|Year : 2019 | Volume
| Issue : 1 | Page : 47-51
Effects of Vitamin D3 supplementation on the hematological indices in women presented with iron deficiency anemia: An open-labeled clinical trial
Marwan S. M Al-Nimer1, Raz M HamaSalih2
1 Department of Clinical Pharmacology and Therapeutics, College of Pharmacy, Hawler Medical University, Erbil; Department of Clinical Pharmacology and Therapeutics, School of Medicine, Faculty of Medical Sciences, University of Sulaimani, Sulaimani, Iraq
2 Department of Pharmacology, School of Medicine, Faculty of Medical Sciences, University of Sulaimani, Sulaimani, Iraq
|Date of Web Publication||22-Aug-2019|
Marwan S. M Al-Nimer
Department of Clinical Pharmacology and Therapeutics, College of Pharmacy, Hawler Medical University, Erbil; Department of Clinical Pharmacology and Therapeutics, School of Medicine, Faculty of Medical Sciences, University of Sulaimani, Sulaimani
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objectives: Vitamin D inhibits erythropoiesis in healthy, young individuals, despite its positive effect on the absorption of iron. This study aimed to investigate the effects of Vitamin D supplements as add-on therapy on the hematological indices of adults presented with iron deficiency anemia (IDA). Materials and Methods: Eighty-two women aged 20–45 years with IDA were recruited from Shar Teaching Hospital and the Center of Blood Diseases in Sulaimani city, North Iraq. The patients were grouped into Group I (n = 35) treated with elemental iron and Group II (n = 47) treated with elemental iron plus Vitamin D3 supplements (oral dose of 300,000 IU every 2 weeks), for 8 weeks. Hematological indices and the serum ferritin were determined before the treatment and after 8 weeks of treatment. Results: Vitamin D3 supplements significantly elevate the total white cell count and decreased platelet indices values. It decreased the platelet-to-lymphocyte ratio significantly from 123.24 ± 32.00 to 107.68 ± 30.06, P < 0.001. The serum ferritin level did not normalize after 8 weeks of treatment with elemental iron and Vitamin D3 supplements. Conclusions: Vitamin D3 supplement as the add-on therapy is less effective in IDA, and it impacts negatively against the blood platelet indices.
Keywords: Hematological indices and ratios, iron deficiency anemia, Vitamin D3
|How to cite this article:|
Al-Nimer MS, HamaSalih RM. Effects of Vitamin D3 supplementation on the hematological indices in women presented with iron deficiency anemia: An open-labeled clinical trial. J Pharm Negative Results 2019;10:47-51
|How to cite this URL:|
Al-Nimer MS, HamaSalih RM. Effects of Vitamin D3 supplementation on the hematological indices in women presented with iron deficiency anemia: An open-labeled clinical trial. J Pharm Negative Results [serial online] 2019 [cited 2020 Mar 28];10:47-51. Available from: http://www.pnrjournal.com/text.asp?2019/10/1/47/265152
| Introduction|| |
Vitamin D is the fat-soluble vitamin that acts in the body as a nutrient molecule and pro-hormone which required activation in the kidney into 1,25 dihydroxyvitamin D by 1α-hydroxylase enzyme. Serum concentration of Vitamin D level depends on the diet and the sunlight exposure (specifically to the ultraviolet light of wavelength 290–315 nm). It plays a role in the homeostasis of the calcium and phosphate in the body. Vitamin D as an add-on therapy is of benefit in the management of many diseases ,, as its level is low in some chronic and idiopathic diseases., Vitamin D inhibits erythropoiesis by a mechanism being still unknown. Vitamin D inversely correlated with hemoglobin (Hb), red cell count, and mean corpuscular Hb in healthy. Women soldiers under basic combat training are prone to iron deficiency anemia (IDA) which did not improve after using calcium/Vitamin D supplementation in a fortified food product containing 2000 mg calcium and 25 μ Vitamin D daily, for 9 weeks., The risk of developing anemia in children aged 9–12 years is high when the serum levels of Vitamin D are in the range of deficiency (>20 nmol/L) or insufficiency (25–50 nmol/L), with a cutoff value of <44 nmol/L (equivalent to 17.6 ng/dL). A recent study found that women with IDA have subnormal levels of Vitamin D, but there are nonsignificant correlations between Vitamin D level with serum iron indices. Vitamin D facilitates the absorption of iron and thereby may improve the anemia in patients with IDA. Therefore, this study aimed to investigate the effects of Vitamin D supplementation in addition to iron supplementation on the hematological indices in women presented with IDA.
| Materials and Methods|| |
The Ethical Scientific Committee at the University of Sulaimani in Sulaimani, Iraq, approved the study according to the guidelines which fulfill the requirement of postgraduate research to conduct a clinical trial (No. 7-129-3143 on December 9, 2018). Each medicine or device used by a patient should be harmless without adverse reactions. The patient can withdraw from this study at any time he/she wished. The authors informed the patients the study design and the medicines used in this study. Each patient signed consent form at the time of entry into the study.
The authors recruited the patients with IDA from Shar Teaching Hospital and the Centre of Blood Diseases in Sulaimani, Iraq.
Eligible patients were women aged 20–45 years. The criteria for inclusion were women with IDA. The diagnoses of IDA were based on the laboratory investigations including Hb level of <12 g/dL, serum ferritin < 30 μ/L, and/or two of the following hematological indices; mean corpuscular volume (MCV) <80 fL and red cell distribution width (RDW/coefficient variation) >14.5%, or blood film showing hypochromic microcytic red cells with anisocytosis, poikilocytosis). The criteria for exclusion included pregnancy and individuals with congenital hemoglobinopathies, acute blood loss for any cause, helminthic infestation, renal or kidney failure, and terminal illness.
A total number of 82 patients fulfilled the above criteria were included in this open-labeled clinical trial. All the patients had a history of using iron supplement (iron sulfate, of 150 mg elemental iron) for 8 weeks. The patients grouped into:
- Group I (n = 35) treated with iron sulfate (150 mg elemental iron), for 8 weeks
- Group II (n = 47) treated with iron sulfate (150 mg elemental iron) plus Vitamin D3 supplement as an add-on-therapy (300,000 IU/every 2 weeks, orally), for 8 weeks.
A venous blood sample drew from each patient into an EDTA test tube and a plain test tube for the determination of hematological indices using an automated hemocytometer analyzer (Swelab Alfa, Sweden). Serum ferritin and Vitamin D3 levels were determined according to the manufacturer's instruction. Laboratory investigations were carried before commencing Vitamin D3 and after 8 weeks of treatment. Ratios derived from hematological indices, including granulocyte-to-lymphocyte ratio (GLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), were calculated. The following red cell indexes that indicated IDA were calculated: Mentzer index >13; modified Mentzer index <23.85; Srivastava index >3.8; Shine and Lal index >1530; England and Fraser index positive; RDW index >220; Ricerca index >4.4).
The results are expressed as number, percentages, and mean ± standard deviation (SD). The data were analyzed using two-tailed paired t-test, taking the P value of ≤0.05 as the lowest level of significance. All the data were analyzed using the Microsoft Excel 2010 program for Windows (Microsoft Corporation, Redmond, USA).
| Results|| |
Table 1 shows that Vitamin D3 supplementation induced significant changes in the complete blood picture. Vitamin D3 significantly increases the total leukocytes by 6.3% and lymphocyte count by 7.2% and nonsignificantly induces changes in the number of granulocyte and monocyte. Vitamin D3 supplementation significantly improves the red cell indices. Effects of Vitamin D on the red cell indices in Group II are similar to corresponding indices in Group I [Table 1]. Vitamin D supplementation significantly decreased the platelet count, plateletcrit, mean platelet volume, and large cell platelet ratio, which decreased by 7.4%, 18.1%, 11.5%, and 24.9%, respectively.
|Table 1: Effect of Vitamin D3 supplementation on the hematological indices compared with untreated with Vitamin D3 of patients with iron deficiency anemia|
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Serum ferritin level significantly increased from 9.95 ± 6.01 to 24.96 ± 10.11 ng/mL in Group I patients compared with 16.77 ± 12.27–19.78 ± 11.6 ng/mL in Group II patients. Vitamin D supplementation significantly improved the red cell indices of IDA except for the Shine and Lal index and the MCV [Table 2]. [Table 3] shows a significant decrease of the PLR (12.5%, P < 0.001), while the GLR or LMR was nonsignificantly changed. The mean ± SD of the serum Vitamin D level in Group II before supplementation was 12.9 ± 14.0 ng/mL (range 2–39.1 ng/mL, n = 47) which significantly increased to 61.4 ± 25.2 ng/mL (range 14.88–107.9, n = 47, P < 0.001) after supplementation.
|Table 2: Effects of Vitamin D supplementation combined with iron therapy compared with iron therapy alone on the diagnostic criteria of iron deficiency anemia taking the cutoff value of each index|
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|Table 3: Effect of Vitamin D3 supplementation on the ratios derived from the hematological indices compared with untreated with Vitamin D3 of patients with iron deficiency anemia|
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| Discussion|| |
Vitamin D3 supplementation negatively impacts on the platelet indices of patients with IDA, and it alters the inflammatory markers that derived from hematological indices. A significant increase in total leukocytes is due to the effect of Vitamin D3 supplementation on the total number of lymphocytes., Therefore, Vitamin D3 supplementation can improve the immune system in IDA. This study was carried on patients aged between 20 and 45 years, which means that the possibility of concomitant iron and Vitamin D deficiency is excluded. Nutritional deficiency of both Vitamin D3 and iron was observed in children under 5 years old. Significant improvement of red cell indices is related to both iron therapy and Vitamin D3. Iron therapy significantly decreased the value of RDW, which is a marker of risk factors of the IDA complications, indicating that iron therapy alleviates IDA complications even in patients with low serum Vitamin D.
The significant negative effects of Vitamin D3 supplement on the platelet indices may be of benefit rather than adverse reactions. Previous studies showed that Vitamin D3 produces significant low values of platelet indices. Vitamin D significantly decreases the mean platelet volume, which considered as an independent risk for many disorders that affect health., Therefore, Vitamin D supplementation can halt or prevent risk factors associated with IDA or that resulted from iron therapy.
Table 2 shows the diagnostic indices of IDA. It is well known that iron supplementation, for short duration, can ameliorate some of these indices. Vitamin D supplement corrected most of these indices, which indicates that concomitant administration of Vitamin D3 with iron therapy may reduce the duration of iron therapy. It is important to mention here that under physiological condition, serum Vitamin D level impacts inversely on the red cell indices, indicating that Vitamin D inhibits erythropoiesis. Another study found that Vitamin D supplement (5000 IU, oral dose daily for 8 weeks) did not significantly alter the hematological indices in young soccer players. Serum ferritin level is highly increased in Group I patients compared with Group II. This observation agreed with other studies that Vitamin D supplementation reduced the serum level of ferritin. Vitamin D3 supplement significantly decreased the PLR in Group II. PLR was found to be elevated in anemia. Therefore, Vitamin D3 supplement alleviates inflammation that concomitantly associated with anemia. Limitations of the study included that the determination of serum Vitamin D was not done in Group I. The other limitation is that the effect of Vitamin D3 supplement without iron therapy on the hematological indices was not studied because this approach is not logic and against the ethical considerations.
| Conclusions|| |
We conclude that Vitamin D3 supplement as the add-on therapy should be used with caution in IDA because its impacts negatively against blood platelet, and it reduces the effect of iron as a therapeutic remedy against red cell indices and serum ferritin.
We thank the patients for their cooperation in this study.
Financial support and sponsorship
The University of Sulaimani supported this study.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bergwitz C, Miyamoto KI. Hereditary hypophosphatemic rickets with hypercalciuria: Pathophysiology, clinical presentation, diagnosis and therapy. Pflugers Arch 2019;471:149-63.
Ebeling PR, Adler RA, Jones G, Liberman UA, Mazziotti G, Minisola S, et al.
Management of endocrine disease: Therapeutics of Vitamin D. Eur J Endocrinol 2018;179:R239-59.
Khosravi ZS, Kafeshani M, Tavasoli P, Zadeh AH, Entezari MH. Effect of Vitamin D supplementation on weight loss, glycemic indices, and lipid profile in obese and overweight women: A clinical trial study. Int J Prev Med 2018;9:63.
] [Full text]
Grzelak T, Mikołajczyk K. Pleiotropic effect of Vitamin D in cystic fibrosis. Adv Respir Med 2018;86:192-6.
Cubbon RM, Lowry JE, Drozd M, Hall M, Gierula J, Paton MF, et al
. Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure. Eur J Nutr 2018 (In press). doi. org/10.1007/s00394-018-1806-y.
Bener A, Ozdenkaya Y, Al-Hamaq AO, Barisik CC, Ozturk M. Low Vitamin D deficiency associated with thyroid disease among type 2 diabetic mellitus patients. J Clin Med Res 2018;10:707-14.
Doudin A, Becker A, Rothenberger A, Meyer T. Relationship between serum 25-hydroxyvitamin D and red blood cell indices in German adolescents. Eur J Pediatr 2018;177:583-91.
Yanovich R, Karl JP, Yanovich E, Lutz LJ, Williams KW, Cable SJ, et al.
Effects of basic combat training on iron status in male and female soldiers: A comparative study. US Army Med Dep J 2015:67-73.
Hennigar SR, Gaffney-Stomberg E, Lutz LJ, Cable SJ, Pasiakos SM, Young AJ, et al.
Consumption of a calcium and Vitamin D-fortified food product does not affect iron status during initial military training: A randomised, double-blind, placebo-controlled trial. Br J Nutr 2016;115:637-43.
Nikooyeh B, Neyestani TR. Poor Vitamin D status increases the risk of anemia in school children: National food and nutrition surveillance. Nutrition 2018;47:69-74.
El-Adawy EH, Zahran FE, Shaker GA, Seleem A. Vitamin D status in Egyptian adolescent females with iron deficiency anemia and its correlation with serum iron indices. Endocr Metab Immune Disord Drug Targets 2019;19:519-25.
World Health Organization. Iron Deficiency Anemia: Assessment, Prevention, and control. World Health Organization; 2001.
Okan V, Cigiloglu A, Cifci S, Yilmaz M, Pehlivan M. Red cell indices and functions differentiating patients with the beta-thalassaemia trait from those with iron deficiency anaemia. J Int Med Res 2009;37:25-30.
Ganz T. Iron and infection. Int J Hematol 2018;107:7-15.
Youssef SR, Hendawy SF, Boshnak NH, Sedhom MS. Effect of intra-cellular trafficking on flow cytometric measurement of neutrophil's oxidative status in iron deficient pregnant females. J Clin Lab Anal 2018;32:e22210.
Adam I, Ibrahim Y, Elhardello O. Prevalence, types and determinants of anemia among pregnant women in Sudan: A systematic review and meta-analysis. BMC Hematol 2018;18:31.
Bujak K, Wasilewski J, Osadnik T, Jonczyk S, Kołodziejska A, Gierlotka M, et al.
The prognostic role of red blood cell distribution width in coronary artery disease: A review of the pathophysiology. Dis Markers 2015;2015:824624.
Gur EB, Karadeniz M, Genc M, Eskicioglu F, Yalcin M, Hepyilmaz I, et al.
Relationship between mean platelet volume and Vitamin D deficiency in gestational diabetes mellitus. Arch Endocrinol Metab 2015;59:448-54.
Dougherty KA, Bertolaso C, Schall JI, Smith-Whitley K, Stallings VA. Safety and efficacy of high-dose daily Vitamin D3 supplementation in children and young adults with sickle cell disease. J Pediatr Hematol Oncol 2015;37:e308-15.
Bobescu E, Covaciu A, Rus H, Radoi M, Badea M, Moga SN, et al
. Correlation of cardiovascular risk factors and biomarkers with platelet reactivity in coronary artery disease. Am J Ther 2018. (In press). doi.org/10.1097/MJT.0000000000000869.
Nageeb RS, Abozaid MM, Nageeb GS, Omran AA. Mean platelet volume to platelet count ratio as a laboratory indicator of mortality in pneumonia following ischemic stroke. Egypt J Neurol Psychiatr Neurosurg 2018;54:27.
von Haehling S, Jankowska EA, van Veldhuisen DJ, Ponikowski P, Anker SD. Iron deficiency and cardiovascular disease. Nat Rev Cardiol 2015;12:659-69.
Jastrzebska M, Kaczmarczyk M, Suárez AD, Sánchez GFL, Jastrzebska J, Radziminski L, et al.
Iron, hematological parameters and blood plasma lipid profile in Vitamin D supplemented and non-supplemented young soccer players subjected to high-intensity interval training. J Nutr Sci Vitaminol (Tokyo) 2017;63:357-64.
Walentukiewicz A, Lysak-Radomska A, Jaworska J, Prusik K, Prusik K, Kortas JA, et al.
Vitamin D supplementation and Nordic walking training decreases serum homocysteine and ferritin in elderly women. Int J Environ Res Public Health 2018;15. pii: E2064.
Emokpae MA, Aruomaren A, Osime E. Relationship between neutrophil-to-lymphocyte ratio and inflammatory markers in sickle cell anaemia patients with proteinuria. Med Sci (Basel) 2016;4. pii: E11.
[Table 1], [Table 2], [Table 3]