Medicine must improve because we want to treat the sick better and because we need to keep up with the new diagnoses being created that turn healthy people into patients.
It seems every 5 year increment of recent time has its darling vitamin, protein, mineral or supplement. Ferritin is the current "it girl". I have been around long enough to remember so many others: Vitamin E, Antioxidants, Calcium, Vitamin D, and a dozen others. We see so often the phenomenon of how large-scale, rigorous clinical trials contradict previous observational studies. While early, observational research suggests that taking ferritin supplements could prevent all sorts of chronic issues --we wait (im)patiently for true data. Meanwhile, Iron infusions abound.
The social media space where such battles are faught has already declared a victory. Iron deficiency with anemia and a ferritin level of at least 70. Many will be forced into such diagnostic boxes with a few placebo wins but mostly continuing to suffer because of other underlying causes that go on unaddressed.
"First, the flaws of using ferritin to diagnose iron deficiency. A Cochrane review from 2021 found insufficient evidence to recommend ferritin as a screening tool for iron deficiency in healthy populations."
This is technically accurate, and there were few tests in healthy patients. Low ferritin is definitely saying something, and where the cutoff should be in healthy people is debated. But at the same time the authors' conclusions:
"Ferritin concentrations appear consistently lower in patients with iron deficiency compared with iron overload, and low ferritin concentrations therefore indicate iron deficiency. A ferritin threshold below 15 to 30 µg/L appears to indicate absent bone marrow iron stores in healthy populations, but there are too few studies to confidently recommend a particular threshold."
Also in the "non-healthy" population (inflammation or cormorbid disease), broadly defined:
"The pooled estimates for the studies on non‐healthy *adults using a 30 µg/L threshold indicate a very specific test (sensitivity of 79% and specificity of 98% with DOR = 134), although the quality of the evidence was low and did not allow us to reach strong conclusions (see Table 3). No accuracy estimates have been pooled for thresholds of 12 µg/L or 15 µg/L since there were not enough studies available for each target population."
From time to time, patients with low ferritin and normal Hb levels are sent to me for GI studies. The patients, of course, have been advised by the referring professionals that endoscopic studies are necessary, and the rationale seems quite plausible to the patients. I cannot recall discovering significant findings in this scenario. At times, if there is a sollid explanation for low ferritin, such as regular blood donations, menstruating female, I offer observation as an option. As in all dx tests, ferritin should be checked to answer a specific clinical question and we should know in advance how the results may affect our care of the patient.
This seems as misguided as “pre-diabetes” or “pre-hypertension”. I agree with the author that this seems to be an exercise in medicalizing healthy people.
I am not a lab med doc. My understanding is that normal ranges reflect the spread from the 2.5 percentile to the 97.5 percentile of the results of healthy volunteers. So by definition, 5% of “healthy” people will already have abnormal lab values.
So I would first ask: have humans changed? Does the new reference range reflect a change in the 2.5-97.5 percentile healthy population results for ferritin?
And second, I would like to see the evidence that this lower diagnostic threshold for iron deficiency (as well as any resultant therapies triggered by such a diagnosis) changes downstream outcomes. I’m a bit skeptical about the existence of such evidence.
I realized that medicine has become a Pill as a Service (PaaS) industry. There's not much talk of healing anyone but managing health. And like in SaaS or IaaS software/tech businesses, ARR (annual recurring revenue) is a key metric. And PUPY (per user, per year) is the lever you can change. And let Adobe be a warning to all doctors. They were the darling of PE as they went from lifetime licenses to SaaS model. And they are CRATORING because at some point, users get sick and tired of never ending "fees" It's also why CD is making a comeback over streaming.
I understand the concern about medicalization and overdiagnosis. Medicine does plenty of that, sometimes at huge cost and with very little benefit. As a hematologist, I just see this topic differently.
To me, ferritin is the warning zone, like the warning track in baseball. It does not mean the outfielder has already hit the wall. It means the wall is getting closer, and there is still time to slow down. A ferritin of 20 or 25 with a normal hemoglobin still needs context, but I do not think it should be ignored.
There is also a reason 30 keeps coming up as the cutoff. Older single-digit ferritin thresholds were very specific for advanced iron deficiency, but they miss a lot of patients whose iron stores are already depleted. When you look at markers of iron-restricted red blood cell production, the point where the body starts showing changes in RBC production is much closer to 30. Hemoglobin can stay normal for a long time while iron stores are falling, so waiting for anemia means waiting until later in the process.
I see this over and over again. Patients show up after they are already symptomatic and anemic. Some are even getting blood transfusions or expensive IV iron. Some then need urgent GI workups. Then you look back and see a ferritin of 18, 22, or 30 from a year or two earlier that was treated as normal because the hemoglobin had not dropped yet.
The risk-benefit ratio here is very different from many of the things we argue about in medicine. Ferritin is a cheap test. It is not perfect, but when it is low, it is a pretty useful marker of depleted iron stores. The bigger problem with ferritin is usually in the other direction: inflammation can make it look falsely normal or high and hide iron deficiency. A low value is much harder to dismiss.
So when I compare the downside of checking ferritin and acting on a low value in context against the downside of waiting, the balance is not close. On one side is a low-cost blood test and, for many patients, an over-the-counter oral iron supplement. On the other side are ED visits, symptomatic anemia, expensive IV iron, urgent referrals, delayed evaluation for blood loss, and sometimes red blood cell transfusions.
So yes, I agree we should be careful about expanding diagnoses. But in this case, waiting for anemia often creates the very thing we are trying to avoid: more testing, more cost, more invasive care, more anxiety, and more missed chances to intervene earlier. Recognizing low ferritin in context feels like common-sense prevention to me.
I agree completely. I own and operate a small Assisted Living Home in South FL. When it comes to making patients out healthy people, low iron is one of the things that does it most. This condition happens gradually, so it looks to the public, Exactly like "dementia, fatigue, COPD" and "They're old - we shouldn't make them walk, let's let them watch TV.
Our residents often have lethargy, confusion, increased fall risk, ALL the symptoms and the ferritin and Threshholds issue is Not letting us Help them.
It would be totally different if I were a newbie, but I Study, following threads like this, poring over labs, I see that when doctors are also reluctant to reduce BP meds, and this condition is present, it's adding up to more fall risk.
Further, in my world, there's polypharmacy, with blood thinners, PPIs, NSAIDs, Thyroid meds, Parkinson's meds, antibiotics, all can bind to iron, leading to poor absorption, so it's really frustrating to hear time and again, "It's kind of low but not that bad. People at this age normally have..."
In my experience, people with proper iron levels live longer, happier, more active lives.
So well put. Agree with everything you said, especially that there are many more examples in medicine of: “overmedicalizing normality” that carry much greater cost with little to no benefit. What is the risk of adding more iron to one’s diet or taking an iron supplement other than constipation? It’s REALLY hard to consume enough iron to reach a toxic range.
As a family physician, I check ferritin in patients with depression, insomnia, thyroid disease, chronic PPI use, and especially in endurance athletes, namely females of child bearing age. That has been my practice in patients with depression and in athletes since 2004 (the others I have added through the years) because the test is cheap, and if it’s low or low-normal there is an easy and inexpensive treatment that can improve their quality of life. I understand there can be trends in medicine, but I would not place screening for iron deficiency in that category. I agree with the author that it should not be ordered indiscriminately on every healthy patient, but certainly anyone with fatigue or other risk factors for anemia.
I agree, and have seen many times where the ferritin (and MCV) preceed the hemoglobin in cases of slow blood loss (menstruation, blood donation, GI bleed, pheresis).
I'm not saying that we should start screening all healthy people for ferritin.
But if your patient has a hgb of 12.6 and a ferritin of 23, you should ask her about her periods and it's totally reasonable to start oral iron. You don't have to wait until the hgb shows up in red on the lab screen to notice a trend.
Mantra repeated frequently during residency by our hematology chief : anemia is never normal. At times we suffer from alarm fatigue and that’s where historical data being graphed is an easier way to find clinically significant changes. The fact that the lab changes kits which have different ranges makes this more difficult to interpret. It is also easier to get the patient to visualize the point being made.
I do think we need to keep in mind that the patients we see are not a uniform group . The implications of iron deficiency in pregnancy for example , are radically different than those for other groups . While ferritin is not the be all and end all , it can be a helpful marker along with other things to help decide whether to offer IV iron ( for example ) in this population. Oral iron supplements are poorly tolerated and work only over long periods of time . Not to mention that many Americans have a very poor diet . Ferritin is but one tool in the tool box , but we shouldn't throw it out . It is pretty good at distinguishing between normal dilutional " anemia " of pregnancy and true nutritional deficiency in this population. I do agree that treating lab generated numbers and not the patient is poor care.
The line between pathology/disease and enhancement is becoming blurred. A legitimate question is whether there is some well-being advantage to iron supplementation, low dose thyroid replacement, testosterone therapy or what have you, in the context normal blood levels (essentially what we would call “doping” in sport) including potentially a placebo effect. I don’t think we know the answer in most cases, nor do we know if there are any risks aside from potentially increased health care costs.
That's an interesting thought, if the placebo effect could be justification enough for implementing low-cost interventions that have possible benefits. Placebos are more effective than most drugs that are conceptualized. I think we greatly underutilize the placebo effect in practice
You really can’t go by the ferritin alone anyway because it is elevated in inflammatory conditions. The art of medicine is being able to synthesize multiple input points, including symptoms or lack thereof.
My ferritin is 13. No anemia. No symptoms. Or maybe there are? I am 45 and perimenopausal, so it is difficult to know what is what. Several years ago, my ferritin was a 4, and I was anemic. I have had pelvic ultrasounds and GI scopes. Spent $$$ on iron supplements because the prescription iron has side effects I did not like. I cannot imagine 13 is “good,” but that is because I have been living with a “goal” of 50.
“ We have a pill for that “…. Wonder if the wellness clinics are going to raise it to 60 and offer the cure. Have seen holistic clinics change the normal values ranges on things like water quality and other environmental factors so as to find what the symptomatic but with unremarkable lab results pts have, then offer them tinctures and drops and detoxification treatments custom designed for them, cash only. Just like with the HRT push by the stop the aging clinics, providers of the cure for the Dorian Grey Syndrome, we medicalize everything then act surprised when the cure is worse than the illness. “ The species has amused itself to death “
This is all the rage among the wellness industry. A thyroid above 1.5, a high uric acid without gout, a low ferritin without anemia, a detectable TPO w normal TSH are all sub-optimal states that can be treated for a low monthly subscription fee. Sorry to see a professional society has jumped on this wellness influencer trend. It is much easier to blame my overall not feeling well on my low ferritin than on the fact that I get 2,000 steps / day and eat pop tarts for every meal.
I agree that over diagnosis is itself becoming a disease. Ferritin reduction seems apt to be included. It is after all a storage form of iron and in the absence of anemia or symptoms is not a malady that demands treatment. (Think sub clinical hypothyroidism). The issue of “iron deficiency (low Fe/high TIBC) with out anemia” is possibly a similar situation although most sources recommend treating this in appropriate symptomatic patients.
It seems every 5 year increment of recent time has its darling vitamin, protein, mineral or supplement. Ferritin is the current "it girl". I have been around long enough to remember so many others: Vitamin E, Antioxidants, Calcium, Vitamin D, and a dozen others. We see so often the phenomenon of how large-scale, rigorous clinical trials contradict previous observational studies. While early, observational research suggests that taking ferritin supplements could prevent all sorts of chronic issues --we wait (im)patiently for true data. Meanwhile, Iron infusions abound.
The social media space where such battles are faught has already declared a victory. Iron deficiency with anemia and a ferritin level of at least 70. Many will be forced into such diagnostic boxes with a few placebo wins but mostly continuing to suffer because of other underlying causes that go on unaddressed.
"First, the flaws of using ferritin to diagnose iron deficiency. A Cochrane review from 2021 found insufficient evidence to recommend ferritin as a screening tool for iron deficiency in healthy populations."
This is technically accurate, and there were few tests in healthy patients. Low ferritin is definitely saying something, and where the cutoff should be in healthy people is debated. But at the same time the authors' conclusions:
"Ferritin concentrations appear consistently lower in patients with iron deficiency compared with iron overload, and low ferritin concentrations therefore indicate iron deficiency. A ferritin threshold below 15 to 30 µg/L appears to indicate absent bone marrow iron stores in healthy populations, but there are too few studies to confidently recommend a particular threshold."
Also in the "non-healthy" population (inflammation or cormorbid disease), broadly defined:
"The pooled estimates for the studies on non‐healthy *adults using a 30 µg/L threshold indicate a very specific test (sensitivity of 79% and specificity of 98% with DOR = 134), although the quality of the evidence was low and did not allow us to reach strong conclusions (see Table 3). No accuracy estimates have been pooled for thresholds of 12 µg/L or 15 µg/L since there were not enough studies available for each target population."
From time to time, patients with low ferritin and normal Hb levels are sent to me for GI studies. The patients, of course, have been advised by the referring professionals that endoscopic studies are necessary, and the rationale seems quite plausible to the patients. I cannot recall discovering significant findings in this scenario. At times, if there is a sollid explanation for low ferritin, such as regular blood donations, menstruating female, I offer observation as an option. As in all dx tests, ferritin should be checked to answer a specific clinical question and we should know in advance how the results may affect our care of the patient.
This seems as misguided as “pre-diabetes” or “pre-hypertension”. I agree with the author that this seems to be an exercise in medicalizing healthy people.
I am not a lab med doc. My understanding is that normal ranges reflect the spread from the 2.5 percentile to the 97.5 percentile of the results of healthy volunteers. So by definition, 5% of “healthy” people will already have abnormal lab values.
So I would first ask: have humans changed? Does the new reference range reflect a change in the 2.5-97.5 percentile healthy population results for ferritin?
And second, I would like to see the evidence that this lower diagnostic threshold for iron deficiency (as well as any resultant therapies triggered by such a diagnosis) changes downstream outcomes. I’m a bit skeptical about the existence of such evidence.
Humans haven't changed. Our diet has.
This doesn't mean that we should all supplement with magnesium and selenium and B12 and, and, and...
I realized that medicine has become a Pill as a Service (PaaS) industry. There's not much talk of healing anyone but managing health. And like in SaaS or IaaS software/tech businesses, ARR (annual recurring revenue) is a key metric. And PUPY (per user, per year) is the lever you can change. And let Adobe be a warning to all doctors. They were the darling of PE as they went from lifetime licenses to SaaS model. And they are CRATORING because at some point, users get sick and tired of never ending "fees" It's also why CD is making a comeback over streaming.
I understand the concern about medicalization and overdiagnosis. Medicine does plenty of that, sometimes at huge cost and with very little benefit. As a hematologist, I just see this topic differently.
To me, ferritin is the warning zone, like the warning track in baseball. It does not mean the outfielder has already hit the wall. It means the wall is getting closer, and there is still time to slow down. A ferritin of 20 or 25 with a normal hemoglobin still needs context, but I do not think it should be ignored.
There is also a reason 30 keeps coming up as the cutoff. Older single-digit ferritin thresholds were very specific for advanced iron deficiency, but they miss a lot of patients whose iron stores are already depleted. When you look at markers of iron-restricted red blood cell production, the point where the body starts showing changes in RBC production is much closer to 30. Hemoglobin can stay normal for a long time while iron stores are falling, so waiting for anemia means waiting until later in the process.
I see this over and over again. Patients show up after they are already symptomatic and anemic. Some are even getting blood transfusions or expensive IV iron. Some then need urgent GI workups. Then you look back and see a ferritin of 18, 22, or 30 from a year or two earlier that was treated as normal because the hemoglobin had not dropped yet.
The risk-benefit ratio here is very different from many of the things we argue about in medicine. Ferritin is a cheap test. It is not perfect, but when it is low, it is a pretty useful marker of depleted iron stores. The bigger problem with ferritin is usually in the other direction: inflammation can make it look falsely normal or high and hide iron deficiency. A low value is much harder to dismiss.
So when I compare the downside of checking ferritin and acting on a low value in context against the downside of waiting, the balance is not close. On one side is a low-cost blood test and, for many patients, an over-the-counter oral iron supplement. On the other side are ED visits, symptomatic anemia, expensive IV iron, urgent referrals, delayed evaluation for blood loss, and sometimes red blood cell transfusions.
So yes, I agree we should be careful about expanding diagnoses. But in this case, waiting for anemia often creates the very thing we are trying to avoid: more testing, more cost, more invasive care, more anxiety, and more missed chances to intervene earlier. Recognizing low ferritin in context feels like common-sense prevention to me.
I agree completely. I own and operate a small Assisted Living Home in South FL. When it comes to making patients out healthy people, low iron is one of the things that does it most. This condition happens gradually, so it looks to the public, Exactly like "dementia, fatigue, COPD" and "They're old - we shouldn't make them walk, let's let them watch TV.
Our residents often have lethargy, confusion, increased fall risk, ALL the symptoms and the ferritin and Threshholds issue is Not letting us Help them.
It would be totally different if I were a newbie, but I Study, following threads like this, poring over labs, I see that when doctors are also reluctant to reduce BP meds, and this condition is present, it's adding up to more fall risk.
Further, in my world, there's polypharmacy, with blood thinners, PPIs, NSAIDs, Thyroid meds, Parkinson's meds, antibiotics, all can bind to iron, leading to poor absorption, so it's really frustrating to hear time and again, "It's kind of low but not that bad. People at this age normally have..."
In my experience, people with proper iron levels live longer, happier, more active lives.
So well put. Agree with everything you said, especially that there are many more examples in medicine of: “overmedicalizing normality” that carry much greater cost with little to no benefit. What is the risk of adding more iron to one’s diet or taking an iron supplement other than constipation? It’s REALLY hard to consume enough iron to reach a toxic range.
As a family physician, I check ferritin in patients with depression, insomnia, thyroid disease, chronic PPI use, and especially in endurance athletes, namely females of child bearing age. That has been my practice in patients with depression and in athletes since 2004 (the others I have added through the years) because the test is cheap, and if it’s low or low-normal there is an easy and inexpensive treatment that can improve their quality of life. I understand there can be trends in medicine, but I would not place screening for iron deficiency in that category. I agree with the author that it should not be ordered indiscriminately on every healthy patient, but certainly anyone with fatigue or other risk factors for anemia.
I agree, and have seen many times where the ferritin (and MCV) preceed the hemoglobin in cases of slow blood loss (menstruation, blood donation, GI bleed, pheresis).
I'm not saying that we should start screening all healthy people for ferritin.
But if your patient has a hgb of 12.6 and a ferritin of 23, you should ask her about her periods and it's totally reasonable to start oral iron. You don't have to wait until the hgb shows up in red on the lab screen to notice a trend.
Homeostasis makes sense to me.
I have to like any reply that uses a baseball analogy.
Mantra repeated frequently during residency by our hematology chief : anemia is never normal. At times we suffer from alarm fatigue and that’s where historical data being graphed is an easier way to find clinically significant changes. The fact that the lab changes kits which have different ranges makes this more difficult to interpret. It is also easier to get the patient to visualize the point being made.
I do think we need to keep in mind that the patients we see are not a uniform group . The implications of iron deficiency in pregnancy for example , are radically different than those for other groups . While ferritin is not the be all and end all , it can be a helpful marker along with other things to help decide whether to offer IV iron ( for example ) in this population. Oral iron supplements are poorly tolerated and work only over long periods of time . Not to mention that many Americans have a very poor diet . Ferritin is but one tool in the tool box , but we shouldn't throw it out . It is pretty good at distinguishing between normal dilutional " anemia " of pregnancy and true nutritional deficiency in this population. I do agree that treating lab generated numbers and not the patient is poor care.
Sounds like Vitamin D
The line between pathology/disease and enhancement is becoming blurred. A legitimate question is whether there is some well-being advantage to iron supplementation, low dose thyroid replacement, testosterone therapy or what have you, in the context normal blood levels (essentially what we would call “doping” in sport) including potentially a placebo effect. I don’t think we know the answer in most cases, nor do we know if there are any risks aside from potentially increased health care costs.
That's an interesting thought, if the placebo effect could be justification enough for implementing low-cost interventions that have possible benefits. Placebos are more effective than most drugs that are conceptualized. I think we greatly underutilize the placebo effect in practice
You really can’t go by the ferritin alone anyway because it is elevated in inflammatory conditions. The art of medicine is being able to synthesize multiple input points, including symptoms or lack thereof.
My ferritin is 13. No anemia. No symptoms. Or maybe there are? I am 45 and perimenopausal, so it is difficult to know what is what. Several years ago, my ferritin was a 4, and I was anemic. I have had pelvic ultrasounds and GI scopes. Spent $$$ on iron supplements because the prescription iron has side effects I did not like. I cannot imagine 13 is “good,” but that is because I have been living with a “goal” of 50.
“ We have a pill for that “…. Wonder if the wellness clinics are going to raise it to 60 and offer the cure. Have seen holistic clinics change the normal values ranges on things like water quality and other environmental factors so as to find what the symptomatic but with unremarkable lab results pts have, then offer them tinctures and drops and detoxification treatments custom designed for them, cash only. Just like with the HRT push by the stop the aging clinics, providers of the cure for the Dorian Grey Syndrome, we medicalize everything then act surprised when the cure is worse than the illness. “ The species has amused itself to death “
Dorian Grey Syndrome. Love it.
I should trademark it but will allow Dr Cifu to use it ad lib in his writings and teachings 🤪
This is all the rage among the wellness industry. A thyroid above 1.5, a high uric acid without gout, a low ferritin without anemia, a detectable TPO w normal TSH are all sub-optimal states that can be treated for a low monthly subscription fee. Sorry to see a professional society has jumped on this wellness influencer trend. It is much easier to blame my overall not feeling well on my low ferritin than on the fact that I get 2,000 steps / day and eat pop tarts for every meal.
Timely. I read this today.
https://drmaryclairehaver.substack.com/p/the-labs-i-run-on-every-menopausal?r=n8zko&utm_campaign=post-expanded-share&utm_medium=post%20viewer
Trying to get up the energy to respond.
Forgot the credit score and wallet biopsy
Fantastic! Thank you!
I agree that over diagnosis is itself becoming a disease. Ferritin reduction seems apt to be included. It is after all a storage form of iron and in the absence of anemia or symptoms is not a malady that demands treatment. (Think sub clinical hypothyroidism). The issue of “iron deficiency (low Fe/high TIBC) with out anemia” is possibly a similar situation although most sources recommend treating this in appropriate symptomatic patients.