Ferrous Sulfate: Uses, Dosage & Side Effects

Generic name: ferrous sulfate [ FARE-us-SUL-fate ]
Brand names: Feosol, Fer-In-Sol, Ferrousal, Slow Fe, Slow Release Iron,
… show all 23 brands
Mol-Iron, Feratab, Ferrospace, Fero-Gradumet Filmtab, Fer-in-Sol, Ferra T.D. Caps, Ferro-Bob, Chem-Sol, Fer-Gen-Sol, FeroSul, Ferro-Time, Yieronia, Lydia E. Pinkham, Ferra-TD, Fe 50, Feosol Iron, MyKidz Iron 10, Fer-Iron

Dosage forms: oral delayed release tablet (324 mg; 325 mg), oral elixir (220 mg/5 mL), oral liquid ((as elemental iron) 15 mg/mL,
… show all 7 dosage forms
300 mg/5 mL), oral tablet (200 mg; 325 mg), oral tablet, extended release ((as elemental iron) 45 mg, 160 mg)

Drug class: Iron products

Medically reviewed by Sanjai Sinha, MD. Last updated on Jun 27, 2023.

What is ferrous sulfate?

Ferrous sulfate is a type of iron. You normally get iron from the foods you eat. In your body, iron becomes a part of your hemoglobin and myoglobin. Hemoglobin carries oxygen through your blood to tissues and organs. Myoglobin helps your muscle cells store oxygen.

Ferrous Sulfate is an essential body mineral.

Ferrous sulfate is used to treat iron deficiency anemia (a lack of red blood cells caused by having too little iron in the body).

Warnings

Ask a doctor or pharmacist if it is safe for you to take ferrous sulfate if you have iron overload syndrome, hemolytic anemia (a lack of red blood cells), porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system), thalassemia (a genetic disorder of red blood cells), if you are an alcoholic, or if you receive regular blood transfusions.

Seek emergency medical attention if you think you have used too much of this medicine, or if anyone has accidentally swallowed it. An overdose of iron can be fatal, especially in a young child.

Overdose symptoms may include nausea, severe stomach pain, bloody diarrhea, coughing up blood or vomit that looks like coffee grounds, shallow breathing, weak and rapid pulse, pale skin, blue lips, and seizure (convulsions).

Take ferrous sulfate on an empty stomach, at least 1 hour before or 2 hours after a meal. Avoid taking antacids or antibiotics within 2 hours before or after taking ferrous sulfate.

Ferrous sulfate is only part of a complete program of treatment that may also include a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you should eat to make sure you get enough iron from both your diet and your medication.

Before taking this medicine

Ask a doctor or pharmacist if ferrous sulfate is safe to use if you have ever had:

• iron overload syndrome;

• a red blood cell disorder such as thalassemia; or

• a condition for which you receive regular blood transfusions.

Ask a doctor before using this medicine if you are pregnant or breastfeeding.

Do not give ferrous sulfate to a child without medical advice.

How should I take ferrous sulfate?

Use ferrous sulfate exactly as directed on the label, or as prescribed by your doctor.

Take on an empty stomach, at least 1 hour before or 2 hours after a meal.

Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Swallow the tablet whole and do not crush, chew, or break it.

You may need to follow a special diet. Follow all instructions of your doctor or dietitian. Learn about the foods you should eat or avoid.

Store at room temperature, away from moisture and heat.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Get emergency medical help if a child has accidentally swallowed a tablet. An overdose of iron can be fatal to a young child.

Overdose symptoms may include severe vomiting, coughing up blood, bloody diarrhea, urinating less, thirst, dry skin, muscle cramps, dizziness, or fainting.

What should I avoid while taking ferrous sulfate?

Avoid taking other iron supplements. Do not take any vitamin or mineral supplements without asking a doctor or pharmacist.

Ferrous sulfate side effects

Get emergency medical help if you have signs of an allergic reaction to ferrous sulfate: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe stomach pain or vomiting;

• cough with bloody mucus or vomit that looks like coffee grounds;

• fever; or

• bloody or tarry stools.

Common ferrous sulfate side effects may include:

• diarrhea, constipation;

• nausea, stomach pain;

• green-colored stools; or

• loss of appetite.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ferrous sulfate dosing information

Usual Adult Dose for Iron Deficiency Anemia:

Initial dose: 600 mg/day ferrous sulfate (120 mg/day elemental iron) for 3 months
-Give in divided doses (1 to 3 times daily)

Usual Adult Dose for Anemia Associated with Chronic Renal Failure:

Initial dose: 1000 mg/day ferrous sulfate (200 mg/day elemental iron) orally in divided doses (1 to 3 times daily)

Comments:
-If goals are not met with oral iron after 1 to 3 months, consider IV iron supplementation.
-Smaller daily doses may be better tolerated.

Usual Adult Dose for Vitamin/Mineral Supplementation:

Initial dose: 1 tablet orally once a day

or

Initial dose: 30 to 90 mg/day ferrous sulfate (FeSO4) (6 to 18 mg/day elemental iron) orally, in divided doses (1 to 3 times daily)

51 and over: 25 to 40 mg/day FeSO4 (5 to 8 mg/day elemental) orally, in divided doses (1 to 3 times daily)

Usual Pediatric Dose for Iron Deficiency Anemia:

0 to 5 years: 15 to 30 mg/kg/day ferrous sulfate (FeSO4) (3 to 6 mg/kg/day elemental iron)
5 to 12 years: 300 mg FeSO4 (60 mg/day elemental)
12-18 years male: Two 300 mg FeSO4 (60 mg elemental) tablets orally daily
12-18 years female: 300 to 600 mg/day FeSO4 (60 to 120 mg/day elemental)
-Give in divided doses (1 to 3 times daily)

Usual Pediatric Dose for Vitamin/Mineral Supplementation:

Preterm infant (less than 37 weeks gestation), 0 to 12 months: 10 mg/kg/day ferrous sulfate (FeSO4) (2 mg/kg/day elemental iron)
0 to 6 months: 1 to 1. 35 mg/day FeSO4 (0.2 to 0.27 mg/day elemental)
7 to 12 months: 35 to 55 mg/day FeSO4 (7 to 11 mg/day elemental)
1 to 3 years: 20 to 45 mg/day FeSO4 (4 to 9 mg/day elemental)
4 to 8 years: 20 to 50 mg/day FeSO4 (4 to 10 mg/day elemental)
9 to 13 years: 30 to 40 mg/day FeSO4 (6 to 8 mg/day elemental)
14 to 18 years: 40 to 75 mg/day FeSO4 (8 to 15 mg/day elemental)
-Give in divided doses (1 to 3 times daily)

or

Tablets (325 mg FeSO4, 65 mg elemental iron)
12 years and older: 1 tablet orally once a day

What other drugs will affect ferrous sulfate?

Take your ferrous sulfate dose 2 to 6 hours before or after taking any of the following:

• an antacid;

• an antibiotic; or

• a laxative.

This list is not complete. Other drugs may interact with ferrous sulfate, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Frequently asked questions

• What is the typical dose of ferrous sulfate?

More about ferrous sulfate

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• Drug class: iron products
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Patient resources

• Patient Information
• Iron Tablets and Capsules
• Ferrous Sulfate Drops
• Ferrous Sulfate Liquid

Other brands

Feosol Original, Fe Caps, Fer-Gen-Sol, Feratab

Professional resources

• Prescribing Information

Related treatment guides

• Iron Deficiency Anemia
• Anemia Associated with Chronic Renal Failure
• Vitamin/Mineral Supplementation during Pregnancy/Lactation
• Vitamin/Mineral Supplementation and Deficiency

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use ferrous sulfate only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Copyright 1996-2023 Cerner Multum, Inc. Version: 5.01.

Benefits, Uses, Side Effects, and More

The iron supplement ferrous sulfate is an iron salt with the chemical formula FeSO₄.

Iron salts are one type of the mineral iron. People often use them as a supplement to treat iron deficiency.

Ferrous sulfate is also called iron sulfate, green vitriol, and iron vitriol.

This article is an overview of ferrous sulfate, its benefits and side effects, and how you can use it to treat and prevent iron deficiency.

Ferrous sulfate is just one of many forms of the metal element iron.

In its natural state, the solid mineral resembles small crystals. The crystals are typically a shade of yellow, brown, or bluish-green — hence why ferrous sulfate is sometimes called green vitriol (1).

Supplement makers use multiple types of iron in dietary supplements. Aside from ferrous sulfate, the most common are ferrous gluconate, ferric citrate, and ferric sulfate.

Most types of iron in supplements are in one of two forms — ferric or ferrous. This depends on the chemical state of the iron atoms.

The body absorbs ferrous forms of iron better than ferric forms. Thus, healthcare providers often consider ferrous forms, including ferrous sulfate, to be the best choice for iron supplements (2, 3, 4, 5).

Summary

Dietary iron supplements often use ferrous sulfate, a solid crystalline form of the mineral iron.

The primary benefit of taking ferrous sulfate supplements is to maintain normal iron levels in the body.

Doing so may prevent you from experiencing iron deficiency, as well as the range of mild to severe side effects that often accompany it.

Here’s a closer look at the benefits of taking ferrous sulfate supplements.

Helps maintain normal blood iron levels

Iron is one of the most common elements on earth, and it’s an essential mineral. That means people need to consume it in their diet for optimal health.

The body primarily uses iron as part of the red blood cell proteins myoglobin and hemoglobin, which are essential for transporting and storing oxygen (6).

Iron also plays an important role in the formation of hormones, the health and development of the nervous system, and basic cell functioning (6).

Although many people consume iron as a dietary supplement, you can also find it naturally in many foods, including beans, spinach, potatoes, tomatoes, and particularly meat and seafood, including oysters, sardines, poultry, and beef (6).

Some foods, such as fortified breakfast cereals, are not naturally high in iron, but manufacturers add iron to make them a good source of this mineral (6).

Many of the highest sources of iron are animal products. Therefore, vegans, vegetarians, and people who do not consume many iron-rich foods as a part of their normal diet may benefit from taking ferrous sulfate iron supplements to help maintain their iron stores (7).

May prevent symptoms of iron deficiency

Taking ferrous sulfate supplements is a simple way to treat, prevent, or reverse low blood iron levels.

Preventing iron deficiency not only ensures that your body has enough of the essential nutrient to continue functioning properly but also can help you avoid many of the unpleasant side effects of low iron levels.

Some of the most notable side effects of low iron levels include (6, 8, 9, 10):

• fatigue
• headaches
• feeling weak
• low energy levels
• difficulty concentrating
• difficulty thinking clearly
• hair loss
• brittle nails
• upset stomach
• poor immunity
• heart palpitations
• restless leg syndrome
• shortness of breath
• the inability to regulate body temperature
• pica, an urge to eat nonfood items, such as paint or soap

This is a general overview — not a comprehensive list — of all the symptoms of low iron levels.

Symptoms may worsen as an iron deficiency progresses from mild to severe.

Used to treat iron deficiency anemia

Anemia is a condition that occurs when your blood has low amounts of red blood cells or hemoglobin (11).

Because iron is a critical part of the red blood cells responsible for transporting oxygen throughout the body, having iron deficiency is one of the most common causes of anemia (9, 12, 13).

Iron deficiency anemia (IDA) is a severe form of iron deficiency that has significant effects on the human body and may cause some of the more serious symptoms associated with iron deficiency.

One of the most common and effective treatments for IDA is taking an oral iron supplement, such as ferrous sulfate (14, 15).

Might improve surgical outcomes

Multiple research studies have cited having iron deficiency as a risk factor for increased rates of complications and mortality following surgery.

One study looked at the outcomes for 730 people who underwent heart surgery, including those with ferritin levels below 100 mcg per liter — a sign of iron deficiency (16).

The iron deficient participants were more likely to experience serious adverse events during surgery, including death. They also required a longer stay in the hospital, on average, after surgery (16).

Iron deficiency appears to have similar effects in other types of surgery. One study analyzed more than 227,000 surgical procedures and determined that even mild IDA prior to surgery increased the risk of health complications and mortality following the procedure (17).

Because ferrous sulfate supplements can treat and prevent iron deficiency, taking them prior to having surgery could improve the outcome and reduce the risk of complications (18).

However, it may take time to increase iron levels via supplementation.

Though oral iron supplements like ferrous sulfate are an effective way to increase iron stores in the body, a person may need to take supplements every day for 2–5 months to bring their iron stores up to normal levels (18, 19).

Thus, people with iron deficiency who do not have multiple months to try and increase iron stores prior to surgery may not benefit from ferrous sulfate supplements and require another type of iron therapy instead (20, 21).

Furthermore, research studies on iron therapy for people who have anemia before surgery are limited in size and scope. Scientists still need to conduct more high quality studies to investigate the best ways for people to increase their iron levels before surgery (21).

Summary

People primarily use ferrous sulfate supplements to prevent iron deficiencies, treat iron deficiency anemia, and maintain normal iron levels. The supplements may prevent the adverse side effects of iron deficiency.

At certain stages of life, some groups of people have an increased need for iron. As such, they’re at a greater risk of low iron levels and iron deficiency. Others have lifestyles and diets that may lead to low iron levels.

People at the greatest risk of having low iron levels include (6, 15):

• infants
• children
• female adolescents
• pregnant people
• premenopausal people
• people with some chronic diseases
• people who donate blood often
• vegetarians and vegans

These groups may benefit most from ferrous sulfate supplements.

Summary

People in certain stages of life have increased iron needs and are more susceptible to iron deficiency. Children, female adolescents, pregnant people, and those with a chronic disease are some of the groups that may benefit most from ferrous sulfate.

Ferrous sulfate supplements usually come in the form of oral tablets. You can also take them as a liquid drop.

The tablets are often red, green, or white.

The supplements may be listed under a variety of names, including:

• ferrous sulfate
• iron (Fe)
• Slow Fe
• Ironorm
• Feratab
• Ferosul
• Feosol
• Feospan
• Ferrograd
• Fer-In-Sol

If you want to take ferrous sulfate, it’s important to look closely at the label for the words “ferrous sulfate” rather than choosing any iron supplement.

This is because iron supplements can contain different types of iron.

Most supplements will clearly state the type of iron on the front label.

Many daily multivitamins also contain iron. However, there’s no guarantee that the iron they contain is ferrous sulfate unless it says so on the label.

Suggested dosage

In some cases, knowing the amount of ferrous sulfate to take can be tricky. Always talk to your healthcare provider to determine the right dosage for you.

There’s no official recommendation regarding the amount of ferrous sulfate you should take each day. The amount will vary depending on factors like your age, sex, health status, and the reason why you’re taking the supplements.

Many of the multivitamins containing iron provide around 18 mg or 100% of the Daily Value (DV) for iron. However, one ferrous sulfate tablet typically provides closer to 65 mg of iron, or 360% of the DV (6).

The general recommendation for treating iron deficiency or anemia is to take one to three 65-mg tablets daily.

That said, the total amount you should take each day may vary.

Some preliminary research suggests that taking iron supplements every other day — rather than daily — may be just as effective, if not more effective, than taking the supplements daily (22, 23).

Your healthcare provider will be able to provide a more specific and personalized recommendation regarding how much ferrous sulfate to take and how often, depending on your blood iron levels and personal circumstances.

When to take it

Certain foods and nutrients, such as calcium, zinc, or magnesium, might interfere with iron absorption and vice versa. Therefore, some people try to take ferrous sulfate supplements on an empty stomach for the greatest absorption (14, 24, 25).

However, taking ferrous sulfate supplements — or any other iron supplement — on an empty stomach may cause stomach pain and distress.

As such, healthcare providers generally recommended taking ferrous sulfate supplements with a meal.

Try taking ferrous sulfate supplements with meals that are low in calcium and do not include beverages that are high in phytates, such as coffee and tea (14, 26).

On the other hand, vitamin C may increase the amount of iron absorbed from ferrous sulfate supplements. Taking ferrous sulfate together with vitamin-C-rich juice or food might help your body absorb more iron (14, 27, 28).

Summary

There are many different forms of ferrous sulfate supplements on the market. Most are oral tablets, though liquid drops are also available. Always check with your healthcare provider before deciding how much ferrous sulfate to take.

Side effects from ferrous sulfate supplements are fairly common (10).

The side effects people report most often are various types of gastrointestinal distress, including nausea, diarrhea, vomiting, abdominal pain, constipation, and dark or discolored stools (14, 29).

Some people have also reported experiencing heartburn after taking the supplements (29).

Furthermore, ferrous sulfate supplements may interact with certain medications.

Before starting ferrous sulfate supplements, be sure to let your healthcare provider know if you’re taking any of the following medications (6, 14):

• antacids, to treat indigestion
• proton pump inhibitors, to treat ulcers and gastroesophageal reflux disease (GERD)
• laxatives, to treat constipation
• levodopa, to treat Parkinson’s disease
• levothyroxine, to treat goiters, thyroid disease, and cancer

Summary

People taking ferrous sulfate commonly report side effects like nausea, heartburn, and abdominal pain. Furthermore, iron supplements may interact with certain medications, including antacids and proton pump inhibitors.

Ferrous sulfate is safe if you take it as a qualified healthcare provider has prescribed. However, this compound — and any other iron supplement — can be toxic in large amounts, especially in children (6, 30).

Some symptoms that may result from taking too much ferrous sulfate are coma, convulsions, organ failure, and even death (6).

Therefore, it’s extremely important to never take more ferrous sulfate than the amount your healthcare provider recommends.

Summary

Ferrous sulfate supplements may be toxic and even deadly in large amounts. Never take more than the dosage recommended by your healthcare provider, and always keep the supplements out of reach of children.

Ferrous sulfate is an iron salt that the body absorbs well. People commonly use it as an iron supplement to maintain normal blood iron levels or treat iron deficiency, including anemia.

Certain groups of people, including women, frequent blood donors, and people with a chronic disease, are at a greater risk of iron deficiency. They may benefit most from ferrous sulfate supplements.

The amount of ferrous sulfate you should take can vary significantly by individual.

Furthermore, the supplements are toxic in large amounts, and they may have side effects and interact with other medications.

For all these reasons, always check with your healthcare provider before taking ferrous sulfate or any iron supplement.

90,000 food, supplements or drugs?

Abstract. Iron deficiency is the most common nutritional disorder in the world and is widespread among children, adolescents and women of reproductive age. In these populations, a balanced diet does not fully meet the physiological need for iron. Fortified foods and dietary supplements can be used to optimize the diet. With identified iron deficiency anemia, it is necessary to use drug therapy, taking into account the effect of individual nutrients on the absorption of iron.

Iron deficiency is the most common micronutrient deficiency in the world, affecting more than 2 billion people [1]. The most vulnerable population groups include women of reproductive age, especially pregnant women, children, adolescents, and people suffering from certain chronic diseases (chronic kidney disease, Crohn’s disease, chronic heart failure, etc.) [2]. Iron deficiency occurs in all regions of the world, including high-income countries [3]. The World Health Organization (WHO) officially recognizes iron deficiency as a public health problem of epidemic proportions [4] and declares a 50% reduction in the incidence of anemia among women of reproductive age as one of the global nutrition goals by 2025 [5].

Iron deficiency can be based on both external causes (insufficient content in the diet) and the action of numerous internal factors (increased need during periods of growth or pregnancy, heavy blood loss, dysfunction of the gastrointestinal tract, the use of certain drugs, etc. ).

Depending on the status of iron in the body (normal, prelatent deficiency, latent deficiency, iron deficiency anemia), different ways of providing the body with this trace element can be used:

• • natural foods – sources of iron;
• • products fortified with iron;
• • Biologically active food supplements (BAA) and iron preparations for oral and parenteral administration.

NATURAL FOODS – SOURCES OF IRON

The best sources of iron are animal products – by-products and meat. Pork liver leads in iron content – 20.2 mg per 100 g of the product. For beef, lamb, duck and rabbit, the same figure is 1.9-3.3 mg, mussels and oysters – 3.2-6.2 mg.

In meat, fish and poultry, 40% of the iron is in the form of heme, an easily digestible form of a trace element. Despite this, most of the absorbed iron comes from plant-based foods. Of these, the highest iron content is characteristic of legumes (5.9–11.8 g/100 g), nuts and seeds (2. 3–6.1 mg/100 g), cereals (buckwheat, oatmeal). However, when calculating, it should be taken into account that when cooking legumes and cereals, the Fe concentration decreases by 2–4 times. Ready-to-eat plant sources of iron are spinach (3.5 mg/100 g) and dried fruits (dried apricots, prunes, etc.) [6]. At the same time, iron in plant products is in the non-heme form, the assimilation of which depends on the action of a large number of factors [7].

Recommendations for red wine, pomegranates, buckwheat, or apples to increase iron levels are questionable. The content of this trace element in red wine does not exceed 0.5 mg per 100 ml, in 100 g of pomegranate – 1 mg, in apples – 2.2 mg, in finished buckwheat – 1.6 mg [6]; moreover, the phytates and polyphenolic compounds present in them will reduce the absorption of iron [7].

Heme iron from meat, fish and poultry is absorbed by an average of 25% (15–35%) [7], and its absorption is practically independent of other factors, except for the body’s need for this trace element. However, high consumption of heme iron is associated with an increased risk of developing coronary heart disease (CHD): each gram increases the likelihood of the disease by 7% (hazard ratio (RR) 1.7; 95% confidence interval (CI): 1.01–1.114) [8]. Also, with a high consumption of heme iron, the likelihood of developing diabetes mellitus increases both in the population as a whole [9] and in the category of the population most vulnerable to iron deficiency – pregnant women [10]. Consumption of more than 1.5 mg of heme iron per day (approximately 150 g of beef) increased the risk of developing gestational diabetes by 1.5-3.3 times compared with those who consumed less than 0.5-0.6 mg per day [11]. Non-heme iron, iron preparations and iron in general do not have such an effect on the development of diseases.

FOODS ENRICHED WITH IRON

Enrichment (fortification) of food products with certain vitamins and minerals is carried out in most countries of the world. This is a highly effective way to address micronutrient deficiencies in the general population. Iron is most commonly added to flour, which is then used to make bread and other baked goods. So, in the UK, flour fortification with iron has been carried out since the 40s. 20th century In the United States, the mandatory iron fortification of wheat, corn flour and rice is regulated by law [12].

There are no laws in Russia requiring manufacturers to fortify flour or other foodstuffs. However, the development of the production of fortified products is one of the objectives of the Strategy for Improving the Quality of Food Products in the Russian Federation until 2030 [13]. In our country, iron is most often added to ready-made breakfasts and juices for children.

BIOLOGICALLY ACTIVE FOOD SUPPLEMENTS – SOURCES OF IRON

Food supplements are specialized food products used to compensate for the deficiency of those micronutrients that are lacking in the diet of a modern person (vitamins B, D, iron, calcium, etc.). They are needed for the prevention and compensation of prelatent and latent iron deficiency. In contrast to enriched foods, dietary supplements for food allow you to meet the individual need of a particular person for iron, taking into account age, gender and functional state. Dietary supplements are of great importance in the nutrition of women and girls involved in fitness or sports, when it is necessary to simultaneously control the calorie content of the diet and compensate for the increased need for iron caused by intense physical activity [14].

Dietary supplements containing 37.5 mg of iron help donors reduce the risk of developing iron deficiency and accelerate the recovery of hemoglobin concentrations reduced after blood donation [15].

The content of iron in dietary supplements sold in Russia and other countries of the Eurasian Economic Union (EAEU) is regulated by the Uniform Sanitary and Epidemiological and Hygienic Requirements for Goods Subject to Sanitary and Epidemiological Surveillance (Control) [16]. Adequate levels of iron intake in the composition of specialized foods and dietary supplements correspond to the physiological need (18 mg for women, 10 mg for men), the upper allowable level is 40 mg for women, 20 mg for men [17]. Supplements containing higher doses of iron are rejected at the stage of state registration and are prohibited for sale in the territory of the EAEU countries.

Food supplements along with iron often contain other mineral substances that can have a depressing effect on its absorption. This ability has been shown in experiments on the simultaneous intake of iron with calcium or zinc. Consumption of 300-600 mg of calcium led to a decrease in the absorption of iron by 50-60% from bread, however, with regular intake of calcium preparations, their negative effect on iron metabolism in adults was not revealed [18].

Zinc, like iron, is a micronutrient that is often deficient in the diet of people in developing and developed countries, as a result of which they are often used together as part of food supplements and fortified foods. It is known that the same carrier is involved in the assimilation of these minerals, which differs from the divalent metal transporter (DMT-1), which ensures the transport of most of the free Fe2+ through the rim of the apical membrane into the enterocyte [19]. With the simultaneous use of zinc and iron can adversely affect the absorption of each other. Iron dose-dependently inhibits fasting zinc absorption from supplements at a 2:1 ratio of these micronutrients. However, in complex food compositions similar to the natural diet, even very high (25:1) ratios of iron and zinc do not always have a negative effect on the metabolism of the latter [20]. Zinc, in turn, can reduce the absorption of iron from an aqueous solution by 56% if its amount exceeds the Fe content by 5 times. As part of a mixed food (for example, a hamburger), zinc, even in high concentrations, does not interfere with the absorption of iron, but in the composition of fortified flour, its individual forms (zinc sulfate) can have a more pronounced inhibitory effect on the bioavailability of iron than other compounds (zinc oxide) [19].

IRON MEDICINES

In the presence of iron deficiency conditions, the total iron deficiency is calculated using the Ganzoni formula: total iron deficiency (mg) = patient’s body weight (kg) × [Hb norm (g/l) – patient’s Hb (g/l)] × 0. 24 + iron depot (mg).

At a body weight of less than 35 kg, the iron depot is 15 mg/kg, the target concentration of Hb is 130 g/l, and at a body weight of more than 35 kg, 500 mg and 150 g/l, respectively [21].

With a body weight of 65 kg and mild anemia (hemoglobin 100 g/l), the total iron deficiency is 1280 mg. It is impossible to cover such a significant deficiency only at the expense of food (natural and enriched) or dietary supplements. A balanced diet is important to prevent the development of iron deficiency, but with pre-existing iron deficiency anemia, medications are needed, the iron content of which is usually from 45 to 100 mg per tablet or capsule.

The optimal regimen for iron supplementation depends on several factors related to both the patient and the dosage form. Its determination should take into account the underlying pathological condition, the degree of anemia, the need for a rapid increase in hemoglobin, tolerance or refractoriness to previous treatment, history of allergies, the cost of drugs and their side effects.

Parenteral administration of drugs is indicated if it is necessary to quickly compensate for a profound iron deficiency, impaired absorption due to intestinal pathology (enteritis, malabsorption syndrome, resection of the small intestine, stomach and duodenum), exacerbation of gastric or duodenal ulcer, as well as in case of absolute intolerance to oral iron preparations, which does not allow continuing treatment (provided that dose reduction and / or replacement of the iron preparation for oral administration is not effective).

Oral iron supplementation remains the gold standard for treating iron deficiency. However, they can vary significantly in dosage, composition, cost and bioavailability. We emphasize that bioavailability is defined as the proportion of iron present in an oral preparation that is absorbed and incorporated into erythrocytes [22–23]. This clarification is important in light of the fact that the terms “bioavailability” and “absorption” are often used interchangeably.

Divalent (sulfate, fumarate, gluconate, glycine sulfate, etc.) and trivalent (protein succinylate, polymaltose complex hydroxide, etc.) forms of iron are currently available from oral forms [24–25].

Ferric iron must be reduced to ferrous iron before being taken up by enterocytes [26]. Trivalent iron preparations do not have prooxidant properties, are well tolerated by patients and enter the blood only through active absorption, which reduces the risk of overdose [27]. At the same time, the bioavailability of iron from trivalent forms is usually 3–4 times lower than from ferrous sulfate [22–23, 28]. A large number of studies have shown that trivalent iron supplementation is less effective than ferrous iron supplementation, and there are populations in which the use of trivalent iron supplementation does not lead to an increase in hemoglobin concentration in anemia [28-29].

Yes, Mehta B.C. in 2003 showed that in 27 patients with anemia who received various preparations of polymaltose iron for 4–52 weeks, there was no significant increase in hemoglobin concentration. After replacing the drug with iron fumarate or succinate after 4–13 weeks, the increase in hemoglobin amounted to 0.8–6.7% [30].

Ruiz-Arguelles G.J., examining 240 patients with iron deficiency anemia, found that 75 (31%) people aged 0.8 to 68 years had no effect when taking 178-356 mg of polymaltose hydroxide for 4-14 months. Replacement of polymaltose with ferrous fumarate resulted in an increase in hemoglobin concentration from 10.3 g dL to a median level of 12.5 g/dL [31].

In parallel treatment of iron deficiency anemia in 2 groups of children with ferrous and ferric iron preparations at a dose of 6 mg/kg/day, in 21% of patients in the polymaltose group, after a month, there was not an increase, but a decrease in hemoglobin concentration [32].

In a meta-analysis comparing the efficacy of polymaltose and ferrous sulfate, of the 14 studies found, 6 were in adults. The four initially selected pediatric studies were rejected due to heterogeneity of data. As a result, it was found that after 8–13 weeks of taking iron preparations, the hemoglobin content was similar. However, the ferritin concentration, which reflects the replenishment of iron stores in tissues, was 12.72 µg/L lower in the polymaltose group [33].

Currently, all major world guidelines for the prevention and correction of iron deficiency recommend the use of divalent iron salts [34-39].

IRON BIOAVAILABILITY

The absorption of iron from foods, dietary supplements and medicines is influenced by a large number of factors: the body’s need for iron, the form of iron, the state of the gastrointestinal tract, diet and taking certain medications.

The main factor regulating the absorption of iron is the body’s need for this trace element. In this case, the enterocytes of the duodenum and proximal jejunum act as the main springboard for iron metabolism. They capture iron from the intestinal lumen with the participation of DMT-1, intracellular transport from the apical to the basolateral membrane, and the entry of iron from the enterocyte into the bloodstream due to the action of the transport protein ferroportin. The key regulator of iron metabolism is hepcidin, which is formed mainly in the liver. It blocks the function of ferroportin, thereby reducing the flow of iron into the bloodstream. Iron accumulated in enterocytes in the form of ferritin is excreted during the natural renewal of intestinal cells [40].

With a decrease in iron stores in tissues, which in most cases can be traced by the concentration of ferritin, the ability of enterocytes to absorb iron and ensure its entry into the bloodstream increases sharply, and the loss of iron with the intestinal epithelium decreases. In pregnant women with low ferritin stores, the degree of iron absorption can increase by 60% compared to normal values ​​[41].

IRON ASSOCIATION INHIBITORS

In addition to the body’s need for iron, some nutrients may also stimulate or inhibit the absorption of iron preparations. Iron obtained from drugs can form indigestible complexes with various food components in the intestinal lumen. Substances that can inhibit the absorption of this trace element include phytates, polyphenols, soy protein, as well as drugs that reduce the production of hydrochloric acid or lower the pH in the stomach.

Phytates

Whole grains, legumes, nuts, seeds and dried fruits are rich in phytic acid and its analogues, which can bind iron in the intestinal lumen and interfere with its absorption. The inhibitory effect of phytates is dose-dependent and begins to manifest itself at a content of 2–10 mg per serving of food. In almonds, the content of phytates is 2452 mg/100 g, in walnuts – 2070 mg/100 g, in cashews – 697 mg/100 g [42]. Phytate levels in cereals can range from 0.1 to 2.2% depending on the type of these foods. Thus, polished rice contains the least amount of phytates – less than 250 mg/100 g, brown rice – 1000 mg/100 g, but in different types of wheat this indicator ranges from 400 to 1400 mg/100 g [43]. Phytates are also found in avocados (356 mg/100 g), papaya (up to 180 mg/100 g), carrots (88 mg/100 g), and even pomegranate (45 mg/100 g) [44].

Dietary intake of phytates ranges from 112 to 1367 mg per day in developed countries, depending on the food mix. In developing countries, where the main diet is cereals and legumes, phytate intake reaches 2000 mg per day or more [43]. It is phytates that are the main obstacle to the absorption of iron from food.

Polyphenols

Polyphenolic compounds are important phytonutrients that provide antioxidant protection, improve microcirculation and suppress chronic inflammation. At the same time, they have a dose-dependent inhibitory effect on the absorption of iron from food and drugs: 20-50 mg of polyphenols reduce this absorption by 50-70%, 100 mg reduce the absorption of iron 400 mg – by 60 reduce the absorption of iron 90%. A cup of black tea reduces iron absorption by 79–94%, mint tea by 84%, cocoa by 71%, chamomile tea by 47% [45], and coffee by 39% [46]. Polyphenols are also high in dark chocolate (1664 mg/100 g), blueberries (836 mg/100 g), black currants (758 mg/100 g), plums (377 mg/100 g), strawberries and raspberries (215–235 mg/100 g), hazelnuts and pecans (493). –495 mg/100 g), etc. [47].

The use of iron supplements with plant foods rich in phytates and polyphenols will result in a dose-dependent decrease in the absorption of ferrous iron. Therefore, it is recommended to take iron supplements on an empty stomach, if possible, at least one hour before meals. Fractional absorption of iron from preparations varies from 2 to 13% when taken with food and from 5 to 28% when taken on an empty stomach [48]. In non-anemic women, the mean fractional absorption of iron with oral administration of 50 mg of iron on an empty stomach was ≈10%, and only 3% with food [49].

IRON ASSOCIATION STIMULANTS

The main stimulator of iron absorption is ascorbic acid. In addition to it, organic acids (except oxalic acid), galactooligosaccharides, meat products, beta-carotene, vitamins A and B2 have demonstrated the ability to improve the absorption of iron from food or drugs.

Vitamin C

Ascorbic acid is the strongest stimulator of iron absorption from food and drugs [7, 50]. It ensures the reduction of ferric iron to ferrous in the intestinal lumen, which improves its bioavailability, and also neutralizes the effect of food factors that reduce the absorption of iron (phytates, polyphenols, etc.). The consumption of food or drinks containing 50 mg of ascorbic acid, together with oral iron preparations, can dramatically increase its absorption. The indicated amount of vitamin C is found in 90 g spinach, 30 g parsley, 110 g white cabbage or 125 ml orange juice [6]; this amount is sufficient to overcome the inhibitory effect of 100 mg of tannic acid (tannins) [51].

With a high content of iron absorption inhibitors (soy protein-based products) in food, the molar ratio between ascorbic acid and iron should exceed 4:1. With a low content of absorption inhibitors, a ratio between vitamin C and iron equal to 2:1 is acceptable [50, 51].

Thus, if fasting iron preparations are not well tolerated, they can be taken with food or drinks containing at least 50 mg of ascorbic acid, for example, with a half glass of orange juice.

Galactooligosaccharides

Galactooligosaccharides are short chain polysaccharides found in breast milk, dairy products, legumes and some root vegetables. They have prebiotic properties, selectively stimulating the growth and biological activity of representatives of the protective human microbiota. Galactooligosaccharides increased iron absorption by 62% from a micronutrient premix containing ferrous fumarate, but had no pronounced effect on iron sulfate absorption [52].

Low molecular weight proteins in meat, fish and poultry

Certain fractions of proteins in meat, fish and poultry stimulate the absorption of non-heme forms of iron when added to a vegetarian diet, while 30 g of muscle tissue is considered equivalent in effectiveness to 25 mg of ascorbic acid. Adding beef to corn porridge resulted in a three-fold increase in non-heme iron absorption. Proteins of eggs, milk and albumin, on the contrary, inhibit the absorption of iron [7].

Other vitamins

Vitamin A and beta-carotene can complex with iron, keeping it soluble in the intestinal lumen and preventing iron from binding to dietary phytates and polyphenols. The addition of beta-carotene contributed to an increase in the absorption of iron by more than 3 times from rice and 1.8 times from wheat and corn [53]. However, this effect depends on the initial status of iron and vitamin A sufficiency and requires further study [7]. Vitamin B2 (riboflavin) does not have a pronounced effect on the absorption of iron, but is involved in the regulation of erythropoiesis [54].

Drugs affecting iron metabolism

In addition to the above nutritional factors, certain drugs also affect iron metabolism. Drugs that reduce hydrochloric acid production, such as proton pump blockers, H2 blockers, antacids, and cholestyramine, can interfere with iron absorption. Allopurinol, on the contrary, may stimulate the deposition of iron in the liver and should not be used concomitantly with iron preparations. Iron, in turn, impairs the absorption or reduces the effectiveness of levodopa, methyldopa, levothyroxine, penicillamine, fluoroquinolones, tetracyclines and bisphosphonates. It is recommended that they be spaced apart by at least 2 hours [46, 55].

IRON DOSAGE REGIME

It is known that the increase in hemoglobin concentration in response to iron supplementation is dose-dependent. The traditionally recommended treatment regimen for iron deficiency anemia in adults is 100–200 mg of ferrous iron per day, divided into 2–3 doses and taken on an empty stomach. The 325 mg ferrous sulfate tablet contains 65 mg of elemental iron; accordingly, three tablets per day provide 195 mg of iron [24]. Children under 3 years of age are prescribed liquid preparations at the rate of 3 mg/kg body [21].

However, it should be noted that the dose and regimen of iron supplementation can also affect iron absorption. Of 40 mg of ferrous iron, 22.7% is absorbed, of 240 mg – 13%. The level of hepcidin naturally increases during the day from 8 a. m. to 5 p.m. by 1.8 times, and its concentration negatively correlates with iron bioavailability [56]. Against the background of taking iron preparations, an even more pronounced increase in the concentration of hepcidin is observed even with depleted iron reserves (ferritin <20 mg/l), and this rise persists for more than 24 hours. After 10 days of regular intake, only 16.7% of iron is absorbed from 40 mg, and 7.5% from 240 mg [56]. The maximum absorption of iron (18-22%) is observed when it is taken in doses from 40 to 80 mg. The upper tolerable intake level, at which no significant side effects from the gastrointestinal tract are observed, is 45 mg [18].

As a result, the advisability of changing the dosing regimen of iron preparations to increase bioavailability, reduce the incidence of adverse reactions and increase patient adherence to treatment is currently being discussed [57–58]. It has been suggested that a single dose of lower doses of iron in the morning and possibly every other day may be optimal [24, 25, 59, 60].

CONCLUSION

Thus, nutrition is one of the key factors determining the supply of the human body with iron, as well as regulating the bioavailability of iron-containing preparations. Heme iron is better absorbed than non-heme iron, but eating large amounts of heme iron in foods is associated with an increased risk of cardiovascular disease and diabetes. Among the many nutrients, ascorbic acid stimulates the absorption of non-heme forms of iron the most, and phytic acid and polyphenols are key inhibitors of its absorption.

When taking iron supplements, it is advisable to combine them with foods containing 50 mg or more of vitamin C, but not rich in phytates and polyphenols, such as orange juice.

Svetlana Vladimirovna Orlova, Doctor of Medical Sciences, Head Department of Dietetics and Clinical Nutrition of the Faculty of Continuous Medical Education of the Medical Institute of the Federal State Autonomous Educational Institution of Higher Education “Peoples’ Friendship University of Russia” (PFUR). Address: 119571, Moscow, Leninsky pr., 148. E-mail: [email protected]
Elena Aleksandrovna Nikitina, Candidate of Medical Sciences, Associate Professor of the Department of Dietetics and Clinical Nutrition of the Faculty of Continuous Medical Education of the Medical Institute of the FSAEI HE “Peoples’ Friendship University of Russia” (PFUR). Address: 119571, Moscow, Leninsky pr., 148. E-mail: [email protected]
Elena Valerievna Prokopenko, endocrinologist, nutritionist, methodologist of the medical department of MS Group LLC. Address: 117105, Moscow, Nagatinskaya st., 1, building 33. E-mail: [email protected]
Angelina Nikolaevna Vodolazskaya, dietician-endocrinologist of the medical center LLC “El-Clinic”. Address: 141421, Moscow region, Khimki, st. Mikoyan, 10, room 18. E-mail: [email protected]

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