Anemia, Folic Acid Deficiency  

What Is Folic Acid Or Folate Deficiency Anemia?

[dropcap]F[/dropcap]olic acid deficiency anemia, also called folate deficiency anemia, is a macrocytic anemia characterized by defective DNA synthesis of red blood cells that results from a lack of folate in the body.

Q: How does folate deficiency cause anemia?

A: Folates are a family of B vitamins and folic acid is an active form.

Folate is required for the formation of both red and white blood cells in the bone marrow and for their maturation.

Also, folate serves as a carrier in the formation of heme, which contains iron, and is the non-protein part of the hemoglobin molecule.¹

Red blood cells provide oxygen to body tissues. When there are not enough red blood cells or when they cannot properly carry oxygen, the condition is called anemia. In folic acid deficiency anemia, the red blood cells are abnormally large. Such cells are called macrocytes (macro size cells). They are also called megaloblasts (mega size cells) as seen in the bone marrow where they are produced. This is why this macrocytic anemia is also called megaloblastic anemia.²

Tests that may be done to determine folate adequacy are complete blood count (CBC), red blood cell folate level, methylmalonic acid level, and homocysteine level. Folic acid deficiency anemia shows a decrease in red blood cell folate and/or serum folate levels and normal plasma methylmalonic acid level with elevated homocysteine blood level. These levels distinguish folic acid deficiency anemia from vitamin B12 deficiency anemia.³

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

• Relationship between folate deficiency anemia and celiac disease. Folate deficiency anemia is a classic symptom of celiac disease that results from malabsorption of folate.⁴
• Relationship between folate deficiency anemia and deficiency. Celiac disease should be considered in folate deficiency.⁵
• Relationship between folate deficiency anemia and antibodies. Study patients with positive IgA gliadin antibodies showed significantly lower serum folic acid concentrations than healthy controls.⁶
• Relationship between folate deficiency anemia and mucosal damage. Malnutrition and nutritional deficiencies of folic acid also predispose to mucosal damage of the small intestine.⁷

How Prevalent Is Folate Deficiency Anemia?

• Folate deficiency anemia is common and a classic presentation of celiac disease.⁵
• In an American retrospective study of 405 patients at diagnosis of celiac disease, macrocytic anemia with concurrent folic acid deficiency was under 3% while folic acid deficiency was 12%.⁸
• In a prospective Dutch study of 80 newly diagnosed patients, prevalence of folic acid deficiency was reported as 20%.⁹

What Are The Symptoms Of Folate Deficiency Anemia?

Folate deficiency anemia is marked by these symptoms:

• Weakness.
• Diarrhea.
• Tissue hypoxia (not enough oxygen) including fatigue, headache, lightheadedness, angina, dyspnea, pallor, and tachycardia.
• In pregnant women, folate deficiency has been associated with neural tube or spinal defects (such as spina bifida ) in the infant.²
• Other complications may include: Curly graying hair, increased skin color (pigment), worsening of heart disease.²

How Does Folate Deficiency Anemia Develop In Celiac Disease and/or Gluten Sensitivity?

• Folate deficiency anemia in celiac disease results from folate malabsorption.¹⁰

Does  Folate Deficiency Anemia Respond To Gluten-Free Diet?

Yes. Celiac disease-related folate deficiency anemia responds to gluten free diet and folic acid supplementation. Experts recommend that women take 400 micrograms (mcg) of folic acid supplement every day before getting pregnant through the first 3 months of pregnancy.²

6 Steps To Improve Folate Deficiency Anemia Related to Celiac Disease and/or Gluten Sensitivity:

• [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 folate deficiency 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.¹¹
• 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.¹²
• 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.¹²
• 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.¹².
• 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.¹²
• 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.¹²
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹²[/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 lettuce, kale, 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:

[box type=”shadow” ]

Certain prescription drugs deplete folic acid that promotes folate deficiency anemia. Ask your doctor or pharmacist about this possible adverse effect if you are taking any of the drugs listed below. Do not stop prescribed medications without supervision.

This is not a complete listing.

FEMALE HORMONES disrupt intestinal permeability.

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

DIURETICS

• Potassium Sparing Diuretics (Midamor®, Aldactone®, Dyrenium® and others) deplete Folic Acid.

DIABETIC DRUGS 

• Metformin® depletes Folic acid.

ANTI-INFLAMMATORIES – Disrupt Intestinal permeability.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Folic Acid.
• NSAIDS (Motrin®, Aleve®, Advil®, Anaprox®, Dolobid®, Feldene®, Naprosyn® and others) deplete Folic acid.
• Aspirin and Salicylates deplete Folic acid.

ANTICONVULSANTS

Phenobarbital and Barbituates; and Dilantin®, Tegretol®, Mysoline®, Depakane/Depacon® deplete Folic Acid.

ANTIBIOTICS  disrupt intestinal permeability.

• Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins deplete B Vitamins.

ANTACIDS / ULCER MEDICATIONS

• Pepcid®, Tagamet®, Zantac® deplete Folic Acid.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Folic Acid.
• Alka Seltzer®, Baking Soda deplete Folic Acid.

CHOLESTEROL DRUGS

• Colestid® and Questran® Folic acid.[/box]

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

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• 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.
• Folic acid tablets as prescribed by physician based on laboratory results of blood testing.

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. Fish oil goes in the refrigerator[/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:

Gentle exercise improves circulation and rids the body of toxins. Exercise only up to the point of pain to prevent tissue damage from lack of oxygen.

• 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 Folate Deficiency Anemia 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 folic acid. 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.⁹

“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. Folate deficiency was seen in approximately 12% of the total sample. Macrocytic anemia with concurrent folate deficiency was 3%.⁸

“Antigliadin antibodies in the absence of celiac disease.” This study measuring IgG and IgA isotypes and IgG subclasses demonstrated significantly lower serum folic acid concentrations in patients with positive IgA gliadin antibodies than in healthy controls.¹³

“Serum folates in man.” This study investigating folate compounds and their breakdown compounds demonstrated that 5-ethyltetrahydrofolate is poorly absorbed by patients with celiac disease and the availability for biological utilization of the major dietary folate compounds will depend on the amount of gastric acidity and of the ascorbate in the intestinal chyme. Many folate compounds may be unavailable for metabolic utilization in the body.¹⁴

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 folate 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.¹⁵

 

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9. 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. [↩] [↩]
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