What happens if I eat too much iron, have too much heme iron stored, or eat too much heme iron?
In simple terms, heme iron acts like a troublemaker at a party, stirring up chaos by causing oxidative damage to cells due to its unstable nature, similar to how a troublemaker might disrupt a social gathering. On the other hand, non-heme iron is like a calm and reliable friend who doesn’t cause any trouble, providing essential nutrients without any harmful side effects. Non-heme iron could be called vegan iron. There is no such thing as vegan heme iron because heme iron is only in animal sources. Animals convert plant based non-heme iron (Fe3+) into animal heme iron ( Fe2+).
For the technically inclined read on. The body can directly utilize heme iron which is contained in animal foods. But your body prefers to regulate the conversion from vegetable sources of non-heme iron to heme iron rather than directly taking in heme iron. This is because excessive levels of heme iron in the body are damaging due to iron’s nature as a redox transitional metal. Iron participates in the following reactions to generate reactive oxygen species, ie ROS such as •OH, OH −, HO2•, H2O.
The reason that heme iron is less advantageous to the body comes down to the velocity of the following reactions which are making the oxidative species, called the Fenton reaction:
HEME (Ferrous) IRON:
Fe2+ + H2O2→Fe3+ + •OH + OH −, velocity (k) = 40−80 L/mol per sec
NON-HEME (Ferric) IRON:
Fe3+ + H2O2→ Fe2+ + HO2• + H+, k = 9×10−7 L/mol per sec
“In Fenton’s reaction, the ferrous and/or ferric cation decomposes catalytically hydrogen peroxide to generate powerful oxidizing agents, capable of degrading a number of organic and inorganic substances (“Chapter 11 – Table Olives,” 2006).”
As you can see from the quantities produced the first reaction occurs extremely fast while the second is quite slow (Scarth, 2004). This is significant because it means that the reaction with the heme iron is making 44,400,000 to 88,900,000 times more oxidants in the body than a reaction with non-heme iron.
If your body is acidic (lower pH) from eating too much animal protein or sugar/refined carbohydrates and not enough vegetables, the reaction with heme iron will occur more readily, making even more oxidants.
What this means is that when you eat heme iron and it is not utilized immediately, this can result in the formation of hydroxyl radicals or other damaging radicals in the body, otherwise referred to as ROS (Reactive Oxidative Species). Oxidative stress from hydroxyl radicals can have deleterious effects on the body, from DNA expression to general inflammation and aging. Iron is a redox-reactive transitional metal that causes the formation of these damaging hydroxyl radicals.
You should be aware that ROS are needed in small amounts in pregnancy as they participate in signal transduction to assist with proliferation, differentiation, and apoptosis. But a nascent embryo does not have a strong antioxidant defense system in place (neither does the sperm or the egg). Consuming too much heme iron is going to proliferate the Fenton reaction and cause harm to your fetus. This is especially true during the first trimester when your embryo is more delicate and your iron needs lower.
It is crucial to be aware that the effects of excess heme iron extend beyond harming other species; they can also disrupt entire pathways and hormone systems within the human body. For instance, dysregulation of iron absorption and storage can lead to oxidation or impair glucose metabolism. When heme iron accumulates excessively or is stored in excess fat, it can inflict damage on various bodily pathways, particularly those associated with insulin secretion and pancreatic function (Rajpathak et al., 2006) (Bowers et al., 2011).
This damage can ultimately result in diseases such as Type 2 diabetes and gestational diabetes. Redox-reactive heme iron can harm the pancreatic cells responsible for insulin production, thus adversely impacting glucose metabolism in the mother’s body (Rajpathak et al., 2006). Moreover, exposure to excessive heme iron at any point in time can also impair these pathways in an unborn baby, increasing the risk of diabetes or heart disease in the child later in life (Rajpathak et al., 2006).
Numerous studies have demonstrated a positive correlation between the development of gestational diabetes and high iron stores (Zaugg et al., 2022), although the exact underlying mechanisms remain to be fully understood. And it’s not limited to diabetes alone. A diet rich in heme iron from meat sources can lead to an overproduction of cortisol, pancreatic damage, and an elevated risk of colon cancer (Lowensohn et al., 2016).
On the other hand, non-heme iron is not oxidative or reactive. And non-heme iron can be stored in your fat cells safely as this species of iron does not cause oxidative damage to the body. This is because the body can regulate needed levels of intake for plant non-heme iron but cannot adapt to heme iron intake when the body has sufficient iron stores. Thus, it is best to get most of your iron from non-heme sources plant sources and allow the body to regulate the intake by converting it to heme iron as needed (Lowensohn et al., 2016).
Another consideration of the effects of increased levels of free radicals due to heme iron’s interaction with oxygen and proton molecules in your body. This may be one reason that meat eaters appear older than vegans/vegetarians because it is well known that free radical damage is associated with aging. Consumption of mostly plant based iron will reduce aging, and research shows that higher consumption of non-heme iron than heme iron also results in better health outcomes such as improved fertility (Chavarro et al., 2006).
While the body does have mechanisms to prevent excess oxidation, you can still overload your antioxidant abilities. There are many other potential negative effects of excessive iron induced ROS including ROS induced brain and body injury or liver damage from hepatic iron overload (Grzeszczak et al., 2020). Liver cirrhosis, liver fibrosis (due to decrease in superoxide dismutase), hypertriglyceridemia, and hypercholesterolemia can all be caused by over consuming heme iron from steak (Grzeszczak et al., 2020). Surprisingly you can even get anemia from excess iron interfering with copper metabolism (10X normal Fe supply) (Grzeszczak et al., 2020).
It is merited to explore some of the biological reasons for the gross amount of damage that can be caused by excess heme iron. For one, the body cannot adapt to a higher intake heme-iron when the body has sufficient stores (Roughead & Hunt, 2000). Additionally, the body does not have any mechanisms to eliminate excess iron in the body in the same way it has for other nutrients (see “Solubility,” above). Because high levels of bioavailable (heme) iron are damaging to the tissue the body has mechanisms in order to tightly regulate iron absorption. For non-heme iron this regulation works very well, to 1% specificity (Roughead & Hunt, 2000). But for heme iron the inverse correlation of a reduction of absorption concomitant with an increased iron store is not as consistent. As iron stores grow the body is less effective at decreasing the amount of heme iron absorbed. The implication of this is that you can greatly exceed your iron stores when consuming heme iron, but not non-heme (Roughead & Hunt, 2000).
Therefore, it is best to get the majority of your iron from non-heme sources and allow your body to regulate your intake by converting it to heme iron as needed. The idea that we must eat meat to get the heme iron is old dogma and outdated by the latest science. Additionally a high meat diet contributes to other negative effects in the body such as hyper-secretion of cortisol and other aforementioned body breakdown in functions (Lowensohn et al., 2016).
Ferroptosis
Ferroptosis refers to cell death caused by iron-induced oxidation. This is different than just damage from oxidation as discussed above. Excessive ferrous (Fe2+/heme) iron availability can lead to cellular damage, either directly or by disrupting antioxidative and anti-inflammatory processes. Recent research has shed light on the role of ferroptosis in events in pregnancy that damage your baby, such as pre-eclampsia, gestational diabetes, trophoblast injury, and preterm birth (Zaugg et al., 2022). Trophoblasts, which are vital placental cells, are particularly susceptible to ferroptosis due to their high iron content (Knöfler et al., 2019) (Zaugg et al., 2022). These complications often occur early in pregnancy at a time when these cells play a crucial role in establishing channels between the fetus and the mother’s body. Trophoblasts evolve into placental cells and hormone-secreting cells that regulate pregnancy progression, fetal growth, nutrient mobilization and saturation, and lactation (Knöfler et al., 2019). Hence, it’s essential to prioritize plant-based iron intake, especially during the first trimester, to prevent excessive (Fe2+/ferrous/heme iron) iron availability from harming these critical cells.
Ferroptosis can also impair placental function, affecting nutrient uptake and oxygenation for the baby (Zaugg et al., 2022). Consuming excessive heme iron from animal-based sources, such as steak, may lead to oxidative damage on various scales. Oxidative stress can originate from multiple sources, and while the body can manage it to some extent, it struggles to eliminate excess iron in a fetus inundated with high iron levels. Studies have even linked ferroptosis to first-trimester miscarriages (Inoue et al., 2021).
Gestational diabetes risk can also increase due to ferroptosis, especially when combined with elevated blood sugar levels (Zaugg et al., 2022). If you develop gestational diabetes, it’s advisable to consume four Brazil nuts daily and possibly consider a selenium supplement to counteract iron dysregulation and ferroptosis (Tan et al., 2001).
Data indicates that a high-heme iron diet is associated with disease
Research indicates that the consumption of heme iron, primarily derived from animal sources, is associated with the development of lifestyle diseases such as Type 2 diabetes (Bačić et al., 2010).
To illustrate the notion that daily meat consumption is necessary to meet your body’s daily iron requirements oversimplifies the complex picture, let us use an analogy with fat and weight gain. Having sufficient body fat stores and a healthy BMI of 19 – 24 when planning to gain 25-35 pounds during pregnancy doesn’t lead to the belief that you must consume more fat daily to nourish your future breastfeeding baby. Such thinking is elementary, as science recognizes the multifaceted nature of these processes.
For instance, hormones like insulin play a role in fat storage, and foods like sugars and carbohydrates have a more significant impact on fat storage than the consumption of (healthy plant-based) fats. Similarly, the idea that daily meat consumption is essential to meet your body’s iron requirements is overly simplistic. In the case of heme iron, excessive intake can lead to an accumulation of this potent pro-oxidant, which can negatively affect various bodily pathways, particularly those related to insulin secretion and pancreatic function. This occurs because the body cannot adjust its heme iron intake when it already has sufficient stores and any heme iron that is not utilized upon absorption can interact with oxygen molecules in a negative manner (Roughead & Hunt, 2000).
Check out this recipe for a high iron plant for 50% of your iron in a 700 calorie, 21 g protein serving:
High Protein Cookie Bars: http://thecarmencooks.com/staging/3924/cacao-chip-high-protein-cookie-bars-and-biotins-role-in-making-energy/
References
(2006). Chapter 11 – Table Olives. Waste Management Series. M. Niaounakis and C. P. Halvadakis, Elsevier. 5: 295-319.
Scarth, L. L. (2004). “Encyclopedia of Energy.” Reference Reviews 18(8): 34-36.
Rajpathak, S., et al. (2006). “Iron intake and the risk of type 2 diabetes in women: a prospective cohort study.” Diabetes care 29(6): 1370-1376.
Bowers, K., et al. (2011). “A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus.” Diabetes care 34(7): 1557-1563.
Zaugg, J., et al. (2022). “Materno-fetal iron transfer and the emerging role of ferroptosis pathways.” Biochemical pharmacology: 115141.
Knöfler, M., et al. (2019). “Human placenta and trophoblast development: key molecular mechanisms and model systems.” Cellular and Molecular Life Sciences 76: 3479-3496.
Inoue, R., et al. (2021). “Role of heme oxygenase-1 in human placenta on iron supply to fetus.” Placenta 103: 53-58.
Tan, M., et al. (2001). “Changes of serum selenium in pregnant women with gestational diabetes mellitus.” Biological trace element research 83: 231-237.
Bačić, I., et al. (2010). “Efficacy of IP6+ inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study.” Journal of Experimental & Clinical Cancer Research 29(1): 1-5.
Roughead, Z. K. and J. R. Hunt (2000). “Adaptation in iron absorption: iron supplementation reduces nonheme-iron but not heme-iron absorption from food.” The American Journal of Clinical Nutrition 72(4): 982-989.
