RELEVATE Nutrients

Hydroxy-cobalamin (B12)

Key Food Groups: Fish

Vitamin B12: Role in Brain Health

Vitamin B12 is vital in preventing the buildup of neurotoxic molecules in the brain. Two of these neurotoxic molecules are homocysteine (Hcy) and propionic acid (PA). The proper breakdown of Hcy and PA is crucial to the proper metabolism of hundreds of types of molecules in the body, spanning DNA, RNA, hormones, proteins, and lipids.1 When Hcy and PA build up, they lead to chronic inflammation and oxidative damage to neurons.2

Two enzymes responsible for the breakdown of Hcy and PA, called methionine synthase and L-methylmalonyl-CoA mutase, respectively, depend on vitamin B12 to function. Without vitamin B12, methionine synthase is unable convert Hcy to the non-toxic methionine, and L-methylmalonyl-CoA mutase is unable to breakdown PA.1 This underscores the importance of vitamin B12 for brain health.

Intake Deficiency and Relevance

The impact of inadequacies in vitamin B12 can be insidious, silently taking place over the long-run, which is why addressing a vitamin B12 deficiency before it becomes obvious is critical to avoid permanent damage to brain function. It is estimated that active vitamin B12 deficiency is prevalent in almost half of the older adult population, many of whom are unaware of it.2 Mild symptoms may be indistinct or may be hidden by excess folate (vitamin B9) intake, a vitamin involved in the same biochemical pathway as B12. More recognizable and severe symptoms that may be irreversible, include neurological complications like sensory disturbances, memory loss, and paranoia.3 If left untreated, these symptoms can progress to neurodegeneration that results in brain atrophy and overall cognitive decline.1 New tests have been developed to detect more subtle B12 deficiency, whose most significant symptom is mild memory loss.3

It is important to talk to your healthcare provider about determining vitamin B12 levels, as there can be many causes that influence B12 deficiency. Atrophic gastritis is a common cause of B12 deficiency and present in almost a quarter of older adults. The result is decreased acid production by stomach cells and less effective uptake of vitamin B12, which relies on stomach acid for digestion and absorption. Factors that affect the risk of developing atrophic gastritis include Helicobacter pylori infection, as well as long-term use of proton pump inhibitors (e.g. Nexium, Prilosec) and biguanides (e.g. Metformin).4

RELEVATE’s Form of Vitamin B12

RELEVATE includes a form of vitamin B12 called hydroxy-cobalamin, which is able to convert into other, active forms of vitamin B12, depending on where they are needed most.3,5 Hydroxy-cobalamin is also the longest lasting B12 in the blood, helping to build-up B12 stores. Additionally, hydroxy-cobalamin is a natural form, meaning that it is the most abundant form of vitamin B12 found in food (particularly clams or mackerel) – unlike the synthetic form of vitamin B12 (cyanocobalamin) that is typically used in nutritional supplements.

Our dose of hydroxy-cobalamin is diet-informed and linked to a reduction in cognitive decline, based on a prospective analysis showing supplementation effects with greater age.6 Furthermore, studies show that the crystalline form of hydroxy-cobalamin used in RELEVATE does not depend on a low stomach pH to separate from food, making this form readily available for digestion and absorption, even in people suffering from atrophic gastritis who would typically have difficulty absorbing B12.1,2

Concluding Thoughts to Consider

There are many promising studies that demonstrate a decrease in neurotoxic molecules like homocysteine and propionic acid and a reduction of cognitive decline with vitamin B12 supplementation.7–9 It is notable that many such studies use supplements with multiple B vitamins, including B6, B9, and B12, that show a decrease in cognitive decline, making it difficult to isolate the specific effect of B12.8 Despite this confounding limitation, we reason that hydroxy-cobalamin is a worthwhile neuroprotective nutrient that can compensate for common subclinical deficiencies (due to conditions like atrophic gastritis) and minimize the significant downside effects of neurotoxic build-up.


Cited Research

  1. Vitamin B12 — Health Professional Fact Sheet. Available at: (Accessed: 10th January 2020)
  2. McCaddon, A. Vitamin B12 in neurology and ageing; Clinical and genetic aspects. Biochimie 95, 1066–1076 (2013).
  3. Combs, G. F. et al. The vitamins [Recurso electrónico] : fundamental aspects in nutrition and health. (2017).
  4. Mendonça, N. et al. Intakes of Folate and vitamin b12 and biomarkers of status in the very old: The Newcastle 85+ study. Nutrients 8, (2016).
  5. Boddy, K., King, P., Mervyn, L., Macleod, A. & Adams, J. F. Retention of cyanocobalamin, hydroxy-cobalamin, and coenzyme B12 after parenteral administration. Lancet 2, 710–712 (1968).
  6. Morris, M. C. et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch. Neurol. (2005). doi:10.1001/archneur.62.4.641
  7. Aisen, P. S. et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial. JAMA – J. Am. Med. Assoc. 300, 1774–1783 (2008).
  8. Smith, A. D. et al. Homocysteine-lowering by b vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial. PLoS One 5, 1–10 (2010).
  9. Vogiatzoglou, A. et al. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology 71, 826 (2008).