Pernicious Anemia

See also anemia

This is basically the cause of iron overload hemochromatosis

Cobalamin

Great lakes and northeast states higher in cobalt [1]

Seems high water areas are washed away of cobalt [2]

Cobalamin C defect [3] also linked to gynecomastia.

Contributors

  1. nitrous oxide destroys B12
  2. Salvinorin has nitrous oxide like effects [4] may destroy B12 as well. Salvinorin does activate nitric oxide synthase [5]. Certain cobalamins can interact with nitric oxide [6] [7]. My insomnia and sleep apnea started after multiple uses of salvia divinorum. Disordered Nitric oxide can also cause sleep apnea [8] and high blood pressure [9]

Symptoms

[10]

brucella infection [11]

Hookworm infection [12]

Kidney damage leads to albumin in urine (pee that foams) due to elevated free iron iron overload due to he pernicious anemia [13]

Many symptoms including grey hair hair loss extreme chronic fatigue and more [14]

Oral manifestations [15] including chapped lips.

Ferritin

Serum ferritin is often elevated in pernicious anemia which can lead to a myraid of problems including sleep apnea

Ferritin levels about double in cobalamin deficiency as healthy people [16]

Low cobalamin and low folic acid linked to high ferritin [17]

Homocysteine

Homocysteine causes red blood cell lysis in pernicious anemia [18] which may be the mechanism for elevated ferritin.

H pylori

Can be a cause [19] [20]

Inrinsic factor reduction

Supplements

  1. [23]
  2. Do not use cyanocobalamin because people with cbl-c defect cannot remove the cyanide [24]. Only methylcobalamin is found in body fluids like blood naturally [25] so this should be the one taken.
  3. High dose thiamine as well as ginger can help reduce the nerve symptoms of taking B12. This may be because B12 treatment may kill h pylori which causes a campylobacter overgrowth.
  4. Stay away from choline like lecithin (and possibly trimethylglycine) in pernicious anemia because it may make things worse and accelerate cancer and other infections by upregulating PGE2

Treatment

Oil based better [26] so you don't pee it out basically. Also anyone under 300 on total b12 test should undergo more workup. Active b12 should be looked at which is holotranscobalamin.

Good vs mild responder factors [27] [28]

Optimum clinical guideline

This should capture well over 90% of b12 deficiency and have a low incidence of false positives. However b12 supplementation is safe without significant risks so testing is not needed for self diagnosis or self treatment.

  1. If someone presents with any complaints that could be related to b12 deficiency continue to step 2. Make sure to record all the patients symptoms whether or not they are related to the standard known symptoms of B12 deficiency. This is because there are still likely unknown or underappreciated symptoms such as chronic insomnia, sleep apnea, constipation, IBS, hair loss, miscarriage, ADHD, OCD, allergy, asthma, multiple sclerosis, fibromyalgia, high blood pressure, parasites, diabetes, eczema, appendix removal, back pain, tinnitus, hashimoto's, depression, anxiety, heartburn, dementia, Brain fog, itchiness, chronic fatigue, balance disorder, cankers, and iron overload for example.
  2. Ask if patient has taken b12 supplementation in the last 5 [29] years. If no then test serum b12 and urinary or plasma methylmelonic acid. If serum B12 is below 400 [30] OR urinary mma is elevated then continue workup to step 3. If they have not taken a supplement and serum B12 tests over 400 and urinary MMA is not elevated then consider other elements of the homocysteine pathway in step 3. If they have taken a supplement go to step 3 with or without testing serum b12 and regardless of what the serum b12 or urinary mma results are. Educate the patient on sources of B12 [31] including clams, red meat especially liver, pork, fish, milk, cheese, yogurt, turkey, crab, and vegan sources like Nori and nutritional yeast as well as fortified foods like some breakfast cereal and vegan milks. Also educate the patient about h pylori infection and symptoms and how it can be involved with b12 deficiency (and what tests and treatments apply to the infection, campylobacter should always be treated for simultaneously as h pylori). Also educate the patient about intrinsic factor and that it may not be working properly which can mean that even with proper nutrition your body may not absorb enough b12 from foods and multivitamins (and what tests can apply). Also educate the patient that methylcobalamin is the only naturally active form of b12 and that cyanocobalamin in cheap supplements may not be able to be utilized properly by the body [32]. Also educate the patient that as the therapy begins there may be an increase in clinical symptoms which should go away over time.
  3. Test patient for holotranscobalamin, methylmalonic acid, and homocysteine. If any 2 are problematic or just holotranscobalamin alone then continue to step 4. If not then continue workup to other causes. If homocysteine alone is elevated consider folic acid, serine, zinc, pyridoxine, riboflavin, thiamine, vitamin d, retinol, selenium, calcium, magnesium in the workup.
  4. Administer a short term test prescription for oral b12 therapy (5mg methylcobalamin and/or hydroxocobalamin per day) or injectable b12 (1mg methylcobalamin or hydroxocobalamin once per week), whichever route the patient desires however they need to pick one of those two options, not both. Methylcobalamin is the most natural and will help those with methylation problems and hydroxocobalamin might help others more probably if they have been exposed to toxins that it helps to detox. The clinician can rather design their own protocol if they want instead, for example one shot and then oral B12 for the remainder of the month or something similar. Follow up in 1 month, ask the patient about their compliance with the treatment, and perform a retest of holotranscobalamin, methylmalonic acid, and homocysteine. If the patient improves then make the diagnosis of pernicious disorder (or symptomatic B12 deficiency) and continue therapy as long as the patient desires, 1-5mg methylcobalamin orally per day or 1mg methylcobalamin injection per month. If homocysteine is still problematic consider other factors in the homocysteine pathway seen in step 3.
  5. Once a year retest holotranscobalamin, methylmalonic acid, and homocysteine to tune treatment.

notes

This guideline protocol also lends itself well to clinical case study research.

Injection frequency [33]

Clinical factsheet [34]

More food sources [35]

Natural B12 forms like methyl and adenosyl are more prone to degradation so commercial products may not contain all of what is listed.

Hydroxo and cyano might also lower methylation for over methylators [36]

Cobalamin injections cause Acne probably because they help the body fight the p acnes bacteria better causing inflammation [37]

Animals

Non-ruminants like horses [38] are suseptible to parasites like strongyloides for which ivermectin is prescribed, likely because they are deficient in cobalamin [39]

Mechanism

The mechanism of why cobalamin deficiency causes all these symptoms is mostly due to the body bieng unable to effectively fight or repair the damage of several types of bacteria without B12. Likely campylobacter, h pylori, mycobacterium, bacillus, and intracellular bacteria like brucella and others, lactic acid bacteria like leuconostoc, gram negative bacteria like e coli, and possibly fusobacterium and clostridium, and listeria, and haemophilus and toxoplasma, and pseudomonas. Parasites such as strongyloides and others probably too. One mechanism of this inability to fight microbes may be due to thinning of epithelium - probably due to elevated homocysteine or methylmalonic acid.

Resources

[40]

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