Conventional and food‐to‐food fortification: An appraisal of past practices and lessons learned

Abstract Food fortification is an important nutrition intervention to fight micronutrient deficiencies and to reduce their incidence in many low‐ and middle‐income countries. Food fortification approaches experienced a significant rise in the recent years and have generated a lot of criticism. The present review aimed to shed light on the actual effect of food fortification approaches on the reduction of malnutrition. A set of 100 articles and reports, which have dealt with the impact of food fortification on malnutrition, were included in this review. This review identified a broad selection of local raw materials suitable for a food‐to‐food fortification approach.


| INTRODUC TI ON
Micronutrient deficiencies often cause malnutrition that is a crucial public health problem, especially in developing countries (Ramakrishnan, Goldenberg, & Allen, 2011). Indeed, they generate several diseases either infectious or chronic and therefore impacts the life's quality and epidemiological parameters such as morbidity and mortality (Verma, 2015). As a consequence, this type of malnutrition leads to premature death, disability, and reduced work capacity (Black et al., 2013) and more often reaches children and women of reproductive age (Method & Tulchinsky, 2015). Food fortification is considered as the most appropriate preventive approach against malnutrition caused by micronutrient deficiencies (Bhagwat, Gulati, Sachdeva, & Sankar, 2014). For many years, food fortification has been used as a cost-effective means to prevent micronutrient malnutrition (Method & Tulchinsky, 2015). Considerable studies have been carried out to develop food fortification in developing countries (Akhtar, Anjum, & Anjum, 2010;Bhagwat et al., 2014;Mishra, 2011). However, effectiveness of food fortification approaches to improve nutritional status has to be coherently analyzed and evidenced. In order to evaluate the most important global trends and historical patterns in food fortification, large databases are required to study the different types of fortification. Indeed, data relevant to the history, impacts, and challenges of food fortification are scattered across literature and existing reviews concern a few countries.
Therefore, though information on food fortification successes and failures may be difficult to assess and compare, key factors of success or failure of interventions need to be identified to inform policymakers and assist countries in the design and implementation of appropriate fortification programs. The present review: (a) presents the history of knowledge and know-how from conventional food fortification to food-to-food fortification, 1 (b) assesses challenges of food fortification, and (c) documents best practices and benefits of food-to-food fortification approaches.

| ME THODOLOGY
A comprehensive literature search was conducted using Web of Science/Knowledge, Google Scholar (http://schol ar.google. com), Elsevier ScienceDirect (http://www.scien cedir ect.com), and Springer Online Journals (http://link.sprin ger.com). The search syntax contained the following keywords: food fortification, micronutrient deficiencies, fortified food, food fortification impact, and food-to-food fortification. The focus was on peer-reviewed articles and government reports between 1990 and 2016. In addition, a few earlier milestone articles published before 1990 were included.
Other major relevant syntheses were also reviewed including those by the World Health Organization (WHO) and the International Food Policy Research Institute (IFPRI). Initially, a total of 410 publications were identified. Further review of the title, abstract, and full texts of these documents led to the elimination of 250 citations due to their lack of relevance. Finally, 160 articles and reports were used of which 100 were actually included in this review.

| Prevalence of undernutrition and micronutrient deficiencies in the world
Malnutrition (overnutrition, undernutrition, and micronutrient deficiencies) is a physiological state characterized by a low or high quantity of macronutrients, micronutrients, or both in human's organism (Ortiz-Andrellucchi, Ngo, & Serra-Majem, 2016). Currently, several cases of obesity and overweight due to overnutrition are recorded worldwide (IFPRI, 2016). Meanwhile, undernutrition and micronutrient deficiencies are recurrent and have significant negative effects on public health (Lopez, Mathers, Ezzati, Jamison, & Murray, 2006). The prevalence of undernutrition varies considerably according to countries. In developing countries, rural people are the most subjected to undernutrition (Shetty, 2009). Indeed, micronutrient deficiencies are often associated with low income and poor access to nutritious foods, situations that are frequent in rural areas (Shetty, 2009). According to recent estimations, about two billion people suffer from micronutrient deficiencies (Allen, de Benoist, Dary, & Hurrell, 2006). Micronutrient deficiencies account for about 7.3% of the global burden of disease, with iron and vitamin A deficiencies among the 15 leading causes of the global disease burden (WHO, 2000). Animal foods are important sources of protein and of micronutrients such as iron, zinc, vitamin A, and vitamin B 12 .
Unfortunately, in developing countries most people cannot afford these foods in their daily diet. As a result, they suffer from micronutrient deficiencies. Folic acid, vitamin D, selenium, and zinc deficiencies, although less recognized, are important as well. A lack of those micronutrients represents a major threat to the health and development of populations in particular in developing countries (Bain et al., 2013;Müller & Krawinkel, 2005).
Many children worldwide suffer from nutritional deficiencies, which can negatively affect their physical and mental development and increase susceptibility to infections. Moreover, undernutrition amplifies the effect of every disease, including measles and malaria.
Undernutrition (53%) causes as much mortality of children younger than 5 years as diarrhea (61%), malaria (57%), pneumonia (52%), and measles (45%; Black, Morris, & Bryce, 2003;Bryce, Boschi-Pinto, Shibuya, & Black, 2005). In addition, according to Black et al. (2008), women and children are the major targets suffering from consequences of micronutrient deficiency such as poor pregnancy outcomes, children's impaired mental, and physical development. Up to 3.1-3.5 million of children under 5 years old die every year and women of reproductive age living in low-and middle-income countries because of undernutrition (fetal growth restriction, suboptimum breastfeeding, stunting, wasting, and deficiencies of vitamin A, iodine, zinc, iron, vitamin D deficiency, rickets, osteomalacia, and thyroid deficiency) (Black et al., 2008(Black et al., , 2003Mandelbaum, 2004;Method & Tulchinsky, 2015). Zinc deficiency is a risk factor with adverse long-term effects on growth, immunity, and metabolic status of surviving offspring (Harika et al., 2017). Therefore, elimination of these deficiencies is essential, not only to improve health, but also for sustained economic growth and national development (Mishra, 2011).

| Classical food fortification: definition and importance
The nutrient intake of basic foods, seasonings, or condiments may be enhanced through a fortification that increases the content of essential micronutrients, such as vitamins and minerals (Mannar & Gallego, 2002). One way to fortify foods is to incorporate synthetic micronutrients to it (Zimmermann, Muthayya, Moretti, Kurpad, & Hurrell, 2006). In many developing countries, the most widely used vehicles for fortification are among the most commonly consumed foods, including oils and fats, milk, sugar, salt, rice, wheat, or maize flour. Some factors related to food fortification such as level of fortification; bioavailability of fortificants; and amount of fortified food consumed have a significant effect on health (Verma, 2015; see Das, Salam, Kumar, & Bhutta, 2013 for more information). Classical food fortification with zinc is very common; in case, the vehicle is cereal flour at a recommended level (100 mg zinc/kg for wheat flour; Brown, Hambidge, Ranum, & Zinc, 2010) of zinc fortification, of which a lower level may have no significant effect on the nutrient improvement of the cereal (Brown, Peerson, Baker, & Sonja, 2009).
Food fortification leads to rapid improvement in the micronutrient status of a population, and at a reasonable cost, especially if advantage is taken from existing technology and local distribution networks. Rice fortification has an advantage to benefit to almost half of the world's population (>3 billion people consumed rice as their main staple worldwide; de Pee, Tsang, Zimmerman, & Montgomery, 2018). Thus, rice can be considered as one of the best staple food vehicles for food fortification in developing counties regarding a population-level intervention (Moench-Pfanner, Laillou, & Berger, 2012). Fortification of rice flour with iron, zinc, and folate allows children under 5 years old, having a rapid iron and zinc absorption, to improve their growth and micronutrient status (Hettiarachchi, Hillmers, Liyanage, & Abrams, 2004). Fortifying flour is much simpler because the nutrients that are available in powdered form can successfully be mixed into the flour. As such, rice flour was recommended as a suitable vehicle for fortification.
Long-term measures have been implemented to combat vitamin A and iron deficiencies, in particular, fortification of cotton oil with vitamin A and of wheat flour with iron, zinc, folic acid, and vitamin B.
Multiple micronutrient fortification appears relatively more beneficial and should be considered because multiple micronutrient deficiencies coexist in many cases ( Table 1). This consideration justifies why many fortification programs are oriented toward multi-micronutrients and vehicles chosen adequately for a good acceptability of fortified foods by the target group. Food fortification can take several forms, and different techniques and procedures can be used (Liyanage & Hettiarachchi, 2011
In the same period, many vitamins were isolated and their molecular structures elucidated. As a result, it was possible to produce vitamins for fortifying foods at a large scale. In the 1930s, iron was mainly used to fortify cereal flours and products for a large population such as fish sauce (Vietnam), soy sauce (China), and rice (Philippines; Mannar & Gallego, 2002). Since 1938, niacin had been added to bread in the United States. From the early 1940s onwards, fortification of cereal products with thiamine, riboflavin, and niacin (Kyritsi, Tzia, & Karathanos, 2011) became a common practice.
Meanwhile, rice fortification received considerable attention due to the great importance of rice in children's nutrition. Margarine was fortified with vitamin A (FAO & OMS, 2006) in Denmark and milk with vitamin D in the United States (Laforest et al., 2007). The fortification of sugar with vitamin A has been introduced for the first time during the 1970s in Guatemala, followed by other Costa Rica, Honduras, and El Salvador, for reaching up to 80% (Honduras) and 95% (Guatemala and El Salvador) of households (Mora, Dary, Chinchilla, & Arroyave, 2000). The success of this fortification allowed many countries to effectively combat micronutrient deficiencies in populations. Enriching flour and cereal products moved from the use of iron, niacin, riboflavin, and thiamin to the use of folic acid in 1996 (Food and Drug Administration, United States) for enriching breads, flours, corn meals, and rice in order to address neural tube defects in newborns (Backstrand et al., 2002). Therefore, folic acid fortification of wheat became widespread, a strategy adopted by Canada and the United States and about 20 Latin American countries (Samaniego-Vaesken, Alonso-Aperte, & Varela-Moreiras, 2010). Thus, folic acid was added to flour on a mandatory basis in over 60 countries to prevent neural tube birth defects (Liyanage & Zlotkin, 2002;Oakley & Tulchinsky, 2010).
Other food vehicles fortified with vitamin A, besides sugar, include fats and oils, tea, cereals, flour, monosodium glutamate, and instant noodles, as well as milk or milk powder, whole wheat, rice, salt, soybean oil, and infant formulas (Lotfi, Venkatesh Mannar, Merx, & Heuvel, 1996). In Asia, the red palm oil was used as a vitamin A fortificant added to other edible oils (Solomons, 1998). Currently, fortifying foods with vitamin A are common in 29 developing countries (Mason et al., 2014). Young children (5-9 years) • The prevalence of iron deficiency was significantly reduced • There was a significant decrease in median blood lead concentration

TA B L E 1 Examples and outcomes of classical food fortification
• The prevalence of blood lead levels 10 g/dl was significantly reduced.
The study was of short duration (16 weeks) and blood lead was only measured twice Zimmermann et al. (2006) Wheat flour and maize meal The huge success of salt iodization was likely a critical factor in generating support for other fortification initiatives. In Ghana, food fortification began in 1996 when legislation was passed to enforce salt iodization. Salt iodization has been ongoing with the target of covering at least 90% of the population (Nyumuah et al., 2012).
Through Africa, maize meal and bread were shown to be the most commonly consumed staples; hence, vitamin A, iron, zinc, folic acid, thiamin, niacin, vitamin B, and riboflavin have been added to maize meal and wheat flour with the aim of improving the growth and micronutrient status of undernourished children (Steyn, Nel, & Labadarios, 2008).

| Socioeconomic factors hindering the practice of food fortification
In most developing countries, national policies do not provide the appropriate importance to food fortification. Due to the low development of their industry sector (including food-processing industries), it is hard to reach poor people who really need fortified foods. Increased food prices remain an issue in undermining food security and livelihoods of the poor. Despite various international aids, expensive foods are still not accessible because unaffordable for vulnerable groups who often grow and process their own staple foods. Temple and Steyn (2011) demonstrated that purchasing healthier food items resulted in 69% higher daily costs. For food fortification development, the absence of centralized food-processing units is a limiting factor. Another one is the lack of simple and affordable technology that can use stable and bioavailable nutrients while maintaining the commonly preferred taste and appearance of foods.
The major challenges of developing countries regarding food fortification rely on the lack of industrial concentration and the socioeconomical level of the large segments of the population that does not allow them affording expensive foods (Bhagwat et al., 2014). Major challenges to local-scale fortification programs include the initial cost of the mixing equipment, the price of the premix, achieving and maintaining an adequate standard of quality control, and sustaining monitoring and distribution systems.

| Technical limits to the practice of food fortification
Technical fortification challenges rely on (a) nonappropriateness of fortification causing nutrients' loss, (b) sunlight exposure of fortified foods by retailers, (c) nonregular monitoring and unreliable quality control procedures by companies. The most important challenge is to ensure a regulatory monitoring that aims at meeting fortified foods to national fortification standards (Method & Tulchinsky, 2015). Governments in developing countries may not have the resources to effectively monitor compliance, especially when there are many small processing companies operating. As Luthringer, Rowe, Vossenaar, and Garrett (2015) showed, financial inputs for monitoring have a proportional significant effect on the effectiveness of detection and enforcement of noncompliant and under fortified products. Cooperative working relationships between regulatory agencies and food producers will be a useful strategy for successful fortification programs. Challenges such as choosing appropriate fortification vehicles, reaching target populations, avoiding overconsumption in nontarget groups, and monitoring nutritional status are relevant to all countries because they occur everywhere where there is an attempt to fortify foods to optimize intake and nutritional status (Dwyer et al., 2015). In Sub-Saharan Africa, dietary diversification can be used effectively to enrich indigenous and traditional foods.

| Communication factors limiting the practice of food fortification
Apart from the socioeconomical and technical challenges, efforts must be done to inform consumers about the existence and importance of fortified foods for their well (Pambo, Otieno, & Okello, 2014). Indeed, media are the most important source of nutrition information and fortification awareness. However, reliable information about food fortification is not widely available for instance some African countries. Under those circumstances, nonfortified food has a price advantage because of the absence of a mandatory provision and low levels of awareness on the benefits of fortification.

| From classical food fortification to food-tofood fortification
Recently, food fortification has motivated many efforts worldwide but it still faces several issues in developing countries. The major challenge of classical food fortification relies on the whole food processing from production to consumption in developing countries, in addition to economic factors especially in Sub-Saharan Africa. Indeed, successful food fortification has a complex relationship with the level of economic development. For achieving a good food fortification, efforts should be done in food processing (by using modern techniques); quality control and monitoring systems; transport (reliable distribution infrastructure); regulatory support; and management of market dynamics (in a way to make ease access to food for low-income families). The unbalanced accessibility to staple foods is a major limit for poor populations who are actually the ones at the highest risk of micronutrient deficiency, to benefit of fortified foods (Wimalawansa, 2013). It is then important to find a technique that uses the fortificant with a highly accessible (i.e., financially and physically) vehicle, already used by the target population. More and more, the aim of food fortification is to improve people health instead of deficiencies' prevention (Dwyer et al., 2015). Thus, to overcome all these challenges, development of nutritious and cheap foods from locally available foods is important. Efforts are being made by employing food-to-food fortification (Onuoha & Ene-Obong, 2005). Foodto-food fortification is an approach that uses an interesting (contain useful amounts of micronutrients), available, and accessible local resource (plant or animal) to fortify another food (Uvere, Onyekwere, & Ngoddy, 2010). Though, it is difficult to find an interesting resource that meets the availability and affordable accessibility conditions. It is also necessary that the fortificant food may not affect sensory properties of the food that needs to be fortified. In most cases, it is preferable to use food vehicles that are centrally processed, and to have the support of the food industry for an effective impact of food-to-food fortification. For this technique, the rate of fortification varies considerably (1%-50%) and depends on the compatibility of the vehicle (the staple food) and the fortificant. For both classical food fortification and food-tofood fortification, the main objective is to improve the nutritional quality of the fortified food without losing sight of the acceptability criteria (mainly the food organoleptic quality).

| Practices and benefits
Food-to-food fortification often uses foods that are available in the area of the target population to enhance nutrient intake. This approach consists of selecting and associating foods (a common staple and a fortifying food) in such a way to optimize the bioavailability of interesting micronutrients to consumers. For example, in Nigeria,   Vuong (2000) for traditional rice dishes in Vietnam, liver chips as a snack in southern Thailand (Wasantwisut, Chittchang, & Sinawat, 2000), and red palm oil incorporated into biscuits in child-feeding programs in South Africa (van Stuijvenberg & Benadé, 2000). In Northeast Brazil, the pulp from the buriti fruit (Mauritia vinifera Mart.) is used daily as a dietary supplement to children at high risk (12 g containing ~800 µg β-carotene or 134 µg retinol) to resolve or attenuate clinical signs of vitamin A deficiency (Mariath, Lima, & Santos, 1989). In South India, the β-carotene-rich blue-green alga Spirulina, prepared as a sweetened product suitable as a snack, improved vitamin A status of preschoolers attending daycare centers (Annapuma, Deosthale, & Bamji, 1999).

| Fortification/substitution rate
The adequate rate of fortification varies considerably between 1% and 50% according to the compatibility between the fortifying and the vehicle foods. For instance, 2% and 3% of dry leaves of M. oleifera can be enough, despite the low rate of fortification, to enrich the nutritional properties of Labneh cheese (Abdullahi et al., 2014) and buttermilk, respectively. As well as the fortification rate is important, for example, 15% of dry M. oleifera leaves in maize-ogi (Abioye & Aka, 2015), the physical properties of the fortificant have to be analyzed in order to select the rate that will provide an optimized nutrient intake and will maintain the food acceptability by consumers. As such, next to the laboratory formulation of the fortified food, a sensorial evaluation is necessary to assess acceptability levels.
However, for ogi produced from sorghum and fortified with pawpaw fruit at substitution levels of 0, 20%, 40%, and 60%, blends with 40% pawpaw and more were acceptable for improving the nutritional value of ogi without affecting the sensory quality (Ajanaku et al., 2010). According to Sankhon, Amadou, and Yao (2013), sensory evaluation indicated that 5%, 10%, and 15% of parkia-fortified flour TA B L E 2 Examples on effectiveness of food-to-food fortification Proteins, fat, and ash Wheat flour is substituted for 5%, 15%, and 20% by defatted seeds of C. lanatus. The substitution rate until 20% of the wheat flour by the seeds of C. lanatus was acceptable in terms of sensorial and physical properties with improvement of nutritional qualities The carbohydrate content in fortified bread is lower than the one in bread made by 100% of wheat flour Meite et al. (2008) Soybean (Glycine max) and melon seed (Citrullus vulgaris): soybeanmelon protein supplements "Gari," a fermented and toasted cassava granule Protein "Gari," a fermented and toasted cassava granule, was enriched with 10% of full fat soy-melon protein supplements, at different processing stages (after toasting and before toasting) The gari enriched prior to toasting was better in most of the pasting properties, bulk density, and gel strength The enriched "gari" sample exhibited high setback and breakdown viscosity values of indicating that its paste will have lower stability against retrogradation than the un- Crude proteins, phosphorus, fat, and ash, manganese, iron, copper, zinc, and potassium Gari was fortified with soybean flour or soybean residue at 25% of dry weight Soybean flour increased the macronutrient and micronutrient content of the fortified gari Difficulty in processing soybean residue-fortified products Kolapo and Sanni (2015) Tapioca from cassava tubers (Manihot esculenta) Crude protein, phosphorus, fat, and ash, manganese, iron, copper, zinc, and potassium Tapioca was fortified with soybean flour or soybean residue at 25% of dry weight Soybean flour increased the macronutrient and micronutrient content of the fortified tapioca Difficulty in processing soybean residue-fortified products Kolapo and Sanni (2015) Acerola ( The addition of dry leaves of M. oleifera tended to make the color (appearance) greener Salem et al. (2013) Moringa leaf powder Maize-ogi Protein, fat, ash, crude fiber, calcium, magnesium, iron, potassium, zinc, and copper The "ogi" produced from maize was fortified with moringa leaves at substitution levels of 0, 10%, and 15%.
The ogi sample with 10% moringa leaves substitution was rated close to the unfortified ogi sample. Improvement of the nutritional and sensory qualities The swelling capacity decreased with increase in the level of moringa leaves substitution Abioye and Aka (2015) TA B L E 2 (Continued) bread were the most acceptable breads. A substitution rate of 15% of wheat flour by mushroom powder to produce bread was also acceptable in terms of sensorial and physical properties (Okafor et al., 2012).
Substitution of 20% of wheat flour by the seeds of watermelon (Citrullus lanatus) was acceptable in terms of sensorial and physical properties but the carbohydrate content in the fortified bread was lower than in bread consisting for 100% of wheat flour. Fortification of wheat flour with M. oleifera seed flour in bread production for up to 15% reportedly increased protein content by approximately 67% without significantly altering the sensory properties (Ogunsina, Radha, & Govardhan Singh, 2010). Ogi based on maize fortified with baobab fruit powder was found to be acceptable for up to 50% substitution with also a decrease in protein, crude fiber, fat, and carbohydrates. Apparently, fortification could cause a reduction in the levels of certain nutrients in the basic food (vehicle) while improving others.

| Step by step toward food-to-food fortification
For a successful fortification, the aim and the approach must be clearly defined before beginning the process. Obviously, the first thing to do is the identification of nutrients that lack and need to be provided. Then, the most appropriate fortificant has to be identified, considering the food habits of the target population and the most appropriate techniques for fortification. According to FAO and OMS (2006), a vehicle food may meet four main features: (a) Its consumption must be common to a large population including the most vulnerable one, (b) its consumption must be regular and in consistent quantity, (c) it should be centrally processed, and (d) it must allow a nutrient premix to be added relatively easily using low-cost technology, and in such a way so as to ensure an even distribution within batches of the product.
For optimizing the acceptability of the fortified food and preventing undesirable chemical reactions (Maillard reaction) (Adenuga, 2010) when using the food-to-food approach, some agents can be added to improve its sensory properties (Lelana et al., 2003). The step at which the fortificant is added to the vehicle also impacts the physical properties of the fortified food. For example, in the case of gari fortified with soybean flour, the soybean flour is added to the gari before or after toasting (Oluwamukomi & Jolayemi, 2012).
Fortificant may also be added to some fermented food vehicle before or after fermentation.

| Way forward
Food fortification is necessary for both developed and developing countries to ensure optimal levels of essential nutrients in processed foods, improving their suitability for human nutrition and preventing many diseases. To ensure the success and sustainability of food fortification, programs should be implemented in concert with cultural consideration; poverty reduction programs; and other agricultural, health, education, and social intervention programs that promote the consumption and utilization of adequate quantities of good quality nutritious foods. According to Mildon, Klaas, O'Leary, and Yiannakis (2015), further work is needed to determine contextually feasible and sustainable mechanisms for premix supply, quality control, and cost recovery. Incorporating this work into national fortification frameworks is recommended for countries where a significant proportion of the population may have limited access to commercially fortified foods and appropriate legislation is needed to overcome challenges faced by classical food fortification (WHO, 2000). Food fortification should thus be viewed as a complementary strategy for improving micronutrient status of the population. In many countries, basic information on existing dietary intake is lacking. Accurately assessing intake of fortification vehicles is needed to determine the dietary impact of any fortification program (Dwyer et al., 2015).
Thus, continuous production and monitoring of quality fortified foods are essential. More emphasis is needed to determine locally sustainable mechanisms for quality control and cost recovery of food fortification in Africa. Furthermore, the foods to fortify as well as the micronutrient mix or food fortificant must be chosen carefully, to identify the most appropriate vehicles for food fortification as well as target the population at risk of inadequacy without creating excessive intake for other subgroups of the population. Fortification must be applied thoughtfully, its effects monitored diligently, and the public informed effectively about its role in dietary intake through appropriate labeling and other sources of consumer education. For research purposes, databases must be constantly updated to reflect the rapidly evolving marketplace, so that the contribution of both added and intrinsic micronutrients accurately estimates population intakes.

| CON CLUS ION
The best way to prevent micronutrient malnutrition is to ensure consumption of a balanced diet that is adequate in every nutrient.
Studies on fortification of foods have shown promising results in the control and prevention of micronutrient deficiency among vulnerable populations, especially women and children. Food fortification is necessary for developed and developing countries to ensure essential nutrients in processed foods, improving their suitability for human nutrition. However, fortification, though promising, is not the only answer to the global widespread nutritional deficiencies. A mix of many food-based approaches is needed to tackle undernutrition, especially in developing countries.

ACK N OWLED G M ENTS
This work is funded by the Regional Universities Forum for Capacity Building in Agriculture (RUFORUM) through GRG Grant ID: Grant No. RU 2015 GRG-125.