the ones that are directly involved in the body’s basic metabolic functions and development. These can be proteins, carbs, amino acids, fats, or nucleic acids like DNA and RNA. They are essential to the human body and it’s functions; that’s what distinguishes them from the non-essential secondary metabolites.
For example: The human body needs to synthesize and produce certain proteins to survive, but a tree that produces rubber would not die if this metabolic function ceased. By understanding the metabolites in the human body and what role they play in the way we function, we can figure out how to manipulate those chemical reactions to treat different health issues.
A lot of the research in the metabolomics industry is currently focused on personalized medicine, specifically drug discovery and treatment development.
No company I know of is taking it upon themselves to figure out ways to change the metabolic processes of the brain to mitigate the symptoms of mental illness, so I took it upon myself to do some research…
The Major Brain Metabolites
As I was studying the different ways that metabolites affect brain activity, I started looking at the Human Metabolome Database (AWESOME resource for anyone learning about metabolites and their function; its basically an encyclopedia of metabolic information!)
I started by looking at a paper titled the “Regional Differences in the Concentrations of Metabolites in the Brain of Healthy Children”, published by a team of scientists in Cracow, Poland. It chronicled the major metabolites in the brain and their concentrations within its different parts (the hippocampus, basal ganglia, frontal lobes, and cerebellum).
Everyone’s brain has different levels of metabolites, and these vary greatly based on the person and the region of the brain. These scientists found that hippocampal levels of the major brain metabolites were lower in this region than other regions, while concentrations of these metabolites in the cerebellum were higher than those in the frontal lobe or hippocampus.
These major metabolites include:
N-acetylaspartate (NAA)
This metabolite is the second most concentrated amino acid in the brain. According to this article, it is found only in neurons and is thought to contribute to their healthy function. When NAA levels get too high, NAA can become…
- A neurotoxin: a compound that disrupts or attacks neural tissue.
- An acidogen: an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems.
- A metabotoxin: an endogenously produced metabolite that causes adverse health effects at chronically high levels.”
Abnormal concentrations of NAA have even been linked to schizophrenia
Basically, too much NAA = potenitally drastic health consequences
Choline (Cho)
An essential metabolite for the synthesis of compound necessary in a form of neurotransmission. Cho is important in cognitive processes and brain development”
A Cho deficiency can lead to cognitive impairments, including deficits of memory and low attention.
Creatine (Cr)
Ah, our last amino acid crucial to neurological function.
Within humans, Cr participates in a number of enzymatic reactions. Humans need creatine to recycle ATP (the energy unit used by our cells), so it’s not surprising that Cr is found in the brain when we know that the brain is responsible for 20% of the body’s energy consumption.
Like NAA, abnormal concentrations of Cr have also been linked to schizophrenia.
Honorable Mentions:
There were a couple more metabolites that also play a major role in our brains, but weren’t especially important when it came to studying their part in mental illness
- Myoinositol
- Lipids
- Lactates
The Relationship between NAA, Cho, Cr, and Mental Illness
A 2015 study run by Drs. Moon, Kang, and Jeong discovered a correlation between Generalized Anxiety Disorder and a low ratio of choline to NAA in the patient’s dorsolateral prefrontal cortex, “which is closely related with symptom severity and cognitive dysfunction.”
In these patients with GAD, their levels of Cho were greatly decreased compared to their levels of NAA. This could mean that either something is inhibiting the production of Cho in the brain, or that this part of the brain is producing way too much NAA.
High levels of NAA don’t just affect anxiety: a study by
Shanghai Mental Health Center found that “the NAA/Creatine ratio was significantly higher among OCD patients than among healthy controls (F = 4.76, P = 0.037).”
As I discussed earlier, high levels of NAA can have catastrophic effects on the brain, while low levels of Cho prevent the brain from focusing or solidifying memories. Either cause of this low ratio is detrimental to brain function.
These findings convey a correlation between high levels of NAA compared to lower levels of Cr and Cho. This definitely plays a role in brain chemistry, ultimately affecting one’s mental health.
So what role does food play in all of this?
Choline is considered an essential vitamin, and it’s actually possible to up your choline intake by eating foods with greater amounts of choline. For someone with an anxiety disorder, this may have an impact on the ratios in your brain, and have an impact on anxiety caused by dysfunctional brain chemistry.
There are a variety of foods that are rich in choline: milk, eggs, liver, and peanuts are just a few.
You could also change your dietary habits to avoid eating things that are rich in NAA. A study published by DuPont Agriculture and Nutrition found that out of all of the foods they tested (fruits, vegetables, meats, grains, and beverages), the highest concentration of NAA was found in roasted coffee beans. Maybe its time to kick that coffee addiction to the curb; if the jitters weren’t worsening your anxiety, the high NAA content probably is!
Creatine is absorbed in our diets more regularly. Humans obtain about 1 gram of Cr per day from an omnivorous diet according to the HMDB. In addition, a Cr deficiency could be combatted by eating animal-based proteins, although oats have also been found to contain Cr.
Why does this matter?
Our dietary habits obviously aren’t the only reasons why we experience mental illness. There are so many different factors; your genetic makeup, environment, and connectome all play a role in the way your brain functions, and therefore they are responsible for dysfunction as well. While therapy and medication can have a major effect on people experiencing debilitating conditions like GAD and OCD, an integrative approach can also have an impact.
In addition, too much or too little of anything is not a good thing. It is important to be balanced in the foods we eat and in the nutrients we obtain. Dietary changes aren’t going to be some miracle cure for mental health issues. It is possible they will have an effect on the brain’s metabolism, but remember that there are so many factors as to why the brain works the way it does.
After all this research, I’ve decided that maybe my mom is on to something when she tells me to watch what I’m putting into my body. As crazy as my mom sounds sometimes, she’s right when she tells me that what I eat affects how I think and how I feel!
She never really meant “You are what you eat”…“You think how you eat!”
Key Takeaways:
- Metabolomics is the study of your metabolome and the metabolties that make it up; basically the products in all the chemical reactions that occur in an organism
- The brain has three amino acids that function as major metabolites: N-acetylaspartate (NAA), Choline (Cho), and Creatine (Cr)
- Higher levels of NAA and lower levels of Cho and Cr are associated with mental illness
- The foods we eat can have an impact on the nutrients we absorb, directly affect the metabolites in our brain and therefore our mental health
Goal for this week: evaluate your dietary habits!
Make sure to leave a clap on this article and email me at faithinello@gmail.com to ask me questions about my continued research into the field of metabolomics, talk to me about mental health, or chat more about different ways we can change our diets to manipulate our brain chemistry!
