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.
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
June 14th, 2013 at 6:34 am
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)
June 14th, 2013 at 6:39 am
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.
June 14th, 2013 at 6:42 am
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.
June 14th, 2013 at 4:00 pm
Thanks, Dan!
June 14th, 2013 at 6:44 am
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.
June 14th, 2013 at 4:15 pm
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.
June 14th, 2013 at 5:08 pm
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.
June 16th, 2013 at 12:47 am
What about polenta that is made from coarse cornmeal, preferably non-gmo, as an Iron source?
June 16th, 2013 at 9:30 am
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.
June 16th, 2013 at 1:30 pm
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. ^_^
August 7th, 2013 at 8:11 pm
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/
August 12th, 2013 at 5:17 pm
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.
April 20th, 2015 at 6:41 pm
I’ve been vegan for over 40 years. Some years ago I had stomach ulcers and GERD and have been taking proton pump inhibitors for about 12 yearss now, on and off. I recently read that the low stomach acid these cause can result in poor absorption of non-heme iron and also vitamin b12. Found this – http://www.medscape.com/viewarticle/490612_3
April 20th, 2015 at 7:30 pm
soilman,
> I recently read that the low stomach acid these cause can result in poor absorption of non-heme iron and also vitamin b12.
B12 from supplements and fortified foods doesn’t rely on having strong stomach acid, so you should be fine as long as you supplement in some way. For iron, it might be worth monitoring your iron status by getting periodic lab tests.
April 20th, 2015 at 8:34 pm
From the article I linked to “Interestingly, although omeprazole produces a profound hypochlorhydric state, clinical studies to date have failed to associate it with iron deficiency even with prolonged use.[7] This may in part be due to the compensation by dietary heme iron, which enables acid-independent absorption” Vegan diets however have only non-heme iron. Article goes on to say “Since therapeutically administered oral iron is entirely nonheme in nature, its absorption may be drastically curtailed by omeprazole. This may in turn lead to a state of unresponsiveness to oral iron replacement with minimal or no improvement in anemia despite therapy that would be considered adequate for most adults.” And finally “We found this to be the case in each of the patients described above…” and goes on to explain how they came to this conclusion.
I at one time did have mild iron-deficiency anemia. It cleared up after I began taking ferrous gluconate tablets. I seem to recall however that all this happened to me BEFORE I developed stomach ulcers. I think more scientific research needs to be done.
April 20th, 2015 at 8:45 pm
More recently my MD insisted on testing my blood for b12 and I tested low despite years of taking cyano cobalamin tablet, 125 mcg 3x per week, for many years. I switched to methyl cobalamin and 1250 mcg 3x per week and will be retested in June. Cool MD – tho I don’t think he was vegan, he went out of his way to find a vegan source of B12 for me to take – even though I didn’t ask, didn’t even mention it. I don’t even remember mentioning that I was vegan. I think things are gradually changing for the better from the way they were 40 years ago.
June 24th, 2016 at 12:37 pm
I’d like to point out that even those who are compound heterozygous for the hemochromatosis gene can absorb too much iron, even if vegan (as is the case with me). In my case, the excessive absorption of non-heme iron was possibly due to taking a 500 mg vitamin C tablet right after lunch, but since quitting I have not yet retested my levels. I should add that I eat a whole plant food diet; no processed food and do not take a supplement with iron, so the extra iron was coming from whole plant foods. My doctor was unfamiliar with this possibility.