Efficacy of standardized extract of Hibiscus sabdariffa L. (Malvaceae) in improving iron status of adults in malaria endemic area: A randomized controlled trial

Abstract

Ethnopharmacological relevance

Indigenous community of Mkuranga district have been using aqueous extract of H. sabdariffa L. for treating anemia. However, there have been neither safety nor efficacy studies to validate this medicinal product in anemia.

Aim

The purpose of this study was to establish efficacy and safety of standardized aqueous extract of H. sabdariffa L. in anemic adults.

Materials and methods

This was a randomized controlled clinical trial in which 130 adults’ men and women aged 18–50 years were involved after meeting the inclusion criteria. Initially, standardized aqueous extract of H. sabdariffa L. was prepared using optimized extraction parameters. Stratified randomization was used to randomize participants into four fixed dose groups. The first group received oral dose of 1000 ml while the 2nd group was randomized to receive 1500 ml orally. The last two groups were given a dose of 2000 ml of extract and 200 mg ferrous sulphate tablet respectively. Primary endpoint was the actual change of iron status indicators at the end of 30 days follow up period as compared to those recorded at baseline. Adverse effects were assessed at every 10th day scheduled visit. In all arms, HB and hematopoietic parameters were measured using HemoCue hemoglobinometer® (HemoCue, Ängelholm, Sweden) and hematology analyzer® respectively at the trial site. Follow up was done for 30 days. A total of 82 participants were included for analysis.

Results

A standardized aqueous extract of H. sabdariffa L. did not improve iron status in anemic adults in malaria endemic region (P>0.005). However, there was evidence to support the safety of the extract for human consumptions as herbal supplement. Iron and organic acids contents of H. sabdariffa L. extract showed the potential of improving hematopoietic parameters. Studies with bigger sample size are therefore needed to establish the efficacy of the extract when concurrently used with malaria chemoprophylaxis in malaria endemic areas.

Introduction

Anemia is indicated and operationally defined by hemoglobin concentration less than 11.0 g/dl when measured at sea level (WHO, 2008). It is the leading cause of morbidity in all age groups. In 2005, anemia affected around 1.62 billion people in the World. Africa continue to bear a disproportionate share of affected individuals reaching 67.6% (WHO, 2008). In Tanzania, at least 40% of women of reproductive age are anemic (Bureau of Statistics, 2011); this contributes to several serious health problems. Anemia has been documented to be among fundamental causes of premature birth and low birth weights (Nair et al., 2016). It is the predominant cause of indirect maternal deaths (Pembe et al., 2014). With its co-presence with chronic diseases such as HIV and TB, management of anemia in adults requires special attention (Makubi et al., 2015.; Petraro et al., 2016).

Anemia is primarily caused by deficiency of iron in human body (DeMaeyer and Adiels-Tegman, 1985; McLean et al., 2009). It is a results of low intake and poor absorption of iron from diets. The problem is more prominent during the period of life when iron requirements are especially high (i.e. growth and pregnancy) (WHO, 2008). In an attempt to combat iron deficiency anemia, WHO and UNICEF formulated a joint policy recommending daily iron supplements to priority target groups (International Nutritional Anemia Consultative Group (INACG), World Health Organization (WHO, 1998). Implementation of iron supplementation program among priority target groups has widely demonstrated its ability to reduce morbidity and other health related problems (Pasricha et al., 2014).

For decades, Tanzania have adopted the use of daily iron and folic acid supplementation strategy and little has been reported on the use of natural products such as herbal extracts. In Tanzania, roselle (Hibiscus sabdariffa L.) juice is among other natural products that are used as alternative therapies for treatment of anemia (Koffi et al., 2012, Peter et al., 2014a, Peter et al., 2014b). Roselle was also noted to be used for treatment of various medical conditions in other countries (Odigie et al., 2003, Herrera-Arellano et al., 2004, Falade et al., 2005) . Already there are clinical trials which evaluated the effect of roselle extracts in lowering cholesterol level and moderate hypertension (Herrera-Arellano et al., 2004) and in controlling type 2 diabetics (Mozaffari-Khosravi et al., 2009). However, there is no clinical trial that evaluated the effect of roselle extract on anemia in the East African region including Tanzania.

Roselle extract is a mixture of at least partially uncharacterized constituents. Analysis of chemical constituents that constitute a sizable percentage of the total ingredients revealed that, aqueous extract of Roselle consists of minerals (calcium, magnesium, potassium, sodium, iron and zinc) and organic acids (ascorbic acids, malic acid, tartaric acids, citric acid) (Ali et al., 2005). Ascorbic acid is the best known and potent enhancer of iron absorption in its natural form both in fruit and vegetables (Ballot et al., 1987) and when added as a free compound (Davidsson et al., 1998). It has also been demonstrated that other organic acids, such as citric, malic and tartaric acids, have a similar though less-marked enhancing effect on iron absorption (Gillooly et al., 1983). Therefore, Iron from sources such as beverages and diets will be absorbed more efficiently when ascorbic and other organic acids are given concurrently. Pharmacological studies in animal models revealed that an aqueous extract of Roselle calyx significantly increase both hematocrit and hemoglobin concentration (Adigun et al., 2006). Therefore, the composition of Roselle calyces, the pharmacological activities in animal models, and the ethno medical practice of community members strongly suggest the potential benefits of using Roselle extract to correct iron deficiency anemia. Clinical study was therefore conducted to establish the effectiveness of Roselle extract in controlling iron deficient anemia as well as to document possible side effects associated with its oral use.