Thursday, March 15, 2012

Antioxidants and Intermittent Fasting – Good For Longevity?

Antioxidants and Intermittent Fasting – Good For Longevity?
Are blueberry antioxidants beneficial for intermittent fasting? (Photo by Simply Bike)

Is it possible to live longer by combining the benefits of intermittent fasting (IF) and plant polyphenols? A new paper claims that taking polyphenol antioxidants during dietary restriction increases the lifespan of mice more than dietary restriction alone. The antioxidants used in the study were blueberry, pomegranate and green tea extracts.

The subject of the paper – "Potentiation of dietary restriction-induced lifespan extension by polyphenols" – is certainly enough grab the attention of anyone interested in life extension. The abstract seems promising too (link). Here's a quote:

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension. [––] Polyphenol compounds may potentiate IF-induced longevity by minimizing specific components of IF-induced cell stress.

Let's look at these claims in more detail. First off, it's not clear from the abstract what exactly the authors mean by "dietary restriction". The full paper, however, reveals that they use the term to describe pretty much any kind of diet where access to food is limited, including traditional calorie restriction and intermittent fasting.

The longevity confusion

The problem with that opening sentence is that dietary restriction extends lifespan across multiple species only when it equals calorie restriction. That is, you can make a mouse live longer by only feeding every other day, as long as it results in less calories consumed. This is an important distinction, because many people – including longevity scientists – keep propagating the myth that intermittent fasting has the same benefits as calorie restriction. It doesn't. The reason that IF prolongs lifespan in some species is because the animals fail to compensate for the missed calories on their feeding days.

The next sentence is just as problematic. Yes, plant antioxidants have been shown to increase lifespan, but the question is, compared to what? So far, no one has succeeded in exceeding the known maximum lifespan of mice by feeding them antioxidants. Instead, what we see in many studies is that the antioxidant group lives longer than the control group.

The problem is that almost always, neither group lives very long. Poor diets, poor animal husbandry, poor environment – all play a role in how long the animals live. So, in essence, the antioxidants merely make the unhealthy mice a bit healthier. But this is like making a human live 70 years instead of 60 years by giving them some veggies with his daily bread and then claiming that "vegetables extend human lifespan".

Comparing lifespans

That said, there are some interesting figures in the full paper. The graph below shows the survival rates of the three groups; one fed the control diet, the second fed the same diet but only every other day, and the third fed a diet supplemented with polyphenols every other day:

Polyphenols, longevity and intermittent fasting

There's a big drop in the survival rate of the control group around 22 months. For the IF groups, the survival curves look a lot better. So how does this compare to the average lifespan of similar mice kept in good laboratory conditions? Here's a graph of age ranges and survivorship of C57BL7/6J mice (the same strain used in this study):

Mouse survival rates

This survival curve is based on a cohort of 150 male and 150 female mice. As you can see, at 28 months half of the mice are still alive. That's about 850 days, which is a pretty normal figure for mean lifespan of this strain of mice in the literature.

Once again, in the antioxidant study the control group dies earlier than is normal. For some reason, half of the mice are dead at 22 months instead of 28 months. One possible reason is the use of a high-fat diet to "mimic the effects of a Western diet", as the authors put it. This seems like a strange idea to me, because a typical Western diet is no more a high-fat diet than it is a high-carbohydrate diet. Furthermore, plenty of humans (myself included) seem to do quite well on a high-fat diet, whereas with mice it's somewhat different.

The survival curve of the IF mice in the first graph is slightly better than that of the normal-fed mice in the second graph. But that is hardly a surprise, given that both the IF group and the IF + antioxidant group had lower body weights than the control group. In other words, the intermittent fasting once again made the mice eat less than the control group, which in turn resulted in a slightly longer lifespan. It's good to keep in mind, however, that with just 10% calorie restriction longer lifespans have been reported in other studies, so the result is not too impressive.


Perhaps the most interesting result is that the IF + antioxidant group lived slightly longer than the IF group. There's no concensus as to whether it's a good idea to combine CR or IF with antioxidants. It may be that plant polyphenols are essential for optimal nutrition and good for activating sirtuins (which play at least some role in longevity), but there is also some evidence suggests that taking antioxidants may interfere with hormesis and thus diminish the effects of CR.

In this study, the antioxidants had a beneficial effect. While the IF diet by itself activated pro-inflammatory pathways, adding plant polyphenols to the diet blocked this effect. The authors identified 20 gene sets that were down-regulated by the addition of polyphenols, most of them related to immune response, inflammation, cell differentation and tumorigenesis. 

This suggests that if you're doing intermittent fasting, adding some blueberries, pomegranates and green tea to your diet may not be such a bad idea. Note, however, than the mice did not have access to polyphenols during their fasting days, so this study tells us nothing about taking antioxidants during fasting. It also doesn't say much about how polyphenols affect regular calorie restriction without IF in humans.

For more information on intermittent fasting and longevity, see these posts:

Lithium in Drinking Water May Lead to Longer Life
Does Intermittent Fasting Increase Lifespan?
Alternate-Day Feeding and Weight Loss: Is It the Calories Or the Fasting?
Slowing Down Aging with Intermittent Protein Restriction

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5 kommenttia:

Aaron March 19, 2012 at 7:48 AM  

Hmmm, In your opinion, do you think adding antioxidants during fasting days would have been an improvement over during eating days? Unless the antioxidant is one that we produce internally (like gluthathione) I bet typical antioxidants would fail.

It would seem to me that antioxidants are more important during surges of free radicals -- like the surges we have when we consume food.

I'm thinking we would need less antioxidants when we are fasting, but here is the caveat. Without an intake of protein -- I bet our glutathione levels would drop (or maybe we'd just eat the protein in our tissues to make more of it. Maybe we can just supplement with glutathione during fasting (maybe tea too) and just rely on the antioxidants in fruits and veggies during our eating times. (maybe tea here too)

JLL March 19, 2012 at 12:04 PM  


I'm along the same lines as you. My guess is that taking antioxidants only during fasting and not during eating days would have been *worse* than antioxidants during eating and not fasting.

As for antioxidants during fasting AND eating, I don't know, but it seems like antioxidants could potentially be harmful for the adaptation to fasting-induced stress. I know there are conflicting studies on antioxidants + exercise, but the ones that show harmful effects are enough to make me skeptical.


nthmost March 21, 2012 at 10:45 AM  

I don't really see the point of trying to hyperdose on plant antioxidants, not when simply consuming whey protein isolate (WPI) induces awesome levels of glutathione all by itself.

As for the intermittent fasting itself, it turns out that you don't actually need to fully abstain from food to get the benefits of fasting -- just carbs and excess protein.

That means you can have a trickle of WPI, as well as things like coconut oil and butter, during the intermittent fasting period, without actually spoiling the fast.

Aaron March 21, 2012 at 9:01 PM  

nthmost, most rat studies show even better longevity from slight feeding during the ADF studies (ie, eating 20% of the calories on fasting days).

I have yet to find people who really feel normal and energetic on extreme low calorie days when eating only fats (like butter, coconut oil, olive oil). Most people display the best energy if they are fully fasted or have some fruit (for carbs).

Lastly, I don't think the ADF studies are going to be too helpful for humans. As others have pointed out, 1 day of fasting for rats would be multiple days of fasting for humans (and noone is going to do this). While some stress is good I think our adrenals do not like being stressed out (just think of how mental stress can ruin longevity). I remember when I took supplements that really burned energy in my mitochondria (like Glycine Propionyl L-Carnitine) or ate lower carb. I could feel the energy, but my adrenals would burn out. I could tell my dopamine would be higher than normal because I'd be more prone to Hemmroids which I'd get when my adrenals were stressed out.

We dont even know the exact number of hours we have to go without food to really activate autophagy. I'd like to see more studies.

At this point. I'm probably just doing to cycle light days of eating into a normal eating pattern. On those days, I might even take some glutathione to lessen my body from breaking down protein for that conversion. I def won't be consuming any more antioxidants as I'd probably already be consuming fruit on those days. Plus, the oxidant load on my body wouldn't be as high so I wouldn't have to worry.

Anonymous September 7, 2012 at 1:26 PM  


Great blog and very interesting.

aLl off-topic:

Firstly, having dug around here a little I've not noticed you mention meditation as part of you health routine - the more research performed exploring meditation the more benefits that seem to emerge, not simply on a day to day well-being basis but also longer term too. Studies appear to show increase brain matter, improved immune system - there still may remain some doubt over causation vs correlation.

On intermittent fasting did you see the bbc horizon programme?

Also, I'm guessing you've caught this on TED

which I believe hints at the benefits offered of fasting over calorific restriction - that when food is scarce the foxo regulator protein is allowed to bind to the gene and in effect code protiens to do lots of repair work (assuming CR doesn't ever trigger this). I believe she terms it youth extension which is a far better term to seed in the public domain than say extreme longevity or perhaps even 'youth expansion' would arouse more interest.

I'm pretty new to fasting and recently I was searching for a fasting time-line and discovered this:

Do you know if this has been validated? It is very interesting and again would suggest benefits beyond those elicited from CR.

On a philosophical note the fable of the dragon tyrant (which recently appeared in 'philosophy now' along with other related articles:

Exposure on life-extension is certainly increasing.

once again thanks for the blog and good luck.


(on yes on Vit D, you take a lot above recommended levels - do you have some research? or is it simply a matter of regulating this with periodic measurements?)

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