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Glucagon-like peptide 1, or GLP-1, is a natural hormone that is released in response to food entering the gut, causing the release of insulin and the feeling of reduced appetite.
A popular medical treatment for obesity is a once-weekly injection of drugs that work to mimic glucagon-like peptide-1 (GLP-1). These drugs, known as GLP-1 agonists, include semaglutide and tirzepatide.
GLP-1 agonist drugs emerged in the treatment of type 2 diabetes beginning in 2005 with Byetta, a form of GLP-1 first identified in the venom of the Gila monster lizard. Byetta and other early GLP-1 agonists immediately acted and required a once or twice-a-day dosage.
In 2017, the first weekly GLP-1 agonist was approved to help type 2 diabetes. In 2021, a higher dosage form of semaglutide, was approved for the treatment of obesity. Tirzepatide is a dual-action agonist as it enhances both GLP-1 and another hormone known as glucose-dependent insulinotropic polypeptide (GIP) to improve blood sugar control as well as reduce appetite and food intake.
Both semaglutide and tirzepatide have shown impressive results in clinical trials in the treatment of obesity, whether a person has type 2 diabetes or not.[1-3] While dietary and lifestyle changes can be effective in promoting ideal body weight, the reality is that in obesity, the use of diet and lifestyle alone produces poor results as only about 5-15% of these people will achieve a 20% loss in body weight and most regain that weight within a year of losing it. In contrast, in human clinical trials with semaglutide or tirzepatide, about 60% of patients achieve a 20% reduction in weight and can keep that weight off with continued use. However, when people stop taking these drugs, most will regain about two-thirds of the weight they lost within a year.[4]
In addition to helping people lose weight, there is a lot of emerging data that GLP-1 agonists may significantly reduce the risk of heart attacks and strokes in patients with a history of cardiovascular disease by as much as 20%. The cardiovascular benefits appear to precede any significant weight loss and apply to people with or without type 2 diabetes.[5-7]
Every major drug company is currently devoting significant resources to developing more GLP-1 agonists alone or coupled with other active hormone-like compounds.[8] Hence, the use of GLP-1 agonists is likely to become an even more popular treatment for obesity and related disorders in the future.
From a nutritional standpoint, there are three areas of concern related to using GLP-1 agonists:
GLP-1 agonists can produce a significant reduction in appetite, or they cause some nausea as well. This makes people taking these drugs feel like they are not eating at all. And that can lead to malnutrition. When on these medications, it is critical to be mindful of the importance of diet and nutrition to your health. It is important to continue to feed the body even while on a metabolic support plan. The body has a lot of work to do with the metabolic and physical form changes due to both the GLP-1 agonist and the metabolic changes it promotes. It is important to continue to eat a highly nutritious diet.
The Mediterranean diet might be the best option when taking GLP-1 agonists. The main foods in a Mediterranean diet are whole foods and include fruits, vegetables, fish, seafood, nuts, legumes, and, of course, olive oil. To ensure adequate intake of vitamins and minerals, especially when food intake is reduced, be sure to take a high potency multiple vitamin and mineral formula to ensure adequate intake.
Important dietary strategies to help deal with the digestive issues associated with GLP-1 agonists or reduced stomach motility include:[9]
One of the concerns about GLP-1 agonists is a higher percentage loss of lean body weight or muscle mass than weight loss achieved through diet and lifestyle changes.[10] This may be the result of inadequate nutrition and/or physical exercise when relying solely on GLP-1 agonists for weight loss.
A key nutritional support formula for people on a metabolic support program is CollagenUp Plus. This formula provides hydrolyzed marine collagen peptides, added essential amino acids, gentle and non-irritating prebiotic dietary fiber sources, and flavonoid-rich extracts from red oranges and grapes. This comprehensive formula is designed to maximize nutritional support for anyone on a calorie-restricted diet.
First, in regard to its support of digestive function, CollagenUp Plus meets the criteria of a small particle-size meal. It also provides significant digestive support by supplying 5 grams of two unique prebiotics: digestive-resistant dextrin from tapioca and partially hydrolyzed guar gum. These dietary fibers are suitable as small particle food components that are helpful in supporting proper stomach function, and they both resist being broken down in the stomach or small intestine. This prevents gas formation and feelings of bloating. It also means that the prebiotic aspects of these dietary fibers occur primarily in the large intestine (colon), where most of the gut bacteria live.[11,12]
Both prebiotics and probiotics promote a healthy gut microbiome and support overall digestive function, especially at a total dosage of 5 grams daily. A healthy microbiome is critical to proper insulin action, blood sugar control, metabolic changes, and other aspects of metabolism, and, of course, as dietary fiber, they also support proper bowel function. It is important to maintain regular bowel movements as metabolic changes mean fat cells are breaking down and releasing stored toxins that must be metabolized and eliminated from the body through the feces rather than being reabsorbed into the general circulation.
In addition to digestive support, CollagenUp Plus can help people on metabolic health programs or calorie-restricted diets in other ways. It provides 5 grams of marine hydrolyzed collagen peptides. The skin is particularly rich in collagen, specifically, the support layer just below the surface called the dermis. Approximately 70% of the structural support provided by the dermis is due to collagen. The word collagen comes from the Greek word for glue. Collagen is the major protein in the human body and forms what is called the ground substance or “intracellular cement” that literally holds us together.
Supplementing the diet with collagen peptides provides the building blocks of collagen manufacture. It has been shown to help maintain skin elasticity and hydration in several double-blind, placebo-controlled clinical trials. Collagen peptides also help to minimize the appearance of skin aging and smooth out fine lines, especially if it is taken for at least six months.[15-17]
Collagen peptide supplementation may also help with typical changes that rapid metabolic changes produce in facial appearance. The skin of the face may lose collagen and fat. And that results in more lines and wrinkles, loose and sagging skin, and a hollowed-out appearance.
The polyphenol-rich extracts from grapes and red oranges included in CollagenUP Plus are also important in supporting both the microbiome and the collagen structures of the skin.[18,19] The microbiome effects include promoting the gut-brain axis for appetite control, while the collagen-supportive aspects also include the stimulation of collagen synthesis.
One of the concerns about any metabolic support program is a higher percentage loss of lean body weight or muscle mass than metabolic changes achieved through diet and lifestyle changes. Muscle mass is the fat-burning furnace of the body. So, any loss of muscle mass may make it more difficult to make metabolic changes if it is ever regained in the future. In addition, loss of muscle mass caused by some metabolic support programs may also accelerate the development of sarcopenia and age-related loss of muscle mass. Most people lose, on average, 3-8% of their muscle mass every ten years after age 30. This rate often accelerates after age 60 and leads to sarcopenia and an increased risk of reduced mobility, frailty, osteoporosis, and cardiovascular disease.
To maintain muscle mass while dieting, it is important to engage in walking or strength and resistance training, as well as consuming adequate amounts of protein. Generally, one gram per kilogram (2.2 pounds) of body weight is recommended. However, the level of intake of the nine essential amino acids is more relevant than the total protein intake. Other amino acids in proteins are termed non-essential as the human body can manufacture them.
In addition to CollagenUp Plus providing 5 grams of marine hydrolyzed collagen peptides that contain essential amino acids, it provides 3 grams of the nine essential amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine). Since the Recommended Dietary Allowance (RDA) for essential amino acids is roughly 7 grams, one serving of CollagenUp Plus provides about 50% of the RDA for the essential amino acids and only 50 calories. In contrast, two servings provide nearly 100% RDA for the essential amino acids and 100 calories.
Digestive distress caused by GLP-1 agonists is often limited to the early stages of treatment. It is thought to be the result of the stomach's GLP-1 receptors that regulate its emptying and motility (contractions). Too much GLP-1 stimulation can lead to a prolonged delay in stomach emptying, which causes nausea or feelings of stomach discomfort, such as a sense of fullness, heartburn, or pain.
To address these side effects, Digestion Pro with ProDigest® for G.I. Ease and Comfort from California Gold Nutrition may be helpful, especially when first starting to use GLP-1 agonists when digestive complaints are most common.
Digestion Pro with ProDigest® for G.I. Ease and Comfort contains a clinically proven, patented combination of unique ginger root and artichoke leaf extracts. While these two traditional herbal approaches to stomach and digestive complaints have been used for thousands of years, modern technology creates the most beneficial form of these traditional remedies for consistent and safe digestive support.
Human clinical studies with this unique ginger-artichoke extract combination have confirmed its benefits in improving the digestive process and stomach motility. For example, one double-blind, placebo-controlled study showed the combination is helpful in functional dyspepsia, a type of indigestion caused by stomach irritation that may cause sensations of abdominal bloating after eating, stomach pains, and cramps, or nausea.[9] In the study, 126 subjects with functional dyspepsia were given two capsules per day of the ginger-artichoke combination or a placebo for 14 days.
Results showed only those subjects taking the herbal product showed significant decreases in bloating, upper abdominal pain, and nausea. These benefits are partly related to the effects of the ginger and artichoke combination in promoting improved stomach motility, resulting in improved digestion and appropriate emptying of the stomach's contents.[12]
Berberine is getting a lot of media attention for its potential ability to promote GLP-1 activity and more in ways that may be useful in supporting those on GLP-1 agonists.[21-23]
Berberine is an alkaloid compound found in many plants, most notably goldenseal (Hydrastis canadensis), barberry (Berberis vulgaris), and goldthread (Coptis chinensis). Over 5,000 scientific studies have been performed with berberine, including over 150 human clinical trials.
Research has shown berberine is involved in many aspects of human health. Many health benefits of berberine supplementation are the result of its improvement in the gut microbiome, or more specifically, the collection of microbes and genetic material within the gut.[24-26] Berberine increases the quantity of the beneficial bacteria Akkermansia muciniphila in the gut. This bacteria plays a key role in the health of the intestinal lining and promotes improved insulin action to help fight obesity and promote blood sugar control.[27,28]
Berberine has been extensively studied in over 50 double-blind clinical trials for supporting normal blood sugar, cholesterol, and blood pressure levels as well as promoting liver health and weight management.[29-34]
Studies with Berbevis®, a patented Berberine Phospholipid Matrix, contained in Berberine Advanced from California Gold Nutrition, have shown even better results compared to regular berberine due to enhanced absorption. For example, in a double-blind, placebo-controlled study of 49 subjects, those receiving 550 mg of Berbevis® twice daily for two months showed significant improvements in blood lipids, blood sugar control, total fat mass (-6%), and abdominal (visceral) fat mass (-11%).[37]
Furthermore, in another double-blind study, Berbevis® at a dosage of 550 mg once daily showed similar benefits on blood lipids, blood sugar control, and body fat measurements, but researchers also showed an 11% decrease in the body fat to muscle mass ratio.[38] This last measurement indicates that Berbevis® may help promote loss of fat preferentially and preserves muscle mass.
While GLP-1 agonists offer hope to millions suffering from obesity, it is important to point out that whatever a person’s health goal, the basic tenet of achieving health is always to focus on diet, lifestyle, and attitude. Any drug or dietary supplement should always be used in the context of a holistic approach to health.
References:
By Dr. Michael Murray, N.D. 
