Integrative Medicine - Part I

Can integrative medicine add value to standard western practices? Some would say absolutely not; others point to new scientific evidence that demonstrates the value of specific modalities in specific situations.  

Health care is complex, expensive and often depersonalizing. It shouldn’t be. At the University of Maryland Center for Integrative Medicine, the staff focuses on evaluating and involving complementary medicine into traditional western or “scientific” medicine. Founded in 1991 by Brian Berman, M.D., a family medicine trained physician, he had learned the certain alternative approaches could complement the usual diagnostic and therapeutic methods that he had been taught in his medical school education and training. He found that his patients’ experiences were enriched by treating the whole person rather than depending on a technology-focused practice. A grateful and forward looking patient offered him a grant to begin the Center with the proviso that it embrace and study evidence-based science along with education and collaborative patient care to create a comprehensive humanistic approach to patient care.  

Since its founding 20 years ago the Center has been awarded over $30 million in NIH grants and has been named as a center of excellence for research. From this work have come over 340 high quality peer-reviewed scientific articles published in the best medical journals. These have been in areas such as acupuncture, herbal remedies and mind-body therapies focusing on arthritis, pain depression, cancer, trauma and inflammation. The center employs a staff for clinical care that includes family medicine and other physician specialists along with licensed acupuncturists, massage therapists, nutritionists and many other disciplines. 

As just one research example, acupuncture was studied in a double blind fashion to determine if the addition of acupuncture to best standard treatment improved the lot of those with knee osteoarthritis. Those who got acupuncture, when compared to those that got sham acupuncture, has less pain, used fewer pain medications and had greater range of motion. 

At the “Health and Wellness Conference” a few weeks ago to celebrate the 20^th anniversary of the founding of Center, Delia Chiaramonte, MD described what an integrative approach to a medical dilemma might look like. She described a medical student who had suffered from severe headaches for many years that were limiting his quality of life and his effectiveness as a student. His physician had identified them as cluster headaches and had tried various standard medications without success. A frustrating situation. 

He was then evaluated differently using an integrative approach. It involved a lot of probing about his headaches, his lifestyle including diet and activity, his stresses and his school work. Like almost all medical students, he studied hard. He said he stayed up until about 3:00am, but in part this was because he couldn’t fall asleep any earlier. His diet included a lot of doughnuts and a lot of other high carbohydrate items plus about 12 cups of caffeinated coffee each day. He had no time for exercise. He sat - hunched over - in front of his computer for many hours each day, and his posture showed it.

 
His headaches fit the description of “cluster” headaches, often with a sense of an ice pick sticking into his right eye - near unbearable pain. The standard medical texts suggest use of ergotamine tartrate for cluster headaches and also note its potential side effects. There is no mention of other modalities or adjustments to lifestyle issues. But cluster headaches can be amplified by stress, worsened by sleep deprivation and the stabbing could well have been posture related. 

So instead of recommending medications, his integrative medicine “prescription” included the following: he was to see a nutritionist to devise a more healthy diet. He was to work with a personal trainer to establish an exercise program - one that could be done anywhere without impacting on his studies. He was to visit a chiropractor to release his sternocleidomastoid muscles and other neck muscles back to their normal length. In addition he was to have no caffeine after noon and he was to get to bed by 11:00pm each night.  

Given the pain and debility of his headaches, he was more than willing to give this prescription a try. It worked. The headaches disappeared, he felt generally better, he was no longer drowsy in class and he began to truly enjoy medical school.  And he was off all medications. 

This is the power of integrative medicine. It used a holistic approach and brought to bear many different disciplines including nutritional medicine, exercise physiology, stress management, chiropractic and family medicine. I wrote about this extensively in The Future of Medicine – Megatrends in Healthcare . 

Note: You can find the Center for Integrative Medicine on Facebook at http://on.fb.me/HWRPKp

Your Genes Need Not Be Your Fate: Nutrigenomics To The Rescue

Genomics Part 4 -- Medical Megatrends 

Are you concerned about a family history of heart disease? Or cancer? Worried that you genes will be your fate? We know that good dietary habits are generally good for us but can foods affect our genes? The new science of nutrigenomics suggests that they can. 

Nutrigenomics is about using what you eat to change your gene expression (meaning how your genes function) to optimize your health.  

Nutrigenomics is the science of how bioactive chemicals in foods and supplements alter the molecular expression and/or structure of an individual’s genetic makeup. It is apparent that one size does not fit all when it comes to nutrition. We have become aware of the limitations of population-wide advice such as the food guide pyramid. Second generation approaches have proliferated with pyramids tailored for children, the elderly, ethnic groups, vegetarians, etc. Although these attempts are steps in the right direction, they do not take full advantage of the breakthroughs in biomedical science. Fortuitously, this realization has come at a time of great expansion of knowledge with the genomics/informatics revolution. 

Nutrigenomics is a young science and built around the revolution in genomics. As such, the science is still evolving. The excitement about nutrigenomics comes from a growing awareness of the potential for modifications of food or diet to support health and reduce the risk of obesity and many deadly chronic diseases.  

Nutrigenomics will become a critical part of the entire “personalized medicine” concept that is revolutionizing medical practice as discussed in detail in The Future of Medicine – Megatrends in Healthcare. Personalized (or “custom tailored”) nutrigenomics medicine is an approach that means it is possible to have a direct impact on long term health and longevity by very specific dietary manipulations. Nutrition will no longer be “one size fits all.” 

Nutrigenomics offers hope to those who know they have a strong family history of heart disease, cancer, diabetes, obesity, and most likely many other diseases as well. At the same time it takes away the excuse of “everyone in my family is overweight so I am too.” One no longer needs to be fatalistic in this regard and hope may lie at the end of a fork.  

Nutrigenomics is not a phenomenon, a fad, or a technique to use in a vacuum. It is best as part of a total approach to lifestyle management. 

It is increasingly apparent that various foods directly affect critical genes – turning them off or on as the case may be – and thereby directly impacting the development of atherosclerosis, diabetes, many cancers and obesity, among others. The foods that we consume play a role in how genes that affect our health are expressed, or “turned on” and “turned off”.  

For example, we know that broccoli is good for us because it is one of the most nutrient dense foods that we can consume. One of the reasons that consuming broccoli may enhance our health is that many of the nutrients in broccoli have been shown to turn on genes that protect from disease and turn off genes that increase the risk of disease. For example, a nutrient in broccoli called sulforaphane has been shown to turn off genes that cause many forms of cancer. The omega-3 fatty acids found in salmon, grass-fed beef, walnuts, flax seeds, and fish oils appear to turn on genes that protect against heart disease and its risk factors. These are just a few examples of how eating a nutrient dense diet can improve health by turning on genes that protect from disease and turning off genes that cause disease.  

It is important to realize that processing foods removes or destroys phytonutrients. Hence, processed foods contain less or no phytonutrients, and this lack of phytonutrients along with chemicals that directly affect our cells’ genes explains, in part, why overconsumption of processed and ultraprocessed foods contributes to chronic disease. 

See the Future of Medicine – Megatrends in Healthcare for a fuller discussion of the implications of genomics. And watch for new developments in this fast moving new science. 

Remember, nutrigenomics has made it clear that your genes need not be your fate! Just because you have a family history of a certain disease does not mean that you are also destined to become a victim.

Genomics Is And Will Be A Transformational Megatrend In Medical Care But The Path to Targeted Drugs Will Be Rocky At Best

Medical Megatrends – Genomics Part III

Genomics promises to fundamentally change much of medical care as described in the two prior posts on this subject.  But the ultimate value of this new understanding of basic human biology will in many cases come with fits and starts. The saga of belimumab (Benlysta) and Human Genome Sciences is illustrative.

Systemic lupus erythematosus (SLE) occurs in somewhere between 300,000 and 4 million Americans according to the Centers for Disease Control. It is more common in women than men and more common in African Americans than Caucasians. SLE is an autoimmune disease of unknown etiology which can affect many body organs and systems and can lead to death. The disease can wax and wane and can flare with activity in the central nervous system and the kidneys. Genomic studies done by Human Genome Sciences (HGS) more than a decade ago showed that it might be possible to create a monoclonal antibody to react against the B lymphocyte stimulator, a cytokine that has been found to correlate with activity in SLE.

            HGS produced the monoclonal antibody – belimumab – and then conducted the required preclinical studies in test tubes and animals to demonstrate its activity and toxicities. With FDA approval it then conducted phase 1 and 2 studies in humans to determine toxicities, side effects and early suggestions of activity in humans. It then proceeded to complete two double blind randomized controlled trials comparing standard treatment to standard treatment plus belimumab in 1684 patients. The results were sufficient to win a 13 to 2 recommendation vote from the FDA’s advisory panel in November, 2010. The FDA announced its approval and the required package labeling in March, 2011. The FDA and HGS have both noted that this is the first new drug for SLE in 50 years and the approval was lauded by the Lupus Foundation of America. The intravenously administered drug is available for about $35-40,000 per year.

            It all sounds straight forward – good science led to a new drug that should benefit many patients who have had limited treatment choices until now. But for HGS it has been a rocky road at best over the years. Founded in 1992, the company set out to use genomic discoveries to create new pharmaceuticals. By 2000, it was being hailed as an up and coming company and it stock price rose to over $100 per share. But the share price then plummeted along with those of other genomic-oriented companies. Fortunately for HGS, its CEO, Dr William Haseltine, made use of the high stock price to lock in a soon to be much needed cash stockpile. The company’s first drug candidate – to treat leg ulcers – met with failure and was dropped. A second drug – for hepatitis C- looked to be very promising and carried the hopes of staff and investors but a key trial was unsuccessful and HGS ultimately had to make the decision to pull the plug on this drug candidate as well – after expending many millions of dollars in the preclinical- and clinical testing phases. The stock price dropped to a low of 52 cents per share and the cash war chest was running lower and lower. Then – finally – came good news with the two belimumab patient studies and the stock price jumped immediately but to no where near the heights of a decade before.

And then the drug did not “take off” as fast as Wall Street had predicted (nor as HGS would have preferred) and the stock price fell back to about $7 per share. But Glaxo which markets the drug for HGS and has contractual arrangements for other HGS compounds in the pipeline has just offered about $14 per share to acquire the company. HGS has said “no thanks” but the story is probably not over yet.

            Belimumab looks to be a useful addition to the SLE treatment armamentarium. But there are questions and critics. SLE is much more common in African Americans but the two patient trials had relatively few blacks enrolled and there was some suggestion that perhaps they responded less well. The drug is also not without potential side effects including predisposing to serious infection. Further, some calculate that it will take about four (or more) patients treated to lead to one patient benefitting. At $35,000 per patient per year, that means a total expenditure of about $140,000 or more to benefit that one patient.

            My message is that genomics is and will be a transformational megatrend in medical care as I discussed in The Future of Medicine – Megatrends in Healthcare. . But “targeted” therapy is not always all that narrowly targeted in a way that either is effective for all nor is the drug necessarily side effect free – and it may be quite expensive. The story of Human Genome Sciences demonstrates that the path from a genomic discovery in the laboratory to a marketed drug can be long, expensive and fraught with many disappointments along the way. But conversely, innovation as demonstrated here is and will be the lifeblood of continued future success and improved human health.

Genomics – a Revolution in Medicine – Part 2

In the previous post I discussed the field of pharmacogenomics. Today I will focus on


Disease classification
Disease prognostication
Early and rapid diagnosis
Prediction of diseases to develop later in life

Genomics is proving to be very valuable in disease classification, especially with cancer. A pathologist’s evaluation looking at a microscopic slide has been the basis for most cancer classification - separating out breast cancer from lung cancer but then sub classifying each such as small cell and non-small cell lung cancer or the various subcategories of lymphomas. To this was added some years ago histochemical analysis to learn if a breast cancer was high in estrogen or progesterone receptors and then molecular diagnosis to find, for example, if the tumor had a high complement of the receptor Her2neu – each being important markers for the approach to treatment. Now genomics is adding an ability to delve much more deeply and find what the DNA mutations are in the individual tumor and how they are similar or different from others. This in turn is leading to searches for new drugs, as discussed last time.

This same work allows for early prognostication. Consider 100 women with breast cancer that appear by all the usual criteria to be the same type and of the same early stage. We know that most of them will respond well to current therapy of surgery, radiation locally and, in certain circumstances, systemic chemotherapy or hormonal therapy. But a small percentage will have a relapse. The problem is that there has been no way to determine in advance who is at risk of relapse. Genomics has begun to answer this problem. Analyzing the genomics of the tumor at the time of diagnosis, it is possible to separate these women into a good prognosis group and a poor prognosis group. The former rarely relapse and one might even consider if they need the same level of aggressive therapy as they are now getting. And the latter group is at high risk of recurrence; they are obvious candidates for clinical trials of alternate approaches to determine if relapses can be reduced. One such genomic prognostic test has been approved by the FDA and others are in the works for multiple cancers.

Genomics can be used for early diagnosis, especially in the field of infectious diseases. Remember the gentleman who flew to Italy on his honeymoon but who had tuberculosis? It led to an international concern that he might have infected others and that his TB might be of the drug resistant variety. One of the problems was that it takes about six weeks to grow the TB bacteria in the laboratory and then, if present, another six weeks to test for antibiotic susceptibility. But genomic tests can speed that process up to just hours. The TB bacteria (Mycobacterium tuberculosis) has a characteristic genomic profile so, if present in a sample from the patient, it can be detected within hours. And since antibiotic susceptibly is driven by the bacteria’s genes, they can be analyzed at the same time. A huge improvement in time to diagnosis and getting the right drug started from the beginning.
We might want to know if we are predisposed to develop a certain disease later in life. It is possible that genomics can be of real assistance here; indeed this has been a major “promise.” It turns out that most of the common, important diseases such as diabetes and coronary artery disease have not one but vast numbers of genes that have some impact on their development. So we will not find a simple answer for many of these. But as more is learned it is very possible that each of us will be able to learn our relative risk to some important and common illnesses. If you knew, for example, that you were at increased risk of heart disease, it might be a stimulus to you to be more diligent in eating a Mediterranean style diet, exercising more often and looking for ways to control stress- and it would be an added inducement to stop smoking. Similarly, if you were at risk for early onset colon cancer, you might be more careful to eat a diet high in fiber and low in fat and begin having colonoscopies at an earlier age.

These are just some of the advances coming from genomics; expect to see many more because genomics represents a true revolution in medicine and we have only seen the beginning.

Here is a video on medical megatrends

Genomics– a Revolution in Medicine - Part I

My last post was about the coming medical megatrends that will have transformative implications for medical practice. To continue the discussion, let’s begin with genomics.

Little more than a decade ago, most people had never heard of the word “genomics;” today it is used frequently. It is indeed a revolutionary science that is and will transform medical research and medical care. To better understand how this new science will markedly change medicine, it is convenient to consider it through a few categories:

Pharmacogenomics
Nutragenomics
Disease classification
Disease prognostication
Early and rapid diagnosis
Prediction of diseases to develop later in life

Pharmacogenomics, the topic of this posting, can itself be subdivided into

Drug creation and development
Drug prescribing to achieve greater efficacy and fewer side effects

The concept of drug development using genomics is to “target” a specific function in the cell, usually an enzyme that is the proximate culprit in a disease process. Here is an example using chronic myelocytic leukemia.

Chromosomes occasionally break apart but the cellular repair mechanisms put them back together. Chromosomes are basically long sections of DNA with collections of multiple genes. One chromosome, #22, carries a normal gene known as BCR. We all have it, it is normal. Another chromosome, #9, carries a gene called ABL (and usually pronounced as “abel”.) As with BCR, we all have it and it is an important normal gene called a tyrosine kinase.

Imagine that some of Chromosome #22 breaks off such that a portion of the BCR gene comes with it. At the same time, Chromosome #9 breaks leaving ABL exposed at the end. Now, instead of the repair mechanisms putting the two pieces back where they came from, instead, the two pieces are “translocated” so that now the piece of the BCR gene is attached to Chromosome #9 next to ABL. This effectively creates a new fusion gene which we will call BCR-ABL. This additional material on the ABL gene is enough to change its active site such that it launches a cascade of additional proteins that cause continuous cell division thereby creating chronic myelocytic leukemia. This single leukemic cell divides without control until eventually the disease is manifested.

The concept of “targeted therapy” is to find a compound that blocks the action of this new abnormal protein without affecting other normal tyrosine kinases. As it turned out, Novartis had a compound on the shelf, created for other purposes, which fit the need. It binds to the BCR-ABL protein’s active site and effectively stops it from working. The cell now dies a normal death and the leukemia is rapidly brought under control with very limited side effects, especially as compared to the major side effects of cancer chemotherapy. Gleevec (imatinib,) the first of a number of now available targeted BCR-ABL tyrosine kinase inhibitors, has been very successful and has dramatically changed the approach to this otherwise fatal disease.

This is an example of knowing the gene that is abnormal, then finding its abnormal protein product and then finding or creating a compound that blocks its action, targeted to just that abnormal enzyme. Other examples to date have mostly been in the cancer field such as Herceptin (trastuzumab) for breast cancer. In the coming years there will be a wellspring of new compounds developed as the underlying genomic basis for many diseases are unraveled.

Genomics can be used not just to develop new drugs but to make the prescribing of drugs more effective and safe. Albuterol is a drug used for acute episodes of asthma. It works for most people but there are a few where it works less well and some where it has no effect at all. The problem is that the prescribing physician has no idea whether an individual patient will respond or not. Too bad for the non-responsive patient who does not discover this until during an attack in the middle of the night. The reason for non response is straight forward. Albuterol is inhaled and binds to a specific site, called a beta adrenergic receptor, on the cells that line the small airways. When this binding occurs, it leads to relaxation of the smooth muscles around the airways, relieving the asthma attack. This receptor is, in turn, created by a gene. In some people there is a “one letter” difference at codon #27 on the gene that codes for this enzyme. This seemingly minimal difference is enough to cause the substitution of the amino acid glycine for the usual arginine in the long chain of amino acids that make up in the beta adrenergic receptor protein. And this is enough that the Albuterol will no longer bind. Since we have two sets of chromosomes, one from Mom and one from Dad, then if one of our parents had this difference, we would still make some of the beta adrenergic receptor but not the full amount. And if both our parents had this different gene, then we would not make any of the typical receptor. So the former people respond somewhat but not fully to albuterol and the latter do not respond at all.

At some point there will be a simple test done in the doctor’s office to check for this occasional difference thus allowing the physician to prescribe a different drug up front.

Just as the doctor does not know if a drug will work or not in an individual patient, he or she does not know if a specific person will or will not have a side effect to a given drug. But if this could be known in advance, adjustments could be made and the side effect avoided. Here is an example with a cancer drug. 6-mercaptopurine (6-MP) is used for children with acute leukemia. The doctor calculates the correct dose based on the child’s height and weight and it is given orally. Normally, it is converted (metabolized) by an enzyme called cytochrome P-450 in the liver. But some people have a much reduced level of this enzyme because of a slightly different gene. When they take a normal dose of 6-MP the drug remains in the blood stream for much longer than usual leading to serious side effects. Now there is a simple test which prevents the child from receiving what could have been a fatal dose of 6-MP.

In the coming years we can expect to learn about new drugs developed using genomic approaches as with Gleevec and Herceptin; tests to advise the doctor as to what drugs will or will not work in a given patient and many new tests to prevent a patient from having an unwarranted side effect. Such is the power of genomics for the future; it will indeed be a revolution.

The next post will continue the discussion of what genomics is doing to change medical practice. There is more on this video

Advances Coming in Medical Science That Will Have a High Impact

There are a series of medical megatrends outlined in my book The Future of Medicine – Megatrends in Healthcare that will profoundly affect health care in the coming five to fifteen years and beyond. Some are due to the explosion of basic understandings of cellular and molecular biology. Others are related to advances in engineering and computer science. Here is a very brief overview.

These are the megatrends in medical care that are coming whether there is any change in health policy or not. First, expect that medical care will become much more custom-tailored to your personal needs. Genomics will allow you physician to select the most appropriate medication for you not just the one that on average works for most people. And he or she [more and more she since 50% of medical school graduates are now women] will also be able to select a drug that is less likely to cause a side effect as a result of you body’s reaction to it – all from knowing your genomic information. The surgeon will use your image such as a CT scan to program the simulator and practice the correct approach for your personal surgery. A vaccine may be made up specifically for you – a designer vaccine – to treat your specific cancer.

Second, expect that medicine will finally begin to focus more and more on prevention. . For example, genomics will allow your doctor to tell you at a young age if you personally are at high-risk for, say, heart disease and then prescribe a regimen of life style changes and medications selected specifically for you to reduce the risk. New vaccines will ward off serous infections and even many chronic debilitating diseases like Alzheimer’s.

Third, there will be major advances in repairing, restoring and replacing damaged and diseased organs and tissues. New surgical techniques will allow for remarkable repairs in a much less invasive manner; medical devices will allow the heart to beat regularly and stop the tremor and rigidity associated with Parkinson’s disease. And stem cells will allow for new tissues when old ones no longer function. Xenotransplantation – using an organ from an animal rather than a human – will be come available so that a person needing a heart or kidney will get it immediately and not need to wait and “hope” for someone else to die.

Medial information will be readily available no matter where you are. This will increase safety, convenience and improve medical care quality immensely.

Finally, care will become much safer as genomics adds to our knowledge of what drugs to prescribe, technologies such as simulators teach and demand competency and digitized medical information is readily available

These are the megatrends coming in medical care. They will occur and are coming in not that many years. Hopefully health care policy can advance as well and as fast, but that is much less certain.

For a video of these megattrends go here http://bit.ly/HnD3gE

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Use It or Lose It: The Price of Inactivity

Do you need a good incentive to exercise? Check out this set of pictures. They may well surprise you.

We all know we should exercise. It feels good during and we feel even better after. We know it burns calories and that our bodies were meant to be used. But all too many of us are sedentary; it just the result of modern life. One result, combined with eating too much, is that one third are overweight and one third are frankly obese. And many of us believe that as we age we will just naturally loose muscle mass and strength. It turns out that is just not correct. We can indeed preserve muscle mass and strength.
A really well trained athlete has little fat in or around his or her muscles. But a person that does not exercise sees his muscles wither and fat take up the space. That is the obvious conclusion from the images shown below.
More and more Americans are living into what used to be called “old age.” With older age often comes various illnesses, many of them chronic such as diabetes, heart failure or cancer. But these chronic illnesses are often preventable with a good diet and moderate exercise. So to is the “sarcopenia” or muscle loss that comes with aging in a sedentary person.

Wroblewski and colleagues at the University of Pittsburgh evaluated persistent exercise over the years. Their study was reported in The Physician and Sports Medicine journal, September, 2011 and sent to me by Frank Jannotta of Harbor Physical Therapy.

Five men and 5 women were recruited in each 10-year age category (40–49 years, 50–59 years, 60–69 years, and ≥ 70 years). Each was an avid exerciser. They were evaluated for their health history, exercise patterns, body composition using the “Bod Pod” and MRI scans of the thighs. The researchers found that despite the age differences, these individuals did not have a significantly different amount of intramuscular adipose tissue; their body fat, BMI, fat mass and muscle mass were all similar. Clearly, continued exercising into the 70’s maintained muscle mass in these individuals.
Here are three images taken by MRI scanning, i.e., a cross sectional picture. They are of the upper leg to show the quadriceps muscle, the large muscle on the front of the thigh that allows us to lift our leg and bend our knee when we walk or run.

The first image is of a 40 year old triathlete. The second is of a 74 year old sedentary person. And the third is of a 70 year old triathlete. The differences are obvious. Use it or lose it. Muscle to flab.

This proves that being older need not mean having no muscle tone. The difference between the two triathletes and the sedentary 74 year old are striking. It is clear that even an older person who exercises can maintain good muscle tone. And although this is of a triathlete, just good regular activity that combines both aerobic and weight bearing exercise will maintain those muscles up to the very last breath. And it means better health, long life, and much less chance that a fall will lead to a broken bone.

Use it or lose it. Here is the proof.