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Iron supplements for fatigue

How are you feeling today? Tired? Is it your active lifestyle wearing you down? Or is it a sign of something more serious? Complaints about fatigue seem ubiquitous. Perhaps it’s a product of a culture with little downtime. Yet from a medical perspective, fatigue can’t be dismissed with a simple instruction to “get more sleep”. When approached in the pharmacy, I take the perspective that anyone actively seeking advice on treatment probably needs a medical assessment. That’s not something I can offer, but I try to impress upon patients the importance of finding the cause, rather than reaching for any quick fix that may be for sale. (5-hour Energy, anyone?) And I can use the opportunity to discuss the appropriate role of supplements for treating fatigue.

I’ve elaborated in other posts why I’m not a fan of routine vitamin or mineral supplementation in the absence of any established need – the risks with some supplements are concerning, and the benefits haven’t been clearly established. Recently I’ve had a my position on supplements questioned by people interested in taking iron supplements to treat fatigue. They’re correct, to a degree: fatigue and iron are usually linked. Iron deficiency is the most common nutritional deficiency in the world. And iron deficiency is the major cause of anemia. The statistics are remarkable – in developing countries, 50% of pregnant women and 40% of children are anemic, a result of iron deficiency as well as other illnesses. In contrast with other vitamin deficiencies, anemia is also present to a significant extent in developed countries: 19% of the population in the Americas and 10% in Europe. The incidence is highest in women, particularly pregnant, and youth.

So why not a trial of iron supplements? “Iron loss explains why you’re tired all the time,” suggested a recent Atlantic article. That statement was based on a recent paper that does suggest that iron supplements may reduce fatigue – even in those without anemia. But is supplementation warranted on this basis? In some cases, it could be the wrong approach. Fatigue is a non-specific symptom, so serious causes should be ruled out before thinking about a treatment plan. Medical or psychiatric issues can cause fatigue – depression among the most common. Medications are also a significant (and frequently overlooked) direct cause of fatigue. The long list include antihistamines, opioid narcotics, muscle relaxants, and some antidepressants. Chronic fatigue syndrome is a rare but disabling cause of fatigue that may also be a consideration.

A medical workup will usually include a physical examination and laboratory investigations to rule out specific causes like thyroid dysfunction, cancer, heart failure and other conditions. Laboratory tests will always include hemoglobin and ferritin, two measure to evaluate the iron stores in the blood. The body holds about 4 grams of iron. Two grams is within the hemoglobin of red blood cells, and most of the remainder is stored in ferritin. Low iron can be spotted here.

If there is a confirmation of anemia present, there’s further considerations. Anemia is usually due to increased iron losses, or decreased intake. Fixing the deficiency, without identifying the cause, is foolish. Iron loss can be a signal of diseases like cancer. Or it may be something more straightforward. Pregnancy and menstruation are common causes. Celiac disease is also possible. Reduced absorption is a less common cause of anemia, but several drugs can make matters worse.

When causes of loss have been investigated, treatment considerations are more straightforward. For most people, oral iron supplements are effective, inexpensive, and (generally) well tolerated. When iron supplements are necessary, here are a few considerations:

  • The degree to which the different types of supplements cause side effects seems to be directly related to the amount of elemental iron per pill. Slow release and other forms of iron are more expensive and may be better tolerated, but may also contain less iron.
  • Iron should be taken on a empty stomach to maximize absorption – but few people seem to tolerate this. It’s a trade off, and you need to determine what works. Better to find a dosing schedule that you’ll stick to, rather than making yourself miserable with supplements, or quitting prematurely.
  • For maximal tolerance and absorption, spread doses out throughout the day.
  • Vitamin C may help iron supplement absorption. Taking a tablet with each dose can be considered. Some prefer orange juice instead.
  • Liquid iron supplements are popular, but they’re an inconvenient and expensive way to replace iron stores. I usually suggest generic iron tablets to start, with liquids only where all other dosage forms have failed.
  • Your stools will turn black. Don’t be frightened. Iron isn’t fully absorbed.
  • To replace low iron levels, you should aim for 150-200 mg of elemental iron per day. 300mg per day is about the maximum that people can tolerate.

There is some data suggesting linkages between iron levels and cancer, and others that draw associations between high iron intake and cardiovascular disease. While the relationships are unclear, it suggests that supplementation in the absence of deficiency may not be risk free. Iron is toxic and even fatal at high doses. In children, excessive iron is much more toxic than many prescription drugs, and is a leading cause of poisoning death. (Ten adult-strength ferrous sulfate tablets can kill a small child.) With respect to daily supplementation in the absence of a deficiency, adults taking up to 45 mg of elemental iron per day is generally considered safe.  Multivitamins for pregnant women will usually a small amount of iron, to offset pregnancy-related losses.

Iron stores can be depleted before any anemia is present. It’s traditionally thought the fatigue related to iron deficiency is due to anemia. That hypothesis was tested in a study published in the CMAJ earlier this year which randomized 198 premenopausal women complaining of fatigue, with low ferritin, but not anemia, to iron supplements or placebo. By Vaucher and associates, it’s entitled, Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. All other causes of anemia had to have been ruled out in order to participate. The two treatment groups were comparable with the notable exception that the “iron” group had more women with significantly lowered hemoglobin or ferritin. However, mean values were similar. Also notably the study was sponsored by the manufacturer of the iron supplement studied.

The treatment consisted of 80mg/day of elemental iron (packaged as a slow-release tablet combined with Vitamin C) for 12 weeks. Both groups improved with treatment, as evaluated by a validated scale that measures fatigue with a score of 0-40. Given fatigue can wax and wane, it’s possible that they entered the study at a more fatigued point, and simply improved with time. There was a modest improvement over placebo in the iron group: Women taking iron reported a net improvement of 3.5 points over placebo, which was barely statistically significant. And given the subtle differences between the groups, however, I’m not convinced it’s relevant. So while this is being heralded by purveyors as a 50% improvement, whether it’s a real and meaningful improvement is difficult to say. In a post-hoc analysis , the authors estimate a number needed to treat of 10, suggesting that 10 women reporting significant fatigue need to be treated for 12 weeks in order for one woman to experience less fatigue after 12 weeks. Not that impressive. In contrast to the subjective reports of fatigue, objective measures all improved as expected, including ferritin, hemoglobin, and other.  Blinding seems to have been maintained – both groups had equal amounts of gastrointestinal discomfort. But given iron stains the stool black, it’s not clear why they didn’t ask participants to guess their allocation. And overall, the treatment was well tolerated. The bottom line from this study seems to be that iron supplements in the absence of anemia restore biochemical measures, but their effect on fatigue is modest.

One group that asks me about iron frequently are marathon runners – because I’m a runner too. Running has been associated with iron loss for decades, so I’m often questioned about supplements to prevent any possible anemia. The data suggests that iron deficiency in male runners is rare, so supplementation in the absence of a known deficiency is not advisable. For female athletes, deficiency and anemia is more common. Whether this justifies routine screening is unclear, but my advice to athletes and non-athletes who are concerned about iron is the same: Maximize the consumption of iron in the diet by ensuring a regular intake of iron-rich foods. Meat products provide “heme iron” which is well absorbed, and “non-heme-iron”, which is not. Plants only contain non-heme-iron.  Vegetarians, particularly females, and especially vegetarian female athletes, must carefully monitor their diets to ensure they’re consuming enough iron.

Conclusion

Fatigue can be caused by an array of conditions. Iron deficiency is a common cause, though whether iron supplements offer benefit in the absence of anemia remains to be established. Children and women, particularly pregnant women, need adequate iron in their diet. While low-dose supplements are considered safe and may be helpful in meeting daily requirements, specific supplementation isn’t necessary or advisable in the absence of a clear deficiency. And just because it’s a supplement doesn’t mean it can’t be harmful. Iron supplements can be toxic in children, and should be stored like any other potential poison.

Reference
Vaucher, P., Druais, P.L., Waldvogel, S. & Favrat, B. (2012). Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial, Canadian Medical Association Journal, 184 (11) 1254. DOI: 10.1503/cmaj.110950

Posted in: Herbs & Supplements, Science and Medicine

Leave a Comment (38) ↓

38 thoughts on “Iron supplements for fatigue

  1. Jeff says:

    I keep reading that iron bisglycinate is the best supplemental form of iron.

    1. Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women: http://www.ncbi.nlm.nih.gov/pubmed/11688081

  2. Janet says:

    I’ve been told twice this week that the newest craze for weight-loss, green coffee bean extract, has “really increased my energy”. Both peoples’ faces fell when I told them it was likely a placebo effect–or the caffeine. I was rather tactless, but I get so sick of this.

    It is appalling that something as potent as iron (in the case of children anyway–only ten tablets!) is so readily available without any consultation whatsoever. My kids could undo those safety caps by age five–not that they got into anything, they just liked to show me they could.

  3. Robb says:

    Good post – just wanted to point out that for vitamin C – its role in aiding iron absorption is with dietary iron, not as useful for iron supplements. The article you linked discusses its role in reducing the effects of anti-nutritives (phytates, etc.) found in food on iron absorption. In addition, vitamin C aids the conversion of iron from its ferric to ferrous form – and supplements are already in ferrous form.
    http://www.ncbi.nlm.nih.gov/pubmed/15743017
    Liquid forms of iron are more expensive and require refrigeration but they are a better choice for people who have absorption issues or who can’t tolerate the tablets forms as well.

  4. biocide says:

    Interesting that you are talking about this today.
    I just made an appointment with a specialist because I found out I have hemochromotosis.

    One of the symptoms of hemochromotosis is fatigue.
    If I had decided to treat myself for the fatigue with iron suppliments without finding out about my condition, I could have just made things a lot worse.

  5. mousethatroared says:

    I don’t know. My blood tests have shown mild anemia for months now. My doctor says it’s not enough to cause fatigue and didn’t seem to think it was worth pursuing. I’m not really sure if it has anything to do with an iron definciency, but just in case it might help, I did try to start eating the RDA of iron for a woman my age. It was HARD. Particularily trying to control calorie intake and increase iron. I can totally see wanting to take a supplement instead.

  6. nybgrus says:

    Lets not forget that if someone has the early signs of a sinister organic disease causing fatigue and self treats with iron, the combination of expectancy (waiting more time to see an effect) and placebo effects (both genuine and self-delusional) could lead to a significant delay in identifying the sinister underlying cause.

    @mouse: one clinical truism (of which I recently had to sternly enforce on a classmate) was that there is no “magic” or “reflex” number for repletion (in our case it was discussing indication for blood transfusion). If you are slightly anemic, but chronically tired, especially when other avenues are dead ends, it is quite reasonable to pursue. Assuming iron can be implicated as the cause supplementation is certainly not unreasonable. The converse is true as well – if you are anemic but otherwise completely asymptomatic there is no need to correct the anemia.

  7. nybgrus says:

    @Robb: But there are many foods and liquids that can decrease bioavailability of iron supplements, and thus vitamin C/OJ can mitigate that. In someone with a varied diet and in need of a few months of iron supplementation, advising the co-consumption of OJ/VitC is prudent to ensure adequate uptake since there is no risk and only potential benefit. And as Scott said in his article:

    Vitamin C may help iron supplement absorption. Taking a tablet with each dose can be considered. Some prefer orange juice instead.

  8. Robb says:

    nybgrus,
    Yes, reading a bit more closely I can see vitamin C plays a role in both reducing from ferric to ferrous form and in chelating anti-nutritives that might otherwise bind with iron.

  9. tmac57 says:

    Some of us older readers are probably thinking about this old classic:

    http://youtu.be/3QbcGigQ5wk

  10. Jan Willem Nienhuys says:

    I wonder whether eating things with iron in them (if possible in heme form) might be just as well as taking pills.

  11. Harriet Hall says:

    I used to get fried blood in select restaurants when I lived in Spain. Delicious with garlic. I bet that’s a great source of iron.

  12. tmac57 says:

    Harriet Hall- It must have taken sang-froid to have eaten fried blood.

    1. Harriet Hall says:

      @tmac 57,

      Love it! A multilingual pun, no less!

  13. lilady says:

    Thanks tmac for that video….and back at you.

    http://www.thevog.net/video/2543/carters-039-little-liver-pills-039-1961-tv-commercial/

    I never was anemic in my lifetime…except toward the end of my two pregnancies…when there was a physiological reason…hemodilution of pregnancy:

    http://www.merckmanuals.com/professional/gynecology_and_obstetrics/pregnancy_complicated_by_disease/anemia_in_pregnancy.html

    Dr. Hall…fried blood? Never! I could never *manage* to choke down fried calves liver, when it was recommended by my OB. I added a lot, a whole lot, of leafy dark green veggies to my diet.

  14. mousethatroared says:

    nybrgus – thanks for the tip.

    Hehe -love the videos. My mom’s family used to refer to “tired blood” It’s a much more entertaining mental image than “anemia”.

    I’m trying to imagine how to fry blood.

    1. Harriet Hall says:

      How to fry blood:
      Collect blood, preferably from a cow.
      Let it coagulate.
      Cut it into little cubes.
      Fry in olive oil with garlic and onion.

      It’s not so weird. It has a taste similar to liver but without the chewy texture. It’s very rich, and portions are small. Blood sausage is good too.

  15. Janet says:

    @HH

    Or blood pudding in Scotland! (the term pudding isn’t used the same way in Britain as here, for those who don’t know). I also ate lots of steak and kidney pie in the 80’s in England and now I can’t give blood for my efforts!

    To you who recoil at food you didn’t grow up on–get over it. You think the beef you cook doesn’t have blood in it? Honestly, if you eat FLESH, why not blood–what’s the difference once it’s cooked?

    I was anemic as a kid and forced to eat tough, overcooked liver–ick. Liver cooked properly (barely) with lots of caramelized onions is a delicacy I occasionally indulge in–as in once a year. The rest of the time I rely on lots of leafy greens–kale, collards, chard, spinach and whole grains.

    @Mouse

    I sympathize with you in trying to get necessary nutrients without exceeding the meager calories my aging metabolism will tolerate without gaining weight, but the greens really help with that. I use them in everything, cooked and raw. I grow them almost year round, so they’re always outside the kitchen door, ready for the picking and under a light in the basement in winter.

  16. mousethatroared says:

    Hmm, I guess I fall into that group who will eat just about anything fried with olive oil and garlic because it sounds pretty good to me. Just not sure where I could get any quantity of cow’s blood.

    I doubt I could sell the kids on it though. Possible the blood sausage. They’ll eat anything that look like a hot dog. :)

    Janet – yeah, I actually really like greens, particularily fried in olive oil and garlic…

  17. nybgrus says:

    German blutwurst (blood sausage) is one of my favorite cold cuts. You should be able to find it at most German deli’s, if you have one around.

    As for getting the blood – you can usually pick it up, cooked or raw, from Asian markets. Back in Southern California we had 99 Ranch Markets which sold blood. It was usually pigs blood, but it all tastes the same to me.

  18. Janet says:

    @HH and Mouse

    You can eat fried food?!

    It simply isn’t possible for me. I get about a Tbsp. of oil/day so I use it for dressing for my greens or to saute my garlic–or spray it on my 2 Tbsp of popcorn. It’s so unfair–but I did get very good results on my recent lipid panel and other tests.

    @nybgrus

    blutwurst! You too (eating stuff I used to love)! Man, I get nothing fun to eat anymore. All that salt and fat–you may be sorry one day. :-)

    Still, I really do LIKE kale–it’s not a penance for past indulgences.

  19. mousethatroared says:

    Janet – Yeah, sorry. Seems I got lucky on the cholesterol genetics. The calories are problematic, but I don’t have trouble with pan-fried in olive oil…don’t really do much deep fried.

  20. mousethatroared says:

    …panfried in olive oil causing high cholesterol that is.

  21. Harriet Hall says:

    @Janet,

    I wonder how you would survive in Spain. Olive oil is essential to Spanish cuisine, from gazpacho to paella.
    And yet the death rate from cardiovascular disease is an order of magnitude lower than in the US.

    Although low-fat diets are still commonly recommended for the prevention and treatment of heart disease, the evidence for effectiveness is questionable. See http://query.nytimes.com/gst/fullpage.html?res=FA0F13FD3F5A0C7B8CDDAB0894DE404482 The contribution of dietary fat to blood cholesterol levels is small.

  22. Robb says:

    Dietary cholesterol is from saturated animal fats – olive oil and other seed oils don’t contain any. Plant oils have phytosterols instead which compete for absorption with cholesterol.
    http://www.ncbi.nlm.nih.gov/pubmed/19091798

  23. tmac57 says:

    Lilady-Thanks for the blast from the past.I had totally forgotten Carter’s Little Liver Pills (Carter’s Pills later I think). Back then I had no idea what ‘regularity’ and ‘laxatives’ were all about,and why people cared so much about them.
    It is really amusing to see just how unsophisticated and clumsy the advertisers were in those days,but I think there is a message in that fact. People were not any stupider in those days,and it has been an arms race between the hawkers of nonsense and the public trying to keep up with the facts,that will probably never end.
    But at least we have SBM on our side now! :)

  24. @HH,

    I have to say – fried blood sounds absolutely disgusting :) But I’m as picky as they come when it come to food. I’m surprised to read you misspeak, when you wrote: “The contribution of dietary fat to blood cholesterol levels is small.” That’s a half truth – it of course depends on the type of dietary fat. Saturated fat greatly contributes to blood cholesterol levels.

  25. tmac57 says:

    Harriet Hall- I’m glad that you appreciated it.
    Most of the time when I make a P.O.W. ,my friends wish that I would become one. Dang!!! Did it again!

  26. Harriet Hall says:

    @SkepticalHealth,

    “Saturated fat greatly contributes to blood cholesterol levels.”

    That’s a common understanding, but it’s not substantiated by the evidence.
    High cholesterol levels usually only decrease by 10% or less with dietary modification, and most patients with high LDLs can’t lower them sufficiently without a statin.
    And this recent meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824152/

  27. Sigh, old Harriet is out of date. Please do better research. Evidence finds that replacing dietary saturated fat with unsaturated fat decreases LDLs and CVD in a dose-response relationship. Really – get with the times.

  28. Harriet Hall says:

    @SkepticalHealth,

    “Sigh, old Harriet is out of date.”
    The 2010 meta-analysis I cited is not out of date.

    “Evidence finds that replacing dietary saturated fat with unsaturated fat decreases LDLs and CVD in a dose-response relationship.” That may be, but the meta-analysis didn’t show any association between saturated fat intake and CVD, and the effect of dietary changes is not very clinically important compared to the effect of statins.

  29. Heh. You’re wrong. You combatted facts that I wrote with something that is unrelated. You can be upset with me because I’m picking on nybgrus for going to a 2nd-rate medical school, but you can’t change facts regarding cardiovascular health. You should know that studies that don’t differentiate between dietary fat never seem to show any benefit until they replace saturated fats with non-saturated fats. Are you implying that diet is unimportant to cardiovascular disease?

    You should probably review the ATPIII guidelines again. Obviously statins are important, and I believe in aggressive statin therapy, but to say that dietary intake is not clinically important compared to statins is just wrong. In fact, that kind of statement is the exact opposite of good medicine. That’s very unlike the Harriet I’ve read in the past.

  30. Harriet Hall says:

    The meta-analysis I cited specifically looked at saturated fat, finding no correlation with CVD.

    Another meta-analysis did indeed find that replacing SFA with PUFA reduced cardiac risk:
    http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000252
    But they said “it is not possible from this evidence alone to distinguish between the benefits of reducing SFA and the benefits of increasing PUFA. Furthermore, the small number of trials identified in this study all had design faults,”

    The book I reviewed, Heart 411, pointed out that only 20% of our cholesterol comes from diet; we manufacture the rest. It said saturated fat contributes to heart disease and recommended the Mediterranean diet, but it didn’t stress PUFAs and it said existing studies were not definitive for the Mediterranean diet.

    And no, I didn’t mean diet is unimportant; I only meant that dietary intervention is seldom sufficient by itself. A review article in AFP estimated that dietary advice only lowers total cholesterol levels by 3-6%. http://www.aafp.org/afp/2005/0315/p1137.html Even if it is more successful than that, I think cutting calories to lose weight is probably more important than worrying about the exact content of the diet.

    Am I missing something more recent or more definitive? If I’m wrong, I’d appreciate being shown why with citations. I’m always willing to learn by being pointed to better published evidence, but I don’t learn anything from gratuitous put-downs.

  31. lilady says:

    @ tmac57: Lucky you. You never had an auntie who read all of Gayelord Hauser’s *nutrition* books. I think he got my auntie *hooked on* Swiss Kriss. When I and my siblings spent weekends with her, she was always dosing us with heaping spoonfuls of dried stuff from the large green box. We learned to not sneeze or blow our noses near her…she believed we needed “a good cleaning out”.

    http://en.wikipedia.org/wiki/Gayelord_Hauser

    http://www.vitacost.com/natural-swiss-kriss-herbal-laxative-bulk?csrc=GPF-PA-075820158354&ci_sku=075820158354&ci_gpa=pla&ci_kw={keyword}&gclid=CKm2q56P2rICFQyZ4AodQjkA2Q

  32. SwissFrank says:

    There is very strong evidence that Vitamin C enhances absorption of non-haem iron (not supplemental) in infants. The following study showed a doubling of absorption when ascorbic acid was administered alongside common weaning foods: http://ukpmc.ac.uk/abstract/MED/7596676/reload=0;jsessionid=LuMxdevW19amVyj7MTPg.0

  33. elburto says:

    @Janet -

    ” Or blood pudding in Scotland! (the term pudding isn’t used the same way in Britain as here”

    “Blood pudding” is typically called “black pudding” here in the UK. However, aside from black pudding, white pudding and Yorkshire puddings, the word “pudding” is only otherwise used for desserts.

    In Northern dialects the word “pudding” is generally used to refer to all desserts, as there are (obviously) fewer French words used in areas not touched by the Norman invasion. So you would ask “What’s for pudding?” rather than “What’s for dessert?”.

    WRT ingesting haem iron from food in an attempt to reverse anaemia, I’d like to add how glad I am that pernicious anaemia no longer requires daily ingestion of raw liver or liver juice, or partially digested and regurgitated minced beef as the only available treatments. I think I might have just given up! At least black pudding is cooked, and can be disguised or drowned in something. Half a pound of raw liver though? To use a colloquialism, that’s proper minging.

    Thanks be to Todd and Folker, for the discovery and isolation of cobalamin!

  34. Bryan Bartens says:

    Raw liver? Yuk. I couldn’t eat half a pound to save my live. Not to mention regurgitated minced beef.

    I don’t think a lot of patients with pernicious anemia were actually treated with that. The majority of them would probably have given up. William B. Castle used stomach content of healthy individuals in an experiment to show that vitamin B12 needed intrinsic factor produced by the stomachs parietal cells to be absorbed.

    Minot and Murphy didn’t win the Nobel prize for designing a diet prescribing raw liver. Rather rare would be just fine. William P. Murphy himself on the subject:

    “The liver and the muscle meat should be eaten rather rare, and may be cooked in various ways in order to make it palatable and appetizing; but it should not be fried or prepared with fat. The liver is usually very satisfactorily cooked by broiling or baking it.”

    W.P. Murphy, Diet In Perniciious Anemia, Am J Public Health, 1927.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1321559/pdf/amjphealth00001-0105.pdf

  35. @Bryan,

    I’ve often thought if I crashed on a deserted island, I’d be the first to die. I don’t know if I could make myself even eat fish. :) Let alone the raw liver of some strange animal.

  36. Bryan Bartens says:

    Me either. No sushi for me ;) We’d have to survive on fruit and veg. That should give a rescue party plenty of time, though. The human body stores enough B12 in your liver to last at least a couple of years. If the island had wifi they wouldn’t have to hurry :)

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