Iron (Ferrous Sulfate/Bisglycinate)
1. Introduction: Product Overview, Chemistry, and Mechanism of Action
Iron is an essential mineral vital for numerous biological processes in the human body. It is a critical component of hemoglobin, the protein in red blood cells responsible for transferring oxygen from the lungs to the tissues, and myoglobin, which provides oxygen to muscle tissue [1]. Beyond oxygen transport, iron is necessary for physical growth, neurological development, cellular functioning, and the synthesis of certain hormones [1].
Dietary iron exists in two main forms: heme (found in meat, seafood, and poultry) and nonheme (found in plants and fortified foods) [1]. Iron supplements typically contain nonheme iron in various chemical forms. This document focuses on two common supplemental forms: Ferrous Sulfate and Ferrous Bisglycinate.
- Ferrous Sulfate is a traditional, inexpensive, and widely used iron salt. It is a ferrous (Fe²⁺) salt, which is the form of iron most readily absorbed by the intestinal mucosa. However, a large portion of the iron remains unabsorbed in the gastrointestinal (GI) tract, which is a primary cause of common side effects [2].
- Ferrous Bisglycinate (also known as iron bisglycinate chelate) is a newer, chelated form of iron where the iron atom is bound to two molecules of the amino acid glycine. This chelation protects the iron from inhibitors in the gut, leading to higher bioavailability and absorption compared to traditional iron salts [3]. The increased absorption means less unabsorbed iron reaches the lower intestine, which significantly reduces the incidence of GI side effects [2, 4].
The primary mechanism of action for supplemental iron is to replenish the body’s iron stores (ferritin) and increase the production of hemoglobin, thereby treating or preventing iron deficiency (ID) and iron deficiency anemia (IDA) [1].
2. Chemical Composition and Key Bioactive Roles
The key bioactive compound is elemental iron, which is delivered in the form of a ferrous salt or a chelate.
| Compound | Chemical Formula | Bioactive Role | Notes |
|---|---|---|---|
| Elemental Iron (Fe) | Fe | Essential mineral | Central to oxygen transport and cellular metabolism. |
| Ferrous Sulfate | FeSO₄ | Iron salt | A highly soluble and common source of elemental iron (Fe²⁺). |
| Ferrous Bisglycinate | Fe(C₂H₄NO₂)₂ | Iron chelate | Iron (Fe²⁺) bound to two glycine molecules, offering superior bioavailability and GI tolerance. |
| Glycine | C₂H₅NO₂ | Amino acid | The chelating agent in ferrous bisglycinate; also a non-essential amino acid. |
3. Health Benefits
The primary health benefit of iron supplementation is the prevention and treatment of iron deficiency anemia (IDA).
Prevention and Treatment of Iron Deficiency Anemia (IDA)
Iron deficiency is the most common nutritional deficiency worldwide, leading to IDA, which is characterized by low hemoglobin concentrations and reduced red blood cell size [1]. IDA can cause fatigue, weakness, impaired cognitive function, and difficulty concentrating [1]. Supplementation is highly effective in reversing these symptoms by restoring iron stores and hemoglobin levels.
Superior Gastrointestinal Tolerance with Ferrous Bisglycinate
A significant benefit of ferrous bisglycinate over traditional iron salts like ferrous sulfate is its improved tolerability. Oral iron supplementation can cause GI side effects such as constipation, nausea, and bloating in up to 60% of patients, often leading to poor adherence to treatment [2]. These side effects are largely due to unabsorbed iron in the gut causing oxidative stress and inflammation [2].
Ferrous bisglycinate’s chelated structure allows for better absorption, meaning less unabsorbed iron is left in the gut to cause distress. A randomized, double-blind study comparing the two forms in pregnant women found that the frequency of gastrointestinal complaints was significantly lower in the bisglycinate group compared to the sulfate group (P=0.001) [4].
Efficacy in High-Risk Groups (e.g., Pregnancy)
Pregnant women have a significantly increased need for iron (RDA of 27 mg/day) and are a high-risk group for IDA [1]. A randomized trial demonstrated that a lower dose of ferrous bisglycinate (25 mg elemental iron/day) was non-inferior and equally effective as a higher dose of ferrous sulfate (50 mg elemental iron/day) in preventing iron deficiency and anemia during pregnancy [4]. This finding highlights the superior bioavailability of the bisglycinate form, allowing for a lower dose with fewer side effects to achieve the same clinical outcome.
4. Dosage and Usage
Recommended Dietary Allowances (RDAs)
The Recommended Dietary Allowances (RDAs) for iron vary significantly by age and sex, particularly for women of reproductive age [1]:
| Group | RDA (Elemental Iron) |
|---|---|
| Adult Males (19–50 years) | 8 mg/day |
| Adult Females (19–50 years) | 18 mg/day |
| Pregnancy | 27 mg/day |
| Lactation | 9 mg/day |
Supplemental Dosage
For the treatment of diagnosed iron deficiency anemia, therapeutic doses are significantly higher than the RDA and should be determined by a healthcare professional. Common therapeutic dosages range from 50 mg to 100 mg of elemental iron per day.
For prophylactic use or mild deficiency, the following dosages have been studied:
- Ferrous Bisglycinate: 25 mg of elemental iron per day [4].
- Ferrous Sulfate: 50 mg of elemental iron per day [4].
Usage: Iron supplements are typically best absorbed on an empty stomach, but to minimize gastrointestinal side effects, they are often taken with a small amount of food. Taking iron with a source of Vitamin C (ascorbic acid) can enhance nonheme iron absorption [1].
Food Sources
| Source Type | Examples | Iron Form |
|---|---|---|
| Heme Iron | Red meat, poultry, fish | Heme |
| Nonheme Iron | Beans, lentils, spinach, nuts, fortified cereals, enriched bread | Nonheme |
5. Safety and Precautions
Side Effects
The most common side effects of oral iron supplementation are gastrointestinal in nature, including [2, 4]:
- Nausea
- Constipation
- Bloating
- Abdominal pain
- Darkening of the stools
As noted, ferrous bisglycinate is generally associated with a lower incidence and severity of these side effects compared to ferrous sulfate [4].
Contraindications and Warnings
Serious Warning: Accidental Overdose
Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Iron supplements must be kept out of reach of children. In case of accidental overdose, seek medical help immediately [1].
Hereditary Hemochromatosis
Individuals with a genetic condition called hereditary hemochromatosis or other disorders of iron overload should not take iron supplements, as this can lead to excessive iron accumulation in organs, causing severe damage [1].
Tolerable Upper Intake Level (UL)
The Tolerable Upper Intake Level (UL) for iron from supplements and food is 45 mg/day for adults. Chronic intake above the UL can lead to gastrointestinal distress and, in severe cases, more serious health risks [1].
Drug Interactions
Iron supplements can interact with several medications, potentially reducing the absorption or efficacy of either the iron or the drug [1]:
- Levodopa and Levo-thyroxine: Iron can reduce the absorption of these medications.
- Proton Pump Inhibitors (PPIs): These medications reduce stomach acid, which can potentially impair iron absorption.
- Antibiotics: Iron can reduce the absorption of some antibiotics (e.g., tetracyclines and quinolones).
Patients taking any of these medications should consult a healthcare provider before starting iron supplementation.
6. References
[1] Office of Dietary Supplements (ODS). Iron – Health Professional Fact Sheet. National Institutes of Health (NIH). Available at: https://ods.od.nih.gov/factsheets/Iron%20%20-HealthProfessional/ [2] Bloor, S. R., Schutte, R., & Hobson, A. R. (2021). Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota. Microorganisms, 9(6), 1272. Available at: https://www.mdpi.com/2036-7481/12/2/33 [3] Ethical Nutrition. Everything You Need to Know About Chelated Iron. Available at: https://ethical-nutrition.com/blogs/supplements/iron-bisglycinate-explained-everything-you-need-to-know-about-chelated-iron [4] Milman, N., Jønsson, L., Dyre, P., Pedersen, P. L., & Larsen, L. G. (2014). Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial. The Journal of Maternal-Fetal & Neonatal Medicine, 27(8), 759-766. Available at: https://pubmed.ncbi.nlm.nih.gov/24152889/ [5] Duque, X., et al. (2014). Effect of supplementation with ferrous sulfate or iron bis-glycinate chelate on the status of iron and zinc in women of childbearing age in Colombia. Nutrition Journal, 13(1), 71. Available at: https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-13-71Category: Mineral
