Using GLP-1 agonist medicine—significantly for weight reduction—are trending in an enormous approach. In accordance with a brand new report,1 GLP-1s have been the best-selling drug class in 2024, with roughly $50 billion in annual gross sales, and forecasted to surpass $100 billion by 2029 with an astounding compound annual progress fee of 19.2 %. Definitely, anybody who attended SupplySide West in Las Vegas, NV in October of 2024 would have been arduous pressed to have missed the plethora of nutraceuticals claiming to be GLP-1 stimulants—however extra on that later. In any case, the effectiveness of GLP-1 agonist medicine for weight reduction is related to some frequent opposed results which might, at the least partially, be mitigated by the concurrent use of choose nutraceuticals.
Overview of GLP-1 Agonist Medication
A standard GLP-1 agonist drug is semaglutide (Ozempic). It operates as a GLP-1 receptor agonist, sharing a exceptional 94 % structural homology with human GLP. Semaglutide delivers its advantages in decreasing blood glucose ranges and selling weight reduction by the activation of GLP-1 receptors primarily situated within the gastrointestinal tract, pancreas and mind. This entails enhancing glucose-dependent insulin secretion, offering a physiological response to elevated blood glucose ranges after a meal. Concurrently, it slows gastric emptying, which is a main mechanism by which it delivers its well-known good thing about decreasing urge for food. Complementary mechanisms embody growing pancreatic β-cell proliferation and reduces glucagon launch which additionally contribute to an total discount in urge for food. As well as, semaglutide’s interplay with GLP-1 receptors within the hypothalamus could mitigate sensations of starvation, alleviate meals cravings and improve the emotions of satiety. Semaglutide can be thought of a “long-acting” GLP-1 receptor agonist, alongside different GLP-1 agonist medicine.2
Adversarial & Extreme Adversarial Results of GLP-1 Agonist Medication
Using GLP-1 agonist medicine could end in some opposed results, extreme opposed results, and different undesirable results that influence any time of speedy weight reduction as a consequence of caloric restriction.
Adversarial Results
There are some well-established and customary gastrointestinal side-effects related to the usage of GLP-1 agonist medicine. These embody nausea, vomiting, diarrhea and constipation. These opposed results can persist for a number of days, and will end in dehydration, which if extreme could result in different severe well being issues.3
Nausea is the commonest opposed impact reported with GLP-1 agonists with as much as 50 % of sufferers affected. Most sufferers have delicate to average episodes of nausea, which appear to be dose-dependent and have a tendency to decrease with ongoing therapy—though some sufferers proceed to expertise some extent of nausea.4 Likewise, the prevalence fee of constipation is round 30 %.5
Ozempic Pores and skin/Ozempic Face/Ozempic Butt
So referred to as “Ozempic pores and skin,” “Ozempic face” or “Ozempic butt” is unfastened, sagging pores and skin on the face or buttocks that happens due to speedy weight reduction. To be clear, this isn’t an opposed impact particular to Ozempic or any GLP-1 agonist drug. It could happen in any state of affairs leading to speedy weight reduction. Primarily, with the load loss that occurred, the pores and skin has much less tissue to cowl which makes the pores and skin appear saggy. It’s extra frequent in middle-aged and older adults.
Lack of Lean Mass
Weight reduction, achieved by a calorie-reduced weight loss program, which can or could not contain the usage of GLP-1 agonist medicine, decreases each fats and lean physique mass. Lean physique mass is the whole lot besides fats, together with bones, muscle tissues, organs, blood and pores and skin. Nonetheless, for all sensible functions, the lack of lean physique mass on this context is primarily muscle with some bone density. In individuals with regular weight, the contribution of fat-free mass loss usually exceeds 35 % of whole weight reduction, and weight regain promotes comparatively extra fats acquire. In individuals who’re chubby or overweight, lean mass contributes solely ~20–30 % to whole weight reduction.6 It must be famous {that a} 10 % weight reduction may end up in a 1-2 % lack of bone mineral density (BMD). Nonetheless, the quantity of bone loss varies by inhabitants and skeletal web site.7
Extreme Adversarial Results
A extra extreme opposed results related to the usage of GLP-1 agonist medicine is pancreatitis. This was proven in a research of greater than 4,700 sufferers utilizing GLP-1agonist medicine in comparison with 654 sufferers utilizing bupropion-naltrexone, a distinct sort of medicine used for managing weight problems. Outcomes have been that incidence of biliary illness, i.e., situations that impact the gallbladder/bile ducts, (per 1,000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide (one other GLP-1 agonist), and 12.6 for bupropion-naltrexone and 4.6, 7.9 and 1.0, respectively, for pancreatitis. Using GLP-1 agonists in contrast with bupropion-naltrexone was related to elevated danger of pancreatitis, bowel obstruction, and gastroparesis (a situation that slows or prevents the abdomen from emptying its contents into the small gut), however not biliary illness.8
Nutraceutical Compensation
There are some nutraceuticals which can assist compensate for among the opposed results related to the usage of GLP-1 agonist medicine. These embody the next as indicated beneath.
Gastrointestinal Adversarial Results
As beforehand famous, the commonest opposed of GLP-1 agonist drug use is nausea. So, what will be finished to assist mitigate this symptom? In a phrase, ginger. A study9 revealed within the journal Scientific Diabetes recommended the usage of ginger as an antinausea complement is price making an attempt. This is smart when contemplating that there are a number of research through which ginger extract has been successfully used to cut back nausea. This contains research in nausea related to medicine use,10-15 the nausea of being pregnant,16-18 nausea in some illness states,19,20 nausea related to surgical procedure,21,22 and nausea related to movement illness.23
As one other frequent opposed impact of GLP-1 agonist drug use, constipation will be addressed utilizing fiber dietary supplements. Whereas there are a lot of to select from, the usage of acacia gum is an efficient choice. Acacia gum (also referred to as gum arabic, arabic gum, gum acacia, acacia, Senegal gum and Indian gum24), is derived from the hardened sap of acacia tree species, and a supply of dietary fiber. A single-blind, managed study25 demonstrated that 10 g/day and 15 g/day for 10 days, resulted in considerably elevated concentrations of Bifidobacteria, Lactobacilli and whole lactic acid micro organism teams have been considerably elevated with acacia gum on the dose of 10 g/d in comparison with management—testifying to acacia gum’s prebiotic properties. The impact was additionally vital on the dose of 15 g/d. As well as, the variety of stools per week was elevated with acacia gum (10 and 15 g/day) and every day stool weight was increased throughout acacia gum consumption. This impact is of curiosity for folks affected by constipation, together with these utilizing a GLP-1 agonist. One other double-blind scientific study26 additionally discovered that 10 g/day acacia gum likewise helped relieve constipation in comparison with placebo.
Ozempic Pores and skin/Face/Butt Adversarial Results
Maybe the most effective recommendation to keep away from such a sagging pores and skin is to lose not more than 1-2 lb per week. The subsequent greatest piece of recommendation is to verify energy coaching is a part of your strategy to weight reduction so you may construct muscle whereas shedding fats. From the standpoint of nutraceuticals, I like to recommend contemplating collagen.
Collagen is the principle structural protein discovered within the pores and skin and different connective tissues. It is a perfect nutraceutical for combating saggy pores and skin. Contemplate that bovine-sourced collagen peptides have been shown27 to help and stimulate the physique’s personal collagen manufacturing, growing pro-collagen manufacturing by 65 %, in addition to improve manufacturing of the vital pores and skin protein elastin by 18 %. Likewise, studies28-31 have demonstrated that it has considerably decreased wrinkles, improved pores and skin elasticity and moisture, decreased cellulite and elevated hair thickness.
Lean Mass Loss
Devour pea protein, in addition to creatine monohydrate, to help muscle progress. In a randomized, comparator-controlled, parallel scientific trial,32 randomized to pea protein (PPr) or whey protein (WPr) together with a weekly resistance coaching program for 84 days. Outcomes have been that the contributors supplemented with PPr had a 16.1 % enchancment in in whole-body muscle energy following 84 days of supplementation (p = 0.01), whereas these taking WPr had an enchancment of 11.1 % (p = 0.06). Eighty-four days of PPr supplementation resulted in enhancements in energy and muscle mass corresponding to WPr when mixed with a resistance coaching program in a inhabitants of wholesome sedentary adults. A number of studies33,34 have additionally demonstrated the satiating properties of pea protein, which resulted in folks decreasing their meals consumption.
Creatine serves as an anabolic sign for muscle progress, appearing because the chemical messenger that hyperlinks elevated muscle exercise with the manufacturing of latest muscle tissue.35,36 Essentially the most used and studied supplemental type of creatine is creatine monohydrate. Along with athletic and train enchancment, analysis has proven that creatine supplementation could improve post-exercise restoration, promotes harm prevention, thermoregulation, rehabilitation and neuroprotection.37
To deal with the bone density side of lean mass loss, think about the usage of vitamin D2 and vitamin K2 as MK-7 and MK-4. Vitamin D has lengthy been identified to assist the physique take in and retain calcium and phosphorus and, as such, is vital for constructing bone. Vitamin D3 is healthier than vitamin D2 for this objective since vitamin D2 efficiency is lower than one third that of vitamin D30F.38 A number of research have demonstrated that vitamin D3 and calcium can lower postmenopausal bone loss, assist forestall osteoporosis and reduce the chance of fractures 145F39 146F40 147F41 148F42 149F43 150F44 151F45 152F46 153F.47 Different analysis has demonstrated that vitamin D with calcium or vitamin D alone improved bone mineral density in contrast with no remedy 124F48 125F.49 Likewise, a big scientific trial 138F50,51 discovered that supplementing with a excessive dose of vitamin D3 for 2 years helped cut back declines in in bone mineral density.
Within the September 2024 subject of Vitamin Retailer, I wrote concerning the bone well being advantages of vitamin K2 as MK-7 and MK-4. To reiterate, in a 3 12 months, double-blind, placebo-controlled trial,52 244 wholesome postmenopausal ladies obtained 180 mcg/day of MK-7 or a placebo for 3 years. The outcomes have been that MK-7 decreased age-related decline in bone mineral content material and bone mineral density, and favorably affected bone energy and decreased loss in vertebral peak. Additionally, postmenopausal ladies with osteopenia (bone softening) additionally demonstrated a preservation of bone construction with 375 mcg/day MK-7.53 Vitamin K2 as MK-7 is offered in artificial kind, in addition to in each natto (soy) and chickpea-derived varieties for many who desire a soy-free choice (e.g., K2Go by Nutraland USA).
Analysis has additionally proven that MK-4 additionally has vital analysis to help its function in bone well being. In actual fact, it may very well be argued that it has extra analysis for this objective than MK-7. It also needs to be famous that the doses used of MK-4 are increased (though protected) than MK-7. For instance, in a single randomized, double-blind, placebo-controlled trial,54 1.5 mg/day of MK-4 for six to 12 months in postmenopausal ladies improved carboxylation of VKDPs (related to bone well being) and helped preserve bone mineral density. Comparable outcomes have been seen in one other study55 with 600 mcg/MK-4. When 5 mg/day MK-4 was used there was a major enchancment in carboxylation of VKDPs, with no extra profit in comparison with 45 mg/day MK-4.56
As well as, there’s a synergistic relationship between vitamin Ok and vitamin D. A two-year randomized study57 discovered that the mixed administration of vitamin D3 and vitamin K2 (as MK-4), was efficient in growing the bone mineral density in postmenopausal ladies with osteoporosis. One other study58 in ladies with estrogen deficiency discovered that MK-4 mixed with vitamin D3 partially prevented bone loss attributable to estrogen deficiency.
Nutraceuticals Claiming to be GLP-1 Stimulants
Now let’s take a few minutes to contemplate all these nutraceuticals claiming to be GLP-1 stimulants. In September of 2024, a superb pal and colleague of mine, Dr. Jacqueline Jacques, spoke at a UNPA (United Pure Merchandise Alliance) assembly about peptides, together with GLP-1. She gave such a unbelievable presentation that I requested her for a quote on this matter to make use of on this article. Right here’s what she needed to say:
“GLP-1 receptor agonist medicine are particularly engineered to have vital benefits over the GLP-1 that your physique naturally makes. A few of these benefits embody being a lot stronger than pure GLP-1, having a stronger binding affinity at receptor websites that GLP1 targets, having a protracted half-life (that means they keep round a very long time—two hours to 5 days), and being engineered to withstand breakdown by DPP-4 enzymes (the peptide degrading enzymes that break down GLP-1 and comparable compounds).
“So, if you hear somebody say their complement stimulates GLP-1 launch or will increase GLP-1, that’s not the identical factor and doesn’t make them “nature’s Ozempic.” For a begin, many frequent meals are nice stimulators of GLP-1. For instance, avocado has a identified optimistic profit of accelerating GLP-1 and at the least one research displaying one half an avocado can lower postprandial starvation for a number of hours.59 However actually the listing is lengthy and contains excessive fiber meals, excessive fats meals, excessive protein meals, bitter meals, and fermented meals. The physique produces GLP-1 in response to all types of meals consumption, however it has a really quick period of motion as a result of it’s quickly degraded by DPP-4 enzymes. Pure GLP-1 is damaged down very quickly, with a half-life of just one to 2 minutes. Does this imply there isn’t a worth in merchandise claiming to extend GLP-1? I feel the true query is can additionally they display vital weight reduction in a human scientific trial? Maybe time will inform.”
To elaborate on her final level, from my perspective it’s much less about whether or not a nutraceutical works as a GLP-1 stimulant or agonist, and extra about if it truly demonstrates vital weight reduction.
Black Ginger Extract
For example, in a current episode of my Vitamin Professor podcast (dropped at you by VRM Media), I interviewed the good Dr. Tim Ziegenfuss concerning the results of black ginger extract (test it out when you haven’t already seen it). Through the podcast, Dr. Z talked about how the polymethoxyflavones in black ginger extract helped promote the discount of belly fats (each visceral and subcutaneous) in human research.60,61 For instance, one of many research confirmed the next fats discount (the second had comparable outcomes). (See chart).
Dr. Z additionally talked a couple of new research for belly fats loss he’s conducting utilizing a black ginger extract with a excessive standardization of polymethoxyflavones (ACTIZ!NG from Nutraland USA). In fact, black ginger extract is just one of many potential nutraceuticals with good human scientific analysis supporting weight discount or—extra importantly—fats discount.
Conclusion
Unquestionably, GLP-1 agonist medicine are trending, and that development reveals no signal of slowing down anytime quickly. For many individuals, these medicines have made an enormous distinction in selling significant weight reduction. Nonetheless, GLP-1 agonist medicine are related to some frequent opposed results. Partly, these will be mitigated by the concurrent use of choose nutraceuticals. Additionally, some nutraceuticals might also assist promote fats loss.VR
Gene Bruno, MS, MHS, Professor Emeritus of Nutraceutical Science, is a author, educator and a nutraceutical scientist with greater than 45 years of expertise educating pure product retailers and well being care professionals and formulating pure merchandise for dozens of dietary complement firms. He has written articles on vitamin, natural drugs, nutraceuticals and integrative well being points for commerce, shopper magazines and peer-reviewed publications. Bruno additionally hosts “The Vitamin Professor Podcast” dropped at you by VRM Media. He will be reached at [email protected].
