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Eating like a Viking 'reduces obesity risks'

"A Nordic diet could reduce the dangers of being overweight, a study suggests," The Daily Telegraph reports. The headline comes from the results of a small randomised controlled trial.

Half the people in the trial were put on the Nordic diet, which consists of wholegrain products, vegetables, root vegetables, berries, fruit, low-fat dairy products, rapeseed oil, and three servings of fish a week.

The other half acted as a control group and ate a diet of low-fibre grain products, butter-based spreads, and a limited intake of fish.

Researchers found people on the Nordic diet developed reduced activity (expression) in 128 genes associated with inflammation of their abdominal fat compared with controls.

Inflammation may cause some of the adverse health effects associated with being overweight, such as insulin resistance, which is a risk factor for type 2 diabetes.

However, changes in gene expression are not the same as proven changes in clinical outcomes. The study did not find any correlation between these changes in gene expression and clinical measurements of risk factors, such as blood pressure or cholesterol. 

Nevertheless, it is plausible that the Nordic diet has a protective effect – it is relatively similar to the Mediterranean diet (with a bit more herring and a bit less pasta), which has been associated with a reduced risk of chronic diseases.

 

Where did the story come from?

The study was carried out by researchers from a number of academic institutions in Finland, Norway, Sweden, Iceland and Denmark.

Funding came from several sources in these countries, including research foundations and academic institutes. Several commercial companies provided food products for the study participants.

The study was published in the peer-reviewed American Journal of Clinical Nutrition.

The Daily Telegraph and the Mail Online's coverage was accurate, but both overstated the results of the study, failing to point out that research into gene activity alone is not enough to show the health benefits of a diet.

 

What kind of research was this?

This was a randomised controlled trial, which is the best way to determine the effects of an intervention.

The trial was designed to look at whether a Nordic diet had an effect on the activity of genes in abdominal fat just beneath the skin (adipose tissue) in obese people.

It also aimed to see whether any changes in gene expression were associated with clinical and biochemical effects.

In previous research, "dysfunctional adipose tissue" had been proposed as an important link between obesity and its adverse health effects, such as insulin resistance and an unhealthy balance of blood fats.

However, little is known about how diet influences adipose tissue inflammation at the molecular level.

 

What did the research involve?

Researchers recruited 200 adults to the trial, although only 166 completed it. Participants had to be between the ages of 30 and 65, with a body mass index (BMI) of 27 to 38. A BMI of 25 or above is considered overweight, while a BMI of 30 or above is considered obese.

Participants also had to have at least two other features of metabolic syndrome, a condition characterised by symptoms such as high blood pressure, high blood sugar and abnormal blood fat levels, and is often associated with diabetes.

For a period of 18 to 24 weeks, 104 people were put on the Nordic diet, comprising wholegrain products, berries, fruits and vegetables, rapeseed oil, three fish meals a week, and low-fat dairy products. They also avoided sugar-sweetened products.

96 people were put on the control diet, comprising low-fibre cereal products and dairy fat-based spreads, with a limited amount of fish.

A clinical nutritionist or a dietitian gave instructions about the diets. The participants' dietary intake was monitored throughout using regular food records.

To reduce any confounding factors, the study participants were advised to keep their body weight and physical activity unchanged, and to continue their current smoking habits, alcohol consumption and drug treatment during the study.

Researchers took biopsy samples of the participants' adipose tissue at the beginning and end of the study, and extracted RNA, which is used to carry out DNA's genetic instructions.

A test called a transcription analysis was performed to study the expression of genes in the tissue.

Researchers also took various other clinical and biochemical measurements, including levels of blood sugar, cholesterol and triglycerides.

 

What were the basic results?

56 participants were included in the final analysis – 31 from the Nordic diet group and 25 from the control group.

People were excluded if there was a change in their body weight of more than 4kg, and if they started to use statins, had a BMI over 38, or poor adipose tissue samples.

The researchers report differences between the two groups in the activity of 128 genes.

Many of these genes were associated with pathways relating to the immune response, with a slightly reduced activity among people in the Nordic diet group and increased activity among people in the control diet group.

There were no differences between the groups in terms of clinical or biochemical measurements.

 

How did the researchers interpret the results?

The researchers say their study indicates that the Nordic diet reduced the activity of genes associated with inflammation in adipose tissue when compared with the control diet group.

The quality of diet may be an important factor for regulating adipose tissue inflammation independent of weight change, they say.

 

Conclusion

This study found that the activity of certain genes, some of which are associated with inflammation, was different in obese people who ate a Nordic diet compared to those on a control diet.

Yet there was little correlation between these findings and any changes in measurements of risk factors such as participants' cholesterol or blood pressure. The authors concede that the clinical relevance of their findings is unclear.

As the authors say, one limitation is that volunteers in the study may have had healthy eating habits before the study began.

If these volunteers had been randomised to the control diet group, they may have modified their diet to become more unhealthy, and therefore changes in gene expression would seem to be more evident in this group.

Being overweight or obese increases the risk of chronic illness such as diabetes, heart disease and some cancers, so it's important to maintain a healthy weight.

The Nordic diet is being touted as one of the latest trends in healthy eating. Whether it is a proven method to prevent chronic diseases is uncertain, but it does appear to be based on sensible nutritional principles, such as eating lots of wholegrains, fruit and vegetables, while cutting down on saturated fats.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

High blood pressure? Eat like a Viking. The Daily Telegraph, January 7 2015

High blood pressure? Go Nordic: Eating like a Viking can reduce the damaging effects of being overweight - and stave off diabetes. Mail Online, January 7 2015

Links To Science

Kolehmainen M, Ulven SM, Paananen J, et al. Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome. The American Journal of Clinical Nutrition. Published online November 19 2014

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Could meal-in-a-pill 'trick' body into losing weight?

“Weight loss drug fools body into reacting as if it has just eaten,” The Guardian reports. The drug, fexaramine (or Fex), stimulates a protein involved in metabolism that is usually activated when the body begins eating, though it has only been tested in mice.

Researchers found that obese mice given Fex stayed the same weight despite continuing to eat the same amount of a high-fat diet. However, unlike some media claims, they did not actually lose any weight. It had no effect on mice of normal weight.

The protein that is stimulated, FXR (farnesoid X receptor), is present in many organs of the body and plays a complex role in metabolism that is not fully understood. 

Previous drugs developed to activate this protein have shown conflicting results, possibly because they entered the bloodstream and so acted on all of the organs. Fex has been developed so that it appears to be barely absorbed into the blood stream, and so only acts on the FXR in the intestines. This provided better results for obese mice and also reduces the risk of side effects.

Further animal and primate studies will need to be conducted before the drug would be allowed to progress to human trials, but these are promising results. However, even if these trials passed with flying colours, we would estimate that it would take at least 5-10 years before any drug based on this research came to market.

 

Where did the story come from?

The study was carried out by researchers from the Salk Institute for Biological Studies in California and several other institutes in the US, Australia and Switzerland. It was funded by the US National Institutes of Health, the Glen Foundation for Medical Research, the Leona M. and Harry B. Helmsley Charitable Trust, Ipsen/Biomeasure, the California Institute for Regenerative Medicine, the Ellison Medical Foundation, the National Health and Medical Research Council of Australia, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A financial conflict of interest was reported. Many of the contributing authors “are co-inventors of FXR molecules and methods of use, and may be entitled to royalties from their use”.

The study was published in the peer-reviewed journal Nature Medicine.

In general, the media have reported the story accurately, pointing out that it is in the early stages of development and that it has only been tested on mice. However, as mentioned, headlines such as the Daily Mirror’s “'Imaginary meal' diet pill tricks body into losing weight”, or The Daily Telegraph’s assertion that the “pill makes you feel full” are inaccurate. None of the mice lost weight and none of their appetites were suppressed.

 

What kind of research was this?

This was an animal study to test whether a new drug could improve the metabolism of mice. The researchers conducted a variety of experiments of the drug, comparing their response with mice receiving a placebo.

The drug was created to mimic an effect of eating food. Food causes bile acids to be secreted and this activates a protein called FXR (farnesoid X receptor).

FXR plays a complex role in metabolism that is not fully understood. It is present in many organs of the body, including the kidney, stomach, intestines, gall bladder, liver and both white and brown fat cells.

Previously, drugs have been developed to activate FXR, but they have encountered problems because of activating FXR in all of the organs. This gave conflicting outcomes. For example, mice of normal weight given these drugs had improved glucose tolerance, whereas obese mice put on more weight and had even poorer glucose tolerance. It was not clear why this happened, so the researchers wanted to investigate whether just activating FXR in the intestines improved metabolism.

They developed Fex to activate the intestinal FXR drug instead of food, without it being absorbed into the general circulation, to see if this made a difference. They also say that limiting absorption means there would be less potential for side effects.

 

What did the research involve?

The researchers developed a drug called Fex and performed a number of tests using mice.

They first tested the absorption of Fex into the general circulation. They gave mice either a Fex pill by mouth or an injection of Fex into the fluid that surrounds the abdominal organs. The researchers then measured the level of FXR activation in each organ.

The researchers then gave normal weight mice either a Fex pill or a placebo for 35 days. They then compared their weight, metabolic rate and sensitivity to insulin.

Lastly, mice were fed a high-fat diet (60% fat) for 14 weeks to make them obese. The researchers then gave them different doses of the Fex pill or a placebo for five weeks. They compared their weight, metabolic rate, extent of unhealthy white fat and healthy brown fat, and markers of tissue inflammation.

 

What were the basic results?

The oral Fex pill activated FXR in the intestine and did not activate it in the liver or kidneys. The researchers say this shows that it was only minimally absorbed into the general circulation. This was in comparison to the injection of Fex into the abdominal cavity, which stimulated FXR in the intestine as well as the liver and kidneys.

There was no difference between normal weight mice given oral Fex for five weeks in terms of weight gain (small amount) and other metabolic measurements, compared to normal weight mice given placebo.

In obese mice, the Fex pill caused an improvement in metabolism compared to placebo, including:

  • reduced weight gain
  • increased sensitivity to insulin
  • more unhealthy white fat turning into healthy brown fat
  • reduced inflammation

These obese mice were 34 grams at the start of the experiment (normal weight mice would be around 28 grams). They continued on the high-fat diet (60% fat) for five weeks. Those given placebo increased in weight to 44 grams, but those given the highest dose of Fex did not gain any more weight. None of these mice lost weight. The researchers report that there was no change in appetite or food consumption between the mice given Fex and those given placebo.

 

How did the researchers interpret the results?

The researchers concluded that Fex might be a “promising” approach to stimulating FXR, in order to improve metabolism. The say that the “absence of a change in food intake is notable, as failure of appetite control is a major reason for weight gain”. They say that, as this drug appears to improve metabolism without any change in food intake, it “may offer a viable alternative for obesity treatments”. They also point out that as Fex is only minimally absorbed and only stimulates the intestinal FXR, it offers “improved safety profiles” by not circulating around the whole of the body.

 

Conclusion

This animal study has shown that a new drug called Fex prevents obese mice from further weight gain, despite remaining on a high-fat diet. There were also other metabolic improvements, including improved sensitivity to insulin and a reduction of unhealthy white fat cells. There were no differences in measures of metabolism between mice of normal weight given Fex or placebo, although both groups gained a small amount of weight.

This preliminary study appears to show that, unlike previous drugs that have stimulated FXR from the general circulation and shown conflicting results, by targeting intestinal FXR, obese mice benefit. As it has only been tested in mice for five weeks, there is limited information on what these side effects might be in humans.

Further animal and primate studies will need to be conducted before the drug would progress to human trials, but these are promising results.

As the drug appears to improve metabolic function rather than promote weight loss, it could be a candidate to treat diseases of the metabolism, such as type 2 diabetes or metabolic syndrome (where a person has a combination of diabetes, high blood pressure and obesity).

Due to the length of time it takes to bring a drug to market, as well as the chance of a drug proving to be ineffective or unsafe in humans, we can’t envisage Fex (or a variant) appearing in your local pharmacy anytime soon.

In the meantime, tips to help you lose weight can be found here and you can get online support here.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Links To The Headlines

Weight loss drug fools body into reacting as if it has just eaten. The Guardian, January 5 2015

Could an 'imaginary meal' pill solve the obesity crisis? Drug tricks the body into feeling full - AND lowers cholesterol and blood sugar. Mail Online, January 5 2015

Diet pill that makes you feel full proven to keep weight off in mice, scientists say. The Independent, January 5 2015

'Imaginary meal' diet pill tricks body into losing weight. Daily Mirror, January 5 2015

'Imaginary meal' pill makes you feel full and burns fat. The Daily Telegraph, January 5 2015

An 'imaginary meal' pill to lose weight? Scientists reveal latest weapon to battle obesity. Daily Express, January 5 2015

Links To Science

Fang S, Suh JM, Reilly SM, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nature Medicine. Published online January 5 2015

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