¹National Centre of Excellence and Advanced Research on Anemia Control, Centre for Community Medicine, All India Institute of Medical Sciences, India
²M.Sc. Scholar, Lady Irwin College, University of Delhi, India
³Centre for Community Medicine, All India Institute of Medical Sciences, India
⁴Centre for Community and Family Medicine, Bibinagar, India

^*Corresponding author: Yadav K, National Centre of Excellence and Advanced Research on Anemia Control, Centre for Community Medicine, All India Institute of Medical Sciences, India; Email: dr.kapilyadav@gmail.com

Submission: 14/03/2021; Accepted: 07/04/2021; Published: 10/04/2021

Copyright: © 2021 Vohra K, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Iron deficiency is the most prevalent nutritional deficiency in the world, primarily affecting infants, young children, and women of childbearing age. Different products like animal milk, fermented milk and yogurt can be used as the vehicle for iron fortification.

Objective: To assess the iron status among the population consuming iron-fortified milk and milk products.

Methods: A Systematic, thorough search was done from the available online literature. Different web-based search engines like google scholar and PubMed were used to search the relevant literature on this topic. Different keywords like ‘fortification’, ‘iron’, ‘milk and milk products’, ‘anaemia’ and ‘iron status’ were used to search related articles. Mainly randomized control trial and intervention studies were selected. Research articles relevant to the topic were screened, a total of 652 articles were found through a systematic literature search. Out of 652, 15 articles were read by two authors independently, and results were analyzed.

Results: Significant decrease in the prevalence of anaemia (ranging from 40% to 13.7%) was observed when consuming iron fortified milk and milk products. There is a positive correlation between the intake of fortified milk and haemoglobin status. In most of the studies, a significant increase in the haemoglobin status was observed. A Positive correlation was seen of different vitamins like vitamin A, vitamin C and vitamin D with iron absorption in the body.

Conclusion: Iron fortification of milk and milk products can be used as an effective and efficient way to combat anemia at the national level.

Anemia; Iron; Fortification; Heamoglobin; Milk and milk products; Ferrous sulphate; Microencapsulation

Iron deficiency, a nutritional deficiency affecting approximately 20% of the world population specifically women and young children are at high risk. Iron is an essential component of hemoglobin, the substance in red blood cells that carries oxygen from the lungs and transports it throughout the body [1]. In the state of anemia, oxygen is not adequately delivered to tissue due to iron insufficiency.

The World Health Organisation (WHO) defines iron deficiency as a condition in which there are no mobilizable iron stores and in which signs of a compromised supply of iron to tissues, including the erythron, are noted [2]. Globally, anaemia affects 1.62 billion people (1.50–1.74 billion), which corresponds to 24.8% of the population (22.9–26.7%). The highest prevalence is among preschool-age children (47.4%), and the lowest prevalence is in men (12.7%). However, the population group with the most significant number of individuals affected is non-pregnant women (468.4 million, 95%). In the year 2015-2016, according to NFHS-4, the prevalence of anemia is more in rural parts than in urban areas. 58.5% of children aged 6-59 months followed by non- pregnant women (53.1%) and pregnant women (50.3%) are anemic. The prevalence of anemia has reduced for all the age groups from NFHS-3 (2005-06) to NFHS-4, a drop of 2% in non-pregnant & all women (15-49 years) to nearly 10% in children 6-59 months of age (NFHS-3 2006; NFHS-4 2015).

Anaemia has an adverse effect on health, survival, productivity, income and development of a person. Iron deficiency with or without anaemia impairs cognitive development, limits attention span and shortens memory capacity, resulting in poor classroom performance, high absenteeism, and early dropout rates among schoolchildren. Anaemia due to iron deficiency is among the top 10 leading causes of years lost to disability in low- and middle-income countries, while anaemia is the 7th leading cause of years lost to disability in women .It is estimated that 12.8% of maternal deaths in Asia could be related to anaemia [5]. For Indian population, the normal level of hemoglobin are (Women: 12.1 to 15.1 gm/dl, Men: 13.8 to 17.2 gm/dl, Children: 11 to 16 g/dl, Pregnant women: 11 to 15.1 g/dl) [6].

There are a number of factors which affect the iron status and iron availability in the body. The RDA of iron is different for different age groups as there is an increased demand of iron during childhood, reproductive years and pregnancy. The main factors associated with iron deficiency anemia include consumption of non heme ironbased food as vegetarian diet is prevalent among Indian population. Consumption of more inhibitors for example: consumption of tea and coffee along with the meals is a common practise followed in India resulting in increased intake of inhibitors like tannin in the meal corresponding to poor iron absorption [7]. Also, Lack of education and awareness among the population and food myths are the major contributors.

Cause of anemia is divided into three parts namely nutrition, infectious disease and genetic hemoglobin disorder. Infections, particularly parasitic diseases, including malaria and helminth infections that cause extracorporeal iron loss. Increased inflammation leads to decreased bioavailability of iron to host tissues, genetic disorders such as thalassemia traits in the population also contribute towards the problem. Poor water, sanitation and hygiene (WASH) also play an important role in contributing to high anaemia rates through gastrointestinal infections [8].

The various strategies used to combat the problem of anemia include different government policies, food fortification, iron supplementation and dietary diversity [9]. Home based interventions such as diet diversification, germination and fermentation are cost effective techniques to enhance bioavailability of iron. Behaviour change communication and iron folic acid supplementation are of key importance to prevent the onset of anemia among different age groups. Fortification of food is a safe, cost effective way to improve micronutrient content. According to WHO, Fortification refers to “the practice of deliberately increasing the content of an essential micronutrient, i.e. vitamins and minerals (including trace elements) in a food, so as to improve the nutritional quality of the food supply and to provide a public health benefit with minimal risk to health” [10]. Commonly fortified foods include staple products such as salt, maize flour, wheat flour, sugar, vegetable oil, milk and rice. Milk and milk products are usually used for the fortification process as it is safe, acceptable and is consumed by the majority of the population. They are fortified with a variety of vitamins like Vitamin A, B vitamins, Vitamin D and folic acid and minerals like calcium, iron, zinc. Fortified milk and milk products have several advantages [11].

Iron fortified milk has a high content of ferric sulphate. In addition, vitamin C in fortified milk boosts immunity and increases the body’s absorption of iron. Fortification of milk with Iron will help in preventing iron deficiency anemia in children, a common problem. Moreover, milk is often fortified with iron and other nutrients, such as zinc and B vitamins to increase its nutritional content [12].

This review focuses on the iron fortification of milk and milk products to address the problem of anemia. The paper provides an overview of study design, methodology and sample characteristics from baseline survey data and key lessons learned. A total of 15 studies were reviewed and analysis was done on the basis of different parameters used in different studies like hemoglobin level, ferritin level etc. The study will be helpful to plan appropriate programmes and policies related to iron deficiency anemia and will form the basis of different interventional studies to combat the problem of iron deficiency anemia. Main objective of this review was to evaluate the potential effects of iron fortification in milk and milk products on the haemoglobin status of the participants. Other objectives were:

• To study the acceptance of the fortified products.
• To assess the effect of iron fortified milk and milk products along with other nutrients like Vitamin A, Vitamin C and Zinc.
•To assess the effect of iron fortification on sensory characteristics of milk and milk products.

A systematic, thorough search using different databases like Cochrane Systematic Reviews, google scholar and PubMed was done for relevant literature on the topic. Keywords like ‘fortification’, ‘iron’, ‘milk and milk products’, ‘anaemia’ and ‘iron status’. Free texts and Medical Subject Headings (MeSH) such as ‘micronutrients’, ‘iron’, ‘haemoglobin’ were also used. The available published data were enormous; appropriate articles relevant to the study were chosen. The citations of relevant articles were also referred to find further relevant articles. Only experimental and correlational studies were selected for the review. The quality assessment was performed by two authors who worked independently, and data were extracted from the selected articles and summarized into the tabular form.

Full text articles available in english language were selected for the review. Animal studies, review articles, conference proceedings, editorials bulletins and reports were excluded. To limit the number of articles, articles published after 1996 till June 2019 were selected. Studies were not excluded according to age, sex, gender or location was established.

Finally, selected articles were read by both the authors independently and relevant information like sample description, key intervention given to intervention group and control group, methods of assessment of impact of the intervention and lastly the impact and key findings were extracted from the articles.

Both national and international studies were taken for the review. Out of 15, four studies were reported from Chile and two from Spain (Murica and Madrid) & Brazil (Sao Paulo) and one study each from Birmingham (UK), Brazil, Morocco, Mexico, Jamaica, Senegal (Africa) and Delhi( India).

In this article, we aimed to assess the interventions using iron fortified milk and milk products in relation to its effect on Hb level, bioavailability of iron, acceptability of the product and its overall feasibility to combat the major problem of iron deficiency in the population.

Various vehicles such as cow milk, pasteurized milk and fermented products were used for the fortification. In most of the studies, full fat acidified milk or pasteurized milk were used as the key product for the intervention like in a before and after study by Brito A et al [13]. However, infant formula feed was also fortified with iron and other micronutrients for the intervention product in the Randomized Control Trial (RCT). Few studies used fermented products such as yoghurt and fermented beverages. In a RCT by Port et al, yoghurt was the main test product for the intervention group while in another study, strains of L. bulgaricus and S. thermophilus were incorporated into the fortified fermented beverage. In one of the studies, absorption of iron from iron fortified milk products was compared with iron fortified noodles [14].

Different elemental and compositional forms of Iron were used for Iron fortification. Studies in this review article include various methods and forms of iron for fortification of dairy products.

In almost half of the studies, milk or test product was fortified with ferrous sulphate (FeSO₄). Some RCTs used iron amino chelate for the fortification of the intervention product. It was seen that along with iron, other elements like Zn and Cu were also added to the product to address other nutritional deficiencies. Along these elements, some vitamins were also added like influence of ascorbic acid was seen on iron absorption in longitudinal study done by Davidsson et al in 2018 and Vitamin D was added in a study done by Toxqui et al in 2013 to increase the effect of iron fortification [15]. New techniques like microencapsulated ferric saccharate were used to increase the acceptability of the product.

In most of the studies conventional clinical methods were used for the estimation of iron level in the body. One of such methods is serum ferritin level, which is most often used for estimation of total body iron store concentration. Three studies included haematocrit level i.e. ratio of RBC volume to the total blood volume used for the assessment of the effectiveness of intervention. C-reactive protein was also analysed in one of the studies to assess the past inflammation and infection in the population. Other indicators such as stool test, total transferrin saturation and iron isotope for knowing the impact in other studies.

Each study is summarized in Table 1 with the characteristics of participants, key interventions, and assessment of effectiveness of intervention along with key findings of the research.

This review article aimed to assess the effect of iron fortification in milk and milk products on the hemoglobin status. Research articles relevant to the topic were screened, a total of 652 articles were found through a systematic literature search. Review articles, animal studies, Duplicate studies and articles not relevant to the topic were excluded. Finally, 15 studies were found relevant and were carefully analysed.

Fortification of milk with Iron shows a significant decrease in the prevalence of anemia. The major vehicles used for fortification were cow’s milk, pasteurized milk, infant milk formula, fermented milk products etc. Significant decrease in the prevalence of anaemia (ranging from 40% to 13.7% ) was observed when consuming iron fortified milk and milk products. The study suggested that if an infant is consuming 600 to 700 ml of 10mg/L iron fortified milk then 65% to 70% of the daily RDA is met. In another randomized control trial, the prevalence of anemia from baseline to 6 and 12 months decreased from 44.5% to 12.7 % and 4% respectively in the intervention group [17]. In another study by Brito A et al. (2013), a threefold decrease was observed in anemia prevalence (27% before fortification to 9% after fortification) by the end of 1 year.

Positive correlation between the intake of fortified milk and the hemoglobin status was observed in a Randomized control trial by Silva et al [18]. In this study, there was a 38.2% increase in the hemoglobin among the preschool children consuming the iron fortified beverage. In before-after study by Brito et al., after intervention (iron fortification), there was significant change in hemoglobin level (11.5 ±1.2 g/dL to 12.7 ±1.3 g/dL) [13].

Milk fortified with ferrous sulfate is shown to increase the bioavailability of iron. An intervention study done by Pizarro et al. showed the geometric mean iron absorption corrected to 40% [18]. The fortified formula milk contains highly bioavailable iron, covering toddler’s requirements of the micronutrient.

Along with the iron, incorporation of other vitamins improved the bioavailability of iron. In a longitudinal study by Davidsson et al, the geometric mean iron absorption was significantly greater when 25 mg ascorbic acid was added to the test meal than meal without ascorbic acid, geometric mean iron absorption was 5.1% and 1.6% for the two test meals, respectively [19]. Also, a significant difference in iron absorption was observed when the ascorbic acid content was increased from 25 to 50 mg; geometric mean iron absorption was 5.4% compared with 7.7% respectively. Another type of study by Toxqui L et al. indicated that if the milk is fortified with both iron and vitamin D then there is higher value of erythrocytes, hematocrit and hemoglobin, at week 8 as compared to iron fortification only [15].

So, fortification of milk with iron along with vitamins like vitamin C and vitamin D show a reduction in the prevalence of anemia, increase in the bioavailability of iron and is positively associated with the increase in the hemoglobin concentration.

Iron fortification of milk and milk products has been done using different forms of iron using different techniques. Some forms of iron are able to mask the changes in the characteristics of the product while some forms are unable to do so. For example, ferrous sulfate, and many other soluble iron compounds, cannot be used to fortify liquid whole milk and other dairy products because they cause rancidity and off-flavours [10]. Ferric ammonium citrate, ferrous bisglycinate and micronized ferric pyrophosphate are more suitable as they mask the sensory changes. Ferrous bisglycinate is widely used to fortify whole milk and dairy products in Brazil and Italy while in Japan micronized ferric pyrophosphate is used to fortify the dairy products. A study done by Siddique & Park stated that the process of microencapsulation failed to mask the sensory changes due to fortification of iron such as taste, colour, texture and odour [20]. It was also observed that small microencapsulation was more acceptable than large encapsulation of ferrous salt in terms of flavour and other sensory qualities.

In this review article, it was observed that fortified milk and milk products can significantly improve the iron status in all the age groups thereby decreasing the prevalence of anemia. Similar findings were observed in a study where after fortification there was a reduction in the prevalence of anemia from 40% to 12 % by the end of 6 months [21]. In another randomized control trial by Villalpando et al. (2007), the prevalence of anemia from baseline to 6 and 12 months decreased from 44.5% to 12.7 % and 4% respectively in the intervention group [16].

Clear reductions in the indicators of iron deficiency (low SF and high sTfR) associated with the group consuming fortified milk were documented. Effects on iron stores (SF) were evident both at 6 months and 12 months of intervention [22].

The intake of fortified milk and hemoglobin status was positively correlated in many studies. There was a 38.2% increase in the hemoglobin status among the preschool children consuming the iron fortified beverage [17]. Milk fortified with ferrous sulfate is shown to increase the bioavailability of iron. The fortified formula milk given contains highly bioavailable iron.

Along with the iron fortification, incorporation of other vitamins showed to increase the bioavailability of iron. In a study by Toxqui L et al. indicate that if the milk is fortified with both iron and vitamin D then there is higher value of erythrocytes, hematocrit and hemoglobin, at week 8 as compared to iron fortification only [15]. Also, Fortification of milk with iron along with vitamins like vitamin A, vitamin C and micronutrients like zinc and copper showed a reduction in the prevalence of anemia, increase in the bioavailability of iron and is positively associated with the increase in the hemoglobin concentration [15,19].

So, fortification can be used as a safe method to deliver health promoting, nutritionally dense food products to combat iron deficiency anemia. Fortified dairy products are the most consumed healthy and nutritious food around the country. Therefore, it offers an appropriate potential to reduce this problem by making it a public health intervention at the national level. Fortification of different food products is done in different parts of the world to correct nutrient deficiencies. Fortification of food products like wheat flour, milk and salt etc is done with different nutrients like Vitamin A, iodine, iron, calcium etc. Fortification of milk and milk products is also done with different nutrients like Vitamin A, Vitamin D, Calcium and Iron. Fortification of milk and milk products with Iron is not common. One such program was the Food Fortification Program of Costa Rica to combat iron related deficiencies. Fortification of wheat flour with ferrous fumarate and liquid and powdered milk with ferrous bisglycinate was also done. It was seen that anemia was reduced in children and women when fortified products were used by the population.

There are technological issues relating to food fortification, especially with regard to appropriate levels of nutrients, stability of fortificants, nutrient interactions, physical properties, as well as acceptability by consumers. Also, research on iron fortification in milk and milk products among Indians was limited, thus paper from all over the world was reviewed.

This study provides evidence that delivery of iron via a foodbased vehicle, milk and milk products in this instance, is a feasible option and produces a positive effect on iron status. It provides a potential strategy for achieving reduction in mortality, morbidity, and malnutrition among children due to iron deficiency. Milk provides an acceptable and effective vehicle for delivery of specific micronutrients, especially zinc and iron.

Micronutrient bundles improved growth and iron status and reduced anemia. Further research can also be done in terms of its affordability, availability and acceptance. Fortification of milk and milk products will be an effective measure to combat the problem of anemia among all the age groups. It will also be beneficial for the policy makers to reduce the prevalence of anemia by using these fortified milk and milk products.