A “genetic excuse for obesity ‘is a myth’”, reported The Daily Telegraph. It said, “people could work off around 40 per cent of the extra weight that “fat genes” laid on them by exercising.”

This news report is based on a study that looked at how much physical activity over 20,000 people in Norfolk did and whether they were genetically more likely to be overweight. The researchers found that, although some genes increased the likelihood of having a higher BMI (body mass index), being active meant that these “genetically predisposed” individuals were less likely to be overweight. At the same time, being inactive increased the amount of weight they were likely to gain.

Current recommendations are that everyone should do at least five 30-minute sessions of moderate exercise a week as part of a healthy lifestyle. The results of this research suggest that this is beneficial for maintaining a healthy BMI, even in people who may be genetically prone to being overweight.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and was funded by Cancer Research UK, the Medical Research Council, British Heart Foundation, Food Standards Agency, Department of Health and Academy of Medical Sciences. It was published in the peer-reviewed medical journal PLoS Medicine.

The Telegraph, Sun and Daily Express all accurately reported the results of this study. The newspapers quoted the study’s author, Dr Ruth Loos, who stated: “It goes to show we’re not complete slaves to our genetic make-up.”

What kind of research was this?

This was a cohort study that investigated the extent to which people with a genetic susceptibility to becoming obese can change their weight with exercise. The research was based on previous genetic studies, which had identified 12 possible positions on 11 genes where differences between people in the DNA sequence could influence BMI. However, although the studies showed an association between variations in the genetic sequence at these positions and BMI, they only seemed to have a very small effect on a person’s risk of obesity. This suggested that lifestyle played a greater role, and the new study aimed to investigate this in more detail.

What did the research involve?

The participants were part of a larger cohort study, called the EPIC-Norfolk study, which involved 25,631 people living in Norwich. The participants were aged 39–79 years old during a health check that took place between 1993 and 1997. They had a second health check between 1998 and 2000. During the health checks, the participants’ weight and height were measured and their BMI calculated. In a questionnaire, the participants were asked about the amount of physical activity they usually did each week, at work and during their free time. Based on this questionnaire, they were classified as:

• inactive (sedentary job with no recreational activity)
• moderately inactive (sedentary job with less than half an hour a day recreational activity, or a standing job with no recreational activity)
• moderately active (sedentary job with half an hour to one hour of recreational activity a day, or a standing job with less than half an hour of exercise a day, or a physical job with no recreational activity)
• active (sedentary or standing job with more than one hours’ recreational activity a day, or a physical job with some recreational activity, or a heavy manual job)

The researchers had DNA from 21,631 participants of the larger cohort. These participants were all of white European descent. The researchers looked at the genetic sequence at the 12 positions on the 11 genes to see if the genetic variations associated with susceptibility to obesity were present. At each of the 12 positions, the participants were given a score, which indicated whether their DNA sequence gave them an increased genetic predisposition to becoming obese. The scores were then added together to give an overall score.

The researchers used a standard statistical technique, called logistic regression, to assess the strength of the association between an increased genetic predisposition for obesity and high BMI at the first health check. They then determined if they could still predict whether an individual would be obese, based on their genetic predisposition, if the analysis was repeated with people grouped according to their activity levels.

The researchers then looked at the interaction between genetic predisposition and physical activity, and the likelihood that a participant would put on weight in each year between the first and second health checks (a period of one to seven years).

What were the basic results?

The researchers found that for each of the 12 genetic variations that increased the predisposition for obesity, there was a 0.154kg/m² increase in BMI. This corresponded to a 1,445g increase in body weight for each variation in an individual who was 1.70m tall.

Each increase in physical activity level was associated with a 0.313kg/m² reduction in BMI. This corresponded to a decrease of 904g in body weight for a person who was 1.70m tall.

When the participants were grouped according to the four physical activity levels and the association between genetic predisposition and BMI was assessed, the researchers found that physical activity modified the effect on BMI of the genetic predisposition score. An increase in genetic predisposition score was associated with a 0.205kg/m² increase in BMI in the inactive individuals (an extra 592g for a person 1.70m tall), but only a 0.126kg/m² increase in active individuals (an extra 364g for a person 1.70m tall).

The researchers found that physical activity modified the association between genetic predisposition to obesity and BMI at the first health check and over follow-up.

How did the researchers interpret the results?

According to the researchers, their study shows that “a physically active lifestyle can modify the genetic predisposition to obesity”. They say that “living a physically active lifestyle is associated with a 40% reduction in the genetic predisposition to common obesity” and “promoting physical activity, particularly in those who are genetically predisposed, may be an important approach to controlling the current obesity epidemic.”

Conclusion

This large cohort study found that physical activity decreased the likelihood of having a higher BMI in people with a genetic predisposition to being overweight. One strength of this study is that it looked at a large population, which is important for assessing gene-environment interactions. However, the study has some limitations which the researchers highlight:

• The amount of physical activity was assessed with a self-administered questionnaire. Reporting physical activity in this subjective way may have led participants to over- or under-estimate the amount of physical activity they did.
• The participants included in the study were all white and of European descent. This population may not reflect the UK population as a whole.

This study shows that, although some people may have a genetic predisposition to being overweight, physical activity can prevent weight gain in these individuals. Current recommendations are that people should do at least five 30-minute sessions of moderate activity a week as part of a healthy lifestyle.

Links To The Headlines

Your genes make you fat? Rubbish… Just get some exercise. The Sun, September 1 2010

Weight: why having fat parents is no bar to being trim. Daily Express, September 1 2010

Genetic excuse for obesity 'is a myth'. The Daily Telegraph, September 2010

Links To Science

Li S, Zhao JH, Luan J, et al. Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study. PLoS Med 2010; 7(8)

Shaw KA, Gennat HC, O'Rourke P, Del Mar C. Exercise for overweight or obesity. Cochrane Database Syst Rev 2006, Issue 4

“Smoking cannabis from a pipe can significantly reduce chronic pain in patients with damaged nerves,” reported the BBC. It added that improvements in sleep and anxiety were also seen.

This news story is based on a small randomised controlled trial in 23 people, which found that a low dose of inhaled cannabis (lower than that needed to cause euphoria or a “high”) modestly improved reported pain in patients with neuropathic pain.

This is a well-conducted study, but its small size means that it is not possible to tell whether the results demonstrate a real association between cannabis and pain relief, or if they are due to chance.

More research in larger groups of people over a longer period of time is needed to see if the effects of cannabis for this type of pain can be replicated. In addition, there are health concerns related to the use of smoked cannabis, including mental health problems and lung damage.

It is important to point out that cannabis is a class B drug, which is illegal to possess or supply, and is not licensed in any form for medical use.

 

Where did the story come from?

The study was carried out by researchers from McGill University, Canada, and was funded by The Canadian Institutes of Health. The study was published in the (peer-reviewed) Canadian Medical Association Journal.
 
This research was covered well by The Daily Telegraph and the BBC, though the study did not find any evidence for effects on anxiety or depression, as the Telegraph headline suggests.

 

What kind of research was this?

This randomised controlled trial investigated whether cannabis can relieve neuropathic pain (neuralgia) – severe pain caused by the abnormal activity of nerve cells. Various events can set off neuropathic pain, including surgery, trauma or shingles.

The researchers say that although there are drug treatments for neuropathic pain, such as anticonvulsants, antidepressants, opioids and local anaesthetics, their effectiveness varies between patients. Some patients are put off taking them because of unpleasant side effects. They say there is anecdotal evidence that cannabis relieves chronic neuropathic pain and improves sleep. The researchers wanted to investigate whether these reported effects could be replicated under controlled experimental conditions.

This type of study design is the most appropriate way of determining whether a drug is effective. However, this was a very small trial in only 23 people, so it is not possible to conclude that the results are not down to chance alone.

 

What did the research involve?

The study recruited people who had experienced neuropathic pain for at least three months as a result of trauma or surgery. The participants ranked their current level of pain on a 10-point scale, and patients reporting pain intensity greater than four were included. Excluded from the study was anyone whose pain was due to cancer, those who had heart or lung disease, and those who had any type of substance abuse, a history of psychiatric disorders, or who were pregnant. In total 23 people were eligible to participate in the study.

The effect of smoking cannabis with the active ingredient, tetrahydrocannabinol (THC), was compared to smoking cannabis in which the THC had been removed (the control). Different potencies of THC were also compared to each other. Participants were not told the treatment they were given.

The control cannabis that had the THC removed was provided to the researchers by the US National Institute of Drug Abuse. The cannabis doses were prepared by blending the flowers and leaves of the plant to make three different potencies of the active drug (2.5%, 6.0% and 9.4% of THC).

Cannabis doses were delivered as single smoked inhalations taken through a pipe. The participants were instructed to inhale for five seconds as the cannabis was lit, hold the smoke in their lungs for 10 seconds, then exhale. The patients were observed taking the first dose. They then took subsequent doses at home, three times daily for five days. After 14 days, the participants swapped treatments so that those who had received the cannabis without THC then received cannabis containing the active drug. And those who had received active cannabis then received the placebo or a different dose of cannabis treatment.

In total, participants had four cycles of treatment where they received doses of 0%, 2.5%, 6% and 9.4% THC. Throughout the trial, the participants continued any routine medications that they were taking.

On the first day of each treatment period, the participants were asked about their feelings of pain, and how relaxed, stressed or happy they were. Their heart rate was also measured and a blood sample taken. During the five days of treatment or placebo, the participants were contacted by telephone and asked about their pain, how they were sleeping, their medication, and whether they were having any side effects. A urine sample was taken every day. On the fifth day of each treatment, a blood sample was taken and the participants were asked more questions about their pain, mood and quality of life.

 

What were the basic results?

The study had screened 113 participants but only 23 were eligible. Out of these, 21 completed all four cycles.

The researchers found that the average pain intensity was significantly lower on 9.4% THC cannabis (score 5.4 out of 10) than on 0% THC cannabis (6.1 out of 10) (p=0.023). However, no other comparisons between the different doses were statistically significant.

Participants using 9.4% THC cannabis reported finding it easier to fall asleep and had better quality of sleep than those taking 0% THC. No differences in mood or quality of life were seen with the different THC potencies.

Of the reported side effects, none were serious or unexpected. The most frequent side effects reported by participants when taking 9.4% THC cannabis were headache, dry eyes, burning sensation, dizziness, numbness and cough. Feeling “high” and euphoric was reported once in the 2.5%, 6% and 9.4% THC cannabis treatment periods.

 

How did the researchers interpret the results?

The researchers said that the 25mg herbal cannabis with 9.4% THC, administered as a single smoked inhalation three times a day for five days, significantly reduced average pain intensity compared to placebo in adults with chronic post-traumatic or post-surgical neuropathic pain. They also said that there were improvements in measures of sleep quality, but that long-term safety and efficacy studies are needed.

 

Conclusion

This placebo-controlled trial found that cannabis containing 9.4% THC could reduce neuropathic pain compared to the placebo. However, this was a small trial with only 23 participants, so it is difficult to tell whether these results demonstrate a real association, or if they are due to chance. A much larger trial would be needed for a longer period to assess the long-term outcomes of such a treatment. Additionally there are health concerns related to the use of smoked cannabis, including mental health problems and lung damage. Further research is needed to assess such potential side effects over the long term.

The researchers say that their study provides a way of looking at the short-term effects of smoked cannabis in a placebo-controlled trial. It is important to point out that cannabis is a class B drug, which is illegal to possess or supply, and is not licensed in any form for medical use.

Links To The Headlines

Cannabis may relieve chronic nerve pain. BBC News, August 30 2010

Smoking cannabis 'alleviates pain and depression'. The Daily Telegraph, August 30 2010

 

Links To Science

Ware MA, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. Canadian Medical Association Journal 2010, Published online ahead of print August 30