The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults

[helvella]

Just came across this paper from a few years ago. Thought it interesting as, so often, B12 seems to be though of as a one-trick pony - affecting erythropoiesis and nothing else.

The occasional use of methylmalonic acid and homocysteine as additional tests.

And that's your lot, folks.

In my view, it would have been amazing if it had no other impacts on our bodies.

I leave you to read, if interested.

J Nutr.2017 Oct; 147(10): 1839–1849.

Published online 2017 Aug 9. doi: 10.3945/jn.117.248278

PMCID: PMC5610547

PMID: 28794205

The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults

Alex Brito,1 Dmitry Grapov,2 Johannes Fahrmann,2 Danielle Harvey,3 Ralph Green,4 Joshua W Miller,4,5 Sergey N Fedosov,7 Setareh Shahab-Ferdows,1 Daniela Hampel,1,5 Theresa L Pedersen,1 Oliver Fiehn,2 John W Newman,1,2,5 Ricardo Uauy,8 and Lindsay H Allen

Abstract

Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized.

Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion.

Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography–tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated.

Results: The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001), and reduced tHcy and serum MMA (P < 0.001). Metabolomic changes from before to after treatment included increases (P < 0.001) in acylcarnitines, plasmalogens, and other phospholipids, whereas proline and other intermediaries of one-carbon metabolism—that is, methionine and cysteine—were reduced (P < 0.001). Direct significant correlations (P < 0.05 after the false discovery rate procedure) were identified between acylcarnitines, plasmalogens, phospholipids, lyso-phospholipids, and sphingomyelins compared with vitamin B-12 status and nerve function. Multiple connections were identified with primary metabolites (e.g., an inverse relation between vitamin B-12 markers and tryptophan, tyrosine, and pyruvic, succinic, and citric acids, and a direct correlation between the nerve score and arginine).

Conclusions: The human serum metabolome in vitamin B-12 deficiency and the changes that occur after supplementation are characterized. Metabolomics revealed connections between vitamin B-12 status and serum metabolic markers of mitochondrial function, myelin integrity, oxidative stress, and peripheral nerve function, including some previously implicated in Alzheimer and Parkinson diseases. This trial was registered at controlled-trials.com as ISRCTN02694183.

Keywords: vitamin B-12, metabolomics, omics, nerve function, acylcarnitines, plasmalogens

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[Technoid]

Very interesting paper, thanks!

Very much hope that the nitty gritty of the underlying mechanisms for nerve myelin degradation in B12 deficiency are worked out more in future. This paper seems to point in the right directions, seeing effects on plasmalogens and sphingomyelin, among others, important parts of the myelin. Mention of Acetylcarnitines also perked my interest as several studies report acetylcarnitine helping with nerve damage. I also wonder about whether such studies are missing something when they do not include those with a B12 deficiency but normal or high markers of serum B12, MMA and Homocysteine but I understand it would make things very difficult on a practical level to include such people without risking the inclusion of those who do not have a B12 deficiency. Food for thought in this paper for sure.

[helvella in reply to Technoid]

I have convinced myself that metabolomics has enormous potential.

In some ways, it can side-step genetic analysis and understanding. We simply observe what is happening. Maybe we can later get to understand why one person's specific genome results in a particular metabolomic profile?

In the world of thyroid, the concentration on measuring TSH, which is not even a thyroid hormone, misses so much.

But in all cases, if certain pathways are not working, or are working too well, that will affect the individual - to a greater or lesser extent. If we know that, we can look to why that is the case.