Vitamin B12’s role in the body’s healthy functioning has long been discussed, with numerous studies linking it to metabolic function and homeostasis, the mitigation of oxidative stress, as well as cardiovascular health, red blood cell formation and DNA synthesis.
As the public becomes increasingly aware of the importance of cognitive health, the industry has seen a sharp rise in engagement and sales — with a market forecast suggesting it will grow by USD $4.7 billion during the next 4 years.1
Simultaneously, an ever-growing number of consumers are looking for solutions to help them improve their daily cognitive performance and brain health, with many turning to natural ingredients to achieve this. Therefore, functional ingredient formulators must compete to develop and provide the industry’s best nutraceuticals to maintain a viable market share.
With a wide array of clinical studies pointing to the benefits of healthy blood vitamin B12 levels, there has been a surge in interest regarding its capabilities to boost brain health and cognition through supplementation. Several trials have aimed to delve into this topic and this article will highlight the key findings in the areas of memory retention, mild cognitive impairment (MCI),
neuroinflammation and stroke recovery.
Vitamin B12’s role in memory
Memory is a highly relevant area of cognition for many who purchase supplements, as they look for ways to ace their exams, maintain memory capacity in old age or just enhance their day-to-day ability to retain information. Researchers also appear to have piqued a fascination with the topic, as they look to understand how and what encourages the effective formation of memories and how we can positively modulate this for cognitive enhancement.
Vitamin B12 has shown promise in this area, with a study evaluating the impacts of adequate B12 intake demonstrating a 33.3% reduction in the likelihood of low cognitive performance (LCP) in elderly adults. This was established when performing Consortium to Establish a Registry for Alzheimer’s disease (CERAD) word learning and recall modules, the animal fluency test (AF) and the digit symbol substitution test (DSST).2
B12 has significant mitigative impacts on alcohol-induced reductions in cognition
Another study by Mishra and Thakur (2024) supports this discovery, finding that the collaborative supplementation of B12 and folate could positively alter the metabolic properties of neuronal cells through the mitochondria, mitigating neurodegeneration and supporting spatial memory and recognition in an ageing animal model.3
Most of the studies involving vitamin B12 focus on elderly populations, although there is also evidence to suggest that B12 supplementation can be beneficial for a much younger population too.
Akbari et al. (2023) explored how B12 administration could benefit adolescents with alcohol-induced learning and memory impairment, finding that it had significant mitigative impacts on alcohol-induced reductions in cognition via the regulation of the brain’s oxidant to antioxidant balance. This was seen specifically through the enhancement of brain growth factor BDNF and the reduction of GFAP.4
Going back even further on the ageing timeline, clinical studies have suggested that maternal B12 levels in pregnancy can impact a child’s subsequent cognitive development postnatally. The 2023 ECLIPSES study determined that maternal B12 levels in the first trimester were positively linked to a child’s performance in working memory and cognitive performance tests at 4 years old.5
The children whose mothers had high blood vitamin B12 levels in pregnancy also had better Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) and Neuropsychological Assessment of Development (NEPSY-II) scores, indicating the vitamin’s benefits in cognition throughout the human lifespan.5 
Although this study indicates the benefits of adequate-to-high maternal B12 levels during pregnancy, a recent literature review determined that the impacts of the vitamin were inconclusive from the current data available, underlining the need for further studies to determine the true influence it has on foetal and infant development.6
Vitamin B12 significantly reduces cadmium-associated neurotoxicity, oxidative stress and inflammation
Mitigating neuroinflammation with B12
As vitamin B12 has an impact in a significant portion of the body’s homeostatic functions, researchers have been further investigating the role of B12 in terms of alleviating the impacts of neuroinflammation. As this phenomenon is intimately connected to the natural ageing process, finding ways to assuage it could stave off symptoms and allow for better cognitive processing and functionality in older adults.7
A research paper by Yousaf et al. from 2023 found that vitamin B12 significantly reduced cadmium-associated neurotoxicity, oxidative stress and inflammation in adult mice. It also improved the Morris Water Maze (MWM) and Y-Maze (YM) test results of the models, suggesting the knock-on effect of reduced inflammation was an improvement in memory retention.8
Another supportive study by Mehrdad et al. (2021) found that scopolamine-injected rats were protected from the inflammatory and apoptotic effects of the drug when exposed to supplemental vitamin B12.9 Researchers observed a significant reduction in the presence of inflammatory markers in the hippocampus — the region of the brain responsible for learning and memory.
A further trial implicating vitamin B12 in the modulation of the hippocampus is a 2023 study from Cassiano et al., which investigated its ability to reduce the impact of pneumococcal meningitis — a severe brain infection characterised by neuroinflammation — through the reduction of microglial activation and the diminished presence of proinflammatory markers.10 
The vitamin has also been found to have some neuroregenerative capabilities in those who have suffered a recent ischaemic stroke. Ge et al. (2024) determined that this may occur through B12’s functional regulation of microglia — cells associated with the immune facet of the nervous system.11
Similarly, Jadavji et al. (2017) found that B12 supplementation in a mouse model significantly increased “proliferation, neuroplasticity and antioxidant activity” in the brain area impacted by stroke in a mouse disease model.12
B vitamins ... prevent cognitive decline in elderly adults with MCI significantly better with high levels of omega-3 in the blood
Other factors influencing B12’s health-boosting potential
The human body is a complex system, with hundreds of cellular pathways operating simultaneously to maintain homeostasis. Many of the functional ingredients that feature in today’s nutraceuticals work through a wide range of different mechanisms, so it’s unsurprising that certain combinations can boost or diminish their positive impact on the body.
A notable example of this is omega-3, with a study from the University of Oxford finding that B vitamins — including B12 — work to prevent cognitive decline in elderly adults with MCI significantly better with high levels of omega-3 in the blood.13 In fact, there was no marked impact on MCI prevention with B vitamins alone.
Diet is also a significant factor that should be accounted for when discussing the benefits of supplementation as it is integrally linked to overall health and well-being. Lopez et al.’s 2023 study found that vitamin B12 levels significantly correlated with improved memory retention in older adults, although only when they adhered to a Mediterranean diet.14 
The challenges associated with vitamin studies
Although there’s a significant body of evidence suggesting that vitamin B12 is an asset to cognitive health, it’s evident when reviewing literature on the topic that it’s very difficult to make any conclusive statements about B12’s brain health benefits in a supplemental context.
There are studies focusing on almost every area of cognition that directly contradict the claims made for the vitamin’s benefits, which poses the question: what can we conclude from this knowledge pool?
With the current lack of trial standardisation in study protocol and success measures, there are many research papers that come to vastly different conclusions. This then dramatically reduces the relevance of meta-analysis studies, as only a select few pieces can be compared — resulting in the possibility of false or biased conclusions being drawn from the data.
To mitigate this challenge, there must be a closer collaboration between academics, formulators and developers to standardise their research methods and measures of “cognitive benefits,” allowing more comprehensive comparisons and legitimate conclusions to be drawn.
Another challenge present when reviewing such a topic is the high prevalence of studies focusing on B12 deficiency in those with chronic illnesses, rather than supplementation of B12 in a healthy population with sufficient serum levels.
As vitamin B12 supplementation in those who are deficient has shown such promise in terms of mitigating a range of symptoms, it would be logical for the nutraceutical industry to follow this up in populations who don’t have a deficient serum level to determine whether any benefits are present in this cohort of consumers.
Although that it appears that the interaction between functional ingredients, diet and key nutrients can dramatically alter a person’s health outcomes, these associations are often little understood. Uncovering the optimal nutrient combinations and dietary choices for those experiencing cognitive decline could be a game changer — and a collaborative approach within the healthcare, nutraceutical, functional food/beverage and research industries could help consumers to optimise their health and wellness.
References
1 www.marketwatch.com/press-release/brain-health-supplements-market-size-is-set-to-grow-by-usd-4-7-billion-from-2024-2028-growing-urban-population-to-boost-the-market-growth-technavio-ce7394be.
2 www.ncbi.nlm.nih.gov/pmc/articles/PMC8962758/.
3 www.sciencedirect.com/science/article/abs/pii/S0955286323002693.
4 www.sciencedirect.com/science/article/abs/pii/S0166432822004247.
5 https://onlinelibrary.wiley.com/doi/full/10.1111/mcn.13580.
6 www.mdpi.com/2227-9067/11/5/558#:~:text=The%20results%20of%20most%20of,%2C%20language%2C%20and%20
motor%20development.
7 www.sciencedirect.com/science/article/abs/pii/S0889856109000083.
8 https://openurl.ebsco.com/EPDB%3Agcd%3A4%3A13531716/detailv2sid=ebsco%3Aplink%3Ascholar&id=ebsco%3Agcd%3A172924658&crl=c
9 www.tandfonline.com/doi/abs/10.1080/00207454.2021.1962863.
10 www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1250055/full.
11 www.cell.com/iscience/fulltext/S2589-0042(24)00701-6.
12 https://www.sciencedirect.com/science/article/abs/pii/S096999611730075X.
13 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad150777.
14 www.sciencedirect.com/science/article/abs/pii/S0261561423003540.