The effects of oral iron supplementation on cognition in older children and adults: a systematic review and metaanalysis

Martin Falkingham1, Asmaa Abdelhamid1, Peter Curtis1, Susan Fairweather-Tait1, Louise Dye2, Lee Hooper1

Iron

Iron plays an important role in biology, forming complexes with molecular oxygen in hemoglobin and myoglobin: these two compounds are common oxygen transport proteins Iron is a chemical element with the symbol Fe (from Latin: ferrum), which include ferrous and ferric compounds, have many uses.

HEME Iron Food Source

*Beef, chuck, lean Beef, corned Beef, eye of round, roasted *Beef, flank Beef, lean ground; 10% fat Beef, liver *Beef, round Beef, tenderloin, roasted Chicken, breast, roasted, Chicken, leg, meat only, roasted Chicken, liver Clams, breaded, fried, Oysters, breaded and fried Turkey, dark meat Turkey, white meat

Serving Size (oz.) 3.0 3.5 3.0 3.5 3.0 3.0 3.5 3.0 3.0 3.5 3.5 cup 6 pieces 3.5 3.5

Iron (mg) 3.2 1.9 2.2 3.3 3.9 7.5 3.1 3.0 1.1 1.3 12.8 3.0 4.5 2.3 1.6

NON-HEME Iron Food Source Baked beans, canned Black beans, boiled Kidney beans, boiled Lentils, boiled Lima beans, boiled

Serving Size cup 1 cup 1 cup 1 cup 1 cup

Iron (mg) 2.0 3.6 5.2 6.6 4.5

Molasses, blackstrap
Navy beans, boiled Oatmeal, fortified instant, prepared Pinto beans, boiled Soybeans, boiled Spinach, cooked (boiled, drained) Spinach, canned, drained Spinach, frozen, boiled, drained Tofu, raw, firm

1 tbsp.
1 cup 1 cup 1 cup 1 cup cup cup cup cup

3.5
4.5 10.0 3.6 8.8 3.2 2.5 1.9 3.4

The following factors will increase the iron absorption from non-heme foods

A HEME and NON-HEME food eaten together A good source of vitamin C (ascorbic acid) i.e., oranges, grapefruits, tomatoes, broccoli and strawberries, eaten with a NON-HEME food A NON-HEME food cooked in an iron pot, such as a cast iron skillet

The following factors will decrease the iron absorption from non-heme foods

Excess consumption of high fiber foods or bran supplements (the phytates in such foods inhibit absorption). Large amounts of tea or coffee consumed with a meal (the polyphenols bind the iron). High intake of calcium - take your calcium supplement at a different time from your iron supplement.

Iron Metabolism

Iron Deficiency Causes

Chronic bleeding (hemoglobin contains iron) excessive menstrual bleeding non-menstrual bleeding bleeding from the gastrointestinal tract (ulcers, hemorrhoids, etc.) rarely, laryngological bleeding or from the respiratory tract Inadequate intake (special diets low in dietary iron) Substances (in diet or drugs) interfering with iron absorption Malabsorption syndromes Fever where it is adaptive to control bacterial infection Blood donation

Iron Deficiency Symptom

Fatigue Pallor Hair loss Irritability Weakness Pica Brittle or grooved nails Plummer-Vinson syndrome: painful atrophy of the mucous membrane covering the tongue, the pharynx and the oesophagus Impaired immune function

Iron Supplements

Iron Supplements

Iron supplementation is indicated when diet alone cannot restore deficient iron levels to normal within an acceptable timeframe. Supplemental iron is available in two forms: ferrous and ferric. Ferrous iron salts (ferrous fumarate, ferrous sulfate, and ferrous gluconate) are the best absorbed forms of iron supplements

Iron Supplements

Therapeutic doses of iron supplements, may cause gastrointestinal side effects such as nausea, vomiting, constipation, diarrhea, dark colored stools, and/or abdominal distress Starting with half the recommended dose and gradually increasing to the full dose will help minimize these side effects

Anemia

Anaemia, defined as a reduction in the quantity of the oxygen-carrying pigment haemoglobin in the blood, is a major global public health problem.

Anemia
Microcytic Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies: Heme synthesis defect Iron deficiency anemia Anemia of chronic disease (more commonly presenting as normocytic anemia) Globin synthesis defect alpha-, and beta-thalassemia HbE syndrome HbC syndrome and various other unstable hemoglobin diseases Sideroblastic defect

Anemia
Macrocytic Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid (or both). Deficiency in folate and/or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does. Hypothyroidism Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of liver disease can also cause macrocytosis. Methotrexate, zidovudine, and other drugs that inhibit DNA replication.

Anemia
Normocytic Normocytic anemia occurs when the overall hemoglobin levels are always increased, but the red blood cell size (mean corpuscular volume) remains normal. Causes include: Acute blood loss Anemia of chronic disease Aplastic anemia (bone marrow failure) Hemolytic anemia

Cognition
Cognition refers to mental processes. These processes include attention, remembering, producing and understanding language, solving problems, and making decisions.

Background
In observational studies anaemia and iron deficiency are associated with cognitive deficits, suggesting that iron supplementation may improve cognitive function. However, due to the potential for confounding by socioeconomic status in observational studies, this needs to be verified in data from randomised controlled trials (RCTs).

Aim

To assess whether iron supplementation improved cognitive domains: concentration, intelligence, memory, psychomotor skills and scholastic achievement.

Result
Attention/Concentration The effect of iron supplementation on attention or concentration was assessed in 3 groups of anaemic participants (146 people) and two groups of iron deficient and/or replete participants (33 people) One study in Indonesian primary school children found an improvement in attention and concentration related to iron supplementation, while the remaining four studies (in US adolescents and pre-menopausal women, New Zealand teenagers and Mexican primary school children) found no statistically significant effects on measures of attention or concentration

Result
Intelligence The effect of iron on intelligence quotient (IQ) was assessed in three groups of anaemic participants, two of iron deficient people and six groups of those who were iron replete at baseline Overall there was no evidence of an effect of iron supplementation on intelligence

Result
Memory Four studies addressed the effect of iron supplementation on memory in anaemic participants, none in iron deficient people There was no evidence overall

Result
Psychomotor function The domain of psychomotor function was investigated by 4 studies in those anaemic at baseline, 2 in iron deficient and/or replete participants and 1 in iron replete participants There was no suggestion of an effect of iron supplementation on psychomotor function overal

Result
Scholastic achievement The effects of iron supplementation on scholastic achievement appeared highly heterogeneous - two studies showed statistically significant improvement, and two showed statistically significant impairment to scholastic achievement from iron supplementation compared with the control group at end of study. Overall, there was no suggestion of a significant effect

Conclusions

There was some evidence that iron supplementation improved attention, concentration and IQ, but this requires confirmation with well-powered, blinded, independently funded RCTs of at least one years duration in different age groups including children, adolescents, adults and older people, and across all levels of baseline iron status.