Your Microbiome & Chronic Fatigue syndrome

There is tremendous current interest in the relationship between the microbes in and on our bodies and our state of health and disease. The origins of chronic fatigue syndrome (CFS) have been mysterious; studied for years.  This problem is now believed to be related in some ways to the bacteria in our gut. 

CFS is a condition where normal exertion leads to debilitating fatigue that isn't alleviated by rest. There are no known triggers, and diagnosis requires lengthy tests administered by an expert. Now, for the first time, Cornell University researchers report they have identified biological markers of the disease in gut bacteria and inflammatory microbial agents in the blood.

In a study published June, 2016 in the journal Microbiome, the team describes how they correctly diagnosed chronic fatigue syndrome in 83 percent of patients through stool samples and blood work, offering a step toward understanding the cause of the disease.

"Our work demonstrates that the gut bacterial microbiome in chronic fatigue syndrome patients isn't normal, perhaps leading to gastrointestinal and inflammatory symptoms in victims of the disease," said Maureen Hanson, a professor in the Department of Molecular Biology and Genetics at Cornell and the paper's senior author. "Furthermore, our detection of a biological abnormality provides further evidence against the concept that the disease is psychological in origin."  The researchers concluded that when they have more information, clinicians could consider changing diets, using prebiotics such as dietary fibers or probiotics to help treat the disease.

Cornell researchers collaborated with Dr. Susan Levine, a CFS specialist in New York City, who recruited 48 people diagnosed with CFS and 39 healthy controls to provide stool and blood samples.

The researchers sequenced regions of microbial DNA from the stool samples to identify different types of bacteria. Overall, the diversity of types of bacteria was greatly reduced and there were fewer bacterial species known to be anti-inflammatory in CFS patients compared with healthy people, an observation also seen in people with Crohn's disease and ulcerative colitis.

At the same time, the researchers discovered specific markers of inflammation in the blood, likely due to a leaky gut from intestinal problems that allow bacteria to enter the blood.  Bacteria in the blood will trigger an immune response, which could worsen symptoms.

The researchers have no evidence to distinguish whether the altered gut microbiome is a cause or a whether it is a consequence of disease. In the future, the research team will look for evidence of viruses and fungi in the gut, to see whether one of these or an association of these along with bacteria may be causing or contributing to the illness.

Probiotics are microorganisms that are believed to provide health benefits when consumed. The term probiotic is currently used to name ingested microorganisms associated with benefits for humans and animals. The introduction of the concept is generally attributed to Nobel recipient Élie Metchnikoff, who postulated that yogurt-consuming Bulgarian peasants lived longer lives because of this custom. He suggested in 1907 that "the dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes.”  Although some claims for probiotics have not been substantiated, randomized controlled trials at the University Hospital, Tuebinden, Germany, published in 2016, found that certain commercially available strains of probiotic bacteria when taken by mouth in adequate doses for 1–2 months, possess treatment efficacy in certain psychological disorders, e.g. anxiety, depression, autism spectrum disorder, and obsessive-compulsive disorder – and improved certain aspects of memory.  

Prebiotics are non-digestible fiber compounds that pass undigested through the upper part of the gastrointestinal tract and stimulate the growth or activity of advantageous bacteria that colonize the large bowel by acting as substrate for them. Most fruits and vegetables have indigestible fiber. Some most effective prebiotics include onions, garlic, leeks, wheat bran, asparagus, chicory, and raw banana.

There will be a symposium on the microbiome, in healthy soil and in the human body, on Sunday, December 4^th at 2pm, at Commonweal in Bolinas.  The microbiome is a subject of substantial current research and excitement, with a relationship to many aspects of health and disease. Please attend if you are interested!

Sadja Greenwood, MD, MPH

The Benefits of Dark Chocolate, Placebos, and Safe Abortion in Ireland

Dark Chocolate: Compounds in cocoa called flavanols are believed to benefit cardiovascular health; a systematic review and meta-analysis of 19 randomized controlled trials of cocoa consumption was recently published in the Journal of Nutrition. Dr. Simin Liu, professor and director of the Center for Global Cardiometabolic Health at Brown University, who worked with epidemiology graduate student and lead author Xiaochen Lin, found that “cocoa flavanol intake may reduce dyslipidemia (elevated triglycerides), insulin resistance and systemic inflammation, which are all major subclinical risk factors for cardiometabolic diseases."  Flavanols are plant compounds found in many foods, and are especially high in tea, blueberries and cocoa. 

Liu noted some limitations in the trials. All studies were small and of short duration, not all of the biomarkers tracked in these studies changed for the better, and none of the studies were designed to test directly whether cocoa flavanol consumption leads to reduced cases of heart attacks or type 2 diabetes.

But taking into account some of these heterogeneities across studies, the team's meta-analysis summarizing data from 19 trials found potential beneficial effects of flavanol-rich cocoa on cardiometabolic health. There were small-to-modest but statistically significant improvements among those who ate flavanol-rich cocoa product vs. those who did not. "The treatment groups of the trials included in our meta-analysis are primarily dark chocolate -- a few were using cocoa powder-based beverages," Lin said. "Therefore, the findings from the current study apparently shouldn't be generalized to different sorts of chocolate candies or white chocolates, of which the content of sugar/food additives could be substantially higher than that of the dark chocolate."

Placebo Effects Conventional medical wisdom has long held that placebo effects depend on patients' belief they are getting pharmacologically active medication. A paper published in the journal Pain is the first to demonstrate that patients who knowingly took a placebo in conjunction with traditional treatment for lower back pain saw more improvement than those given traditional treatment alone.

"These findings turn our understanding of the placebo effect on its head," said joint senior author Ted Kaptchuk, director of the Program for Placebo Studies and the Therapeutic Encounter at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School. "This new research demonstrates that the placebo effect is not necessarily elicited by patients' conscious expectation that they are getting an active medicine, as long thought. Taking a pill in the context of a patient-clinician relationship -- even if you know it's a placebo -- is a ritual that changes symptoms and probably activates regions of the brain that modulate symptoms."

Kaptchuk, with colleagues at Instituto Superior de Psicologia Aplicada (ISPA) in Lisbon, Portugal, studied 97 patients with chronic lower back pain (which causes more disability than any other medical condition worldwide.) After all participants were screened and examined by a registered nurse practitioner and board certified pain specialist, the researchers gave all patients a 15-minute explanation of the placebo effect. Only then was the group randomized into one of two groups; the treatment-as-usual (TAU) group or the open-label placebo (OLP) group.

The vast majority of participants in both groups (between 85 and 88 percent) were already taking medications -- mostly non-steroidal anti-inflammatories (NSAIDS) -- for their pain. (Patients taking opioid medications were excluded from the trial.) Participants in both the TAU and OLP groups were allowed to continue taking these drugs, but were required not to change dosages or make any other major lifestyle changes, such as starting an exercise plan or new medication, which could impact their pain.  In addition, patients in the OLP group were given a medicine bottle labeled "placebo pills" with directions to take two capsules containing only microcrystalline cellulose and no active medication twice daily. Patients who knowingly took placebos reported 30 percent less pain and 29 percent reduction in disability compared to control group. 'Open-labeling' addresses longtime ethical dilemma, allowing patients to choose placebo treatments with informed consent.

Dear Reader – this study could be interpreted in various ways – that the caring and interest of health-care providers is powerful, or that doing something for pain is better than doing nothing, or that we have strong cultural belief in the taking of a pill.  All of these are probably operative, but I think the caring and attention from a provider is the most powerful.

Safe Abortion in Ireland Women on Waves is a Dutch organization that sends the pills that can safely produce an early abortion to women in countries where abortion is illegal.  The British Journal of Obstetrics and Gynecology recently reviewed and published the results of 5,650 abortions done in Ireland with these medications.  All abortions were done at home.  Women

were diverse with respect to age, pregnancy circumstances, and reasons for seeking abortion. Study findings include:

•                Among women completing early medical at-home abortion, 97 percent felt they made the right choice and 98 percent would recommend it to others in a similar situation.

•                The only negative experiences commonly reported by women were the mental stress caused by pregnancies they did not want or felt they could not continue, and the stigma, fear, and isolation caused by current restrictive abortion laws.

Women with financial hardship had twice the risk of lacking emotional support from family and friends.

The author of the article stated

“Women in Ireland and Northern Ireland accessing medical abortion through online telemedicine report overwhelmingly positive benefits for health, wellbeing, and autonomy ,This examination and subsequent findings provide a new evidence to inform the policy debate surrounding abortion laws in Ireland and Northern Ireland.”  

Sadja Greenwood, MD, back issues at sadjascolumns.blogspot.com

Habits You Need Throughout Life

In the Science Times of October 25th, Tara Parker Pope wrote a column about the advice eight scholars gave to people in their twenties.  Experts in nutrition, obesity, cardiology and other disciplines each gave one strategy that would help young people stay healthy throughout their lives.  As I read these short pieces I thought that they are relevant at every age – it’s never too late to form healthy habits.  Here they are:

1) Weigh yourself often – buy a scale and keep track of your weight – it’s easier to lose 5 pounds than twenty.  Carrying excess weight is harmful to your overall health and your leg/foot joints.

2) Learn to cook – find tasty ways to boost your intake of vegetables, fruits, whole grains and proteins.  This will save you money, decrease your intake of unhealthy fats, sugar and salt, and possibly help your social life.

3)   Cut back on sugar – by eliminating sugared soft drinks, breakfast cereals with added sugar, and being careful with cookies, cakes, candy et al.  This step alone will prevent unwanted weight gain.

4)   Live an active life – Build physical activity into every day – by biking, walking, gardening, doing housework, upper body exercises, et al.  Move to music!

5)   Practice portion control – let your hand be your guide – a serving of chicken, fish or meat should be the size of your palm, and of whole grain starch should be the size of your fist. 

6)   Eat your veggies – this advice is from Marion Nestle, professor of nutrition at New York University. ’Nutrition science is complicated and debated endlessly, but the basics are well established: eat plenty of plant foods, go easy on junk foods, and stay active. The trick is to enjoy your meals, but not eat too much or too often.”

7)   Adopt a post-party routine – if you do a lot of drinking and snacking, ensure that you exercise a lot to offset all those extra calories.  (Good advice for the holidays)

8)   Find a job you love – this advice is from Hui Zheng, a professor of sociology at Ohio State University.  “If I can give just one piece of health advice for a twenty year old person, I would suggest that he or she find a job they feel passionate about.  This is turn will make them more engaged in life and healthier behaviors, which will have long-term benefits for their well being.” I think this advice is pertinent at every age.  Find ways to make your work life meaningful.  After retirement, it is also important to find activities that you are passionate about – volunteering for a cause you believe in, finding pleasure in a creative project, taking up a paintbrush, modeling clay, or a musical instrument.  Write poems and short stories. Don’t be afraid to be a beginner. 

Submitted by Sadja Greenwood, MD, MPH