The Unexpected Power of the Unconcealed Placebo

The Unexpected Power of the Unconcealed Placebo From Anthony Lembo, MD Since the 1940’s placebo-controlled studies have been the gold standard to evaluate the effectiveness of any kind of therapy, be it dietary, pharmaceutical, or targeted at the mind. Only those treatments found to be better than placebo in a so-called double-blind placebo-controlled trial (a trial in which neither the patient nor the physician know if a person receives the active treatment or the placebo) are considered to be effective in clinical medicine. Within a decade of the introduction of placebo-controlled trials, clinical researcher Henry Beecher published a landmark paper entitled “The Powerful Placebo”.1 In this paper he reported that approximately 35% of patients receiving placebo (generally in the form of indistinguishable sugar pills) had clinical important improvement in symptoms in clinical trials from a number of different diseases. The assumption that he made was that patients responded to placebo because they were “blinded” (i.e., didn’t know whether they were receiving the active treatment or placebo) and that their expectation they might be receiving the treatment led to the improvement in their symptoms. This assumption has since been considered dogma– i.e., that in order to generate expectations about improvement placebos need to be concealed or blinded in order to be effective in clinical trials. Indeed this assumption has shaped much of our understanding and research into the mechanisms of placebo. In 2010, our group at the Beth Israel Deaconess Medical Center in Boston, published the first trial to potential refute this dogma.2 We reported results from a trial in which participants with irritable bowel syndrome (IBS), a chronic disorder characterized by alterations in brain gut interactions, had clinically significant improvement when given non-concealed, ‘open-label’ placebos (OLP), e.g., they as well as the investigator knew they were receiving the sugar pill. In this initial study 82 IBS patients were randomly assigned to receive either OLP or usual care (i.e., no-pill control) for three weeks. Surprisingly, IBS participants who knowingly received OLP reported greater improvement in their IBS symptoms than participants in the no-pill control. Thus, this finding was the first to challenge the conventional belief that placebos, in order to generate expectations of improvement in a patient needed to be concealed in order to be effective. However, since then trials in patients with chronic low back pain, knee pain, cancer-related fatigue, migraine headaches, among others, have found similar results.3, 4, 5…

Why Is It So Hard to Adopt a Diet to One That Is Good for Our Health and the Planet?

Why Is It So Hard to Adopt a Diet to One That Is Good for Our Health and the Planet? By Emeran Mayer, MD I recently ran into a NYT OpEd piece written in 2018 by Paul Greenberg, the New York Times bestselling author of Four Fish, The Omega Principle and most recently The Climate Diet. Reading the piece 3 years after it was first published, certainly doesn’t take away any of its timeliness. The topic he discusses is a major focus of my upcoming book The Gut-Immune Connection. “Cretan diets in the early 50s contained "limited quantities of goat meat and milk, game, and fish swimming in olive oil.” In 1953, a landmark paper written by Leland Allbaugh entitled “Crete: A Case Study of an Underdeveloped Area” analyzing the eating patterns of an isolated Greek population living on the island of Crete. In his article which was part of a writeup of a study the government of Greece commissioned from the Rockefeller Foundation, Allbaugh and colleagues described Cretan diets at the time as rich in "olives, cereal grains, pulses, wild greens and herbs, and fruits" with "limited quantities of goat meat and milk, game, and fish" and "swimming in olive oil.” The findings strongly suggested that a calorie-limited diet high in fresh fruits and vegetables, whole grains, nuts and seeds, and olive oil, a greatly restricted consumption of animal products low in animal fat and protein, particularly red meat – what is now referred to as the traditional Mediterranean diet- could lower the risk of heart attacks, strokes, chronic disease and extend life (we know today these chronic diseases also include cognitive decline, colon cancer and chronic liver disease). While this initial observation and subsequent population-based studies didn’t prove a cause and effect relationship between the Mediterranean diet and healthy aging, and findings were initially challenged by the medical community, medical research over the last half-century has increasingly confirmed the basic conclusions, and a consensus has been building around the health benefits of this diet in the medical world. Advanced scientific studies of the gut microbiome and the brain have provided scientific evidence for the biological mechanisms underlying the reported health benefits. As Greenberg states in his piece: “Weight-loss fads and eating trends come and go, but the so-called Mediterranean diet has stood fast”… “ Furthermore, he quotes Dr. Walter Willett of Harvard’s T.H. Chan School of Public Health…

What You Need to Know About Age-Related Muscle Wasting

What You Need to Know About Age-Related Muscle Wasting By E. Dylan Mayer I have talked about frailty in a previous edition of this Newsletter, emphasizing the importance of shifting dietary habits and adopting a regimen of regular physical exercise. This same advice stands true for age-related muscle wasting, or sarcopenia. Sarcopenia is the loss of muscle mass and function, and frailty can be defined as multi-system impairment, including muscle loss associated with increased vulnerability to stressors.1 Depending on your age, you’ve probably noticed as you get older it is harder to maintain muscle, losing both mass and strength more noticeably - this is known as primary sarcopenia. Keep in mind that this is not a necessary consequence of getting older, but a preventable age-related condition.2 A reduction in nerve cell connections from the brain to your muscles. A natural, age related decrease of the body’s hormone levels. A decline in your body’s ability to convert protein to energy. A reduction in daily intake of calories and protein in order to maintain muscle mass. During COVID-19, where many have been working from home, levels of physical activity have plummeted, leading to accelerated muscle loss and potentially to sarcopenia. Such muscle loss is easily “correctable” at younger ages, but as we get older, the amount of muscle tissue and its composition changes. For example, fat tissue infiltrates the muscle, replacing muscle fibers and compromising its function. Similar to frailty, sarcopenia is associated with reduced physical function, increasing the odds for falls and fractures, impaired mobility, loss of independence, etc. As we age some loss of muscle is inevitable. However, to minimize age related sarcopenia, there are some important things we can do, in particular diet and exercise.3 “The best way to fight sarcopenia is exercise.” The best way to fight sarcopenia is exercise. Resistance training and aerobic exercise (walking, hiking, running, etc.) are two of the best ways to prevent sarcopenia. Resistance training such as weightlifting or bodyweight exercises tensions your muscle fibers and results in growth signals which lead to increased strength. It also increases the actions of growth-promoting hormones. These signals tell the body to make new proteins and to activate muscle stem cells (satellite cells), which reinforce existing muscle.4 Aerobic exercise raises your heart rate and has been shown to control sarcopenia, however most of the studies which tested aerobic exercise as treatment for sarcopenia also included some…

Walnut Dukkah-Crusted Salmon with Lemony Kale

Walnut Dukkah-Crusted Salmon with Lemony Kale Healthy Food Index Calories MACs Polyphenols Omega-3 FA/Total Fats 3.5 264 2.8 0.04 0.32 (Listed amounts are per serving. MACs = Microbe Accessible Carbohydrates. Amounts of MACs, total polyphenols and phenolic compounds are shown in g for all recipes.) Introduction Dukkah is a traditional Egyptian nut, seed and spice blend that is oh-so-good and good for you. Once you try it, you will see why it has been so easy for us to fall in love with. It typically contains hazelnuts, but we wanted to load it with more omega-3 fats so opted for walnuts (which deliver a whopping 3.4 grams of alpha-linolenic acid, ALA, per cup) instead. Dukkah is typically served as a dip with bread and olive oil (which you can absolutely do with this one, too; dip your bread in olive oil first, and then in the dukkah). This dukkah, however, has been used as a decadent crust for salmon (or your fish of choice, please read our notes, below). Wild caught salmon is incredibly high in the omega-3 fats docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and these make this recipe a true omega-3 dream dish! Polyphenols in this recipe are found primarily in the cumin, fennel, and coriander as well as the extra virgin olive oil. In terms of fiber, there is some in the walnuts and sesame seeds. But it really comes in strong with the side dish that this salmon is paired with: lemony kale. Kale is one of the most nutrient dense foods on the planet because it is high in fiber, many vitamins and minerals, and other phytonutrients (plant nutrients). Please keep in mind that many of kale’s (and other vegetables’) nutrients, such as polyphenols, are soluble in water and sensitive to heat. Therefore, sautéing is one of the best ways to retain these important nutrients because this cooking method is quick and doesn't cause nutrients to leech out in water or in high amounts of oil. Besides the kale’s hefty fiber and polyphenol content, this simple side dish also delivers even more polyphenols in the garlic and lemon.

Seared Sea Bass with Cauliflower “Rice” Pilaf and Turmeric Plum Sauce

Seared Sea Bass with Cauliflower “Rice” Pilaf and Turmeric Plum Sauce Healthy Food Index Calories MACs Polyphenols Omega-3 FA/Total Fats 1.62 378 5.3 0.08 0.03 (Listed amounts are per serving. MACs = Microbe Accessible Carbohydrates. Amounts of MACs, total polyphenols and phenolic compounds are shown in g for all recipes.) Introduction This is an ultra-healthy meal with some big flavors that make it feel really decadent. We went with sea bass for the protein in this recipe, primarily due to its omega-3 fat content (it boasts 0.47 grams docosahexaenoic acid, DHA, and 0.18 grams eicosapentaenoic acid, EPA, per 3 ounce serving). If you want to further increase the omega-3 intake, you can also use wild caught salmon. We kept preparation simple, yet elegant, with a gentle sear of our fish in olive oil and seasoned with sea salt and pepper. Rice is delicious, however, white rice falls short as far as fiber and polyphenols are concerned. Therefore, this “rice” is made from high fiber, high polyphenol cauliflower! You may have heard about cauliflower rice before, but if you haven’t: welcome to the new white rice swap! To make it even better for your gut health (and to go beyond the standard, plain cauliflower rice), this “rice” has been transformed into a “polyphenol-pilaf” with the addition of olive oil, red onion, garlic, nigella seeds, carrots, artichoke hearts, kale, and fresh herbs. To complete this dish, we encourage you to make the homemade plum sauce to go with it instead of using a store-bought variety. It is a perfect complement to the sea bass and “rice,” and has no added sugar but boasts a lot of added polyphenols from the ginger, plums, chilis, and tamari. You can use any stone fruit instead of plums during Summer, and in the winter, apples or Asian pears are a great high fiber alternative to plums. Use this sauce liberally in this dish or for any of your stir-fry needs!