Replacing Ozempic: Natural Alternatives to Enhance GLP-1
Overview of GLP-1 Mimetics
Glucagon-like peptide-1 (GLP-1) mimetics, such as Ozempic (semaglutide), have emerged as a class of medications for managing obesity and type 2 diabetes. These drugs mimic the effects of the naturally occurring hormone GLP-1, which is integral in glucose metabolism and appetite regulation. By binding to GLP-1 receptors, these medications enhance insulin secretion in response to meals, inhibit glucagon release, slow gastric emptying, and promote satiety, ultimately leading to significant weight loss [1].
GLP-1 is a naturally occurring hormone secreted by the intestines in response to food intake. It stimulates insulin release from the pancreas and decreases glucagon production, helping to regulate blood sugar levels. Furthermore, GLP-1 slows down the emptying of the stomach, which prolongs the feeling of fullness after eating and reduces appetite. These combined effects make GLP-1 mimetics highly effective for weight loss and blood glucose control [2].
Mechanisms of Action
The mechanism of action of GLP-1 mimetics involves several physiological pathways:
- Enhanced Insulin Secretion: GLP-1 receptors on pancreatic beta cells increase insulin secretion in a glucose-dependent manner, meaning insulin is released when blood sugar levels are high, thereby minimizing the risk of hypoglycemia [3].
- Inhibition of Glucagon Release: By reducing glucagon levels, GLP-1 mimetics decrease hepatic glucose production, which helps lower blood glucose levels [4].
- Delayed Gastric Emptying: Slowing gastric emptying prolongs digestion, which helps control postprandial blood glucose spikes and promotes satiety, reducing overall calorie intake [5].
- Appetite Regulation: GLP-1 receptors in the brain influence appetite centers, leading to reduced hunger and increased feelings of fullness, which aids in weight loss [6].
Downsides and Muscle Mass Loss
Despite their effectiveness, pharmaceutical GLP-1 mimetics are associated with certain drawbacks. A primary concern is the loss of muscle mass that can accompany weight loss. Muscle mass is crucial for maintaining metabolic health, physical strength, and overall well-being. Studies have demonstrated that while GLP-1 mimetics effectively reduce body weight, they also reduce lean body mass, including muscle [7].
A 2024 systematic review investigating the effect of Ozempic on lean mass found that although significant weight reductions were observed primarily due to fat mass loss, in some cases, lean mass, i.e., muscle, decreased by up to 40% [7]. This loss of muscle mass is particularly troubling because muscle tissue is more metabolically active than fat tissue. A decrease in muscle mass can lower the basal metabolic rate (BMR), potentially making it more challenging to lose weight in the long term. Additionally, muscle loss can impact physical strength, endurance, and overall quality of life, especially in older adults. Muscles play a central role in whole-body protein metabolism by serving as the principal reservoir for amino acids to maintain protein synthesis in vital tissues without amino acid absorption from the gut and by providing hepatic gluconeogenic precursors [8].
In other words, when a person’s diet does not provide amino acids and nutrients for proper metabolism, the body turns to muscle for amino acids to support the functions of vital organs [8]. Without this amino acid-muscle storage function, essential organs are more prone to amino acid deficiency, which may lead to complications.
Natural Alternatives for GLP-1 Enhancement: Green Tea, Epigallocatechin Gallate, Berberine, Polyphenols, and Cinnamon Extract
Given the concerns with GLP-1 mimetics, exploring natural alternatives that can enhance GLP-1 secretion without adverse effects on muscle mass is appealing. Green tea, epigallocatechin gallate (EGCG), berberine, polyphenols, and cinnamon extract have shown promise.
Green Tea and Epigallocatechin Gallate (EGCG)
Green tea, derived from the leaves of Camellia sinensis, is rich in bioactive compounds known as catechins. The most potent catechin in green tea is epigallocatechin gallate (EGCG), which has been extensively studied for its health benefits, including its potential to enhance GLP-1 secretion and improve metabolic health.
Mechanisms and Benefits
EGCG has been shown to improve insulin sensitivity, promote fat oxidation, and increase GLP-1 levels [9]. The compound works by activating AMP-activated protein kinase (AMPK), which plays a role in cellular energy homeostasis and can enhance GLP-1 secretion [10] [11].
Clinical Evidence
A 2014 clinical trial set out to see how green tea extract affects blood sugar and fat levels in people with type 2 diabetes and abnormal cholesterol [12]. The study included 92 people with these conditions, divided into two groups of 46 each. One group took 500 mg of green tea extract three times a day, while the other took a placebo in the same amount and frequency for 16 weeks. Measurements of body size, blood sugar, cholesterol, safety factors, and hormones related to obesity were taken at the start and end of the study [12].
The results showed that in the group taking green tea extract, there was a significant reduction in triglycerides (a type of fat) and in the insulin resistance index (a measure of how well the body responds to insulin) [12]. There was also a significant increase in HDL cholesterol (the “good” cholesterol). Further, in the green tea group, the insulin resistance index improved from 5.4 to 3.5. Additionally, certain hormones and proteins related to fat metabolism increased in both groups. Still, only the group taking green tea extract showed increased GLP-1 [12].
The study suggested that green tea extract might help improve insulin resistance and increase GLP-1 [12].
In 2018, 22 healthy adult women participated in a randomized, double-blind, placebo-controlled crossover study [13]. On two separate occasions, one week apart, each woman received either 800 mg of corn starch (a placebo) or 752 mg of EGCG. The researchers measured their appetite by looking at stomach emptying, feelings of hunger, desire to eat, fullness, and levels of insulin, adiponectin, leptin, and glucose in their blood. These measurements were taken while fasting and then at 30, 90, and 150 minutes after taking the supplement [13].
The results showed that EGCG led to a larger stomach volume at 30 and 90 minutes after taking it, indicating slower stomach emptying [13]. The women also felt fuller at 90 minutes in the EGCG group. Additionally, adiponectin levels were higher at 150 minutes with EGCG, but there were no differences in blood sugar, insulin, or leptin levels between the two groups. The researchers concluded that a single dose of EGCG can slow down stomach emptying in healthy women, although the effect is small but statistically significant [13].
Further studies have found that green tea extract enhanced fat oxidation during moderate-intensity exercise, suggesting its role in promoting weight loss. Participants who consumed green tea extract experienced increased fat-burning and improved body composition during exercise [14] [15] [16].
Dosage and Safety
Typical doses of EGCG range from 200-400 mg daily, with one clinical trial providing overweight men 300 mg per day [17]. It is generally considered safe, but while extremely high, long-term doses may cause liver toxicity in some individuals, drinking even a very high dietary amount of green tea would be unlikely to cause these adverse effects in humans [18].
Berberine
Berberine is a bioactive compound found in several plants, including Berberis species, and has been used in traditional Chinese medicine for its anti-diabetic properties. Recent research indicates that berberine can increase GLP-1 levels, improve insulin sensitivity, and promote weight loss.
Mechanisms and Benefits
Berberine activates AMPK, similar to EGCG, which enhances GLP-1 secretion and improves metabolic processes [19]. It also influences gut microbiota composition, which can positively impact GLP-1 levels and overall metabolic health [20]. Finally, berberine can help lower blood sugar by stimulating GLP-1 secretion by activating bitter taste receptors in the gut, specifically the TAS2R38 receptor, in a process dependent on the PLC pathway [21].
Clinical Evidence
A 2008 randomized controlled trial with 116 patients found that those who took berberine for 3 months showed significant improvements in blood sugar levels, HbA1c, triglycerides, total cholesterol, and LDL cholesterol compared to those who took a placebo [22]. Insulin sensitivity also improved with berberine, although the change wasn’t significantly different from the placebo group. Some patients experienced mild to moderate constipation, but berberine was effective and safe overall [22].
A 2024 study investigated berberine’s effect on “lacteal junction zippering” [23]. “Lacteals” are small lymphatic vessels in the small intestine that absorb dietary fats. “Zippering” refers to the formation of tight, stable junctions between cells, crucial for efficient fat absorption. The study found that berberine helps reduce body weight in mice by promoting lacteal junction zippering, improving the body’s handling of fats [23].
A 2009 study investigated how berberine affects GLP-1 release in rats and human cells [24]. They found that berberine boosted GLP-1 secretion in response to glucose in rats and increased the production of genes involved in making GLP-1 in the intestines. In lab tests using human cells, berberine also directly stimulated GLP-1 release and promoted the genes needed to produce GLP-1. They discovered that berberine’s effects on GLP-1 involve pathways like PKC, which could help explain its potential benefits for diabetes treatment [24].
Dosage
A standard dose of berberine used in studies for its effects on GLP-1 secretion typically ranges from 500 mg to 1500 mg per day, divided into two to three doses. This dosage range is effective in various clinical trials and research studies. For example, a 2008 study published in Metabolism used a dosage of 500 mg of berberine three times a day (totaling 1500 mg per day) and observed significant improvements in glucose metabolism, insulin sensitivity, and lipid profiles over three months [25].
Polyphenols
Polyphenols are a diverse group of plant compounds found abundantly in fruits, vegetables, tea, and wine. They are known for their antioxidant properties and have been identified to stimulate GLP-1 secretion and enhance metabolic health [26].
Mechanisms and Benefits
Specific polyphenols, such as those found in apples, berries, and grapes, have been shown to enhance GLP-1 secretion [26] [27]. These compounds can modulate gut microbiota, influence intestinal cell signaling, and improve insulin sensitivity, contributing to better metabolic health [26] [27].
Clinical Evidence
Curcumin is a polyphenol derived from turmeric, and it has been found to induce GLP-1 secretion [28] [29]. One study found that curcumin enhances the release of GLP-1, mainly when glucose levels are high. In rats, at a dose of 1.5 mg/kg, curcumin improved glucose tolerance by stimulating GLP-1 and insulin secretion after glucose intake. This effect was linked to curcumin interacting with G protein-coupled receptors (GPR) 40 and 120. These findings suggest that curcumin could potentially reduce the need for other diabetes medications and may help prevent diabetes by boosting natural GLP-1 production [30].
Anthocyanins are a group of polyphenols and are the pigment responsible for the blue, red, and purple colors in berries and fruits (e.g., blueberries, purple corn, beets, purple cabbage, pomegranates, red grapes, strawberries, raspberries, and cherries). Anthocyanins have been shown to increase GLP-1 secretion [26] [31]. Blackcurrant extract has shown promise in enhancing GLP-1 secretion. In one study, researchers provided rats with blackcurrant extract (BCE), which is rich in a compound called D3R, at a dose of 5 mg/kg. They observed improved glucose processing by enhancing the release of GLP-1 [32]. D3R from BCE remained intact in the rats’ digestive systems for up to an hour, suggesting it directly stimulates GLP-1 secretion rather than its breakdown products [32].
A study found that individuals consuming a diet high in polyphenols had better blood sugar control than those with lower polyphenol intake [34]. Similarly, another study highlighted that specific polyphenols, such as those found in berries, can enhance insulin sensitivity and support weight loss. Participants who consumed polyphenol-rich berry extracts experienced increased insulin sensitivity and improved body composition [35].
In a 2001 study published in the British Journal of Nutrition, participants consumed either a berry purée containing bilberries, blackcurrants, cranberries, and strawberries with sucrose, or a control meal with an equivalent amount of sucrose in water. Results showed that consuming berries with sucrose led to lower blood glucose and insulin levels 15 minutes after the meal than the control (P = 0.021, P < 0.007, and P = 0.028, respectively). At 90 minutes, these levels were higher (P = 0.028, P = 0.021, and P = 0.042, respectively), and there was a modest impact on glucagon-like peptide 1 (GLP-1) response (P = 0.05). Overall, berries improved the glycemic response to sucrose, suggesting they could help manage blood sugar levels after carbohydrate intake [36].
Dosage and Safety
The intake of polyphenols can vary widely based on dietary sources. While there are no established upper limits for polyphenol consumption, it is recommended to include a variety of polyphenol-rich foods in the diet for optimal benefits. There are also many, many kinds of polyphenols, but turmeric and anthocyanins have been studied extensively for their effects on GLP-1.
Cinnamon Extract
Cinnamon extract, derived from the bark of the cinnamon tree, is renowned for its aromatic flavor and therapeutic properties. It contains bioactive compounds like cinnamaldehyde, cinnamic acid, and cinnamate, contributing to its health benefits, including improved metabolic health and insulin sensitivity [37]. These compounds are also polyphenols, but they warrant their own review.
Mechanisms and Benefits
Cinnamon extract has been shown to influence GLP-1 levels by enhancing insulin secretion from pancreatic beta cells [38], inhibiting the activity of the enzyme DPP-4, which degrades GLP-1 [39] [40], and directly stimulating the secretion of GLP-1 from intestinal cells [41] [42].
Clinical Evidence
In a 2007 clinical trial, researchers aimed to find out if cinnamon affects how quickly food leaves the stomach (gastric emptying), blood sugar levels after eating (postprandial blood glucose), and the feeling of fullness (satiety) in healthy people. They found that cinnamon can help slow down how quickly the stomach empties and significantly reduce the rise in blood sugar after eating [43]. A subsequent 2009 trial built on the 2007 findings, noting that GLP-1 levels were significantly higher after consuming food that contained 3 grams of cinnamon [44]. The combined results of the two studies indicate a relationship between the amount of cinnamon consumed and the decrease in glucose and insulin concentrations, along with related effects [43] [44].
Dosage and Safety
In the above studies, researchers provided participants with 3 grams (or 3,000 mg) of cinnamon. However, a lower dosage of cinnamon extract could likely be effective. Consuming cinnamon with and between meals may assist the body in proper insulin regulation and increasing GLP-1 levels, thus promoting a fuller feeling.
Practical Applications and Recommendations
Lifestyle Considerations and Holistic Approach
While these natural supplements can support weight loss and metabolic health, adopting a holistic approach is essential. This includes a balanced diet, regular physical activity, adequate sleep, and stress management. Consulting with a healthcare professional before starting any new supplement regimen ensures safety and efficacy.
Combining Ingredients for Synergy
Combining green tea, EGCG, berberine, polyphenols, and cinnamon can have synergistic effects [46], enhancing overall health benefits. For example, a daily routine might include:
- Morning: A cup of green tea with breakfast to kickstart the metabolism and provide a source of EGCG.
- Midday: A berberine supplement to support glucose metabolism and enhance GLP-1 secretion before lunch.
- Afternoon: A polyphenol-rich snack, such as a handful of berries or an apple, boosts antioxidant intake and promotes metabolic health.
- Evening: Another cup of green tea or matcha before dinner to continue supporting metabolism and satiety.
Healthmasters' supplements can help integrate these ingredients into a person's diet, too. For example, Healthmasters' Cinnamon Extract Fuel Burner contains 100 mg of green tea and cinnamon extracts per capsule. Likewise, Healthmasters' Berberine Ultimate contains 200 mg of dihydroberberine per capsule, which is a form of berberine with high bioavailability. Finally, Healthmasters' Turmeric Force can also help increase polyphenol consumption, in addition to thoughtfully integrating red, blue, and purple fruits and vegetables into one's diet.
Tips for Success
- Consistency: Regularly consuming these supplements is vital to achieving and maintaining benefits. Developing a routine that incorporates these ingredients daily can help ensure consistency.
- Diet Integration: Incorporate these ingredients into your meals and snacks for ease and sustainability. For example, green tea can be used as a base for smoothies or soups, and berberine-rich plants can be added to herbal teas or meals.
- Monitoring and Adjusting: Track your progress and consult a natural-oriented healthcare provider. Monitoring blood glucose levels, body composition, and overall well-being can help tailor the supplementation regimen to individual needs.
Conclusion
GLP-1 mimetics like Ozempic offer significant benefits for weight loss but come with downsides, including muscle mass loss. Natural alternatives such as green tea, EGCG, berberine, polyphenols, and cinnamon can enhance GLP-1 levels and support healthy body composition. Incorporating these supplements into a holistic health regimen, alongside lifestyle modifications, can promote sustainable weight loss.
References:
[1] https://pubmed.ncbi.nlm.nih.gov/29364588
[2] https://pubmed.ncbi.nlm.nih.gov/29617641
[3] https://pubmed.ncbi.nlm.nih.gov/17928588
[4] https://pubmed.ncbi.nlm.nih.gov/23684623
[5] https://pubmed.ncbi.nlm.nih.gov/12832099
[6] https://pubmed.ncbi.nlm.nih.gov/8538742
[7] https://pubmed.ncbi.nlm.nih.gov/38629387
[8] https://pubmed.ncbi.nlm.nih.gov/16960159
[9] https://pubmed.ncbi.nlm.nih.gov/19147161
[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633218
[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941417
[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948786
[13] https://pubmed.ncbi.nlm.nih.gov/30127247
[14] https://pubmed.ncbi.nlm.nih.gov/16286857
[15] https://www.mdpi.com/2072-6643/7/7/5245
[16] https://pubmed.ncbi.nlm.nih.gov/28631582
[17] https://pubmed.ncbi.nlm.nih.gov/17906192
[18] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855614
[19] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621568
[20] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435753
[21] https://pubmed.ncbi.nlm.nih.gov/26206195
[22] https://pubmed.ncbi.nlm.nih.gov/18397984
[23] https://pubmed.ncbi.nlm.nih.gov/38176265
[24] https://pubmed.ncbi.nlm.nih.gov/19945441
[25] https://pubmed.ncbi.nlm.nih.gov/18442638
[26] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866283
[27] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152752
[28] https://pubmed.ncbi.nlm.nih.gov/23660191
[29] https://pubmed.ncbi.nlm.nih.gov/31470039
[30] https://pubmed.ncbi.nlm.nih.gov/27990751
[31] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427495
[32] https://pubmed.ncbi.nlm.nih.gov/28748082
[33] https://pubmed.ncbi.nlm.nih.gov/30175788
[34] https://pubmed.ncbi.nlm.nih.gov/22082311
[35] https://pubmed.ncbi.nlm.nih.gov/20724487
[36] https://pubmed.ncbi.nlm.nih.gov/21929838
[37] https://pubmed.ncbi.nlm.nih.gov/27774415
[38] https://pubmed.ncbi.nlm.nih.gov/15002064
[39] https://www.researchgate.net/publication/322244900
[40] https://www.sciencedirect.com/science/article/pii/S2772566922000234
[41] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384237
[42] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388503
[43] https://pubmed.ncbi.nlm.nih.gov/28556815
[44] https://pubmed.ncbi.nlm.nih.gov/17556692
[45] https://pubmed.ncbi.nlm.nih.gov/19158209
[46] https://search.bvsalud.org/gim/resource/en/wpr-1005426
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