Exhaustion and Iron

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Tired All the Time

Fatigue is a very common clinical presentation and can be due to a myriad of issues including stress, infection, inflammation, hormonal imbalance – the list goes on and on. That said, arguably one of the first things any clinician will think of when faced with a patient complaining of being “tired all the time” is iron, and whether enough oxygen is reaching the cells (or more accurately the mitochondria). However it’s not all about iron, but instead a team of nutrients and cellular transporters contribute to creating the energy we all need to enjoy our days.

Short and Sweet

Named for their bright colour, red blood cells (RBCs) are the most abundant cell in the blood, accounting for approximately 40-45% of blood volume.7 RBCs are produced during erythropoiesis, beginning as immature reticulocytes in the bone marrow, and then released into the bloodstream seven days later as matured RBCs (also referred to as erythrocytes).8 RBCs are abundant in haemoglobin (which, as the name alludes to, contains the iron-rich molecule haem, see Figure 1) and are responsible for binding and delivering vital oxygen to tissues for cellular respiration.9 With an average lifespan of only 120 days,10 ensuring healthy iron status is integral to supporting the ongoing production of healthy RBCs and, therefore, also maintaining cellular energy production.

It’s a Team Effort

That said, healthy RBC production requires more than just iron, with this process also relying on an adequate intake of vitamins B12 and folate.12 Various population groups including vegetarians and vegans,13 pregnant and lactating women,14 the elderly,15 and those with gastrointestinal dysfunction16 are at a greater risk of, in particular, inadequate B12 levels, meaning assessment and supplementation may be required. While dietary sources should lay the foundation for all nutrition, in some cases supplementation is required. For example, unlike B12 found in food, supplemental B12 (such as the activated form methylcobalamin), is not bound to a protein, therefore absorption is not impaired by low stomach acidity,17 which can reduce B12 uptake from dietary sources.

A deficiency of vitamin B12 (and/or insufficient folate intake) can result in large, immature and dysfunctional RBC formation. This is because B12 is a cofactor for the enzymatic conversion of homocysteine to methionine, to produce tetrahydrofolate; which is then converted to thymine monophosphate for incorporation into DNA.18 As such, a lack of either B12 or folate can result in impaired DNA synthesis and elevations in homocysteine, impacting healthy RBC development.19

Another team player in the iron and energy game is vitamin C, which enhances iron absorption and is particularly helpful if your aim is to also maximise iron uptake from dietary sources (e.g. green leafy vegetables). Vitamin C also potentiates the mobilisation of iron from inert tissue stores, which facilitates iron’s incorporation into protoporphyrin – part of the haem molecule.20 Supporting your patients with a highly bioavailable form of iron, activated B12, 5-MTHF (the activated form of folate) and vitamin C, such as with High Potency Vegetarian Iron with 5-MTHF, is a comprehensive way to promote the healthy production of RBCs.

Put a Spring in Your Step

It’s established that poor iron status is associated with symptoms of fatigue and lethargy,21 which is due to irons role in mitochondrial respiration as well as oxygen transfer.22 With RBCs responsible for delivering nutrients (as well as oxygen) to the tissues for cellular respiration,23 ensuring adequate intakes of iron along with vitamin B6 is a key strategy to help optimise energy production and therefore reduce fatigue. Vitamin B6 is required here as it is an essential catalyst for energy production within the Krebs cycle.24 In support of the clinical application of iron for fatigue, in particular, is a randomised, controlled trial of 144 non-anaemic women with unexplained fatigue who were prescribed iron, or placebo, daily for four weeks. At the conclusion of the trial, the women receiving iron had a 29% reduction in their fatigue scores,25 demonstrating patients don’t need to be at a low level of iron status to benefit. This is just one of many successful studies on iron which, along with the understanding of the role vitamin B6 plays in energy production, supports their use for fatigue cases.* In addition, for patients struggling to manage their energy levels there is the Metagenics Energy Program, which comprehensively tackles a range of drivers for what can be a frustrating situation for patients just wanting to go about their daily life with vitality.

Give so They May Grow

The incidence of low iron stores can be high amongst pregnant women, with low iron status reported to be as high as 23% in this population.26 Insufficient iron in pregnancy is of concern as this can increase the risk of premature labour, intrauterine growth retardation, perinatal and maternal mortality, and postpartum depression.27 The World Health Organisation recommends the screening of iron status in all pregnant women and advocates that inadequate iron levels should be treated with iron supplementation.28 One of the challenges with this recommendation is that many iron supplements can create undesirable gastrointestinal effects such as constipation, putting patients off their use. A study in pregnant women found 15 mg/day of iron bisglycinate was more effective at preventing pregnancy-related iron depletion than 40 mg/day from iron sulphate,29 making this a viable option for this population group, particularly as iron bisglycinate has been shown to have fewer undesirable effects.30

Enhancing the Uptake

If iron supplementation is required, its clinical effectiveness (and its likelihood to not create gastrointestinal distress) is dependent on its bioavailability. Iron bound to cations, such as sulphur (iron sulphate), may disassociate in the gut releasing free iron. The absorption of free iron is a difficult and inefficient process and can cause symptoms of constipation and nausea.31, 32, 33In contrast, iron bisglycinate (such as Meta Fe®) is a more bioavailable form of iron (see Figure 2),34 clinically proven to improve and maintain iron status, and associated with fewer undesirable gastrointestinal effects.35 The covalent bonding of two glycine molecules to iron is what creates iron bisglycinate.36 Being bound to glycine, the iron is readily absorbed via peptide channels in the gut, rather than competing for ionic channels with other minerals. It is this strong covalent bonding that makes Meta Fe® resist disassociation in the gut, making it more tolerable to patients. Meta Fe® iron bisglycinate is found in High Potency Vegetarian Iron with 5-MTHF.

Energy From Within

By supporting your patients RBC production with a team of nutrients including highly bioavailable iron, activated B12 and 5-MTHF, vitamins C and B6, cellular energy production can be enhanced; leading to more optimal energy levels and reduced sensations of fatigue. High Potency Vegetarian Iron with 5-MTHF may assist people with increased demands for these nutrients such as pregnant and lactating women, the elderly, and patients with gastrointestinal dysfunction, as well as some vegetarians and vegans. For patients wanting to kick-start their energy, also look ‘bigger picture’ with the Metagenics Energy Program solutions to get your patients back on track and raring to go.

*Iron excess can also manifest with symptoms of fatigue and lethargy. As inappropriately prescribed supplemental iron can be harmful it is recommended to always obtain iron studies to assess baseline iron and ferritin levels first, and routinely afterwards to monitor changes.

References

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Original image courtesy of Toa Heftiba

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