Lest We Forget – Iron Deficiency is Common and a Health Risk!

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Faced as we are with an infectious and mutating agent of illness, the allied focus on nutritional needs has been to identify foods and nutritional concentrates that confer an immunological advantage[1]. Covid-19 does not treat us equally. Undernourished people have weaker immune systems and may be at greater risk of severe illness due to the virus.

Because iron deficiency degrades non-specific immunity, your body’s first line of defence against pathogens, you are more vulnerable to infection and disease, and other health complications[2]. In fact, frequent infections are a lesser-known symptom of iron deficiency. At the same time, poor metabolic health, including obesity and diabetes, is strongly linked to worse Covid-19 outcomes, including risk of hospitalisation and death[3].

Iron deficiency anaemia (IDA)

In summary, iron deficiency anaemia is a global health concern affecting children, women and the elderly, whilst also being a risk factor for infection and a common comorbidity in multiple medical conditions. Yet many practitioners and clinicians forget that it is literally the most common nutrient deficiency in the world[4].

IDA aetiology is variable and has been attributed to several risk factors decreasing iron intake and absorption or increasing demand and loss, with multiple aetiologies often coexisting in an individual, compounding the ease of discovery.

Although presenting symptoms may be nonspecific, there is emerging evidence on the detrimental effects of IDA on clinical outcomes across several medical conditions. Re-exploring and increased awareness about the consequences and prevalence of iron deficiency anaemia should aid early detection and management.

Most IDA patients are asymptomatic and identified through a blood test. Pallor is the most important clinical sign, but it is not usually visible unless haemoglobin falls below 7 g/dL to 8 g/dL or below the averages of 35.5 and 44.9 percent for adult women and 38.3 to 48.6 percent for adult men.

A thorough history may reveal fatigue, a decreased ability to work, shortness of breath, or worsening congestive heart failure. Children may have cognitive impairment (as may adults) and developmental delays[5]. Naturally, detailed questions regarding diet as well as asking about any bleeding from menorrhagia or gastrointestinal sources are the minimum. The physical exam may reveal pale skin and conjunctiva, resting tachycardia, congestive heart failure, and occult blood-positive stool.

Pernicious anaemia

Iron, vitamin B12 and folate are required for essential metabolic functions. Deficiency states of these nutrients, either singly or in combination, are also common clinical findings.

Vitamin B-12 deficiency anaemia is a condition in which the body does not produce enough healthy red blood cells because of a lack of vitamin B-12. Which, whilst not as frequent a deficiency as iron, some 20% of the population are estimated to have marginal or profound insufficiency[6]. These cells are essential to carry oxygen to all parts of the body. Without enough red blood cells, tissues and organs become oxygen deficient.

Folic acid or folate is another B vitamin in which a deficiency state commonly occurs. Either a lack of vitamin B-12 or a lack of folate causes a type of anaemia called megaloblastic anaemia or pernicious anaemia.

Iron deficiency without anaemia (IDWA)[7]

It is estimated that iron deficiency without anaemia is twice as common as with[8]. Diagnosing IDWA relies on a combination of tests, including haemoglobin and ferritin levels, as well as transferrin saturation.

Once identified, treatment should include supplementation and nutritional advice with the aim to consume meat, poultry, or fish at least five times a week, with complementary wholemeal products, legumes, and vegetables, and if vegetarian or vegan, specific direction needs to be given[9].

Oral supplementation of iron

Oral iron is associated with gastrointestinal side effects such as constipation, diarrhoea, dyspepsia, and nausea, which have been associated with poor adherence[10]. Using single doses on alternate days as opposed to multiple doses on consecutive days has been shown to result in higher absorption and better regulation of the hormone hepcidin levels in iron-depleted individuals.

Hepcidin controls the amount of iron in the body by blocking absorption of dietary iron. The more hepcidin produced, the less iron is absorbed from the diet.

After one iron tablet, hepcidin concentrations rise sharply, stopping the absorption of a second iron tablet if it is taken the same day or even the next day. Further enhancements can be made by consuming iron supplements with vitamin C alongside, albeit that some people are able to manage iron uptake without ascorbic acid assistance[11]. Ascorbate modulates iron metabolism by stimulating ferritin synthesis, inhibiting lysosomal ferritin degradation, and decreasing cellular iron efflux. In short, ascorbate is a regulator of mammalian iron metabolism and homeostasis[12].

Iron is best absorbed when taken on an empty stomach with a full glass of water or orange juice. If the client experiences an upset stomach, iron can be given with food or immediately after meals. But note when taken with meals iron absorption decreases to 40%[13].

Conclusion

It is also worth recalling that it is not only red blood cells that need iron. When we make an immune response to an infection or a vaccine, the white blood cells that fight infection and make antibodies also need iron. As such, whilst supplementation with Vitamins A, D, E, B, C and minerals including zinc and magnesium have been reported to be essential for immune enhancement and post exposure via wild type Sars Cov-2, vaccination or both. It has been easy to forget the essential and commonly deficient mineral – iron[14].

References

[1] Calder PC Nutrition, immunity and COVID-19 BMJ Nutrition, Prevention & Health 2020;3

[2] Dev S, Babitt JL. Overview of iron metabolism in health and disease. Hemodial Int. 2017;21 Suppl 1(Suppl 1):S6-S20. doi:10.1111/hdi.12542

[3] https://globalnutritionreport.org/reports/2020-global-nutrition-report/2020-global-nutrition-report-context-covid-19/

[4] GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 [published correction appears in Lancet. 2017 Oct 28;390(10106):e38]. Lancet. 2017;390(10100):1211-1259. doi:10.1016/S0140-6736(17)32154-2

[5] Doets EL, Ueland PM, Tell GS, Vollset SE, Nygård OK, Van’t Veer P, de Groot LC, Nurk E, Refsum H, Smith AD, Eussen SJ. Interactions between plasma concentrations of folate and markers of vitamin B(12) status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study. Br J Nutr. 2014 Mar 28;111(6):1085-95.

[6] Lindsay H Allen, How common is vitamin B-12 deficiency?, The American Journal of Clinical Nutrition, Volume 89, Issue 2, February 2009, Pages 693S–696S

[7] Al-Naseem A, Sallam A, Choudhury S, Thachil J. Iron deficiency without anaemia: a diagnosis that matters. Clin Med (Lond). 2021 Mar;21(2):107-113. doi: 10.7861/clinmed.2020-0582. PMID: 33762368; PMCID: PMC8002799.

[8] Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood 2014;123:615–24.

[9] Angela V Saunders, Winston J Craig, Surinder K Baines and Jennifer S Posen Iron and vegetarian diets Med J Aust 2013; 199 (4): S11-S16

[10] Baird-Gunning J, Bromley J. Correcting iron deficiency. Aust Prescr. 2016;39(6):193-199. doi:10.18773/austprescr.2016.069 /

[11] Li N, Zhao G, Wu W, et al. The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(11)

[12] Darius J.R. Lane, Des R. Richardson, The active role of vitamin C in mammalian iron metabolism: Much more than just enhanced iron absorption!, Free Radical Biology and Medicine,Volume 75, 2014,Pages 69-83,

[13] A.L. Lopez, P. Cacoub, I.C. Macdougall, L Peyrin-Biroulet Iron deficiency anemia Lancet, 387 (2016), pp. 907-916

[14] Hariyanto TI, Kurniawan A. Anemia is associated with severe coronavirus disease 2019 (COVID-19) infection. Transfus Apher Sci. 2020;59(6):102926. doi:10.1016/j.transci.2020.102926

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