Diet, weight and being in pain

Lifestyle changes is not probably a topic that most doctors discuss with their patients in pain. One of the great physicians of the early 1900s William Osler once said ”The good physician treats the disease; the great physician treats the patient who has the disease.” The best way to treat a disease in my opinion is to treat the whole patient with the biopsychosocial approach : see my previous post on slow medicine vs fast medicine. Most diseases occur because of the interaction between genes, lifestyle and environment.

Diet is an essential part of our lifestyles. Currently, the diet of most people in the US is contributing to many diseases. Below is a graph with the prevalence of diabetes in US:

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People can argue which food increased the diabetes prevalence, but I think it is pretty clear that the diet is the cause. Definitely, this increase is not due to purely genetic factors. Our bodies are very efficient in using energy and our food is too high in calories. It is quite remarkable that nowadays we pay more for food with less calories in order to eat healthy. Our ancestors would be incredibly puzzled.

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Interestingly enough many patients I see in my pain clinic do not make a connection between their lifestyle and their pain. Many of them blame osteoarthritis (inflammation) in their joints for their pain. Diet has a very important role for inflammation in our bodies and the standard american diet rich in processed food and sugar is one of the worst. Some diets shown to help with inflammation and prevention of disease are DASH and Mediteranean diet. A few institutions recommend antiinflammatory diets: Harvard link, Cleveland clinic link and University of Wisconsin pdf file. Besides inflammation there are studies showing that food rich in excitatory molecules aggravates chronic pain. One example is monosodium glutamate (MSG) with studies showing that MSG is not good for some fibromyalgia patients (an overview here). A review of the inflammation and chronic pain is on the pain science website.

In addition to the diet obesity creates a state of inflammation in the body that seems to induce diabetes, heart disease, cancer (one scientific paper) and probably pain too. This is a decent review of the relationship between obesity and chronic pain: practical pain management link. One indirect link between obesity and pain is diabetes which damages nerves and creates neuropathies. Obesity also creates mechanical stress and increases the risk of damage in the weight bearing joints. Everybody who is overweight/obese can try the following experiment: get a backpack, put 30 pounds of weight in it and walk around….this is how your 30 pound lighter body feels every day.

If you need motivation to change your diet you should watch a few lectures by Robert Lustig: http://www.robertlustig.com/. If you are interested in biochemistry, metabolism and general science Peter Attia might be a place to start: https://peterattiamd.com/. Serious research about lifestyle changes and various diseases was published in prestigious journals over many years by Dean Ornish who promotes healthy diet, stress reduction, social support and moderate exercise. Obviously diet and lifestyle changes cannot fix everything and that is why we have modern medicine to help. But if there is a choice between medications, surgeries and lifestyle changes I am not sure why somebody would choose the first two options.

The tight integration of the immune and nervous systems

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Years ago, in the medical school I learned about various parts/systems in our body. But nobody spent much time in putting everything together. Nowadays I think the situation is still the same and most doctors end up looking at our bodies as a piece here and there. Of course having so many specialized doctors does not help the integration cause.

Over the last year I spent some time reading about the interactions between the immune system and the nervous systems. Depending where we draw the line I would argue that the immune system and the nervous system are basically one thing. The immune system can be seen as part of the sensory system with a role to inform the brain about potential bacteria/viruses present around the body. Nervous system also modulates the immune system. An interesting presentation by Kevin Tracey (TEDMED talk) describes how the vagus nerve changes the immune response. Another lecture by him goes even in more details: the academy of medical sciences talk. Currently there are efforts to use vagus nerve stimulation to treat autoimmune diseases like Crohn’s disease and rheumatoid arthritis (one article here).

The central nervous system (brain and spinal cord) has a significant amount of immune cells in the form of microglia. It is estimated that microglia are 10-15% of all glial cells in the brain. Microglia are tightly integrated with neurons and have a role in the maintenance and regulation of the synapses between neurons. Things can go wrong. There are theories that some forms of depression are caused by inflammation. Charles Raison is one physician researcher who is working on depression and immunity (this interview with Rhonda Patrick is really good). The other day I read an article in the New York Times where cases of schizophrenia seemed to be related to the immune system. In this article one patient developed what appeared to be schizophrenia, then developed leukemia and had stem cell transplant. His schizophrenia resolved after the stem cell transplant. Another patient had leukemia and got stem cell transplant from his brother who had schizophrenia. Strangely enough this second patient developed schizophrenia himself.

The connection between the immune system and the nervous system has been used for thousands of years in yoga and practices of breathing exercises. One recent version is the Wim Hof method which is a combination of cold exposure, meditation and breathing exercises. For a perspective about Wim Hof, the man, this is a good documentary by Vice. Luckily some researchers got involved and they showed that the practitioners of Wim Hof method had a different response when they were injected with Escherichia coli endotoxin. You can read the article published in PNAS for free: here. Anecdotal evidence from the followers of Wim Hof method suggests an improvement of the autoimmune diseases. There is a book by Scott Carney that discusses more on this topic: link here.

This post is just a little introduction on the this topic. My interest is in chronic pain and I think inflammation and pain create a vicious cycle that maintains both of them. We have to start looking at the bigger picture when we treat complex diseases like chronic pain.

Mismatch diseases

Recently I read the book "The Story of the Human Body: Evolution, Health, and Disease" by Daniel Lieberman. It was a fascinating read. A main idea of the book is that a lot of the current human diseases are mismatch diseases. Our ancestors did not evolve to live in the current environment. Agriculture is just a recent discovery (around 12, 000 years ago) and brought many diseases. After agriculture people started to live in bigger communities which made them prone to infectious diseases. Also agriculture increased the risk of famine and malnutrition because people relied on just a few crops. The industrial revolution worsened living and work conditions for a while. Then in the last one hundred years things started to get better for living and work conditions but surprisingly we fell into the other extreme. Things are too much better. People don’t do much physical work and the modern diet is full of readily available calories. At one point Daniel Lieberman asks the reader to think what would happen if we bring a zebra from Africa to Massachusetts and let it roam around. For sure the zebra would not live long because it is not adapted to the environment in Massachusetts. Human beings are in a similar situation. Our environment is very different than the environment in which we evolved (think hunter gatherers). Our body is not fit to deal with processed food, inactivity, daily stress. There is a trend in science to blame many of the current diseases (e.g diabetes, cardiovascular diseases) on genes. The truth is that the genes have been around for a very long time and only recently the incidence of these diseases exploded. What changed is the environment (more processed food, chemicals and more inactivity). Instead of changing the cause (environment) our society is trying to fix the symptoms (diseases).  I am very supportive of basic science and clinical science. We truly need to understand how our body works. But a lot of the current diseases do not require complicated solutions.  

Slow medicine vs fast medicine

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We live in a fast-paced society. It seems that new technological advances happen every day. We see commercials for better cars, new TV sets, super fast phones (which are pretty much computers in our pockets). I think some of the expectations are transferring to the medical care. Patients expect a fast fix for most diseases. They ask: doctor, do you have a pill to fix this or that? Or an injection, or maybe a surgery?

I think it is worth trying to look at the bigger picture. The time scale in biology is very different than in technology. Little changes happen in our bodies every second and some times these little changes accumulate over many years to cause a disease. Furthermore, we do not live suspended in a vacuum. We interact with our environment; we are part of the environment. During history different trends in medicine tried to make sense of the bigger picture. In 1960 George Engel published “A Unified Concept of Health and Disease”, a paper that I would recommend to everybody (it was recommended to me in a book by Lorimer Moseley and David Butler). George Engel promoted the biopsychoscial model of disease. He criticized the medical practice at that time, medical practice which is still the same today. A few key paragraphs from his paper:

“To be able to think of disease as an entity, separate from man and caused by an identifiable substance, apparently has great appeal to the human mind. Perhaps the persistence of such views in medicine reflects the operation of psychological processes to protect the physician from the emotional implications of the material with which he deals.”

“Patients, certainly, regardless of their level of education and sophistication, prefer to blame their illness on something they "caught" or ate or that happened to them and to think of disease as something apart.”

“A disease, then, has substantive qualities, and the patient can be cured if the diseased ("bad") part is removed. That this often proves to be the case, as attested to by the successes of surgery, is actually not evidence for the validity of such a point of view”

In more recent times the trendy terms are mind-body medicine and integrative medicine. I would argue that both of these new terms are trying to accomplish the same thing as the biopsychosocial model, take the patient as a whole person interacting with the environment. Diseases are caused by a combination of genetic factors, lifestyle and environment. At this point we cannot control most genetic factors, but we have the power to change the lifestyle and the environment. However, changes come through education and with effort. Last national program with meaningful results was the campaign against smoking. Since then other issues took over, one of the most important being the obesity.

Once a disease develops I think it is worth looking again at the cause of the disease and work very hard to change the contributing factors. Also we have to be cognizant that it will take time to reverse biological processes. Usually a disease does not develop overnight and the solution takes time too. This is what I would call slow medicine. Of course, there are medications we can give to patients in the meantime, but the medications should be only a short term solution for most conditions. Medications have many predictable and unpredictable side effects: see my blog post (Side effects of medications). Small incremental positive changes for long term benefit are not that appealing in the current culture. I think we really need a change in culture. In my case I treat chronic pain conditions. I have many patients who come to me and say they had pain for over 10 years. At this point their whole nervous system is changed, their social lives are different, their psychological status is different. One medication or injection is not going to change everything. I tell them that there are things I can do for them (e.g medications, procedures, referral to physical therapy/psychology) and there are things they can do for themselves (e.g. lifestyle changes, weight loss, healthy diet, quit smoking, participate in physical therapy/psychology). We will work together as a team and manage their pain.

The other type of medicine I would call fast medicine. This is very dramatic and appealing to the doctors/patients/general public. Fast medicine includes surgeries, treatment of cancer, curing of possibly deadly infectious diseases. There is definitely a place for fast medicine, we need it. I love fast medicine myself. I am an anesthesiologist and enjoy practicing fast medicine in the OR, fixing things fast. It is very rewarding. Every now and then I am blown away by what fast medicine can accomplish. Recently I read this article in the journal Nature: “Regeneration of the entire human epidermis using transgenic stem cells” (Nature volume 551, pages 327–332, for a general public version of the story here). Basically they had this kid with a genetic disease (Junctional epidermolysis bullosa) that involves the skin (superficial layer called epidermis) and mucosa. His skin had a lot of wounds (60% of his epidermis was lost). They took biopsies from his skin, engineered his skin stem cells to get rid of the genetic mutation, grew epidermis in the lab and transplanted it on the kid. In the end, they were successful in replacing 98% of his skin. It felt like reading a Sci-Fi short novel, truly remarkable stuff. But in the big picture if they stop here it will still be a failure. First, they did not fix his mucosa. Then, the kid likely has already tremendous psychological baggage and that is likely true about his parents. His social situation is also different after living with this disease.

In the big picture we have to understand when to use fast medicine approaches and when to use slow medicine approaches. I would argue that fast medicine needs slow medicine to take over afterwards and look at what caused the situation to occur in the first place, reverse what can be reversed and take care of the long term consequences.

Brain tricks

The human brain is a fascinating structure and we are still far away from understanding how it works. In the last 3-4 months I spent some time trying to put together a website for patient education about pain. One big contribution to pain is how the brain processes the incoming information. This blog post is more about brain in general. I will leave the part about pain for another post.

One role of the brain is to help us safely navigate the environment. The brain has no direct access to the world and has to rely on information coming from the sensory organs (e.g. eyes, ears). It processes this information and tries make the best guess about what is actually happening. But how good is the best guess? Sometimes the brain makes predictable errors like optical illusions (see checker shadow illusion and table illusion). What is common to these illusions is that we expect the world to be in a certain way (illumination/orientation). Some other examples where expectations alter our perceptions: https://youtu.be/xRel1JKOEbI?t=1382 (watch until minute 25 or the whole thing if you feel like it or read the next paragraph)

A really mind blowing theory is that the brain uses predictive processing for a lot (maybe all) of its inputs. Basically, the predictive processing means that the brain predicts what the input is going to be and sends this prediction to certain areas. Then, the input sensory information (e.g. visual or auditory information) comes to the same areas. When the prediction and the input match the brain uses the prediction. When they do not match a prediction error is created. The weight of the prediction error is dependent on attention and small prediction errors may be ignored. There are few options for the brain at this point: change the prediction or change the input to match the prediction (either alter the input at the brain level or activate motor/other body functions to alter the input). The predictive processing theory is pretty well developed for almost every neuroscience field imaginable. Now I am reading the book " Surfing Uncertainty" by Andy Clark. This TED talk by Anil Seth nicely presents some of these points in a shorter talk than the link above. More resources are on this link from reddit.

The implications of seeing the brain as a predictive processing machine are quite big. There was an article in the New York Times by Lisa Feldman Barrett and Jolie Wormwood  and they argue that the prediction for the brain of a police officer to see a gun in certain situations is so high that it overrides the visual input and the brain truly sees a gun. In our daily lives less dangerous examples abound. For example, recently I was helping with a simulated exam for our anesthesia residents. One hour into this somebody mentions that the small exam room I was sitting in has this huge structural pillar for the entire building. The pillar was like a foot from my chair and I had no clue it was there. The prediction of my brain for that room was without any such pillar. My visual system definitely sent the information to my brain but it was completely ignored. In the end, as long as we are aware of our limits I think we can find a way to happily live with them.

Podcasts

There is so much information on the internet. In the end, each of us has to choose some sources to use. In my case, I prefer in depth discussions about random topics and I found the podcast format to offer the best approach. I usually put on my bluetooth headphones and do work around the house or take a walk in the park. I probably listen to about 3-4 hours of podcasts per week.

My favorites podcasts are:
- Tim Ferriss show, I usually skip the first 6 minutes or so because it is mostly commercials
- Think from KERA station
- 99% Invisible
- Freakonomics Radio
- Radiolab
In the medical field I recently found the ASRA RAPP podcast.

Popular apps for podacasts on Android: Podcast addict and Stitcher. On iOS there is the default iTunes. If you have any recommendations for podcasts/apps, please use the comment section.

 

Food, nutrition, culture

Obviously, there is something wrong with the food in US since the percentage of obese people has increased dramatically. Currently, around 7 in 10 adult Americans are obese and overweight (see statistics here and here). That leaves only 3 in 10 adult Americans with normal weight. Increased weight leads to increased health problems from diabetes, high blood pressure to osteoarthritis. 

How did we get here? The best explanation I found was in presentations by Marion Nestle: watch this lecture. There were a few factors in the 1970s-1980s. Up to a point the farmers were paid to keep the land uncultivated. Then this changed and the government paid the farmers to grow crops. Suddenly, there was more food on the market. Another factor was a change in financial regulations and more money were available for Wall Street to use. Wall Street firms started to invest in the food industry and expected fast profits. The food industry became very competitive. It was a race to advertise products in order to sell as much as possible. Even at that time people already had enough calories but the food companies used other tricks to increase sales (added all kind of nutrients/supposed benefits, increased portion size). Another contributing factor was women starting to work and having less time at home to cook. What was not a factor according to Marion Nestle is a decrease in physical activity because people were not active in the 1970s-1980s anyway.

What can we do about this situation? I think everything starts with a healthy diet. But what is a healthy diet in the first place? You turn on the TV and there are tens of commercials about different products to help you lose weight. You go on the internet and there are all kind of diets promoted. We have to remember that the food industry is a business. Most diets advertised on TV, on the internet and in stores are a business too. However, there are people around the world with different habits/environmental conditions that already proved that certain lifestyles are better than others. In my opinion (no business for me) there are a couple of diets worth considering. One is the Mediterranean diet. The other one is the Vegetarian diet. Basically, both of these diets involve eating vegetables and less or no meat. One talk that I found particularly useful about diets is this lecture by David Katz.

For more information about the Mediterranean diet: Mayo clinic link and Healthline link. It is ok to skip the wine associated with this diet. The Mediterranean diet was shown to improve health in various studies (a good resource here). One population that has shown benefit from the mostly vegetarian diet is the Seventh day Adventist population in California (one of the articles here).

Another popular good source for information is Michael Pollan (one of his entertaining talks here).

After countless hours spent on the internet I think the bottom-line is what Michael Pollan said: eat food (real food, not processed food, not nutrients), not too much, mostly plants. For most people following these simple recommendations plus eating a variety of foods will bring all the necessary nutrients. More tips from Michael Pollan: here.

I think the food culture is actually changing in U.S. Farmers markets are more popular than ever. There are even more young people becoming farmers according to this recent article from Washington Post.

 

Side effects of medications

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It is pretty impressive to see how many medications patients take in the U.S. I looked at the official statistics from CDC and my anecdotal observations were confirmed. From 2011 to 2014 approximately 49% of population used at least one prescription drug in the last 30 days. In the same period approximately 12% of population used five or more prescription drugs in the last 30 days.  All this started with the antibiotics, the first real successful class of medications. Then, the medical system tried to apply the same principles to treat all human diseases. It was successful for some diseases (e.g. diabetes, high blood pressure, hypothyroidism) but for other diseases the success was not that great (e.g. cancer, pain). One major difference is that now patients are on medications for years compared with the short therapy with the antibiotics. Long term use of medications comes with side effects.

When you take a medication the goal is for the active chemical to get to a target in the body (usually a receptor or enzyme) and alter an intracellular pathway. The reality is much messier than the textbooks. Nature used the same building blocks many times to create different receptors in the body. Medications are very rarely (maybe never) specific to just one target.  One interesting website that shows possible interactions for medications is: http://stitch.embl.de/. Human receptors and the intracellular pathways can also have genetic variations and result in different effects for certain patients. Also, the medications are usually prescribed for one organ disease, but the molecular targets are present in other organs. One example of effects on other organs is the side effects of NSAIDs (nonsteroidal anti-inflammatory drugs) on gastrointestinal tract, cardiovascular system and kidneys.

The side effects to medications range from something quantifiable (e.g. changes in blood glucose, white blood cell count) to something very vague (e.g. feeling tired). One website that lists side effect to medication is:  http://sideeffects.embl.de/. The problem with the vague side effects is that although they can be very bothersome, sometimes they are not caused by the medication. Most people heard about placebo effect. However, there is the opposite effect, the nocebo effect. Basically, you give a "sugar" pill to somebody and the subject complains of random side effects. Normal people on no medication walk around feeling tired, sleepy, maybe slightly nauseated once in a while. When we give them a pill (active or inactive) they start to attribute their usual feelings to the pill. This is actually a big problem, there are clinical studies showing that 1 in 5 people receiving inactive pills complain of side effects (Barsky et al 2002).

When patients take more than one medication, the interactions are very unpredictable. I watched an intriguing TED talk by Russ Altman. He describes how they found that pravastatin and paroxetine when taken together increase blood glucose. Innovatively, they used a bioinformatics approach and a side effect database. Knowing the mechanism of action of pravastatin (a cholesterol lowering drug) and paroxetine (an antidepressant) the blood glucose effect is very surprising.

What can we do better in the future? We should think twice before prescribing medications long term. Sometimes there are other options, like healthy diet for weight loss (which helps diabetes, high blood pressure) or relaxation/meditation techniques for anxiety and sleep. Only if everything fails we should rely on medications.  Or we can use medications only short term while implementing the other methods. Our society is looking for a quick easy fix for every health problem, but the long lasting fix usually takes time and requires effort.

Human limits

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I have always been impressed by what people can achieve. You look at the human body and it seems so frail but with enough mental strength, the right training and determination a lot of amazing things can be achieved.

This year I was impressed by three accomplishments. First, it was Alex Honnold who did a free climb on El Capitan. I have been following Alex for many years and knew that his dream was to climb the 3,000 foot Freerider route without any ropes. It takes tremendous skills and composure to do such a thing. The story was widely reported on the internet, one link here from Outside magazine. Alex has been doing free climbing for many years and already was a legend in the climbing world. His ability to control fear was actually studied in an fMRI machine.

Another impressive accomplishment was Mark Beaumont who biked around the world in 79 days. This is the link with the story on the BBC website. It was a 18,000 mile trip and he averaged 240 miles per day (16 hours of riding daily and had a few days off to fly from continent to continent). He actually did go around the world before but that was an unsupported trip and took way longer. More about him here and here.

A third incredible accomplishment was Karl Kruger who raced on a paddle board for 750 miles from Port Townsend, WA to Ketchikan, AK (Race to Alaska). His story covered by a Dirtbag diaries podcast episode is very entertaining.  Obviously, a lot of people thought he is crazy. There is also a video version of his race.

We, the regular people, might never accomplish anything close to these three guys, but I think we should push our limits. Most of the time our limits are just imaginary.

 

Opioid therapy

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In the December 2017 issue of the Pain journal I read an excellent article about opioids by Jane Ballantyne and Mark Sullivan: "Discovery of endogenous opioid systems: what it has meant for the clinician’s understanding of pain and its treatment" (full article here).  In the same issue there is also a commentary by Daniel Clauw: "Hijacking the endogenous opioid system to treat pain: who thought it would be so complicated?" (full article here). Both articles describe how opioid receptors in the human body are there to interact with chemicals made in the human body. This innate opioid system is important for many functions in the body (some examples include mood, metabolism) and social functions. Basically, a therapy with high dose opioids alters all these innate mechanisms. Another issues is that a high dose opioid therapy may interfere with other nonpharmacological therapies for pain that likely use the endogenous opioid system: exercise, acupuncture and mind body therapies.

Currently, the U.S. is going through an opioid epidemic and opioids are frequently discussed in the news. I think it is important to look at the bigger picture. Humankind has a long history with opioids. There are some theories that even Neanderthals used poppy seeds. A good timeline is presented here by PBS. There were even opium wars between the British Empire and China with the British Empire promoting opium trade. It is a fascinating read about the first opium war and then the second opium war. At that time people had all kind of ideas about how drugs work. A quote from the first article above: "during the many centuries that opium and its derivatives were used for pain, the efficacy of opiates was often attributed to divine benevolence. Thomas Sydenham, the 17th-century “English Hippocrates,” wrote “Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium.” Sir William Osler called opium, “God’sOwn Medicine.”

Our last excessive use of opioids started in the lat 20 years with a significant increase in deaths. CDC estimates that from 1999 to 2015, more than 183,000 people have died in the U.S. from overdoses related to prescription opioids. This does not include the deaths related to illegal opioids. More statistics are available on the CDC website. In March 2016 CDC came up with guidelines about opioid prescription: long version and short version. Basically, the recommendation is to be very cautious when prescribing more than 50 mg Morphine equivalents daily and have a very good reason to prescribe more than 90 mg Morphine equivalents daily. Most people nowadays are prescribed hydrocodone and oxycodone as outpatient opioid medication. Hydrocodone dosage is equivalent to morphine dosage, so 10 mg hydrocodone is equivalent to 10 mg morphine. Oxycodone is one and a half time more potent than morphine, so 10 mg oxycodone is equivalent to 15 mg morphine. Oxycontin is the slow release version of oxycodone and the same conversion as for oxycodone applies.

New beginning

The internet is an amazing place. There is so much useful information and ways to connect with wonderful people around the world. However, there is also a lot of noise that buries the useful part. I finally decided to start my own website that will be my main way to interact with the outside world.