VeganHealth Update: Iron and Vegetarian Diets

I have been silent lately due to updating the Iron article at VeganHealth.org. In the past, it has been just a mishmash of bits I’ve written as needed. It is now a well-organized, tight piece (I hope).

One new addition worth mentioning is on type 2 diabetes. Excerpt:

“There is evidence that the beta cells of the pancreas, which produce insulin, are particularly susceptible to oxidation from iron due to their weak antioxidant defense mechanisms. A 2012 meta-analysis of prospective studies found that higher iron stores (6 studies) and higher intakes (5 studies) of heme iron [a type of iron found only in meat] at baseline were strongly associated with a higher risk of type 2 diabetes (1). Higher intakes of non-heme iron were not associated.

“A cross-sectional study from the USA found lower ferritin [stored iron] levels in lacto-ovo vegetarians (35 µg/l) than meat-eaters (72 µg/l). The vegetarians also had higher insulin sensitivity. Upon giving phlebotomies to 6 male meat-eaters to reduce their ferritin levels, their insulin sensitivity increased. The authors suggested that the lower ferritin levels could be a reason why vegetarians had greater insulin sensitivity (2).

“It is possible that the lower risk of type 2 diabetes in vegetarians (see Type 2 Diabetes and the Vegan Diet), which has been shown to be independent of body mass index, could be partially explained by their lower iron stores.”

Link to full article: Iron. Warning: It’s long and not required reading. :)

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References

1. Bao W, Rong Y, Rong S, Liu L. Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis. BMC Med. 2012 Oct 10;10:119. | link

2. Hua NW, Stoohs RA, Facchini FS. Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians. Br J Nutr. 2001 Oct;86(4):515-9. | link

12 Responses to “VeganHealth Update: Iron and Vegetarian Diets”

  1. Dan Says:

    There is an academic hematologist in Vermont (white river junction) who treats vascular disease patients with phlebotomy (just as patients with hemochromatosis – primary iron overload) are treated. He published a randomized trial in JAMA with offshoots in Am Heart J and JNCI. The bottom line is large reductions in incident cancer mortality – very intriguing. These weren’t vegans – they were patients with peripheral arterial disease and probably omnivores.

    Counterbalancing this, there have been trials showing that if you provide oral iron supplementation to fatigued people with subclinical iron deficiency (but no anemia – just low ferritin status), they experience significant, clinically relevant relief of their fatigue. One such trial was recently published in CMAJ.

    So I see a real trade-off here — accept low iron stores and have some protection against cancer (and possibly vascular disease) but have to put up with fatigue versus remitting the fatigue to a clinically significant extent but lose the protection against cancer.

    By the way, some suggest that the mechanism of action of aspirin on cancer protection is due to micro-occult loss of iron (due to subclinical bleeding) from the GI tract.

    (sorry not to post URLs for all the above – I would have to do some literature searching to find them. Just remembered – funny how the mind works! – that the PI of phlebotomy study was Dr Leo Zacharski)

  2. Jack Norris RD Says:

    Dan,

    I would think that there is a happy medium between iron levels so low you have fatigue and so high that you are at risk for cancer. If you find that clinical trial from JAMA I’d be interested. I’d be surprised that you could have a clinical trial of phlebotomies so large that you could assess primary prevention of cancer.

  3. Dan Says:

    Jack,

    The trial was powered for cardiovascular events, not cancer. The cancer findings were published separately. PAD (peripheral artery disease) patients are very high risk for malignancy, because they smoke and drink more than the general population; as well they have shared risk factors for cancer and cardiovascular disease such as high cholesterol and hypertension.

    J Natl Cancer Inst. 2008 Jul 16;100(14):996-1002. doi: 10.1093/jnci/djn209. Epub 2008 Jul 8.

    Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial.

    Zacharski LR, Chow BK, Howes PS, Shamayeva G, Baron JA, Dalman RL, Malenka DJ, Ozaki CK, Lavori PW.

    Source
    Research Service (151), White River Junction VA Medical Center, Department of Veterans Affairs Medical Center, 215 North Hartland Road, White River Junction, VT 05009, USA. leo.r.zacharski@dartmouth.edu

    Abstract

    BACKGROUND:
    Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical-mediated oxidative stress.
    METHODS:
    A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease. Patients without a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to control (n = 641) or iron reduction (n = 636). Occurrence of new visceral malignancy and cause-specific mortality data were collected prospectively. Cancer and mortality outcomes in the two arms were compared using intent-to-treat analysis with a Cox proportional hazards regression model. Statistical tests were two-sided.
    RESULTS:
    Patients were followed up for an average of 4.5 years. Ferritin levels were similar in both groups at baseline but were lower in iron reduction patients than control patients across all 6-month visits (mean = 79.7 ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI = 115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the iron reduction group than in the control group (38 vs 60, hazard ratio [HR] = 0.65, 95% CI = 0.43 to 0.97; P = .036), and, among patients with new cancers, those in the iron reduction group had lower cancer-specific and all-cause mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI = 0.29 to 0.83; P = .009, respectively) than those in the control group. Mean ferritin levels across all 6-monthly visits were similar in patients in the iron reduction and control groups who developed cancer but were lower among all patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017).
    CONCLUSIONS:
    Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk.

  4. Dan Says:

    Here is the trial in CMAJ. I’m sure there are others in the literature with similar findings.

    CMAJ August 7, 2012 vol. 184 no. 11 First published July 9, 2012, doi: 10.1503/cmaj.110950
    © 2013 Canadian Medical Association or its licensors
    All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
    Research
    Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial
    Paul Vaucher, DiO MSc, Pierre-Louis Druais, MD, Sophie Waldvogel, MD, Bernard Favrat, MD⇓
    + Author Affiliations

    From the Department of Community Medicine and Primary Care (Vaucher), University of Geneva, Switzerland; the National College of General Practitioners (Druais), Le Port Marly, France; the Blood Transfusion Service of the Swiss Red Cross (Waldvogel), Lausanne, Switzerland; and the Department of Ambulatory Care and Community Medicine (Favrat), University of Lausanne, Switzerland.
    Correspondence to:
    Bernard Favrat, Bernard.Favrat@hospvd.ch
    Abstract

    Background: The true benefit of iron supplementation for nonanemic menstruating women with fatigue is unknown. We studied the effect of oral iron therapy on fatigue and quality of life, as well as on hemoglobin, ferritin and soluble transferrin receptor levels, in nonanemic iron-deficient women with unexplained fatigue.

    Methods: We performed a multicentre, parallel, randomized controlled, closed-label, observer-blinded trial. We recruited from the practices of 44 primary care physicians in France from March to July 2006. We randomly assigned 198 women aged 18–53 years who complained of fatigue and who had a ferritin level of less than 50 ug/L and hemoglobin greater than 12.0 g/dL to receive either oral ferrous sulfate (80 mg of elemental iron daily; n = 102) or placebo (n = 96) for 12 weeks. The primary outcome was fatigue as measured on the Current and Past Psychological Scale. Biological markers were measured at 6 and 12 weeks.

    Results: The mean score on the Current and Past Psychological Scale for fatigue decreased by 47.7% in the iron group and by 28.8% in the placebo group (difference –18.9%, 95% CI −34.5 to −3.2; p = 0.02), but there were no significant effects on quality of life (p = 0.2), depression (p = 0.97) or anxiety (p = 0.5). Compared with placebo, iron supplementation increased hemoglobin (0.32 g/dL; p = 0.002) and ferritin (11.4 μg/L; p < 0.001) and decreased soluble transferrin receptor (−0.54 mg/L; p < 0.001) at 12 weeks.

    Interpretation: Iron supplementation should be considered for women with unexplained fatigue who have ferritin levels below 50 μg/L. We suggest assessing the efficiency using blood markers after six weeks of treatment. Trial registration no. EudraCT 2006–000478–56.

  5. Jack Norris RD Says:

    Thanks, Dan!

  6. Dan Says:

    I just read the update in full. As per your usual, it is excellent! I like the tip about cooking tomato sauce in cast iron pans/pots, which I am going to tell my hypoferritinemic father about (although now that he has been H. pylori-eradicated for a tiny gastric ulcer, he may no longer have need for this).

    From the text of your recommendation, as long as vegans are eating a variety of iron-containing plant-based foods, they should not worry about this issue overly much. I still think that there is fairly good evidence that maintaining LOW iron stores may be healthy in terms of CV and cancer risk. This is potentially one of the reasons that people who regularly donate blood to the Red Cross have lower risks of heart attacks than non-donors (although confounding is also a possibility, in that donors may be innately healthier). Bottom line for me was – keeping eat those legumes! (fortunately, I don’t drink any coffee or tea)

    I also want to reiterate a point I made earlier in response to one of the other commenters on this site, specifically, that one should never assume that iron deficiency anemia is solely due to poor intake (e.g. in veganism). It could just as well be due to microscopic blood loss from the gastrointestinal tract and there are numerous ways this can happen (inflammatory bowel disease, cancer, ulcers, gastritis, hemorrhoids, infections, collagenous colitis, celiac disease, etc). Just putting people on iron replacement is not going to establish the underlying cause for iron-deficiency anemia, which could progress or worsen without treatment. Perhaps this comment is beyond the scope of your article which applies more to vegans/vegetarians, but the clinical teaching remains that a gastroenterology referral is mandatory in a non-menstruating individual with iron deficiency anemia and no obvious cause.

  7. Jack Norris RD Says:

    Dan,

    Good comments. I have added this:

    Any disease or medication that causes bleeding, including internal, or disease of the digestive tract, could potentially aggravate or cause iron deficiency. If you have a case of stubborn iron deficiency, have your doctor consider such conditions and medications before assuming it is simply due to a low iron intake or poor absorption of plant iron.

  8. Andreas Says:

    What about polenta that is made from coarse cornmeal, preferably non-gmo, as an Iron source?

  9. Jack Norris RD Says:

    Andreas,

    > What about polenta that is made from coarse cornmeal, preferably non-gmo, as an Iron source?

    I don’t see any obvious listing for in the USDA database.

  10. Andreas Says:

    http://foodreference.about.com/od/Ingredients_Basics/a/Cornmeal-Vs-Grits-Vs-Polenta.htm

    I think yellow cornmeal is an example of the nutrition value of polenta.

    Sorry for the confusion. ^_^

  11. Mark Osborne Says:

    My understanding is getting your iron from plants rather than animals reduces the risk of iron overload because iron uptake from non-heme sources is better regulated by the body.

    http://www.veganhealthandfitness.com/blog/2011/10/dietary-iron-the-surprising-truth/

  12. Jack Norris RD Says:

    Mark,

    Good article. Yes, iron from plants reduces the risk of overload, I’m not sure if you are objecting to something I wrote in my article or not.

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