Master Life Faster: Newsletter

Mind Over Matter

Posted in Newsletter by Paul Lem, M.D. on April 2, 2009

Volume 2, Issue 4
SMART: Grading the evidence
HEALTHY: Mind over matter
HAPPY: A smile a day

“When the facts change, I change my mind. What do you do, sir?”
-John Maynard Keynes

Grading the Evidence

stethoscopeHave you ever noticed that medical advice often changes? One day, your doctor will recommend Vitamin C for preventing colds. A year later, she’ll tell you that Vitamin C is not effective.

The reason is because medicine is based on the best evidence. When doctors determine that new evidence is superior to old evidence, they change their treatments accordingly.

Standards of Proof
What makes some evidence better than others? The quality of evidence is rated according to the rigorousness of the experiments which generated the results.
There are four main categories:

  • Grade 1: Randomized controlled trials
  • Grade 2: Controlled study without randomization
  • Grade 3: Cohort or case-controlled studies
  • Grade 4: Expert opinions, clinical experience

Notice that the lowest quality of evidence is expert opinions or clinical experience. Although expert opinions may be useful, the history of medicine has shown many times that they can easily be wrong. Two examples are the use of thalidomide in pregnant women, and the mistaken belief that stress is the main cause of ulcers.

The best type of evidence is randomized controlled trials. In these experiments, neither the doctor nor the patient knows who is receiving the real treatment and who is receiving a placebo. This secrecy prevents the doctor from being biased towards a certain treatment, and reveals whether the patient is feeling better due to the placebo effect.


Hidden Bias
Now we can understand why there may be conflicting advice about Vitamin C for colds. Suppose your doctor feels herself coming down with a cold. She takes Vitamin C and gets better. Intrigued, she recommends Vitamin C to a few of her patients. None of them seem to get colds. Now she’s really interested. She decides to recommend Vitamin C to all of her patients for colds. That winter, she sees fewer cases of cold in her clinic. Wow, Vitamin C must really work! Or does it?

There are many alternative reasons for the doctor’s observations, including:

  • It may just be a coincidence that the patients who took vitamin C didn’t develop colds.
  • The cold viruses that winter were not particularly virulent.
  • The patients who got colds stayed at home and didn’t see the doctor so she never learned that Vitamin C didn’t prevent their colds.
  • The patients who followed the doctor’s advice to take Vitamin C were more health-conscious and less likely to get sick in the first place.

Weight of Evidence
This is why controlled trials are better than observational trials or expert experience. They control for these alternative explanations and generate results that are more likely to be right. Of course, there’s always a small possibility that the results from a controlled trial are simply due to chance.

That’s why it’s important for trials to be replicated by a number of researchers. Ultimately, nothing is 100 percent certain. But results from controlled trials are much more likely to be true than other types of evidence.

Medical Myths
In addition to Vitamin C not preventing colds, here are a few more medical myths that have been debunked by controlled trials:

  • Neither vitamin E nor vitamin C reduce the risk of prostate cancer or total cancer in middle-aged and older men.
  • Folic acid supplementation reduces homocysteine levels in the blood, but this does not reduce the risk of heart disease in people with a past history of heart disease.
  • Glucosamine and chondroitin sulfate alone or in combination provides almost the same pain relief as placebo in patients with osteoarthritis of the knee. There may be some effect above and beyond placebo in patients with moderate-to-severe knee pain.
  • Echinacea does not prevent colds or treat them.

The next time your friend tells you about some new “scientifically-proven” treatment he read about on the Internet, consider investigating the evidence for yourself.

Jost WH. (2001). Evidence-based medicine (EBM). Journal of Neurology. 248[Suppl 1]: I/1-I/2. Abstract.

Hemila H et al. (2007). Vitamin C for preventing and treating the common cold. Cochrane Database of Systematic Reviews. 3: CD000980. Full Article.

Gaziano JM et al. (2009). Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 301(1): 52-62. Abstract.

Bazzano LA et al. (2006). Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 296(22): 2720-2726. Abstract.

Clegg DO et al. (2006). Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. NEJM. 354(8): 795-808. Abstract.

Turner RB et al. (2005). An evaluation of Echinacea angustifolia in experimental rhinovirus infections. NEJM. 353(4): 341-8. Abstract.

“Man is made by his belief. As he believes, so he is.”
-Bhagavad Gita

Mind Over Matter

pillsAccording to Wikipedia, the placebo effect is: “a medical phenomenon where the results of a medical treatment are affected by the patient’s ideas about how effective the treatment is. The term is especially used when a patient responds dramatically to a physiologically inactive treatment…inert “sugar” pills and sham surgeries are typical examples.”

Sugar Pills
In a survey of Danish physicians, 86 percent reported prescribing placebos to their patients at least once in the past year. Forty-eight percent prescribed placebos more than ten times. The most common placebo was prescribing antibiotics for viral infections (viruses are not affected by antibiotics). Similarly, 53 percent of doctors in Jerusalem said they prescribed placebos, with 36 percent prescribing them once a month or more.

Scientists believe the placebo effect is generated by two mechanisms:

(1) Suggestion and expectation
Studies with Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) have shown that placebo treatment causes the release of dopamine and opioids in people’s brains. Dopamine is a neurotransmitter that mediates the brain’s reward system.  When people receive a placebo, dopamine primes their brains to expect a reward or benefit from the treatment, and this expectation can become a self-fulfilling cycle. The more active your dopamine system, the more likely you are to experience a placebo response.

In addition to dopamine, placebo treatment causes the release of natural opioids in the brain. Opioids are a class of pain-killing compounds that include drugs such as morphine and oxycodone. This placebo effect is enhanced by the power of suggestion. For example, patients experience much less pain when the doctor tells them they are receiving a powerful drug.

(2) Pavlovian conditioning
If you experience a benefit the first time you take a placebo, this conditions your brain to expect a similar benefit for the next time. Again, this sets up a self-fulfilling cycle.

The Power of Placebo
The placebo effect can be quite powerful. In a study of glucosamine and chondrotin sulfate for osteoarthritis, 60 percent of patients who took the placebo experienced 20 percent less pain at the end of 24 weeks.

The placebo effect can also be long-lasting. Researchers discovered this fact when they reviewed 8 placebo-controlled trials of antidepressants. Patients were initially treated with 6-8 weeks of placebo or antidepressants, followed by another 12 weeks of the same treatment. Of those who responded well to the initial placebo treatment, 79 percent remained well over the following 12 weeks.

Placebos tend to work best for physical symptoms, especially pain. In contrast, placebos don’t have much influence on biochemical markers such as high cholesterol and blood sugar. In addition to pain and depression, strong placebo effects have been observed when placebo dopamine is administered to Parkinson’s patients and when placebo caffeine is given to healthy volunteers.

Outside of clinical medicine, the placebo effect probably accounts for most, if not all, of the benefits of homeopathy. This was the conclusion of a systematic review of 11 systematic reviews of placebo-controlled trials of homeopathy. In total, the reviews analyzed over 100 homeopathic trials. The evidence was clear: “there was no condition which responds convincingly better to homeopathic treatment than to placebo or other control interventions.”

Similarly, a study published in Lancet compared 21 placebo-controlled trials of homeopathy with the same number of conventional-medicine trials matched for the same disease. Results showed “weak evidence for a specific effect of homeopathic remedies, but strong evidence for specific effects of conventional interventions.”
The conclusion? “This finding is compatible with the notion that the clinical effects of homeopathy are placebo effects.”

Say It Ain’t So
As you might expect, homeopathy has a lot of passionate defenders. K.P. Skandhan from Sri Devaraj Urs Medical College in India writes: “Homeopathy is one of the most popular systems of medicine here. Many generations have systematically followed homeopathic treatment… Shang and colleagues’ research report on homeopathy will not affect the growth of the system in our country.”

Flavio Dantas at the Federal University of Sao Paulo in Brazil says: “The popularity of homeopathy is growing worldwide. Yet homoepathic laboratories do not spend nearly as much money on marketing and product promotion as pharmaceutical companies. So, why is its popularity growing? Why are educated people paying for it?”

In answer to Flavio, the reason why educated people are paying for homeopathy is because it works. And the reason it works is because of the placebo effect.

Rather than denying this fact, homeopathy’s supporters should embrace it. After all, placebo is a proven way to get health benefits without the side effects of drugs. Now if only we could figure out a way to get the placebo effect without having to pay for homeopathy…

Hrobjartsson A, Norup M. (2003). The use of placebo interventions in medical practice–a national questionnaire survey of Danish clinicians. Evaluation & The Health Professions. 26(2): 153-165. Abstract.

Nitzan U. (2004). Questionnaire survey on use of placebo. BMJ. 329: 944-946. Abstract.

Enck P, Benedetti F, Schedlowski M. (2008). New insights into the placebo and nocebo responses. Neuron. 59: 195-206. Abstract.

Clegg DO et al. (2006). Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. NEJM. 354(8): 795-808. Abstract.

Khan A, Redding N, Brown WA. (2008). The persistence of the placebo response in antidepressant clinical trials. Journal of Psychiatric Research. 42: 791-796. Abstract.

Ernst E. (2007). Placebo: new insights into an old enigma. Drug Discovery Today. 12(9/10): 413-418. Abstract.

Ernst E. (2002). A systematic review of systematic reviews of homeopathy. Br J Clin Pharmacol. 54: 577-582. Abstract.

Shang Aijing et al. (2005). Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet. 366: 726-32. Abstract.

Dantas F et al. (2005). Correspondence. Lancet. 366: 2083-2085. Abstract.

“Laugh, and the world laughs with you.”
-Ella Wheeler Wilcox

A Smile a Day

how-of-happinessIn “The How of Happiness,” Sonja Lyubomirsky reviews the evidence for how to become happier. As part of her review, she discusses two studies that demonstrate how the body has a powerful influence on the mind.

Smile and Be Happy
In the first study, researchers from Berkeley and UCSF recruited actors from the American Conservatory Theater in San Francisco. With the help of a mirror, a “smile coach” instructed the actors to adjust their facial muscles into a Duchenne smile. A Duchenne smile is where the corners of the eyes crinkle up due to contraction of the orbicularis oculi muscle around the eye.

The actors held the smile for 10 seconds. Afterward, they were asked if they experienced any feelings, memories, or sensations while holding the smile. Throughout the session, the actors were also hooked up to a polygraph machine to measure their autonomic responses.

Most of the actors reported feeling happy when making a Duchenne smile.
As well, their heart rate and muscle responses indicated their bodies were experiencing the physiologic effects of happiness.

Frown Away
In the second study, Dr. Eric Finzi from the Chevy Chase Cosmetic Center in Maryland injected Botox into the glabellar frown lines of 10 patients who were clinically depressed (the glabella is the smooth area between the eyebrows just above the nose).

The patients were women between the ages of 36-63 who had been depressed for 2-17 years. They had already tried drugs and psychotherapy without success. Two months after the Botox injections, 9 out of 10 patients were no longer depressed, and the tenth experienced an improvement in mood.

It seems that happiness or unhappiness can be a self-reinforcing circle. The more you smile and laugh, the more you exercise your facial muscles for smiling and laughing, and the easier it is to smile and laugh even more.

The Giggle Guru
None of these findings would be surprising to Madan Kataria, affectionately known to his followers as the “giggle guru.” Kataria is a family physician from Mumbai, India, and the founder of Laughter Yoga, a technique where you clap in unison with a group and chant Ho Ho Ha Ha Ha. Simulated laughter quickly turns into real laughter, and you feel happy and relaxed as the tension releases from your body.

The most famous stance is the lion laugh, where you roar as your eyes bulge and your hands paw the air. Try it with a friend, and I bet you won’t stop laughing.

Levenson RW, Ekman P, Friesen WV. (1990). Voluntary facial action generates emotion-specific autonomic nervous system activity. Psychophysiology. 27:363-84. Abstract.

Finzi E, Wasserman E. (2006). Treatment of depression with botulinum toxin A: a case series. Dermatologic Surgery. 32:645-50. Abstract.

Trump E. (2002). Got the giggles? Join the club. New York Times. July 27. Full Article.

Copyright 2009 by Paul Lem, M.D. All Rights Reserved.
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