David Brown, a bariatric surgeon specializing in weight loss and metabolic surgery, discusses the increasing use of weight loss injections like Ozempic, Mounjaro, and Wegovy. He emphasizes the importance of understanding the physiological effects of these medications, both for physicians prescribing them and individuals considering their use. Brown highlights a significant paradox and potential long-term risks associated with these injections.
The Weight Loss Paradox
A key observation is that individuals with less weight to lose often experience more dramatic results from these injections compared to those who are severely overweight or obese. Furthermore, Brown argues that those who respond most impressively to the injections may be at a higher risk of experiencing more severe side effects in the long run.
Reported Side Effects
Several concerning side effects are being reported, including:
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Muscle Loss: Clinics are observing a significant loss of muscle mass, sometimes accounting for 40-50% of the total weight loss. Studies published in JAMA and other journals also support these claims.
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Gastroparesis: An increasing number of individuals are experiencing gastroparesis, a partial paralysis of the stomach, leading to persistent nausea, vomiting, and difficulty eating, even after discontinuing the medication.
How the Injections Work: A Physiological Perspective
These injections contain synthetic forms of GLP-1 (glucagon-like peptide-1), a naturally occurring peptide and neurotransmitter in the human body. Normally, GLP-1 plays a crucial role in signaling between the gut and the brain. These injections flood the system with high levels of this synthetic peptide, essentially using a neurotransmitter as a hormone.
The Brain-Gut Connection
The brain acts as a central computer, controlling appetite, metabolism, cravings, and other vital functions. The gastrointestinal tract, with its extensive surface area packed with enteroendocrine (neuropod) cells, provides critical input to the brain.
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These specialized cells act as sensors, detecting nutrients and releasing neurotransmitters to signal to nerve endings connected to the vagus nerve.
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The vagus nerve serves as the primary communication pathway between the gut and the brain.
Bypassing the Natural Pathway
Weight loss injections containing synthetic GLP-1 bypass the normal physiological route through the vagus nerve. Instead, the high levels of GLP-1 in the blood cross the blood-brain barrier and directly activate receptors in the brain. The doctor argues that the effect of the drugs using the normal system and what's happening in the injections is not the same,
- This disruption of the natural signaling process is concerning because the distribution and function of GLP-1 receptors in the gut differ from those in the brain.
Exogenous Insulin
Dr. Brown draws a parallel to type 2 diabetes, where increased insulin levels are common. Typically, the medical approach for the problem of elevated insulin is to give more insulin, which can improve blood glucose levels. However, the bigger picture can demonstrate significant problems and increase mortality rate.
The Autonomic Nervous System and Its Role
The autonomic nervous system, responsible for involuntary functions like digestion and heart rate, has two branches:
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Sympathetic Nervous System: The "fight or flight" response.
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Parasympathetic Nervous System: The "rest and digest" response, crucial for digestion, healing, and restoration.
In conditions like obesity, diabetes, and aging, there's often an imbalance with increased sympathetic activity and decreased parasympathetic activity. The vagus nerve plays a central role in the parasympathetic system.
Dysfunction and Muscle Loss
Brown suggests that bypassing the vagus nerve with these injections contributes to its dysfunction. This "use it or lose it" principle applies, leading to autonomic nervous system imbalance and, consequently, muscle loss. He posits that by bypassing the vagus nerve and its normal function, that it may become even more dysfunctional. This is also why the stomach paralysis issue is rising.
Heart Rate Variability
Heart Rate Variability (HRV) is a measure of the balance of the autonomic nervous system. Studies are showing that those taking these injections are experiencing lower HRV, indicating a decreased function of the parasympathetic nervous system.
Implications and Cautions
Dr. Brown argues that these injections may accelerate the aging process, particularly in those with otherwise healthy metabolisms. He highlights that the initial studies focused on individuals with existing metabolic diseases, potentially masking the risks for those using the injections solely for weight loss.
The healthiest people may respond best to the injections because they don't have the GLP-1 resistance. However, those people are at a higher risk for vagus nerve damage and worse side effects.
He urges doctors to understand this physiology and warns that individuals ordering these medications online may not be aware of the potential long-term consequences. He believes cognitive decline is possible as a result of using these injections.
He posits that while he may be biased as a bariatric surgeon, he notes that bariatric surgery has better results because bariatric surgery restores the vagus nerve function, while the injections bypass it.