The shift toward plant-based eating has long been accompanied by concerns about the “poor” bioavailability of non-heme iron. While traditional education suggests that vegans are at a significant disadvantage compared to omnivores, emerging research is beginning to tell a more nuanced story of physiological adaptation.
In this Ask the Expert conversation, we speak with the lead authors, Dr Miguel López-Moreno, of the 2025 study “Dietary adaptation of non-heme iron absorption in vegans: a controlled trial.” Facilitated by Sabina Aliieva, RD Candidate, the discussion examines how long-term vegan diets may enhance the body’s efficiency in absorbing plant-based iron.
Using pistachios as a whole-food iron source, the study challenges the idea of bioavailability as a fixed property of foods, instead highlighting a dynamic, regulated process that helps habitual vegans maintain adequate iron status.
Q: The “poor bioavailability” of plant-based iron is a cornerstone of dietetic education. What led you to believe the current model of static bioavailability was incomplete and needed to be tested through the lens of adaptive regulation?
A: What initially drew our attention came from a previous review conducted by our group, in which we synthesized the available evidence on the relationship between plant-based diets and iron status. Across observational and population-based studies, a consistent pattern emerged: despite relying almost exclusively on non-heme iron, individuals following long-term vegan diets did not show a markedly higher prevalence of iron deficiency anemia compared with omnivorous populations.
This finding created a clear physiological paradox if plant-based iron is assumed to be intrinsically and uniformly “poorly bioavailable” in a fixed sense. Rather than viewing bioavailability as a static property of foods, we approached it as a dynamic interaction between diet and the body’s regulatory systems. Iron absorption is tightly controlled by physiological signals of need, particularly through the hormone hepcidin. Based on the patterns observed in our initial review, we hypothesized that habitual exposure to a non-heme–based iron pattern could lead to regulatory adaptations that enhance absorption efficiency over time.
Q: Using 150g of pistachios provides a significant “real-world” dose of non-heme iron. Why was a whole-food source like pistachios preferable to a purified iron supplement for this trial, and do you believe the fats or proteins in the nuts played a synergistic role in the absorption you measured?
A: Our primary goal was to study iron absorption as it occurs in a real dietary context, not under pharmaceutical conditions. A purified iron supplement isolates the mineral from the food matrix, whereas whole foods reflect how people actually consume iron in daily life. Pistachios provided a meaningful dose of non-heme iron while maintaining the complexity of a plant-based food matrix. Our study was designed to capture the integrated physiological response to a food, rather than isolate a single nutrient effect.
Q: Despite higher iron absorption in vegans, baseline iron markers such as ferritin and hemoglobin were similar between groups. How should clinicians interpret this apparent paradox?
A: We interpret this as evidence of effective physiological regulation rather than a paradox. Ferritin and hemoglobin reflect relatively stable iron status over time, while our measurements captured acute absorption dynamics. Vegans in our study absorbed more iron in response to the test meal, yet their long-term iron status markers were similar to omnivores. This suggests that the body adjusts absorption efficiency to maintain iron within a healthy range, even when dietary bioavailability is lower. In other words, similar iron status can be achieved through different regulatory strategies rather than identical absorption rates.
Q: Hepcidin played a central role in your findings. Can you explain how lower hepcidin levels in vegans enhance non-heme iron absorption, and why this mechanism is so important?
A: Hepcidin is the master regulator of iron homeostasis. It controls the activity of ferroportin, the protein that exports iron from intestinal cells into the bloodstream. When hepcidin levels are high, ferroportin is internalized and degraded, reducing iron absorption. When hepcidin levels are low, ferroportin remains active, allowing more dietary iron to enter circulation. In our study, vegans had significantly lower baseline hepcidin levels, and hepcidin was a strong predictor of iron absorption in this group. This suggests that long-term exposure to a plant-based, non-heme iron–rich diet may downregulate hepcidin, effectively “opening the gate” for increased absorption to compensate for lower dietary bioavailability. This mechanism is central because it allows the body to match iron uptake to physiological demand.
Q: The finding that ferritin and hemoglobin were similar despite significantly higher acute absorption is fascinating. Does this suggest that vegans are not just “absorbing more”, but perhaps “utilizing iron more efficiently” or maintaining lower, yet more functional, iron pools?
A: Our data point more strongly toward regulated absorption rather than enhanced cellular utilization per se. We did not observe differences in soluble transferrin receptor levels, which are often used as a marker of tissue iron demand and utilization. This suggests that the primary adaptation we detected occurs at the level of intestinal absorption rather than downstream cellular uptake. However, the fact that ferritin and hemoglobin were maintained within similar ranges despite different absorption dynamics supports the idea that vegans may operate with tightly regulated, functionally adequate iron pools rather than simply accumulating larger stores.
Q: How should an RD explain a “low-normal” ferritin to a concerned vegan patient in light of your data?
A: A low-normal ferritin value does not automatically indicate dysfunction, especially in the absence of anemia or symptoms. Our findings suggest that individuals following a long-term vegan diet may compensate for lower iron stores by increasing absorption efficiency when needed. For patients, this means that ferritin should be interpreted alongside hemoglobin, clinical symptoms, dietary intake, and overall health status. Rather than focusing on a single number, clinicians should consider whether the body is maintaining adequate functional iron, which often reflects effective regulation rather than deficiency.
Q: While your study focused on healthy young adults, these results are incredibly hopeful for high-demand groups. Do you suspect that the “hepcidin-lowering” adaptation would be even more pronounced in women of reproductive age or endurance athletes, who have a naturally higher physiological drive for iron?
A: Physiologically, that is a strong possibility, and there is already experimental evidence supporting adaptive responses under conditions of higher iron demand or suboptimal iron stores. For example, a study in young women with low iron stores has shown that habitual consumption of high-phytate diets can attenuate the inhibitory effect of phytate on non-heme iron absorption, leading to significantly greater postprandial iron uptake over time.
Hepcidin is naturally suppressed in states of increased iron demand, such as menstruation, pregnancy, hypoxia, and sustained endurance training. These conditions favor the maintenance of active ferroportin at the intestinal level, thereby facilitating greater dietary iron transfer into circulation. In this context, it is plausible that these regulatory mechanisms are activated to an even greater extent in populations at higher risk of iron insufficiency, such as women of reproductive age and endurance athletes.
At the same time, this adaptive capacity is not unlimited. There are physiological thresholds beyond which regulatory mechanisms alone may not be sufficient to fully compensate for a pronounced or prolonged iron deficit. Under such conditions, dietary strategies, fortification, or supplementation may still be necessary to restore and maintain adequate iron status. Our findings therefore support a model of flexible but bounded regulation, rather than unlimited physiological compensation.
Q: If you could rewrite the chapter on iron in a clinical nutrition textbook, how would you succinctly summarize the relationship between a long-term vegan diet and the body’s iron-regulatory flexibility?
A: Iron bioavailability is not determined solely by the food itself, but by a dynamic process of physiological regulation. In individuals following long-term plant-based diets, the body appears capable of adapting by modulating key regulatory pathways—particularly hepcidin—to enhance non-heme iron absorption and maintain functional iron status despite lower dietary bioavailability.
References
Armah SM, Boy E, Chen D, Candal P, Reddy MB. Regular Consumption of a High-Phytate Diet Reduces the Inhibitory Effect of Phytate on Nonheme-Iron Absorption in Women with Suboptimal Iron Stores. J Nutr. 2015 Aug;145(8):1735-9. doi: 10.3945/jn.114.209957. Epub 2015 Jun 3. PMID: 26041677.
López-Moreno M, Castillo-García A, Roldán-Ruiz A, Viña I, Bertotti G. Plant-Based Diet and Risk of Iron-deficiency Anemia. A Review of the Current Evidence and Implications for Preventive Strategies. Curr Nutr Rep. 2025 Jun 18;14(1):81. doi: 10.1007/s13668-025-00671-y. PMID: 40528105; PMCID: PMC12174276.
