Molly Knudsen, M.S., RDN


September 16, 2023

Molly Knudsen, M.S., RDN

Registered Dietitian Nutritionist

By Molly Knudsen, M.S., RDN

Registered Dietitian Nutritionist

Molly Knudsen, M.S., RDN is a Registered Dietician Nutritionist with a bachelor’s degree in nutrition from Texas Christian University and a master’s in nutrition interventions, communication, and behavior change from Tufts University. She lives in Newport Beach, California, and enjoys connecting people to the food they eat and how it influences health and wellbeing.

Healthy, Vibrant Mature Woman Picking Tayberries In The Garden

Image by Rob and Julia Campbell / Stocksy

September 16, 2023

With each passing year comes new experiences, memories, and relationships that shape how you think and move about the world. Because wisdom really does come with age.

But at the same time, the brain undergoes a series of physiological shifts 1that threaten the longevity of a sharp mind: the brain shrinks, blood flow changes (often decreasing, and communication between neurons becomes less effective. 


This ad is displayed using third party content and we do not control its accessibility features.

Adopting healthy lifestyle habits (like eating an antioxidant-rich diet, moving your body regularly, and keeping alcohol intake low) can protect you against cognitive decline and neurodegenerative diseases. 

A new scientific review published in the journal Nutrients calls out three compounds in particular—vitamin B12, folate, and choline2—that may provide an extra layer of protection for the brain when supplemented in the diet. 

Here’s what you need to know.

Methylation plays a big role

First, the study authors shed light on the role of one-carbon (1C) metabolism in aging processes. This is a broad term to describe the reactions in the body that regulate cell multiplication and stress resistance. 

In the brain, 1C metabolism plays an important role in methylation, the breakdown of fats, and DNA repair. 

Vitamin B12, folate (aka vitamin B9), and choline are all highly influential in these pathways—primarily through their role in the methylation of homocysteine to methionine. 

Now, studies link high amounts of circulating homocysteine in the blood to poor brain health and even Alzheimer’s disease, stroke, and vascular dementia (dementia from blood flow problems). 

So low intake levels of these nutrients (or poor absorption of them), can lead to high homocysteine levels and negatively impact the brain. 

While these nutrients are found naturally in the diet, this new review summarizes the important role of supplementation for additional health benefits. 


This ad is displayed using third party content and we do not control its accessibility features.

The synergy of vitamin B12 and folate

Optimal intake and blood levels of these nutrients can be challenging for people to maintain.

For vitamin B12, levels tend to decline from possibly eating less animal proteins, metabolic changes, and impaired absorption of the nutrient. Some research even shows the deficiency of this vitamin may exacerbate the loss of brain volume with aging—with greater loss seen in those with high homocysteine levels at the beginning. 

And about half the population 3has the MTHFR gene variation that impedes their ability to convert folate from foods (or folic acid from supplements) to its active 5-MTHF form. The trick around this? Take an already methylated form of folate.

Researchers are looking at the impact of both of these nutrients on brain health. 

When used with standard therapy for dementia2, B12 and folic acid helped improve measures of cognition compared to taking a placebo. 

And when people with mild cognitive impairment received B12 and folic acid, they also had improved cognitive testing scores and decreased levels of inflammation compared to others and those who only took B12 or folic acid individually. 

Choline may help with memory

Choline is neither a vitamin nor mineral, but it’s a feeder of those metabolic pathways in the brain and is a precursor for two critical brain compounds: acetylcholine and phosphatidylcholine4.

The scientists of this review cited a study showing that elderly folks with daily choline intake ranging from 187 to about 400 milligrams5 had about half 50% of the risk of cognitive impairment.  

Another study showed choline intake was linked to better verbal memory, visual memory, verbal learning, and executive function in older adults. 

A favorite choline-containing compound for memory and cognition is citicoline. Citicoline is a nootropic has been shown to help slow (and even reverse) cognitive decline.


This ad is displayed using third party content and we do not control its accessibility features.

The takeaway 

One way to protect your brain health as you age is to keep your homocysteine levels at the low levels they should be (ideally 15 mcmol/L or less). 

Making sure you’re getting enough of these three essential nutrients in their most readily absorbable forms (aka folate as L-5-methyltetrahydrofolate and B12 as methylcobalamin) may be an effective way to protect your brain. Consider a high-quality multi with a built-in B complex (here are some of our top choices).