Brain Protection from New Form of Vitamin B12

People with vitamin B12 deficiencies frequently suffer anemia, weakness, and fatigue.

But there are more dangerous effects.

Low vitamin B12 levels have been associated with progressive brain atrophy (shrinkage).

One study found an astounding 517% greater rate of brain volume loss in people with lower vitamin B12 than those with higher B12 levels.^1,2

Even B12 levels in the “low normal” range are associated with cognitive impairment.³

Many people already take methylcobalamin, one of two bioactive forms of vitamin B12, in their multivitamin.

But the other active B12 form—adenosylcobalamin—has unique properties that methylcobalamin does not.

New in-vitro research shows that adenosylcobalamin can protect neurons and prevent a decline in levels of the critical neurotransmitter, dopamine.⁴

A combination of both active forms of vitamin B12 offers protection for aging brain cells.

Activated Forms of Vitamin B12

Vitamin B12 is essential for nerve function, cell metabolism, the formation of red blood cells, and DNA health.^5-7

Vitamin B12 is found in animal sources, including meat, fish, poultry, eggs, and dairy products. Because of this, vegans and some vegetarians are at higher than average risk of developing vitamin B12 deficiency.⁸

B12 becomes more difficult to absorb as we age.This is one reason older people often have lower levels in the body.^9,10

Vitamin B12 exists in various forms called cobalamins. The two active forms of cobalamins used by enzymes in the body are:¹¹

• Methylcobalamin, which is active in the cytosol (liquid) inside the body's cells, and
• Adenosylcobalamin, which is active in the mitochondria, the fuel plants within each cell.

Adenosylcobalamin is the most prevalent form of vitamin B12 in human tissues, making up as much as 70% of all forms of this vitamin in the body.¹¹ But it is missing from most B12 formulas and multivitamins.

The B12 Link to Neurodegeneration

Up to one million Americans suffer from Parkinson's disease, a degenerative disease of the central nervous system. Roughly 60,000 new cases are diagnosed each year. The risk increases after age 50, but about 4% of patients are diagnosed before then.^12,13

Common symptoms include tremors, muscle rigidity, slowness and difficulty with movement, poor balance, sleep disturbances, loss of coordination, cognitive decline, and—in very advanced cases—dementia.

Mitochondrial dysfunction has been identified as a central feature of Parkinson's disease.^14-16

Since the adenosylcobalamin form of vitamin B12 supports mitochondrial function, scientists reasoned that it might help treat Parkinson's.

They made some remarkable discoveries.

Inhibiting Neurodegeneration

To investigate the therapeutic potential of adenosylcobalamin, scientists performed a series of experiments in in-vitro models, worms, and mice.

They administered this unique form of B12 to the larvae of worms that carried a mutation linked to Parkinson's disease.⁴

Worms with this mutation suffer from abnormal movement control. But mutated worms that had been treated with adenosylcobalamin as larvae were able to move normally as adults.⁴

Worms with the Parkinson's mutation experience accelerated degeneration of their dopamine-producing neurons.

As a result of this neurodegeneration, less than 60% of these nervous system cells remained in untreated mutated worms after nine days of life. But in mutated worms that had been treated with adenosylcobalamin, close to 75% of these neurons survived after the same period.⁴

This near 75% neuron survival rate matched the percentage of neurons that survived in worms without the Parkinson's mutation.

Preventing Decreases in Dopamine

Scientists next studied the specific effect of adenosylcobalamin treatment on dopamine levels in mice with this mutation.

For this experiment, scientist prepared brain slices of these mice and treated them with adenosylcobalamin.

Then, every two minutes for 20 minutes, they stimulated the dopamine-producing neurons.⁴

At the end of the 20-minute period, the stimulated neurons of the control slices were releasing 20% less dopamine.

But the brain slices treated with adenosylcobalamin exhibited sustained dopamine levels, showing dopamine output equal to that of animals without the mutation.⁴

Taken together, these findings suggest that adenosylcobalamin could prevent dopamine loss, brain cell depletion, and neurotoxicity.

Importance of Methylcobalamin

Adenosylcobalamin shouldn't replace methylcobalamin in a supplementation program. Instead, they should be used together for maximum benefit.

Methylcobalamin is a form of vitamin B12 that is active in the central nervous system, and it is essential to the growth and replication of cells.^5-7

Protecting brain cells against neurodegeneration is critical for aging individuals seeking to maintain their cognitive function.

Several studies have connected homocysteine to negative effects on the brain and brain vasculature.^17,18 Elevated homocysteine has been associated with as much as a 10.5-fold greater risk of vascular dementia, and to brain shrinkage.^1,19-21

Homocysteine has been tied to destructive effects that can accompany aging. These include chronic inflammation, atherosclerotic plaque, shrinkage of brain areas (e.g., hippocampus) involved in memory formation, development of beta-amyloid plaque, and hindrance of the DNA repair needed for brain cell maintenance.^21-28

Methylcobalamin lowers homocysteine, which helps protect against these effects.^29,30

This new pre-clinical evidence suggests that adding adenosylcobalamin, the other active form of vitamin B12, may provide additional protection for brain cells and help prevent a decline in dopamine levels.

Daily oral dosages of 500 mcg of adenosylcobalamin and 500 mcg of methylcobalamin can help provide broad protection of both body and brain.

Summary

There are two bioactive forms of vitamin B12, adenosylcobalamin and methylcobalamin. Your body needs both to function youthfully and optimally. Together, these are the best forms of vitamin B12.

Many people already take the methylcobalamin form of B12 based on data showing it is essential for proper DNA synthesis, red blood cell formation, cell growth, and more.

But the adenosylcobalamin form is active in the mitochondria, the powerhouses of the cells.

A preclinical study has shown it has the ability to protect brain neurons and to prevent a decline of the neurotransmitter dopamine in animal models.

Vegans, vegetarians, and the aging often develop vitamin B12 deficiencies. Oral intake of both active forms of vitamin B12 can support brain and body health.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

1. Grober U, Kisters K, Schmidt J. Neuroenhancement with vitamin B12-underestimated neurological significance. Nutrients. 2013 Dec 12;5(12):5031-45.
2. Vogiatzoglou A, Refsum H, Johnston C, et al. Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology. 2008 Sep 9;71(11):826-32.
3. Kobe T, Witte AV, Schnelle A, et al. Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment. Am J Clin Nutr. 2016 Apr;103(4):1045-54.
4. Schaffner A, Li X, Gomez-Llorente Y, et al. Vitamin B12 modulates Parkinson's disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection. Cell Res. 2019 Apr;29(4):313-29.
5. O'Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010 Mar;2(3):299-316.
6. Nohr D, Biesalski HK. Vitamin B12. Reference Module in Food Science: Elsevier; 2016.
7. Available at: https://www.ncbi.nlm.nih.gov/books/NBK114302/. Accessed February 10, 2021.
8. Available at: https://www.ncbi.nlm.nih.gov/books/NBK441923/. Accessed February 10, 2021.
9. Allen LH. How common is vitamin B-12 deficiency? Am J Clin Nutr. 2009 Feb;89(2):693S-6S.
10. Watanabe F. Vitamin B12 sources and bioavailability. Exp Biol Med (Maywood). 2007 Nov;232(10):1266-74.
11. Authority EFS. 5'-deoxyadenosylcobalamin and methylcobalamin as sources for Vitamin B12 added as a nutritional substance in food supplements - Scientific opinion of the Scientific Panel on Food Additives and Nutrient Sources added to food. EFSA Journal. 2008;6(10):815.
12. Available at: https://www.parkinson.org/Understanding-Parkinsons/Statistics. Accessed February 10, 2021.
13. Heisters D. Parkinson's: symptoms, treatments and research. Br J Nurs. 2011 May 13-26;20(9):548-54.
14. Park JS, Davis RL, Sue CM. Mitochondrial Dysfunction in Parkinson's Disease: New Mechanistic Insights and Therapeutic Perspectives. Curr Neurol Neurosci Rep. 2018 Apr 3;18(5):21.
15. Chen C, Turnbull DM, Reeve AK. Mitochondrial Dysfunction in Parkinson's Disease-Cause or Consequence? Biology (Basel). 2019 May 11;8(2):38.
16. Winklhofer KF, Haass C. Mitochondrial dysfunction in Parkinson's disease. Biochim Biophys Acta. 2010 Jan;1802(1):29-44.
17. Briani C, Dalla Torre C, Citton V, et al. Cobalamin deficiency: clinical picture and radiological findings. Nutrients. 2013 Nov 15;5(11):4521-39.
18. Soni RM, Tiwari SC, Mahdi AA, et al. Serum Homocysteine and Behavioral and Psychological Symptoms of Dementia: Is There Any Correlation in Alzheimer's Disease? Ann Neurosci. 2019 Jan;25(3):152-9.
19. Tan C, Peng W, Deng Y. [Risk factors and predictive factors of cognitive deterioration in patients of vascular cognitive impairment no dementia with subcortical ischemic vascular disease]. Zhonghua Yi Xue Za Zhi. 2014 Feb 11;94(5):352-5.
20. Cervellati C, Romani A, Seripa D, et al. Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer's Disease or Vascular Dementia. J Neurol Sci. 2014 Feb 15;337(1-2):156-61.
21. Tan B, Venketasubramanian N, Vrooman H, et al. Homocysteine and Cerebral Atrophy: The Epidemiology of Dementia in Singapore Study. J Alzheimers Dis. 2018;62(2):877-85.
22. Papatheodorou L, Weiss N. Vascular oxidant stress and inflammation in hyperhomocysteinemia. Antioxid Redox Signal. 2007 Nov;9(11):1941-58.
23. Weiss N, Keller C, Hoffmann U, et al. Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia. Vasc Med. 2002 Aug;7(3):227-39.
24. Kruman, II, Kumaravel TS, Lohani A, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci. 2002 Mar 1;22(5):1752-62.
25. Li JG, Chu J, Barrero C, et al. Homocysteine exacerbates beta-amyloid pathology, tau pathology, and cognitive deficit in a mouse model of Alzheimer disease with plaques and tangles. Ann Neurol. 2014 Jun;75(6):851-63.
26. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010 Sep 8;5(9):e12244.
27. Choe YM, Sohn BK, Choi HJ, et al. Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden. Neurobiol Aging. 2014 Jul;35(7):1519-25.
28. Guthikonda S, Haynes WG. Homocysteine: role and implications in atherosclerosis. Curr Atheroscler Rep. 2006 Mar;8(2):100-6.
29. Koyama K, Usami T, Takeuchi O, et al. Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation. Nephrol Dial Transplant. 2002 May;17(5):916-22.
30. Yuan M, Wang B, Tan S. Mecobalamin and early functional outcomes of ischemic stroke patients with H-type hypertension. Rev Assoc Med Bras (1992). 2018 May;64(5):428-32.
31. Available at: https://lpi.oregonstate.edu/mic/vitamins/vitamin-B12. Accessed February 21, 2021.
32. Available at: http://www.fao.org/3/Y2809E/y2809e0b.htm. Accessed February 15, 2021.
33. Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf. 2013 Jun;4(3):125-33.
34. Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pract. 2012 Sep;97(3):359-67.
35. de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010 May 20;340:c2181.
36. Palmery M, Saraceno A, Vaiarelli A, et al. Oral contraceptives and changes in nutritional requirements. Eur Rev Med Pharmacol Sci. 2013 Jul;17(13):1804-13.
37. Pepper MR, Black MM. B12 in fetal development. Semin Cell Dev Biol. 2011 Aug;22(6):619-23.
38. Kominiarek MA, Rajan P. Nutrition Recommendations in Pregnancy and Lactation. Med Clin North Am. 2016 Nov;100(6):1199-215.
39. Brinkman DJ, Bekema JK, Kuijenhoven MA, et al. [Thiamine in patients with alcohol use disorder and Wernicke's encephalopathy]. Ned Tijdschr Geneeskd. 2017;161:D931.
40. Jabbar A, Yawar A, Waseem S, et al. Vitamin B12 deficiency common in primary hypothyroidism. J Pak Med Assoc. 2008 May;58(5):258-61.
41. Achamrah N, Coeffier M, Rimbert A, et al. Micronutrient Status in 153 Patients with Anorexia Nervosa. Nutrients. 2017 Mar 2;9(3).
42. Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, et al. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients. 2013 Sep 30;5(10):3975-92.
43. Huang S, Ma J, Zhu M, et al. Status of serum vitamin B12 and folate in patients with inflammatory bowel disease in China. Intest Res. 2017 Jan;15(1):103-8.
44. John S, Hoegerl C. Nutritional deficiencies after gastric bypass surgery. J Am Osteopath Assoc. 2009 Nov;109(11):601-4.
45. Rizzo G, Lagana AS, Rapisarda AM, et al. Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients. 2016 Nov 29;8(12).
46. Savage DG, Lindenbaum J. Neurological complications of acquired cobalamin deficiency: clinical aspects. Baillieres Clin Haematol. 1995 Sep;8(3):657-78.