Friday August 8 2008
What is good for rats, may not be good for humans
“A pill has been shown to stop the natural tendency to pile the pounds back on after a diet”, the Daily Mail reported. It said a study has found that alpha-lipoic acid has no effect when taken with a normal diet, but can “lock in” the benefits of a six month weight loss programme if taken afterwards. The newspaper also said the supplement, sold as a dietary supplement in health food shops, has an anti-ageing effect.
The story is based on a laboratory study in rats. The Daily Mail mentions this, saying that ‘the researchers are divided about whether the findings, observed in rats, can be applied to humans’. The newspaper also reported that one of the lead researchers is “sufficiently convinced to try the approach himself”. Given that this is preliminary research and there is a lack of evidence that antioxidant supplementation has any survival benefit, this seems premature. Although the newspapers focused on the dietary aspects of this research, the study was actually aimed at exploring the relationship between a restricted diet and survival in rats. These results will no doubt precipitate further research, which is important as at present the relevance of these particular findings to dieting, anti-ageing or increasing lifespan in humans is not clear.
Where did the story come from?
Doctors Brian Merry, Austin Kirk and Malcolm Goyns from the University of Liverpool and a research company called Immorgene carried out the research. The work was funded by the Biotechnology and Biology Research Council. The study was published in the peer-reviewed medical journal: Mechanisms of Ageing and Development.
What kind of scientific study was this?
This laboratory study was a further attempt to understand what biological mechanisms lead to the often-observed increase in survival in rats who feed on a calorie-restricted diet. Calorie restriction is often used to extend lifespan and has been shown in rats to delay ageing. The researchers were particularly interested in the effect on survival of supplementing the diet with alpha-lipoic acid, which has strong antioxidant properties and has been shown to prevent age-related damage to rat hearts, and to DNA and fats. In older rats, alpha-lipoic acid has also been shown to improve memory and to reduce age-related damage in the brain. Despite this however, alpha-lipoic acid has no apparent effects on lifespan in rats and the researchers wanted to explore this further.
Laboratory rats were given a diet not supplemented with alpha-lipoic acid until they were two months old. They were then randomly assigned to one of 12 dietary groups. The largest group contained the controls; 102 rats who continued to feed at will on the commercial rodent diet (not supplemented with alpha-lipoic acid). A group of 75 rats were put on a calorie-restricted diet of commercial rodent food (to maintain their body weight at 55% of age-matched controls). Another group of 75 rats were allowed to eat freely from the commercial rat food, but which had been supplemented with alpha-lipoic acid. There were nine other smaller groups of rats (about 25 in each group) that were given different combinations of diet, for example freely eating non-supplemented commercial rodent food then switching to dietary restriction at 6 or 12 months and other combinations of switching to and from calorie restriction and supplemented diets.
The lifetime survival of the animals in each group was compared with that of the control rats. This allowed the researchers to estimate what effect each dietary pattern had on lifespan.
What were the results of the study?
The researchers found that rats fed a restricted (non-supplemented) diet, i.e. those whose body weight was maintained at 55% that of age-matched controls, survived significantly longer than control rats (who freely ate the non-supplemented diet), living an average of 1,047 days compared to 926 days for the controls.
Supplementing the diet with alpha-lipoic acid did not significantly change this pattern (i.e. dietary restriction plus supplementation still led to increased lifespan). The survival of the rats who were allowed to eat freely was not greatly affected by having their food supplemented with alpha-lipoic acid. Similarly, supplementing the diet and also restricting it did not significantly increase rat survival compared to just restricting it.
The researchers also found that rats that ate freely until 12 months of age and were then switched to a calorie restricted diet lived as long as those who had been on a restricted diet since the beginning. However, switching from calorie restriction to free eating at 12 months did not improve survival compared to those eating freely for their whole lifespan.
The newspapers picked up on the finding that rats who were fed a non-supplemented calorie-restricted diet until six months and 12 months and then switched to feeding freely on a supplemented diet, increased in weight, but had an extended lifespan similar in degree to those who were fed the calorie restricted diet from the beginning. Switching in this way to a non-supplemented free diet did not have this effect.
What interpretations did the researchers draw from these results?
The researchers concluded that rat survival can be increased by feeding them a diet supplemented with alpha-lipoic acid after they have been on a calorie restricted diet for some time. They say that this increase in lifespan appears to be due to the ability of alpha-lipoic acid to ‘fix the subsequent survival trajectory to that established by the initial DR [dietary restrictions] feeding regime’.
What does the NHS Knowledge Service make of this study?
This study was conducted in rats. As with all animal studies, the main issue with interpretation is how relevant the findings are for humans. The following points are important:
- The news story extends the findings of this study to weight loss and ageing in humans. Although the paper suggests that the lead researcher is so convinced that the findings are relevant to humans that he will try the approach himself, this seems premature. The ‘pill’ to which the paper refers is alpha-lipoic acid which is sold widely as a dietary supplement and is claimed to be able to prevent age-related illnesses (including heart disease, Alzheimer’s and decline in cognition). It is an antioxidant, and there is little evidence to suggest that antioxidant supplements actually increase survival (in fact some studies find the opposite for some antioxidants), and over supplementation can be dangerous.
- Rats are likely to age differently to humans and have very different metabolisms. The weight of dietary restricted rats in this study was maintained at 55% of the control rats’ weight. Extrapolating this restriction to humans would mean those on a diet would be severely underweight. A diet in humans that reduced their weight to 55% of ‘normal’ would be akin to starvation. The negative effects of severely under eating are well known.
- Dosing is another issue. How comparable the doses of supplement in the rat diet are to the doses of alpha-lipoic acid in supplements one can buy is unclear.
This research should be viewed as preliminary. The results will be of interest to the scientific community and will precipitate further research into this area. The prevention of ageing and increasing lifespan is a hot topic and rodent models are useful in the exploration of this area. However, whether the alpha-lipoic acid supplements currently available over the counter will have these effects in humans remains to be seen.
The long-standing advice to maintain a healthy diet is as relevant as ever. There is evidence to link high intake of fruit and vegetables with reduced risk of chronic diseases, although researchers are still unclear as to exactly what it is in these foodstuffs that is responsible for this benefit. Research has focused on the antioxidant properties of some constituents, for example vitamin A, vitamin C, selenium and vitamin E. However, the results so far have been unconvincing either way with some studies reporting increased mortality associated with some supplements. What is known is that over-supplementation can be harmful and it is important that people who supplement their diets follow dosing recommendations.
Sir Muir Gray adds...
This is good news for rats. Humans who want to maintain a healthy weight should build an extra 30 minutes of walking into their routine.