Iron Balance: From Absorption to Anemia, Understanding the Key Factors

Iron is vital for the body, forming hemoglobin and aiding oxygen transport. Iron deficiency can cause anemia, but anemia is not always due to low iron intake. This article covers iron absorption, maintaining iron balance, and factors affecting it, besides insufficient intake. It also discusses nutrition and diets to combat iron-deficiency anemia without merely increasing iron intake.

One-third of the global population faces iron deficiency. Iron deficiency progresses through stages, each with specific changes in the body’s iron status. The first stage involves depleting iron stores to compensate for decreasing hemoglobin, leadi#Refng to fatigue and exercise intolerance [1].

As iron stores deplete further, the second stage, “latent iron deficiency” or iron-deficient erythropoiesis, occurs. Labile iron from red blood cell turnover supports normal red blood cell production, but persistent iron losses and inadequate dietary intake can lead to anemia [2].

Anemia, the severe third stage, is marked by low hemoglobin levels and smaller red blood cells with reduced iron content. Laboratory findings include low ferritin and serum iron, increased transferrin, low percent saturation of transferrin, and increased unsaturated iron binding capacity.

Iron Absorption and Iron Homeostasis

In the body, iron mainly exists as heme, with daily iron balance around 2mg. Dietary iron is either “non-heme” or “heme.” Plant-based foods, like grains and veggies, are iron-rich but less efficiently absorbed due to their mainly trivalent iron (Fe3+). Stomach acidity aids conversion to absorbable ferrous iron (Fe2+), while alkaline conditions favor Fe3+. Vitamin C enhances iron absorption, but low stomach acid or acid-suppressing meds hinder it. Compounds like phytic acid, oxalates, tannins, and polyphenols in foods like green tea reduce iron absorption in plant-based diets. In contrast, heme iron from animals is easily absorbed without ion conversion, making it more bioavailable [3].

Iron absorption mainly occurs in the duodenum, with 15% absorption there, while the large intestine absorbs about 14% of dietary iron. Iron-deficient bodies can increase absorption to 35%, while excess iron leads to only 5% absorption.

Excessive iron causes health risks. The body regulates absorption in multiple steps: dietary iron settles in intestinal cells, where a “mucosal block” process controls absorption. Only when iron attaches to “ferroportin” can it leave intestinal cells, enter the bloodstream via “transferrin,” and reach various destinations. Cells reduce transferrin receptor expression when iron isn’t needed. Hepcidin further reduces iron transport from the intestine when stores are sufficient.

The iron absorption process relies on co-factors, including copper-dependent enzymes like ceruloplasmin and ferroxidase. Adequate copper is essential for transferring iron from ferritin to the membrane iron transport protein. Excess iron intake, particularly from heme sources or supplements, can increase oxidative stress and raise the risk of aging and chronic diseases.

Gut bacteria impact iron absorption, with antibiotics reducing its efficiency. Excessive dietary iron disrupts gut microbiota balance, increasing Salmonella infections and reducing beneficial probiotics in infants, causing gut inflammation. High heme iron diets decrease gut microbiota diversity. Approximately 13% of the elderly have excess iron, posing health risks. Thus, moderation is key, as more dietary iron doesn’t necessarily mean better health.

Animal studies reveal antibiotics can reduce iron absorption. In a 2016 study, germ-free mice had more iron absorption carriers in their intestinal cells but lacked proper iron storage. Colonizing their intestines with bacteria resolved their iron deficiency, demonstrating the influence of gut microbiota on iron balance [4].

Micronutrients Associated with Anemia

Iron supplementation doesn’t always solve anemia, as other factors like autoimmune issues, B12 deficiencies, and genetic conditions can be causes. “Microcytic anemia” and “iron-deficiency anemia” are not just about iron levels.

Vitamin A boosts iron absorption and reduces anemia risk by 26%. Anemic individuals with vitamin A deficiency can see improvements with supplementation [5-6].

Vitamin B2 affects iron absorption and transport, increasing anemia risk, especially in pregnant women. Combining vitamin A and B2 with iron and folate is more effective [7-9].

Vitamin B6 is crucial for heme synthesis and hematopoiesis. B6 deficiency can lead to macrocytic anemia. Supplementing with B6 can improve iron-deficiency anemia, especially in cases of unresponsive microcytic anemia during pregnancy [10-11].

Copper is crucial for iron metabolism and red blood cell production. It enables iron ion oxidation and binding to transport proteins for circulation. Copper deficiency leads to abnormal red blood cell production and anemia [12].

Dietary Factors

Research suggests that more heme iron from meat can increase oxidative stress, while higher non-heme iron intake from plant sources offers protection, with elevated serum ferritin reflecting this correlation[13].

In a 2020 animal study, mice on a high-fat diet for four weeks developed insulin resistance, gained weight, and increased white adipose tissue. As fat tissue grew, liver iron levels dropped, leading to iron deficiency by week 16. This demonstrates how an unhealthy diet can trigger insulin resistance, weight gain, and eventual iron deficiency [14].

Heme iron in red meat is more absorbable, but a Mediterranean diet with less red meat and more fish, whole grains, vegetables, and fruits enhances iron absorption. In a 2009 clinical trial, children on the Mediterranean diet absorbed and stored double the iron compared to the Western diet, making iron deficiency less likely [15].

Onions and garlic, along with phytate-rich grains and legumes, increase iron absorption by 73% with just small amounts (0.5g of garlic and 3g of onion per 10g of grains) [16]. Lime juice enhances iron absorption in grains and legumes by 86% [17].

Phytates, while reducing iron absorption, may benefit diabetes by lowering protein glycation and AGEs. In a 2018 trial, phytate supplementation in type 2 diabetes patients improved HbA1c levels [18].

Excess iron is linked to neurological disorders like Parkinson’s disease [19]. Phytates can chelate iron, potentially benefiting Parkinson’s disease [20].

Summary

Iron deficiency is common but not solely due to low iron intake:

Iron metabolism is complex, involving coenzymes and micronutrients. Factors like low stomach acid, acid-suppressing drugs, or antibiotics can affect iron absorption.

Excess iron can lead to oxidative stress and gut microbiota imbalance, raising chronic disease risks.

Excessive heme iron from meat can increase chronic disease risk. Moderation is key.

Plant-based iron, combined with vitamin C and acidic foods, boosts absorption. Healthy food combos increase iron utilization.

Balance is crucial as both iron deficiency and excess can harm health.