Iron supplementation

Question 1

Prevalence of iron-deficiency and iron-deficiency anaemia worldwide

Answer 1

• Deficiency: 4-6 billion worldwide

- Deficiency anaemia: 1.24 billion worldwide

Question 2

The key functions of Fe

Answer 2

• O2 transport in Hb and myoglobin to support everyday functions and exercise
• Energy metabolism in redox centres in the electron transport chain

Question 3

Overview of Fe metabolism (including Hepcidin regulation)

Answer 3

• Our bodies have 3-4g of Fe, and recycle 25-30mg per day
• we need to ingest 10-15mg per day to absorb 1-2mg to replace losses
• no excretion pathway- just lost through menstruation or sloughing of cells
• Fe levels are regulated by UPTAKE. It is recycled via spleen macrophages breaking down erythrocytes
• Hepcidin (released from hepatocytes) levels are upregulated during infection/inflammation/high Fe: this blocks ferroportin channels and stops absorption, leading to high levels of Fe in macrophages but low levels in serum, haemoglobin and hepatocytes
• Hepicidin is low when Fe are low/hypoxia/stress: this allows for high levels of Fe in serum, haemoglobin and hepatocytes but low levels in macrophages

Question 4

Why is upregulation of hepcidin during infection/inflammation adaptive? (including microbial piracy)

Answer 4

• Bacteria can undergo iron-piracy for growth, producing siderophores which chelate serum Fe, and transferrin which can capture
• malaria mortality and morbidity is upregulated during oral Fe supplementation
• high levels of Fe can also cause dysbiosis

Question 5

Key differences and challenges between oral and IV Fe supplementation

Answer 5

• Oral: Ionic Fe, simple salt (ferrous 2+ sulfate) or Fe chelate (ferric 3+ citrate). Although can cause GI upset. Only really used for asymptomatic Fe-deficiency (i.e. no fatigue, breathlessness 10

Question 6

The difference between iron-deficiency anaemia and iron-deficiency

Answer 6

• Deficiency: low storage Fe (ferritin <30ug/L), Hb is normal (12-13g/dL), transferrin saturation <30%
• anaemia: low storage Fe (<15ug/L), low Hb (<12-13g/dL), transferrin saturation <10%

Question 7

Why we cannot just supplement with Fe?

Answer 7

• When supplement, increases reticulocyte (intermediate RBC) which increases susceptibility to malaria transiently until mature to RBC
• causes dysbiosis and gut inflammation
• increases free radical production via the Fenton reaction

Question 8

What is IHAT?

Answer 8

• Engineered Fe supplement which mimics food sources

- unique molecule which is nano+insoluble+disordered which makes it highly bioavailable