Chapter 29 Accommodating Your Biology

So if our biology was pretty much set in ancient days, what can we do to adjust to our strange new environment in which food is plentiful and no physical work is required?

 Mother Nature set up overlapping, redundant systems to make sure we seek out food and eat as much of it as possible. We have cravings that cause us to seek relief by foraging for food, and reward systems that give us pleasure while we are eating. And we are in an environment that exploits these cravings and reward systems.

 Decades ago, scientists began looking at the pleasure centers in the brain to find solutions to the problem of overeating. Through the ensuing years, they mapped the pathways and interactions of pleasure neuropathways that fire when we eat. They even created a species of mice that could not taste or smell so scientists could study food pleasures.

 What they found is when these little guys ate, their brain scans exploded with color in the pleasure centers of the “hind brain” even though they could not taste or smell the food they were eating. The conclusion is that more is at stake than the taste of food when it comes to our desire to eat. In fact, brain chemistry drives much of how we live.  And here we thought we controlled all this by just making decisions with our wonderful thinking “front brain.”

 Scientists theorized that those with a heavy biology may not produce enough of the brain chemical called dopamine when they are eating. This would mean these people would have to eat more to get the same amount of pleasure as a thin biology person would.  You will remember that we discussed the effect of dopamine in chapter 15 when we were explaining the addictive nature of sugar. 

 Let us think of it this way, a thin biology person and a heavy biology person eat the same sized chocolate square. Let’s say that when the thin person eats the chocolate, they get ten units of dopamine pleasure from the tasty, sugary delicacy. But when the heavy person eats the exact same chocolate, they get only five units of dopamine pleasure.

 Now, you’d think that with a low dose of dopamine pleasure, they wouldn’t be as attracted to the chocolate as the thin person, but that isn’t the case. Instead, the heavy biology person wants even more chocolate to get to ten dopamine pleasure units. The problem is the more chocolate they eat, the more

slowly those pleasure units accumulate. They can’t simply double the amount of chocolate to get double the pleasure points.

 Of course it isn’t just dopamine levels that cause us to become overweight. There are a host of other factors that cause us to either crave food or be satisfied while eating. There is constant communication between our stomach, fat cells, hind brain (our hypothalamus and brainstem), even our pancreas, gall bladder, and liver.

 For instance, when we eat food or drink liquids our stomach becomes distended, and this sends signals to our brain. Further down the digestive system, in our small and large bowel, hormones are secreted that tell our brain that all is well. Even our fat cells communicate with our brains to let us know that they are “stuffed” and we should stop eating and start burning calories. And you already know about the insulin and the effect of insulin resistance. And this is just the beginning of things that control our appetite and our fat stores.

 This means there are plenty of places where things can go wrong and cause us to get heavy. When one system becomes dysfunctional, it can cause problems in other systems. Similarly, though, when things are corrected in one area of the body, we’ll often see improvements in other systems. Which brings us back to pharmaceutical accommodation.

 Back in the 1950s, researchers discovered and developed a group of medications that stimulate the brain through several brain pathways that caused people to become satisfied with less food. They lost weight and reported that they had fewer food cravings for sugars and refined carbohydrates. This group of medications included phentermine, phendimetrazine, and diethlyproprion, with the brand names of Adipex, Ionomin, and Tenuate, among others. 

 This group of medicines were commonly used to treat obesity through the 1970s. In fact, they became a prototype for medications that augmented the pleasure centers of the mind. People had reduced food cravings, they eliminated unconscious eating, and even quit eating past when they were full.

 Unfortunately, during these early days of medication treatment for obesity, it was not understood that obesity was a long-term biological medical disease. We were still operating under the myth that obesity was a moral or societal problem. The Food and Drug Administration (FDA) approved this group of medications for only three months of use after which time the patient was thought to be cured. Authorities believed overweight people could maintain their weight loss through sheer willpower and fortitude. But of course, by now you know that obesity is based on a lifelong biology that does not work well in our current environment. A short-term fix will not have long-term success. It’s a little bit like giving a diabetic patient insulin for a few months and expecting them to be cured of diabetes.

 Researchers later noticed that people had more success when they paired  phentermine with  medications that stimulated another pleasure hormone called serotonin. You may have read about this hormone in relation to the treatment of depression. One of the first medications in this class was known as fenfluramine. Through the subsequent years, there were a number of similar brands and formulae that were lumped under the term “Phen-Fen.”  It’s important to note that this was back when fewer than ten percent of Americans were significantly overweight. 

 Because both of these medication groups have broad, neurological effects, it appeared that there were a number of significant side effects, particularly with patients who were overly sensitive to medications in the serotonin and phentermine medication families.  These hypersensitive people could experience an increase in blood pressure and pulse rate. But these side effects were generally minor compared to the effects of obesity on a person’s overall health. For a few people though, the stimulation of the metabolism caused palpitations and dangerous elevation in blood pressure. I have also seen a few changes in personalities in patients. A person who is usually calm can become “snappy” toward others. And a few older men may struggle with urinary retention.   In 1997, the Mayo Clinic reported 24 cases of a cardiac mitral value disorder in women who were taking phentermine and fenfluaramine medications. It was alleged that as many as 30% of all of the people taking these two medications could develop mitral value disease.

 Unfortunately for the history of obesity science and treatment, this action was not based on the usual standard of medicine.   No double-blinded placebo controlled intervention studies were done to assess the presence or absence of mitral value disease before the medications were begun. The study was simply offered as “antidotal” evidence.

 In fact, insulin resistance, hypertension, and diabetes are all closely linked to mitral valve disease. This means, from a scientific perspective as well as medical standards, we’d have to ask whether it was obesity or Phen-Fen that caused the mitral valve disease in the 24 patients. And given the health benefits for thousands of people who lost weight with this combination of medications, we would also want to research safe limits for those with and without mitral valve disease.

 So, without trials or scientific proof, a correlation between fenfluramine and the 24 cases was declared and published. Class-action lawyers got involved, and the FDA pulled fenfluramine from the market.

 Fortunately, the phentermine class of medications were deemed safe and are still available. They are the most commonly prescribed medication for long term weight loss.

 In 2016, the Endocrine Society appointed a task force of experts, methodologists, and a medical writer to formulate guidelines for the pharmacological treatment of diabetes. This task force concluded that during the 20 years that phentermine has been prescribed for off-label, long-term treatment of obesity, there have been almost no reported serious side effects. So even though we don’t have long term studies proving safety and effectiveness, it seems reasonable to continue using these medications. However, as with all medications, this class of drugs must be used according to the guidelines established for all anti-obesity medications.

 It’s also important to note that despite being in a restricted medication class, there has been no evidence that the phentermine type  medications are addicting. In fact, the Obesity Medical Association has made careful inquiry at national drug rehabilitation facilities, and they have not found histories of any patient being admitted for drug addiction to phentermine.

 I recommend discussing Phentermine with your physician if they have been informed about the biology of obesity and have experience with the pharmacotherapy for obesity. Because of the media hype decades ago over PhenFen, some physicians don’t understand how safe phentermine is. Rest assured, there have been randomized drug trials that document the overall safety of this medication. That said, there are a few side effects, like with any medication. If you use this medication, you may note some dry mouth symptoms which will remind you to drink plenty of water.  During weight loss, drinking a lot of water will facilitate the disposal of the waste products. .

 Perhaps ten percent of my patients experience nervousness when taking Phentermine. To make sure you are not one of these people, break the tablet in half. Take half the first day and the second half the next day. On the third day, take half the pill in the morning and the second half in the afternoon. Then, on the fourth day, take the whole pill. You will feel more energy, and hopefully you’ll also enjoy the benefits of phentermine without any uncomfortable side effects.

 Understand that you will probably be taking this medication the rest of your life. If you quit taking it, your obsession with food will return. Think of phentermine as eye glasses. While you wear them, you see fine. But take them off, and you will struggle to see clearly.

  During the last 10 years, a number of newer drugs and drug combinations have been approved by the Federal Drug Administration. The medications that can be taken seriously all address the central nervous system where the “obese biology” resides.

 For instance, Qysemia combines two older drugs that are now generic: phentermine (Adipex), and topiramate (Topramax), used for pain syndromes and seizures. Studies show that at the one year mark, Qysemia resulted in 8.6% more weight loss than lifestyle changes alone. It’s important to note that topiramate has been associated with birth defects; therefore, it should be used with caution by women of child-bearing age.

  Also, the serotonergic medication lorcaserine (Belviq) can be used by those who can’t take phentermine type medications because of cardiovascular risks that are not well controlled such as uncontrolled hypertension. This medication has no stimulator capacity, but it does interact with the appetite centers in the brain.

 Contrave is another combination of two older medications, buproprion (Wellbutrin) and naltrexone (Vivitrol). Buproprion raises dopamine levels, and it has been used as an antidepressant. It also helps people quit smoking. Naltrexone is a complicated medication that has been used to treat a number of conditions from codeine addiction to fibromyalgia. Contrave has proven to be helpful when other medications lose their effectiveness.

 What’s frustrating is that these medication (Qysemia, Belviq, and Contrave) result in only modest weight loss and appetite suppression. On the other hand, we have to consider the biology and environment that they are working against. From the biological side, there are so many variables to address, from insulin to leptin to ghrelin. Then there is what is going on with our gut bugs and microbiome. On the environmental side, you will remember that we have over 88,000 packaged processed foods, 82 percent of which have sugar, all priced lower than wholesome foods. When we take all this into account, it’s a wonder any medication can help us lose weight.  We must also remember that a 5-10% weight loss results in a 50-60% improvement in the risk factors for the chronic diseases such as diabetes, hypertension, heart disease and some cancers. 

 Right now, your brain chemistry isn’t helping you achieve your weight-loss goals, but with medication, you have a fighting chance. You’ll be accommodating and working with your very own biology to create success.

If you are a thin biology person who is “unaware” until now that you are 10-15 pounds overweight, you may be wondering if anti-obesity medications are your answer as well.  Well the answer is clearly no.  The FDA has made very specific limitations to the use of anti-obesity medications and as with all medications, they should not be used unless the benefits outweigh the risks.  Anti-obesity medications can be used when the BMI is greater than 27 with the presence of what are called co-morbidities.  These problems could be high insulin levels and pre-diabetes or hypertension or sleep apnea.  Even osteoarthritis counts.  If your BMI is greater than 30, medication is definitely approved for you if all other conditions are equal. 

Many of my patients have asked, “What happens after I lose weight and my BMI is no longer qualifying?”  Your beginning weight is the qualifier.  Obesity is a lifelong disease and long term medication may be essential.  It isn’t cheating to take medications, and it certainly isn’t a weakness.  You are who you are, with the biology you have in the midst of an awesome Clash. Medications simply help you reach a healthy weight by accommodating your reality.

So don’t think of medications as a quick fix. All they do is help you with your brain chemistry so that you can make better choices. They won’t keep you from reaching for the cookies on the plate; what they will do, however, is help you stop at one. Over time, you may even be able to walk right past the plate of cookies.