So you found some science on the Internet... (Part 2)

10 amazing findings about placebos

In part 1 of the series I brought up placebos briefly and I promised you more. It’s important to discuss placebos because many successes of health products and interventions that are not supported by the medical community can at least be attributed in part to the placebo effect. Your brain is a powerful machine and the effects of the placebo can be extremely convincing. Here are some interesting facts about placebos:

1.     Placebos can be somewhat of a self-fulfilling prophecy: if someone is told a placebo acts as a muscle relaxant, their muscles actually relax.

2.     For some conditions (such as mild depression, or some coughs), placebos work just as well as drugs with active ingredients. 

3.     Rats experience the placebo effect.

4.     The placebo effect can work even if the patient is told they are taking a placebo (but keep in mind: in this kind of trial, it’s impossible to blind the participants!).

5.     The placebo effect works better if the intervention is more invasive or severe. The placebo effect is stronger and works on more people when a fake drug is injected with a needle than when it's simply swallowed in pill form.

6.     To properly control for the effect of certain surgeries, clinical trials are sometimes conducted with a group receiving a sham (fake) surgery. The ethics of doing this are often debated (your thoughts in the comments!).

7.     Pills with a visible, well-known name brand work better than pills that look generic.

8.     The placebo effect can work in reverse: if given a placebo and told it will produce negative side effects (like headaches), nearly 1 in 5 people will experience those side effects. This is called a nocebo.

9.     The color of placebo pills matters: “hot” colors like red and orange work better as stimulants, and “cool” colors like blue and green pills have a tranquilizing effect.

10. In some countries, doctors can prescribe placebos. A common use case? Placebo antibiotics for… viral infections*!

References: 

Flaten MA et al. (1999) Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosomatic Medicine 61(2):250-5. 

Pittrof R (2011) Placebo treatment in mild to moderate depression. The British Journal of General Practice 61(584):222. 

Nolan TA et al. (2012) Placebo-induced analgesia in an operant pain model in rats. Pain 153(10):2009-16. 

Kaptchuk TJ et al. (2010) Placebos without deception: a randomized controlled trial in irritable bowel syndrome. Plos one 5(12):e15591. 

Kaptchuk TJ et al. (2006) Sham device v. inert pill: randomized controlled trial of two placebo treatments. British Medical Journal 332(7538):391-7. 

Dowrick AS and Bhandari M (2012) Ethical issues in the design of randomized trials: to sham or not to sham. The Journal of Bone and Joint Surgery 94(suppl 1):7-10. 

Branthwaite A and Cooper P (1981)Analgesic effects of branding in treatment of headaches.British Medical Journal 282(6276):1576-8. 

Rosenzweig P et al. (1993) The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Clinical Pharmacology and Therapeutics 54(5):578-83. 

de Craen AJ et al. (1996) Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness. British Medical Journal 313(7072):1624-6. 

Hrobjartsson A and Norup M (2003) The use of placebo interventions in medical practice – a national questionnaire survey of Danish clinicians. Evaluation and the Health Professions 26(2):153-65.

*Avid Scientific Chick readers will know that antibiotics cannot treat or cure infections caused by viruses.

So you found some science on the Internet... (Part 1)

Cats and science together on the Internet

The Internet hosts a wealth of information, and, for those concerned with their health and well-being, this can be both a blessing and a curse. I’ve recently come across a website that promotes various health and nutrition measures under the label of “science” (and even “real good science”!) all the while discrediting the work of some academics. While it’s obviously not the first time I’ve seen this sort of thing, this particular website hit home because it targets a community that’s close to me. The truth is, you can find science to support nearly anything, but not all science is created equal. I can’t prevent people from using “science” to support their claims, but I *can* tell you about what actually is “real good science”, how to spot it, and how to make informed decisions.

For this first post in the series, I want to introduce you to the gold standard for scientifically proving that something works (for example, that a drug treats a disease, or that a diet makes you lose weight): the double-blind, randomized controlled trial. Let’s start at the end:

A controlled trial means that the intervention you are testing (for example, a pill to treat stomach ulcers) is compared with a control intervention. The control can be a placebo (a fake intervention), like a sugar pill. You might think that anything works better than a sugar pill. Not so! Placebos are very effective for many conditions (for more on placebos, stay tuned for Part 2!). That’s why it’s very important to make sure that the effectiveness of your pill for stomach ulcers is not due to the placebo effect.

While placebos can be the ideal control, it’s not always practical, or ethical, to conduct a trial using a placebo. If for example you are testing a new cancer drug, you don’t necessarily want your control group to receive a placebo, and so go drug free, for the duration of the trial. Another type of control would be to use a drug that is already on the market, has known effects, and has already been tested thoroughly.

Randomization in the context of a controlled clinical trial means assigning participants randomly to either the new intervention group or the control group. Why is randomization important? It helps avoid a phenomenon called bias. Imagine that researchers really believe the new pill for stomach ulcers will work better than anything that already exists. They might be tempted to assign the sickest participants to the intervention group and the others to the control group. Seems like the right thing to do, yes? Unfortunately, not so. It’s possible that as stomach ulcers progress, they respond differently to various drugs, and by not assigning the participants randomly you might mask or exaggerate the effects of your new product. Well-designed trials should be randomized whenever possible.

In a double-blind randomized controlled trial, two groups of people are “blinded”. The participants are blinded in that they don’t know whether they are receiving the new intervention or the control, and the experimenters are blinded in that when they are analyzing the data, they don’t know who received what. Blinding a study really helps to limit the biases. That said, it’s not always possible to blind everyone. Sometimes an intervention (like an exercise program) is pretty obvious. But like randomization, it should be done whenever possible.

Double-blind, randomized controlled trial are pretty much as  

good as it gets when you’re trying to prove something – they 

are the most reliable form of scientific evidence because they have all the possible elements in place to avoid false cause-and-effect evidence. Let’s look at one last example. Say I’m trying to prove that a special diet involving eating large quantities of bacon helps people lose weight. So I recruit 10 overweight participants and I closely monitor their diet, making sure they eat their extra-large amounts of bacon. At the end of my study, I find that 6 out of 10 participants lost weight. What does this mean? Pick the right answer:  

a) Bacon is an effective weight-loss tool (60% success! Is  
    that a lot?) 
b) Bacon didn’t change anything – had the participants just    
    gone on with their regular diet, 6 of them would have lost  
    weight anyway  
c) Bacon worked as a placebo for 6 of the participants  
d) The experience of being monitored closely by researchers 
    led the participants to pay closer attention to their diet and 
    exercise, and 6 of them lost weight because aside from 
    bacon they improved their diet 
e) Bacon worked as a weight-loss tool for 2 participants and 
    4 participants experienced the placebo effect 
f) The researchers secretly worked for the Bacon  
    Consortium and this whole thing was a marketing exercise
g) We have no idea what this means because the  
    experiment was not designed well.

That’s right.

Double-blind randomized controlled trials are not entirely without flaws (no scientific method is!). They typically take a very long time to come together and are very expensive to conduct, which can sometimes (but not always) mean that relatively wealthy organizations pay for them (for more on who pays for science, stay tuned for a later installment in this series). Other flaws are shared with many different types of research. That said, while these trials are not perfect, they are still the gold standard. So the first thing to look for when you are researching a health intervention online is whether a double-blind, randomized controlled trial has been done.

 Stay tuned for part 2, on the placebo effect!

Save your brain cells

I’m not the most coordinated person on this planet. You know that kid who could never tap on her head and make circles on her belly at the same time? That was me. While I can hold my own on the mountain bike trail and poke at mice brains, there are certain things I will never do well, like dancing. Don’t even get me started on “zumba”. So naturally I was a little nervous when I joined a new gym class recently, especially since it involves learning new movements. I’m always so envious of those who seem to learn new things effortlessly, whose bodies respond immediately to what their brains are saying. So I was very excited when I found out about new research that suggests all my pain and suffering might pay off in the end.

It’s a common misconception that adult brains don’t grow. For a long time, scientists thought adults had a finite number of brain cells, and it was all downhill from there (grim, I know). We now know there is hope for us all – some areas of your brain continue to grow brain cells throughout your entire lifetime, at a rate of 5,000 to 10,000 new cells per day. Good news right? Don’t get too excited. We also know that over half of those new cells die within a few weeks of their birth.

Ok, get excited again (what a rollercoaster!): there are things you can do to prevent the death of those brain cells, and one of those things is learning new stuff.

In one recent experiment, scientists had three groups of rats undergo a procedure called eyeblink conditioning. This experiment is based on Pavlov’s work – he’s the one who found out that if you ring a bell shortly before you feed your dog every day, eventually just ringing the bell will be enough to activate the dog’s saliva glands. Eyeblink conditioning is very similar – it involves ringing a bell and then stimulating the rat’s eye, leading to a blink. Eventually the rat learns to blink when it hears the bell without the need for the actual stimulation.

The researchers carried out the eyeblink conditioning with three groups of rats. One group received a drug that prevented them from learning anything, one group received a drug that made learning easier, and one group didn’t get any drug (that would be the control group). After the rats went through learning (or attempting to learn) the eyeblink procedure, the researchers looked at how many new brain cells had been saved by the process.

The rats that received the drug that prevented from learning predictably didn’t learn anything and also predictably didn’t save any new brain cells. The rats that received the drug that helped them learn saved new brain cells, but no more and no less than the group of rats that learned without any drug. Pretty boring results so far, yes?

But wait! The researchers then closely looked at all the animals that learned the task and reanalyzed how many new brain cells they saved based on how long the rats took to learn to blink. What they found was most intriguing: the longer a rat took to learn the task, the more new brain cells it saved, regardless of whether it received the drug or not.

What this means is that the best way to save a maximum amount of new brain cells is by having a hard time learning something but ultimately being successful.

Now don’t go bragging about being a slow learner just yet - for one thing, the timing of the experiments I described above is very tricky (especially the timing between the eyeblink conditioning and when new cells are counted). We also know very little about the role of those new brain cells and whether they get integrated in existing networks in the brain, and I don’t need to remind you that results obtained in rats don’t necessarily apply to us. That said, it’s well proven that learning is good for your overall brain health, so go ahead and join that zumba class. 

Reference: Curlik DM and Shors TJ (2011) Learning increases the survival of newborn neurons provided that learning is difficult to achieve and successful. J Cogn Neurosci 23(9):2159-2170.