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Written by Erin Yeh
Last month Integrative Healthcare SymposiumGLP-1s have been one of the main topics, especially regarding their effect on weight loss and obesity treatment. But for Monique Klass, co-founder of the Center for Functional Medicine and the Institute for Functional Nursing, GLP-1s are more than just weight-loss drugs. During my presentation, I suggested that GLP-1 could be used as metabolic, neurobehavioral, and anti-inflammatory tools that can stimulate sustainable changes when used strategically—specifically, through microdosing.
“The most interesting thing about this drug is that you lose weight,” Klass said. “The most interesting thing is its global impact on the system.”
Not everyone should use GLP-1s, and some people need to use them forever, Klass explained. For others, low doses that would reverse their physiology, provide them with opportunities to make the right decisions, and activate their endogenous GLP-1s, are the right way to go, with the ultimate goal of reverse-engineering their systems and eventually eliminating them.
Mitochondria are power
It’s a common story. Patients struggling with weight loss have tried different methods to lose weight. Yet many of them are stuck. These patients become frustrated and fall back into old habits, resulting in them staying at their current weight or regaining the weight. To overcome this, patients need the right tools to empower them and educate themselves on what they can do to achieve metabolic balance.
“The system wants to be balanced,” Klass said. The body uses carbohydrates and glucose as the easiest source of energy, but it can also burn fatty acids for fuel when carbohydrates are not available. Metabolic flexibility is key.
At the center of creating metabolic flexibility are mitochondria, which take proteins, carbohydrates and fats and turn them into energy for the body. The strategy is to stimulate the mitochondria to start burning rather than storing energy. To get your mitochondria to convert macronutrients into energy, it takes a little inflammation and oxidative stress to kick the system into gear. But many prevent the system. Eating multiple times a day is one way to increase inflammation and oxidative stress. The average American has about 11 eating events every day.
This is where GLP-1 medications can provide support. When prescribed in low doses, these medications can provide a patient with a moment of hesitation and an opportunity to choose not to eat or drink something, preventing inflammation and oxidative stress. However, Klass cautioned against getting carried away by the excitement of appetite suppression, as that also has harmful side effects.
“[Patients]think they should have no appetite at all,” Klass commented. “This is bad news; this is a bad drug. They’re wasting their muscle mass creating all these metabolic adaptations that keep them stuck on these drugs.”
GLP-1s also have an anti-inflammatory effect. Klass cited her own experiences with her clients. Those who were prescribed even just one milligram saw anti-inflammatory benefits, such as reduced joint pain. Small doses also reduce inflammation in the brain, leading to improvement in depression, although Klass also warns of the opposite effect. Some clients have reported increased anxiety due to low blood sugar levels and the patient not eating enough to get their blood sugar to a balanced level.
Reduce food noise, but not completely
GLP-1 drugs are often touted as completely eliminating food noise. However, Klass did not encourage the idea of completely erasing food noise. Rather, it must be reduced. Otherwise, patients can fall back into old habits and fall into the trap of yo-yo dieting.
“Shutting down the food noise is not what you want to do,” she said. “You want to reduce the food noise so that people aren’t starving and so driven by the ebb and flow of insulin and glucose that they create a vicious cycle.”
Furthermore, reducing food noise gives patients an opportunity to stop and make intentional choices. It empowers them, moves them from compulsion to awareness, and puts their health back under their control.
This applies to addiction as well. Klass recalled how one of the first things she noticed was that her clients no longer had the desire to drink alcohol. Although she was initially hesitant to prescribe GLP-1, she realized that providing her clients with small amounts helped them stop drinking alcohol and sugar.
Lifestyle still matters
Like most medications, GLP-1 should not be used as a cure-all for all diseases. They are tools that can help patients get where they need to go. Lifestyle interventions, ultimately, make up the bulk of sustainable weight loss. These interventions include diet, gut microbiome, exercise, and timed eating, which are positioned as mechanisms to stimulate endogenous GLP-1 production and restore mitochondrial function.
Obviously, diet is a major asset of lifestyle. In the body, L cells – the backbone of endogenous GLP-1 – in the intestine react to food entering the body. The microbiome stimulates L cells in the intestine. As such, maintaining a healthy gut microbiome will allow for better interactions. “When you look at what stimulates our endogenous GLP-1, it’s protein…it’s fiber and fermented foods.”
Eating even a forkful of fermented foods, including kimchi and sauerkraut, can fundamentally alter the gut microbiome which can stimulate short-chain fatty acids that stimulate L-cell differentiation that help the body make its own endogenous GLP-1s, Klass explained. She also recommended a modified Mediterranean diet that emphasizes whole foods, fiber, lean protein, and healthy fats. Carbohydrates should also ideally be consumed in the morning. This is because endogenous GLP-1 levels are highest in the morning and lowest at night. Eating carbohydrates – or meals in general – at night will cause them to be stored in the body and not metabolized in the same way compared to during the day, thus accumulating fat in the body.
GLP-1 drugs also do not address nutritional gaps. Patients may actually be further nutrient deprived due to decreased appetite caused by GLP-1s. The class recommends multivitamins if necessary and vitamin D, a hormone signaling molecule. She highlighted the importance of fish oils, or omega-3 fatty acids. The anti-inflammatory effects of fish oils cause cell membranes to become more flexible and flexible, allowing insulin and hormones to bind better. Protein can also help treat brain fog and fatigue. For example, five grams of creatine provides a phosphate group that can quickly convert ADP into ATP.
“The only side effect I’ve seen is sometimes (patients) can get gastrointestinal distress because of it. But it helps with inflammation (and supplies) soluble fiber for short-chain fatty acids.”
Time-restricted eating, or fasting, increases endogenous GLP-1, and starting at night is ideal. Klass pointed out that not all fasting is equal and that it varies from one patient to another. But there are many different methods and patterns of fasting that can be offered. This includes intermittent fasting (e.g. 12-12 hours, 10-14 hours, 8-16 hours), as well as prolonged fasting of up to 48 hours. Fasting allows for cellular clearance of broken DNA and other debris, essentially cleansing the body, and increases endogenous GLP-1 production.
“If you want to clean up cells, don’t start here with someone who’s crazy about their metabolism,” Klass noted. “Start there once they’re stable.”
Exercise also plays a big role. All exercise, even light exercise, increases mitochondrial biogenesis. “Sitting is the new smoking,” says Klass. Even if people exercise for half an hour a day, if they remain inactive for the rest of the day, it does not allow the body to metabolize and start mitochondrial biogenesis.
Small movements and consistency are a good place to start, such as getting up every hour to walk around the house or do some chores. The key, according to Klass, is to get patients moving through “little things” and “little pulse movements” throughout the day. Other forms of exercise also include resistance training and high-intensity interval training (HIIT) which triggers mitochondrial biogenesis. However, HIIT can also cause more inflammation and oxidative stress, so it will not be suitable for everyone, especially patients with complex chronic diseases. It is possible to over-metabolize some patients and make them sicker.
GLP-1 medications are not only intended to be a weight-loss drug and a cure-all, but can be used as a bridge for patients to achieve their health goals. “People don’t lack motivation, they just lack a really good plan,” Klass said. “These drugs have the ability to reset mentality and physiology, and that is the end of sustainable change.”
