Placebo Effect

During my years of study, although what day isn't ripe for learning, I remember sitting dumbfounded in a class on research design. The instructor was enthusiastically (thank the holyheavens for enthusiastic instructors) outlining the challenges to designing good research.

He posed the question, "If results of an intervention were equivalent to those of a control group, does that mean the intervention was ineffective?"

He loved watching 20 young, impressionable, occasionally arrogant minds attempt to fend off a leading question.

"So, you see, it depends," he said, "on how the study is controlled." There he launched into a discussion on randomization, blinding, and the meaning of "placebo", the last of which left my jaw slack, my mouth ajar, and my expression, I guess, one more of dumbfoundedness than of academic acumen. To this day, I still don't understand the placebo effect.

Placebo has come to refer to a substance or therapy, often administered to a control group, which is thought to be inactive or inert, e.g. a sugar pill. But if a placebo is so benign, why can we measure an effect from it? Why do we go to the bother of providing a "dummy" therapy to a control group? What exactly is that sugar pill, or the act of taking that sugar pill doing that it can dissolve a migraine, erase a wart, or in the case of the study in the prior post, lower cholesterol?

While I'm talking about that policosanol study ... It astounds me that researchers, healthcare workers, industry cheeses, the media, etc. are quick to highlight the ineffectiveness of some therapy when it fares poorly against a placebo, but fail to shine a floodlight on the effectiveness of the placebo. The sugar pill in this study, a lactose monohydrate and microcrystalline cellulose formulation, was as good as, if not at times better than, the policosanol (for reasons yet to be fully elucidated) at lowering lipids. If you say it worked because the participants believed it would work, what exactly is the mechanism for that? And why doesn't an answer to that question spark more research? Especially when it could mean ditching a $100/month statin habit for a cheap, side-effect-free, easily obtainable sugar pill?

Doesn't anyone have the courage to stand up at one of those stuffy pharmaceutical conference-clambakes and decry the state of the placebo?

In 1998, the American Psychological Association (APA) published a controversial study.¹ It was a review of 19 double-blind, placebo-controlled trials investigating the effectiveness of antidepressant medications. Their findings:

"As a proportion of the drug response, the placebo response was constant across different types of medication ... The inactive placebos produced improvement that was 75% of the effect of the active drug ... and the correlation between placebo effect and drug effect was .90. ... These data raise the possibility that the apparent drug effect is actually an active placebo effect."

Eight years later, the antidepressants Zoloft and Effexor are 2 of the top 20 drugs sold in the US, with 2005 sales in excess of $5 billion.

I'm not saying drugs don't hold sway. I'm just trying to elicit more discussion about the piddling placebo.

~~~~~~¹ Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication

Policosanol Update

Results of a study appearing in this week's Journal of the American Medical Association (JAMA)¹ will not bring joy to supplement manufacturers:

Effect of Policosanol on Lipid Levels Among Patients With Hypercholesterolemia or Combined Hyperlipidemia

German researchers found that policosanol, at varying doses, was no better than placebo at improving lipid levels.

The study used excellent research protocol. It was randomized, placebo-controlled, double-blinded, parallel-run, with a pre-baseline wash-out period. Since it was conducted in Germany (which unlike the US does not maintain a trade embargo with Cuba), it could access the very same sugar-cane-derived policosanol used in the Cuban studies which found it effective for lowering cholesterol. The sample size, n=129, wasn't large, but probably big enough to deliver significance.

So why, given the impressive body of evidence in favor of policosanol did these researchers find otherwise? Some considerations:

1. The bulk of previous research was supported by a Cuban company with vested interest in policosanol sales.
   
   
2. Policosanol may be more effective in select populations. From the JAMA study: "Ethnic and nutritional differences between European white and Latin American patients might play a role."
   
   
3. Absorption of the researchers' formulation of the policosanol was not verified. A similar Dutch study reported that most of their orally administered policosanol went out with the stool.

This won't be the last word on policosanol effectiveness, but it's sure a muscular one.

Update: November 15, 2006 - Another thumbs-down study.

~~~~~~¹ Thanks to Melinda for the heads-up.

Dry-Roasted Salted Cashews

There's nothing like the taste of a freshly roasted cashew. Why is it, among nuts, cashews alone develop that caramelly come-hither aroma? Could it be their higher starch content?

Starch content of 1 oz. of nuts (a handful):

Cashews - 6.66 grams
Pistachios - 0.47
Almonds - 0.21
Filberts - 0.14
Brazilnuts - 0.07
Walnuts - 0.02

While I'm talking nutrition content, cashews also have the least fat among the nuts listed, 12.4g per ounce. Calories in an ounce, about 160.

More starch would contribute to the Maillard reaction - a browning reaction involving an amino acid (protein) and a reducing sugar (carbohydrate), macronutrients which cashews have in about equal amounts.

The Maillard reaction is also responsible for the coveted crust on bread, and the color and taste of coffee, chocolate, and beer. Curiously, although it operates in the production of milk-based caramels, the Maillard reaction is not the same as caramelization. Wikipedia calls its resultant products "interesting but poorly characterized odor and flavour molecules." I can attest to the "poorly characterized" part. In food lab, when we were obliged to list sensory traits of cooking/cooked foods, people were sometimes at a loss for adjectives. Mostly you heard, in reference to a bread crust or heated milk item, "Mmmmmm, it's the Maillard reaction".

Back to cooking...

It took some experimentation before I settled with this recipe. I didn't want to add oil. Although it would conduct heat more evenly around the nut, giving it a uniformly distributed glow and helping the salt to stick, it would also slightly increase the fat content of some naturally fatty fare. Oils add their own flavor too, either from the food they were pressed or from rancidity. I didn't want to muddle the cashew taste. (I would venture the taste of some store-bought cashews owe at least a little to the oxidation of the fat they were cooked in.) So I dry roasted, replacing the oil with a little water.

Ingredients

• Raw cashews - a little more than a cup or enough to cover a cookie sheet without crowding.
  
• Cold water - a teaspoon or two.
  
• Kosher salt - the coarse kind you see in the picture, about 1/2 to 1 tsp. or to taste.

~~~~~~1   Marinate cashews - Combine raw cashews, water, and about 1/2 tsp. salt in a bowl. Use enough water to coat the cashews, but not so much that it pools in the bottom of the bowl. Stir periodically for 5 or 6 hours to distribute the salted water and assist evaporation.

Note: Raw cashews are not actually raw. They're heat-treated to remove the shell ¹, a thin skin, and some liquid inside the shell. The liquid contains urushiol, the same irritant found in poison-ivy, and can cause painful blisters. Some refer to the cashew as the "blister nut".

2   Preheat oven to a slow 285ºF.

3   When the cashews are almost dry - but still damp so the salt sticks - stir in about 1/4 tsp. kosher salt. (Salt to your preference. Saltaholic that I am, I probably use about 1/2 tsp. here and 1/2 tsp. to marinate.) Spread the nuts in an even layer on a cookie sheet. Roast for 15 minutes at 285ºF, stir, then roast for about 15 minutes more. Depending on the size of your nuts, browning may begin midway into the 2nd 15 minutes, so be on the look-out. They can go from a light amber (like a pilsner*) to much darker (like a brown ale*) in a matter of minutes.

* Beer descriptions compliments FRE (Fanatic's Resident Eater).

Note - Try not to dawdle when you open the oven to stir. You don't want to lose so much heat that the oven stays on for a while to recover. My experience has been that a hotter oven will result in a spotted nut, instead of one evenly browned.

4   Remove from oven. Let cool completely on the pan. Refrigerate once cool.

Enjoy!

~~~~~~¹ This post was a real education for me. The cashew nut, or what we call a nut but botanists call a seed, is inside that kidney-shaped drupe hanging off the bottom of the pear-shaped fruit, rather, pseudofruit. The real fruit is the drupe. The pear-shaped fake fruit, known as the cashew apple, is pretty bitter but makes a delectable jam I hear.

The great photo is from tetatate's moblog.
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Photo of dry-roasted cashews: Homegrown

Eating Locally

Last week, a web site supporting the consumption of local foods came online:

100-mile Diet

It's based on the experiment of Alisa Smith and James MacKinnon, a couple who made a commitment to live for a year on food and drink originating from within 100 miles of their home in Vancouver, British Columbia.

I've read about eating locally and generally support it. But something about the eat-local movement has been nagging at me.

As an educational tool, I think the 100-mile diet is useful. But when I apply the concept of eating locally to those around me, I find it discriminates against those with lower incomes, fewer transportation resources, a lack of time, know-how, and availability of a kitchen for cooking, the institutionalized, etc.

Also, not that I'm a default supporter of big business, but I think it can limit the growth, by limiting the market, of what begins as a small family business. A dairy farm with 20-head that sells its milk locally might not be able to offer its employees the wage structure and benefits (health, pension, etc.) of a dairy farm that, say, joins a cooperative (like Organic Valley) and increases its market reach.

I can't see my 75-year-old neighbor who lives alone, on a fixed income, who doesn't drive, and who copes with a number of health issues, existing on local tubers all winter. With the US population aging, she's not an exception. (By 2030, 20% of Americans are projected to be older than 65. That's over 70 million people.) I also wonder how many people would voluntarily limit the diets of their children to support this movement.

I believe in supporting local food producers. I also believe in supporting local businesses that aren't directly food related. But, as a means for change, I question the propriety of applying eat-local expectations to individuals. I prefer to see government action that protects small business, that creates incentives for local food diversity, that addresses small-business' ability to provide a living wage with benefits, that addresses fuel-dependency, etc. At least this top-down approach might, among other things, offer an eat-local choice to groups who are otherwise excluded from this type of movement. Maybe I'm in a minority, but I believe voting can be a powerful tool for social change.

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Below is a photograph with caption by Kathleen Laraia McLaughlin, from her series "Color of Hay: Maramures, Romania". Her photos depict one face of 21st century sustainable-agriculture living. You can explore more of her award-winning photos here.


Palăguţa and Vasile Borodi, Budeşti, România, 2000
Romanians from the cities sometimes complain that in Maramureş the people have everything.
"They just go to the woods and get what they need."