Iron Deficiency – A Major Global Health Problem

Iron Deficiency – A Major Global Health Problem

Working at NatMed, I see many women who are particularly low in iron and struggling with fatigue which is impacting their overall health. For many, it is an inherited problem, but other factors are:

  • Heavy blood loss during menses.
  • Low dietary intake, particularly in vegetarian or vegan diets.
  • Poor gut health reducing absorption.
  • Increased demand – such as pregnancy and lactation.

Iron deficiency is a major global health problem that may occur with or without anaemia.

Red blood cells are the most numerous cells in the human body (excluding the microbiome), accounting for 84% of all cells, with an average of 200 billion being produced every day. Iron is an essential mineral for health. Not only is it a crucial component for many biochemical reactions in our bodies, but it is also required for proper oxygen transport.

For optimal iron levels, the requirement is a daily supply of 20-25 mg of iron to erythrocytes, in the bone marrow.

We often use supplementation and are careful to optimise the absorption of iron uptake. There are many factors that impact the uptake.

Factors that influence iron absorption:

  • Irons absorption regulation – Hepcidin
  • Ferritin levels
  • Mucosal block theory
  • Dosing regime
  • Forms of iron
  • Co-factor availability (nutrients that support iron uptake)

Iron availability is controlled by the liver peptide hormone hepcidin. Iron supplementation causes the production of hepcidin, which is released into circulation and acts on its receptor ferroportin, a transmembrane iron exporter protein, expressed on red blood cells.

Hepcidin is suppressed in iron deficiency, allowing increased absorption of iron and therefore replenishment of iron stores. The increased erythropoietic activity also suppresses hepcidin production (bone marrow production). Hepcidin is increased in inflammation and infection as a strategy to limit iron availability to micro-organisms.

Hepcidin influences

  1. People with genetic mutations in the gene encoding for hepcidin inhibition, present with abnormally high hepcidin have iron deficiency or iron deficiency with anaemia and have a poor response to oral iron.
  2. Conditions with chronic low-grade inflammation. Plasma Hepcidin has a circadian influence over the day, morning iron supplementation enhances this increase affecting iron supplementation given in divided doses or in the evening.
  3. The mucosal block theory is a process in which an initial dose of iron can reduce the absorption of a subsequent dose. Researchers have found that 20 mg did not induce this process and 30-60 mg was found to be “the blocking dose.”
  4. Intermittent dosing – (Cochrane review) (25 studies included 11, 000 pre-menopausal women). Intermittent dosing reduced the risk of having anaemia and iron deficiency, improving the concentration of haemoglobin and ferritin. Intermittent dosing was just as effective with daily administration …. WITH NO SIDE EFFECTS. An alternative daily dosing regime has the benefit to give the Hepcidin time to return to baseline – enhancing iron absorption it also minimised gastro adverse effects which are related to the unabsorbed fraction of iron.

Forms of iron

The different forms of iron include ferrous sulphate, ferrous gluconate, ferrous glycinate, ferric citrate, ferric sulphate.

Ferrous iron is more bioavailable than ferric iron forms.

Glycinate is superior to sulphate for bioavailability with fewer side effects.

A recent study – with 7000 participants, looked at GI effects of ferrous sulphate, the “gold standard” in oral iron therapy. This confirmed that ferrous sulphate is associated with a significant increase in GI specific side effects, there was no relationship with dose.

The threshold for dosing with ferrous sulphate for benefit appears to be very low-20mg per day.

Further research looked into the difference between iron sulphates and bis-glycinate, the sulphate form was 26.7 % and bis-glycinate 90%.  At a lower dose, iron bis-glycinate improved haematological and iron status to the same extent as a double dose of ferrous sulphate, GI effects were significantly lower and newborn weight slightly higher.

Cofactors for iron absorption, nutrients that support iron levels in the body

  • Vitamin A – (declared a worldwide deficiency by WHO in 1995).

Inflammation reduces plasma retinol concentrations. Research shows a link between anaemia and vitamin A deficiency. Mild deficiency reduces bone marrow production and impairs mobilisation of iron stores, increasing susceptibility to infection.

 Trials from 2002: Supplementation of Vitamin A alone in anaemic children elevated serum iron by 2umo/L, transferrin saturation by 3% and Haemoglobin by 9g/L.

Vitamin A and iron supplementation elevated serum iron by 6 umo/L and transferrin saturation by 8 %, Haemoglobin by 12g/L.

  • Ascorbic acid (vitamin C)

Supports absorption of iron and reduces adverse Gastrointestinal effects.

  • B2 (riboflavin)

Factors that increase deficiency of Vitamin B2 include:

  • Women on the OCP as their body can’t absorb adequate amounts of B2
  • Athletes, as vigorous exercise, depletes B2.
  • The elderly due to poor absorption and low dietary intake
  • Children and adolescents (mainly teenage girls) due to dietary deficiency.
  • Alcohol and pharmaceutical medications reduce B2 absorption.
  • Pregnant and lactating mothers. Riboflavin falls in the third trimester, with clinical signs of deficiency at birth, The baby is born deficient if the mother is deficient during pregnancy.

B2 supplementation has been shown to improve the absorptive capacity of the gastrointestinal villi.

Interpretation of iron studies

  • Serum iron – unbound iron < 10 suggests low stores
  • Total binding capacity – ability to bind more iron > 70 suggests low stores
  • Transferrin – transport protein (1 molecule binds 2 atoms of iron) <16% suggests low iron stores.
  • Serum ferritin, the iron within a storage protein, 1 molecule of ferritin binds 4,500 atoms of iron. Levels of under 30 ug/L shows deficiency

Ferritin is an acute-phase protein elevated in the presence of inflammation or infection.

Dosing – Children and adolescents

 7- 12 months recommended iron intake is 11 mg/day, upper limit is 20mg
1-3 years old recommended iron intake is 9mg per day, upper limit 20
4-8 years old 10mg per day, upper limit 40 mg
9-13 years old  8mg per day and upper limit 40mg
 Boys 14-18  11 mg per day, upper limit 44mg per day
Girls 14-18 15 mg per day and upper limit 45 mg

 

Adults

Men                                                                      8 mg per day, upper limit 45mg

Women 18-50 years                                            18 mg, upper limit 45 mg

Women >50                                                     8mg per day upper limit 45 mg

 

Pregnancy                                                           27mg per day, upper limit 45 mg
 Lactation 14-18 years                                         10 mg per day upper level 45
 Lactation > 18 years                                            9 mg per day, upper level 45 mg

 

The upper limit is based on gastrointestinal stress, doses under 45 mg are not likely to cause symptoms such as nausea and constipation.

High iron doses can cause oxidative stress and compromise the balance of the gut microbiome and cause tissue damage to the mucosa.

Diet: Supporting iron intake 

Heme vs. nonheme

In food, iron is present in two different forms: heme iron and non-heme iron.  Heme iron, which is bound to haemoglobin and myoglobin, is found in meat, fish, and poultry. Only foods derived from animal flesh provide heme iron (they also provide nonheme iron as well).

Nonheme iron is present in vegetables, grains, fortified foods, and supplements.

The absorption of heme iron is approx. between 15-35%. Heme iron is more readily absorbed by the body than nonheme iron (about 3-20%). Even though heme is better absorbed, most of the iron in our diets is derived from nonheme sources. It is therefore essential to understand some of the factors that enhance and inhibit our absorption of non-heme foods.

Non-heme iron absorption: This is influenced by several factors 

Phytates, fibres, and oxalates
Phytates and fibre are found in foods such as whole grains, soy, nuts, and legumes, and can decrease the amount of nonheme iron that is absorbed from a meal. If you are eating foods high in phytates and fibres (such as spinach, beetroot, rhubarb, or leafy vegetables), also consume foods that enhance non-heme absorption. Spinach is an excellent nonheme iron source that is also high in phytates and fibres. Dress your greens with a homemade, citrus-based dressing to enhance nonheme absorption.

Oxalates
Oxalates are common, naturally occurring food chemicals found in numerous food sources such as fruits, vegetables, nuts and seeds, grains, and black tea. They may inhibit the body’s iron absorption by combining with iron to form a compound called iron oxide. While some research suggests that certain oxalate-containing foods, such as spinach and fruits, may have minimal effect on nonheme iron absorption, pair these healthy foods with nonheme enhancing foods.

Calcium and phosphorous
Calcium and phosphorous can significantly impact iron absorption. Try to increase the amount of time between your calcium- and phosphorous-rich snacks (dairy, milk yoghurt, or cheese) and your nonheme foods. To maximize the benefits of calcium-rich and iron-rich foods, if you can tolerate dairy consume a couple of hours before or after your nonheme meal.

Tannins and polyphenols
Tannins and polyphenols are biological compounds present in tea and coffee that can have an inhibitory effect on iron absorption. These compounds can bind with iron, therefore making nonheme iron insoluble. While research suggests that certain beverages and foods rich in polyphenols, such as red wine, may not significantly reduce iron absorption, if you are iron deficient, leave a couple of hours between your nonheme iron-rich lunch and your afternoon tea.

Excess intake of other minerals
Excess intake of other minerals can inhibit nonheme iron absorption. Like iron, zinc, calcium, magnesium, and copper are also positively charged. This means that these minerals compete for the same binding sites as iron and may prevent it from binding and being absorbed.

Low stomach acid
Stomach acidity can greatly decrease the amount of iron absorbed in your stomach. The elderly often have less acidic stomachs, frequent antacid use can affect your stomach’s iron absorption. (as well as Nexium and Pariet)

Eggs
Eggs contain phosphoprotein, a compound with iron-binding capacity that can impair iron absorption. Some studies have shown that one hardboiled egg can reduce the absorption of iron in a meal by as much as 28%. To maximize iron absorption, consider having your egg as a snack.

Jacky Dixon
[email protected]
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