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Effect of Alpha Lipoic Acid on the Blood Cell Count and Iron Kinetics In Nutr Hosp. 2015;31(2):883-889 ISSN 0212-1611 • CODEN NUHOEQ S.V.R. 318 Original / Farmacia Effect of alpha lipoic acid on the blood cell count and iron kinetics in hypertensive patients Paula Renata Florêncio Mendes, Danielle dos Santos Félix, Paulo César Dantas da Silva, Guêdijany Henrique Pereira and Mônica Oliveira da Silva Simões Dean of Graduate Studies and Research, State University of Paraiba, Campina Grande, Brazil. Abstract EFECTO DEL ÁCIDO LIPOICO EN EL RECUENTO DE SANGRE Y EL METABOLISMO Introduction: The α-lipoic acid (ALA) has been used DE HIERRO EN PACIENTES HIPERTENSOS as a treatment to reduce oxidative damage in Systemic Arterial Hypertension (SAH), but there are no in vivo studies reporting the effect of its mechanism of action on Resumen iron metabolism. Introducción: El Ácido α-Lipóico (ALA) ha sido uti- α Objective: To evaluate the antioxidant effect of -lipoic lizado como recurso terapéutico para reducir daño oxi- acid on Blood cell count (CBC) and iron metabolism in dativo en la Hipertensión Arterial Sistémica (HAS), pero hypertensive subjects with or without anemia. aún no existen estudios in vivo que reporten sobre su me- Method: Double-blind, randomized, placebo-contro- canismo de acción en el metabolismo del hierro. lled clinical trial. The sample consisted of 60 hyperten- Objetivo: Evaluar el efecto antioxidante del ácido Al- sive patients that were randomly divided into treatment fa-Lipóico sobre el hemograma y metabolismo del hierro group (n = 32), receiving 600 mg / day of ALA for twelve en individuos hipertensos con o sin anemia. weeks and control group (n = 28), receiving placebo for Métodos: Estudio clínico doble-ciego, randomizado y the same period. Blood cell count, serum iron, ferritin, controlado con placebo. La muestra fue constituida por Latent Iron-Binding Capacity (LIBC), Total Iron-Bin- 60 individuos hipertensos, distribuidos aleatoriamente ding Capacity (TIBC), Transferrin Saturation Index en grupo tratamiento (n = 32), que recibió 600 mg/día (TSI) and transferrin were assessed before and after in- del ALA por doce semanas y grupo control (n = 28), que tervention. To assess changes between groups, the Stu- recibió el placebo por el mismo período. Fueron analiza- dent t-test and ANOVA were used, adopting a significan- dos antes y después de la intervención, los parámetros ce level of 5%. del hemograma, Hierro Sérico, Ferritina, Capacidad La- Results: After intervention, ALA supplementation tente de Enlace del hierro, Capacidad Total de Enlace del showed a statistically significant (p < 0.05) association Hierro, Índice de Saturación de la Transferrina (ISI) y with the reduction of total leukocytes, increase in the Transferrina. Para evaluar las alteraciones entre los gru- number of neutrophils and reductions in the serum levels pos, se utilizó el teste t de Student y el análisis de varianza of iron and TSI. ANOVA, adoptándose el nivel de significación de 5%. Conclusion: Oral administration of ALA as a thera- Resultados: Después de la intervención, el suplemen- peutic adjuvant changes the hematologic response of to con el ALA demostró una asociación estadísticamente white blood cells and reduces the absorption of iron. It significativa (p < 0,05) con la reducción de los leucocitos is observed that the mechanism of metals chelation by totales, aumento del número de neutrófilos y reducciones lipoic acid may be responsible for these changes and, en los niveles de Hierro Sérico e ISI. consequently, could trigger a condition of iron deficiency Conclusión: La administración oral del ALA como un anemia in hypertensive individuals. adyuvante terapéutico, altera la respuesta hematológica (Nutr Hosp. 2015;31:883-889) del leucograma y reduce la absorción del hierro. Cabe senãlar que el mecanismo de quelación de metales por el DOI:10.3305/nh.2015.31.2.7403 ácido lipoico puede ser responsable de estos cambios y, Keywords: Lipoic Acid. Iron. Hypertension. Anemia. en consecuencia, podría desencadenar una condicion de anemia ferropénica en individuos hipertensos. (Nutr Hosp. 2015;31:883-889) Correspondence: Paula Renata Florêncio Mendes. Rua Cristina Procópio Silva, 650, apto 302. DOI:10.3305/nh.2015.31.2.7403 Edifício Érick - Catolé, CEP: 58410-255, Palabras clave: Ácido Lipóico. Hierro. Hipertensión. Ane- Campina Grande - Paraíba, Brasil. mia. E-mail: [email protected] Recibido: 5-III-2014. 1.ª Revisión: 1-V-2014. 2.ª Revisión: 12-X-2014. Aceptado: 1-XI-2014. 883 047_7403 Effect of Alpha Lipoic Acid on the Blood cell count (CBC) and iron kinetics in hypertensive patients.indd 883 08/01/15 15:28 Introduction Study population and patients The etiology of Non-Communicable Diseases The total study population consisted of 105 hyper- (NCDs) has been linked to oxidative damage produ- tensive patients, diabetic or not, registered on system ced by Reactive Oxygen Species (ROS), and iron has of follow-up of hypertensive and diabetic patients been associated with the establishment of an oxidative (HIPERDIA) and aged over 40 years. Patients with stress condition by acting as a catalyst of ROS for- other chronic diseases and those with inflammation, mation reactions, especially when iron is in excess. infections, frequent or excessive alcohol consump- However, studies have reported that deficiency of this tion, smoking, pregnancy and use of other antioxidant mineral affects the production of proteins with antioxi- or drugs that could interact with iron were excluded. dant potential, suggesting that oxidative stress may be Among the 67 patients selected, there were seven los- associated with iron deficiency anemia, contributing to ses and the total sample consisted of 60 patients. complications in the pathophysiology of other diseases that are influenced by oxidizing agents1,2,3. Anemia is an aggravating or precipitating factor for Ethical considerations heart failure and has encouraged the performance of studies to understand this cause / precipitation rela- The study followed the ethical guidelines and was tionship, becoming prognostic factor in hypertensive approved by the Ethics Research Committee under patients, since Systemic Arterial Hypertension (SAH) CAAE No. 02505712.0.3001.5182. All participants and Diabetes mellitus have been indicated as key res- signed the Informed Consent Form and completed a ponsible for heart failure (HF) in African descent4,5,6. questionnaire that addressed demographic and econo- Thus, it becomes important to evaluate iron metabo- mic issues, as well as questions on lifestyle, clinical lism and the prevalence of anemia in a population with condition and use of medications. SAH, due to its role as an aggravating factor for car- diovascular risks7. Considering the potential of alpha-lipoic acid Interventions (ALA) as a treatment for reducing oxidative damage, studies on its use as a therapeutic agent in pathologies Participants underwent pre-intervention clinical related to the overproduction of free radicals should and laboratory assessment and received guidance on be carried out, because this is considered a univer- the treatment duration, which would be twelve weeks sal antioxidant and for knowing the role of oxidati- and dosage of 600mg/day divided into two daily do- ve stress in the pathophysiology of hypertension and ses (morning and evening), as usual dose recommen- other NCDs4,7,8. ded in literature. Then, bottles containing capsules of In this context, this study aims to evaluate the effect 300mg of lipoic acid or placebo, both with the same of supplementation with ALA on the blood count and physical characteristics, were randomly delivered to iron metabolism parameters in hypertensive indivi- each participant. Thus, patients were divided into two duals, anemic or not, in order to obtain information groups: treatment group (n = 32) who received supple- that may be used to prevent or slow the progression mentation with Alpha-Lipoic Acid, and control group of pathological events in SAH and / or iron deficiency (n = 28) who received placebo and at the end of the anemia. intervention, new laboratory tests for purposes of in- ter- and intra-group comparisons were performed. Methods Laboratory studies Design Blood counts were performed on automated equip- This is a clinical double-blind randomized place- ment Mindray BC- 5380 (Mindray). The reference va- bo-controlled trial conducted between October 2012 lues ​​considered for hemoglobin followed those adop- and January 2013 in a Basic Health Unit of a Munici- ted by WHO to define anemia (< 12 g/dL for women pality in Northeastern Brazil. and < 13 g/dL for men)10 and the other parameters fo- llowed values adopted by national literature. Ferritin analyses were performed in equipment Ac- Sample Size cess® 2 Immunoassay Ssystem (Beckman Coulter) using the Access Ferritincom assay and immunoassay Formulas for sample size calculation differ depen- methodology by chemiluminescence for quantitati- ding on the type of study design and the studies out- ve measurement11 and Serum Iron was determined in come(s). The sample size was based Noordzij et al9. In Cobas Mira Plus® apparatus using Iron Liquiform kit this study the sample obtained 27 patients per group from Labtest Diagnóstica by Colorimetric methodolo- (alpha = 0,05; power = 80%). gy (modified Goodwin)12. Latent Iron-Binding Capa- 884 Nutr Hosp. 2015;31(2):883-889 Paula Renata Florêncio Mendes et al. 047_7403 Effect of Alpha Lipoic Acid on the Blood cell count (CBC) and iron kinetics in hypertensive patients.indd 884 08/01/15 15:28 city (LIBC) was determined using
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