Mark’s Daily Apple

The Power of the Placebo8

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Don’t Underestimate the Simple Sugar Pill

A number of months ago we reported that some 45% of Chicago internists (among those who responded to a survey) said they offered placebos to their patients from time to time. The report got people around the country talking – and maybe even wondering about their own prescription history.

Clearly, physicians recognize the impact of placebos, and research has time and again shown their efficacy. So, how does it really work? And who seems to benefit the most from the placebo effect? Is there anyone who can’t be “taken in�? In light of this recent NY Times article about a company that sells cherry-flavored sugar pills to be administered by parents to their unsuspecting children as a placebo we thought we’d investigate.

The placebo effect encompasses a person’s psychological and physiological response to some inactive treatment or procedure. The relief or improvement resulting from the placebo effect is highly dependent on the patient’s expectations, the nature of their condition, and other physical and personality-based aspects. Additional factors, such as the patient’s perception of the care provider and even the color and cost of a placebo pill, can influence the resulting relief or lack thereof. Subjects receiving what they were told were higher cost placebos reported pain reduction in higher numbers than those who received “lower priced� placebo medication. Placebo effect has been shown to have both short-term and long-term impact.

Although it might be easy to chalk it up to mere psychological phenomenon, researchers have identified biological bases of the placebo effect. A study out of the University of Michigan used brain scans to measure activity as subjects were told they were receiving pain-relieving substances to curb the discomfort induced by concentrated salt water injections in their jaws. (Fun, eh?) The scans as well as subjective self-reports showed that subjects did indeed experience physical relief from the “suggested� medication dose. Scans showed increased activity in parts of the brain known to be integral to the processing of pain. The scans also revealed activation of the subjects’ mu opioid endorphin system. Researchers chose to use healthy young men for subjects in order to rule out any impact of medical conditions or pre-existing pain on test results. Researchers say further study will determine if similar results can be found in women and older adults.

In terms of what people may be “high placebo responders,� research suggests that a person’s response may be related to the amount of activity in the nucleus accumbens, a part of the brain with a large number of receptors for endorphins and dopamine. Some of us, apparently, anticipate more benefit than others, and our brain activity and hormonal release follows suit regardless of whether a treatment is fake or the real deal.

Other research shows that people with widely fluctuating as opposed to chronic pain respond better to placebo. And those with chronic fatigue do not seem to respond as well to placebo.

Research also suggests that placebo treatments can offer relief not just from physical pain but from psychological distress. As subjects viewed disturbing photos on the first day of a study, researchers administered legitimate anti-anxiety medication and a short time later an antidote to the drug. Subjects were told what they were receiving and the general impact each medication should have on their experience. On the second day, the researchers repeated the same procedure but administered placebos in place of the drugs. Researchers measured the subjects’ experience through their self-report and through functional magnetic resonance imaging. Subjects reported similar relief on the second day, and scans indicated increased brain activity in the part of the brain associated with pain relief even on the day of placebo administration.

When it comes to harnessing the power of the placebo, those of us on the other side of the prescription pad may have varying responses. Clearly for most of us, the use of placebos in research studies falls into a different category. Subjects know ahead of time that they may receive a placebo rather than an active therapy. But when it comes to the assignment of placebo as presumed legitimate treatment, the picture isn’t so clear. Some question the ethics of placebo use in these situations, particularly the pretense that accompanies it. Others applaud placebos as a safe and reasonably effective means to many positive ends.

Dr. Howard Brody, a professor and medical ethicist at Michigan State University, criticizes the use of physical placebo treatments but offers an alternative view of harnessing the power of “mind-body interactionâ€� in medical care: “Doctors may never prescribe placebos – dummy pills – but can make use of the placebo effect every time they see a patient.â€� By recognizing and maximizing the power of the physician-patient interaction itself, a patient can experience relief from the knowledge and thoughtful attention his/her doctor conveys. Dr. Brody explains, “Features of the healing environment usually include a physician or healer that listens carefully to what you say and gives you a realistic and sound explanation of what is happening to you. … People express care and compassion for your fears and suffering, and you leave feeling more in control of your life and your illness.” Dr. Brody’s perspective offers a view of the placebo effect that, he believes, isn’t dependent on the physical placebo itself.

And so we turn the questions over to you. Is the deception of placebo worth its potential positives? How can physicians and other care medical providers (indeed, the set-up of our medical system itself) further harness the power of the placebo as Dr. Brody suggests? Tell us your thoughts on the ethics of placebo pretense and the power of suggestion in health.

purchio Flickr Photo (CC)

Further Reading:

No Advantages from Aromatherapy?

Homeopathy: Can We Please, As a Society, Let This One Go?

Mind Hacks: Placebo is Not What You Think

NY Times: Experts Question Placebo Pill for Children

Posted: Big Pharma, Health, Prevention, Raise Healthy Seedlings, Worker Bees' Weekly Bites

Epigenetics and Depression2

There’s hope.

We just can’t help it. This epigenetics stuff really floats our boat. The last few weeks we’ve brought you a Dear Mark primer on gene expression as well as news on recent studies examining the role of lifestyle/environment on genetic expression. Diabetes, heart disease, even lung function are impacted by external factors like nutrition, exercise, and pollution exposure. But mental health is part of the epigenetic picture as well: chronic stress and even early emotional experiences, it turns out, may be significant enough to alter our genes’ expression.

Earlier this month at the American Psychiatric Association annual meeting, scientists shared their latest research uncovering the link between epigenetics and depression. According to the scientists, significant stress or primary experiences can influence “supporting structures of DNA� like chromatin.

Depression, because of its duration and slow response to medication, has been an intriguing area for epigenetic research. Eric Nestler, one of the presenting researchers from the University of Texas Southwestern Medical School in Dallas, explains that depression’s “persistence is thought to be influenced by slowly developing but stable adaptations, which might include epigenetic regulation.�

Research conducted by Nestler and colleagues found that chronic social stress can cause chromatin changes in genes in the brain’s nucleus accumbens and hippocampus. ‘In both brain regions, we have been able to directly relate these chromatin changes to some of the behavioral abnormalities observed,’ Nestler said. In animal models of chronic stress, he and his colleagues were able to manipulate these two brain areas in ways that produced antidepressant-like effects.

via Medline Plus

Another group of scientists from the University of Massachusetts Medical School in Worcester has observed that chemical alterations of DNA “are dynamically regulated from the perinatal period to old age.� In animal studies at McGill University in Montreal, rat pups’ early separation from mothers resulted in chemical modifications to genes found in the hippocampus. These changes coincided with enduring changes in behavior. The care pups receive from their mothers in practices like grooming apparently influence their long term “hormonal and behavioral response to stress.� Michael Meaney, one of the McGill University researchers, says the findings suggest an “experience-dependent adaptability in the chemistry of the DNA and chromatin structure.�

Environment and “experience-dependent adaptability.� That’s the crux of epigenetics. We have more influence on our mental and physical health than we previously thought. While we can’t control every aspect of our environment or our emotional experiences, we have the considerable potential to ameliorate those factors. In terms of physical health, we can eat well, supplement wisely, exercise strategically, sleep adequately, and reduce our exposure to toxins as much as possible. For our mental health, we can do all of the above as well as learn effective ways to cope with the stress in our lives (as well as find overall fulfillment). While physical activity can help us feel less stressed in the short term, a personally beneficial meditation practice (yoga, Tai Chi, Transcendental, etc.) can fundamentally change our response to stress. Over time, our efforts can potentially modify the expression of those genes that are involved in stress response and very likely related areas of mental health like anxiety and depression. While some of us might be more genetically predisposed to certain physical and mental health conditions, epigenetics offers hope that our own choices and practices can play a significant role in their prevention and treatment.

Comments? Questions? Send ‘em our way.

Meredith Farmer Flickr Photo (CC)

Further Reading:

Emotional Eating: A Salad with Your Sorrow?

7 Tips to Reduce Stress Right Now

Banish Nervousness Forever in 1 Easy Step

Posted: Health, Personal Improvement, Prevention, Primal Health, Worker Bees' Weekly Bites

Safe Cooking Temperatures11

Where does “bloody” come in on the scale?

Let’s face it. Some of us grew up in houses where our fathers habitually burned the toast and set off the smoke alarm on a daily basis. Perhaps our mothers roasted the Thanksgiving turkey until you could weave an absorbent bath towel with its fibers. Or maybe grandpa’s grilling style charred every piece of meat beyond visual recognition. Yes, comparative tales of over-cooking are the stuff of familial nostalgia and domestic comedies. We knew it tasted bad (O.K., wrenchingly bad), but was it that bad for us?

Let’s first say that MDA is not about to go raw foodie. We love our veggies and meats, and we say this first and foremost: eat ‘em any way you can. Nonetheless, the bulk of research seems to suggest that cooking, specifically with certain temperatures and methods, can do a real number on the food we eat.

First let’s get the arguments on the table. There’s Grandma Mabel in her house dress sitting in one corner spouting off on how all her relatives lived to 90+ and had two sides of cooked vegetables and well done meat (of course!) at every meal, thank you very much. On the other side is the raw foodie in slouchy jeans saying carcinogenic compounds are waiting to attack your every cell if you dare put that spoonful of cooked carrots in your mouth. O.K., that’s not exactly how it is on either side of the food fence, but we love the visual

Much of the argument for “raw� boils (teehee) down to this. When food is cooked, the natural enzymes and micro-organisms are eliminated, nutrient levels plummet, and harmful compounds such as heterocyclic amines are formed.

Hmmm. Grandma? “Ha! Then what about my homemade cooked tomato sauce and the increase in lycopene and overall antioxidant activity?� (Never underestimate Grandma.)

Well, we’ll leave you two to duke it out in the corner with that basket of raw beets. As for the rest of us, why don’t we just take a closer look. When it comes to cooking, what’s lost? What’s gained? If we tend to side with Grandma, are there things we can do to maintain or enhance the healthfulness of the foods we cook?

Before we move onto the specifics, one overall principle seems to be this: low temperatures are generally better for retaining the highest nutrient content of food and for reducing oxidation and its associated toxic by-products. High heat, prolonged cooking? Not so good. But we’ll get to that.

Negating Nutrients?

First, the nutrient question. As we reported in January, Italian scientists had found that different cooking methods had varying impact on the vegetables tested. Sometimes cooking depleted nutrients (as in frying) and sometimes it enhanced them (boiling and especially steaming). But that doesn’t tell the whole story. Other researchers at the University of Warwick found that steaming, microwaving and brief stir frying of Brassica vegetables (e.g. broccoli, cauliflower, Brussel sprouts) maintained the veggies’ anti-cancer properties otherwise known as glucosinolates.

Boiling, however, resulted in significant loss of glucosinolates: “broccoli 77%, Brussel sprouts 58%, cauliflower 75% and green cabbage 65%.� The researchers in the Warwick study boiled the vegetables for 30 minutes, which was a much longer duration than that used with the other cooking methods. High, direct heat and long duration both contribute to the leeching of nutrients into the water. Other cooking methods such as frying and broiling use very high heat as well and are not recommended. Another tip: hold off on adding lemon juice and other acids for flavoring. Acids can break down vegetables, particularly more delicate varieties, encouraging additional nutrient loss.

To maintain nutrient levels (PDF), let your senses be a guide. Remember those dull, anemic, limp little mushy cylinders that passed for green beans in school lunch? There’s a reason they looked gross to you then (and now). It turns out the more appealing a bean looks, the healthier it probably is. Green beans, for example, that are briefly steamed or “poached� in a few tablespoons of water will be even more vibrantly colorful than they were before that quick dip in the pot. The texture will be tender but still a bit crisp. This is what you’re looking for when cooking produce: when they look like they belong on the cover of Bon Appetit, they’re done. (Hint: you may even want to briefly blanch them in some ice water to completely halt the cooking process.) And, as a general rule, keep the lid on while you’re cooking/steaming. The food will cook faster, and less time subjected to the heat is good). Low and enclosed does it.

Cooking, as in the example of Grandma’s lycopene-rich tomato sauce, can “activate� nutrients, and can even make them more bioavailable. Certain foods are to some degree poisonous or unhealthy to humans in their raw state. Many tubers, for example, must be cooked to be a healthy and digestible nutrient source for humans.

Transferring Toxins?

The question of cooking involves not just retaining the good but avoiding formation of the bad. One of the foremost toxins associated with cooking are heterocyclic amines (HCAs), a variety of carcinogenic compounds formed during the cooking of muscle meats through a reaction involving creatine and amino acids. (HCAs form with the “carmelization� and charring we see most prominently when grilling.) Studies have linked the intake of HCAs with cancer of the stomach.

High heat cooking such as frying, broiling and grilling produces higher levels of HCA. In fact, HCA levels can triple when temperatures are raised from 392 degrees to 482 degrees Fahrenheit.

A better cooking option for meat is oven roasting. Even better yet are stewing or braising, which keeps temps at or below boiling (212 degrees). With these slower, lower cooking methods, it’s still advisable to cook meats to “medium� doneness. Check the meat rather than let the crock pot decide when it’s ready.
Other harmful substances associated with high heat cooking are AGEs (a.k.a. glycotoxins), which have been associated with inflammation, oxidative stress and aging. A diet that contains meats cooked with high heat methods such as grilling, broiling and frying has been associated with higher levels of AGEs.

Another word on oxidation and cooking. While stir frying at low to medium temperatures offers a good option for veggies and meat strips, it’s important to not undo the good by using oils that will be cooked rancid in the process. Use broth, coconut oil, clarified butter or refined oils that are appropriate for higher temperatures.

Mitigating Measures

Some of us love our grills and cooked foods of all varieties. And, as we mentioned earlier, we’re all about meat and vegetables in a pot, on a house, with a spork, etc., etc. So, are there “measures� we can take to minimize the damage our cooking methods and their accompanying temperatures may cause?

Using the microwave to partially cook meats before grilling or broiling can cut HCAs by as much as 90%. Likewise, using marinades with herbs such as rosemary, thyme, oregano, garlic, basil or parsley can lower HCAs by up to 87% (and adds some antioxidant action to boot).

Our final word: Eating a diet rich in vegetables and meats is what we’re all about. But we’re always looking for ways to make a good thing even healthier. We think there’s enough reason to eat raw when it makes sense to and when you prefer it that way. Yet, cooking figures into the picture for most of us, and we think a little information can make a healthy (and tasty) difference.

Comments, suggestions for cooking? We’d love to hear them.

kpishdadi, In Praise of Sardines, feministjulie, canonsnapper, . SantiMB . (toobusy), bennylin0724 Flickr Photos (CC)

Further Reading:

When Do Foods Really Go Bad?

DIY Household Cleaners

13 Simple, Timeless Kitchen Hacks (Banish Tears, Cuts, Burns, Smells & Stains!)

Diet Hack: Practical Tips for Cooking Vegetables

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Posted: Health, How To, Prevention

Dear Mark: Cooking Omegas11

Dear Mark,

What are your thoughts on Barry’s suggestion that there is some sort of problem in cooking O-3 enhanced eggs? I’ve seen similar things related to flax seed oil and roasted & toasted walnuts, etc. What is the bottom line on cooking with omega-3s?

Thanks to Ed and others who offered up similar questions in response to last week’s Enough Omegas? post.

Polyunsaturated fats (which include omega-3 fatty acids) are, indeed, very prone to oxidation when exposed to heat, light or oxygen. This oxidation essentially renders them rancid to some extent, and this will result in less appealing taste (and smell) as well as decreased nutritional value. Add to that the damage imposed by the resulting free radicals, and that “healthy� food has now become a health hazard.

I would never use a polyunsaturated oil for cooking, and I don’t recommend eating roasted nuts because of the oxidation risk. Polyunsaturated oils, like flaxseed oil, should be properly stored (refrigerator or freezer) and added to cold food (like my daily salad) or cooked food only after reasonable cooling. Additionally, I recommend buying polyunsaturated oils, for example, in opaque or dark bottles and using them quickly.

As to the question that came up last week about cooking foods with omega-3 content like fish or enriched eggs, the answer is more complicated. Most research on omega oxidation has been done with straight oils themselves rather than whole foods (e.g. fish oil versus fish fillet). One interesting study showed the bulk of omega-3s were lost when fish oils were heated to 150 degrees Fahrenheit for 30 minutes (only 15.9% of DHA and 18.5% of EPA retained); however, that oxidation was slashed when rosemary or oregano extracts were added to the oils (65.9% of DHA and 69% of EPA retained). Both herbs significantly decreased oxidation, but rosemary proved more effective than oregano.

And this strategy has applications beyond our own kitchens. Egg farmers who enrich their hens’ diets with omega-3 fatty acids are using the herbal principle to reduce oxidation in high omega-3 eggs. (Note about the study (PDF): the authors are Greek and the English is a bit garbled in sections, but the research itself is compelling.) This particular study observed the effects of herbal (as well as vitamin and mineral) supplementation in chicken feed and the eggs’ relative susceptibility toward oxidation. (By the way, this same study showed that chickens fed flax meal produced eggs that were high in both ALA and DHA. The digestion of the feed apparently allowed for the synthesis.) So, when it comes to cooking an enriched egg? Well, I guess it depends on the exact feed. In this case, the more you know about the farm, the better you can judge. If you get plenty of omega-3s from good supplements, as I suggested last week, choosing high omega-3 eggs aren’t a necessity. Nonetheless, it’s still useful to know what kind of feed your food is getting.

One last note on reducing oxidation… Anti-oxidants like mixed tocopherols (Vitamin E) appear to reduce oxidation of omega-3s, and companies are increasingly incorporating Vitamin E in omega-3 rich (or enriched) products. Other synthetic additives apparently do the same, but I’d have less faith in their relative safety.

My bottom line? Know your eggs. Eat your herbs. As for cooking itself? Let’s just say that I’m not about to give up grilled salmon, but I’m going to make sure I don’t cook it any more than I have to. And I’ll also be sure to have a nice big salad on the side.

Thanks for your comments, and look for more on best cooking practices later this week. In the meantime, keep your questions coming!

Steve Wampler, The Beast, maxnathans Flickr Photos (CC)

Further Reading:

Dear Mark: Saturated Fat

The Definitive Guide to Fats

Omega 3s: A Closer Look

Whole Health Source: Olive Oil Buyer’s Guide

Posted: Dear Mark, Diet, Health, How To, Nutrition, Prevention

Hormones and Heart Disease9

Balancing Act

We aren’t talking estrogen here, but this latest news does concern the ladies of the community.

In the recent “Hunt Study� conducted by researchers at the Norwegian University of Science, women with thyroid function in the less active part of the “normal� clinical reference range showed an increased risk for fatal coronary heart disease relative to those with numbers in the more active part of the clinical range.

The findings were based on a follow-up with 17,311 women and 8,002 men who had shown no signs of heart disease, diabetes or thyroid disorder at the beginning of the study in the mid-1990s. All participants were 40 years or older when initial tests were done to measure levels of thyrotropin, a hormone released by the pituitary gland that is known to stimulate the thyroid. During the follow-up examinations that were completed in 2004, researchers found that 192 women and 164 men had died of heart disease. Of these subjects, none had shown signs of thyroid malfunction. However, women whose readings showed the relative lowest (but still clinically normal) thyroid gland activity were “69 percent more likely to die from heart disease than women with more active glands.�

Compared with women in the lower part of the reference range (thyrotropin level, 0.50-1.4 mIU/L), the hazard ratios for coronary death were 1.41 (95% confidence interval [CI], 1.02-1.96) and 1.69 (95% CI, 1.14-2.52) for women in the intermediate (thyrotropin level, 1.5-2.4 mIU/L) and higher (thyrotropin level, 2.5-3.5 mIU/L) categories, respectively.

via Archives of Internal Medicine

According to the researchers, “These results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal coronary heart disease.” The researchers noted that lower thyroid function has been associated with traditional risk factors for heart disease: “Emerging evidence indicates that levels of thyrotropin within the reference [normal] range are positively and linearly associated with systolic [top number] and diastolic [bottom number] blood pressure, body-mass index and serum lipid concentrations with adverse effects on cardiovascular health.”

The researchers added that no clinical research has studied the impact thyroid medication might have on this added heart disease risk. The study findings did not show the same connection between thyroid function and fatal heart disease risk for men.

We’ve always made the argument here that health is more than the sum of a few clinically measured parts. It’s ultimately a whole package, an interactive design. Hormone balance is absolutely key to good health, and an imbalance is assuredly sign of wider havoc. Thyroid function is part of the body’s intricate hormonal symphony and is tied to a number of lifestyle related choices and circumstances, including environmental toxin exposure (most notably but not exclusively perchlorate, a chemical used in rocket fuel that is present in water and milk and has been linked to thyroid malfunction in animal studies) and chronic inflammation that may be caused by factors like a consistently poor diet and/or autoimmune disorder.

We always advise making the most of preventative medical care. For women in particular, getting a thyroid function test and talking about the results with your doctor is one step toward knowing more and taking charge.

Questions? Comments? Experiences in this area and suggestions to add?

Further Reading:

Yoga Good for Reducing Breast Cancer Risk

Top 10 Reasons to Stay Healthy

Questions About Soy Formula

Posted: Health, Prevention, Worker Bees' Weekly Bites