The Link Between B-12, Brain Function, and Memory

DR GROUP–Due to vitamin B-12’s association with energy metabolism, you might wonder what purpose it serves in your brain’s health and memory. There are a few complex roles that this B vitamin participates in—beyond releasing energy—that play a role in neurological function. This article will shed light on the primary reasons B-12 is indispensable to healthy brain aging.

Vitamin B-12 primarily functions as an enzyme cofactor. This role includes the production of red blood cells, the synthesis of myelin (a protein that coats nerves), genetic expression, amino acid balance, and the detoxification of hormones, neurotransmitters, and other chemicals. These activities are essential to maintaining brain function and preventing memory loss and cognitive decline.[1, 2]

A number of brain diseases are associated with low B-12 status, particularly those conditions characterized by cognitive difficulties like muddled thinking and forgetfulness. But the precise mechanism wasn’t identified until relatively recently. More researchers and doctors are beginning to see that cognitive issues associated with advanced age might be due, at least in part, to undiagnosed low B-12 status.[1, 3]

Brain atrophy is a normal part of the aging process, but years of unhealthy diet and lifestyle choices can significantly increase this rate of decline. Nearly 23% of Americans who reach their 70s will develop at least some degree of cognitive impairment. For far too many, this is an irreversible, progressive decline that requires specialized care by family members or costly facilities.[4, 5]

One study found that low B-12 status was associated with poorer memory performance in older adults when compared to those with adequate intake. Remarkably, older adults with insufficient B-12 had structural anomalies in the region of the brain most associated with memory, the hippocampus.[2] Emerging research has found that B vitamin supplementation—specifically with folate, B6, and B-12—slows the progression of brain tissue loss and cognitive impairment. These benefits are limited to those with a low B vitamin status. If you already have normal serum levels of these B-vitamins, adding extra doesn’t seem to have any beneficial effects on brain health.[3, 6] That said, a variety of factors increase the likelihood of poor nutritional status in aging populations.

A Primer on B-12 Absorption

From food to cell, B-12 meanders through a complicated, multi-step route, meaning that adequate intake isn’t the only factor that determines whether you have enough in your body. Your B-12 status is determined by how much you get in your diet, how well your digestive system frees the vitamin from food, how much you can absorb from your small intestine, and how easily you can convert dietary B-12 to an active form your cells can use.[7]

B-12 attaches and detaches itself to and from several carrier proteins along this route with the aid of digestive juices. Essentially, it needs to catch several different buses to reach its destination, i.e., before it can be absorbed from the digestive tract into your body. It first attaches to R-factor (haptocorrin) in your saliva and is then cleaved from this complex by the hydrochloric acid in your stomach. From here, B-12 binds to intrinsic factor (IF) at the beginning of the small intestine. The last stretch of the small intestine absorbs the IF/B-12 complex, transporting it across the intestinal wall and inside the body. Before the vitamin circulates in your blood, it has to decouple from IF and join another carrier protein called transcobalamin. Once attached to transcobalamin, it travels to where it’s needed in the body. Once it makes its way inside individual cells, it may require further processing if it’s not in its active form.[7]

Absorption of B-12 in Older Adults

As we age, we begin to slow down in more ways than one. Organ function becomes less efficient, a consequence that extends to the stomach. As many as 30% of older adults (seniors aged 60+ years) develop a condition called atrophic gastritis, or achlorhydria. This condition means that the stomach secretes less acid with which to digest food. Without gastric acid, B-12 is not able to separate from R-factor and bind to IF for absorption, preventing B-12 absorption despite sufficient dietary intake. To analogize, the B-12 you ate can’t get off the bus (R-factor), as it drives past the exit for the airport (last third of the small intestine), and misses its flight from the digestive system into the blood.[8, 9]

Elderly populations also manifest a lifetime of damage and immune and organ decline that leads to decreased B-12 absorption. The specific health issues that contribute to low B-12 status include intestinal inflammation, autoimmune disorders that prevent the production of B-12 carrier proteins, damage to the wall of the intestine, hostile gut organism overgrowth, pernicious anemia, and certain medications.[9]

Age-associated Factors That Affect B-12 Status

With age, the body’s ability to absorb and use vitamin B-12 can change. Below are common, age-associated factors that affect B-12 status.

  • Insufficient gastric acid output
  • Chronic H. pylori overgrowth
  • Imbalance of the gut microbiota
  • Taking medications such as proton pump inhibitors and Metformin
  • Folate deficiency
  • Decreased production of intrinsic factor (IF), usually associated with autoimmune disorders
  • A prolonged history of inflammation in the intestine
  • Decreased appetite associated with aging or illness

How Low B-12 Status Harms Brain Health

B-12 status intersects with brain health a few different ways. Inadequate B-12 in the body promotes brain shrinkage and atrophy (similar to muscle wasting), harms cardiovascular health, and decreases your brain’s ability to break down hormones and neurotransmitters.

The Neurological Effects of B-12 Deficiency

According to the NIH, B-12 deficiency manifests as the following neurological symptoms:[2]

  • Difficulty balancing
  • Unhappy mood
  • Confusion
  • Poor memory
  • Developmental delays in infants

Accelerates Brain Aging

Low B-12 status accelerates mental decline by inhibiting the methionine cycle, a process that converts the essential amino acid methionine into other amino acids to build proteins. You need folate, B6, and B-12 to convert the nonessential amino acid homocysteine into methionine. Homocysteine is a normal metabolic product, but it also comes from diets that contain excess animal protein. With inadequate B-12, the homocysteine levels build up in your blood and brain, leading to nerve damage, delayed communication between nerves, and brain shrinkage.[4, 10]

Low B-12 status also decreases the production of a prolific detoxifier called SAMe (S-adenosylmethionine), a cosubstrate involved in the modification of other molecules. SAMe donates a piece of itself, its methyl group, to other molecules. Estrogen, neurotransmitters, and other chemicals require this methyl group to breakdown into safer molecules for recycling or elimination. When you don’t have adequate B-12, you cripple the production of SAMe; impeding this detoxification process contributes to a buildup of unnecessary molecules in the brain and degraded neural tissue.[10]

Inhibits Production of Neurotransmitters

Low B-12 status appears to significantly depress production of neurotransmitters such as norepinephrine, serotonin, and dopamine. It acts as a coenzyme during the synthesis of these neurotransmitters, so a deficiency limits your brain’s ability to produce these important chemical signallers. This effect disrupts emotional stability and can affect your sleep quality.[1, 11]

Reduces Blood Flow to the Brain

As if homocysteine didn’t cause enough damage to your brain, it also targets your vascular health. Elevated levels of homocysteine contribute to arterial thickening, stiffness, and the development of atherosclerosis. All of these effects reduce blood flow to the brain and contribute to stroke risk, which compounds damage to the brain.[12, 13,14]

Healthy Brain Aging With Adequate B-12

B-12 supplementation offers promise for decreasing the risk of accelerated brain atrophy and may even lead to limited cognitive improvement in B-12 deficient older adults. One Oxford study on older adults found that B vitamin supplementation over the course of two years slowed brain atrophy by an astonishing 30% compared to the group that didn’t receive any vitamin supplementation. Participants with the highest levels of homocysteine responded with a remarkable 53% reduction in brain atrophy, compared to their placebo-controlled counterparts.[3, 4]

Staying Sharp at Any Age

Taking your B vitamins isn’t the only way to keep your brain healthy throughout your lifetime. A healthy diet and regular exercise keep your arteries strong and flexible so that they can carry necessary nutrients to your brain and waste products away from it. If you smoke, keep in mind that you’re not only harming your lungs; the effects of smoking also extend to your brain. One study found that smoking has debilitating effects on memory, processing speed, and general brain function.[15]

You can also try a low methionine diet, a plant-based diet that specifically limits methionine intake to prevent high homocysteine levels before they cause any damage. Consuming animal protein contributes to high homocysteine levels, along with the additional deleterious effects of a high meat diet.

Meditation and stress management are—pardon the pun—a no-brainer when it comes to your cognitive health.[16] I also highly recommend lifelong learning as another way to delay age-associated cognitive decline. Challenging your mind, even well into adulthood, forms new neural connections in the brain that safeguard against these kinds of difficulties.[17]

Do you have any suggestions for protecting your brain? Share your tips in the comments!