Do You Have a B12 Deficiency?

Warning Signs of a B12 Deficiency:

B12 deficiency is one of the most common and overlooked conditions in the world.  Vitamin B12 is involved in the metabolism of every cell of the body.  It is crucial for processes such as DNA synthesis and energy production (1).  B12 deficiencies are a hidden epidemic in our society.  Boost your energy and mental clarity with high quality sources of Vitamin B12.

Vitamin B12 is very critical for neurological, cardiovascular, digestive, & immunological function (2).  Together, B12 and folate reduce the metabolic end-product homocysteine (3).  This pathway is responsible for the body’s entire sulfur-based detoxification system.

B12 deficiency, Warning Signs of a B12 Deficiency

Vitamin B12 Deficiency:

Many researchers believe that the standard American tests that measure serum B12 levels are far too low.  In America, B12 deficiency is evidenced as a serum level below 200 pg/ml (145 pM).  In Japan, a deficiency is found in levels under 550 pg/ml (400pM).  Most B12 researchers and advanced functional nutritionists agree with the Japanese model.

Research done through Tufts University Framingham Offspring Study has suggested that 40% of people between the ages of 26 and 83 have low-normal plasma B12 levels.  They found that 9% had an outright deficiency and 16% exhibited a “near deficiency.”  Many of these individuals were suffering from neurological symptoms (4).

B12 deficiency is present in close to 50% of people over 60 years of age. It’s entirely possible that at least some of the symptoms we attribute to “normal” aging – such as memory loss, cognitive decline, decreased mobility, etc. – are at least in part caused by B12 deficiency.  Here are some of the major causes of B12 deficiencies.

B12 deficiency, Warning Signs of a B12 Deficiency

Causes of B12 Deficiency:

The absorption, assimilation and methylation of B12 is a very complex process and there are many factors that reduce our bodies ability.  For this reason, even those who consume sufficient amounts of vitamin B12 in their diets could still have a functional B12 deficiency.  Some causes of B12 deficiency are:

  • Pernicious Anemia
  • Auto-Immune Diseases
  • Leaky Gut Syndrome
  • Ulcerative Colitis, Crohn’s and Celiac Disease
  • Small Intestinal Bacterial Overgrowth (SIBO)
  • H Pylori Infection
  • Prolonged Usage of Gastric Reflux meds
  • Vegan and Vegetarian diets
  • MTHFR gene mutations
  • Pernicious anemia
  • Bariatric Surgeries
  • Excessive Alcohol Consumption

B12 and the Methylation Cycle:

Methylation is a critical process that happens trillions of times in every cell each minute.  It is one of the most essential metabolic functions of the body and is dependent upon a variety of enzymes.  Adapting to stress and the challenges of life is an aspect that methylation provides the body.

Without adequate methylation processes the individual cannot adapt or heal effectively and will suffer the delirious effects of accelerated aging (5).  Normal methylation cycles absolutely depend upon adequate levels of vitamin B12 as well as other key nutrients such as folate, riboflavin, B6, niacin, magnesium and zinc.

With normal amounts of folate and B12 the body is able to convert homocysteine into glutathione and SAMe (S-adenosylmethionine).  Folate and B12 deficiencies cause the body to produce less glutathione and elevate unmetabolized homocysteine (6).  This is a red flag warning sign of elevated inflammation and tissue degeneration.

Individuals with gene mutations such as MTHFR or MTRR have trouble with the process of methylating B12.  These individuals often need larger doses of B12 to fulfill the important roles B12 has in human physiology.

B12 deficiency, Warning Signs of a B12 Deficiency

Vitamin B12 Deficiency & Chronic Disease

Vitamin B12 deficiencies are associated with chronic diseases.  B12 deficiencies lead to high homocysteine which is a strong risk factor in cardiovascular disease and Alzheimer’s disease.   Mood disorders such as depression and bipolar are very much associated with B12 deficiencies (78).

Researchers found that a diet deficient in folate, B12, & B6 caused cognitive dysfunction and a significant reduction in the length & density of brain capillaries (910).  This increases neurodegenerative conditions in the body leading to dementia and often times peripheral neuropathy.

B12 deficiency, Warning Signs of a B12 Deficiency

Vitamin B12 Deficiency’s and Medications

About 10% of the population appears to have normal serum B12, however, their bioavailable B12 is reduced.  The telling sign of this is elevated homocysteine and methylmalonic acid despite normal folic acid, B6, & B12 levels (11).

Vitamin B12 deficiencies are common in people who have used medications for a period of time.  The medications most commonly associated with B12 deficiencies include metformin (diabetes), antacids, anti-ulcers, blood pressure, cholesterol meds, and birth control pills (1213).  If you have ever taken any of these medications it is imperative to check your B12 levels and supplement if necessary.

B12 deficiency, Warning Signs of a B12 Deficiency

Vegans are At Risk for B12 Deficiency’s:

One population group that is especially vulnerable to B12 deficiencies are strict vegans.  The most bioavailable form of B12 is found in animal products.  Many vegans use blue-green algae as a form of B12.  The algae forms are called pseudo –B12 because they are active in tests but do not have the same human biological activity (1415).

The best sources of B12 are found in organic meat and eggs.  Be sure to find humanely raised, grass-fed sources of these meat products.  Organ meats such as liver and heart are the richest source of bioavailable B12 (16).

B12 deficiency, Warning Signs of a B12 Deficiency

Intrinsic Factor and B12 Absorption:

Vitamin B12 is a very large molecule compared to other vitamins and requires an enzyme called intrinsic factor to metabolize effectively.  High stress, infections, antacids and other medications deplete intrinsic factor.  Without adequate intrinsic factor the body cannot effectively metabolize b12 and deficiencies will occur over time.

The stomach must also be able to produce enough stomach acid for optimal B12 absorption.  It is estimated that 30% of Americans over the age of 50 and 70% over the age of 70 do not produce enough stomach acid and intrinsic factor and are currently dealing with some level of b12 deficiency (17).

B12 deficiency, Warning Signs of a B12 Deficiency

Testing For B12 Deficiency:

There are several different ways you can test for a functional B12 deficiency.  Clinical levels are measured off of a plasma level of B12.  In functional medicine, we look at functional components of health and measure blood and urinary biomarkers for functional deficiencies of key nutrients such as B12.

Here are several tests I analyze routinely for functional B12 deficiencies.

1.  Complete Blood Count (CBC)

This test, when it reveals the red blood cells to be very large, can indicate megaloblastic anemia, which is caused by a B12 and/or folate deficiency (18).  This is a simple test that every physician runs but not all physicians are trained to look at functional methylation issues and how they effect the size and development of blood cells.

Health practitioners trained in functional medicine will see slight elevations in MCV, MCH and MCHC and be suspicious of functional methylation issues.  I look at both the blood volume and a blood B12 level on our Comprehensive Blood Analysis test here

B12 deficiency, Warning Signs of a B12 Deficiency

2.  Organic Acid Test:

This is a very common test that I use to look at methylation factors, nutrient deficiencies, detox pathways and neurotransmitter function.  Elevations in Methylmalonic acid indicate a functional deficiency in B12 (20).

There are over 70 markers on the organic acids test including vitamins and antioxidants, oxidative stress, energy production, detoxification, neurotransmitter levels, oxalates, and intestinal yeast and bacteria. The test is a simple, non-invasive, at home urine test that gives a great deal of information.  You can find this test here

B12 deficiency, Warning Signs of a B12 Deficiency

B12 deficiency, Warning Signs of a B12 Deficiency

3.  MTHFR Genetic Test

When people have MTHFR gene mutations, in particular a homozygous trait, they require more B12, folate, and B6 for their detoxification pathways and body to function optimally.  You can find genetic testing with various companies such as

It’s estimated that those with one mutation (heterozygous) decrease their ability to methylate by 30% and those with two mutations (homozygous) decrease their ability to methylate by 70%, making it virtually impossible get adequate B12 from diet alone (19).

B12 deficiency, Warning Signs of a B12 Deficiency

4.  Homocysteine test

Homocysteine is a metabolic byproduct of protein metabolism and in particular the metabolism of methionine.  Methionine is found in meats, seafood, dairy products, eggs, sesame seeds and Brazil nuts.

Homocysteine is metabolized through two pathways: remethylation and transsulfuration.  Remethylation requires folate and B12 coenzymes while transsulfuration requires pyridoxal-5-phosphate, the B6 coenzyme.

Typically, about 50% of homocysteine is remethylated and the remaining homocysteine is transsulfurated to cysteine.  The cysteine that is formed is then used to produce glutathione.  Glutathione is a powerful anti-oxidant that protects cellular components against oxidative stress.

Vitamin B2 and magnesium are involved in homocysteine metabolism.  Without proper levels of methylated B6, B12, folate, B2 and magnesium, dangerous levels of homocysteine may build up in the body.

Elevated homocysteine causes excessive clotting which diminishes blood flow to major regions of the body.  The lack of blood supply to the heart may cause heart attacks and the lack of blood supply to the brain accelerates the development of dementia and may lead to strokes (34).

Very low or high blood levels of homocysteine can indicate a B12, folate, and/or B6 deficiency (21).  Ideal levels are between 6-9 umol/L of homocysteine.

B12 deficiency, Warning Signs of a B12 Deficiency

Proper Supplementation is Key:

For many individuals B12 supplementation is a necessity.  This is due to damage to the gastrointestinal system that limits their B12 absorption and genetic polymorphisms that reduce their B12 utilization.

There are several different forms of B12 including cyanocobalamin (Cyano-B12), Methylcobalamin (Methyl B12), Hyroxocobalamin (Hydroxy-B12) and Adenosylcobalamin (Adeno-B12).

1.  Cyanocobalamin

This is an unnatural synthetic form of vitamin B12 that is created in a lab.  It is the cheapest but most stable form of B12.  This form is not easily absorbed, produces a cyanide molecule that must be detoxified by the liver and it requires extra energy from our body for proper metabolism (22).

2.  Methylcobalamin

This is the most active form in the human body. It converts homocysteine into methionine, which helps protect the cardiovascular system.  Methylcobalamin is easily absorbed by the body and crosses the blood-brain barrier without assistance to protect brain and neurological cells (23).

Methyl-B12 is the main form that is used within the body.  This is the form that contributes to the key methylation groups that are needed for DNA repair, detoxification and hundreds of other metabolic functions.

B12 deficiency, Warning Signs of a B12 Deficiency

3. Hydroxocobalamin

This form is naturally created by bacteria fermentation and is the main type that is found in food.  It is easily converted into methyl-B12 within the body.  This is often the form that is used with injections for B12 deficiencies and as treatment for cyanide poisoning.

4. Adenosylcobalamin

This is the least stable form of B12 outside of the human body and therefore is not recommended in supplement form.  It is considered the energy formation form of B12 that naturally occurs within the cells of the body during the biochemical citric acid cycle.


Methyl-B12 is the most absorbable and easily useable form of B12 (24 ,25).   With the previously mentioned B12 absorption challenges, it is not adviseable to use forms that are either unstable (adeno-B12) or forms (cyano) that take more energy to convert into the active methyl-B12.

This is the form that I trust to get results with the clients I consult with after having seen it improve hundreds of pre/post lab tests. B12 Power is a pure form of methyl-B12 and what I use in my clinical practice.  I typically use a dosage of 5mg – 1x per day for 60 days and then retest.

B12 deficiency, Warning Signs of a B12 Deficiency

Sources For This Article Include:

1. Micronutrient Information Center – Vitamin B12
2. Watanabe T, Kaji R, Oka N, Bara W, Kimura J. Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy. J Neurol Sci. 1994 Apr;122(2):140-3. PMID: 8021696
3. Harvard Health Publications – Link Here
4. USDA – B12 Deficiency May Be More Widespread Than Thought Link Here
5. Genome Biology – Aging of blood can be tracked by DNA methylation changes at just three CpG sites Link Here
6. Watson WP, Munter T, Golding BT. A new role for glutathione: protection of vitamin B12 from depletion by xenobiotics. Chem Res Toxicol. 2004 Dec;17(12):1562-7. PMID: 15606130
7. MayoClinic – What’s the relationship between vitamin B-12 and depression? Link Here
8. Harvard Health Publications – Vitamin B12 deficiency can be sneaky, harmful Link Here
9. Three of the B Vitamins: Folate, Vitamin B6, and Vitamin B12 Link Here
10. Zehetner C, Bechrakis NE. White Centered Retinal Hemorrhages in Vitamin B12 Deficiency Anemia. Case Reports in Ophthalmology. 2011;2(2):140-144.
11. Watanabe T, Kaji R, Oka N, Bara W, Kimura J. Ultra-high dose methylcobalamin promotes nerve regeneration in experimental acrylamide neuropathy. J Neurol Sci. 1994 Apr;122(2):140-3. PMID: 8021696
12. Well – Acid-Suppressing Drugs Linked to Vitamin B12 Deficiency Link Here
13. Shojania AM. Oral contraceptives: effect of folate and vitamin B12 metabolism. Canadian Medical Association Journal. 1982;126(3):244-247.
14. Watanabe F, Katsura H, Takenaka S, Fujita T, Abe K, Tamura Y, Nakatsuka T, Nakano Y. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J Agric Food Chem. 1999 Nov;47(11):4736-41. PMID: 10552882
15. Watanabe F, Takenaka S, Kittaka-Katsura H, Ebara S, Miyamoto E. Characterization and bioavailability of vitamin B12-compounds from edible algae. J Nutr Sci Vitaminol (Tokyo). 2002 Oct;48(5):325-31. PMID: 12656203
16. Vitamin B12 Content of Organ Meats Link Here
17. Russell RM. Factors in aging that effect the bioavailability of nutrients. J Nutr. 2001 Apr;131(4 Suppl):1359S-61S. PMID: 11285355
18. Oosterhuis WP, Niessen RW, Bossuyt PM, Sanders GT, Sturk A. Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency. Scand J Clin Lab Invest. 2000 Feb;60(1):9-18. PMID: 10757449
19. Zittan E, Preis M, Asmir I, Cassel A, Lindenfeld N, Alroy S, Halon DA, Lewis BS, Shiran A, Schliamser JE, Flugelman MY. High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H860-5. PMID: 17449548
20. Methylmalonic Acid: A biomarker for vitamin B12 deficiency Link Here
21. McMullin MF, Young PB, Bailie KE, Savage GA, Lappin TR, White R. Homocysteine and methylmalonic acid as indicators of folate and vitamin B12 deficiency in pregnancy. Clin Lab Haematol. 2001 Jun;23(3):161-5. PMID: 11553056
22. Wikipedia – Vitamin B12
23. Shibuya K, Misawa S, Nasu S, Sekiguchi Y, Beppu M, Iwai Y, Mitsuma S, Isose S, Arimura K, Kaji R, Kuwabara S. Safety and efficacy of intravenous ultra-high dose methylcobalamin treatment for peripheral neuropathy: a phase I/II open label clinical trial. Intern Med. 2014;53(17):1927-31. PMID: 25175124
24. Vitamin B12 absorption and malabsorption Link Here
25. Adams JF, Ross SK, Mervyn L, Boddy K, King P. Absorption of cyanocobalamin, coenzyme B 12 , methylcobalamin, and hydroxocobalamin at different dose levels. Scand J Gastroenterol. 1971;6(3):249-52. PMID: 5560708


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