What Is Pernicious Anemia and How Do You Diagnose And Treat It?

Vitamin B12 has the largest and most complex chemical structure of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason cobalamin is the term used to refer to compounds having vitamin B12 activity. Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 used in the human body. Pernicious anemia occurs when the body doesnt make enough intrinsic factor in the stomach to help convert and absorb Vitamin B12 in the intestines and occurs more commonly in people of African and European origin. Vitamin b12–deficiency anemia, also known as cobalamin deficiency, however can also occur because of a lack of access in the diet. Vitamin B12 (cobalamin) is essential for the body to make healthy red blood cells, white blood cells, and platelets. Since your body doesn’t make vitamin B12, you have to get it from the foods you eat or from supplements. Without enough vitamin B12, blood cells do not form properly inside the bone marrow, the sponge-like tissue within bones - these blood cells die sooner than normal, leading to anemia.

Vitamin B12 plays a crucial role in various essential bodily functions:

1. Neurological Health:

Vitamin B12 is pivotal for maintaining a healthy nervous system. It participates in the synthesis of myelin, a protective sheath that covers nerve fibers and facilitates efficient nerve signal transmission. Deficiencies in B12 can lead to demyelination, nerve damage, and a range of neurological symptoms, including numbness, tingling, and muscle weakness. In severe cases, B12 deficiency can result in irreversible nerve damage, affecting balance, coordination, and cognitive functions.

2. DNA Synthesis:

Vitamin B12 is essential for DNA synthesis and cell division. It aids in the conversion of homocysteine, an amino acid, into methionine, another amino acid involved in DNA production. Proper DNA synthesis is crucial for the growth, repair, and maintenance of cells, which in turn supports tissue regeneration, immune function, and overall health.

3. Red Blood Cell Formation:

Vitamin B12 is integral to the p  roduction of red blood cells in the bone marrow. It is involved in the synthesis of heme, a component of hemoglobin, which carries oxygen from the lungs to the body's tissues. B12 deficiency can lead to inadequate red blood cell production, resulting in anemia. Anemia can cause fatigue, weakness, and shortness of breath due to reduced oxygen-carrying capacity.

4. Energy Metabolism:

B12 plays a vital role in energy metabolism. It assists in breaking down fatty acids and amino acids, allowing the body to generate energy from these substrates. Without sufficient B12, the body's ability to efficiently utilize these nutrients for energy production is compromised.

5. Homocysteine Regulation:

Vitamin B12, along with other B vitamins like folate and B6, helps regulate homocysteine levels in the blood. Elevated homocysteine levels are associated with an increased risk of cardiovascular disease, as they contribute to inflammation and damage to blood vessels.

6. Cognitive Function:

Adequate B12 levels are essential for cognitive function, including memory, concentration, and mood regulation. B12 deficiency has been linked to cognitive decline, memory impairment, and an increased risk of neurodegenerative disorders, such as dementia and Alzheimer's disease.

Dietary Sources

While ‘Lack of Absorption’ because of lack of intrinsic factor resulting in pernicious anemia is the most obvious form of b12 deficiency, it is certainly not the only pathway for deficiency. ‘Lack of Access’ is the more common reason for deficiencies. The only dietary sources of vitamin b12 are of animal (or yeast) in origin, therefore, it is VERY common for vegetarian, vegan, and raw-foodists to be b12 deficient. Even people with a omnivore diet are sometimes deficient in vitamin B12 and other core nutrients when the foods they are consuming are either insufficient for the bodies needs (as is the case with most ‘carbatarians’ - my word for when carb consumption is over 80% of their diet) and/ or the foods they’re consuming actively block the absorption of the nutrients or it’s co-factors. Additionally, Certain medications, like proton pump inhibitors, can also interfere with B12 absorption.

Foods that are high in vitamin b12 are as follows : organ meats, clams, beef, salmon, sardines, milk, eggs, and nutritional yeast.

Supplementation Forms

To consume enough vitamin b12 for dietary sources alone, one must consume at least 1 serving of the above foods at every meal. If that is not possible or desired, supplementation must be considered. There are three natural forms of b12 available as commercial supplements: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxycobalamin (OHCbl), “all of which have been shown in clinical studies to improve vitamin B12 status. They are bioidentical to the B12 forms occurring in human physiology and animal foods. In contrast, cyanocobalamin (CNCbl), a synthetic B12 compound used for food fortification and in some supplements, occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources” (Paul, C & Brandy, D., 2017).

In studies of bioavailability, all three natural supplements seem to convert into the correct ration of cobalamin in the body regardless of the ratios taken, so any or a combo of the three natural supplements is appropriate, although methylcobalomin is generally the least expensive.

The preservation of DNA integrity is dependent on folate and vitamin B12 availability. Poor vitamin B12 status has been linked to increased risk of breast cancer in some, but not all, observational studies. There is a need to evaluate whether supplemental vitamin B12, along with folic acid, could help reduce breast cancer incidence (Carmel, R., 2006). The enzymes that are produced as a result of proper b12 uptake in the body also play an important role in the production of energy from lipids and proteins and is also required for the synthesis of hemoglobin, the oxygen-carrying pigment in red blood cells (Shane, B., 2000).

Diminished gastric function in individuals with atrophic gastritis can result in bacterial overgrowth in the small intestine and cause food-bound vitamin B12 malabsorption. Vitamin B12 levels in serum, plasma, and gastric fluids are significantly decreased in individuals with H. pylori infection, and eradication of the bacteria has been shown to significantly improve vitamin B12 serum concentrations (Lahner E, Persechino S, Annibale B. 2012).

Observational studies have found as many as 30% of patients hospitalized for depression are deficient in vitamin B12 (Hutto BR, 1997).

Symptoms

Vitamin B12 deficiency can manifest with a range of symptoms, which can vary in severity and presentation. The symptoms can affect different bodily systems and organs due to the diverse roles of vitamin B12 in various physiological processes. Some common symptoms of vitamin B12 deficiency include:

1. Anemia-related

Symptoms:

• Fatigue and weakness

• Pale or jaundiced skin

• Shortness of breath

• Dizziness or lightheadedness

2. Neurological Symptoms:

• Numbness or tingling in the hands and feet (paresthesia)

• Balance problems and difficulty walking (ataxia)

• Muscle weakness

• Memory problems and cognitive difficulties

• Difficulty concentrating

• Mood changes, including depression and irritability

• Tremors or other involuntary movements

3. Digestive Symptoms:

• Loss of appetite

• Weight loss

• Digestive discomfort, such as nausea and vomiting

• Diarrhea or constipation

4. Cognitive and Behavioral Symptoms:

• Confusion and disorientation

• Trouble finding words or speaking clearly

• Personality changes

• Psychiatric symptoms, including anxiety and paranoia

5. Cardiovascular Symptoms:

• Rapid heart rate (tachycardia)

• Shortness of breath, even with minimal exertion 

6. Dermatological Symptoms:

• Pale or jaundiced skin in white folks

• Hyperpigmentation in black folks

• Jaundice of the eyes (yellowing of the sclera)

• Glossitis (inflamed tongue), making it appear smooth and red OR scalloped and ridged.

7. Visual Disturbances:

• Blurred or double vision

• Optic neuropathy, which can cause visual impairment or even blindness in severe cases

It's important to note that some of these symptoms can also be associated with other medical conditions, so a proper diagnosis is crucial - when in doubt always draw labs. But many of these symptoms have become synonymous with pregnancy its self - so always investigate and believe your clients if they are complaining of these symptoms.

Effective Treatment

Initial laboratory assessment should include a complete blood count and serum vitamin B12 level. Measurement of serum methylmalonic acid should be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12. Optimal Lab values for serum B12 are 600- 1000 pg/mL, but they may appear higher during periods of high dose supplementation.

Oral administration of high-dose vitamin B12 (1 to 2 mg daily) is as effective as intramuscular administration for correcting anemia and neurologic symptoms. Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms. Absorption rates improve with supplementation; therefore, patients older than 50 years and vegans or strict vegetarians should consume foods fortified with vitamin B12 or take vitamin B12 supplements. Patients who have had bariatric surgery should receive 1 mg of oral vitamin B12 per day indefinitely (Langan, R.C. & Goodbred A.J., 2017 & Carmel R., 2008).

No toxic or adverse effects have been associated with large intakes of vitamin B12 from food or supplements in healthy people. Doses as high as 2000 mcg orally or 1000 mcg injection weekly have been used to treat pernicious anemia without significant side effects (Langan, R.C. & Goodbred A.J., 2017). When high doses of vitamin B12 are given orally, only a small percentage can be absorbed, which may explain the low toxicity (Carmel R., 2008). Because of the low toxicity of vitamin B12, no max upper intake level has been set by the US Food and Nutrition Board.

References

Baik, H. W., & Russell, R. M. (1999). "Vitamin B12 deficiency in the elderly." Annual Review of Nutrition, 19, 357-377.

Carmel, R. (2008). How I treat cobalamin (vitamin B12) deficiency. Blood, 112(6), 2214-2221.

Carmel, R. (2006). Cobalamin (Vitamin B-12). In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. Philadelphia: Lippincott Williams & Wilkins; 2006:482-497.

Green, R., & Miller, J. W. (2013). "Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population." Clinical Chemistry and Laboratory Medicine, 51(2), 319-327.

Herrmann, W., & Obeid, R. (2012). "Cobalamin deficiency." Subcell Biochem, 56, 301-322.

Hutto, B. R. (1997). Folate and cobalamin in psychiatric illness. Compr Psychiatry, 38(6), 305-314.

Lahner, E., Persechino, S., & Annibale, B. (2012). Micronutrients (Other than iron) and Helicobacter pylori infection: a systematic review. Helicobacter, 17(1), 1-15.

Langan, R. C., & Goodbred, A. J. (2017). Vitamin B12 Deficiency: Recognition and Management. American Family Physician, 96(6), 384-389.

O'Leary, F., & Samman, S. (2010). "Vitamin B12 in health and disease." Nutrients, 2(3), 299-316.

Shane, B. (2000). Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.

Watanabe, F. (2007). "Vitamin B12 sources and bioavailability." Experimental Biology and Medicine, 232(10), 1266-1274