How redefining 'normal' iron levels could help women's health
Fatigue, depression and anxiety are all symptoms of iron deficiency
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Nicole Williams often felt tired when she was in high school and university, relying on coffee to chase away fatigue. Then the persistent exhaustion was followed by anxiety that left her unable to concentrate.
"I was getting dysfunctional," Williams, now 43, recalled. "It made it hard to drive, made it hard to get through the day at work and have a kid."
Around 2015, Williams was going from doctor to doctor, trying to figure out the source of her tiredness. Blood test results seemed normal, including those that measure low iron, a common cause of fatigue in women.
Doctors attributed the Toronto woman's symptoms to mental health issues. It took years until a specialist uncovered the real cause: iron deficiency.
Dr. Michelle Sholzberg, a hematologist and scientist at St. Michael's Hospital in Toronto, told Williams her exhaustion and anxiety could "100 per cent" be explained by low iron. But Williams's levels weren't low enough to match what Ontario defined as "low," at that time.
The problem, Sholzberg contends, is that medicine has long been wrong about what a "healthy" level of iron is.
Earlier this month, Ontario updated its limit on ferritin — the protein that stores iron — to 30 micrograms per litre. Previously, the threshold between low and normal varied by lab, from 10 to 15 micrograms per litre.
Sholzberg wants to raise the bar across Canada on what a "normal" level of iron is to 30 micrograms per litre, which she said is based on the best available scientific evidence to avoid symptoms. Doing so could catch and treat the deficiency earlier.
Physicians call iron deficiency a largely hidden problem that often goes undiagnosed. The Canadian Health Measures Survey conservatively estimates it hits seven per cent of Canadians and about 20 per cent of females of child-bearing age.
"Every single day of my career, I have met patient after patient with unaddressed iron deficiency," Sholzberg said.
Yet once iron deficiency is treated, with oral supplements or, in some cases, IV infusion, patients report feeling better.
"I've had many patients tell me that their life has changed, that they feel like Superwoman, that they can concentrate again, that they can go through a day without feeling exhausted."
Iron stores in blood paramount
Red blood cells require iron to ferry oxygen to the brain and heart. The nutrient also fuels the chemical reactions keeping us alive.
Iron deficiency can manifest as anxiety or depression because the element is needed to make neurotransmitters like serotonin and dopamine that are important for mental health.
People may experience cognitive symptoms like brain fog or lack of concentration and have difficulty multitasking. Fatigue, weakness, dry skin, hair and nails can also occur. When ferritin is low and hemoglobin falls below 120 grams per litre for women and below 130 grams per litre in men then the person has iron deficiency anemia, where oxygen-carrying red blood cells are reduced.
Sholzberg said part of the problem diagnosing iron deficiency is the lack of guidance on evaluating people, especially those who menstruate. It arose because "normal" was defined by sampling individuals who were already iron deficient.
Blood is the richest store of iron in our body. Losing too much blood for whatever reason, including a heavy period, can lead to iron deficiency.
Sholzberg and her colleague Grace Tang, a senior research associate working in hematology oncology research at St. Michael's Hospital, as well as laboratory scientists, blood specialists and other advocates for women's health across Canada, the U.S., U.K., Australia and other parts of the world have joined together to lower limits of "normal" ferritin for clinical decision making, such as diagnosing iron deficiency.
'Insidious' problem that's often overlooked
Lowering the threshold where iron deficiency is recognized is a first step to helping their patients, say the doctors.
Iron stores in the blood, or ferritin, reflect an important balance in the body. Until now, labs have set different reference ranges for ferritin, which are often based on historical definitions, said Dr. Menaka Pai, a professor of hematology at McMaster University in Hamilton and Ontario's clinical lead for hematology.
"Within Canada, Ontario is certainly a leader," said Pai. "We are working with colleagues across the country and we're hoping that change is going to happen in every province."
Major lab chains across Canada like Lifelabs, Dynacare and Alpha Labs, have already signed on to Ontario's new ferritin levels, which doctors use to guide their determination of iron deficiency in a patient.
"It's a massive problem and it's insidious," said Dr. Malcolm Munro, an obstetrician and gynecologist who trained in Canada and now works at the University of California Los Angeles medical school.
Munro is optimistic other provinces and U.S. hospitals will follow Ontario and move away from the World Health Organization's current level of less than 12 micrograms of ferritin per litre in serum. That level was adopted by some provincial labs and doctors to determine iron deficiency.
Half of menstruating women in North America would be considered iron deficient under Ontario's new limits, Munro said.
Very heavy periods can be associated with iron deficiency, but many women may not realize it, or their health-care provider may tell them that it's normal.
"You can sort of see how the scope of the problem is diminished because it's normalized not only by the society and the family, but by the doctors," Munro said.
Cutoff debate
However, the move to check seemingly healthy people for iron deficiency is meeting with resistance.
Just last month, the U.S. Preventive Services Task Force concluded there's "insufficient" evidence to support screening and treating iron deficiency in pregnant people without symptoms of iron deficiency.
Dr. Amy Cantor, the task force's lead investigator on the systematic review, said the lack of standardized cutoffs make it harder to build a case for change.
"Conflicting guidelines, variable clinical practices, changing cutoffs for diagnosis, and access to health-care services may affect the accuracy of reported rates of screening and supplementation in all populations and in those at risk for experiencing health disparities," said Cantor, who is also a family physician based at Oregon Health & Science University's medical school, in an email.
Iron deficiency can be treated with oral pills. Pai said many tolerate the pills, while others may have side-effects like constipation or stomach upset.
If pills don't work or patients stop taking them, doctors may recommend intravenous iron therapy, though it costs more.
"That's harder to access in Canada and the funding climate isn't really consistent," Pai said.
Heavy periods can be treated with hormonal birth control and nonhormonal options, such as combined oral contraceptives known as the pill, intrauterine devices or IUDs, tranexamic acid and ibuprofen, Pai added.
Beyond helping women themselves, nurse Nicole Letourneau of the University of Calgary sees benefits of treating iron deficiency for the next generation.
Letourneau's ongoing nutrition and related research shows how low iron can be a predictor of postpartum depression.
"If we can prevent mothers from becoming depressed postnatally by addressing a pretty easy thing — low iron during the early pregnancy or middle of pregnancy — then we are going to be likely having downstream impacts on mothers' mental health and children's health and development," Letourneau said.
For Williams, while the benefits of taking iron weren't instantaneous, she no longer feels sleepy all the time. She says she has the energy to chase her preschooler, work full time and cheer on Sholzberg's efforts.
Williams hopes the new guidelines will help other women with similar symptoms to find relief sooner than when her ferritin dropped from 12 to nine micrograms per litre. "All it would have taken is a real conversation," she said.
Corrections
- A previous version of the story said the Canadian Health Measures Survey conservatively estimates iron deficiency hits seven per cent of women of child-bearing age. In fact, that figure is an estimate for the total population.Sep 16, 2024 7:18 PM ET