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Just a few weeks ago, a study was published in the Journal of Nutrition that many reports in the news media said proved that honey was no better than sucrose as a sweetener, and that high-fructose corn syrup was no worse.

But did it? This study, and what it says about nutrition research in general, are the topics of this week's Healthcare Triage.

This is based on a column Aaron wrote for the Upshot. References can all be found in links there: http://www.nytimes.com/2015/10/27/upshot/surprising-honey-study-shows-woes-of-nutrition-research.html

Episode references:
Weight Loss: https://www.youtube.com/watch?v=hdY-NJq6zVQ
Dietary Guidelines: https://www.youtube.com/watch?v=PhEwfaFLrd0
Exercise and Weight Loss: https://www.youtube.com/watch?v=fCtn4Ap8kDM
Coffee: https://www.youtube.com/watch?v=ly1NjibK79U
Milk: https://www.youtube.com/watch?v=hzyFZcuHmeI
Red Meat: https://www.youtube.com/watch?v=aOVBOwbqcT8
Artificial Sweeteners: https://www.youtube.com/watch?v=Mf82FfX-wuU

John Green -- Executive Producer
Stan Muller -- Director, Producer
Aaron Carroll -- Writer
Mark Olsen -- Graphics

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Just a few weeks ago, a study was published in The Journal of Nutrition that many reports in the news media said proved that honey was no better for health than sucrose as a sweetener and that high fructose corn syrup was no worse, but did it?  This study and what it says about nutrition research in general are the topics of this week's Healthcare Triage.

(Intro)

Let's waste no time.  To the research!  This study shocked people on all sides of the sweetener debate.  It has become an article of faith among many that natural sweeteners like honey are better for you than engineered sweeteners like high fructose corn syrup, but not so fast.  A more careful reading of this research would note its methods.  The study that I'm talking about involved only 55 people and they were followed for only two weeks on each of the three sweeteners.  

Sure, glucose and insulin levels and measures of insulin resistance were no different for honey, sugar, and high fructose corn syrup over those two weeks, but should we really place so much faith in such a small, short-lived trial that didn't focus on actual health outcomes?  The truth is that research like this is the norm, not the exception. 

We've done lots of Healthcare Triage episodes on nutrition, on weightless, dietary guidelines, healthy food choices, the role of exercise in weight loss, the benefits of coffee.  A lot of the time, we're countering conventional wisdom, for example, about  milk or red meat or artificial sweeteners.  You often ask me how myths about nutrition get perpetuated and why it's not possible to do conclusive studies to answer questions about the benefits and harms of what we eat and drink.  

Almost everything we know is based on small flawed studies.  The conclusions that can be drawn from them are limited, but often oversold by researchers in the news media.  This is true not only of the newer work that we see and talk about now, but also the older research that forms the basis for much of what we already believe to be true.  

I'm not ignoring blockbuster studies that you love because I don't agree with their findings.  I'm usually just underwhelmed by what I can meaningfully conclude from them.  The honey study is a good example of how research can become misinterpreted.  That's not because it's weak.  It's actually among the stronger studies we have available, because it's a randomized controlled trial, and as I've noted before, we often make inferences not from clinical trials but from epidemiologic research which is limited in many ways.  

Randomized controlled trials, on the other hand, allow us to make much stronger arguments about causality and can account for many other confounding factors that might bias cohort or case control studies.  A 2011 systematic review of studies looking at the effects of artificial sweeteners on clinical outcomes identified 53 randomized controlled trials.  Now, that sounds like a lot.  Unfortunately, only 13 of them lasted for more than a week and involved at least 10, yes, 10 participants.  10 of those remaining 13 trials had a (?~2:57) score, which is a scale from 0 to 5 to rate the quality of randomized controlled trials of 1.  This means that they were rather low quality.  None of these trials adequately concealed which sweetener participants were receiving.  The longest trial was 10 weeks in length.  

Think about that.  This is the sum total of evidence available to us about sweeteners.  These are the trials that allow articles, books, television programs, and magazines to declare that honey is healthy or that high fructose corn syrup is harmful.  Ironically, this review didn't even find the latter to be the case.  They could find no harms from high fructose corn syrup and non-caloric sweeteners were found to lead to reduced caloric intake and small but statistically significant decreases in body mass index.  That hasn't stopped many people from arguing the opposite to be true.

Even when we manage to pull off higher quality studies in this area, we often fail to reproduce reality.  A study published this year in the journal Frontiers in Nutrition looked at eight different meta-analyses on the effect of fructose consumption on cardiometabolic risk.  They found that the average dose of fructose given to people in those trials was more than 2-3 times what people really consume in the United States, so even if they found some sort of result, it isn't terribly helpful because it doesn't apply to what most people are actually eating.

My point is not to criticize research on sweeteners.  This is the state of nutrition research in general.  Study after study after study has shown that people, even those trying to lose weight, cannot stick to prescribed diets for long periods of time and that's the research looking at highly motivated people who've taken it upon themselves to change what they eat.  If they can't stick to a certain regimen, how can we expect study participants who aren't as invested to follow strict instructions for months at a time?  This is especially true when people aren't seeing immediate results, which happens often when it comes to food changes.  If they think something isn't working, they're unlikely to continue.

Moreover, unlike drugs, which people can get from only a limited number of places, people can get food from all.  It's impossible to control peoples' intake of sugar, for instance, when it's added to so many foods today, including pasta sauce, crackers, and even soy milk.  You can try to get them to replace sugar packets with honey or high fructose corn syrup, but when sweeteners are in so much of what we eat, it's nearly impossible to control intake as closely as we need for as long as we'd like.

This is why some of the most powerful research on nutrition comes from prisons or mental hospitals where we can control what people eat more directly, but this type of work comes with its own ethical concerns.  The outcomes people care about most, death and major disease, are actually pretty rare.  Detecting differences in rates of those occurrences requires huge numbers of people, especially if you choose not to focus on the elderly.

This is why we often focus on process measures like glucose or insulin levels, which sometimes don't translate into measurable changes in health.  Finally, the research we require, long-term randomized controlled trials with many participants, is very expensive.  Most organizations lack the deep pockets of the pharmaceutical industry when it comes to that kind of work.

Many food companies don't feel like they will see a great return on investment from this type of research.  They can sell their products without proving that they're healthy, so why bother?  The study on honey I discussed earlier in this episode was funded by the National Honey Board, and I'm guessing they weren't thrilled with the results.  When industry does fund research, people tend to view it with great skepticism anyway, making it a losing proposition.  Because of this, we will probably continue to see results mostly from small, sometimes flawed, short-term studies of nutrients and additives.  Treat the results of that research with the respect they deserve, though.  Ignore the grandiose proclamations.

Healthcare Triage is supported in part by viewers like you through patreon.com, a service that allows you to support the show through a monthly donation.  Your support helps us make this bigger and better.  We'd especially like to thank our research associate Cameron Alexander and our first ever surgeon admiral, Sam.  Thanks Cameron.  Thanks, Sam.  More information can be found at patreon.com/healthcaretriage.  

This is why some of the most powerful research on nutrition comes from prisons or mental hospitals where we can control what people eat more directly, but this type of work comes with its own