Health - Iron - Anamnesis [2]

Some specialists question whether iron deficiency is always a cause for concern – especially if it arises in the absence of any physical symptoms and if the patient does not have anaemia.

Pasricha co-authored a review to help inform the World Health Organization's guidelines on iron supplementation in women. In that research, he found something interesting. 

While those women in clinical trials who were iron deficient and reported feeling fatigued found that their fatigue improved upon taking iron supplements, the intervention didn't change the energy levels of women who were also iron deficient, but who had not reported fatigue. 

"This hints to us that, at least in adults, if you're clinically unwell with an iron deficiency, then of course you should be treated and that will improve how you feel," Pasricha says. "But it also suggests that, if you're feeling perfectly fine, and someone just finds that you have a low iron level – then it's hard to be sure that that treating you then would boost you to feel any different."

Overall, iron deficiency in the absence of anaemia has been studied less than iron-deficiency anaemia. But there are some broad conclusions we can make, researchers say.

"The consensus is that iron-deficiency anaemia is certainly worse," says Zimmermann. "But iron deficiency is also associated with impairment."

According to some studies, the effects of iron-deficiency anaemia – particularly in children – can be long-lasting. "It's not just about [poor health outcomes] – it is that you didn't maximise your development," Corkins says.

One review, for example, found a "consistent association" between children with iron-deficiency anaemia having poorer cognitive performance compared to controls. However, the researchers note, perhaps it's not iron-deficiency anaemia that's the problem. It could be the effect of anaemia in general, which depresses energy levels. The researchers also say in their review that it is hard to rule out the influence of socioeconomic factors on children’s behaviour and cognition.

This complexity lies at the heart of all nutrition research: is it the absence of a nutrient itself that's the problem, or is that deficiency a sign of something else going on?

To complicate matters further, the criteria for defining iron deficiency in children is still up for debate, says Zimmermann. Because children are growing so fast, he adds, iron deficiency normally quickly leads to anaemia – which means it's not easy to find, and study, iron-deficient children who are not anaemic.

To supplement or not to supplement

Given that, and the potential consequences for their development, guidelines often advise supplementing children with iron at any sign of deficiency – or even to supplement as a prevention measure. 

In the US, for example, the American Academy of Pediatrics recommends that babies who are exclusively breastfed receive iron drops from four months old, for example. This is because breastmilk has low levels of iron, while formula milk is usually fortified.

But some researchers question this approach.

Pasricha was involved in the largest trial to date that has examined the effect of supplementation on child development, he says. The study, of 3,300 eight-month-old babies in Bangladesh, randomised children into groups that received either daily iron supplementation for three months, or a placebo. He and colleagues measured the children's neurodevelopment before and after the supplementation. "We did not see any evidence of a functional benefit," he says, although they also saw no harm either way.

"We did see that haemoglobin and iron status did improve in the children that received iron – but we didn't see that affect child development," says Pasricha. The "why", he says, "is something that the team is really grappling with".

Other research has yielded similar findings. For example, in one study, even after infants with iron-deficiency anaemia received supplementation that corrected their anaemia, they continued to show more restless sleep patterns than their cohorts – sometimes even years later.

One possible reason might be that even a brief period of deficiency can lead to long-lasting harm. One study, for example, found that when children had had iron deficiency at birth, they had less activation in the regions of their brain related to cognitive control at eight to 11 years old – even if their iron levels had been corrected. 

But another possibility, Pasricha says, is that it isn't the low iron itself that causes poorer development, but that low iron is an indicator of something else – such as other nutrients in a person's diet that are missing.

Meanwhile, there could also be downsides to supplementing children who don't actually have a deficiency. Some studies have found that babies and toddlers who had adequate iron levels, but received supplementation, had poorer weight gain and less growth compared to controls. Randomised controlled trials have found that babies randomly assigned to high-iron formula milk scored more poorly on cognitive tests of abilities like visual memory, reading comprehension and mathematics at both 10 years old and 16 years old, compared to those on a low-iron formulation. However, exactly how much iron supplementation would avoid these effects remains unclear, the researchers say as other factors could also be involved.

Given results like this, however, some experts have criticised US guidelines to supplement all breastfed infants.

Supplements can also have other side effects. Zimmermann, for example, has studied how supplementation can affect people's microbiome. Bacteria thrive on iron, he says. The very small amount of iron that breastmilk has is bound to protective substances like lactoferrin, which helps to keep iron away from potential pathogens in the gut – especially protective for babies, who have immature immune systems. Giving a baby aged six months old micronutrient powders containing iron, which is what many experts recommend, could result in a negative outcome, says Zimmermann.

"These powders have very high amounts of iron in them… which can cause a very rapid shift in the microbiome," says Zimmermann. The babies can't absorb all that iron, which ends up impacting their gut microbiome – potentially towards a balance favouring "the pathogens we worry most about in babies", he says. This includes E. coli, which grows prolifically in the presence of iron.

Many clinicians and researchers agree, however, that when someone has iron deficiency or iron-deficiency anaemia along with symptoms, supplementing can be one of the fastest ways to help them improve. One review of iron deficiency in endurance athletes, for example, found that supplementation not only improved ferritin and haemoglobin, but athletes' aerobic capacity, too. 

Whether to take supplements – or give them to a child – is something that people should decide with the help of a doctor, experts say.

A balanced diet

But in an ideal world, people would get sufficient iron by eating a balanced diet that includes iron-rich foods, and avoid developing a deficiency in the first place – though this is not always possible. Ingredients such as liver or red meat, pulses, including kidney and edamame beans and chickpeas, as well as nuts and dried fruits are all considered good sources of iron.

The American Academy of Pediatrics recommends that infants aged six to 12 months need 11 mg of iron per day. For toddlers, they recommend 7 mg, and for four- to eight-year-olds, 10 mg.

Part of the higher recommendation for younger babies is because of their rapid development, experts say. But it's also because there is an assumption being made that most infants' first solids will be foods like iron-fortified cereals, as well as fruits and vegetables – non-heme sources of iron, which the body absorbs less readily than heme sources, which are animal-derived, like meat, fish and eggs.

"Diet is the best approach. Your body tends to take it up better. Your body tends to use it better," Corkins says. "Now, if someone is profoundly anaemic, and you're trying to get them fixed faster – then you do supplementation."

As for Ryan, she was able to correct her iron deficiency both times it happened: in pregnancy, with a supplement, and in 2023, with iron infusions, administered at her hospital, every two weeks for five months. "It wasn't a quick fix," she says. With time, however, she noticed her fatigue fade.

- Author: Amanda Ruggeri, BBC