|Year : 2020 | Volume
| Issue : 3 | Page : 171-178
Ferrum phosphoricum 3X and Ferrum metallicum 3X in the treatment of iron deficiency anaemia in children: Randomized parallel arm study
Anil Khurana1, Renu Mittal1, Padmalaya Rath2, Karunakara Moorthy3, Divya Taneja1, Uttam Singh4, Kabita Mishra2, Raj K Manchanda1
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Dr. DP Rastogi Central Research Institute for Homoeopathy, NOIDA, Uttar Pradesh, India
3 National Homoeopathic Research Institute of Mental Health, Kottayam, Kerala, India
4 Clinical Research Unit, Port Blair, Andaman and Nicobar Islands, India
|Date of Submission||03-Jan-2020|
|Date of Acceptance||21-Aug-2020|
|Date of Web Publication||28-Sep-2020|
Dr. Renu Mittal
Central Council for Research in Homoeopathy, 61-65, Institutional Area, Opposite D Block, Janak Puri, New Delhi
Source of Support: None, Conflict of Interest: None
Background: Anaemia in children has significant adverse health consequences and is a major public health problem. Objective: The objective of this study is to identify efficacy of Ferrum phosphoricum 3X (FP) and Ferrum metallicum 3X (FM) in changing haemoglobin (Hb) levels in school-going children, 12–14 years of age with Iron Deficiency Anaemia (IDA). Materials and Methods: School children were screened for Hb levels using a portable haemoglobinometer at Noida, Kottayam, Guwahati and Imphal. Children with Hb levels ≤11.9 g% and ≥8 g% were investigated for IDA by measuring serum ferritin level and other parameters. Children enrolled were divided into two categories, i.e., mild (Hb 11–11.9 g%) and moderate anaemia (Hb between 8 and 10.9 g%). Children in both the groups were randomised into FP and FM groups and prescribed accordingly for 3 months. Hb levels were repeated after 3 months. Results: 2,878 children were screened and 792 (27.5%) were identified to have Hb between ≤11.9 g% and ≥8 g%. 102 (mild anaemia: FP-30; FM-29, moderate anaemia: FP-21, FM-22) were enrolled after investigations and consent. Significant increase in Hb was seen in children with moderate anaemia in FP group (9.95 ± 0.749–10.97 ± 1.51). Increase in Hb in other groups was not significant. Conclusion: Percentage of children with low iron reserves and having true IDA was <4%. FP has a potential to improve Hb levels in children with no side effects.
Keywords: Ferrum metallicum, Ferrum phosphoricum, Haemoglobin, Homoeopathy, Iron Deficiency Anaemia, School Children, Serum Ferritin
|How to cite this article:|
Khurana A, Mittal R, Rath P, Moorthy K, Taneja D, Singh U, Mishra K, Manchanda RK. Ferrum phosphoricum 3X and Ferrum metallicum 3X in the treatment of iron deficiency anaemia in children: Randomized parallel arm study. Indian J Res Homoeopathy 2020;14:171-8
|How to cite this URL:|
Khurana A, Mittal R, Rath P, Moorthy K, Taneja D, Singh U, Mishra K, Manchanda RK. Ferrum phosphoricum 3X and Ferrum metallicum 3X in the treatment of iron deficiency anaemia in children: Randomized parallel arm study. Indian J Res Homoeopathy [serial online] 2020 [cited 2021 Jan 20];14:171-8. Available from: https://www.ijrh.org/text.asp?2020/14/3/171/296248
| Introduction|| |
Anaemia, defined as low blood haemoglobin (Hb) concentration, is a public health problem that affects low, middle, and high income countries, has significant adverse health consequences, and impacts social and economic development. Although the most reliable indicator of anaemia at the population level is blood Hb concentration, measurements of this concentration alone do not determine the cause of anaemia. Anaemia may result from a number of causes, with the most significant contributor being iron deficiency. Approximately 50% of cases of anaemia are considered to be due to iron deficiency.
A survey published in 2010 identified a very high prevalence of iron-deficiency anaemia (IDA) among the study population in India and reported that more than 95% of children, adolescent girls and pregnant women suffer from anaemia. The prevalence is the highest among the adolescents, i.e., 97.8% out of which 27.1% of adolescent girls, are severely anaemic.
The cause of anaemia is identified by complete blood examination (Hb, mean corpuscular volume [MCV] or mean corpuscular haemoglobin [MCH], packed cell volume [PCV], iron studies, serum ferritin indices, etc.). Serum ferritin level is the most useful index of the diagnosis of iron deficiency. In an anaemic adult, a ferritin level below 15 μg/L is diagnostic of iron deficiency, and levels between 15 and 30 μg/L are highly suggestive. Lower thresholds (from 10 to12 μg/L) have been used for children.
The prevention of IDA requires an approach that addresses all the potential causative factors. Interventions to prevent and correct iron deficiency include the measures to increase iron intake through food-based approaches, namely dietary diversification and food fortification with iron, iron supplementation and improved health services and sanitation. Iron supplementation, however, is the mainstay of treatment.
Homoeopathy treatment focuses on better absorption and utilisation of iron in the body, rather than on supplementation as per the recommended dietary allowances per se. As per homoeopathic literature, Ferrum phosphoricum 3X (FP) increases Hb  and is useful for treatment of anaemia. Ferrum metallicum 3X (FM) is best adapted to young weakly persons who are anaemic. Empirically, these medicines are used frequently by homoeopathic practitioners, alone or with other medicines for the treatment of anaemia in all age groups. A specific trial of FP or FM in IDA has not, however, been conducted.
This study was undertaken to identify the efficacy of homoeopathic FP and FM in changing Hb levels in children in the age group of 12–14 years suffering from IDA.
The study was approved by the Institutional Ethical Committee of the Central Council for Research in Homoeopathy vide its letter dated 4 July 2014 and retrospectively registered with Clinical Trial Registry of India under CTRI/2019/05/019077, dated 13 May 2019. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects.
| Materials and Methods|| |
The study was conducted in school settings in the community to screen children suffering from IDA, who may as yet be undiagnosed. Further, provision of medicines and clinical assessments were undertaken in the school settings to ensure regular intake of medicines and assessments whilst reducing extra efforts on part of children or parents when the children as yet would be asymptomatic and therefore, not sick enough to visit health facility.
Identification of children with low haemoglobin (screening 1)
The study was undertaken by four centres of Central Council for Research in Homoeopathy at Dr. D. P. Rastogi Central Research Institute for Homoeopathy, Noida; National Homoeopathic Research Institute in Mental Health, Kottayam; Regional Research Institute for Homoeopathy, Guwahati and Regional Research Institute for Homoeopathy, Imphal. The schools where the Weekly Iron Folic Acid supplementation (WIFA) Program of the Government of India  had not been implemented at Noida (Uttar Pradesh), Kottayam (Kerala), Guwahati (Assam) and Imphal (Manipur) were approached. The study was undertaken where the school authorities gave approval for participation. A short orientation of identified teachers of the school was conducted. The parents of the children were informed about the study and voluntary written informed consent of parents was undertaken to measure Hb levels in the children in the age group of 12–14 years, using a portable haemoglobinometer. Verbal assent of the child was taken before undertaking the investigation.
The study duration was between July 2015 and March 2018.
Testing for iron deficiency anaemia (screening 2)
After screening 1, children with Hb levels ≤11.9 g% and ≥8 g% were invited to participate in the study. A participant information sheet was sent to the parents and written voluntary informed consent of the parents and assent from children was taken for conducting detailed investigations for IDA. The investigations were serum ferritin, Vitamin B12 levels, C-reactive protein (CRP), serum iron, total iron-binding capacity (TIBC), red cell count, MCV, PCV, MCH and mean corpuscular haemoglobin concentration (MCHC). Stool examination was conducted to identify parasitic infestations. Parents of the children identified with severe anaemia (i.e., Hb level <8 g%) were advised to get appropriate treatment for their children, and these children were not included in the study.
Children with serum ferritin levels below 15 μg/L, low MCV (<87 fl), CRP, Vitamin B12 levels within normal range, no complaints of malaria (recent within the past 6 weeks), worm infestation, concurrent heart, liver or renal systemic condition were enrolled in the study. However, during the course of the study, very few children were identified with low serum ferritin (data presented in results), and the inclusion criteria were modified to include children with serum ferritin up to 50 μg/L with raised red cell distribution width. The criteria of low MCV were removed. However, in spite of this, adequate sample of children could not be enrolled (data presented in results section) and the criteria were further modified to include all children irrespective of serum ferritin levels.
In the absence of reliable prevalence of low serum ferritin in children with low Hb, it was proposed to enrol an initial sample of 80 children in each group, i.e., 80 with mild and 80 with moderate anaemia to be further randomised and 40 allocated in each FP and FM groups. The total sample size was 160 children, including 10% dropouts.
Randomisation, blinding and intervention
Children enrolled were divided into two groups, i.e., those having mild anaemia (Hb between 11 and 11.9 g%) and those having moderate anaemia (Hb between 8 and 10.9 g%). Children in both the groups were allotted serial numbers separately and randomised into two groups, i.e., FP group and FM group by using computer-generated random numbers. This was a single-blind study, where the participants at the study site were kept blind about drug allocation. Two tablets of FP or FM was prescribed to these children as per group allocation, to be taken twice a day for a period of 3 months. The medicines were procured from The Kerala State Homoeopathic Cooperative Pharmacy (HOMCO), Kerala, in a single batch, as tablets in blister packs.
Follow ups and assessments
Institutionally qualified homoeopathic practitioners conducted screening, assessments and follow-up of all children enrolled in the study. Fortnightly follow-ups, for a period of 3 months, were conducted at the school premises. The presence of a school teacher was mandatory during these assessments. Parents were free to contact the study investigators at these pre-scheduled follow ups in the school or could contact the investigators at the research centres on other days. Laboratory investigations were conducted at the end of 3 months. Change in Hb levels, serum ferritin, serum iron, TIBC, red cell count, PCV, MCV, MCH and MCHC and symptomatology of children was assessed. Adverse events during the period of treatment, if any, were also recorded. Mean values before and after the treatment were compared using the paired t-test.
| Results|| |
The study was conducted in 19 identified schools at the 4 centres. 2,878 children were screened and 792 (27.5%) were identified to have Hb between ≤11.9 g% and ≥8 g%. Nine children, who had Hb level below 8 g%, were not included in the study and their parents were informed to take treatment for their children from physician of their choice. Out of 792 children, consent of parents and assent of 474 (60%) children was obtained for undergoing detailed investigation for IDA. Out of these, 474 children were investigated for IDA. 368 children were excluded due to non-fulfilment of inclusion criteria and 4 children withdrew their consent. Out of 368 cases excluded, 354 (96%) cases had serum ferritin above 15μg/L signifying that their iron reserves were normal, which is considered a hallmark for IDA. 102 children were enrolled under the study. Centre-wise details of screening and enrolment are given in [Table 1].
The desired sample of 160 children could not be achieved, in spite of best efforts of undertaking screening continuing from July 2015 to November 2017 in different schools. The screening could not be continued further because 'WIFA programme' had got initiated in almost all the schools. Conducting screening in children on regular supplementation of iron and folic acid would have defeated the study objectives, and identifying the very small percentage of children not taking supplements in schools posed logistic problems.
It was identified that though 27.83% of school children screened had low Hb, the percentage of children with low iron reserves and having true IDA was <4%. Out of 102 children enrolled, 59 had mild anaemia and 43 had moderate anaemia. 51 children were prescribed FP and other 51 were prescribed FM [Figure 1], which included 29 boys (28.43%) and 66 (64.70%) girls. Out of these 102 children, 2 with mild and 1 with moderate anaemia dropped out from FP group, while 2 each with mild and moderate anaemia from FM group dropped out of the study, and their post-intervention investigation could not be done. Data of only those children who completed the study were analysed. All children were between the age group of 12–14 years, with a mean age being 12.96 ± 0.79 years [Table 2].
Change in haematological parameters in children with mild anaemia
Out of 30 children in FP group and 29 in FM group, 28 and 27 respectively, completed treatment, and their post-intervention investigations were conducted. Out of 28 cases on FP, Hb increased in 19 cases and reduced in 9 cases. Out of 27 cases on FM, Hb increased in 17, remained static in 2 and reduced in 8 cases.
In most of the children, serum Iron, TIBC, MCV, MCH and MCHC were found to be normal at baseline and continued to remain within normal range post-treatment. In cases where the values were not within normal, pre- and post-values have been compared to identify treatment response. Change in these parameters before and after treatment is given in [Table 3].
|Table 3: Change in haematological parameters in children with mild anaemia|
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Serum ferritin increased from 6.5 μg/L to 95 μg/L, 13 μg/L to 97 μg/L and 6.4 μg/L to 9.9 μg/L, in 3 children on FP and from 5.5 μg/L to 9.5 μg/L in one child on FM.
Change in haematological parameters in children with moderate anaemia
Out of 21 children in FP group and 22 in FM group, 20 in each group completed treatment, and their repeat investigations were conducted. Hb was repeated in all children. Out of 20 cases on FP, Hb increased in 18 cases, remained static in 1 and reduced in 1 case. Out of 20 cases on FM, Hb increased in 12 cases, remained static in 1 and reduced in 7 cases.
In most of the children, serum iron, TIBC, MCV, MCH and MCHC were found to be normal at baseline and continued to remain within normal range post-treatment. In cases where the values were not within normal, pre- and post-values have been compared to identify treatment response. Change in these parameters before and after treatment is given in [Table 4].
|Table 4: Change in haematological parameters in children with moderate anaemia|
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Change in serum ferritin in cases where serum ferritin was low, i.e., below 15 μg/L was seen in only 4 cases, which increased from 4.3 μg/L, 2.6 μg/L, 7.3 μg/L, 2 μg/L to 9.1 μg/L, 6.9 μg/L, 12.4 μg/L and 8.6 μg/L, respectively in children on FP. In children taking FM, serum ferritin, 5 cases had serum ferritin below 15 μg/L i.e., 2.8 μg/L, 5.8 μg/L, 7.4 μg/L, 8.3 μg/L, 13 μg/L which increased to 7 μg/L, 15.2 μg/L, 9.5 μg/L, 16.5 μg/L and 98 μg/L, respectively.
In children enrolled with serum ferritin below 15, change in Hb and serum ferritin was seen with both FM and FP [Table 5].
|Table 5: Change in haemoglobin and serum ferritin in children with low iron reserves|
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| Discussion|| |
To our knowledge, this is the first study to identify the specific changes in the haematological pattern in children with IDA after 3 months of regular intake of Ferrum phosphoricum/Ferrum metallicum. Out of 102 children enrolled, data of 95 children treated in either group [Figure 1] showed that 66 (69.47%) children had an increase in Hb percentage, whereas 4 (4.12%) children remained static and 25 (26.31%) had a decrease in Hb levels. The change in Hb was statistically significant in the 20 children being treated with FP who presented with moderate levels of anaemia. To detect the changes in mild anaemia of only 1 g%, on statistically significant parameters, a larger sample of children is needed than that what was enrolled in the study. The response of children in FM group was not significant in either mild or moderate anaemia. This could also be due to lower sample size. No adverse events were reported in any child in either group.
These children were attending their school regularly and were not 'unwell' or 'ill' to miss school, in spite of low Hb levels. They were largely healthy due to maintenance of iron reserves, i.e., normal serum ferritin levels. On specific questioning, they complained of non-specific muscular pains, weakness, tiredness, breathlessness on exertion or menstruation-related complaints. Most of them reported improvement in their complaints irrespective of change in Hb after 3 months. None of the children were on any additional treatment for IDA or for any of these complaints. The study objective was however, not to identify symptomatic indications for the use of the medicines, but to identify change in Hb and other laboratory parameters associated with IDA. The role of dietary factors cannot be ruled out in cases of anaemia, particularly in IDA. During the period of study, the dietary intake of children was identified by specifically asking them about their dietary habits. No major change in dietary habits in children was seen during the period of the study.
The choice of study medication was not based on symptom presentation, but was rather a pathological prescription, based on low Hb as the only criteria. This was undertaken to explore utility of homoeopathic medicines in large scale public health care programmes, where classical individualisation process becomes practically difficult to be implemented.
In two studies published in 2017, one identified prevalence of low Hb as 53.5% in children studying in 5th to 10th standards in schools on Ambalapuzha Taluk in Kerala, whereas another study identified only 4.23% boys having low Hb as compared to 52.17% of girls in age group of 10–15 years. A systematic review on the prevalence of anaemia in Kerala concluded that accurate estimate of anaemia prevalence could not be made due to inconsistency in estimation methods, proportion of severe anaemia among school children and adolescents in general population were less in recent studies as compared to studies published during 1990–2000. A national survey on 72,660 non-pregnant women (age group 15–49 years) identified lowest percentage of low Hb in Kerala (22.4%) and Manipur (25.8%) as compared to the national average of 49.6% (with all other states having a prevalence of more than 30% at least). No similar large-scale survey of recent years for children in age group of 12–14 years could be identified.
Considering the variation in the proportion of low Hb and iron deficiencies, it has been suggested that where ever possible, national surveys should measure IDA prevalence so that program planners and national stakeholders can better understand the aetiology of anaemia in their country. Not many studies could be identified in the literature where haematological profile of anaemia has been conducted to examine the prevalence of IDA vis-à-vis prevalence of low Hb levels. Our study highlights the importance of detailed anaemia profiling both in survey and intervention studies considering wide variations between the regions.
Notwithstanding, low sample size as a limitation, the pragmatic approach adopted by undertaking the study in the population settings, rather than in health-care settings increase its external validity. To our knowledge, no other study reports identification of true IDA in children in the age group of 12–14 years in multiple schools in 4 cities and their response to Homoeopathic medicines. The study shows that homoeopathic medicine FP 3X has a potential to improve Hb in children with no side effects. The medicine can be used on a larger scale to ascertain true effects. A larger population-based study to explore utility of FP 3X as an alternative to iron supplements at a mass level, particularly in children, is suggested, especially where supplementation is reported to have caused side effects like gastro-intestinal disturbances and skin pigmentation.
| Conclusion|| |
Percentage of children with low iron reserves and having true IDA was <4%. Homoeopathic medicine Ferrum phosphoricum 3X has a potential to improve Hb in children with no side effects. Further, validation with larger sample size is required.
The screening at Guwahati was conducted and coordinated by Dr. Sarbjit Sarkar, RO(H) and Dr. Umakant Prusty, RO(H), RRI Guwahati. Dr. Ojith Singh, RO(H), Dr. Tejaswini S. Patole, RO(H), RRI Imphal conducted and coordinated screening at Imphal. We acknowledge the cooperation provided by Dr S. Gopinadhan, RO(H) at NHRIMH Kottayam during the conduct of the study. We acknowledge the contribution of Dr. Priyanka Nim, former SRF, CCRH in development of the protocol. Dr. Nazia Nikhat, former SRF assisted in conduct of the study at DDPRCRIH Noida. Dr Meera Sharma, former SRF, CCRH assisted in data verification from the case records.
Financial support and sponsorship
The study was funded by Central Council for Research in Homoeopathy, autonomous body of the Ministry of AYUSH, Government of India.
Conflicts of interest
| References|| |
WHO. The Global Prevalence of Anemia in 2011. Geneva: World Health Organisation; 2015.
Chellan R, Paul L Prevalence of Iron-Deficiency Anemia in India:Results from a Large Nationwide Survey. Prevalence of iron-deficiency anemia in India:Results from a large nationwide survey. J Popul Stud Soc Stu. 2010;19:59-80. Available from: https://so03.tci-thaijo.org/index.php/jpss/article/view/84686
. [Last accessed on 2019 May 09].
World Health Organization. Serum Ferritin Concentrations for the Assessment of Iron Status and Iron Deficiency in Populations. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization 2011 (WHO/NMH/NHD/MNM/11.2). Available from: http://www.who.int/vmnis/indicators/serum_ferritin.pdf
. [Last accessed on 2019 Aug 31].
Pasricha SR, Flecknoe-Brown SC, Allen KJ, Gibson PR, McMahon LP, Olynyk JK, et al
. Diagnosis and management of iron deficiency anaemia: A clinical update. Med J Aust 2010;193:525-32.
World Health Organization, Regional Office for South-East Asia. Prevention of Iron Deficiency Anemia in Adolescents. WHO Regional Office for South-East Asia; 2011. Available from: https://apps.who.int/iris/handle/10665/205656
. [Last accessed on 2019 Aug 31].
Boericke W. Pocket Manual of Homoeopathic Materia Medica Repertory. New Delhi: B Jain Publishers; 2008.
World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013;310:2191-4.
Government of India. Operational Framework: Weekly Iron and Folic Acid Supplementation Programme for Adolescents. Delhi: Ministry of Health and Family Welfare; 2012.
Soman SK, Areekal B, Murali AJ, Varghese RG. Adolescent anaemia its prevalence and determinants: A cross-sectional study from South Kerala, India. Int J Community Med Public Health 2017;4:2750-6.
Devi SH. Prevalence of anaemia among the adolescent athletes of national sports academy. Int J Dev Res 2017;7:17717-9.
Rakesh PS. Prevalence of Anaemia in Kerala State, Southern India-A Systematic Review. J Clin Diagn Res 2017;11:LE01-4.
Bharati P, Som S, Chakrabarty S, Bharati S, Pal M. Prevalence of anemia and its determinants among nonpregnant and pregnant women in India. Asia Pac J Public Health 2008;20:347-59.
Petry N, Olofin I, Hurrell RF, Boy E, Wirth JP, Moursi M, et al
. The Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys. Nutrients 2016;8:693. Available at: https://doi.org/10.3390/nu8110693
. [Last Accessed on 2019 May 09].
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]