Recently, we hosted an AMA with our Medical Advisor, Dr. John Thomson Smith, where we discussed chronic diseases and their management. Among the many insightful questions from our Rejuve.AI community, it was no surprise that drugs like Ozempic, blockbuster therapies for obesity and type 2 diabetes, came up.
These drugs have definitely taken the medical world by storm over the past decade. In a new paradigm where obesity is recognized as a disease, this class of medications could provide up to 25% weight loss [1]. Moreover, new studies keep emerging as well suggesting that these drugs may offer benefits beyond their current uses.
For instance, a recent analysis from the SELECT trial, which included 17,604 participants aged 45 and older with cardiovascular disease, revealed that those taking the active ingredient in Ozempic had lower rates of all-cause mortality. They experienced reduced risks of death from cardiovascular events and even COVID-19 compared to those on a placebo [2].
As research continues exploring the impact of Ozempic and similar drugs on other conditions, such as neurodegenerative diseases, the pharmaceutical industry is betting heavily on these medicines. Market projections suggest it could exceed $100 billion by 2030 [3].
In today’s article, we wanted to break down the mechanisms behind these drugs and how metabolic health could be a key to longevity. Also, in light of TikTok trends like “Ricezempic”, we aim to investigate whether there’s truth to claims that one could achieve the benefits of drugs like Ozempic without taking medications.
How Do Ozempic and Friends Work?
Ozempic, Wegovy, and Rybelsus (active ingredient: semaglutide), Mounjaro and Zepbound (active ingredient: tirzepatide), and Saxenda and Victoza (active ingredient: liraglutide) all belong to the same class of drugs with a similar target — the GLP-1 receptors. In scientific circles, these drugs are known as GLP-1 receptor agonists (GLP-1 RAs).
GLP-1 receptors are found in several tissues in our bodies. When they are activated in the pancreas, they trigger the so-called incretin effect, which enhances insulin secretion in response to food intake [4]. Insulin facilitates the uptake of glucose into cells which helps regulate blood sugar levels. This is why GLP-1 RAs were initially developed to manage type 2 diabetes.
However, during clinical trials for Ozempic in 2017, researchers noticed that patients not only had improved blood sugar control but also experienced significant weight loss [5]. This was attributed to two key mechanisms.
First, GLP-1 receptor activation in the stomach delays gastric emptying, meaning food moves more slowly through the digestive tract, enhancing digestion and extending feelings of fullness [6]. Second, since GLP-1 receptors were also found in the brain, particularly in areas that control food-related cues, it was found that these receptors drive signaling from the brain to the gut to feel satiated more quickly [7].
As a result, GLP-1 RAs have become recognized for their effectiveness in suppressing appetite, helping individuals consume fewer calories and achieve weight loss. Their dual action on both metabolic and appetite-regulating systems makes them a compelling option for managing weight and metabolic health.
Potential Side Effects Plus Lack of Research on Healthier Individuals
Like most medications, GLP-1 RAs come with their fair share of potential side effects. The most common are digestive issues, such as nausea and vomiting. Other side effects that can come with such pronounced weight loss are loss of muscle mass and loss of subcutaneous fat in the face, a phenomenon often referred to as “Ozempic face.” More serious complications, though rarer, include risks of pancreatitis and thyroid cancer [8].
Ultimately, these side effects can be seen as trade-offs for patients with obesity or type 2 diabetes, as GLP-1 RAs can significantly improve disease outcomes. But what about healthier individuals? Could they also benefit from these drugs?
To answer that, prevention trials on GLP-1 RAs would be needed. Such trials could examine whether these medications could prevent healthy people from developing metabolic disorders in the future. However, clinical trials investigating GLP-1 RA’s typically involve individuals with existing health issues rather than healthy participants.
Given the lack of research on healthy individuals and the known side effects, self-experimentation with GLP-1 RAs might not be advisable at this point in time for those without a clinical need. However, in this era of preventative health, could there be ways to harness the metabolic benefits associated with GLP-1 RAs without exposing oneself to unnecessary risks?
Taking a Step Back: What’s GLP-1?
Sometimes the answer is in the question. Can you guess what the GLP-1 receptor is named after? GLP-1! Shocker, right?
Okay, but what exactly is GLP-1? GLP-1, or glucagon-like peptide 1, is a naturally occurring hormone released from specific cells in the gut when we eat. It plays a key role in managing our body’s response to food [9].
So while many — including those on GLP-1 RAs — don’t know, our bodies essentially have a built-in Ozempic system. This system helps ensure that the energy from food is efficiently used, blood sugar levels are controlled, and metabolic health is optimized.
However, the body’s naturally secreted GLP-1 has a short half-life — it’s rapidly cleared from the bloodstream. That’s why people with metabolic disorders like obesity and diabetes benefit from external supply of GLP-1 RAs, which are longer-acting versions of this hormone [10].
For those with healthier metabolic profiles, however, the GLP-1 pathway offers a slew of benefits. Remember, GLP-1 receptors are widespread in the body, indicating multiple roles for GLP-1 beyond appetite and blood sugar control.
For instance, GLP-1 in muscle tissues can boost glycogen synthesis, improving the way muscles store and use energy. In the kidneys, GLP-1 increases sodium excretion, which helps regulate blood pressure. In blood vessels, it enhances endothelial function, supporting better circulation and vascular health [10].
Additionally, human studies have shown that healthy older adults have higher levels of GLP-1 than those with Alzheimer’s, pointing to neuroprotective properties [11]. These effects might be linked to GLP-1’s anti-inflammatory actions in the brain [12], potentially extending to other organs as well.
Given these promising roles, boosting GLP-1 levels could present an exciting opportunity for improving longevity and overall health.
How to Naturally Boost Your GLP-1 Levels
So far, we’ve explored the importance of metabolic health and how the GLP-1 pathway is central to this equation. Now, let’s turn to the second part of our article: Can we boost GLP-1 levels naturally, without resorting to medications?
Research suggests that the answer is yes [13] [14]. There are several lifestyle practices that can help increase GLP-1 levels in the body. Next up, we’ll discuss five effective methods for enhancing GLP-1 production through natural means.
1- Adopt a High-Protein Diet
Since GLP-1 is naturally secreted from the gut in response to food, it’s no surprise that most strategies to boost its levels involve dietary choices — starting with protein.
Protein intake is a hotly debated topic in longevity discussions, with arguments both for and against increasing protein for longer lifespan. However, when it comes to raising GLP-1 levels, consuming more protein seems to be effective.
One study involving 12 women compared the effects of a high-protein diet (30% of daily intake) versus a low-protein diet (10%). Those on the high-protein diet not only experienced significantly higher GLP-1 levels but also felt fuller and had a higher basal metabolic rate [15].
To make sure you’re getting enough, aim to meet your protein needs based on your body weight. The Recommended Dietary Allowance (RDA), which is set by health authorities to meet the nutritional requirements of most healthy people, advises 0.8 grams of protein per kilogram of body weight. However, some longevity doctors recommend higher intake — like Dr. Peter Attia, who suggests 2 grams per kilogram.
Another interesting finding is that the order in which you eat your meal matters — some studies suggest that consuming protein before carbohydrates may further optimize GLP-1 secretion [16].
2- Prioritize Healthy Fats
The majority of dietary fats are triglycerides, which break down into free fatty acids that can stimulate GLP-1 secretion [17]. While all fats seem to boost GLP-1 levels, healthier fats have a greater impact.
What are healthy fats? They include unsaturated fats like monounsaturated fats and omega-3 polyunsaturated fatty acids — both found in olive oil. These fats outperform saturated fats, such as butter, in stimulating GLP-1.
A study from 2003 found that healthy adults who consumed a meal containing olive oil experienced higher post-meal GLP-1 levels than those who ate a meal containing butter [18].
On the long run, further research showed that following a Mediterranean diet rich in olive oil for 28 days resulted in significantly higher GLP-1 levels after meals in individuals with obesity and insulin resistance [19].
3- Load up on Fiber
Earlier, we mentioned the “Ricempic” craze. It turns out it exists also for “Oatzempic”, “Potatozempic”, and 'who knows what else -zempic'.
These trends encourage soaking any of the aforementioned food in water — sometimes with a dash of lemon juice — before drinking the liquid. While this practice might sound harmless, it’s both unscientific and potentially hazardous. Consuming uncooked byproducts of these foods can introduce harmful bacteria that could lead to food poisoning.
However, there is a legitimate idea behind these trends: dietary fiber. Unlike other nutrients, fiber isn’t digested by our gut. Instead, it feeds our gut bacteria, which produce short-chain fatty acids (SCFAs) as a byproduct. These SCFAs are the potent GLP-1 boosters that many are unknowingly seeking [20].
In the past, fiber was easy to consume through unprocessed, whole foods. But today, many processed foods have had their fibers stripped out to extend shelf life. This widespread reduction in dietary fiber has contributed to declining microbiome diversity and an increase in metabolic disorders [21].
So instead of considering trendy shortcuts, we should focus on unrefined foods rich in fiber. Research in adults with insulin resistance showed that consuming a high-fiber wheat cereal daily — 24 grams of fiber — for one year significantly increased both SCFA production and GLP-1 levels compared to low-fiber cereals [22].
4- Don’t Forget Exercise
Exercise may not involve food, but it can still positively impact GLP-1 levels. While the exact mechanisms are still being researched, studies have already demonstrated this effect.
For instance, a clinical trial found that 90-minute sessions of moderate-intensity exercise in patients with type 2 diabetes significantly raised GLP-1 levels, which remained elevated for up to 24 hours [23]. Similarly, aerobic exercise in healthy individuals not only increased GLP-1 levels but also reduced subsequent caloric intake [24].
Interestingly, the type of exercise may not even matter. A study of healthy young adults found that one hour of cycling elevated GLP-1 levels and decreased hunger [25]. These findings suggest that exercise — regardless of intensity — could be a powerful tool for naturally boosting GLP-1.
5- Chew up!
It’s probably starting to ring some bells for you now that most of these strategies for boosting GLP-1 levels echo lifelong advice you’ve heard from your mother about overall health.
Well, here comes the Mom-liest advice of the day: chew more!
GLP-1 research supports this age-old advice. A study found that chewing each bite 30 times increased naturally secreted GLP-1 compared to normal eating [26]. Another study showed that eating the same meal slowly over 30 minutes, rather than in just 5 minutes, also resulted in higher GLP-1 concentrations [27].
So, taking the time to chew thoroughly might be a simple yet effective way to enhance GLP-1 production.
Note on Spices and Supplements
Many supplements, like berberine and curcumin, have shown promise in improving metabolic health, but their effects on GLP-1 levels in humans haven’t been assessed yet. However, one spice where that has been studied is a crowd favorite: cinnamon. Human trials have shown that consuming three grams of cinnamon can indeed increase GLP-1 levels [28].
Keeping Lifestyle and Medications Hand in Hand
At the end of the day, if you or someone you know has been prescribed a GLP-1 receptor agonist for obesity or type 2 diabetes, these lifestyle practices are certainly not a replacement for this essential medication.
On the other side of the coin, Professor Jens Juul Holst from the University of Copenhagen, who spearheaded the discovery of the GLP-1 hormone and the development of GLP-1 RAs, once said about the importance of lifestyle for GLP-1 RAs patients:
“You have to continue to do something to maintain your new weight besides using the medications. Making these lifestyle changes is a tremendous help.”
Thus, for metabolic disorder patients, GLP-1 RAs and a healthy lifestyle go hand in hand.
But reflecting back, is there a future where healthy individuals will also boost their lifestyles with GLP-1 RAs?
Interestingly, Professor Holst himself doesn’t see a benefit coming for healthy individuals. Despite that, longevity scientists like Dr. Nir Barzilai and Dr. David Sinclair include GLP-1 RAs in their respective reviews of potential agents to slow down aging [29] [30]. Research is ongoing to explore their effectiveness in increasing healthspan [31].
Until the data is clearer, it’s never a bad idea to boost your body’s GLP-1 through lifestyle optimization.
References
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