Nozempic: Meandering Away From Root Cause Medicine AND a Call to Action for RDNs & Nutrition Experts

By / Bitter foods, Diet, glp-1, Nutrition, Root Cause, Weight loss

With the explosion and ensuing rampant use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for weight loss, it may be time for a reminder of what functional nutrition is, what makes it a more advanced and thorough approach to health, and what our dictum is as practitioners, according to ethics, morals, standards of practice, and informed consent. With approximately 50% of the population eligible and interested in taking these medications, it is absolutely imperative that RDNs and nutrition experts inject themselves into the conversation.1 Pun intended. While our approach is patient-centered, thus imploring us to meet clients where they are, we also should understand that giving a supraphysiological dose of a manmade hormone does not fix diabetes, does not increase long term health, is not a guarantee for permanent weight loss, and importantly, is not root cause medicine. While there are checks and balances in place to assure our use of food, supplements, and various integrative therapies are evidentiary, those same standards should be applied to conventionally used interventions. In other words, and with equal justice, there are plenty of rules and regulations, at times with hyper-reactivity, regarding archaically called “alternative” use of what truly creates health, ie, diet and lifestyle. However, where are the same standards for pharmacological interventions, especially those that intersect with metabolic health—our area of expertise—and have potentially significant other detrimental effects? In fact, the Academy’s recent paper states “RDNs can also advise clients to consider safety of obesity medications.”2

Nutrition Support

We acknowledge as integrative practitioners that at very specific times, for the right patient or client, pharmaceuticals may be needed in certain circumstances to be used as a bridge or to assist a return to homeostasis. In some functional medicine practices, holistic protocols that include personalized GLP-1RA dosing, nutrition and lifestyle recommendations are having success. Importantly, when there is accompanying diet and lifestyle support, some of these deleterious effects may be mitigated. It is vitally important that RDNs and nutrition experts have a supportive and prescriptive role for the most optimal outcomes. However, for the majority, this nuanced approach is not how the drug is being used. Physicians are offering or being asked for these medications, and they are being doled out without this crucial personalized support. RDNs should be knocking on physician’s doors—not waiting in the wings to be asked, but offering their services to every medical practice in the country.

What is GLP-1?

GLP-1 is a peptide and enteroendocrine hormone naturally produced in the intestine, brain, and pancreas in response to food intake and has a critical role in regulating blood sugar, appetite, and digestion. Specifically, it enhances insulin secretion, inhibits glucagon, and slows gastric emptying thereby creating a prolonged sense of satiety. Semaglutide is a GLP-1RA, sold under the brand names Ozempic for diabetes and Wegovy for weight loss, and is a synthetic recombinant version with a lipid side chain and phenol and amino acid substitutions that enable it to stay in the blood stream for up to 7 days.3 (A chart outlining a complete list of medications can be found in resource 1). The longer acting component is the key to semaglutide’s apparent therapeutic effect as GLP-1 is naturally degraded by dipeptidyl peptidase-4 (DPP-4) enzymes within minutes. It was, in fact, discovered via a long-acting peptide in the venom of a lizard called the Gila monster.4

Co-effects

While these peptides have been used for diabetes management for the past two decades, they have only been used for obesity in the last two years; thus safety or effectiveness long-term is unknown.5 In the semaglutide trial, up to 75% of participants experienced nausea, vomiting, diarrhea, abdominal pain, and bloating.6 Many have stopped for these exact reasons. Another 10% experienced gastroparesis, kidney disease, and pancreatitis. There is a black box warning for thyroid cancer and pancreatic cancer, and the FDA has added additional warnings of suicidal ideation and ileus (intestinal blockage). Additional reports include constipation and reflux. As always, depending on individual health status, responses are variable. More complete risks and precautions for all ages are on the manufacturer’s site.7

Additional Physiological and Psychological Considerations

There are GLP-1 receptor sites in the heart, lungs, brain, muscles, and pancreas, therefore affecting all systems of the body. The rapid degradation of GLP-1 is a regulatory step that has evolved over eons to elicit the exact relationship between food, metabolism, and health. How an injected dose lasting 7 days, as opposed to minutes, will affect these organs long term is unknown. Further, there are over 7000 peptides and an orchestra of 20 or so enteroendocrine hormones along with GLP-1 such as peptide YY (PYY), vasopressin, gastric inhibitory polypeptide (GIP), ghrelin, somatastatin, etc that are released when we eat.8 There are orchestrations and communications that cannot be mimicked by giving an injected versus consumed dose of a single peptide overriding and suppressing the very process it means to activate. Over time, will there be other hormone imbalances and missed or dampened signals affecting other bodily functions? At best and for many, taking a weight loss drug is a bit of a medical experiment.

Most of the US population is deficient in one vitamin or mineral, and this is based on older data.9 With less intake, there will be greater nutrient deficiency. The body will steal what it needs, most notably from muscle, but from other areas of the body as well. Less adequate nutrition will cause other systemic, tissue, or cellular effects depending on individual health status.

We know that there is constant communication between the gut and brain via the vagus nerve. Through these medications, food remains in the stomach, paralyzing and/or slowing the intestinal process, signaling the brain that you are full. However, this metabolic trickery is an interruption to mind-body-brain circuitry. Potentially, it is creating a dysfunction, a change in perception, and a redirect that does not exist naturally. As a result, GLP-1RAs are also credited with quieting food noise, or decreasing brain chatter about food. However, food noise is often a very real response to hunger and under-eating, which can lead to longer term undernourishment. Regardless of body size, these medications give people permission not to eat. What about other reasons for food noise? Processed, highly palatable foods are scientifically designed to keep you obsessed, addicted, and coming back for more. What about pleasure from food? Anecdotally, some say that although the food thoughts disappear, a kind of gray, lack of pleasure in life appears. Similar to bariatric surgery, if food was potentially being used as form of emotional comfort and support, and that is no longer an option, without addressing underlying issues with counseling and guidance, what will become the substitute?

Research thus far reports that a majority regained the weight once the medication was stopped, or, after taking it for one year, the weight loss plateaus. With the regained weight, any benefits purported (eg, cardiometabolic, glucose levels, blood pressure, cholesterol) all worsen.10 This doesn’t consider any psychological harms from weight regain and cycling. Not only does this point to the need for counseling, support, and diet and lifestyle change, but it leads physicians to respond to these issues by prescribing for life. This then leads to further indoctrination that medications are the way to health and a first line of defense—especially concerning when given to children. Importantly, this robs the individual of their unique and empowering health journey, skipping potential lessons learned and habits formed about cooking, nutrition, and health.

What IS the Root Cause?

At present, 88% of the population is metabolically unfit due a multiplicity of factors including a toxic, overly processed food environment, a collective dysbiotic microbiome, environmental obesogens, circadian rhythm disruption, disconnection from nature, and more. Ultraprocessed foods make up 70% of the food supply and do not provide the body with the necessary information for sound metabolic health.11 This imbalanced diet, or the Standard American diet (before ultraprocessed foods became the title), induces alterations in the gut microbiome that affect not only GLP-1 but the entire group of enteroendocrine hormones, bodily systems, blood sugar balance, and inflammatory processes and has created what has been called a pandemic of obesity and ill health. Not coincidentally, 70% of the population is also overweight or obese and are on at least one medication.12 If we are just speaking of GLP-1, which is only one hormone important to metabolic function, it follows that GLP-1 mechanisms will be reduced or altered in some way.

Ideally our body makes all we need to make as long as it is given the correct information—ie, food and all of its constituents, phytochemicals, polyphenols, vitamins, minerals, pre- and probiotic fibers—which enables a level of health greater than one injection could confer. Thus, this true misinformation from the diet and lifestyle is causing dysbiosis, disharmony, dysfunction and logically, a decrease in GLP-1 production. If root cause is the goal, then we must look upstream to the dietary signals, or lack thereof, that regulate these systemic processes.

Increasing Endogenous GLP-1: The #1 Missing Food in Modern Diets

To repeat ad nauseum, functional nutrition is an approach and philosophy that personalizes diet and lifestyle recommendations based an individual’s specific biology and biography in order to restore physiological function and vitality. As we are nutrition experts, it is almost an unwritten but explicit tenet that we use food or diet first, before supplementation or other integrative therapies. We inherently and passionately recognize the synergistic and transformative effect of food in its ability to not only prevent disease but create health. We’ve been witness to this power, in ourselves and for clients, throughout our entire careers. Therefore, it is our first and foremost duty as nutrition experts to be the champions of supporting endogenous production of GLP-1s from diet. Food first. This statement needs to be repeated, but in this age of pharmacotherapy, it falsely appears radical.

There are five universally accepted tastes that stimulate and are perceived by our taste buds: sweet, salt, sour, umami (savory), and bitter. They each have their own intestinal receptors that induce the release of different hormones. We ingest most of these flavors often, with a heavy collective penchant for sweet and salt. However, the most ignored flavor, and therefore the most missing food in modern American diets, are bitter leafy green vegetables. Is it too much irony and coincidence that the most missing food in the American diet is bitter greens, and bitter taste receptors, called taste receptor type 2 (TAS2R), are the central activators of GLP-1 release?!12-13 It has been known since ancient times that bitter gourd or melon helps to control blood sugar and therefore GLP-1 activation.14

Most of the population gets bitter from coffee and chocolate15 (or cacao), but we are missing many of the fruits, vegetables, herbs, and spices that naturally release GLP-1, like collards, arugula, radicchio, watercress, cabbage, grapefruit, dill, coriander, ginger, radish, olives and many more that any Google search will reveal. The majority of these bitter foods contain polyphenols and flavonoids, compounds in plant foods that supply their rich color and provide a myriad of health benefits. Polyphenols stimulate the L cells to release GLP-1 and inhibit DPP-4, thereby increasing its hang time, and has positive effects on insulin.16 As part of a Mediterranean diet, olive oil phenolics activate bitter receptors which in turn stimulate GLP-1.17

Foods that provide soluble fiber are, logically, also key in increasing GLP-1 and include the same fruits, vegetables, earth-made grains, and seeds like barley or oats, legumes, and flax seeds. Pre- and probiotics promote GLP-1 release by fermenting dietary fibers to short chain fatty acids (SCFAs) via beneficial gut microbes. These SCFAs bind to receptors on the L cells which then activate GLP-1.18

Additional studies also show that yerba mate,19 curcumin,20 and berberine21 all may contribute to GLP-1 release. Bitter hops has more recently been used to formulate a natural supplement alternative to GLP-1RAs and is called Amaraste.22,23

Most in the nutrition space and beyond understand full well the health benefits of these whole nature-made foods, over and above their influence on enteroendocrine hormones. They not only provide proper GLP-1 levels but are also many of the foods that quell inflammation, balance blood sugar, create a diverse gut microbiome, and enable a symbiotic relationship between food, weight, and health. Instead of cutting calories and further restricting, maybe it’s time to start adding these foods from the earth back into our diets. Often when this addition happens, the less nutrient-rich foods fall away.

Furthermore, as practitioners, we address not only diet, but elements of lifestyle, with good reason. The context in which food is eaten, the amount of stress, sleep, sunlight, and movement all play a role in metabolic processes. Optimizing these lifestyle factors will also have downstream effects on GLP-1.24 Thus all diet and lifestyle practices that better connect us to nature and its bounty increase well-being and overall health, including hormone release.

Conclusion

The Ozempic revolution is not the solution to the current health of the population. Certainly, there is recognition of a palpable pressure to reduce body size, a kind of “weight hate,” culturally forcing many to shed as much as possible no matter the consequences. And, to be fair, it is also acknowledged that the correct use of these peptides in the right patients at the right low doses with mandatory RDN/nutrition involvement, education, and behavioral change is possible. However, for the majority of the population, this is not how they are being used. It is with hope that with these medications we have reached the tipping point, where we shift gears from drug dependency for weight loss to fixing our food system, incentivizing health-related behaviors, and using RDNs and nutrition experts as guides and support to increase the health of the population. No pharmaceutical has ever lessened the prevalence or incidence of any chronic disease. It is becoming too costly—economically, physically, biologically, mentally—to continue fueling pharmacology and our bodies in this way when we know and have clear evidence of what truly creates health.

References

  1. Shi I, Khan SS, Yeh RW, Ho JE, Dahabreh IJ, Kazi DS. Semaglutide eligibility across all current indications for US adults. JAMA Cardiol. Published online November 18, 2024. doi:10.1001/jamacardio.2024.4657
  2. Gigliotti L, Warshaw H, Evert A, et al. Incretin-based therapies and lifestyle interventions: the evolving role of registered dietitian nutritionists in obesity care. J Acad Nutr Diet. Published online November 7, 2024. doi:10.1016/j.jand.2024.10.023
  3. National Center for Biotechnology Information. PubChem Compound Summary for CID 56843331, Semaglutide. Accessed December 1, 2024. https://pubchem.ncbi.nlm.nih.gov/compound/Semaglutide.
  4. Extendin-4: from lizard to laboratory…and beyond. National Institute on Aging. Published July 11, 20212. Accessed December 1, 2024.  https://www.nia.nih.gov/news/exendin-4-lizard-laboratory-and-beyond
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  13. Lee SH, Ko HM, Jee W, et al. Isosinensetin stimulates glucagon-like peptide-1 secretion via activation of hTAS2R50 and the Gβγ-mediated signaling pathway. Int J Mol Sci. 2023;24(4):3682. doi:10.3390/ijms24043682
  14. Huang TN, Lu KN, Pai YP, et al. Role of GLP-1 in the hypoglycemic effects of wild bitter gourd. Evid Based Complement Alternat Med. 2013;2013:625892. doi:10.1155/2013/625892
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