Monday, March 10, 2014

Chewing the antibiotics-make-us-fat story

A piece in the New York Times yesterday, "The Fat Drug" by Pagan Kennedy, asks whether antibiotics are making us fat.  As far back as 1948 people knew that antibiotics could make animals grow faster, bigger and fatter. Even after more than a half-century, it still isn't wholly clear why the 'sub-therapeutic' doses given to animals cause them to gain weight, though there is some thought that perhaps they kill off the animals' gut flora, thus allowing all calories consumed to go directly into growth of the host. But Kennedy (and others, including a September 2013 paper in Nature) suggests that the same thing could be happening to us.

Some ethically questionable studies were done way back in the 1950's to test this, Kennedy reports.  Schoolchildren in Guatemala were fed antibiotics everyday for a year, and a doctor in Florida carried out the same experiment on a group of mentally disabled children; they did indeed grow larger.

This isn't a surprise really.  But the piece also raises a few questions that it doesn't answer, because few of us are consuming antibiotics daily.  First, could there possibly be a direct link between consumption of antibiotic-laced meat and obesity?  About this Kennedy says,
Of course, while farm animals often eat a significant dose of antibiotics in food, the situation is different for human beings. By the time most meat reaches our table, it contains little or no antibiotics. So we receive our greatest exposure in the pills we take, rather than the food we eat.
Antibiotics in meat
But I'm not sure what the evidence is for this.  Animals are eating 'sub-therapeutic doses' -- in fact, so are we, given that residual antibiotics are often found in meat.  I've tried to find evidence as to what kind of effect the amount we consume in meat might have, but have found nothing, though it's possible that cooking it before we eat it will denature the antibiotics so they don't do anything.  So, how little we consume, or how much it might take to produce the same effects in us as in food animals isn't clear, at least to me.  (The effects of antibiotic usage in food on antibiotic resistance in people are another matter, and fairly clear, but not part of this particular issue.)

So here's a very crude test of the effect of eating meat laced with antibiotics.  Consider the following:  Americans now eat more meat per capita than anyone but Luxembourgians.

Meat consumption, 2007; UN Food and Agriculture Association, in The Economist

We use more antibiotics by kilogram of meat produced than any other country.

Antibiotics by kg of meat produced; Source

And the prevalence of obesity in the US is higher than anywhere in the world.

Obesity rates, 2009; The Economist
So, the US has the highest rates of obesity, and the highest rates of antibiotic usage in meat, and nearly the highest meat consumption rates.  Does this mean, then, that the antibiotics we're consuming in our meat are causing us to become obese?  It sure looks like it.

Until you look at obesity rates in the countries that are just below the US in the amount of antibiotics we use in animals -- Greece, Netherlands, France, Spain, with obesity rates all over the map.  And, while the correspondence between countries isn't great among these charts, countries with the highest obesity rates that are also on the antibiotic usage chart don't have among the highest usage rates.  So this crude attempt to answer the question of whether antibiotics in the meat we consume are making us fat seems to point to no, though certainly not definitively.

What about prescribed antibiotics?
But, I really like the question, not only because it might have explained the obesity epidemic, but because it doesn't immediately assume a genetic cause.  But we can still steer away from genetics and ask the question as Kennedy did -- is it the antibiotics we're giving our children to treat things like ear infections that's responsible for obesity?

According to Kennedy, mice fed high calorie diets and antibiotics in one study gained a lot more weight than mice fed the same food minus the antibiotic, the controls.  We aren't mice, and we aren't pigs, but it does start to sound like there might be a connection.

But if so, what would the dosage have to be?  There must be a significant difference between being fed even sub-therapeutic doses of antibiotics daily and having a therapeutic dose once or twice a year (I haven't been able to find an actual figure for average antibiotic use in the US, so this is a guess, but I'd bet it's not too wild).  And, we don't know whether there's a particularly at-risk age of antibiotic use -- does it have to be in childhood, or would adult users be at risk as well?

So, dosage and timing would seem to be important questions to answer, as well as context (as our friend Charlie Sing would remind us).  Would there be particular lifestyles or diets that increase risk of antibiotic-induced obesity?

Finally, the August Nature paper on the 'microbiome' and obesity reports that obese people have different gut flora than thin people.
Low richness of gut microbiota has been reported in patients with inflammatory bowel disorder (IBD), elderly patients with inflammation and in obese individuals, but the differences of richness within these groups or among non-obese individuals were not previously detected. As the composition of the gut microbiota seems to be rather stable over long periods of adulthood, its richness may well be a characteristic feature of an individual. In mice, the richness seems to be affected by repeated antibiotic treatments, and host genetics could also have a role. 
The suggestion seems to be that antibiotics could be responsible for the difference.  But, it's very premature to conclude from this paper that antibiotics cause obesity, because, for one thing, it's not clear whether the richness of the gut flora preceded obesity, or is a consequence.  And, certainly the drug/obesity connection isn't going to sidestep the question of a genetic influence for long.  Geneticists know very well how to keep their share of the pie.  They've been doing it for years:  "Yes, of course, the rapid change in disease X rates is due to environment, but that's because some people have genes that make they hyper-responders.  So we need to do genome mapping to find these few sensitive genotypes!"  Unfortunately, mapping for most of the common diseases, like obesity or diabetes or asthma or autism or you-name-it -- or even just human stature -- has been justified on the 'a few sensitive hyper-responding-genes-are-responsible' argument......and all have shown no evidence for that.  Instead, it's clear that environmental changes really are responsible for many major risk changes, not unlucky genotypes.

Anyway, the antibiotics/obesity connection in humans is an intriguing idea, but there's still a lot we don't know.


Manoj Samanta said...

Looks like all Anglo-Saxon countries are at the top in the obesity chart, Mexico and Chile being two exceptions.

Mexico is too close to US to be argued to be highly influenced by US practices. So, I guess Chile is the country to design an experiment on to figure out what is going on. Did Chile import too many US practices after Pinochet, or did they grow obese in their own way?

I traveled extensively in Chile 12 years back, but people did not seem obese at all.

Manoj Samanta said...

In India, obesity among city people has been rising very fast, but the number of poor rural people is so large that you do not see the influence in your chart. Singapore govt carried out a study on fast food and found very interesting results -

Manoj Samanta said...

Original paper is here -

Incidentally, I noticed many US fast food restaurants entering Chile around 2000.

Anne Buchanan said...

Interesting. But, there is so much correlation here -- with obesity and increased sugar intake, increased process food consumption, decreased activity, antibiotic-laced meat, etc. -- that I think it's impossible to conclude anything from these population measures.