Homocysteine, Elevated Blood Level (Hyperhomocysteinemia)

What Is Elevated Homocysteine?

[dropcap]E[/dropcap]levated homocysteine in blood, called hyperhomocysteinemia, indicates an abnormal blood level of this transient amino acid.

Q: How does the level of homocysteine become abnormal?

A: In metabolism, homocysteine is briefly formed in the breakdown of the amino acid methionine. It is normally converted to cystathione and then to the amino acid cysteine by means of an enzyme that requires vitamin B6.

In the reverse, conversion of homocysteine to methionine requires an enzyme dependent on adequate folic acid and vitamin B12 levels.

Insufficient methionine levels and/or inefficiency in this process results in elevated homocysteine plasma levels that are toxic to blood vessels.

Folic acid, vitamin B12 and vitamin B6 are involved in the metabolic removal of homocysteine, but folic acid deficit occurs the most often.¹

What Is Elevated Homocysteine In Celiac Disease and/or Gluten Sensitivity?

• Hyperhomocysteinemia and celiac disease. An elevated homocysteine level is a classic feature of untreated celiac disease and a frequent finding in untreated celiac disease.
• Hyperhomocysteinemia and longstanding celiac disease. Elevated homocysteine is characterized by altered endothelial (cells that line blood vessels) function that keeps vessels from relaxing as needed. Inability of vessels to relax or dilate normally results in increased blood pressure and promotes the development of hardening of the arteries (arteriosclerosis). Hardening of the arteries increases the risk of venous thrombosis (clots), cardiovascular disease, and stroke which have been demonstrated in adults with longstanding untreated celiac disease.
• Hyperhomocysteinemia and thrombosis (clots). A retrospective study investigating clinical features and risk factors for thrombosis that may occur in adult celiac disease provides evidence that risk factors for thrombosis should be identified in patients in adult celiac disease in order to correct them and add a thromboembolic prophylaxis or prevention.²
• Hyperhomocysteinemia and deficiencies of B vitamins. Compromised absorptive capacities of vitamins B6, B12, and folate in untreated patients make them susceptible to homocysteine abnormalities.³

• Hyperhomocysteinemia and inflammation. A recent study investigating folic acid and inflammation in persons with primary arterial hypertension showed that administration of folic acid not only caused a decrease in the concentration of homocysteine in serum but also a decrease in inflammation. Previous studies show that hyperhomocysteinemia stimulates the synthesis of CRP (C-reactive protein), which is a marker of inflammation, and the expression of adhesion molecules.⁴

• Hyperhomocysteinemia and gluten free diet. Fortunately, gluten exclusion improves folate status and normalizes homocysteine concentrations. Homocysteine concentrations were significantly higher and red cell and serum folate significantly lower in untreated patients compared with controls, while all three reached normal levels in patients with recovered villous atrophy.⁵
• Hyperhomocysteinemia and recurrent miscarriage. Hyperhomocysteinemia has been implicated in recurrent miscarriage, a recognized manifestations of celiac disease.⁶
• Hyperhomocysteinemia and broken bones in osteoporosis. Hyperhomocysteinemia has been implicated in osteoporotic fracture, recognized manifestations of celiac disease.⁶

How Prevalent Is Elevated Homocysteine In Celiac Disease and/or Gluten Sensitivity?

Celiac patients show a higher total plasma status  of homocysteine than the general population.⁷

What Are The Symptoms Of Elevated Homocysteine?

Elevated homocysteine is marked by these symptoms:

• Reversible hypertension.
• Arteriosclerosis with risk of venous thrombosis, coronary heart disease, and cerebral vascular disease (stroke).¹,⁸
• Increased risk for recurrent miscarriage.
• Increased risk for bone fractures from osteoporosis.

How Does Elevated Homocysteine In Celiac Disease and/or Gluten Sensitivity Develop?

• Elevated homocysteine results from vitamin cofactor malabsorption of  folic acid, vitamin B12, and vitamin B6 (pyridoxine) in celiac disease.

Does Elevated Homocysteine Respond To Gluten-Free Diet?

Yes. Celiac disease-related hyperhomocysteinemia improves on a strict gluten free diet and resolves with supplementation of deficient B vitamins.

Adults with longstanding celiac disease taking extra B vitamins for 6 months showed normalized tHcy (plasma total homocysteine) and significant improvement in general well-being, suggesting that B vitamins should be considered in people advised to follow a gluten-free diet.⁹

In persons with primary arterial hypertension the administration of folic acid not only caused a decrease in the concentration of homocysteine in serum but also a decrease in inflammation. Previous studies found that hyperhomocysteinemia stimulates the synthesis of CRP (C-reactive protein) and the expression of adhesion molecules.⁴

6 Steps To Improve Elevated Homocysteine 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 elevated homocysteine 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.¹⁰
• 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.¹¹
• 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.¹¹
• 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.¹¹.
• 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.¹¹
• 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.¹¹
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.¹¹[/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 vitamin B12, vitamin B6, or folic acid causing deficiency that promotes elevated homocysteine. 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 Vitamin B6, Vitamin B12, Folic Acid.
• Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others) deplete Vitamin B6, Vitamin B12, Folic Acid.

DIURETICS

• Loop Diuretics (Lasix®, Bumex®, Edecrin®) depletes Vitamin B6.
• Potassium Sparing Diuretics (Midamor®, Aldactone®, Dyrenium® and others) deplete Folic Acid.

DIABETIC DRUGS 

• Metformin® depletes Folic acid, Vitamin B12.

CARDIOVASCULAR DRUGS

• Antihypertensives (Catapres®, Aldomet) deplete Vitamin B6.

ANTI-INFLAMMATORIES – Disrupt Intestinal permeability.

• Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Vitamin B6, Vitamin B12, 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, Vitamin B12.

MAJOR TRANQUILIZERS   

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

ANTIBIOTICS  disrupt intestinal permeability.

• Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins deplete B Vitamins.
• Tetracyclines deplete Vitamin B6.

ANTACIDS / ULCER MEDICATIONS

• Pepcid®, Tagamet®, Zantac® deplete Folic Acid, Vitamin B12.
• Magnesium and Aluminum Antacid preparations (Gaviscon®, Maalox®, Mylanta®) deplete Folic Acid, Vitamin B12.
• Prevacid®, Prilosec® depleteVitamin B12.
• Alka Seltzer®, Baking Soda deplete Folic Acid.

CHOLESTEROL DRUGS

• Colestid® and Questran® Folic acid, Vitamin B12.

ANTIVIRAL AGENTS

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

ANTI-DEPRESSANTS

• Adapin®, Aventyl®, Elavil®, Pamelor®, and others deplete these nutrients: Vitamin B12.[/box]

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

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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.
• 100% of the B vitamins, or as prescribed by a doctor. Please note about B Vitamin Complex supplements:  some labeling can be confusing, for example, “B 100” does not mean 100% as we should expect. If the ingredient list shows  an excessive amount like 3000% or more, look for another brand because this excessive amount will cause the loss of mineral in the urine.

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:

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 Elevated Homocysteine In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Impact of administration of folic acid on selected indicators of inflammation in patients with primary arterial hypertension.” This study investigated whether administration of folic acid to patients with primary arterial hypertension influences concentrations of indicators of inflammation: hsCRP, sICAM-1 and sVCAM-1. Results show  that administration of folic acid to persons with primary arterial hypertension in a dose of 15 mg/ day for 45 days caused a decrease in the concentration of homocysteine in serum.

The examination was carried out in 41 patients with primary arterial hypertension, aged 19-65 (21 men and 20 women), without complications of hypertension and/or coexisting diseases. The examined patients were administered 15 mg of folic acid once a day for 45 days. Before and after administration of folic acid, concentrations of folic acid, homocysteine, hsCRP, sICAM-1 and sVCAM-1 in serum were assessed.

After the administration of folic acid in patients with primary arterial hypertension, a significant decrease in median concentrations of homocysteine in blood was observed. Simultaneously, the median hsCRP, ICAM-1 and VCAM-1 concentrations in serum in patients with primary arterial hypertension were significantly reduced.

Administration of folic acid to persons with primary arterial hypertension caused a decrease in the concentration of homocysteine in serum. That could indirectly result in the decrease in concentrations of the indicators of inflammation (hsCRP, ICAM-1 and VCAM-1), as it is apparent from previous studies that hyperhomocysteinemia stimulates the synthesis of CRP and the expression of adhesion molecules.⁴

“Adult celiac disease with thrombosis: a case series of seven patients. Role of thrombophilic factors.” This retrospective study investigating clinical features and risk factors for thrombosis that may occur in adult celiac disease provides evidence that risk factors for thrombosis should be identified in patients in adult celiac disease in order to correct them and add a thromboembolic prophylaxis or prevention.

 Of 87 patients with adult celiac disease  seven cases of thrombosis were identified. Researchers looked to see if risk factors for thrombosis were identified and tested retrospectively antiphospholipid antibodies on the serum.

Results: The overall prevalence of thrombosis was 8 %, and 5.7 % for spontaneous thrombosis. Five patients had venous thrombosis, one had arterial thrombosis, and two had both. The seven patients consisted in six women and one man with a mean age of 44.8 years at time of thrombosis. Thrombotic events occurred before the diagnosis of celiac disease in four cases. In three cases, venous thrombosis was in unusual sites: 2 in the portal vein and one splenic vein thrombosis.

In six cases, risk factors for thrombosis were identified, which could be linked to celiac disease: one case of hyperhomocysteinemia, 3 cases of protein C and S deficiency due to vitamin K deficiency, and 2 cases of antiphospholipid antibodies.²

“Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet.” This study investigating the biochemical and clinical effects of B vitamin supplementation in adults with longstanding celiac disease found that adults with longstanding celiac disease taking extra B vitamins for 6 months showed normalized tHcy (plasma total homocysteine) and significant improvement in general well-being, suggesting that B vitamins should be considered in people advised to follow a gluten-free diet.

In a double blind placebo controlled multicenter trial, 65 celiac patients (61% women) aged 45-64 years on a strict gluten-free diet for several years were randomized to a daily dose of 0.8 mg folic acid,0.5 mg cyanocobalamin and 3 mg pyridoxine or placebo (no vitamin pill) for 6 months. The outcome measures were psychological general well-being and the plasma total homocysteine (tHcy) level, marker of B vitamin status.

Fifty-seven patients (88%) completed the trial. The tHcy level was baseline median 11.7 micromol/L (7.4-23.0), significantly higher than in matched population controls [10.2 micromol/L (6.7-22.6)]. Following vitamin supplementation, tHcy dropped a median of 34%, accompanied by significant improvement in well-being, notably anxiety and depressed mood for patients with poor well-being.⁹

“Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery.” This study investigating plasma homocysteine levels and biomarker status of metabolically related B vitamins (folate, vitamin B12, B6 and riboflavin) in treated and untreated celiac patients and healthy controls found that gluten exclusion in celiac disease improves folate status and normalizes homocysteine concentrations. Celiac patients attending a clinic for either initial or follow-up biopsy (at least 12 months after commencing a gluten-free diet) were categorized into three groups: 1) 35 newly diagnosed patients; 2) 24 patients with persistent villous atrophy (VA) at follow-up;  or 3) 41 patients with recovered VA at follow-up. Blood samples were analyzed for plasma homocysteine, serum and red cell folate and serum vitamin B12 levels, and for plasma pyridoxal 5-phosphate (PLP, vitamin B6) and riboflavin (vitamin B2) status.

Homocysteine concentrations were significantly higher and red cell and serum folate significantly lower in untreated patients compared with controls, while all three reached normal levels in recovered VA patients. Although untreated and persistent VA patients tended to have lower B12 levels, these did not reach significance. There was no evidence of compromised B6 or riboflavin status, even in untreated CD patients. Homocysteine concentrations were inversely associated with both serum and red cell folate and with serum vitamin B12. Reducing the risk of homocysteine-related disease may be another reason for aggressive diagnosis and treatment of celiac disease.¹²

“Folic acid: new indications for an old well-known drug.” This study investigating the vitamin nutrition status of patients 45 to 64 years old with diagnosed Celiac Disease in biopsy-proven remission who were on a Gluten Free Diet for 10 years, demonstrated half of the patients showed a poor vitamin status. Plasma levels of folate were low in 37% and pyridoxal 5′-phosphate levels were low in 20% and accounted for 33% of the variation of the total plasma homocysteine level. The mean daily intakes of folate and vitamin B12, but not of pyridoxine, were significantly lower in Celiac Disease patients than in controls. This may have clinical implications considering the linkage between vitamin deficiency, elevated total plasma homocysteine levels and cardiovascular disease. Follow-up should include review of vitamin status.⁷

CASE REPORT SUMMARIES

“Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years.” This case report of a 49 year old woman with uncomplicated sustained hypertension describes investigation of raised homocysteine levels with low vitamin B12 level and endothelial dysfunction and subsequent diagnosis of Celiac Disease. Treatment of Celiac Disease normalized her blood pressure with parallel normalization of homocysteine levels and endothelial function. These observations suggest that sub-clinical Celiac Disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of etiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.¹³

Sources:

1. Lim PO, Tzemos N, Farquharson CA, et al. Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction. Journal of Human Hypertension. Jun 2002;16(6):411-5. [↩] [↩]
2. Berthoux E1, Fabien N, Chayvialle JA, Ninet J, Durieu I. Adult celiac disease with thrombosis: a case series of seven patients. Role of thrombophilic factors. Rev Med Interne. 2011 Oct;32(10):600-4. doi: 10.1016/j.revmed.2011.02.025. [↩] [↩]
3. Hozyasz K, Mostowska A, Szaflarska-Poplawska A, Lianeri M, and Jagodzinski P. Polymorphic variants of genes involved in homocysteine metabolism in celiac disease. Mol Biol Rep. 2012 March; 39(3): 3123–3130. [↩]
4. Baszczuk A, Kopczyński Z, Kopczyński J, Cymerys M, Thielemann A, Bielawska L, Banaszewska A. Impact of administration of folic acid on selected indicators of inflammation in patients with primary arterial hypertension. Postepy Hig Med Dosw (Online). 2015 Apr 7;69:429-35. [↩] [↩] [↩]
5. Dickey W, Ward M, Whittle CR, Kelly MT, Pentieva K, Horigan G, Patton S, McNulty H. Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery. Scand J Gastroenterol. 2008;43(6):682-8. doi: 10.1080/00365520701881118. [↩]
6. Dickey W, Ward M, Whittle CR, Kelly MT, Pentieva K, Horigan G, Patton S, McNulty H. Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery. Scand J Gastroenterol. 2008;43(6):682-8. doi: 10.1080/00365520701881118. [↩] [↩]
7. Nowakowska E, Chodera A, Bobkiewicz-Kozlowska T, Hertmanowska H. Folic acid: new indications for an old well-known drug. Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego. Nov 2003;15(89):449-51. [↩] [↩]
8. Hallert C, Grant C, Grehn S, et al. Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years. Alimentary Pharmacology and Therapeutics. Jul 2002;16(7):1333-9. [↩]
9. Hallert C, Svensson M, Tholstrup J, Hultberg B. Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet. Aliment Pharmacol Ther. 2009 Apr 15;29(8):811-6. doi: 10.1111/j.1365-2036.2009.03945.x. [↩] [↩]
10. 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. [↩]
11. 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. [↩] [↩] [↩] [↩] [↩] [↩]
12. Dickey W, Ward M, Whittle CR, Kelly MT, Pentieva K, Horigan G, Patton S, McNulty H. Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery. Scand J Gastroenterol. 2008;43(6):682-8. doi: 10.1080/00365520701881118. [↩]
13. Hallert C, Grant C, Grehn S, et al. Alimentary Pharmacology and Therapeutics. Jul 2002;16(7):1333-9. [↩]