Thursday October 23 2014
High levels of iron could reset the 'hepatic clock'
"Shift workers should avoid tucking into steak, brown rice or green veg at night," because these foods "disrupt the body clock," the Mail Online reports.
But the research in question involved lab mice who were fed different amounts of dietary iron for six weeks to see what effect this had on the daily regulation of glucose production in their livers.
The research found mice fed lower-iron diets tended to have better regulated glucose production pathways than those on the higher iron diets. The mice did not have disturbed sleep patterns.
In a press release, the researchers raised the possibility their findings could have "broad implications" for people who do shift work, which could increase their risk of type 2 diabetes. This speculation has been mistakenly highlighted by the media.
The results suggest sustained high iron intakes may compromise our glucose regulation in the liver, but we should interpret these results with caution. The results do not prove that high iron intake has any effect on the risk of type 2 diabetes, as diabetes outcomes were not examined.
If you are concerned about diabetes, there are steps you can take to reduce your risk, such as maintaining a healthy weight (which is recommended whatever hours you work).
Where did the story come from?
The study was carried out by researchers from the University of Utah in the US and was funded by the Research Service of the Department of Veterans Affairs and the National Institutes of Health.
It was published in the peer-reviewed medical journal, Diabetes.
By taking the press release at face value, the Mail Online has overextrapolated the implications of this research, which has looked at how different dietary iron intakes in mice influence the daily regulation of glucose production in the liver.
This study is not related to shift work – subheadings such as, "for people who work night shifts, it puts the liver's clock out of sync", are not supported by the evidence.
The press department of the University of Utah appears to have misrepresented and overinterpreted the study in the hopes of hitting the headlines. While they have been successful in getting in the papers, they have perhaps done the science a disservice.
In this study, all mice were kept on a 12-hour light/dark cycle. All that was altering was their iron intake, not their sleep/wake patterns.
What kind of research was this?
This was an animal study investigating the role that dietary iron has on the circadian (daily) rhythm of glucose metabolism in the liver.
The researchers describe how the liver maintains a daily balance in regulating glucose, and point out that disruption of this rhythm is associated with type 2 diabetes.
Dietary intake is one of the factors that influence the biological clock in our bodies, but little is said to be known about the role of specific dietary components.
This research focused on dietary iron, as iron is an essential component of several proteins in the body concerned with electron transport and metabolism. Also, haem, the chemical compound containing iron, is necessary for the formation of several proteins involved in regulatory pathways.
What did the research involve?
In this study, researchers fed mice chow with different iron concentrations. They did this to create iron levels in the body tissues that would be within the range produced by a normal human diet.
Three-month-old male mice were fed on diets containing low (35mg/kg), medium (500mg/kg) or high (2g/kg) amounts of iron. The upper 2g/kg level is said to be within the fourfold range of iron seen in human livers. The mice were fed on these diets for six weeks while they were maintained in a 12-hour light/dark cycle.
After between six and eight weeks on these diets, the researchers also tested the effect of giving the mice three different chemicals in their daily drinking water.
These chemicals either increased haem synthesis, inhibited haem synthesis, or acted as an antioxidant. They gave the mice these chemicals so they could work out how dietary iron was affecting glucose production in the liver.
The mice were then given various tests, including glucose tolerance tests (GTT) and a variation on the GTT: the pyruvate tolerance test (pyruvate is one of the molecules involved in the production of glucose).
The mice also had their blood levels of haemoglobin, red blood cell volume, insulin and glucagon (the hormone produced when blood glucose levels are low) measured. After death, the mouse liver was analysed in the laboratory.
What were the basic results?
The researchers found dietary intake influences the daily rhythm of glucose production in the liver.
Mice fed the lower-iron diet had higher blood glucose levels in response to pyruvate injection than mice on the higher iron diets. This result suggests their livers had better regulated glucose production pathways than those who had been on the higher iron diets.
The researchers found haem production varied with dietary iron intake, and haem influences the activity of an enzyme (Rev-Erbα) key to regulating the liver's daily rhythm. This Rev-Erbα enzyme regulates many aspects of glucose metabolism.
To confirm that dietary iron was affecting haem production, the researchers looked at the effect of chemicals that either increased haem levels or blocked haem production. Treatment with either chemical caused the differences in blood glucose regulation seen to disappear.
The researchers thought dietary iron may cause changes in haem synthesis through reactive oxygen species. This is because the protein that regulates the production of one of the enzymes involved in haem synthesis is regulated by reactive oxygen species, and iron creates reactive oxygen species.
Reactive oxygen species are molecules containing oxygen. Depending on the specific context in which they are formed, reactive oxygen species can be both helpful and harmful to the cells of the body.
To test the above hypothesis, mice were fed an antioxidant to mop up reactive oxygen species. This resulted in many of the differences seen between mice fed different diets to disappear.
Iron intake had no effect on haemoglobin concentration or red blood cell volume.
How did the researchers interpret the results?
The researchers say their findings demonstrate that dietary iron affects the circadian rhythm and glucose production in the liver by modifying haem levels in the liver.
This animal research demonstrates how dietary iron intake affects the daily regulation of glucose production in the liver. Mice fed lower-iron diets tended to have better regulated glucose production pathways than those who had been on the higher iron diets.
This happens because iron intake influences the production of the iron compound haem, which in turn influences the activity of an enzyme involved in regulating glucose production in the liver.
Overall, it is difficult to draw any meaningful conclusions from these findings. The researchers suggest sustained high iron intakes may compromise our glucose regulation in the liver, but interpretations from this research should be made with caution. The results from this mouse study do not prove that a high iron intake increases the risk of type 2 diabetes.
The results certainly do not have any immediate implications for shift workers. This leap seems to have been made because the study looked at daily rhythms of glucose production, but all mice in this study were maintained on the same light/dark cycle – only their iron intake was altered.
The most effective method of reducing your diabetes risk is to achieve and then maintain a healthy weight. If you are struggling to get the weight off, why not try the NHS weight loss plan, a free evidence-based diet and exercise plan designed to deliver sustainable weight loss.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.