High dose vitamin supplements may reduce lifespan by up to a quarter: Animal data

By Nathan Gray

- Last updated on GMT

"Our findings suggest that major differences exist in the effects of high doses of antioxidants on oxidative damage and lifespan across species.”
"Our findings suggest that major differences exist in the effects of high doses of antioxidants on oxidative damage and lifespan across species.”

Related tags Antioxidant

A high intake of vitamin C and vitamin E could 'dramatically' reduce life expectancy by up to 26%, according to new research in voles.

The findings, published in Biology Letters, ​investigated the effects of high-dose vitamin supplementation in voles after previous work in mice suggested that a high intake of vitamin C and vitamin E slowed the process of cellular aging and increased life expectancy.

However, the new findings in voles suggest that high-dose supplementation may actually reduce lifespan.

“When we began our research, we expected that voles’ lifespans would be boosted by the vitamin supplements in a similar way to the mice we had tested previously, so we were surprised to see that was not the case,"​ said Professor Colin Selman from the University of Glasgow- who led the research.

"Our findings suggest that major differences exist in the effects of high doses of antioxidants on oxidative damage and lifespan across species.”

Study details

Speakman and his team fed field voles a diet supplemented with high levels of vitamin E or vitamin C from the age of two months in either warm or cold conditions and compared their longevity to groups of voles fed a regular diet.

The team found that voles in both cold and warm conditions that were fed supplements of vitamin E or vitamin C lived much shorter on average than those fed a regular diet.

Compared to animals on a regular diet, lifespan was reduced by 11% and 26% for vitamin E and C voles in the cold and by 17% and 18% for vitamin E and C voles in the warm, the team said.

Animal caution

Commenting on the research, Graham Keen, executive director of the  Health Food Manufacturers' Association (HFMA) said it is important to note it is 'impossible' to extrapolate the results from this small amount of data on voles and mice to humans, adding that the vitamin and mineral supplements industry has 'an exceptional record' of both safety and efficacy, in the UK and worldwide.
Figures published by the Food Standards Agency showed that there were only 11 reported reactions to food supplements over an 11 year period, the majority of them in the lowest category of harm," ​said Keen. "Compared to other foods or medicines, food supplements have an enviable record.”

Chris Whitehouse of The Whitehouse Consultancy, also commented that the findings cannot be extrapolated to human, adding that “The Vole Rights Society should be furious at this pointless and cruel use of animals in scientific experiments."

Professor John Speakman from the University of Aberdeen, senior author of the study, said randomised controlled trials examining the effects of antioxidant supplementation on human lifespan are 'unlikely' to be possible, "so we are dependent on the results of animal studies."

"It’s impossible at this stage to extrapolate the results from this small amount of data we have on voles and mice but it does suggest that caution is warranted in the use of high doses of antioxidant vitamins,"​ said Speakman.

Pro-oxidant doses?

Adding to the debate, Dr Robert Verkerk, executive and scientific director at the Alliance for Natural Health (ANH) International, commented that researchers are 'going around in circles' trying to better understand the oxidative damage theory of ageing - adding that the new study is a case in point.

"The scientists appear to be obsessed with using isolated vitamin E and vitamin C forms as their antioxidants,"​ said Verkerk. "This is odd given the good body of evidence now showing that these vitamins can act as pro-oxidants at high doses."

He added that  the dose of vitamin E used in the study equates to around 10 grams of alpha-tocopherol for an adult human "which is, in anyone's book, a 'horse dose'."

"It's no surprise it caused a shortening of lifespan as it almost certainly would have acted as a pro-oxidant, this having been widely demonstrated in other species. While the dose of vitamin C was lower, equating to around 4 grams for an adult human, humans are among relatively few mammals that have lost the ability to synthesise our own vitamin C. So once again, the dose offered in the diet, along with the vole's self-produced vitamin C, may have behaved as a pro-oxidant."

Verkerk commented that it would have been useful for the researchers to test a range or doses and different forms in addition to testing antioxidant status.

Speakman and his team noted that their findings "do indicate is that significant variation exists in the effects of antioxidants on oxidative damage and lifespan across species."

"We suggest that there is a need for further comparative studies in this area, and that caution should be used when advocating that antioxidants might protect against oxidative damage and ageing in humans, based on studies of limited numbers of species."

The full study can be found here.

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Failure to cite relevant human evidence

Posted by Frederic S.,

Senior study author Speakman states we never going to do a "randomised control trial of high dosage vitamin supplementation that has as its end point human longevity". Yet there are several sound randomized controlled studies on humans that found reduced mortality, or higher longevity respectively from the intake of high dose supplements.
Now, which set of good evidence, either on voles or humans, should you -as a human- most likely put trust into? These investigators failure to mention such highly pertinent scientific data ON HUMANS raises concerns that perhaps politics is involved in this "research"...

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Again a misconception?

Posted by Guido R Haenen,

See: http://www.nutraingredients.com/Research/10-misconceptions-about-antioxidants

”The expectations for antioxidants were set too high and it is apparent that these compounds cannot remedy everything. Moreover, unrealistic health claims will disappoint consumers and scientists.”

“Clearly, ‘the more the better’ is not the case. Identification of an optimal dose with a high benefit-risk ratio is required, along with adequate knowledge of the biotransformation of antioxidants.”

See misconception #1 and #3
Trends in Pharmacological Sciences
Published online ahead of print, doi: 10.1016/j.tips.2013.05.0104
Ten misconceptions about antioxidants
Authors: A. Bast and G. RMM. Haenen

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some clarification

Posted by John Speakman,

I thought it might be worth just clarifying some things in connection with our study on the voles since the message by Dr Ruth and some others in the above story seem to have misinterpreted some of the things we found

1) Are voles a suitable study species?

Dr Ruth has pointed out that voles may be an inadequate species to use for this research because of their naturally very short lifespan and the inability to extrapolate between voles and mice.
His statements are as follows.
Clearly, the findings of your study on voles cannot be extrapolated to humans. Indeed, it appears that they can’t be extrapolated to mice either….. AND The maximum lifespan for field voles (the type used in the “study”) is 18 months, although very few individuals survive to reach their second autumn. The average life of the smaller vole species is three to six months. These voles rarely live longer than 12 months. As many as 88% of voles are estimated to die within the first month of life

In reply:
The information provided by Dr Ruth refers to what happens to voles in the wild where predation is intense and the main cause of mortality. Hence voles in the wild don’t live very long. In fact if you consult the figure 1 of our paper you will see that the longest lived voles in captivity lived around 1000 days (3 years) and the median lifespan of the unsupplemented group was about 400-500 days (about 15 months). Therefore demographically voles are quite similar to mice. I do not therefore agree that voles are any worse as a choice of animal to study lifespan than any other rodent like mice or rats.

Regarding extrapolation. My statement in the press release was as follows. ‘It's impossible at this stage to extrapolate the results from this small amount of data we have on voles and mice but it does suggest caution is warranted in the use of high doses of antioxidant vitamins.’ I think this is an accurate way to describe the experiment and its implications. One thing is certain and that is we are never going to do a randomised control trial of high dosage vitamin supplementation that has as its end point human longevity. So end of the day we have to rely on animal studies. All we wanted to show in our paper was that in fact the results of the studies depend on the animals you choose. Previous work has been done almost exclusively on mice. It is hard to know how far this work can be extrapolated. Our findings show that the mouse work done previously, in our and other labs, cannot be extrapolated uncritically to humans, since it cannot predict the response in voles. In that sense this is a valuable piece of work because it urges caution in extrapolating the little data we have to infer that using high doses of antioxidants will be beneficial.

2) were the doses too high?

As Dr Nelson points out the simple calculations made by Dr Ruth are erroneous because they do not account for scaling effects. We were well aware of this issue and the doses were calculated with this in mind. It is true that this is not an exact conversion but we tailored the doses as best we could to be equivalent to 1000 mg vitamin c and 200 IU of vitamin E. From our reading at the time the work was started this seemed to be the sort of dose that many people were taking. The calculations by Dr Verkerk that this was a ‘horse sized’ dose are incorrect.

3) were the doses acting as a pro-oxidant?

Dr Verkerk states that the result is unsurprising because at the doses we used these compounds act as pro-oxidants. Aside from the miscalculated dose equivalence above it is important to note that we actually measured oxidative damage and found that hepatic lipid peroxidation was significantly REDUCED in the supplemented groups consistent with the supplements acting as antioxidants. DNA oxidation was not significantly affected. There is consequently no evidence that these doses acted as pro-oxidants or that this pro-oxidant effect was the cause of the shortened lifespan. The supplemented animals died quicker despite having lower oxidative damage to their liver lipids.

4) were the sample sizes too small?

Dr Ruth also claimed that the sample sizes in the study were ‘very small’
However, it is simply impossible to look at a sample size and judge how useful it is, because the key question is how much power do you have to detect an effect, which is related to the sample size, but also dependent on the variance in the trait in question. In fact in our case we powered the sample a priori so that we had 80% power to detect an effect size of 10% in lifespan. Relative to most lifespan studies in rodents this is extremely well powered. This is in part a powerful design because we used sibling pairs of voles where one sib was given antioxidants and the other not thus removing a lot of the genetic variance in response. In fact the effect sizes were all massively greater than 10%, so the significance of the effects were routinely better than p < .001. In other words the chance that the effect was not real but a random chance effect when the lifespans were actually not different is less than one in a thousand.

I hope these clarifications help.
best wishes
John Speakman
(senior author on the study)

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