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Vitamin B12 Deficiency (Holistic)

Vitamin B12 Deficiency (Holistic)

About This Condition

Your body relies on B12 for healthy blood. Too little of this vital vitamin can lead to anemia and other health issues. According to research or other evidence, the following self-care steps may be helpful.
  • Get your B12

    Manage mild deficiency with over-the-counter vitamin B12 supplements

  • Add vitamins to your vegan diet

    If you follow a strict vegan diet, take a daily B12 supplement of at least 2.4 mcg

About

About This Condition

An abnormally low level of vitamin B12 (cobalamin) is a factor in many disorders.

The absorption of dietary vitamin B12 occurs in the small intestine and requires a secretion from the stomach known as intrinsic factor. If intrinsic factor is deficient, absorption of vitamin B12 is severely diminished. Vitamin B12 deficiency impairs the body’s ability to make blood, accelerates blood cell destruction, and damages the nervous system. The result is pernicious anemia (PA). In the classical definition, PA refers only to B12 deficiency anemia caused by a lack of intrinsic factor.

True pernicious anemia is probably an autoimmune disease. The immune system destroys cells in the stomach that secrete intrinsic factor. Many people with PA have both chronic inflammation of the stomach lining, called atrophic gastritis, and antibodies that fight their intrinsic factor-secreting cells.1

The term pernicious anemia is sometimes used colloquially to refer to any anemia caused by vitamin B12 deficiency. Vitamin B12 deficiency can be due to malabsorption of dietary B12 despite normal levels of intrinsic factor. For example, celiac disease and Crohn’s disease may cause B12 malabsorption, which can lead to anemia. Less common causes of B12 deficiency include gastrointestinal surgery, pancreatic disease , intestinal parasites , and certain drugs. Pregnancy , hyperthyroidism, and advanced stages of cancer may increase the body’s requirement for B12, sometimes leading to a deficiency state.

Low stomach acid , known as hypochlorhydria, interferes with the absorption of B12 from food but not from supplements. Aging is associated with a decrease in the normal secretion of stomach acid. As a result, some older people with normal levels of intrinsic factor and with no clear cause for malabsorption will become vitamin B12-deficient unless they take at least a few micrograms per day of vitamin B12 from supplements.

Caution: Pernicious anemia is a serious medical condition. When fatigue, often the first symptom of PA, is present, a qualified healthcare practitioner should be consulted. Symptoms of PA can be caused by other conditions, none of which would respond to vitamin B12 supplementation. Moreover, if true vitamin B12 deficiency exists, the cause—lack of intrinsic factor, general malabsorption conditions, lack of stomach acidity , or dietary deficiency—must also be properly diagnosed by examination and blood tests before the appropriate treatment can be determined.

Symptoms

Symptoms of severe vitamin B12 deficiency (regardless of the cause) may include burning of the tongue, fatigue, weakness, loss of appetite, intermittent constipation and diarrhea , abdominal pain, weight loss, menstrual symptoms, psychological symptoms, and nervous system problems, such as numbness and tingling in the feet and hands. Most symptoms can occur before the deficiency is severe enough to cause anemia. Healthcare professionals have a series of laboratory tests that can determine B12 deficiency at earlier stages that are not accompanied by anemia.

Healthy Lifestyle Tips

Alcohol abuse can lead to gastritis and damage to the lining of the intestines, both of which can interfere with vitamin B12 absorption. If B12 deficiency is due to alcoholism , abstinence may prevent further impairment of B12 absorption.2

Eating Right

The right diet is the key to managing many diseases and to improving general quality of life. For this condition, scientific research has found benefit in the following healthy eating tips.

Recommendation Why
Eat foods high in vitamin B12
Even small amounts of meat, poultry, fish, eggs, and dairy products supply sufficient amounts of vitamin B12 for healthy people.

Vitamin B12 is found in significant amounts only in animal protein foods—meat and poultry, fish, eggs, and dairy products. Even small amounts of these foods supply sufficient amounts of vitamin B12 to provide enough for healthy people.

Add B12 to your vegan diet
If you follow a strict vegan diet, take a daily B12 supplement of at least 2.4 mcg.

Except for vegans (vegetarians who also abstain from eggs, dairy, and other animal products), virtually no one in North America has a diet deficient in vitamin B12. Those who avoid animal protein foods can easily take vitamin B12 supplements instead. Strict vegans generally develop a dietary deficiency of vitamin B12, but it is often many years before a deficiency becomes severe enough to cause symptoms or to be diagnosed. Doctors recommend that all vegans supplement with vitamin B12.

Take supplements if you have low stomach acid or malabsorption
People who have a vitamin B12 deficiency due to malabsorption or low stomach acid need to depend on high amounts of vitamin B12 from supplements and not the smaller amounts found in food.

People who lack intrinsic factor or have a malabsorption condition need to depend on high amounts of vitamin B12 from supplements and not the lower amounts found in food. Similarly, older people with a vitamin B12 deficiency due to a lack of stomach acid, but not a lack of intrinsic factor, cannot depend on food-based vitamin B12.

Supplements

What Are Star Ratings?

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by some in the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Supplement Why
3 Stars
Vitamin B12
Consult a qualified healthcare practitioner
Learn More

Normally, only 3 to 4 mcg per day of vitamin B12 is required to prevent dietary deficiency. If gastrointestinal function is normal, even these small amounts of vitamin B12 from oral supplementation can prevent deficiency in vegans.3 If a deficiency already exists, most doctors will recommend an initial vitamin B12 injection, then oral amounts ranging from 500 mcg to 1,000 mcg per day until symptoms subside; this is followed by a maintenance level of approximately 10 mcg per day to prevent future deficiencies.

In a person with true PA, initial B12 supplementation should begin with an injection given by a qualified healthcare professional. After blood abnormalities are reversed, maintenance supplementation can be successfully accomplished with oral vitamin B12 at 1,000 to 2,000 mcg (1 to 2 mg) per day and does not require further injections.4 In a person lacking intrinsic factor, only about 1% of this oral amount (10–20 mcg) will be absorbed, but that amount is more than sufficient to prevent future vitamin B12 deficiency.5 , 6 Many physicians are unaware of this well-researched option and thus unnecessarily recommend lifelong B12 injections.7

3 Stars
Vitamin B12 (Depression)
See a doctor for evaluation
Learn More

Deficiency of vitamin B12 can create disturbances in mood that respond to B12 supplementation.8 Significant vitamin B12 deficiency is associated with a doubled risk of severe depression, according to a study of physically disabled older women.9 Depression caused by vitamin B12 deficiency can occur even if there is no B12 deficiency-related anemia.10

Mood has been reported to sometimes improve with high amounts of vitamin B12 (given by injection), even in the absence of a B12 deficiency.11 Supplying the body with high amounts of vitamin B12 can only be done by injection. However, in the case of overcoming a diagnosed B12 deficiency, one can follow an initial injection with oral maintenance supplementation (1 mg per day), even when the cause of the deficiency is a malabsorption problem such as pernicious anemia .

3 Stars
Vitamin B12 (Anemia)
600 to 1,000 mcg daily
Learn More

Deficiencies of iron , vitamin B12 , and folic acid are the most common nutritional causes of anemia.12 Although rare, severe deficiencies of several other vitamins and minerals, including vitamin A ,13 , 14 vitamin B2 ,15 vitamin B6 ,16 , 17 vitamin C ,18 and copper ,19 , 20 can also cause anemia by various mechanisms. Rare genetic disorders can cause anemias that may improve with large amounts of supplements such as vitamin B1 .21 , 22

2 Stars
Vitamin B12 (Age-Related Cognitive Decline)
Consult a qualified healthcare practitioner
Learn More

Supplementation with vitamin B12 may improve cognitive function in elderly people who have been diagnosed with a B12 deficiency. Such a deficiency in older people is not uncommon. In a preliminary trial, intramuscular injections of 1,000 mcg of vitamin B12 were given once per day for a week, then weekly for a month, then monthly thereafter for 6 to 12 months. Researchers noted “striking” improvements in cognitive function among 22 elderly people with vitamin B12 deficiency and cognitive decline.23 Cognitive disorders due to vitamin B12 deficiency may also occur in people who do not exhibit the anemia that often accompanies vitamin B12 deficiency. For example, in a study of 141 elderly people with cognitive abnormalities due to B12 deficiency, 28% had no anemia. All participants were given intramuscular injections of vitamin B12, and all showed subsequent improvement in cognitive function.24

Vitamin B12 injections put more B12 into the body than is achievable with absorption from oral supplementation. Therefore, it is unclear whether the improvements in cognitive function described above were due simply to correcting the B12 deficiency or to a therapeutic effect of the higher levels of vitamin B12 obtained through injection. Elderly people with ARCD should be evaluated by a healthcare professional to see if they have a B12 deficiency. If a deficiency is present, the best way to proceed would be initially to receive vitamin B12 injections. If the injections result in cognitive improvement, some doctors would then recommend an experimental trial with high amounts of oral B12, despite a current lack of scientific evidence. If oral vitamin B12 is found to be less effective than B12 shots, the appropriate treatment would be to revert to injectable B12. At present, no research trials support the use of any vitamin B12 supplementation in people who suffer from ARCD but are not specifically deficient in vitamin B12.

2 Stars
Vitamin B12 (Thalassemia)
If deficient: 300 to1,000 mcg daily
Learn More

Test tube studies have shown that propionyl-L-carnitine (a form of L-carnitine ) protects red blood cells of people with thalassemia against free radical damage.25 In a preliminary study, children with beta thalassemia major who took 100 mg of L-carnitine per 2.2 pounds of body weight per day for three months had a significantly decreased need for blood transfusions.26 Some studies have found people with thalassemia to be frequently deficient in folic acid , vitamin B12 ,27 and zinc .28 , 29 Researchers have reported improved growth rates in zinc-deficient thalassemic children who were given zinc supplements of 22.5 to 90 mg per day, depending on age.30 , 31 Magnesium has been reported to be low in thalassemia patients in some,32 , 33 but not all,34 studies. A small, preliminary study reported that oral supplements of magnesium, 7.2 mg per 2.2 pounds of body weight per day, improved some red blood cell abnormalities in thalassemia patients.35

2 Stars
Vitamin B12 (Delayed Gastric Emptying, Helicobacter Pylori Infection, Indigestion, Heartburn, and Low Stomach Acidity)
1,000 mcg daily
Learn More

Vitamin B12 supplementation may be beneficial for a subset of people suffering from indigestion: those with delayed emptying of the stomach contents in association with Helicobacter pylori infection and low blood levels of vitamin B12. In a double-blind study of people who satisfied those criteria, treatment with vitamin B12 significantly reduced symptoms of dyspepsia and improved stomach-emptying times.36

2 Stars
Vitamin B12 (Sickle Cell Anemia)
Consult a qualified healthcare practitioner
Learn More

Sickle cell anemia may result in vitamin B12 deficiency. A study of children with sickle cell anemia found them to have a higher incidence of vitamin B12 deficiency than children without the disease.37 A study of 85 adults with sickle cell anemia showed more of them had vitamin B12 deficiency than did a group of healthy people.38 A subsequent preliminary trial demonstrated that for patients with low blood levels of vitamin B12, intramuscular injections of 1 mg of vitamin B12 weekly for 12 weeks led to a significant reduction in symptoms.39 Researchers do not know whether people with sickle cell anemia who are found to be deficient in vitamin B12 would benefit equally from taking vitamin B12 supplements orally.

Preliminary research has found that patients with sickle cell anemia are more likely to have elevated blood levels of homocysteine compared to healthy people.40 , 41 Elevated homocysteine is recognized as a risk factor for cardiovascular disease .42 In particular, high levels of homocysteine in sickle cell anemia patients have been associated with a higher incidence of stroke .43 Deficiencies of vitamin B6 , vitamin B12, and folic acid occur more frequently in people with sickle cell anemia than in others44 , 45 , 46 and are a cause of high homocysteine levels.47 A controlled trial found homocysteine levels were reduced 53% in children with sickle cell anemia receiving a 2–4 mg supplement of folic acid per day, depending on age, but vitamin B6 or B12 had no effect on homocysteine levels.48 A double-blind trial of children with sickle cell anemia found that children given 5 mg of folic acid per day had less painful swelling of the hands and feet compared with those receiving placebo, but blood abnormalities and impaired growth rate associated with sickle cell anemia were not improved.49 In the treatment of sickle cell anemia, folic acid is typically supplemented in amounts of 1,000 mcg daily.50 Anyone taking this amount of folic acid should have vitamin B12 status assessed by a healthcare professional.

1 Star
Vitamin B12 (Phenylketonuria)
Refer to label instructions
Learn More

People with PKU may be deficient in several nutrients, due to the restricted diet which is low in protein and animal fat. Deficiencies of long-chain polyunsaturated fatty acids (LC-PUFAs),51 , 52 , 53 selenium ,54 , 55 , 56 , 57 vitamin B12 ,58 and vitamin K may develop on this diet.59

Vitamin B12 is found almost exclusively in foods of animal origin, which are restricted on the PKU diet. People on the PKU diet who are inconsistent in their use of a vitamin B12 supplement may become deficient in this vitamin. In a survey of young adults with PKU, 32% were found to have low or low-normal blood levels of vitamin B12.60 Vitamin B12 deficiency can cause anemia and nerve problems.

1 Star
Vitamin B12 (Dermatitis Herpetiformis)
Refer to label instructions
Learn More

People with DH frequently have mild malabsorption (difficulty absorbing certain nutrients) associated with low stomach acid (hypochlorhydria) and inflammation of the stomach lining (atrophic gastritis).61 Mild malabsorption may result in anemia 62 and nutritional deficiencies of iron , folic acid ,63 , 64 vitamin B12 ,65 , 66 and zinc .67 , 68 , 69 More severe malabsorption may result in loss of bone mass.70 Additional subtle deficiencies of vitamins and minerals are possible, but have not been investigated. Therefore, some doctors recommend people with DH have their nutritional status checked regularly with laboratory studies. These doctors may also recommend multivitamin-mineral supplements and, to correct the low stomach acid, supplemental betaine HCl (a source of hydrochloric acid).

1 Star
Vitamin B-Complex (Indigestion, Heartburn, and Low Stomach Acidity)
Refer to label instructions
Learn More
Vitamin B12 supplementation may be beneficial for a subset of people suffering from indigestion: those with delayed emptying of the stomach contents in association with Helicobacter pylori infection and low blood levels of vitamin B12. In a double-blind study of people who satisfied those criteria, treatment with vitamin B12 significantly reduced symptoms of dyspepsia and improved stomach-emptying times.71

References

1. Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck and Co., Inc., 1999, 868.

2. Gozzard DI. Experiences with dual protein bound aqueous vitamin B12 absorption test in subjects with low serum vitamin B12 concentrations. J Clin Pathol 1987;40:633–7.

3. Little DR. Ambulatory management of common forms of anemia. Am Fam Physician 1999;59:1598–604.

4. Kuzminski AM, Del Giacco EJ, Allen RH, et al. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 1998;92:1191–8.

5. Kondo H. Haematological effects of oral cobalamin preparations on patients with megaloblastic anaemia. Acta Haematol 1998;9:200–5.

6. Berlin R, Berlin H, Brante G, Pilbrant A. Vitamin B12 body stores during oral and parenteral treatment of pernicious anaemia. Acta Med Scand 1978;204:81–4.

7. Lederle FA. Oral cobalamin for pernicious anemia. Medicine’s best kept secret? JAMA 1991;265(1):94–5.

8. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720–8.

9. Penninx BW, Guralnik JM, Ferrucci L, et al. Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women’s Health and Aging Study. Am J Psychiatry 2000;157:715–21.

10. Holmes JM. Cerebral manifestations of vitamin B12 deficiency. J Nutr Med 1991;2:89–90.

11. Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973;30:277–83.

12. Little DR. Ambulatory management of common forms of anemia. Am Fam Physician 1999;59:1598–604 [review].

13. Hodges RE, Sauberlich HE, Canham JE, et al. Hematopoietic studies in vitamin A deficiency. Am J Clin Nutr 1978;31:876–85 [review].

14. Bloem MW. Interdependence of vitamin A and iron: an important association for programmes of anaemia control. Proc Nutr Soc 1995;54:501–8 [review].

15. Lane M, Alfrey CP. The anemia of human riboflavin deficiency. Blood 1965;25:432–42.

16. Orehek AJ, Kollas CD. Refractory postpartum anemia due to vitamin B6 deficiency. Ann Intern Med 1997;126(10):834–5 [letter].

17. Iwama H, Iwase O, Hayashi S, et al. Macrocytic anemia with anisocytosis due to alcohol abuse and vitamin B6 deficiency. Rinsho Ketsueki 1998;39:1127–30 [in Japanese].

18. Hirschmann JV, Raugi GJ. Adult scurvy. J Am Acad Dermatol 1999;41:895–906 [review].

19. Summerfield AL, Steinberg FU, Gonzalez JG. Morphologic findings in bone marrow precursor cells in zinc-induced copper deficiency anemia. Am J Clin Pathol 1992;97:665–8.

20. Freycon F, Pouyau G. Rare nutritional deficiency anemia: deficiency of copper and vitamin E. Sem Hop 1983;59:488–93 [review] [in French].

21. Borgna-Pignatti C, Marradi P, Pinelli L, et al. Thiamine-responsive anemia in DIDMOAD syndrome. J Pediatr 1989;114:405–10.

22. Neufeld EJ, Mandel H, Raz T, et al. Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping. Am J Hum Genet 1997;61:1335–41.

23. Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc 1992;40(2):168–72.

24. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720–8.

25. Palmieri L, Ronca F, Malengo S, Bertelli A. Protection of beta-thalassaemic erythrocytes from oxidative stress by propionyl carnitine. Int J Tissue React 1994;16:121–9.

26. Yesilipek MA, Hazar V, Yegin O. L-Carnitine treatment in beta thalassemia major. Acta Haematol 1998;100:162–3.

27. Saraya AK, Kumar R, Kailash S, Sehgal AK. Vitamin B12 and folic acid deficiency in b-heterozygous thalassemia. Indian J Med Res 1984;79:783–8.

28. Silprasert A, Laokuldilok T, Kulapongs P. Zinc deficiency in b-thalassemic children. In Fucharoen S, Rowley PT, Paul NW, eds. Thalassemia: pathophysiology and management, part A. New York: Alan R Liss, 1988 [review].

29. Bashir NA. Serum zinc and copper levels in sickle cell anaemia and beta-thalassaemia in North Jordan. Ann Trop Paediatr 1995;15:291–3.

30. Arcasoy A, Cavdar AO, Cin S, et al. Effects of zinc supplementation on linear growth in beta thalassemia. Am J Hematol 1987;24:127–36.

31. Akar N, Berberoglu M, Arcasoy A. Effects of zinc supplementation on somatomedin-C level, in beta-thalassemia. Am J Hematol 1992;41:142–3 [letter].

32. Cohen L, Bitterman H, Froom P, Aghai E. Decreased bone magnesium in beta thalassemia with spinal osteoporosis. Magnesium 1986;5:43–6.

33. Hyman CB, Ortega JA, Costin G, Takahashi M. The clinical significance of magnesium depletion in thalassemia. Ann N Y Acad Sci 1980;344:436–43.

34. Arcasoy A, Cavdar AO. Changes of trace minerals (serum iron, zinc, copper and magnesium) in thalassemia. Acta Haematol 1975;53:341–6.

35. De Franceschi L, Cappellini MD, Graziadei G, et al. The effect of dietary magnesium supplementation on the cellular abnormalities of erythrocytes in patients with beta thalassemia intermedia. Haematologica 1998;83:118–25.

36. Gumurdulu Y, Serin E, Ozer B, et al. The impact of B12 treatment on gastric emptying time in patients with Helicobacter pylori infection. J Clin Gastroenterol 2003;37:230–3.

37. Osifo BO, Adeyokunnu A, Parmentier Y, et al. Abnormalities of serum transcobalamins in sickle cell disease (HbSS) in Black Africa. Scand J Haematol 1983;30:135–40.

38. al-Momen AK. Diminished vitamin B12 levels in patients with severe sickle cell disease. J Intern Med 1995;237:551–5.

39. al-Momen AK. Diminished vitamin B12 levels in patients with severe sickle cell disease. J Intern Med 1995;237:551–5.

40. van der Dijs FP, Schnog JJ, Brouwer DA, et al. Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients. Am J Hematol 1998;59:192–8.

41. Houston PE, Rana S, Sekhasaria S, et al. Homocysteine in sickle cell disease: relationship to stroke. Am J Med 1997;103:192–6.

42. Alpert MA. Homocysteine, atherosclerosis, and thrombosis. South Med J 1999;92:858–65 [review].

43. Houston PE, Rana S, Sekhasaria S, et al. Homocysteine in sickle cell disease: relationship to stroke. Am J Med 1997;103:192–6.

44. al-Momen AK. Diminished vitamin B12 levels in patients with severe sickle cell disease. J Intern Med 1995;237:551–5.

45. Lin YK. Folic acid deficiency in sickle cell anemia. Scand J Haematol 1975;14:71–9.

46. Natta CL, Reynolds RD. Apparent vitamin B6 deficiency in sickle cell anemia. Am J Clin Nutr 1984;40:235–9.

47. Alpert MA. Homocysteine, atherosclerosis, and thrombosis. South Med J 1999;92:858–65 [review].

48. van der Dijs FP, Schnog JJ, Brouwer DA, et al. Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients. Am J Hematol 1998;59:192–8.

49. Rabb LM, Grandison Y, Mason K, et al. A trial of folate supplementation in children with homozygous sickle cell disease. Br J Haematol 1983;54:589–94.

50. Waterbury L. Anemia. In Barker LR, Burton JR, Zieve PD. Principles of ambulatory medicine, 4th ed. Baltimore: Williams & Wilkins, 1995, 605.

51. Agostoni C, Marangoni F, Riva E, et al. Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children negatively correlate with dietary compliance. Prostaglandins Leukot Essent Fatty Acids 1997;56:219–22.

52. Giovannini M, Agostoni C, Biasucci G, et al. Fatty acid metabolism in phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S132–5.

53. Poge AP, Baumann K, Muller E, et al. Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake. J Inherit Metab Dis 1998;21:373–81.

54. Jochum F, Terwolbeck K, Meinhold H, et al. Effects of a low selenium state in patients with phenylketonuria. Acta Paediatr 1997;86:775–7.

55. Kauf E, Seidel J, Winnefeld K, et al. Selenium in phenylketonuria patients. Effects of sodium selenite administration. Med Klin 1997;92 Suppl 3:31–4 [in German].

56. Sierra C, Vilaseca MA, Moyano D, et al. Antioxidant status in hyperphenylalaninemia. Clin Chim Acta 1998;276:1–9.

57. Gropper SS, Naglak MC, Nardella M, et al. Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets. J Am Coll Nutr 1993;12:108–14.

58. Hanley WB, Feigenbaum AS, Clarke JT, et al. Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S145–7.

59. Schulpis KH, Platokouki H, Papakonstantinou ED, et al. Haemostatic variables in phenylketonuric children under dietary treatment. J Inherit Metab Dis 1996;19:603–9.

60. Hanley WB, Feigenbaum AS, Clarke JT, et al. Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur J Pediatr 1996;155 Suppl 1:S145–7.

61. Yancy KB, Lawley TJ. “Immunologically Mediated Skin Diseases.”Harrison’s Online. 1999. http://www.harrisonsonline.com/hill-bin/Chapters.cgi (Jan 10, 2000).

62. Kastrup W, Mobacken H, Stockbrugger R, et al. Malabsorption of vitamin B12 in dermatitis herpetiformis and its association with pernicious anaemia. Acta Med Scand 1986;220:261–8.

63. Gawkrodger DJ, Ferguson A, Barnetson RS. Nutritional status in patients with dermatitis herpetiformis. Am J Clin Nutr 1988;48:355–60.

64. Hoffbrand AV, Douglas AP, Fry L, Stewart JS. Malabsorption of dietary folate (Pteroylpolyglutamates) in adult coeliac disease and dermatitis herpetiformis. Br Med J 1970;4:85–9.

65. Davies MG, Marks R, Nuki G. Dermatitis herpetiformis—a skin manifestation of a generalized disturbance in immunity. Q J Med 1978;47:221–48.

66. Kastrup W, Mobacken H, Stockbrugger R, et al. Malabsorption of vitamin B12 in dermatitis herpetiformis and its association with pernicious anaemia. Acta Med Scand 1986;220:261–8.

67. Crofton RW, Glover SC, Ewen SW, et al. Zinc absorption in celiac disease and dermatitis herpetiformis: a test of small intestinal function. Am J Clin Nutr 1983;38:706–12.

68. Gawkrodger DJ, Ferguson A, Barnetson RS. Nutritional status in patients with dermatitis herpetiformis. Am J Clin Nutr 1988;48:355–60.

69. Hoffbrand AV, Douglas AP, Fry L, Stewart JS. Malabsorption of dietary folate (Pteroylpolyglutamates) in adult coeliac disease and dermatitis herpetiformis. Br Med J 1970;4:85–9.

70. Di Stefano M, Jorizzo RA, Veneto G, et al. Bone mass and metabolism in dermatitis herpetiformis. Dig Dis Sci 1999;44:2139–43.

71. Gumurdulu Y, Serin E, Ozer B, et al. The impact of B12 treatment on gastric emptying time in patients with Helicobacter pylori infection. *J Clin Gastroenterol* 2003;37:230–3.

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