Vitamin B12-related neurological issues
This research article needs some introduction:
Our preliminary clinical study among alpha-1 MZ patients observed a very high prevalence of Alphas with vitamin B12 deficiency, and we developed a thesis that may explain the root cause of this deficiency among the MZ population.
The abstract of this study, shown below, suggests a possible alternative root cause, which may be affiliated with an alpha-1 antitrypsin deficiency. This research paper shows that a particular autoimmune issue may cause severe neurological problems caused by a B12 deficiency at the cell level while the blood B12 level is normal.
We also know (based on research papers) that a low AAT will cause autoimmune issues (antibodies) in alpha-1 patients.
This fascinating paper provides evidence that while your B12 blood level is completely normal, you may still have a serious B12 deficiency induced by antibodies stopping B12 from entering the cells where it has to do its work. This particular autoimmune issue is causing transcobalamin (B12) receptor antibodies, which means that the B12 is not reaching the cells (in this case, the brain) Adding high levels of B12 (something we see in our clinical practice) enabled an alternative pathway for B12 to enter the cells and, as such, provided a solution.
Abstract of the paper
Vitamin B12 is critical for hematopoiesis (blood cell production) and myelination (formation of an isolation layer around a nerve). Deficiency can cause neurologic deficits, including loss of coordination and cognitive decline.
However, diagnosis relies on the measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. We identified an autoantibody targeting the transcobalamin (B12) receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement.
Optofluidic screening enabled the isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, the detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.
Source:
Form of B12 Deficiency Affecting the Central Nervous System May Be New Autoimmune Disease
Author: Lucy Hicks
The key takeaway of the above is:
Alpha-1 is known to cause autoimmune issues
Autoimmune issues may lead to serious, B12-related neurological issues.
You can have a B12 deficiency leading to severe neurological problems despite having a normal blood level of B12 .
Adding high amounts of B12 via injections resolved the deficiency by using an alternative path into the cell (currently used by many Alpha’s).