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Updated: 11 hours 10 min ago

No need for nightshift workers to avoid steak

Thu, 2014-10-23 04:30

"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.

 

Conclusion

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.

Links To The Headlines

Why shift workers should avoid tucking into steak, brown rice or green veg at night: Iron-rich foods 'disrupt the body clock'. Mail Online, October 22 2014

Links To Science

Simcox JA, Mitchell TC, Gao Y, et al. Dietary Iron Controls Circadian Hepatic Glucose Metabolism through Heme Synthesis. Diabetes. Published online October 14 2014

Categories: News

Do dopamine drugs lead to compulsive shopping?

Thu, 2014-10-23 04:10

“Drugs for restless leg syndrome cause gambling, hypersexuality and compulsive shopping,” Metro reports.

Researchers in the US have looked at serious drug side effects reported to the FDA over a 10-year period. In particular, they were interested to see how often reports of impulsive behaviours such as gambling were linked to a group of drugs called dopamine receptor agonists.

These drugs (such as pramipexole) mimic the effect of dopamine on the brain. They are most commonly used to treat Parkinson’s disease and other conditions such as restless legs syndrome.

The drugs have sometimes been known to trigger extremely severe patterns of compulsive behaviours, so the researchers wanted to estimate exactly how common this side effect was.

The study found that 710 events – just under half of all impulse control disorders reported during this 10-year period – were attributed to dopamine receptor agonists. Given the number of prescriptions of these drugs that are likely to be prescribed every year in the US, this would suggest that the compulsive side effect – or at least the reporting of it – is quite rare. We would expect to see a similar pattern in the UK.

The risk of mental health-related adverse effects with these drugs, including impulse control disorders, is already recognised by the UK's medical profession. You or your carer should seek medical advice if there are any changes to your behaviour after taking a dopamine receptor agonist. 

 

Where did the story come from?

The study was carried out by researchers from The George Washington University and Harvard Medical School in the US, and University of Ottawa and Risk Sciences International in Ottawa, Canada. No sources of funding are reported. Two of the authors declare being consultant or expert witnesses in civil and criminal litigation involving many psychiatric drugs, though none involving the drugs that are at the centre of this research. This article is also reported to be based in part on data obtained under license from the National Prescription Audit.

The study was published in the peer-reviewed medical journal  JAMA International Medicine.

The Mail Online’s headline that, “Drugs for Parkinson’s disease can turn patients into gamblers, sex addicts and compulsive shoppers” is not justified by this study alone because – as the study authors acknowledge – the results did “not prove a causal relationship, only that such a relationship was suspected”. The study also only looked at one group of drugs, so the study results do not apply to all Parkinson’s treatments.

 

What kind of research was this?

This was an analysis of adverse drugs events (more commonly known as side effects) reported to the US Food and Drug Administration (FDA) involving six FDA-approved dopamine receptor agonist drugs.

These drugs are used in the initial treatment of Parkinson’s disease – a neurological condition with an unknown cause, where not enough of the chemical dopamine is produced in the brain. This causes the three classic symptoms of tremor, with stiff, rigid muscles and slow movements, as well as a range of other effects, including dementia and depression. While there is no cure, treatments that aim to control this dopamine imbalance are used to try and control symptoms.

Dopamine receptor agonists act directly on dopamine receptors, effectively taking the place of dopamine and stimulating the receptor in the same way. There are a group of these drugs licensed in the UK, including drugs called pramipexole, ropinirole and rotigotine. Dopamine receptor agonists are a different group of treatments from the well-known Parkinson’s treatment Levodopa, which works in a different way.

Dopamine receptor agonists are also sometimes used in restless legs syndrome if a person is having very frequent symptoms.

The drugs are already known to be associated with a risk of adverse mental health issues. This study reports that severe impulse control disorders such as gambling, hypersexuality and compulsive shopping have been reported following the use of these drugs, in both case series and patient surveys. This study aimed to further investigate the potential link between these drugs and this side effect.

 

What did the research involve?

The researchers looked at all domestic and foreign serious adverse drug events concerning impulse control disorders reported to the FDA between 2003 and 2012. They looked at the number of impulse control disorder events that were associated with the use of dopamine receptor agonists, and with all other drugs, to look for differences.

They specifically looked for 10 impulse control disorders as listed in the Medical Dictionary for Regulatory Activities:

  • pathological gambling
  • hypersexuality (experiencing extremely frequent sexual urges)
  • compulsive shopping
  • gambling
  • poriomania (wandering impulses)
  • binge eating
  • excessive masturbation
  • compulsive sexual behaviour
  • kleptomania (impulses to steal)
  • excessive sexual fantasies

For the individual dopamine receptor agonists, they calculated the proportional reporting ratio (PRR).

This involves calculating the frequency of impulse control adverse events for each dopamine receptor agonist drug, as a proportion of all adverse events reported for that drug.

 

What were the basic results?

Overall, the researchers identified 1,580 reports of impulse control disorders associated with any drug over the 10-year period. Gambling was the term mentioned in around half of these reports: pathological gambling in 628 (39.7%) and gambling in 186 (11.8%). This was followed by hypersexuality, which accounted for just under a third of impulse control events (465, 29.4%), and then compulsive shopping, which accounted for around an eighth (202, 12.8%).

Just under half of all the impulse control events were related to dopamine receptor agonists (710, 44.9%) and the remainder to other drugs. The reports related to dopamine receptor agonists occurred in people with an average age of 55 years, and over half of whom were male. Most of these prescriptions had been for Parkinson’s disease (61.7%), with most of the remainder prescribed for restless legs syndrome.

The six specific dopamine receptor agonists examined were pramipexole, ropinirole, rotigotine, bromocriptine, cabergoline and apomorphine – all of which are used in the UK.

The PRR was significant for dopamine receptor agonists, meaning that the proportion of impulse control events was significantly higher than all other events with these drugs. For all dopamine receptor agonists, the PRR was 277.6. Most of the impulse control events associated with these drugs had occurred with pramipexole (410 events; PRR 455.9) followed by ropinirole (188 events; PRR 152.5). The number of reported impulse control events with the other four drugs was between 56 for cabergoline and 12 for apomorphine.

 

How did the researchers interpret the results?

The researchers say that their findings, “confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings”.

 

Conclusion

This study analysed serious adverse drug events reported to the US FDA over a 10-year period, and found that 710 events (just under half of all impulse control disorders reported during this period) were attributed to dopamine receptor agonists. Most of these disorders involved gambling, followed by hypersexuality and compulsive shopping.

This group of six drugs are used in Parkinson’s disease (and a small number of other conditions) where there is a lack of the chemical dopamine. The drugs act directly on dopamine receptors, effectively taking the place of dopamine and stimulating the receptor in the same way.

Dopamine receptor agonists are known to have mental health-related adverse effects; impulse control disorders are already recognised.

This study further highlights this risk, demonstrating that impulse control disorders account for more serious adverse events than all other events associated with these drugs that have been reported to the FDA.

The study is based on US FDA data only, but it could give a good indication of the data reported to UK medicines regulatory authorities. The study also only covers adverse events that are formally reported, and it is unclear how many impulse control disorders may occur, but are not reported.

As the researchers acknowledge, this study still cannot prove that it is the dopamine receptor agonist that has directly caused the adverse events reported.

UK prescribing information for dopamine receptor agonists advises patients and prescribers of the risk of impulse control disorders. If symptoms develop, doctors are advised to reduce the dose or stop prescribing the drug until symptoms resolve.

People in the grip of a compulsive pattern of behaviour are often unaware that their behaviour has changed and that they are acting strangely, so do not seek medical advice. Therefore friends, family members or carers can help by being vigilant for any strange changes in the behaviour of a person taking these drugs.

Analysis by Bazian. Edited by NHS ChoicesFollow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Links To The Headlines

Drugs for restless leg syndrome cause gambling, hypersexuality, and compulsive shopping. Metro, October 21 2014

Drugs for Parkinson's disease can turn patients into gamblers, sex addicts and compulsive shoppers. Mail Online, October 22 2014

Links To Science

Moore TJ, Glenmullen J, Mattison DR. Reports of Pathological Gambling, Hypersexuality, and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs. JAMA Internal Medicine. Published online October 20 2014

Categories: News