Nocebo and Aspartame

Dear Students,

Continuing our discussion last week of the placebo effect, is the placebo's lesser known evil twin: the nocebo effect.

Like the placebo effect, the nocebo effect is when a pill, agent or treatment that should not have any chemical, physical or mechanical effect, actually has an effect. In this case, however, it is not a positive effect based on the patients expectations, but a negative one. Some examples are listed here, and the common theme is that if a patient believed a treatment to be dangerous, it gave the feared side effect. Simply telling a patient about the side effects of a medication can increase the chances of it occurring, enough so that that the nocebo effect can possibly reverse the effect of real medication from good to bad.

The placebo effect explains, for example, explains why acupuncture can relieve headaches, and homeopathy. I have always noticed a curious argument from those that promote alternative medicine and other placebos: real medicine is harmful! It seems, although I suspect it's done unknowingly, that not only do 'alternative medicine' cheerleaders reap the benefits of the placebo effect, they also drive people away from real medicine with the nocebo effect. Since real medicine is evaluated through scientific inquiry, we know the effects of drugs and procedures and how much they do (and do not) work. It seems more than a little strange that these warnings from the alternative medicine camp dismiss out of hand scientific evidence, yet wish people to accept their claims uncritically. Propagating a fear of medicine is similar to the fear of chemicals that I have written about before (aka Chemical Free Veggies).

What prompted this weeks post was my science class's reaction to my version of "coffee" aka diet cola with lovely, lovely aspartame. Lots of people seem to think aspartame is harmful, but a quick check of reputable sources clearly proves otherwise:

A sweeping review of research studies of aspartame says there is no evidence that the non-nutritive sweetener causes cancer, neurological damage or other health problems in humans. - ScienceDaily (Sep. 15, 2007)

There is no evidence to suggest that the consumption of foods containing this sweetener, according to the provisions of the Food and Drug Regulations and as part of a well-balanced diet, would pose a health hazard to consumers. In addition, other scientific advisory bodies such as the Scientific Committee for Food of the European Community, and the Joint Expert Committee on Food Additives (JECFA) of the United Nations Food and Agriculture Organization and World Health Organization have reviewed all the available safety studies and have found aspartame to be safe. More than ninety countries world-wide, including the United States, countries of the European Union, and Australia and New Zealand, have also reviewed aspartame and found it to be safe for human consumption and allow its use in various foods. - From Food and Nutrition by Health Canada

Or just go to the Snopes page and scroll to the bottom and click and read the statements from the FDA, among all the others.

Of course, as the Health Canada website linked above states, aspartame is dangerous if you have phenylketonuria (don't worry, you'd know if you had it), but otherwise it's perfectly safe.

What does this have to do with the nocebo effect? People do report adverse effects from aspartame anecdotally (i.e. personal stories), and claim that they know aspartame is bad.

How is this resolved? From a scientific perspective, we know that aspartame is safe, insofar as we can know anything.

From Health Canada : The Safety of Sugar Substitutes

"Some people have reported sensitivities to aspartame. However, researchers have been unable to confirm these reports through clinical studies. There is ongoing research investigating this issue."

From Health Canada : Aspartame

"One study was conducted on children and adults claiming to have experienced aspartame-induced seizures. On some days they were given a placebo and on other days they were given a large single dose of aspartame. Monitoring by EEG of their brain signals demonstrated that aspartame was no more likely to cause seizures than a placebo."

But where there's smoke, why isn't there fire? If that many people report reactions, why can't we find them when we study them?

Nocebo effect.

Aspartame is an evil 'chemical', and emails such as this have been floating around for at least a decade. It is difficult to test (I suspect it would be hard to get ethical approval for studies that intend harm, even if it's just for testing a nocebo effect), but Occam's razor can serve us well here. Which is more likely? A phantom bad effect that inexplicably goes away when studied, or a nocebo effect combined with some selective thinking? If I was misinformed about aspartame to begin with, it would be not unexpected that I would attribute any bad reaction I had to any aspartame I consumed, combined with the added booster the nocebo effect gives to actually experiencing a side effect.

There is an upside, however. Given aspartame fears, it would not be unusual or unreasonable for anyone to be suspicious of aspartame. This isn't all that harmful, other than they've eliminated one method to lower their sugar intake. We don't run and check every little bit of information we come across, but if there is one area we truly need accurate and tested information, it is for our health. Whenever someone tries to inform me of their newest health fad (or even when I'm seeing a new doctor), I'll ask what they think of aspartame.

If they believe aspartame to be bad, I know that whatever fad they're trying to convince me of needs to be double-checked very carefully. Knowing truths that are easy to confirm with appropriate authorities, but very few commonly believe, is useful.

Cheers,

Ron Neufeld
Canada's Best Boarding School

Placebo

Dear Students,

The placebo effect is a perfect topic for any science class, and nearly always comes up when discussing the scientific method. It comes up in the house all the time as well. Boys are sick, and the want some cough medicine. Or a money chit to buy some health product. Or to buy that particularly Canadian version of pseudoscience, Cold FX.

The placebo effect is when a pill, agent or treatment is given that should not have any chemical, physical or mechanical effect, but a cure occurs because of the treatment. A sugar or starch pill instead of pain medication, creating an incision without actually performing surgery, etc.

Of course it's not just that. It isn't just taking a sugar pill, and then getting better. People get better for all sorts of reasons, including the disease just running its course. The sniffling, snorting colded up person who's finally had enough goes and buys some pills and gets better in two days. It doesn't matter what they took: cold Fx, echinacea, chicken soup, nothing, etc. The cold's almost done, and no matter what, you're going to be better in two days. We just naturally credit the last thing we did to address the problem. A real placebo effect would require that a sugar pill actually prevent or reduce the duration of a cold.

As the preceding single example shows, it's complicated. There's lots of reasons people who are sick can get better, so much so that even the placebo effect itself is disputed. It is also differs depending on what you're trying to cure. Pain is notoriously amenable to the placebo effect, possibly because pain is so much a product of our mind and our expectations. Many women endure the pain of childbirth more than once, and apparently willingly. Yet if one forced such a pain onto a person against their will would be an agonising and traumatic event. Regrowing an arm or a leg, however, is a completely different story. (If you're thinking that the placebo effect works best on those areas that alternative medicine seems to emphasize, you're right. Funny kind of coincidence...)

So it would be obvious that any attempt to determine if a procedure or pill works, one would have to put a lot of effort into checking if it actually works.

Cold-FX did that. For example there are two separate studies, both of which showed that it did nothing. Then they combined the studies with some fancy statistical footwork, squinted their eyes, and presto! A faint result.

Even if one accepts the faint result, it does not claim to work as people think Cold-FX works. People feel a cold coming on, so they start popping some Cold-FX pills, expecting it to work like real medicine such as tylenol or antibiotics. Then, no matter how ineffective Cold-FX may be, some people will get better. Whether that's a misdiagnosis (they weren't really getting a cold after all!), luck (3 day cold instead of 7, hurrah!), ignorance (my cold only lasted 7 days!) or placebo (it worked just like a sugar pill!), for some people, for some of the time, anything will work. Throw in some good marketing, word-of-mouth, and a healthy dose of Skinner, and soon you'll have perfectly ordinary people claiming drinking urine is good for you.

Once you have a large group of people giving anecdotal stories, evidence and science are often ineffective. See all of this for examples.

The point of this long introduction, was that a student mentioned gluten-free diets, and asked for my opinion. I, naturally, don't have one, but as a science teacher our classes often examine evidence, learn about credibility, and how to determine true from false information. In essence, it might work, it might not, there's no real good evidence that it does according to what sites we could find that weren`t biased. At most, some parents found it helpful, which isn`t much given what we know about how easy it is to fool oneself.

What it does have, however, is the placebo effect combined with concerned parents. If my daughter needed help, and if someone told me that something as simple as changing her diet would help, I'd try it. And I would desperately want it to work. Add in all the previous caveats about why people can get better, plus all the reasons why someone could appear slightly better, and multiple positive anecdotal reports would be expected. Changing the diet of an autistic child appears unlikely without really good, plentiful evidence outside of anecdotes.

People like to pick on pharmaceutical companies for making expensive drugs. Nobody seems to recognize the vultures picking over the worry and guilt of parents that is the alternative health care industry.

There`s a lot of garbage out there. My students know not to believe me, but it bears repeating. Research. Check credibility. Periodically re-examine the evidence. And remember that when you think you`ve found the truth, and all the scientists are on the other side, you might want to double-check your results.

A bonus question for my student ethicists. If the placebo effect does work, it involves lying to patients. Should a health care professional be allowed dishonesty in order to cure their patients this way? Is charging for it justifiable?

Cheers,

Ron Neufeld
Canada's Best Boarding School