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    Health Supplement Skepticism - The Negative Effects Of Vitamins
    By News Staff | July 21st 2013 02:00 PM | 14 comments | Print | E-mail | Track Comments
    A new paper in Biology Letters raises more questions about the benefits of vitamins as a health supplement.

    High doses of dietary antioxidants such as vitamins are claimed to slow the process of cellular aging by lessening the damage to proteins, lipids and DNA caused by free radicals. Some research has found that the longevity of mice could be extended by administering particular vitamin supplements, despite the supplements' limited effectiveness in reducing free radical damage. However, the opposite was found to be true in voles in a new study.

    Instead, vitamin C and vitamin E were found to dramatically reduce the lifespan of voles, found the biologists. The 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.

    Voles in cold conditions fed supplements of vitamin E or vitamin C lived much shorter on average than those fed a regular diet. Similarly, in warm conditions, supplemented voles fed vitamin E or vitamin C lived much shorter 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. Despite the effect on the voles' lifespans, the researchers found that the vitamin supplements did have some effect in decreasing free radical damage.


    Kaplan–Meier survival curves of voles maintained in the cold (a) 7 ± 2°C or warm (b) 22 ± 2°C and given access to either a control diet, a vitamin E-supplemented diet or a vitamin C-supplemented diet from two months of age. (a) Solid blue line denotes control, stippled green line denotes vitamin E and broken orange line denotes vitamin C groups. (b) Solid red line denotes control, stippled green line denotes vitamin E and broken orange line denotes vitamin C groups. Credit and link:doi: 10.1098/rsbl.2013.0432

    Professor Colin Selman of the University of Glasgow's Institute of Biodiversity, Animal Health and Comparative Medicine, who was first author on the work, said, "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. Our findings suggest that major differences exist in the effects of high doses of antioxidants on oxidative damage and lifespan across species."

    Professor John Speakman, of the University of Aberdeen, who led the work, said, "It's unlikely that randomized controlled trials examining the effects of antioxidant supplementation on human lifespan would 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."

    The work was funded by BBSRC.

    Citation: Colin Selman, Jane S. McLaren, Andrew R. Collins, Garry G. Duthie and John R. Speakman, 'Deleterious consequences of antioxidant supplementation on lifespan in a wild-derived mammal', Biol. Lett. 23 August 2013 vol. 9 no. 4 doi: 10.1098/rsbl.2013.0432

    Comments

    Gerhard Adam
    On the idea that antioxidants such as those in colorful berries fight cancer: "The time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer."
    James Watson
    http://www.reuters.com/article/2013/01/09/us-usa-cancer-watson-idUSBRE90805N20130109

    Professor John Speakman, of the University of Aberdeen, who led the work, said, "It's unlikely that randomized controlled trials examining the effects of antioxidant supplementation on human lifespan would 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."
    In other words, perhaps we should stop extrapolating the positive results when we know that such animal studies don't really tell us anything.

    Mundus vult decipi
    John Hasenkam
    Voles in cold conditions fed supplements of vitamin E or vitamin C lived much shorter on average than those fed a regular diet.
    What type of vitamin E? Alpha T is the typical supplement and it can be worse than useless because it impedes the absorption of much better E types and tocotrienols. Of course they used .. 22 mg kg−1 α-tocopherol),



    Vitamin C for voles? I thought most animals produced their own vitamin C, we primates being a notable exception. So why go down that route? High vitamin C loading may be occurring and vitamin C can and does act as a pro-oxidant. They got they right but it does raise the question of too much Vitamin C in the voles, especially if on a high iron intake diet... vitamin C can act as a pro-oxidant under certain conditions [28], 


    Multi-vitamin studies for humans suffer similiar problems because they typically have high levels of alpha T and beta carotene, the latter is often regarded as a pro-vitamin A carotenoid but recent research highlights it can antagonise Vitamin A function though there is no obvious explanation for that. Additionally there is the suggestion from that famous study on smokers that beta-carotene may induce lung cancer. 


    Yet still there are many voices out there promoting anti-oxidants, Mercola being one of the worst. There are now studies suggesting high anti-oxidant loading may inhibit the benefits of exercise. One possible avenue: insulin receptor requires a certain redox status to function effectively. Another: oxidation events induce HSF-1 and NFkB transcription, both of which can provide important protection and cellular repair functions. 


    It's difficult and people, especially some health nuts, need to stop thinking in such simplistic linear associations. 




    Whales dive to depths of 1,000 ft so it stands to reason these depths are just fine for unprotected humans. Cows can thrive on a diet of grasses so humans should do well on a similar diet. Lizards don't get rabies so your dog should be fine without a vaccination.
    Let's look at humans who take mega doses of vitamins to see how they made out. Jack Lalanne, dead at 97. Charles Atlas...snuffed it at 90. Linus Pauling...struck down in his prime at 93.
    Who are you going to believe. Some folks who played with some numbers or the folks that have the numbers that really matter. Ignore these fools and keep taking your vitamins...in big doses!

    Hank
    Highlighting exceptions is not the way to go - my great grandmother lived to be 101 and never took a vitamin supplement. That would not be evidence they have no value.
    Gerhard Adam
    Ignore these fools and keep taking your vitamins...in big doses!
    I think the point is to avoid any kind of global recommendations without understanding more about the context in which this advice is being given.  As with so many things, the accurate answer is much more nuanced than is generally proposed, so one cannot confidently say that megadoses of vitamins are good or bad.

    Even the examples you cited are suspect because there were numerous other factors involved in someone like Jack LaLanne and Charles Atlas.  Similarly we have seen many very athletic people die quite young for no apparent reason.

    In general, there are no specific statements one can make regarding longevity that have any real credibility beyond the common sense notions of not doing anything to extremes.
    Mundus vult decipi
    Thank you. I couldn't have said it better myself.

    John Hasenkam
    Let's look at humans who take mega doses of vitamins to see how they made out. Jack Lalanne, dead at 97. Charles Atlas...snuffed it at 90. Linus Pauling...struck down in his prime at 93.
    If examples constitute an argument then everything is true. 


    Studies on centenarians raise some difficult questions: 


    • They often have experienced considerable trauma in their lives but demonstrate remarkable resilience.  
    • They are frugal eaters, so frugal they would not even meet the RDA requirements let alone mega dosing.  
    • They are not health nuts but they are often shiny happy people.  
    • They are not afraid of dying.   




    There is a huge confounder with centenarians, that being longevity is concentrated in family lines, pointing to potential genetic influences being a key driver in longevity and that is more than being "statistically significant". It could be familial transmission of attitudes and lifestyles but I'm inclined to think the genetics is very important. 


    There is increasing evidence the endurance athletes are wearing out their hearts. Take this with a grain of salt but someone recently told me how a doctor at our a hospital had commented that there are increasing numbers of 40ish fit healthy men in cardiac wards. Note though I live on the Gold Coast Australia and the body beautiful craze is alive and well here, which makes me a real outsider. :)  (I did read recently that this trend has been observed in other regions.) Along with that craze goes steroids etc ... . 

    Keep in mind that there are now numerous studies that high loading of some nutrients can exacerbate pathology or increase the likelihood of pathology.




    Bonny Bonobo alias Brat

    John you say that studies on centenarians raise some difficult questions: 

    • 'They are frugal eaters, so frugal they would not even meet the RDA requirements let alone mega dosing.'
    Where do you get those stats from? 

    The longest living, oldest recorded woman in the world Jeanne Calment ascribed her longevity and relatively youthful appearance for her age to olive oil, which she said she poured on all her food[4] and rubbed onto her skin, as well as a diet of port wine, and ate nearly one kilogram (2.2 lb) of chocolate every week.[12]

    I know its only anecdotal but she is the oldest person documented in the world and her diet doesn't sound very frugal to me, a kilo of chocolate every week! 

    It looks like she might have also enjoyed a fair bit of birthday cake too :)
    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at http://www.science20.com/forums/medicine
    John Hasenkam
    Where do you get those stats from? 

    "Living to 100" Perls et al. 
    What protein levels have the voles and mice in comparison to humans, also whats the water PH regulation, of skin blood, tissue, gut, urine, etc, etc: of the two species you've been testing on.
    Acid helps break proteins down, i experimented on self, so i know this...
    This means if the voles and mice haven't a regular diet, which involves the right protein levels, what you will get is high acidity in the species and they will get ill sooner and die sooner.
    Seems like a careful balance of do's and don't's

    Hank
    Voles are better than mice as a model in some cases because they can form social bonds - not relevant here - but that they had a decrease in longevity, unlike mice, so the question becomes how close they are for predicting effects in humans. Generally, you shouldn't go all crazy anyway.
    Acid helps break proteins down, i experimented on self, so i know this...
    Luckily, that is not how science actually works.
    John Hasenkam
    Some years ago I read a fascinating study on a standard mice strain that was also genetically engineered to produce high growth factor production. The GM mice showed very accelerated cognitive decline, which is to be expected because high growth factor expression beyond the developing years doesn't help brains it rots them. 
    The controls received the normal chow and then both groups, the norms and GM mice, received a specially designed diet. The results were remarkable because the GM mice not only showed preserved cognition in middle age but had cognitive capacities more like young mice and much superior to the controls receiving the special diet. 

    The point here is not it is not enough to just look at redox status, there has to be a careful consideration of all the relevant physiological issues. The diet itself was very complex and to the credit of the researchers the diet contents were a wide mixture of various compounds, not just about antioxidant status. 

    So yes, it is very much about a careful balance of nutrients. 
    If you read the study they used an absurd amount of DL-alpha tocopherol for vitamin E, the equivalent of ~300 regular capsules a day for an adult human. Since vit E is a bit of a blood thinner, this dose could have made them bleed out.

    Gerhard Adam
    What's interesting in comparing the dosages is an earlier study from 2009.
    "Very-high-dose alpha-tocopherol supplementation increases blood pressure and causes possible adverse central nervous system effects in stroke-prone spontaneously hypertensive rats."

    Therefore, we investigated the effects of alpha-tocopherol ( approximately 44 mg/kg body weight; equivalent to 2,600 mg/human/day) on the central nervous system (CNS) of stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP treated with high dose alpha-tocopherol had significantly higher blood pressure than untreated controls fed a basal diet that contained approximately 4 mg tocopherols/kg body weight,
    http://www.ncbi.nlm.nih.gov/pubmed/18942769
    Yet, apparently [as was pointed out previously] this study used a 12.5 times higher dosage than that previously reported as a "very-high-dose".
    At two months of age, animals at each temperature were randomly assigned to either a control diet (RM1 diet containing 10 mg kg−1 ascorbyl-2-polyphosphate and 22 mg kg−1 α-tocopherol), a vitamin C-supplemented diet (RM1 + 180 mg kg−1 of ascorbyl-2-polyphosphate) or a vitamin E-supplemented diet group (RM1 + 550 mg kg−1 α-tocopherol).
    http://rsbl.royalsocietypublishing.org/content/9/4/20130432.full
    Yes, I think we know why the results turned out as they did.  Even in 2008, there was a study that already suggested such an outcome.
    There are several potential reasons why dietary antioxidants, such as vitamin E, have not become robust and repeatable pro-longevity treatments. Firstly, vitamin E supplementation may indeed quench ROS and reduce oxidative stress, but this may have no or little impact on aging and life span if the importance of these processes has been overestimated in vivo.
    http://business.highbeam.com/437525/article-1G1-183490648/lifelong-alphatocopherol-supplementation-increases
    I suppose the most amazing thing about this study is that anyone would've expected that their life expectancy would increase.
    Mundus vult decipi