Monday April 11 2016
The drug targets reward pathways in the brain
"Anti-smoking drugs could stub out your sugar cravings," the Daily Mail reports.
A study in rats suggests that varenicline (Champix), used to relieve nicotine cravings, could also help reduce the desire to consume sugary foods and drinks.
Varenicline targets what are known as the "reward pathways" of the brain. These are areas that respond to certain stimuli, which can range from illegal drugs, sex or gambling to sugary foods.
They react by releasing more of the "feel-good" neurotransmitter dopamine, which can stimulate feelings of pleasure.
The smoking cessation drug varenicline blocks receptors in the pathway, preventing nicotine from stimulating the same reward and response cycle. The researchers wanted to see if it would work the same way with sugar.
Rats were given sugar solution for 4 or 12 weeks, and when they were given varenicline after this time it reduced their sugar consumption for 30 minutes. The research provides evidence that sugar consumption involves the same reward pathway as other potentially addictive substances, such as nicotine – at least in rats.
The drug would need to undergo testing to see if it was similarly effective for excessive sugar consumption in humans, if the benefits outweighed the risks of the drug, and also whether it offered any advantage over other standard approaches to treating obesity.
Overall, this is interesting research, but varenicline is currently only licensed for smoking cessation in humans. Whether it may or may not have a future role in sugar addiction is unknown.
Where did the story come from?
The study was carried out by researchers from the Queensland University of Technology, Brisbane, and SRI International in California. Funding was provided by the Australian Research Council, National Health & Medical Research Council, and the National Institute of Health.
The study was published in the peer-reviewed scientific journal PLOS One. This is an open-access journal, so the study is freely available to read online.
The Mail's coverage is highly premature, with claims that: "Discovery could prove a significant breakthrough in the war on obesity". Despite calling this "groundbreaking research", the fact the study involved rats was only mentioned once, halfway down the article, and even then, the Mail incorrectly reported that the researchers used mice.
What kind of research was this?
This was an animal study investigating the reward pathways in the brain that are involved when we eat sugar.
The researchers say previous studies where rats have been fed an excessive amount of sugary drinks have been shown to elevate levels of dopamine in an area of the brain called the nucleus accumbens. This is part of the mesolimbic pathway, often referred to as the reward pathway. Pleasurable activity such as eating food or taking particular drugs causes the release of the chemical dopamine in this pathway, which causes further desire for stimulus.
It is this pathway that is known to be involved in substance use and addiction. The rat studies have shown that when the excessive sugar is subsequently withdrawn, this causes a similar effect to that seen among people who are dependent on substances such as nicotine, alcohol or heroin.
This research aimed to see whether there could be a therapeutic target for reducing sugar consumption. Varenicline (brand name Champix) is a tablet licensed for smoking cessation. It works by binding to specific nicotinic acetylcholine receptors (α4β2). Normally, when nicotine activates these receptors, it reinforces the release of dopamine and associated behaviour.
Champix blocks these receptors, preventing the reinforcement and reward experienced with smoking. The study's aim was to see whether these drugs may also be effective in reducing sugar consumption.
What did the research involve?
The study involved five-week old rats housed under standard conditions and given unlimited access to food and water. On about three days a week, they were also presented with another drinking bottle that contained 5% sugar solution. The researchers then started giving varenicline after short-term sugar exposure in one group of rats – four weeks on the sugar drinks – and after long-term sugar exposure in another group – 12 weeks. Varenicline was given by injection and the researchers tested different doses.
They also carried out different control scenarios. In one, another group of rats were given continuous exposure to sugar solution to look at voluntary consumption when it was available all the time, rather than intermittently. Instead of sugar, another group of rats were given saccharin solution three times a week, as per the standard protocol. This was to look at the effects of varenicline on consumption of a non-calorific sweetener.
The researchers also tested the effects of another drug called mecamylamine (not licensed in the UK) which binds to the receptors in a similar way.
The rats' weight, and volume of fluid consumed, were measured throughout. The brains of some rats were also examined after death.
What were the basic results?
The researchers found that varenicline significantly reduced sugar consumption after both the short- and long-term intermittent sugar exposures. However, varenicline was only effective at the higher dose (2mg/kg) in the short-term group. In the long-term group, it was effective at both lower and higher doses (1 and 2mg/kg). The drug effect lasted for up to 30 minutes, but was no longer effective when the rats were assessed two and 24 hours after injection.
Interestingly, varenicline also reduced consumption of saccharin solution. However, it was not effective in the rats with continuous access to sugar solution. Mecamylamine was similarly effective to varenicline at both 1 and 2mg/kg doses, and unlike varenicline was effective up to two hours after injection.
Examination of the rat brains also confirmed what the researchers had expected – that sugar consumption had been associated with increased binding at the nicotinic acetylcholine receptors in the nucleus accumbens, in a similar way to nicotine.
How did the researchers interpret the results?
The researchers conclude: "our results suggest that [nicotinic acetylcholine receptors] drugs such as varenicline may represent a novel treatment strategy for reducing sugar consumption."
This animal research provides evidence that, as expected, the chemical reward pathways within brain – involving a region called the nucleus accumbens – are involved when excessive amounts of sugar are consumed on a regular basis. This is similar to that involved with substance addiction, such as nicotine. The researchers subsequently found evidence that the smoking cessation drug varenicline can reduce sugar consumption when injected into rats.
However, it is difficult to draw many further implications from the research at this stage. For one thing, we don't really know what type of dietary intake in humans this intermittent exposure to sugar solution in rats would be equivalent to. Also, the only evidence we have is that giving varenicline reduced sugar consumption in the immediate term for only 30 minutes after administration. After this, sugar consumption returned to previous levels. The drug would need to keep being given to be effective.
It seems highly unlikely that people would be given a varenicline tablet every day to stop them eating sugar. Such an approach on a population basis would be unfeasible and unsafe. Even for smoking cessation, the drug is normally only given for a maximum of 24 weeks.
The issue of side effects is an important one. People who take varenicline have often reported psychological effects such as irritability, anxiety, and even depression and suicidal thoughts in rare cases. It has often been difficult to know how much of this is a direct effect of the drug and how much could be due to pre-existing mental health problems or withdrawing nicotine itself. It is not known whether people taking varenicline because they had a “sweet tooth” would also experience similar side effects, but it would be an important issue to consider.
The only theoretical implication it is possible to see at this stage, is that obese people who find it hard to stop eating sugar-laden foods and snacks could possibly be given varenicline in the short term to try and help them "quit".
However, this is only a speculation. The drug would first need to undergo testing in people to see if it was effective for excessive sugar consumption, if the benefits outweighed the risks of the drug, and whether it offered any advantage over other standard approaches to overweight and obesity, such as dietary control, physical activity and behavioural support.
Overall, this is interesting research, but varenicline is still only licensed for smoking cessation in humans. Whether it may or may not have a future role in sugar addiction is unknown. What is known is that a healthy, balanced diet is currently the best way to reduce excessive sugar consumption and associated health risks of diabetes, overweight and obesity.
Read more advice about how to reduce the amount of sugar you eat throughout the day.