As consumer focus continues to shift towards natural solutions for better well-being, many have turned to nutraceuticals for a wide range of applications — with one of the most popular being mental health. Commonly used supplements include those that assist with memory retention and cognitive performance, reducing oxidative stress and neuroinflammation. As such, several functional ingredient developers are now working to create the most efficacious formulas for this area of health.
In Part I of this two-part article, the role of vitamin B12 in memory formation and mitigating inflammation was explored; Part II will focus on how vitamin B12 supplementation can impact neurodegenerative diseases such as Alzheimer’s and mild cognitive impairment (MCI), as well as mental health conditions such as depression.
High serum levels of vitamin B12 result in slower cognitive decline
B12 in Alzheimer’s and MCI
Because vitamin B12 has been proven to reduce the presence of various biomarkers of cognitive decline, a number of studies have been done to decipher what impact vitamin B12 supplementation has on the risk of developing progressive diseases such as Alzheimer’s (AD) and MCI with varying results. Homocysteine (HCy), an amino acid produced during methionine metabolism, has been associated with cognitive decline when present in high levels in the body.1
It’s often considered to be a notable risk factor for the development of Alzheimer’s and vascular dementia.2,3 HCy has also recently been directly implicated in the progression from MCI to dementia.4
As vitamin B12 plays a fundamental role in regulating the body’s plasma homocysteine levels, researchers have theorised that controlling vitamin B12 can have positive knock-on effects in terms of preventing the MCI and cognitive decline associated with dementia.5
A review by Smith & Refsum supports this sentiment; in studies with patients at high risk of developing Alzheimer’s, a high serum level of vitamin B12 results in slower patient cognitive decline — as well as a reduction in the atrophy (shrinkage) of critical regions of the brain — facilitating better cognition and brain functionality.6
Another investigation backing the role of B12 supplementation for better cognitive outcomes in the elderly is the study by Smith et al. They found that patients with MCI given B12 exhibited a reduced rate of brain atrophy compared with those who weren’t given the vitamin.7 Although this indicates that supplementation with vitamin B12 can slow the impact of mild cognitive impairment through the optimised retention of the brain’s mass, it’s not yet clear if this impact on atrophy has any influence on the development of Alzheimer’s disease.
Jianan et al. found a similar trend, with a linear regression model revealing that a low serum B12 level correlated with a heightened risk of developing MCI.8
A review from 2023 further adds weight to these claims, with vitamin B12 supplementation positively influencing “Aβ generation via β- and γ-secretase cleavage,” while also modulating the homocysteine cycle to reduce the impact of Alzheimer’s disease pathology in animal models.10 The literature also highlights B12’s protective effects against amyloid and tau formation, which are key
factors associated with AD progression.9
A decreased risk of depression and behavioural problems
The vitamin’s role in mental health
Although the positive impact of vitamin B12 supplementation on mental health is a little more tenuous than other aspects of cognition, there are several studies that find the vitamin to be promising as a tool to manage depression. One investigation that found B12 supplementation to be useful in terms of improving mental health was Tan et al. This meta-analysis of 56 studies revealed a correlation between higher vitamin B12 intake and a decreased risk of depression and behavioural problems in adolescents.10
This was supported by Hui et al. who found that low B12 levels may have a causal relationship with major depressive disorder — although this trend was observed in adults.11
A similar trend was reported by Kennedy et al. who found “limited evidence” to support the role of vitamin B12 supplementation in augmenting the effects of antidepressants in adults being treated for depression.12 However, the tenuity of this claim should not be ignored and more research should be conducted to substantiate vitamin B12’s role as a potential adjuvant therapy.
The association between vitamin B12 levels and depression can also be noted from the observations of Laird et al. Researchers noted that increasing B12 levels resulted in a reduction in incidents of depression in elderly adults.13 For those with a deficient/low B12 status, there was a 51% increase in the likelihood of incident depression within the next 4 years following the trial.
Although this conclusion doesn’t suggest any benefits regarding B12 supplementation for the wider population, it does point to a simple solution for those who are experiencing depressive symptoms and have low serum vitamin B12 levels.
This apparent trend in the data highlights the need for those in the nutraceutical industry to partner with academics to further investigate B12’s true impact on mental health. It could potentially be used as a cost-effective and efficacious adjuvant to traditional therapeutic interventions such as selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy.
B12 improves symptoms of MCI ... in elderly participants — with the exception of those who regularly used aspirin
Aspirin and B12: a far from ideal combination
There are many cellular pathways through which drugs and nutraceutical products can exhibit their effects. However, it’s entirely possible that such substances can either function through the same metabolic cascades or modulate an associated pathway — meaning that they can potentially influence each other’s activity.
Therefore, it’s unsurprising that the positive effects of supplementation with vitamin B12 can be both bolstered and diminished by its interaction with other functional ingredients and pharmaceuticals.
This can be seen from the interaction between vitamin B12 and aspirin, with a study from Wu et al. finding that vitamin B12 improves symptoms of MCI and reduces brain atrophy in elderly participants — with the exception of those who regularly used aspirin.14
Owing to the negative interactive effects aspirin can have on the efficacy of B12 supplementation, it may be sensible for
supplement providers working with the vitamin to make consumers aware of this — although more evidence will likely need to be collated to substantiate this claim.
It’s also interesting to note that experts discourage consumers from taking vitamin B12 with vitamin C as taking these two vitamins at the same time can reduce the amount of B12 that the body can absorb and utilise.15 The same can be said for the concurrent supplementation of B12 and folate (vitamin B9), although this combination can be a little more detrimental as excessive folate intake can hide a vitamin B12 deficiency.16
More research necessary to determine B12’s true impacts
A growing body of evidence suggests that vitamin B12 plays a key role in cognitive health. However, there less published data regarding the benefits of vitamin B12 supplementation; this makes drawing conclusions in terms of its efficacy as a dietary adjunct more difficult. Yet, a trend towards vitamin B12 supplementation being advantageous for cognitive health can definitely be
observed and this should be enough to encourage both members of the functional ingredients industry and academics to delve deeper into the vitamin’s role.
To effectively boost our knowledge about the true impacts of vitamin B12 supplementation for cognitive health, researchers and industry professionals must forge collaborations to standardise their studies, determine a universal objective measure of an “improvement in cognition” and endeavour to use only a specific group of standardised cognitive tests.
Implementing these changes will strengthen the validity of both individual and analytical studies, allowing for better comparisons and more accurate conclusions to be drawn in terms of how B12 supplementation can influence the human body.
References
1 www.cmaj.ca/content/171/8/897.short.
2 www.ncbi.nlm.nih.gov/pmc/articles/PMC5836397/.
3 www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00350/full.
4 www.sciencedirect.com/science/article/pii/S0197018624000901.
5 www.ncbi.nlm.nih.gov/pmc/articles/PMC1283514/.
6 www.annualreviews.org/content/journals/10.1146/annurev-nutr-071715-050947.
7 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012244.
8 https://huicui.hebmu.edu.cn/EN/abstract/abstract18041.shtml.
9 www.mdpi.com/2218-273X/12/1/129#B35-biomolecules-12-00129.
10 www.ncbi.nlm.nih.gov/pmc/articles/PMC10591166/
11 www.mdpi.com/2072-6643/16/13/2042
12 https://link.springer.com/article/10.1007/s11920-024-01505-4.
13 www.cambridge.org/core/journals/british-journal-of-nutrition/article/abs/low-vitamin-b12-but-not-
folate-is-associated-with-incident-depressive-symptoms-in-communitydwelling-older-adults-a-
4year-longitudinal-study/B1EA518340197FA07B97FF04766F6E22.
14 www.sciencedirect.com/science/article/pii/S1279770723007406.
15 www.medicinenet.com/what_vitamins_should_not_be_taken_together/article.htm.
16 https://academic.oup.com/nutritionreviews/article/65/10/451/1879937.
