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May 15
free vitamin water!
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Yesterday, I posted a blog piece that talked about a recent paper which found that taking antioxidant vitamins wiped out some of the effects of exercise (glucose infusion and insulin sensitivity). Well that paper reminded of a paper I wanted to blog about for a while, and now is the obvious time.

Bjelakovic et al., 2007 published a systematic review and meta-analysis in JAMA. The meta-analysis included 68 randomized trials with 232,606 participants (which included 385 publications!).

What they were specifically studying was: ‘All randomized trials involving adults comparing
beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either
singly or combined vs placebo or vs no intervention were included in our analysis’ - on the outcome of all-cause mortality.

Results:

When looking at low-bias risk trials they found:

Multivariate meta-regression analyses showed that low-bias risk trials (RR,
1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-
1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.

Wow! you might say. Increase mortality with the intake of various antioxidants.

Their conclusion were:

We did not find convincing evidence that antioxidant supplements have beneficial
effects on mortality. Even more, beta carotene, vitamin A, and vitamin
E seem to increase the risk of death
. Further randomized trials are needed
to establish the effects of vitamin C and selenium.

Really makes you think about your ‘morning vitamin pill’ regimen.

Now of course you are all asking why would taking various vitamins result in worse outcome? Good little scientists. Well the authors do provide a possible explanation (which sounds very similar to the explanation given in yesterday’s post).

Although oxidative stress has a hypothesized role in the pathogenesis
of many chronic diseases, it may be the consequence of pathological conditions.
133 By eliminating free radicals from our organism, we interfere with
some essential defensive mechanisms like apoptosis, phagocytosis, and
detoxification.134-136 Antioxidant supplements are synthetic and not
subjected to the same rigorous toxicity studies as other pharmaceutical
agents.137 Better understanding of mechanisms and actions of antioxidants
in relation to a potential disease is needed.138

And rightfully the authors also mention they only examined synthetic vitamins (because it is with these pill form of vitamins that you can run nice little (well actually very large) clinical trials) and we should not translate these results into vegetable and fruit intake.

These studies were performed in developed nations were minimal food intake is not a problem, the results might be completely opposite in less developed countries where they don’t get adequate amount of food and vitamins.

This large data set, and other similar data, are indicating that the pill based formed of a number of vitamins might be detrimental, but there is no data to suggest that eating fruit and vegetables (where you get most of your vitamins) results in a negative outcome - and everything indicates they have a very positive effect on your health (see: apple a day keeps cancer away, plums and peaches, blueberries, Mediterranean diet I, Mediterranean diet II)

Take home message:

You might want to carefully consider your intake of synthetic vitamins - they might block some of the bodies normal/required signalling, which can lead to a worse overall outcome.

May 14
SAN FRANCISCO - APRIL 06:  Bottles of vitamin ...
Image by Getty Images via Daylife

We have all been told to eat/take our vitamins - but if it is in pill form you might want to re-think things.

A new paper (Ristow et al., PNAS 2009 -freely available) looked exercise when combined with the use of antioxidants. One general thought is that it might be wise to take antioxidants if you exercise to reduce the oxidative damage induced by exercise. However, the question also is does the antioxidants inteferre with the normal adaptations that occur with exercise?

Experiment:

Subjects in this experiment were engaged in a 4 week exercise program to improve insulin sensitivity and glucose metabolism to help prevent diabetes. The subjects were considered untrained as they did less that 2 hours of exercise per week (but they also used 2 pretrained groups and saw the same results - see below). Exercise consisted of 5 days a week of: 20 minutes of biking or running, 45 minutes of circuit training, and 20 minutes for warming up and cooling down. So we can say roughly 65 minutes, just over an hour, of exercise 5 days a week.

One group took vitamin C (1,000 mg/day), and vitamin E ( 400 IU/day) (this is in the range of what many people take), while the other group received an identical looking placebo pill.

Results:

The placebo group (no antioxidants) displayed improvements in glucose metabolism and insulin sensitivity. However, the antioxidant taking group did not see any improvements. Wow! While the placebo control group received the positive benefits of exercise - improved glucose infusion rates, and insulin sensitivity - those taking antioxidants failed to see the expected improvements in these parameters.

(there were two other groups: pretrained placebo, and pretrained antioxidant consumers (pretrained were subjects that did at least 6 hours of exercise per week) - which did the same exercise program as above. The researchers wanted to see if it made a difference if subjects were already well adapted to exercise. I left these out for simplicity sake - but they basically saw the same results - antioxidant use interfered with the normal adaptation to exercise - as measured by glucose use and insulin sensitivity).

The subjects who did not take the antioxidants showed an increase in reactive oxygen species (ROS), while those that took the antioxidants did not. This means the antioxidants were indeed doing their job and reducing/preventing free radicals in those that took them - but that is the problem. The free radicals/ROS are part of the natural signaling.

Via future pundit article the lead-author Michael Ristow said this:

Exercise causes repeated boosts of free radicals, which - according to our results - induce a health-promoting adaptive response in humans. Subsequently, our body activates molecular defense systems against stress, and metabolizes carbohydrates more efficiently, both of which prevents diabetes, and possibly other diseases. Blocking these boosts of free radicals by antioxidants accordingly blocks the health promoting effects of exercise.” He further says that “short-term doses of free radicals may act like a vaccine, helping the body to defend itself from chronic stressors more efficiently by inducing a long-term adaptive response”

Sometimes when we try to stop the bodies own system we end up doing more harm than good. Stress (if not overdone) via exercise induces various signals, including free radicals, to initiate positive changes/adaptations.

This following diagram nicely summarizes the paper:

The authors conclusion was: ‘Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.’ Pretty clear and simple.

But they flesh things out a bit more here:

Taken together, we find that antioxidant supplements prevent
the induction of molecular regulators of insulin sensitivity and
endogenous antioxidant defense by physical exercise. Consistent
with the concept of mitohormesis, we propose that transiently
increased levels of oxidative stress reflect a potentially healthpromoting
process at least in regards to prevention of insulin
resistance and type 2 diabetes mellitus.

The living body is a pretty incredible entity - and sometimes when we try to help it with our interventions we actually hurt its natural ability.

Tune in tomorrow to hear even more shocking results (all-causes of mortality) of intake of antioxidant vitamins pills (update: link to the piece). Also you will hear a bit about the difference between the intake of synthetic vitamin pills versus fruits and vegetables

Caveat: very high levels of exercise  may require the use of antioxidants so there is not excessive levels of oxidative damage from free radicals (see inverted U shape curves for a general discussion on this subject). However, we do not know at this time of what level of exercise where it might be smart to take some antioxidants (3+ hours is my guess), but it is still probably better to get these extra antioxidants from fruits and vegetables.

see also: inverted U shape dose curve - the shape of biology

May 9
91.365 "Tell them to remember hope. We ha...
Image by ashley rose, via Flickr

“Pain or suffering of any kind, if long continued,
causes depression and lessens the power of
action; yet it is well adapted to make a
creature guard itself against any great or
sudden evil.”
The Life and Letters of Charles Darwin,
Charles Darwin, 1887

This is a bit of a dangerous post, but so is depression.

The post is largely based on Nesse 2000, ‘Is Depression an Adaptation?’, which I heavily quote from.

Take home message if you don’t have time to read all the article:

Some negative and passive aspects of depression may be
useful because they inhibit dangerous or wasteful actions in situations
characterized by committed pursuit of an unreachable goal,
temptations to challenge authority, insufficient internal reserves to allow
action without damage, or lack of a viable life strategy.

Though, the author also points out that many depressions are disease states - so the notion that depression is an adaptive response might only be a subset of the range of potential depressions.

Continue to read to learn the more fleshed out idea:

I think most of us can agree that depression causes an immense level of suffering, for the person undergoing to depression, but also for the rest of the people close to the depressed. However, with such a large percentage of the population (see depression’s cost to the individual and society) experiencing this malady one might wonder if depression has a ‘function’. And this point Darwin was trying to convey in the opening quote of this piece.

Okay, if we are going to entertain this notion we must still wonder what could possibly( be the function of depression?

Nesse, offers a number of possibilities but emphasizes the idea that depression may play a role in drastically reducing motivation for unreachable goals.

If a commitment to pursue a goal encounters an obstacle, efforts increase and become aggressive. If the obstacle cannot be overcome, low mood helps to disengage the commitment
and end the cycle. If the individual cannot disengage, low mood escalates. Klinger concludes, “depression is ordinarily, therefore, a normal, adaptive part of disengaging oneself from an incentive.”56(p21).

If failure to reach a goal might induce depression to ‘encourage’ the organism to stop pursuing a particular goal (that is unobtainable), then one might surmise that those seeking the highest goals might suffer more depression in an attempt by the system to alter the pursuit of lofty goals.

Clinicians have long noted that depression is common in people who
are pursuing unreachable goals.47,48 “Failure to yield” may be an example,
in the status competition domain, of this more general situation.
When current life plans are not working, the distress and lack of motivation
that characterize depression may motivate planning and reassessment49
or escape, even by suicide.50

To bring in some neuroeconomic aspects to shine light on this problem one needs to think of the commitment of resources (time and energy) in pursuit of a goal with payoff X. Obviously the loftier the goal the greater potential reward, but also the probability is lower. However, if feedback with the environment is indicating that this goal is unobtainable for a particular individual there is a need for a signal to stop pursuing this ‘unprofitable’ wager.

In the article Nesse quotes Wender and Klein:

. . . biologically based self-esteem— and mood in general—seems to us to
have evolutionary utility . . . If one is subject to a series of defeats, it pays to
adopt a conservative game plan of sitting back and waiting and letting others
take the risks. Such waiting would be fostered by a pessimistic outlook.
Similarly if one is raking in the chips of life, it pays to adopt an expansive risk
taking approach, and thus maximize access to scarce resources.73(p204)

This starts becoming interesting and I would like to refer you to a couple articles I have written about optimism and hope (The neuroscience of hope, optimism is good for your health, is the glass half full or half empty: rACC brain activation, are organisms by nature optimists?).

This line of thinking suggests that depending on your probability of success one needs to appropriately adjust your ratio of optimism/pessimism. Of course this just makes common sense that we adjust our behavior based on probability of success, however the question is does depression play a role in adjusting your ‘attitude’, your goals?

Going back to Darwin, one needs to think of how something that seems so hideous like depression would actually improve ‘fitness’ (fitness defined as reproductive success - passing on the genes). If depression reduces the pursuit of an unobtainable goal, and forces a reassessment of the persons overall situation, and an eventual choosing of a goal that will result in a payoff then this could increase the person’s fitness level - then maybe depression could improve the individuals fitness.

I will give an example. Take a 21 year old person who moves to Paris (or Prague, etc) to become an artist (just to take a well know dream/pursuit) for that is their passion. They have an incredible level of drive and determination. This person does whatever is needed to pursue their goal of becoming an artist. Of course it is difficult, as is becoming an actor, athlete, etc. Despite the dogged determination this person has had very little success when nearing their 29th birthday. They might continue to pursue their goal, supplementing their income with low-income, temporary work like they have been doing for the last 8 years. But their reproductive fitness in the culture is low - they are not considered a ‘good catch’ due to the uncertainty of their future, and total lack of success (money or otherwise). Now if the person becomes depressed because of their lack of success and lose all motivation to create their art, this might induce them to give up on their dream. Having abandoned their dream they start a normal job, say based somewhat on their background, as a graphic designer for computer games. The person doesn’t consider themselves an artist for they do not get to draw what they want, but instead what they are told. But the person becomes gainfully employed and his reproductive fitness increases.

However, since depression inhibits all activity then it might just contribute the person to staying in their current situation. If you are stuck in a well and depressed then you don’t have the mental energy to attempt climbing out. This would be a bit of a paradox to the potential adaptive advantage of depression. Nesse then argues that a quick dropping of a dream and a mad rush of to a new un-thought out pursuit would also be disadvantageous.

When depression is instead seen as a state shaped to cope with unpropitious
situations, it is clear how it could be useful, both to decrease investment
in the current unsatisfying life enterprise and also to prevent
the premature pursuit of alternatives. Failure to disengage can
cause depression, and depression can make it harder to disengage. This
may explain why the low-mood system is so prone to getting stuck in
positive feedback loops.88-91 Mood dysregulation may now be so prevalent
because we are bereft of kin, beliefs, and rituals that routinely extracted
our ancestors from such cycles.92

Nesse suggests that he conundrum of depression resulting from failure in life is resolved by accepting the reality of the individual’s life situation. And then the person moves on by giving up on the unlikely probability of their former goal. How this exactly happens was less clear to me. However, what was clear is that if the person fails to disengage then ‘serious pathology‘ is likely to occur.

Earlier in Nesse article he uses the example of an animal behavioral choices while foraging a food patch.

As the food in a patch is depleted, organisms give up on that patch at close to
the optimal time, namely, when the rate of return in the current patch declines
below the average rate of return over all patches. If the overall
rate of return from all patches drops below the cost, foraging stops.

Nesse then returns to this theme when discussing the neuroeconomics of the choice of people when it is apparent they need to move on. Changing your goal engagement is considerably more difficult than simply jumping to the next food patch because of the emotional investment in these various goals.

At least as important as the risks and costs of making a
change is the threat to the person’s identity, reputation, and sense of a
secure place in a social network and the cosmos.

At the end of his paper Nesse offers a few testable hypotheses, which are interesting.

The simplest untested prediction is that depression should be
common in people who are unable to disengage from unreachable goals.
Graduate students who are failing and faculty who are unlikely to make
tenure are obvious candidates for study, but other situations are far
more common: unrequited love, inability to get work, pursuing an elusive
large life goal….

Ability to repress such wishes should prevent depression.

Finally, Nesse wonders about the possibility that foraging/feeding patterns may be linked with the behavior of depression.

If the brain mechanisms that regulate foraging are related to those that mediate depression, then antidepressants should change the duration of foraging time in a depleted patch and the willingness to exert effort even when the net rate of return is negative. They might also change preferences for working hard for a large intermittent reward vs easily getting small, frequent rewards. If low mood is an active coordinated state, then the brain mechanisms that mediate it can be blocked at different points, so antidepressants should be effective via multiple mechanisms.

I find this last point particularly intriguing as I have written previously about the relationship between antidepressants and antipsychotic use, increase levels of ghrelin, and subsequent weight gain.

Take home message:

I guess one needs to know when to hold them, and when to fold them. In specific situations depression may be a signal emanating from your system to give up. The trick is not to give up on life, but rather only give up on the specific unobtainable goal. But on the other side of the coin, ‘what if life without a dream’.

I do not know if a subset of depressions is an evolved adaptive response to stop us from chasing after fruitless endeavors (empty food patches), but it does provide food for thought.

(some of Nesse’s followup papers: Nesse 2004Keller and Nesse, 2005, Keller and Nesse 2006, Nesse and Ellsworth 2009.)

Apr 21
Film poster for An Inconvenient Truth
Image via Wikipedia

Thankfully the current generation of young people are far more aware of the environmental issues and willing to do something about it. They have taught their parents to recycle, use reusable grocery bags, to buy carbon credits (though controversial), etc, etc.  However, this same young generation is the fattest in our history (and potentially the least fit).

Does being overweight really coincide with the principles of trying to keep the planet healthy?

I have wanted to write a piece about this issue for awhile but didn’t have a nice published journal arguing what I thought were various obvious points, but now one has come out.

In a study published in the International Journal of Epidemiology by Edward and Roberts (2009) argues that food production is one of the main contributors (20%) to greenhouse gas emissions (H/T to esciencenews). If you have a population of people in the developed nations that are overweight (ranging from 20-65+ % of the population) this would have a number of implications. It costs more to transport the heavier people but also they are eating more than someone of normal weight and hence use up a greater amount of the valuable and dwindling energy resources and a greater amount of food producing land. This is not exactly rocket science to realize this.

Being overweight is equivalent to deciding to drive around in a SUV (or any other gas guzzler).

If people slimmed down (via escience news):

Transport-related emissions will also be lower because it takes less energy to transport slim people. The researchers estimate that a lean population of 1 billion people would emit 1.0 GT (1,000 million tonnes) less carbon dioxide equivalents per year compared with a fat one.

Really the comparison here was between a population of ‘lean’ with a mean body mass index (BMI) of 24.5 vs a more typical ‘developed’ country with a BMI of 29 (to give you a frame of reference normal weight is 18.5 -24.9, overweight is 25-29.9m and obese is 30+). The heavier population would consume 19% more food than the lean population.

I really don’t have to give you a bunch of numbers and facts I think all of you intuitively know that it only make sense that an overweight population consumes more energy and contributes a greater amount to environmental issues (including global warming).

I think the authors give a pretty clear statement in their discussion (GHG = global green house gases):

We argue that increased population adiposity, because of its contribution to climate change from additional food and transport GHG emissions, should be recognized as an environmental problem.

So if you care about the environment, be it you are young or old, then do your part and stay (or become) slim (meaning normal weight) - which will also contribute to your own health.

If you care about the planet’s health, then do something about it by taking care of your own health - by maintaining a healthy weight. Something for all of us to think about, but maybe this message has the best chance in taking hold in the current young generation who as a whole do care about the planet’s health.

Are you a gaz guzzler, a hybrid, an all electric, or even a highly efficient bicycle?

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