Beyond Weight Loss and Diabetes, GLP-1 Agonist Medications Could Be The Biohacking Tool We Have Been Waiting For:
Homo Sapiens, from the Paleolithic Era to modern times, have survived and thrived because of our ability to adapt to repeated environmental pressures. Genetic adaptions that improve health and promote survival, generally take many thousands of generations. However, during the last 50 or so years, modern leisure advances have affected our lifestyle so rapidly and radically, the human genome has not been able to keep up. We are still hard-wired for survival as if we were still living in caves, fighting off saber-toothed tigers. Our software has not been updated yet. It is still set to store extra fat and fluid whenever possible to avoid starvation and dehydration in times of famine and drought.
We are still genetically programmed and neurologically driven to seek salt, sugar and fat for consumption despite there being an excess of each available at all times.
Eight thousand generations ago, in the Paleolithic era, approximately 75% of deaths were caused by infection, most commonly were likely diarrheal diseases that resulted in dehydration and starvation. Life expectancy was approximately 33 years of age. To perpetuate our species, the genes of our ancestors mutated over time, accumulating beneficial mutations to protect against food and water shortages, infections and hemorrhage from traumatic encounters (predators, enemy cavemen).
Our early human ancestors especially craved the tastes of sugar and fat and would gorge when these rare, life-saving items were available. The caveman genotype was programmed to help store a little extra fat whenever possible. This explains why at least 25% and perhaps as much as 80% of modern obesity and type 2 diabetes is heritable.
Our ancestors loved the taste of salt, too. This, combined with thirst and our renin-angiotensin-aldosterone axis, helped avoid dehydration during water shortages, diarrheal illnesses, and extensive periods of exercise. However, with plenty of salt and water, this is not so beneficial now. Rather, it promotes high blood pressure and its mortal effects.
Because almost 15% of Paleolithic humans died violently, they learned how to be fearful and submissive in order to minimize violent confrontations when neither fight nor flight was possible. To avoid severe bleeding, whether from trauma or childbirth (which probably killed approximately one mother in 100), their genes evolved toward efficient clotting. Sadly this clotting benefit is not so helpful with later-in-life thrombotic diseases like stroke and heart attack.
Constant modifications of our genome are always occurring in response to an organism’s stressors. Modifications can be epigenetic (regulates the expression of the genome) or genetic (absolute changes in structure or quantity of the DNA that makes up the genome). Epigenetic and genetic modifications give us structural, behavioral and functional uniqueness or phenotypic variability. Over time, the traits that favor thriving and surviving of an individual and of the species as a whole, become “selected” and appear more frequently with subsequent generation, while the less desirable traits begin to vanish.
It takes thousands of generations of a species as complex as ours to evolve genetically, especially as we lengthen the time between generations with later childbearing, longer life expectancy and increasing numbers of ways to manipulate fertility. Many millions of babies are born every year via assisted reproductive technology, creating a whole subset of our population who’s existence is not the result of winning an “in utero” (in vivo) amazing race through surviving naturally applied environmental pressures. Rather the gametes and embryos in the lab (in vitro) have much less required of them to survive. The ones chosen to finish the race with in-vitro embryo, oocyte, and sperm selection are chosen for qualities and traits that might not have been selected naturally. Either random guessing or selection based on individual desired physical and medical traits genetic traits identified with genome sequencing prior to embryo implantation in the mother’s uterus.
Thus, the evolutionary concepts of Natural Selection and Sexual Selection by evolutionary biologist Charles Darwin, now have another variable to add to the equation…..Artificial Selection, meaning the in vitro selection of gametes and embryos in the fertility, lab either by mostly random guessing or with scrutiny of the genetic sequence prior to embryo selection. The process also loses much of the natural pressure to evolve as we develop ever more ways of getting around our evolutionary unfitness. Perhaps in time we will take over our own evolution by leveraging advances in the fields of genomic, epigenomic and proteomic editing technologies. I imagine the lengthy evolutionary process could be whittled down from many 100’s of thousands of years, to a few generations with emerging technological innovations.
But for now, we still have epidemic rates of lifestyle-related diseases, such as overweight and obesity, diabetes, cancer, cardiovascular disease, and neurodegenerative illnesses, as examples of what happens when environmental factors change more rapidly than we can evolve. Indeed, the current facts are that up to 90% of us will end up living with and managing one of these lifestyle-related diseases.
Our modern lifestyle of longevity, material abundance, western diets, and increasing leisure behavior has developed over about six generations, which is far too short a time for our genes to adapt. This mismatch between our genes and our modern environment helps explain why approximately 38% of Americans are now obese, 12% to 14% have diabetes, one third have hypertension, and 25% die from thrombotic heart disease and stroke. Anxiety and depression, linked to our ancestors’ tendencies toward fear and submissiveness, are the 9th and 11th leading causes of disability-adjusted life-years lost in the United States, and suicide now kills far more Americans than murder and war combined. Other leading modern causes of death and disability, such as cancer, neurodegenerative diseases, and musculoskeletal maladies, may not be as specifically related to modern gene–environment mismatches but rather represent previously indifferent genes that had not been widely exposed to the consequences of aging in prior generations with shorter life expectancies.
However, our future is more in our hands than any other time in human history. Our rate of scientific discovery is moving at lightening speed in many areas. It has been our technological advances that have brought us to our current state of health and it will have to be technological advances that bring us back to health. We have crippled ourselves by exploiting the complex and brilliant design for fitness and survival, built into our genetic code. We are programmed to not have to think about our food, activity, and even sexual choices. We were given the tools to naturally make healthy choices as prehistoric humans. But with time and evolutionary help, we became smarter and smarter and learned how to outlive our “natural expiration date” and to prevent and treat deadly infections and t0 build ways to protect ourselves from violence and danger. Leading to our current state of obesity, new diseases and inappropriate immune function.
To reverse our current state of health will take more than willpower. We have been brilliantly designed to survive in difficult environmental conditions. We are programmed, within the most primitive parts of our brain, to behave according to our instincts. Many of our instinctual drives are still critical to our health and well-being—however, many of them are now more likely to make us sick rather than assist in our survival. Survival means something very different now, except the instinct for it is just as strong. It is possible to influence what epigenetic modifications occur to our genome through manipulation of factors we know enhance our organism’s adaptability in a molecular epigentic way. What we do to and for our bodies does effect the genetic blueprint we pass on to subsequent generations. Hormetic practices are one example…….fasting, cryotherapy, heat therapy, even meditation and yoga can all play a role in epigenetic modifications with resultant positive effects on our organism.
Hormetic practices are but one of many ways we can positively “bio-hack” our genome to get the most out of it while limiting much of the negative inherited traits. Gene expression can be turned on or off through epigenetic modifications triggered or supported by hometic variables, bio-identical hormones, immuno-modulators, neuro-modulators, endocrine-modulators, restriction or supply of essential nutrients and food types, microbiome support and manipulation, use of autologous growth factors and stem cells, and dietary choices. The challenge now is to figure out the right balance of modulation of our instincts, biochemical processes and immune behavior.
DIET AFFECTS THE HUMAN BODY IN MORE WAYS THAN YOU THINK
Beyond energy and building supplies, some of the molecules in our foods directly communicate with our genome invoking epigenetic effects, resulting in variable expression and inheritance patterns of genetic data. This differential expression of phenotypic traits is what helps us adapt to variable environmental factors as well as effecting what is passed on genetically to our progeny. This complex relationship is the essence of nutrigenomics.
Daily communication between diet and the genome/epigenome modulates gene expression in metabolic organs such as fat tissue, skeletal muscle, liver, pancreas, brain and the immune system. The cellular and molecular biology behind these gene regulatory processes maintains homeostasis. This mechanism is what prevents the development of “life-style diseases” such as obesity, diabetes, cardiovascular disease and cancer.
Since the origin of Homo sapiens, most of these pathways of communication between nutrients and genes have not changed. However, our genome has experienced a series of evolutionary pressures caused by environmental changes including the transition from a hunter-gatherer lifestyle to an agricultural one. Human populations have responded to these challenges through specific anthropometric adaptations such as skin color and body height, but also through variation in dietary intake and differential resistance to complex diseases such as cancer and immune disorders. Therefore, insights into the variability of our genome/genome in the context of individual risk of developing complex diseases help us understand the evolutionary basis of how and why we get sick. The key to effectively helping people get well lies in how well the cause of the sickness is understood.
HUMAN LIFESTYLES ARE CHANGING TOO FAST FOR OUR GENOME TO KEEP UP
The adaptation rate of the human genome to environmental changes usually takes many generations, or hundreds to thousands of years. However, only during the last two generations, or about 50 years, human lifestyles including eating habits have changed so rapidly and radically that most of us are not genetically/epigenetically prepared for the challenge of a “Western” diet combined with a sedentary lifestyle. Indeed, the current facts are that up to 90% of us will end up living with lifestyle-related diseases, such as metabolic syndrome (e.g. overweight and obesity, diabetes, high blood pressure) which herald the onset of worse pathology to come. Chronic inflammation in all parts of the body results from the derangements seen with metabloic syndrome. Then dependent on individual genetic predisposition, pathology develops in the form of cardiovascular disease, neurodegenerative disease, cancer and organ failure secondary to the chronic inflammation. The resultant fibrosis in various body parts causes dysfunction of the organ involved and eventually death. It is estimated that 50% of all human mortality is the result of fibrosis from chronic inflammation.
The genome/epigenome has not kept up with adaptation to the modern diet. For example, humans have been eating low-salt products for most of time. – As a result, our body has developed an efficient system for absorbing this salt from our diet, which was essential in ancient times, but creates many problems today. Today’s diet contains a lot of salt – excess salt causes high blood pressure, which kills 10 million people worldwide each year.
BEYOND WEIGHT LOSS AND DIABETES, GLP-1 AGONIST MEDICATIONS MAY SAVE THE HUMAN RACE
In response to a growing global need for a solution to this problem, GLP-1 agonist medications have emerged as powerful players in combating our species’ accelerated rate of lifestyle changes that have not been so healthy for us.
As a modulator of metabolism of glucose, a modulator of satiety, a modulator of the behavior-reward axis, a modulator of endocrine systems and a modulator of immune functions, the GLP-1 agonist medications have the potential to help us help ourselves out of this absurd scenario we have created ourselves to exploit the very processes designed to promote our health. That exploitation has back-fired, so it is now our responsibility to fix it or suffer the consequences of eventual extinction of the human race.
In addition to enhancing glucose metabolism and appetite suppression in diabetes and overweight and obesity, the new GLP-1 agonist medications seem to have promising effects on multiple other lifestyle-related illnesses and behaviors. Specifically, mental health conditions such as depression, anxiety, and obsessive-compulsive disorder, as well as addictive conditions involving the dopamine reward system of the brain such as alcohol use disorder, drug addiction, smoking, social media addiction, and anything else that triggers a burst of dopamine to encourage the behavior to be repeated again. There is also emerging evidence of neuroprotective and cardioprotective effects by reducing chronic inflammation systemically.
Initial reports of halting progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s and improving cognition unrelated to gylcemic effects are very exciting. Especially because, when taken correctly under a knowledgeable medical professional’s supervision and guidance, the GLP-1 agonists seem to be extraordinarily safe.
If quality of life is important to you and exploring safe and innovative ways to get as much of an edge up as you can in the health and longevity game, you might consider adding GLP-1 receptor agonists like Tirzepatide and Semaglutide to you regimen. There are many doctors and clinics offering these options today. The options are the branded medications Mounjaro, Ozempic, Wegovy, Zepbound. These are typically only covered by insurance in specific scenarios like diabetes, morbid obesity or overweight with significant obesity related diseases. It will also depend on your insurance plan details and requires a preauthorization process from your doctors office. Still, many get denied coverage despite good arguments for medical need.
Another ongoing issue is supply. There has been a shortage of one or all of these medications for some time now, making them hard to find often even for those dependent on them for management of diabetes. For this reason, the FDA put these medications on the national drug shortage lists, which makes it possible for compounding pharmacies to offer generic versions of them despite the fact their patents have not expired, which is what typically prevents production and sale of more cost effective generic versions of medications. Once a drugs patent runs out, then generics are not an issue.
The generic versions of these medications are compounded and sold by compounding pharmacies. There are many wonderful things about compounding pharmacies. I have worked with many and have learned how to vet them for quality, consistency and safety. I cannot vouch for all compounding pharmacies, but I can for the ones we currently work with. They produce an effective, safe and consistent product every time. They provide us with batch analysis details and adhere to the highest standards. We currently prefer Tirzepatide from our pharmacy as we have seen it work better than Semaglutide, with more weight loss and leess incidence of side effects. Compared to Tirzepatide from other pharmacies, it has also proven superior as well.
During my career as a physician, there have only been a handful of advances that I have been truly excited about. For me to be interested in new medical treatments or new uses of existing ones, they must satisfy a few very important qualities.
First, they must be extraordinarily safe with a very low risk of serious long term sequelae. This is actually a very rare thing in medicine. Many of the seemingly most benign therapies, such as antibiotics, can have life-threatening and life-long consequences for some. There is almost nothing in medicine without some degree of risk relative to side effects, but there are a few with enough historical safety data that are also extremely effective in most patients.
Secondly, it must be effective in a way other treatments are not…meaning either fill a gap where other existing treatments fail to solve a problem or provide a solution where there is not already a good one. In other words, they must be somehow better than what is already available.
Lastly, it must be practically possible for most patients and most physicians to utilize. For example, if the treatment can only be done in a hyperbaric chamber by a interventional radiologist in Europe, its probably not going to be able to help many people. But if almost any licensed physician can learn or be trained to evaluate a patient for the condition and appropriateness of the treatment and how to provide the treatment, then the masses can benefit.
Examples of the above are most regenerative modalities in my office, such as PRP (Platelet Rich Plasma), Bio-identical Hormones, Hyaluronic Acid Fillers used properly, and Botulinum Toxin used. Additionally, there are a few therapeutic medical devices I utilize regularly- shockwave therapy and transcutaneous electromagnetic neuromodulation (EmSella and EmSculpt) are examples of safe and effective devices that meet the above criteria. These modalities or combinations of them have changed more of my patients lives for the better than I can count. Interestingly, despite the extraordinary saftey profiles and remarkable results in all parts of the body we see and research supports, none of these modalities are currently covered by insurance.
After extensive experience with with GLP-1 receptor agonist medications, I feel comfortable adding them to my list of therapies that fulfill my criteria for how I care for my patients. They are extraordinarily safe when given to the right patient and monitored appropriatley. They are even safer with some of the methods I have developed to mitigate side effects and improve eficacy over the standard protocols. For the first time in my career in medicine, I am seeing patients lose weight they have been unable to lose no matter what they have tried and they are able to keep it off when they follow our plan. The result has been incredible. I’ve seen hypertensive patients get off their medications, hyperlipidemic patients have normal lipid profiles, patients with autoimmune condiitons improve or go into remission and depression and anxiety symptoms get significantly better. When people’s health improves, their life improves in every area. Relationships get better, careers improve, and happiness replaces suffering.
Healing ‘dis-ease’ can be more than simply ‘easing’ suffering, it can be remarkably transformative. If you think I can help you or someone you love to lose weight with GLP-1 medications and restore your health and vitality, please visit our Medical Weight Loss page or call our office (210) 483-6255 to get started.
