Thursday August 21 2008
The dose needed to cause weight loss in humans is not known
An epilepsy drug being touted as a possible tool to fight obesity could also pose a threat to patients' sight, the Daily Mail reports. It says the drug vigabatrin (sold as Sabril in the UK) is being tested by US scientists as a possible treatment for addiction, and that rats bred to be obese lost between 12-20% of their weight as a result of the study. However, the newspaper says that the Royal College of Ophthalmologists has reported that “the drug can affect sight, reducing peripheral vision and limiting the field of vision in other ways, perhaps irreversibly”.
This animal study found that rats lost 12 to 20% of their weight after 14 days of vigabatrin injections. The drug is currently being tested for a number of addictions as it works on the chemical pathways in the brain known as dopamine pathways. The Royal College of Opthalmologists has pointed out that the drug might affect peripheral vision and so people who are prescribed it for epilepsy are assessed carefully. Although the researchers claim in the Daily Mail that the dose needed for weight loss in humans is probably lower than the dose that causes side effects, the drug has not yet been assessed for weight loss purposes in humans. It has been tested for cocaine and methamphetamine addiction in humans, but the dose used is not reported. If the drug is effective, the degree of weight loss and the dose needed to achieve it are currently unknown.
Where did the story come from?
Dr Amy Demarco and colleagues mostly from the Medical Department, Brookhaven National Laboratory in New York, conducted the research. The study was funded by the Office of Biological and Environmental Research and the National Institute on Drug Abuse. The study was published in the (peer-reviewed) medical journal: Synapse.
What kind of scientific study was this?
This was an animal study in which the researchers tested whether the chemical gamma vinyl-GABA (GVG) the active ingredient in vigabatrin, could produce weight loss in a group of 50 adolescent male rats as well as genetically modified obese rats. The researchers say that GVG has been shown to be a safe and effective treatment for cocaine and methamphetamine dependence, and they wanted to see if it would produce weight loss.
The rats were housed in pairs and allowed to eat freely. The researchers used adult and adolescent Zucker fatty rats, as this type of rat provides a genetic model of obesity, and the animals can inherit characteristics such as early-onset obesity, insulin resistance and hypertension. The researchers also used another type of adolescent rat, the Sprague Dawley rat, which had already been shown to lose weight with GVG.
The adolescent rats were randomly assigned to treatment and control groups whereas all the adult rats received treatment. GVG was given to the rats by injection once per day during the daylight hours, and daily food intake and weight were monitored. The adolescent Zucker fatty rats received GVG at three doses (75, 150, and 300mg/kg GVG) with a control group receiving water injections. The Sprague Dawley adolescent rats received the highest dose (300mg/kg GVG) or control injections and all the adult Zucker rats received active treatment with 300mg/kg GVG.
The animals were treated for no longer than 14 consecutive days and monitored for periods ranging from 19 to 40 days, depending on the group they were assigned to.
What were the results of the study?
The researchers say that “GVG effectively produces weight loss in both adolescent and adult animals” and that this effect was dependent on the dose that was given, with higher does yielding more of an effect in the adolescent fatty rats. They claim that the effects were substantial, as average decreases of 12–20% of original body weight were observed.
What interpretations did the researchers draw from these results?
The researchers conclude that the findings suggest that GVG could potentially treat human obesity, and as the results occurred in genetically obese animals there is a possibility that GVG may even help manage severe obesity resulting from binge eating. They mention that binge eating is a disorder involving food consumption in a pattern similar to the compulsive drug-seeking behaviour observed in cocaine and methamphetamine dependent subjects, but do not explain the rationale for the link in detail.
What does the NHS Knowledge Service make of this study?
This animal study used a rat model for testing the effect of a drug that is already in use in humans. There are several limitations to the study, some of which could be addressed by human studies if approval for these could be obtained.
- It is unclear how the 20% weight loss (50-100g) in animals weighing 250g to 370g translates into an expected weight loss in humans. Reanalysis of weight outcomes in the human studies of this drug for epilepsy could provide useful data.
- The side effects of the drug, particularly the eye complications or reduced peripheral vision mentioned in the newspaper article, were not addressed by the researchers. In addition, there are a number of other cautions and adverse effects associated with GVG, including a risk of neurological problems and depression and irritability. The drug should be used carefully in people with mood or behavioural disorders. It should also not be used during pregnancy or breastfeeding.
There may have been some over interpretation of this study and its implications for new treatments for obesity. A careful evaluation of the drug’s benefits and risks is needed.
Links to the headlines
Anti-obesity drug could be harmful to eyesight. Daily Mail, August 21 2008
Links to the science
DeMarco A, Dalal RM, Kahanda M, et al. Subchronic racemic gamma vinyl-GABA produces weight loss in Sprague Dawley and Zucker fatty rats. Synapse 2008; 62:870-872Further reading
Minozzi S, Amato L, Davoli M, Farrell M, Lima Reisser AARL, Pani PP, Silva de Lima M, Soares B, Vecchi S. Anticonvulsants for cocaine dependence. Cochrane Database Syst Rev 2008, Issue 3
Hemming K, Maguire MJ, Hutton JL, Marson AG. Vigabatrin for refractory partial epilepsy. Cochrane Database Syst Rev 2008, Issue 3