Predictors of iron levels in 14,737 Danish blood donors: results from the Danish Blood Donor Study.

Rigas AS, Sørensen CJ, Pedersen OB, Petersen MS, Thørner LW, Kotzé S, Sørensen E, Magnussen K, Rostgaard K, Erikstrup C, Ullum H.

Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.

Abstract

BACKGROUND: Dietary studies show a relationship between the intake of iron enhancers and inhibitors and iron stores in the general population. However, the impact of dietary factors on the iron stores of blood donors, whose iron status is affected by blood donations, is incompletely understood.

STUDY DESIGN AND METHODS: In the Danish Blood Donor Study, we assessed the effect of blood donation frequency, physiologic factors, lifestyle and supplemental factors, and dietary factors on ferritin levels. We used multiple linear and logistic regression analyses stratified by sex and menopausal status.

RESULTS: Among high-frequency donors (more than nine donations in the past 3 years), we found iron deficiency (ferritin below 15 ng/mL) in 9, 39, and 22% of men, premenopausal women, and postmenopausal women, respectively. The strongest predictors of iron deficiency were sex, menopausal status, the number of blood donations in a 3-year period, and the time since last donation. Other significant factors included weight, age, intensity of menstruation, iron tablets, vitamin pills, and consumption of meat and wine.

CONCLUSION: The study confirms iron deficiency as an important problem, especially among menstruating women donating frequently. The risk of iron depletion was largely explained by sex, menopausal status, and donation frequency. Other factors, including dietary and supplemental iron intake, had a much weaker effect on the risk of iron depletion.

PMID: 24372094

SUPPLEMENT:

Iron is essential for both cellular metabolism and oxygen transport in multicellular organisms.  However, because of the toxic effects of iron homeostatic mechanisms are needed to closely regulate iron levels. In humans, iron homeostasis is controlled at the site of intestinal and cellular absorption since no active excretion method exits. The largest iron store is within the red blood cells where iron is bound to hemoglobin but iron is also present in myoglobin, cellular organelles and in iron binding proteins such as ferritin.  The circulating ferritin protein level is considered to be the best measure of current iron stores.  Even though iron is found in abundance in various food sources, iron deficiency is the most prevalent nutritional deficiency worldwide. An estimated high proportion (80%) of the global population might be iron deficient. Low intestinal absorption of iron probably contributes to this phenomenon. A variety of factors inhibit iron absorption such as eggs, milk (dairy products), tea, coffee and calcium. Among the enhancing factors are ascorbic acid and a “meat-factor”, which has not yet been fully identified, but possibly cysteine-containing peptides are responsible for its enhancing effect. Furthermore, physiological factors such as sex, age, height, weight and menopausal status also influences iron status. Lastly, alcohol, vitamin pill intake, and supplemental iron tablets contribute to higher iron levels.

In the blood banking community it has long been known that blood donors are at an increased risk of iron deficiency because of loss of iron through blood donations. Various blood donor management regimes have been implemented to ensure the well-being and safety of blood donors. Amongst these has been a regular hemoglobin control in conjunction with blood donation. However, in recent years a growing interest has evolved in measuring blood donors iron levels (ferritin levels) and a high number of iron deficient donors has been reported.

The Danish Blood Donor Study is an ongoing epidemiological cohort study currently comprising more than 90,000 Danish blood donors enrolled from all regions of Denmark.

We sat out to investigate to which extend the above-mentioned factors and blood donation influence iron stores in blood donors.

A statistical model for predicting ferritin levels for men, premenopausal women, and postmenopausal women was constructed because there were distinctive differences in ferritin levels between these groups. In addition, statistical analyses for the same groups were performed in order to identify factors associated with low iron stores i.e. iron deficiency defined as a ferritin level below 15 ng/ml.

The study included data on more than 14,000 blood donors enrolled in 2010. For the sake of clarity the investigated factors were divided into the following 4 groups: blood donation factors (number of donations in the previous 3 years and time since last donation), physiological factors (weight, age, height, giving birth, and duration of menstruation), Lifestyle or supplemental factors (smoking status, vitamin pills, and iron tablets), and dietary factors (meat, fish, egg, milk tea, coffee, beer, wine, and liquor).

We found that the blood donation factors (especially number of donations in the previous 3 years) were the strongest predictors of ferritin levels along with sex and menopausal status. Weight, age, vitamin pill intake, meat and wine consumption all correlated positively with ferritin levels but were less useful to predict current iron status in blood donors. Intake of iron supplements correlated negatively with iron levels for all groups. However, this latter finding is most likely biased by participants with low iron stores having prescribed iron tablets.

Overall, the composition of dietary inhibitors and enhancers influenced iron stores to a much lesser degree when compared to blood donation factors. If bled more than nine times in the preceding 3 years, 9 %, 22 %, and 39 % of men, postmenopausal women, and premenopausal women were iron deficient, respectively. In fact, among high- frequency donors with more than nine blood donations in the preceding 3 years, a substantial proportion of donors were iron deficient, even when the “protective” effect of certain physiologic, supplemental, and dietary factors were accounted for.

This study does not answer whether a guided iron supplementation regime or a restriction in donation activity is needed to avoid iron deficiency in blood donors. However, the applied dietary recommendation concerning iron rich food items appear inadequate for active blood donors.