Around the world, about 2 billion people suffer from iron deficiency, which can lead to anemia, impaired brain development in children, and increased infant mortality.
To combat that problem, MIT researchers have come up with a new way to fortify foods and beverages with iron, using small crystalline particles. These particles, known as metal-organic frameworks, could be sprinkled on food, added to staple foods such as bread, or incorporated into drinks like coffee and tea.
"We're creating a solution that can be seamlessly added to staple foods across different regions," says Ana Jaklenec, a principal investigator at MIT's Koch Institute for Integrative Cancer Research. "What's considered a staple in Senegal isn't the same as in India or the U.S., so our goal was to develop something that doesn't react with the food itself. That way, we don't have to reformulate for every context — it can be incorporated into a wide range of foods and beverages without compromise."
The particles designed in this study can also carry iodine, another critical nutrient. The particles could also be adapted to carry important minerals such as zinc, calcium, or magnesium.
"We are very excited about this new approach and what we believe is a novel application of metal-organic frameworks to potentially advance nutrition, particularly in the developing world," says Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute.
Jaklenec and Langer are the senior authors of the study, which will appear in the journal Matter. MIT postdoc Xin Yang and Linzixuan (Rhoda) Zhang PhD '24 are the lead authors of the paper.
Iron stabilization
Food fortification can be a successful way to combat nutrient deficiencies, but this approach is often challenging because many nutrients are fragile and break down during storage or cooking. When iron is added to foods, it can react with other molecules in the food, giving the food a metallic taste.
In previous work, Jaklenec's lab has shown that encapsulating nutrients in polymers can protect them from breaking down or reacting with other molecules. In a small clinical trial, the researchers found that women who ate bread fortified with encapsulated iron were able to absorb the iron from the food.
However, one drawback to this approach is that the polymer adds a lot of bulk to the material, limiting the amount of iron or other nutrients that end up in the food.
"Encapsulating iron in polymers significantly improves its stability and reactivity, making it easier to add to food," Jaklenec says. "But to be effective, it requires a substantial amount of polymer. That limits how much iron you can deliver in a typical serving, making it difficult to meet daily nutritional targets through fortified foods alone."
To overcome that challenge, Yang came up with a new idea: Instead of encapsulating iron in a polymer, they could use iron itself as a building block for a crystalline particle known as a metal-organic framework, or MOF (pronounced "moff").
MOFs consist of metal atoms joined by organic molecules called ligands to create a rigid, cage-like structure. Depending on the combination of metals and ligands chosen, they can be used for a wide variety of applications.
"We thought maybe we could synthesize a metal-organic framework with food-grade ligands and food-grade micronutrients," Yang says. "Metal-organic frameworks have very high porosity, so they can load a lot of cargo. That's why we thought we could leverage this platform to make a new metal-organic framework that could be used in the food industry."
In this case, the researchers designed a MOF consisting of iron bound to a ligand called fumaric acid, which is often used as a food additive to enhance flavor or help preserve food.
This structure prevents iron from reacting with polyphenols — compounds commonly found in foods such as whole grains and nuts, as well as coffee and tea. When iron does react with those compounds, it forms a metal polyphenol complex that cannot be absorbed by the body.
The MOFs' structure also allows them to remain stable until they reach an acidic environment, such as the stomach, where they break down and release their iron payload.
Double-fortified salts
The researchers also decided to include iodine in their MOF particle, which they call NuMOF. Iodized salt has been very successful at preventing iodine deficiency, and many efforts are now underway to create "double-fortified salts" that would also contain iron.
Delivering these nutrients together has proven difficult because iron and iodine can react with each other, making each one less likely to be absorbed by the body. In this study, the MIT team showed that once they formed their iron-containing MOF particles, they could load them with iodine, in a way that the iron and iodine do not react with each other.
In tests of the particles' stability, the researchers found that the NuMOFs could withstand long-term storage, high heat and humidity, and boiling water.
Throughout these tests, the particles maintained their structure. When the researchers then fed the particles to mice, they found that both iron and iodine became available in the bloodstream within several hours of the NuMOF consumption.
The researchers are now working on launching a company that is developing coffee and other beverages fortified with iron and iodine. They also hope to continue working toward a double-fortified salt that could be consumed on its own or incorporated into staple food products.
The research was partially supported by J-WAFS Fellowships for Water and Food Solutions.
Other authors of the paper include Fangzheng Chen, Wenhao Gao, Zhiling Zheng, Tian Wang, Erika Yan Wang, Behnaz Eshaghi, and Sydney MacDonald.
