Iron-rich blood and metabolic syndrome

Hyperferritinemia Is Associated with Insulin Resistance and Fatty Liver in Patients without Iron Overload
Original source: PLoS ONE 3(10): e3547
Authors: Robert Brudevold (corresponding author), Torstein Hole, Jens Hammerstrøm
Publication date: October 28, 2008
DOI (digital document ID): 10.1371/journal.pone.0003547
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Publicly-available abstract: Yes

Synopsis:
Over the past ten years, the investigators have seen a rise in patients with hyperferritinemia (high blood ferritin) -- excess iron in the blood. A certain amount of this is to be expected given the increasing awareness of hereditary hemochromatosis -- a genetic condition in which the blood retains an overload of iron. High blood ferritin is also seen in cases of inflammation and in cancer. Over the same period, there has been an increase in patients whose high ferritin levels cannot be explained by these conditions. Most of these patients are overweight, middle-aged men.

Previous research suggested links between elevated ferritin levels and non-alcoholic fatty liver disease (NASH -- in technical terms, non-alcoholic steatohepatitis), and between high ferritin and insulin resistance. Both NASH and insulin resistance are often seen in patients with metabolic syndrome. The authors chose to examine this possible link in more detail.

They examined forty consecutive patients referred to them for hyperferritinemia. After examination, 34 patients remained with unexplained hyperferritinemia -- 1 woman and 33 men. Fasting blood samples were taken and analyzed for iron, liver enzymes, c-reactive protein (a marker for inflammation), and c-peptide (a marker for insulin production). Liver biopsies were obtained for 29 of the patients, and liver iron stores were assessed for 16 of them.

The majority of the patients had either markers for metabolic syndrome, or could be clinically diagnosed as having metabolic syndrome, showing increased body mass index, elevated diastolic blood pressure, and insulin resistance. Nineteen of the 29 patients biopsied had steatosis (fatty livers). Only four patients showed increased levels of iron in their livers -- of which two could be explained by alcohol consumption. Ferritin levels were higher in subjects with insulin resistance than in those without.

Fourteen of 16 patients normalized ferritin levels after phlebotomy (removal of an amount of blood -- a standard medical procedure for persons with hemochromatosis), but after a while, their ferritin levels rose again. Those who changed lifestyle (diet and exercise) -- first-line therapy for patients with metabolic syndrome -- had stabler ferritin levels. Since NASH is often seen in obese patients and in patients with metabolic syndrome, this evidence supports the theory associating NASH with increased ferritin levels.

These observations suggest that fatty livers and insulin resistance, but not increased iron storage in the liver, may be frequently seen in patients referred to specialists because of high ferritin levels. The authors conclude that ferritin levels seem to be higher in people with insulin resistance and suggest that high ferritin levels are markers of metabolic syndrome with NASH and insulin resistance, rather than iron overload.

Reliability:
There were very few subjects examined in this study, and no indication of how common this complaint is within the population affected by insulin resistance and/or metabolic syndrome. Because of this, there is a possibility of skewed data.

The tests support previous research, adding information to the existing body of knowledge and suggesting directions for further research.

The authors are associated with accredited medical institutions and the article is published in a peer-reviewed journal.

Practical Applications:
Understanding the entire extent of physiological changes associated with metabolic syndrome can help doctors and pharmacists better understand both metabolic syndrome in general and how best to treat the individual patients.

While the population studied is small, it supports our understanding that lifestyle management -- maintenance of a stable, healthy weight through diet and exercise -- is of vital importance for maintaining or improving our overall health.

Ethics note: All patients gave oral consent to the examination program and to the use of clinical data for research purposes.

This synopsis was based on the entire article.