Folic Acid for Thalassemia Major? Yes.

This article explains why thal majors do need folic acid supplements and the thinking behind why many doctors think that majors don't need it. Once again, we see that thal majors have serious deficiencies when actually measured. Hypothesis is one thing, but what doctors have argued about not needing folic acid is just plain wrong. Majors should take folic acid daily.

http://journal.shouxi.net/html/qikan/zgyx/ylyxyxqk/2006793/20080831232751334_180093.html

The effect of folic acid supplementation in beta-thalassemia major: A randomized placebo-controlled clinical trial
Department of Pediatrics, Thalassemia Research Center, Bou-Ali Sina Hospital,
Department of Pharmacology, Mazandaran University of Medical Sciences, Sari, Iran.

    Folic acid is a coenzyme for many important biochemical reactions including synthesis of purines, pyrimidines, and nucleoproteins. The recommended daily allowance of folic acid is 65 � 200 μg/day for infants and children. The recommended dose for deficiency states is 1000 μg/day; the effects of excess amounts of folic acid are unknown. The role of folic acid in preventing progression of arteriosclerosis is rather a new issue. Thrombotic events related to slightly elevated levels of homocystein in adults may be decreased by daily consumption of 1 mg of folic acid together with 5 � 100 mg of pyridoxine.

    Keywords: Beta-thalassemia major (thalassemia major);deficiency;folic acid;Mazandaran;treatment

    Introduction

    Folic acid deficiency results in complica-tions such as anorexia, growth failure, increased susceptibility to infections, and gastrointestinal disorders. However, megaloblastic anemia is the best known side effect of folic acid deficiency.1, 2 Some conditions such as prematurity, pregnancy, lactation, chronic liver diseases, severe infections, chronic and severe hemolysis, and administration of some drugs are mentioned as risk factors for this vitamin deficiency. Nutritional sources are usually enough, as folic acid is found ubiquitously in most vegetables.1, 2

    Undertransfused patients with β-thalassemia major may need more folic acid as they continue to have ineffective erythropoiesis.3�5 Recent treatment protocols6 do not say anything about folic acid supplementation for patients with thalassemia, because it is supposed that regular blood transfusions prevent bone marrow hyper functioning.

    As microcytosis of thalassemia major may mask the hematologic hallmark of folic acid deficiency, i.e., megaloblastic anemia, and since blood tests for folic acid are not routinely available, folic acid deficiency may simply be ignored and the patient may suffer from other complications of folic acid deficiency.

    A recent study showed that folic acid deficiency is common and severe in our thalassemia major patients. In fact, in all 30 cases, the serum folic acid level was well below the minimum normal level.7

    In order to determine whether folic acid supple-mentation has a beneficial effect on patient’s anemia, this study was conducted on thalassemic patients in Bou-Ali Sina Hospital in May 2004.

    Patients and Methods

    This study was a randomized placebo-controlled clinical trial. The patients enrolled in this study had thalassemia major on regular blood transfusion. None was pregnant/lactating, had chronic liver disease, used folic acid supplements or medicines affecting folic acid metabolism. After explaining the project, a written informed consent form was signed by each patient or their parent/guardian. The sample size was calculated as 20 in each group by the following assumptions: a power of 90%, confidence level of 95%, standard deviation of hemoglobin (Hb) level = 1 g/dL and anticipated effect of folic acid on Hb of 1 g/dL. The socioeconomic status of patients was determined through questions regarding their formal educational level, job, ownership of residential place, and the type of their medical insurance. A blood sample was then taken and serum folic acid measured by the radioimmuno- assay (RIA) method, using the standard method8 (Delshid gamma counter, Iran). Kits were obtained from the ICN Pharmaceutical (USA). Normal serum levels determined by the kit were in the range of 1.5 � 16.9 ng/mL with a sensitivity of 0.6 ng. Patients were then ranked according to their serum folic acid and each pair of patients with the same folic acid level was randomly assigned (head/tail) to take either placebo (controls) or folic acid (cases). Placebo tablets made by Faculty of Pharmacy, Mazandaran University of Medical Sciences , had the same size and color as the test drug―folic acid tablets (1 mg tablets, obtained from Iran Daru Pharmaceutical Company, Iran). The patients were asked to take one tablet per day and return for blood test four weeks later while continuing their treatment routines, as usual. The mean values of hemoglobin, hematocrit, red cell count, MCV, MCH, MCHC, and blood transfusion intervals during a period of three months, before and after the intervention, were recorded.

    Data were analyzed using SPSS-10 statistical software, through the Student’s t-test between groups and the paired t-test within the groups.

    Results

    Fifty-one participants (23 controls and 28 cases) were studied with a drop-out of 5 patients in control group. The control group, consisting of 12 (43%) females and 16 (57%) males, had a mean ± SD age of 16.8 ± 6 years. The study cases, comprised 8 (28.5%) females and 20 (71.5%) males, had a mean ± SD age of 17 ± 5 years. The socioeconomic status of the patients was poor in 40% of control and 48% of case groups. The mean ± SD serum folic acid level was severely low―0.8 ± 0.6 ng/mL―in 15 (29%) patients before the trial. Considering the minimum accepted level,2 68% of patients had folic acid deficiency (serum level <3 ng/mL).

    After treatment with placebo, the blood transfusion interval in the control group became significantly (P < 0.03) longer (Table 1).

    There were several patients in both groups with severe folic acid deficiency eight belonging to the control group (mean ± SD serum folic acid level of 0.8 ± 0.7 ng/mL) and seven to the case group (mean ± SD serum folic acid level of 0.7 ± 0.5 ng/mL). After folic acid supplementation, these levels were found to be 1.5 ± 2 ng/mL in the control and 8.8 ± 1.9 in the case groups (P < 0.0001). However, in this subgroup again, complete blood count and transfusion intervals were not changed significantly. No side effects were reported.

    Discussion

    We found that folic acid deficiency was present in 29 � 68% of subjects, depending on how we define the deficiency threshold.

    Although folate deficient, these patients had still low mean corpuscular volume (MCV). Therefore, MCV is not a good predictor for the presence of the concomitant folic acid deficiency. Consequently, either serum folic acid should be measured periodically or preventive supplementation of folic acid should be administered routinely to undertransfused thalassemic patients. The latter condition is unfortunately the case in the most developing countries where there is a large number of patients and limited supply of donated blood.

    Even in this group of patients, correction of folic acid deficiency had no benefit in terms of the anemia and blood requirements. Therefore, admi-nistration of large amounts of folic acid to improve patient’s anemia is not recommended. This practice is done by some physicians, who take care of thalassemic patients.

    Prolongation of transfusion interval in controls is not significant clinically and it may be due to coincidence factors like holidays in follow-up period.

    Encountering folic acid deficiency was rather a surprise in our first study,7 because diet of people in the region is full of fresh vegetables and they usually drink plenty of tea. In spite of under-transfusion, these patients received red cells donated by people who are not folic acid deficient. This shows that patients with thalassemia major are really in need of extra folic acid to fulfill their requirements.

    Regarding the role of homocystein (Hcy) as a risk factor for arteriosclerosis, Harker et al in 1976 published a paper; thereafter, other studies confirmed his findings.9 A meta-analysis of 27 researches showed that the risk for developing coronary disease in patients with a high serum Hcy is up to 3.2 times of those with normal serum Hcy; the risk for development of cerebral and peripheral vessel disease is between 1.6 and 6.8.10

    Folic acid supplementation for uremic patients under chronic dialysis has been explored by other scientists.9 McGregor et al showed that administration of 5 mg/day folic acid to uremic patients could decrease their blood Hcy level.9

    We showed that administration of 1 mg/day of folic acid for one month could correct its deficiency. As the follow-up period was short, effects on growth or susceptibility to infections were not investigated.

    In conclusion, we recommend prophylactic and routine folic acid supplementation for all patients with β-thalassemia major and intermedia.

    References

    1 Behrman RE, Kliegman RM, Jensen HB. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders; 2004: 163.

    2 Lee GR. Wintrobs Clinical Hematology: Megaloblastic and Nonmegaloblastic Microcytic Anemias. 9th ed. Philadelphia: Lee and Febiger; 1993: 773.

    3 Vatanavicharn S, Anuvatanakulchai M, Na-Nakorn S, Wasi P. Serum and erythrocyte folate levels in thalassaemic patients in Thailand. Scand J Haematol. 1979; 22: 241 � 245.

    4 Castagna PC, Fedeli F, Fusco AM, Montani L, Radaelli F, Tartara R. Behavior of blood folate in children with thalassemia major under transfusion therapy and in thalassemia trait. Acta Vitaminol Enzymol. 1984; 6:183 � 188.

    5 Danel P, Girot R, Tchernia G. Thalassemia major manifested by megaloblastic anemia caused by folate deficiency. Arch Pediatr. 1983; 40: 799 � 801.

    6 Eleftherio A. About Thalassemia. Cyprus: Thalassemia International Federation Publication; 2003.

    7 Kosaryan M, Mahdavi MR, Shahmoradi M, Arabzadeh M, Maleki I. Is it necessary to give folic acid to thalassemia minor or major? International Congress on Pediatrics. Tehran, Iran; 2003.

    8 Sullivan LW. Megaloblastic anemias. In: Mengel CE, Frei E, Nakhman R, eds. Hematology; Principles and Practice. Chicago: Yearbook Medical Publishers; 1972: 95 � 131.

    9 McGregor D, Shand B, Lynn K. A controlled trial of the effect of folate supplements on homocysteine, lipid, and hemorheology in end-stage renal disease. Nephron. 2000; 85: 215 � 220.

    10 Hankey GY, Eikelboom JW. Homocystein and vascular disease. Lancet. 1999; 354: 407 � 413.

Thank you, Andy. I have forwarded it accordingly.

thanks andy for the important information

OH dear
      thank you Andy for all that information you let me go baaaaaaaaaaaaaack all the way to the nearest yesterday i was researching a bout the Folic acid and how good is't for my child and i remember one day in the hospital there is a man he got a thala.major child he was confeusion he don't know what he should do and asking the nurses many thousand time a bout folic acid should he gave it to his son or no he was a freid to gave it to his son also his english is bad ,, He start to be angry for not understandin the setuation ,, i start to explain for him and the nurses was realy surprise a bout what i did i explain for him that the FOLIC ACID is the important thing now in this term i remember he took my phone number and talk with me after for almost one month  he told me you are better than nurses his son now almost 10 years old he did for him the BMT and he is good now  .
 
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