Thursday, 7 August 2014

Critical fitness series – a critical look at the science behind popular fitness advice

We all have this person in our life – the health nut. He or she might be a certified personal trainer or just really addicted to exercise. However, these people have one thing in common that really ticks you off sometimes (or just annoys you slightly depending on how much you think they know what they’re talking about): they are always trying to tell you the best way to exercise and eat. Whenever this happens, which is quite often, that voice in your mind (or at least my mind) goes, “where is he/she getting this information? Is this actually true? Will this even work?” If the voice in your mind doesn’t say this or something along the lines of this, you will probably not be interested in this blog.

Chances are, the source of information for them is someone else, who heard it from someone else, and not from actual research. Chances are, that even if they did glimpse it from a study (and I emphasize glimpse), the study was not done in a manner that warrants the conclusions that were made. Chances are, you are a curious, intelligent person like me who just wants the best information out there about health and fitness. Sounds like you? Then follow this blog series, where I will critically assess the scientific literature behind popular fitness advice (if any exists at all). I will judge the body of research behind a claim using my scientific eye, and help you assess whether the claim is actually close to the truth, and the advice worth following. 

Popular fitness advice #1: Cardio is ineffective for weight-loss
            I’m starting my blog on this popular fitness myth that a lot of health nuts like to hand out. It was inspired by a conversation I had with a friend who loves cardio but hates weight-lifting. I realized that I have this conversation with people ALL the time! Usually, I hand out the advice I was given: weight-lifting along with cardio is most effective for weight-loss. (You probably realize by now that yes, I am a health nut to many people). I got this advice from the internet, probably one of the gazillion websites that give fitness advice. I also confirmed this with a personal trainer friend of mine (my health nut, yes it’s like a pyramid scheme, get used to it - this is the fitness industry folks). After diving into the literature though, I think the answer is not as clear-cut as it might seem. However, before we get deep into the science, we need to start from the basics.
            First, what is weight-loss? I think most people think of weight-loss simply as reducing the number on the scale. But I think most people would also like those lost numbers to be coming from dying fat cells. This is where it starts to get complicated.
In order for scientists to do science, we need to be able to measure something accurately and reproducibly. However, scientists are people, and people are naturally lazy, so we like to simplify problems (see my previous post for what can go wrong when people get REALLY lazy).
A given experiment usually goes something like this: an older professor or health professional got some money to do some work about a given topic (here weight-loss and exercise). He recruits a few young, bright, eager minds (could be undergraduates, graduate students and/or health professionals, sometimes even high-school students) to do the research. They write up a plan for the experiment. At least two groups will be involved: a control group and the treatment group. In this example, depending on how ambitious the professor is, the control group could be doing no exercise at all or their regular routine. The treatment group will receive a more rigorous exercise schedule to be followed. Then the professor tells the students to do the work. They recruit some people who want to lose weight. Initially, there might be a lot of volunteers or people interested. Some of these poor people will be put in a control group and not achieve the goals they wanted to achieve. These people might get mad and drop out. As the experiment continues, some people might not be following what they are supposed to do. Some people might get into some family issues and forget about their experiment, or simply drop out. As time progresses, more and more people drop out, and most people will not have followed the program to the level that the researchers would hope for. At last, the initially eager young minds become frustrated and bitter young minds. They might themselves quit, leaving the experiment in tatters. They might push through all the problems and finish up the research. However, for an experiment to be trustworthy (for us to believe that their conclusions are justified, that what they saw is real, that the same things will occur in real life again and again), many things need to happen. There needs to be enough difference in terms of the measurements made between the groups, and enough people in each group, for the statistical gods to bless us with a significant P-value (or “real”, although this point is also arguable). Since so many people have dropped out of the experiment, we can probably imagine that the results from this hypothetical experiment are not trustworthy.
As you can see, a lot of things can go wrong when doing science. Of course, everything could go smoothly and you get great results, but this rarely happens (Murphy’s law – everything that can go wrong, will). Luckily, scientists are not stupid. We try to circumvent these problems before they happen by designing experiments that avoid running into these types of issues. Most of the science done in the fitness field these days are done using high-tech machines to accurately measure athletic performance (ex. force output, activation of certain muscles/neural circuits) in a short time frame. This way you get definite and reproducible measurements quickly. However, you can’t measure weight-loss in a short time frame (unless you sit in the sauna for a few hours).
I digress. Now that I have dealt with the scientific sidebar, and you know what real science is like, we can deal with the question in mind. However, things continue to be complicated.
You know when you have a family dinner. Your mom and dad are cooking, and they have an argument over how to cook the roast. You dad read somewhere that straight 350F for 3 hours is the best, while your mom knows from experience that searing the meat first, then 300F for 4 hours leads to be most tender and juicy roast. The point is, people are very opinionated, and have very different ideas about how one should approach a problem. Well, scientists are also people, so they also like to approach the same question – here, what is the most effective way to lose weight – in very different ways. This makes assessing which experiment has the most definitive answer to the question much more difficult, because everyone wants to roast the beef at a different temperature. 
To be continued...

Thursday, 24 July 2014

When science goes wrong, and what we can learn from it

            Cells develop in an embryo in a step wise manner, like children going into school and finally choosing a career. Initially, children may choose whatever career they want and potentially become any kind of person they want to be. As the environment changes over their lifetime, children evolve and eventually become the stubborn and narrow-minded adults they were destined to become. Jokes aside, cells from an embryo are also given signals by the environment to become the cells they were destined to become. Essentially all the cells in our body are made of a specific set of cells in a developing embryo called pluripotent stem cells – master cells capable of becoming any cell type in the body. Most of the cells in our body now are terminally differentiated cells, meaning they have already chosen their path and arrived at them, and will never be able to turn into another type of cell.
The generation of master pluripotent stem from normal cells that have already become specialized has recently sparked a revolution in the biomedical sciences. This technique, called induced pluripotent stem cells, discovered by a Japanese scientist Dr. Shinya Yamanaka and earning him a Nobel prize in 2012, holds incredible promise in the field. One could envision taking skin cells from a patient who needs an organ transplant, changing these skin cells to master pluripotent stem cells, then giving them signals to become cells that make up the organ that the patient needs, growing and transplanting the organ back into the patient – all with minor risk of rejection by the patient’s immune system. During normal transplants, organs from another person are usually rejected by the patient because the immune system can recognize the organ as foreign and attack it, whereas an organ made from cells of the patient will be much less likely to be recognized as foreign. The technique as originally described by Dr. Yamanaka requires the infection of cells by viruses carrying four master genes. Genes are packets of information encoding proteins that ultimately play a function in the cell. Essentially, these four genes, called the Yamanaka factors, drive the cell into an identity crisis, causing them to morph back into their infantile state. This technique, while effective, is difficult, tedious, and expensive. Moreover, the technique has been thought to be dangerous, since it requires infection of cells by old inactive viruses that can lead to other potentially deadly mutations (think malignant cancer) if injected back into a patient. Therefore, many researchers have since been attempting to discover a faster, more efficient, and less dangerous way of driving terminally differentiated cells into an identity crisis, with success stories few and far between.
Enter another group of Japanese scientists, who published a paper in Nature back in January claiming that these master cells can be made simply by putting normal terminal cells into a slightly acidic environment. This paper took the field by storm – people were incredulous that cells could by coaxed into an identity crisis simply by tripping them out with some acid (pun intended). Not surprisingly, slews of researchers in the field tried to reproduce master cells in their labs using this technique. Soon, rumors started spreading that the technique was irreproducible. The murmurs soon became a loud din in the field, and many questioned the legitimacy of the paper in public. Various independent groups with a goal of revealing false data in peer-reviewed journals found that two pictures of cells in the paper that are supposed to represent different cells are in fact identical pictures. Parts of the methods were also found to be plagiarized. The authors quickly apologized for these mistakes, and called them honest mistakes, but enough doubt was casted on the paper that the research center where most of the research was conducted – the Riken center in Japan – began an investigation. The investigation eventually revealed inadequacies in data management, record keeping and oversight. Data described as coming from different lines or strains of mice were in fact found to be from the same strain of mice, and more cases of replication of the same data was found. The lead author of the paper, Haruko Obokata, a young researcher whose career looked so bright a few months before, was charged with misconduct – a death sentence for her scientific career. She quickly lawyered up and vehemently denied any misconduct with intent, and appealed charges of her misconduct, but these charges were later reaffirmed by Riken. The prestigious journal Nature that published the paper found itself in a public relations nightmare, and finally decided to retract the paper earlier this month.
Backlash in the scientific community is widespread. Ironically, earlier in the year, Nature ran a series of articles about how they were taking steps to improve their peer review process. Many scientists believe that the big journals in the field – Nature, Science, and Cell – are so eager to publish the next big thing that they don’t invest enough time, man-power and level of scrutiny needed to truly peer-review and weed out the faulty science. A recent investigation into big landmark papers in the cancer field found that results from only 6 out of 53 papers were actually reproducible (1). Another paper looking at a wider array of studies found that only 20% of papers have results that are precisely reproducible (2). While most researchers believe that cases like the acid-bath stem cells, where researchers clearly falsified results on purpose in order to advance their own careers, are rare, honest mistakes still lead to irreproducible data that confound and waste months of other researchers’ lives, and millions of dollars of the tax-payers and donors’ money.
            So what can we learn from this debacle? A colleague of mine summarizes the problem well: “most of us know that 90% of the papers in Nature, Science, and Cell are bull****, so God help the graduate student who’s the first to reproduce the results of these papers.” While it is easy to say that we should all take responsibility for our work and take pride in producing excellent, reproducible research that will actually contribute to our knowledge of how the world works, real life problems like shrinking funding sources, pressure to advance in one’s career, and maybe just pride can lead one astray. Maybe what we can really learn from this is that pressure may break us all down into another lesser, or infantile state, although sometimes it might just be a bad case of an acid trip. 

If you would like to read more about this, follow this link:
http://www.nature.com/news/stap-retracted-1.15488
http://www.nature.com/news/stem-cell-method-faces-fresh-questions-1.14895

1. http://www.nature.com/nature/journal/v483/n7391/full/483531a.html#t1
2. http://www.nature.com/nrd/journal/v10/n9/full/nrd3439-c1.html