Vitamin B12 Deficiency Anemia

What Is Vitamin B12 Deficiency Anemia?

[dropcap]V[/dropcap]itamin B12 deficiency anemia is a megaloblastic anemia that is characterized by defective DNA synthesis of red blood cells due to a lack of vitamin B12. Vitamin B12 is essential for normal blood cell formation.

In turn, defective blood cells cause a low red blood cell count (blood analysis result) that is anemia.

Q: What is the meaning of megaloblastic?

A: Megaloblastic describes a form of blood cell called a megaloblast. Megaloblasts are abnormally large blood cells that are oval and slightly irregular. In contrast, the blood cells in iron deficiency anemia are normal shaped but small.

Megaloblastic anemia can be caused by both vitamin B12 and folic acid deficiencies so that it is absolutely necessary to distinguish which, or if both, are involved for proper treatment of this anemia.

Decreased vitamin B12 blood level and elevated plasma methylmalonic acid level with elevated homocysteine level (a transient amino acid) distinguish vitamin B12 deficiency anemia from folic acid deficiency anemia.¹ Vitamin B12, but not folic acid, is required in the metabolism of methylmalonic acid while both vitamin B12 and folic acid keep the level of homocysteine in blood from rising above normal.

Although the most important features are usually hematological ones, presence of neurological involvement, in the absence of blood count alterations, has just been described in the literature.²

What Is Vitamin B12 Deficiency Anemia In Celiac Disease and/or Gluten Sensitivity?

• Relationship between vitamin B12 deficiency anemia and celiac disease. Vitamin B12 deficiency anemia is a classic presentation of celiac disease and does not respond to therapy with vitamin B12 supplementation before treatment with gluten free diet.
• Relationship between vitamin B12 deficiency anemia and  deficiency. Celiac disease should be considered in vitamin B12 deficiency.³
• Relationship between vitamin B12 deficiency anemia and development. Although anemia is still a common presentation of celiac disease, nutritional deficiencies alone do not explain this phenomenon in all cases; inflammation appears to contribute as evidenced by the presence of anemia of chronic disease in some individuals.⁴
• Relationship between vitamin B12 deficiency anemia and degree of villous atrophy. Vitamin B12 deficiency was found counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. Therefore, extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in celiac disease treatment.⁵

How Prevalent Is Vitamin B12 Deficiency Anemia in Celiac Disease?

• Vitamin B12 deficiency anemia is common in untreated patients with celiac disease.⁶
• In an American retrospective study of 405 patients at diagnosis of celiac disease, macrocytic anemia with concurrent vitamin B12 deficiency was under 3% while vitamin B12 deficiency was 5%.⁴
• In a prospective Dutch study of 80 newly diagnosed patients, prevalence of vitamin B12 deficiency was reported as 19% and of these no patient had atrophic gastritis as a cause.⁵

What Are The Symptoms Of Vitamin B12 Deficiency Anemia?

Vitamin B12 deficiency anemia is marked by these symptoms:

• Weakness.
• Intermittent diarrhea.
• Nausea.
• A sore, swollen, red tongue or bleeding gums.
• Lemon yellow tint to skin.
• Hypoxia (not enough oxygen delivered to the body by faulty red blood cells) causing fatigue, headache, lightheadedness when standing up or with exertion, difficulty concentrating, shortness of breath mostly during exercise, angina, dyspnea, pallor, and tachycardia.
• Low vitamin B12 levels for a long time cause nerve damage. Symptoms of nerve damage include confusion or change in mental status, dementia in severe cases, depression, loss of balance (ataxia), inability to stand without support, falling, and numbness and tingling of hands and feet (neuropathy).
• Long-term deficiency can cause nerve damage. This may be permanent if treatment is not started within 6 months of when symptoms begin. Early diagnosis and prompt treatment can reduce or prevent complications related to low levels.
• Women with low vitamin B12 levels may have a falsely abnormal pap smear. That is because vitamin B12 affects the way certain cells, called epithelial cells, look on a slide.⁷

How Does Vitamin B12 Deficiency Anemia Develop in Celiac Disease?

• Vitamin B12 deficiency anemia results from vitamin B12 deficiency state induced by malabsorption in celiac disease.
• Vitamin B12 is typically absorbed in the terminal ileum. Apparently, the distal small bowel (ileum) is functionally more affected than previously believed, based on patho-histological analysis of distal small bowel biopsy samples.⁵

Does Vitamin B12 Deficiency Anemia Respond To Gluten-Free Diet?

Yes. Celiac disease-related vitamin B12 deficiency anemia responds to gluten free diet containing adequate vitamin B12. Supplementation is recommended to normalize levels.

6 Steps To Improve Vitamin B12 Deficiency Anemia:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both anemia and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.⁸
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.⁹
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.⁹
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.⁹.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.⁹
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.⁹
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.⁹[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes green leafy vegetables such as lettuce and kale, also onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

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Certain medications deplete vitamin B12.  Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. DO  NOT STOP TAKING PRESCRIPTION MEDICATIONS WITHOUT CONSULTING YOUR PHYSICIAN.

This is not a complete listing.

 ANTACIDS / ULCER MEDICATIONS

• Pepcid®, Tagamet®, Zantac® deplete Vitamin B12.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Vitamin B12.
• Prevacid®, Prilosec® deplete Vitamin B12.

ANTI-DEPRESSANTS

• Adapin®, Aventyl®, Elavil®, Pamelor®, and others deplete Vitamin B12.

ANTI-INFLAMMATORIES disrupt intestinal permeability which complicates celiac disease.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Vitamin B12.

ANTICONVULSANTS

• Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® deplete Vitamin B12.

ANTIVIRAL AGENTS

• Zidovudine (Retrovir®, AZT and other related drugs) deplete Vitamin B12.

CHOLESTEROL DRUGS

• Lipito®r, Crestor®, Zoco®r, and others deplete Coenzyme Q10.
• Colestid® and Questran® deplete Vitamin B12.

DIABETIC DRUGS 

• Metformin® depletes Vitamin B12.

FEMALE HORMONES disrupt intestinal permeability which complicate celiac disease.

• Oral Contraceptives (Norinyl®, Ortho-Novum®, Triphasil®, and others) deplete Vitamin B12.
• Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others) deplete Vitamin B12.

MAJOR TRANQUILIZERS  

• Thorazine®, Mellaril®, Prolixin®, Serentil® and others deplete Vitamin B12.

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• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

• Multivitamin/mineral combination once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
• Vitamin B12 as prescribed following blood test for status.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Vitamin B12 Deficiency In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients.” This study aiming to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult celiac disease (CD)-patients in the Netherlands found that vitamin/mineral deficiencies are still common in newly “early diagnosed” CD-patients, including vitamin B12. Eighty newly diagnosed adult CD-patients were included and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations.

Nutritional status and serum concentrations of folic acid, vitamin A, vitamin B6, vitamin B12, and (25-hydroxy) vitamin D, zinc, hemoglobin (Hb) and ferritin were determined before prescribing gluten free diet. Almost all CD-patients (87%) had at least one value below the lower limit of reference. Specifically, for vitamin A, 7.5% of patients showed deficient levels, for vitamin B6 14.5%, folic acid 20%, and vitamin B12 19%. Likewise, zinc deficiency was observed in 67% of the CD-patients, 46% had decreased iron storage, and 32% had anemia.

Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment.⁵

“Anemia in celiac disease is multifactorial in etiology.” This study assessed the characteristics of anemia from a cohort of patients seen at a hospital care center for celiac disease. Hematological parameters measured less than 3 months of diagnosis and degree of villous atrophy from 405 patients diagnosed after 1995 was analyzed.  Vitamin B12 deficiency was seen in approximately 5%. Macrocytic anemia with concurrent B12 or folate deficiency 3%.

Although anemia is still a common presentation of celiac disease, nutritional deficiencies alone do not explain this phenomenon in all cases; inflammation appears to contribute as evidenced by the presence of anemia of chronic disease in some individuals.⁴

CASE REPORT SUMMARIES

“Carpopedal spasm in an elderly man: an unusual presentation of celiac disease.” This case report describes diagnosis of celiac disease in a 68-year-old single Caucasian man admitted to the hospital with a 24-hour history of carpopedal spasm of both hands. Apart from generalized weakness, he reported no other symptoms. Physical examination revealed carpopedal spasm, clubbing of fingers and cachexia (body mass index 14 kg/m2). This patient was found to have several unusual features of celiac disease, including a low vitamin B12 level causing anemia, severe hypocalcemia and electrolyte disturbances as the initial manifestations, minimal gastrointestinal symptoms, and negative tTG-antibodies.

Blood tests showed severe hypocalcemia, with a total serum calcium of 1.06 mmol/L (normal range [NR] 2.05-2.55 mmol/L). He also had low serum potassium (2.8 mmol/L; NR 3.5-5.5 mmol/L) and magnesium (0.36 mmol/L; NR 0.65-1.05 mmol/L). Other significant results included hemoglobin 10.6 g/dL (NR 13-18 g/dL), mean corpuscular volume 98.1 fl (NR 82-98 fl), vitamin B12 157 ng/L (NR > 165 ng/L), folate 2.8 g/L (NR 3.1-17.5 μg/L), ferritin 252 μg/L (NR 30-250 μg/L), prothrombin time 20 s (NR 11-14 s), thyroid stimulating hormone 0.87 mu/L (NR 0.35-4.5 mu/L), phosphate 0.57 mmol/L (NR 0.8-1.45 mmol/L), albumin 32 g/L (NR 34-48 g/L) and alkaline phosphatase 313 IU/L (NR 47-141 IU/L). Subsequent results revealed vitamin D deficiency with a low serum 25-OH vitamin D of < 7 μg/L (NR 7-40 μg/L), a low 24-hour urinary calcium excretion of 0.9 mmol (NR 2.5-7.5 mmol) and a raised serum parathyroid hormone of 22.7 pmol/L (NR 1.6-6.9 pmol/L). Serology for tissue transglutaminase (tTG) antibodies was negative, and a serum IgA level of 4.95 g/L (NR 0.8-4.0 g/L) excluded selective IgA deficiency. Electrocardiograph at admission showed prolonged QT interval.

In view of cachexia, clubbing and negative tTG-antibodies, he was further investigated for an occult malignancy. Barium meal and follow through showed dilated proximal bowel loops and absence of normal feathery pattern of the jejunum, features suggestive of a malabsorptive state. Upper gastroscopic examination was normal; however, the duodenal biopsy showed partial and subtotal villous atrophy with increased intra-epithelial lymphocyte infiltration, consistent with the diagnosis of coeliac disease.¹⁰

Sources:

1. Mark Beers and Robert Berkow. The Merck Manual, 17th Edition. Whitehouse Station, N.J. USA: Merck Research Laboratories, 1999. [↩]
2. Mansueto P, Di Stefano L, D’Alcamo A, Carroccio A. Multiple sclerosis-like neurological manifestations in a coeliac patient: nothing is as it seems. BMJ Case Rep. 2012 Jul 4;2012. pii: bcr2012006392. doi: 10.1136/bcr-2012-006392. [↩]
3. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
4. Harper JW, Holleran SF, Ramakrishnan R, Bhagat G, Green PH. Anemia in celiac disease is multifactorial in etiology. Am J Hematol. 2007 Nov; 82(11):996-1000. [↩] [↩] [↩]
5. Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients. 2013 Sep 30;5(10):3975-92. doi: 10.3390/nu5103975. [↩] [↩] [↩] [↩]
6. Murray JA, the widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999; 69(3):354-365. [↩]
7. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001600/ [↩]
8. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
9. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
10. Schmidt K, Powari M, Shirazi T, Vaidya B. Carpopedal spasm in an elderly man: an unusual presentation of coeliac disease. J R Soc Med. 2007 Nov;100(11):524-5. [↩]