Effect of almond consumption on iron status in inflammatory states

Project Summary/Abstract
Anemia of inflammation (AI) is the second most prevalent form of anemia. It is caused by chronic inflammation
associated with aging and chronic diseases such as cancer and rheumatoid arthritis. While people with AI have
sufficient body iron, increased sequestration due to elevated concentration of the protein hepcidin leads to
insufficient circulating iron for red blood cell synthesis. AI is also exacerbated by the destruction of red blood
cells (RBCs) by macrophages due to inflammation. Unfortunately, current therapies, including blood transfusion,
do not reduce the elevated concentrations of hepcidin; furthermore, transfusion increases risk of excess iron,
which can cause adverse effects. While experimental drugs targeting hepcidin are being developed, their long-
term adverse effects are not known, warranting new non-pharmaceutical approaches. Our long-term goal is to
identify dietary approaches for mitigating AI. Consumption of almonds may mitigate AI by different mechanisms;
these include (i) reducing inflammation, (ii) altering the gut microbiome composition, and (iii) improving
robustness of RBCs by increasing their vitamin E content, which protects them from oxidative damage. In this
proposed R15 study, we will test the overall hypothesis that almond consumption will improve iron status in
inflammatory states, using obese and aging mice. We chose these mouse models because both conditions are
associated with inflammation, increased hepcidin, and impaired iron status markers. Our preliminary 8-week
study using a mouse model of obesity provided suggestive evidence that regular almond intake reduced hepcidin
and improved iron concentrations in plasma; however, a longer-duration study is needed for conclusive evidence.
Our proposed study will investigate the effects of a 24-week high-fat diet with almonds (15% calories from
almonds) on circulating iron concentrations in C57BL/6 mice. We hypothesize this treatment will significantly
improve iron status compared to high-fat and low-fat diets. We will also investigate whether this intake of almonds
can mitigate aging-related AI in C57BL/6 mice, a frequently used model in aging research. We will further probe
underlying mechanisms that may influence these effects, including changes in gut microbiota composition,
hepcidin concentrations, and the antioxidant system in RBCs. If our hypotheses are borne out, we will
demonstrate the potential of almonds as a dietary approach to mitigating AI. Furthermore, this work would be
the first to elucidate the contributions of gut microbiota and RBC antioxidant system in mitigating AI.