Iron Part 2—Research


by Jack Norris, RD • Last updated June 2013

More Information on Iron

See Iron Part 1—Basics for general recommendations about increasing iron absorption. Below is a more detailed discussion about increasing iron absorption, followed by a review of the research on the iron status of vegetarians and a discussion of iron and chronic disease.

Contents

Iron Absorption from Plant Foods

Phytates and polyphenols, found in many plant foods, can inhibit the absorption of plant iron, while vitamin C is a strong enhancer of plant iron and can overcome the inhibitors.

Phytates

Phytates are found in legumes and grains. One study found that various doses of phytate reduced iron absorption by 10–50%. But adding 50 mg of vitamin C counteracted the phytate, and adding 150 mg of vitamin C increased iron absorption to almost 30% (3).

Polyphenols in Coffee and Tea

Polyphenols, which include tannic acid, can inhibit iron absorption and are found in coffee, cocoa, and black, green, and many herbal teas (1).

One study showed that, over four weeks, green and black tea lowered iron levels primarily in people with serum ferritin levels less than 20 µg/l (2). Drinking tea an hour before or after a meal markedly reduces its effects on iron absorption (44, 45).

However, although short-term studies suggest that tea inhibits iron absorption, adaptation may occur and in apparently healthy adults, tea-drinking does not appear to increase the risk of becoming iron deficient (46). And in the presence of a large dose of tannic acid, 100 mg of vitamin C increased iron absorption from 2–8% (3).

Our recommendations are that if you normally drink coffee or tea with meals and haven’t had iron deficiency, then there’s no need to change. But for those who have iron deficiency, it’s best to avoid coffee or tea within one hour of most meals.

Curing Anemia in Vegetarians with Vitamin C

In one study, vegetarian children with anemia and low vitamin C intakes in India were given 100 mg of vitamin C at both lunch and dinner for 60 days. They saw a drastic improvement in their anemia, with most making a full recovery (4).

In another study, researchers used 500 mg of vitamin C twice daily after meals to increase hemoglobin and serum ferritin in Indian vegetarians. They concluded that vitamin C was more effective at increasing iron status than iron supplements (5).

Cooking foods in cast iron pans can increase iron consumption. A 2007 study in Brazil showed that cooking tomato sauce in an iron skillet increases the amount of iron in the sauce and also increased iron status among teen-aged and young adult lacto-ovo vegetarians (6). The authors considered it important for the food cooked to be both acidic and water-based, such as tomato sauce.

Lysine and Iron Absorption

The amino acid L-lysine plays a part in the absorption of iron and zinc.

Among plant foods, L-lysine is found in high amounts mainly in legumes (peanuts, beans, lentils, and peas) and quinoa, and a vegan who doesn’t eat many legumes could find themselves falling short on lysine.

In some women, iron supplementation does not lead to an increase in iron stores. In one study of such women, adding the amino acid L-lysine (1.5 – 2 g/day for 6 months) to iron supplementation did increase iron stores (7).

Ferritin and Iron Absorption

When assessing studies on iron absorption, it’s important to realize that a person’s serum ferritin level is the main determinant of, and inversely proportional to, non-heme iron absorption (8).

Iron Status of Vegetarians

Just as in the greater population, it’s not unusual for premenopausal vegetarian women and teenage girls to have iron deficiency and sometimes anemia. There’s anecdotal evidence that some premenopausal women who become vegetarian develop iron deficiency and such women should make sure they’re following advice about increasing iron absorption.

The American Dietetic Association’s Position Paper on Vegetarian Diets says, “Incidence of iron deficiency anemia among vegetarians is similar to that of nonvegetarians. Although vegetarian adults have lower iron stores than nonvegetarians, their serum ferritin levels are usually within the normal range (9).”

The ADA’s statement is based on cross-sectional studies. The iron status of vegetarians or vegans on self-selected diets hasn’t been followed through time.

Cross-sectional studies show that average iron intakes of male vegetarians (including lacto-ovo vegetarians and vegans) range from 14–18 mg/day from food and 23 mg/day including supplements (10, 11).

Average male vegetarian serum ferritin levels range from 30–75 µg/l (11, 12, 13). In the one study that explicitly stated it, no vegan men were iron deficient or anemic (11).

Cross-sectional studies show that female vegetarians’ average iron intakes range from 12-15 mg/day from food (10, 14, 15, 16), although one study measured it at 20 mg/day from food (17) and another at 26 mg/day from food and 42 mg/day from food and supplements (11).

Average female vegetarian serum ferritin levels range from 11–35 µg/l (12, 13, 14, 16, 17).

White vegetarian women have high rates of iron deficiency ranging from about 25–50%, although omnivore women’s rates of deficiency ranged from 20–60% in those same studies (11, 14, 15, 17), possibly suggesting that women with iron deficiency issues are more likely to take part in studies on iron deficiency. Vegan women over 50 had a deficiency rate of only 12% (17).

In three studies measuring hemoglobin, two had no female vegetarians with anemia (15, 16), while another had 2 out of 15 (11), and one had 3 out of 75 (17).

One of the above studies included Indian, female, lacto-ovo vegetarians living in Britain, of which 15 out of the 19 were iron-deficient and two had anemia (15).

There’s been one prospective study on iron status using a vegetarian diet (18) in which men aged 59–78 were placed on either a lacto-ovo vegetarian or omnivorous diet for 12 weeks during which they also participated in resistance training. After 12 weeks, serum ferritin in the vegetarian group went from 95 to 72 µg/l, while omnivore ferritin levels stayed the same. Other iron parameters stayed about the same, with no change in vegetarian hemoglobin.

Polish Vegetarian Children

A 2013 study from Poland measured iron intakes and iron status of vegetarian children (19). The study compared 22 vegetarian children (5 ate fish, none were vegan) to 18 omnivores, aged 2–18 years old. Of the vegetarians, eight (36%) had iron deficiency compared to only two (11%) of the omnivores.

Of the vegetarian girls of menstruating age, 2 of the 5 had iron deficiency anemia, whereas none of the 4 omnivore menstruating girls had anemia. The researchers noted that their anemia was not due to menstrual period disorders and that they’d been trying to lose weight for “quite a long time.”

It’s likely the iron deficiency in these Polish children was due to not eating enough iron-rich foods.

There’s more information about this study in Iron Status of Polish Vegetarian Children.

The Food and Nutrition Board and Vegetarian Diets

The Food and Nutrition Board (FNB) of the Institute of Medicine sets the Dietary Reference Intakes for nutrients which include the Recommended Dietary Allowance (RDA). The FNB suggests that iron in vegetarian diets is absorbed at a rate of 10% compared to 18% in omnivorous diets and that iron absorption could be as low as 5% for vegans. The FNB does not explicitly give a separate RDA, but says that the “requirement for iron is 1.8 times higher for vegetarians (20).”

The FNB bases their recommendations on two clinical trials:

Hunt and Roughead (21) performed a crossover study in which participants spent 8 weeks on a typical lacto-ovo vegetarian diet and 8 weeks on an omnivorous diet. Iron absorption on the lacto-ovo vegetarian diet was 1.1% compared to 3.8% on the omnivorous diet.

Cook et al. (22) divided people without anemia into 3 groups:

  • Normal diet
  • Diet with iron absorption enhancers
  • Diet with iron absorption inhibitor

Over the course of two weeks, non-heme iron from meals was absorbed at the respective rates of 7.2%, 13.5%, and 2.5%, whereas the absorption rates for the entire two weeks were 7.4%, 8.0%, and 3.4%.

The authors said that although iron absorption from meals can vary up to 20-fold within the same meal, depending on enhancers and inhibitors, large population surveys have not demonstrated a clear relationship between iron status and daily consumption of such factors.

These two trials shouldn’t be viewed as conclusive as they don’t account for the body adapting its absorption mechanisms over longer periods of time (such as a year or more) or using iron absorption enhancers, especially vitamin C.

Until prospective studies investigate iron levels in free-living vegetarians over a period of years, it’s impossible to know exactly what impact a vegetarian diet might have on iron levels.

Iron Supplements in Early Functional Deficiency

Two studies from Switzerland have shown that iron supplementation can reduce fatigue in premenopausal women (23, 24) whose hemoglobin levels are above 120 g/l (and thus not diagnosed with anemia).

The most recent, from 2012 (24), was a double-blinded, randomized controlled trial in which 80 mg of ferrous sulfate (an iron supplement) per day for twelve weeks increased hemoglobin in women who had average serum ferritin levels of 22.5 µg/l. This increase in hemoglobin was matched with a 50% reduction in symptoms of fatigue compared to only 19% for placebo. Improvements in hemoglobin were seen after 6 weeks.

Another study showed that cognition in adolescent girls has been improved by iron supplements in those with early functional deficiency (25).

Iron Deficiency and Manganese

It’s important to resolve iron deficiency because it can increase manganese accumulation in the brain. In iron deficiency, manganese is absorbed instead of iron and vegans, in particular, have high manganese intakes. The good news is that while phytate decreases both iron and manganese absorption, vitamin C increases only iron absorption.

For references and more information, see the VeganHealth article, Manganese.

Hemochromatosis

Hemochromatosis is a genetic disease in which someone absorbs abnormally large amounts of iron, resulting in very high serum ferritin levels of > 300 ng/ml in men, 200-300 ng/ml in postmenopausal women, and > 200 ng/ml in premenopausal women (26).

Less than 1% of people of northern European descent are homozygous for the hemochromatosis gene. Hemochromatosis typically begins to cause problems, especially for men, around age 40 to 60.

If untreated, hemochromatosis can result in liver cirrhosis, liver cancer, heart failure, and other problems. Symptoms include joint pain, fatigue, abdominal pain, and impotence.

People should talk to their doctors about their risk factors.

Iron and Chronic Disease

Because hemochromatosis can lead to significant health problems, research has looked at whether high iron levels, in the absence of hemochromatosis, might also lead to health problems—this was of particular interest regarding vegetarianism because of the lower iron stores in vegetarians.

Indeed, early research found that high serum ferritin levels were associated with heart disease. But since then, the research has been less convincing. Here’s a summary of where things stand (as of 2013):

  • High iron stores and higher intakes of heme iron are associated with a higher risk of type 2 diabetes.
  • Heme iron intake is associated with colon cancer, while non-heme iron isn’t.
  • Iron supplementation of < 20 mg/day isn’t associated with colon cancer (studied in women).
  • High iron serum ferritin levels aren’t associated with cardiovascular disease or increased mortality.
  • Transferrin saturation has been found to be associated with mortality in various ways and at different levels, though it’s not clear why or what can be done about it.

Type 2 Diabetes

There’s 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 of heme iron (5 studies) at baseline were strongly associated with a higher risk of type 2 diabetes (27). There was no association for higher intakes of non-heme iron.

A cross-sectional study from the U.S. found lower ferritin levels in lacto-ovo vegetarians (35 µg/l) than in 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 (28).

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

Colon Cancer

Many studies have looked for an association between iron stores, iron intakes, and colon cancer, and the results have been mixed (29, 30, 31, 32).

One study found that high iron intake was associated with colon cancer only when combined with a high-fat diet (30).

The Nurses Health Study and Health Professionals Follow-up Study found no relation between iron intake or iron supplements and risk of colorectal cancer. The highest quintiles of iron intake for men and women were, respectively, > 24.6 and > 22.7 mg/day with median supplemental iron intake at 10 and 15 mg/day (33).

The Iowa Women’s Health Study analyzed iron supplement intake, fermentable substrates (fiber plus resistant starch), and colon cancer. They hypothesized that the acidic environment created by fermentable substrates in the colon could interact with the iron supplements, possibly increasing colon cancer. Women taking ≥ 50 mg/day had a significantly increased risk of distal (but not proximal) colon cancer if they also were above the median for fermentable substrates (26 g/day). Supplements of 1–19 mg/day didn’t appear to increase risk (34).

As distinct from total iron or non-heme iron intakes, heme iron intake has been consistently associated with a greater risk of colon cancer. A 2011 meta-analysis of 5 cohort studies found a significant and consistent, but modest, increase in the risk of colon cancer associated with high heme iron intake, with a risk of 1.18 (1.06–1.32) for subjects in the highest category of heme iron compared with the lowest (35). The researchers said there are plausible mechanisms to suggest it’s the heme iron in red meat causing colon cancer.

Cardiovascular Disease

A meta-analysis of observational studies (36) found that serum ferritin levels of 200 µg/l were not associated with coronary heart disease compared to levels below 200 µg/l. A more recent systematic review found the association between iron stores and cardiovascular disease to be mixed, with the majority of studies showing no association (37).

Cardiovascular disease might not be caused by high storage levels of iron, but rather through repeated bouts of toxic exposure that would not necessarily be evident in serum ferritin levels (38).

The question isn’t settled, and it may be that levels somewhat higher than 200 µg/l are more indicative of damage. It could also be that tissues are protected against oxidative damage by iron when the iron is bound to storage and transfer proteins, such as ferritin.

Mortality

A 12-year prospective study from the United States National Health and Nutrition Examination Study (NHANES) II examined the relationship between iron intake, transferrin saturation, and mortality among people aged 30–70 years at baseline. High iron intake led to an increased mortality risk when, and only when, it was combined with elevated transferrin saturation. High vs. low iron intake was ≤ 18 mg/day vs. > 18 mg/day (39).

A prospective report from NHANES II (31) found no relationship for mortality among white men, white women, or black men when comparing serum ferritin levels of 100-200 µg/l or > 200 µg/l with 50-100 µg/l.

In a large sample of U.S. adults, from NHANES III, who were without hemochromatosis and weren’t taking iron supplements, serum ferritin and transferrin saturation weren’t associated with mortality (40).

However, another analysis from NHANES III, limited to adults 50 years and older, found that higher transferrin saturation was associated with lower all-cause and cardiovascular mortality in both men and postmenopausal women.

Men also showed an inverse association between transferrin saturation and cancer mortality (41). High transferrin saturation was > 30-35% compared to < 15-18%.

No association with mortality for elevated serum ferritin was found in NHANES III (40, 41).

Using data from NHANES I, Mainous et al. (42) found transferrin saturation above 55% to be associated with a 60% greater risk of mortality.

Using data from NHANES II, Wells et al. (43) found neither elevated LDL or elevated transferrin saturation (> 55%) to be independently associated with mortality, but when combined were strongly associated with mortality.

References

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