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Iron and Folic Acid Fortification



This is one of our charity profiles, where we present our shallow, preliminary research on a potential, promising charity idea. We believe that this idea could be a potential contender for a GiveWell top charity, if further research confirmed the idea and if someone started the charity, executed it well, and resolved some of our outstanding questions and reservations

Basic Idea Lobbying lower and middle-income country (LMIC) governments to legislate mandatory iron and folic acid fortification of a staple food (such as flour or salt). Summary Cost-effectiveness: High -- Iron fortification has been estimated to be $70 per DALY and appears to have a positive impact on a relatively large number of different metrics. Folic acid fortification is less cost-effective, with an estimate of $11K per life saved, but can be combined with iron fortification in the same efforts so there is little actual increase in cost. Strength of Evidence: Medium -- The case for iron and folic acid fortification are covered by several studies, including some systematic reviews. However, like with tobacco taxation, significant government lobbying would be needed and the effectiveness of such campaigns are less clear. Counterfactual Scalability: Medium -- There appear to be over a dozen countries and Indian states with large populations that aren’t currently being lobbied for fortification. However, there are a fair number of organizations focusing on this already, and it may be a matter of time before they focus on these areas. Ease of Testing: Low -- Performing an impact evaluation on a lobbying campaign is exceedingly difficult due to high interference from other campaigns, the all-or-nothing nature of lobbying, and an inability to effectively randomize. Flexibility: Medium -- While it appears we could move lobbying efforts to other areas as we gain more generalized skills and contacts, we would likely not build much infrastructure that is useful for areas outside lobbying. Logistical Possibility: Medium -- Lobbying poses significant logistical challenges and draws on skills we do not yet possess. Why We Think This Could be an Effective Opportunity Iron Iron deficiency is perhaps the most common micronutrient deficiency in the world (Baltussen, Knai, & Sharan, 2004). Fortifying food with iron could have immense benefits. A Copenhagen Consensus report notes that iron fortification is one of the top cost-effective interventions (Hoddinott, Rosegrant, & Torero, 2012, p33). The DCP-2 estimates that iron fortification results in $70 per DALY and costs $0.09-$0.12 per year per person treated (DCP2, p560)[1], though we haven’t yet vetted any of these estimates. Anemia is frequently linked to iron deficiency (and also to other factors). Increasing iron intake can decrease a significant portion of anemia cases (Guo, et. al., 2014; Gera, et. al., 2012; Zimmermann, et. al., 2004; Andersson, et. al., 2008; Sari, et. al., 2001; Lakshmy, et. al., 2007) which reduces fatigue, irritability, dizziness, shortness of breath, and other conditions. Increased iron is also possibly connected with decreased premature births (Pena-Rosas, et. al., 2012), increased income (Thomas, et. al., 2006; Niemesh, 2012), and decreased behavioral problems of children (Zhou, et. al., 2006). Iron has also been linked to decreased depression rates (Beard, et. al., 2008; Ballin, et. al., 1992; Rahn, et. al., 2008; Luca, et. al., 2008), though this effect is less well established than other conditions, as it’s mostly observational data. Lastly, it has also been linked to increased cognitive abilities of children (Baumgartner, et. al., 2012; Low, et. al., 2013), though this has been undermined by a more recent meta-analysis from Guo, Liu, and Qian (2015) and we’ve noted before that we have concerns with the importance of improving IQ. While many of these studies are for iron supplementation instead of iron fortification, the effects should be similar, since fortification also increases iron intake but at a lower dose (Hoa, et. al., 2005; Le, et. al., 2006). Iron fortification seems to us logistically more easy to do, because you can add it to a staple food people already get and eat, rather than create new distribution plans and behavior changes to get people to have and consume an iron supplement. This could be why some studies have shown iron fortification is also likely more cost-effective than iron supplementation (Baltussen, Knai, & Sharan, 2004; Le, et. al., 2006; Ramsay & Charles, 2015). Folic Acid Folic acid is a form of folate, also known as vitamin B9. Maternal folic acid deficiency caused over 300,000 annual neural tube defects (NTDs) in 2012 and 2013 (CDC, 2012; Pachón, et. al., 2013), though now the number appears to be below 280,000 annually (WHO, 2015). NTDs frequently result in death or severe lifetime mental and/or physical disability for newborns (Ibid.). Folic acid deficiency can be reduced through folic acid supplementation (De-Regil, Peña-Rosas, Fernández-Gaxiola, & Rayco-Solon, 2015). Folic acid fortification is less cost-effective than iron fortification, estimated at $1200 per NTD averted and $11K per life saved (Llanos, et. al., 2007). However, folic acid fortification can be done alongside iron fortification (Copenhagen Consensus, 2008; WHO, 2012) and one could lobby the government to do both forms of fortification with the same lobbying effort. This means additional folic acid fortification would likely have some additional benefit with very little additional cost, resulting in what would likely be a marginally better cost-effectiveness than iron fortification alone. A Possible Implementation Plan If we were to explore iron and folic acid fortification, we’d aim to hire a local expert with expertise in fortification and local politics. We’d aim to find a country that has a large population, a relatively centralized production of the staple food, doesn’t have other charities already working in that area, and has a stable government without any armed conflicts. Once we had identified a country that fit these criteria, would would talk to experts to understand if this country was neglected for a particular reason. It’s important to keep in mind that lobbying the government to make fortification mandatory is likely the best way to implement fortification. The government is able to pass along the costs of fortification to the consumer, which is a negligible $0.00063 per kg of flour (0.16% of current retail price) (Food Fortification Initiative FAQ). Other models, such as paying companies for fortification, cannot take into account these economies of scale and would have to end up paying a lot of money and undercut any potential for political change. Who is Already Working in this Area? We found a few big organizations working on this, such as the Micronutrient Initiative, which works primarily on lobbying for iron and folic acid fortification. While GAIN works primarily in salt iodization, they do have some iron and folic acid fortification programs. UNICEF works on iron fortification of flour, among many other things. Food Fortification Initiative does a variety of food fortification programs, including iron and folic acid fortification. Project Healthy Children works to encourage the implementation of mandatory food fortification programs by governments. Helen Keller International also works on iron fortification, among many other programs. Smarter Futures works on food fortification, including iron and folic acid. They are a partner of GAIN. Our understanding from talking to experts is that it is very common for these organizations to partner together, so any additional work we did would likely be in partnership with some of these groups. Reservations Lobbying The evidence for lobbying succeeding in LMIC is far weaker than the evidence for the impact of successfully implemented fortification. It’s often difficult to credit responsibility for legislative change to particular players in advocacy campaigns because multiple campaigns operate simultaneously and it’s unclear whether the government would have changed anyway, absent lobbying efforts. While there is considerable evidence that government implementation of fortification is highly cost-effective, there is a dearth of analysis on the return of investment of actual lobbying campaigns. We find the difficulty of testing this project to be a barrier to attempting an implementation, given our desire for rigorous impact evaluation and prioritizing against other charity ideas, as well as this making it difficult to receive feedback to refine our lobbying approach. However, depending on policy, this specific charity idea may be able to be completed at the state level before attempting it on the national scale. We’re also not enthusiastic about would could be the zero-sum and all-or-nothing nature of lobbying. It would very likely be necessary to hire local lobbyists to reach the needed policy makers, which could be expensive. This also creates flexibility concerns, as the contacts we build would likely not be useful for a charity other than lobbying. Moreover, if lobbying requires a high degree of specialization, it may not even be possible to move easily between different lobbying campaigns. Access to Fortification We would guess it is plausible that the people in most need of iron fortification would be less likely to buy their food from a centralized source; instead, being more likely to grow it on their own or trade with other locals. This would prevent these people from being reached by a centralized food fortification effort. However, we have not seen any literature one way or another on this effect and we are unsure how it would affect the cost-effectiveness for iron even if the effect was true. Long-term, Large-scale Track Record While many countries have already implemented large-scale mandatory iron fortification programs targeting wheat flour, there are very few studies that seek to evaluate these programs. More troublingly, evaluations that have taken place have found that in half the countries where large-scale iron fortification has taken place, iron deficiency did not decline in children, though it did for women (Pachón, Spohrer, & Serdula, 2015). However, most of the countries studied did not fortify according to WHO standards, which can dramatically impact the effectiveness of the iron (Ibid., p12). Ultimately, we’re unsure about how heavily to weigh this consideration. There are also no studies we could find that seek to verify the long-term effects of iron fortification. This means it remains possible that the positive effects found so far could be fleeting over a longer time-horizon. For one example, Protzko (2015) found evidence of a fade-out effect in raising IQ, and GiveWell raises concerns about fadeout effects in their review of salt iodization (GiveWell, 2014). Side-effects of Fortification There has been some concern that iron supplementation might negatively affect malaria rates, which is why the WHO recommends fortification to be done in conjunction with improved anti-malarial practices. However meta-analyses drawing on over 20 RCTs (Shankar, 2000; Gera, 2002) found no significant effect on malaria. This would be especially true for fortification, which is at much lower levels than supplementation. Our overall conclusion is to avoid high malaria zones whenever possible, but not to put too much weight on this concern. Another potential “side effect” is masking Vitamin B12 deficiency. B12 deficiency is often detected by the presence of anemia (NIH Fact Sheet, 2016) and the deficiency can cause long-term neurological damage (Lachner, Steinle, & Regenold, 2012), which means that a decrease of anemia through iron fortification could delay diagnosis. Iron supplementation may also result in excess iron, which can slow physical development (Ianotti, Tielsch, Black, & Black, 2006; Paricha, Hayes, Kalumba, & Biggs, 2013). It’s not clear whether iron fortification would carry the same risk because only small amounts are added to the staple food. While folate supplementation prevents cancerous tumors, folate can also increase the growth rate of existing cancerous tissue (Smith, Kim, & Refsum, 2008). This makes it unclear whether folate increases or decreases cancer risk (see discussion in Kim, 2007; Mason, et. al., 2007; Kim, 2008; Luebeck, et. al., 2008; Hirsch, et. al., 2008). Any rollout of iron and folic acid fortification may need to carefully target specific populations to reduce the risk of negative side-effects. Differences between Fortification and Supplementation Lastly, it’s worth noting that we’re suggesting a fortification program, but in the process we rely on evidence of the effect of supplementation (though we also do use evidence of fortification). As we discussed in the section on side-effects, the dosage of fortification is meaningfully lower than the dosage involved with supplementation, which can involve changes in effects. We have not yet thought seriously about how much, if at all, this would undermine the case for fortification. Remaining Questions

  1. How difficult is it to lobby a LMIC government to mandate micronutrient fortification?

  2. What is the base rate for lobbying in the developing world? How much variation is there in lobbying success between different countries?

  3. Would governments have implemented micronutrient fortification anyway, even if we didn’t lobby them?

  4. How amenable are food companies to implementing micronutrient fortification? Would they try to counter-lobby the government? If so, how much?

  5. How seriously should we take the health risks that iron and folic acid fortification may pose? Are there other long-term negative effects on health?

  6. How similar is fortification to supplementation? Would we expect fortification to have the same benefits as supplementation? The same risks?

  7. Which food is the best to fortify? Should we focus on wheat or flour? Is there any promise to salt fortified with iron and iodine?

  8. Why does the evidence for iron fortification and supplementation look so good in individual studies, yet look weak when specific government programs are evaluated?

Footnotes [1]: DCP has had flaws in the past which overestimated cost-effectiveness (GiveWell, 2011) which could make the true estimate worse. Additionally, the DCP estimate does not account for effects on income, depression, and irritability, which could make the true cost-effectiveness estimate better.

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