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With science showing how supplements achieve their benefits via multiple mechanisms of action—and without potentially adverse side effects.
When does it pay to be the butt of a joke? When that joke reaches an audience of nearly 20 million American television viewers1, that’s when.
And by that reckoning, comedian Jimmy Kimmel’s sly lampooning of Ozempic and its famous fans at the 95th annual Academy Awards did the once-unassuming diabetes drug a reputational favor.
Not that Ozempic needed the boost: Almost overnight, the prescription injectable went from near-obscurity to viral sensation thanks to the attention of influencers and celebrities who touted its promise as the latest weight-loss wonder drug.
And while that frenzy’s subsided somewhat, Ozempic as a weight-management tool isn’t going away—nor are the questions it raises about how best to “do” weight loss in an environment as rife with barriers to success as it is with hopes for it.
No wonder Andrea Zangara, head of scientific communications and marketing, Euromed (Mollet del Vallès, Spain), sees the saga of Ozempic as “a never-ending story.”
“There will always be demand for easy and effective weight-loss solutions,” he says. “And that recurring pattern underscores the importance of understanding the factors that contribute to weight management. For supplement brands, that means making R&D the priority when creating products that tick all the boxes: convenient, natural, safe, and effective.”
If occasional dramas in the weight-management space are nothing new, the forces animating the current Ozempic buzz, as well as the urgency of tackling real issues around excess bodyweight, are.
As Zangara says, “As we emerge from the pandemic with a renewed awareness of the importance of health, weight management has become a priority as consumers aim to improve their well-being—particularly after adopting unsatisfactory dietary and lifestyle habits during lockdown.”
And consumers are taking that aim not a moment too soon: The World Obesity Federation predicts that by 2035, 51% of the globe will be overweight or obese should current patterns continue, Zangara notes.
But urgent need shouldn’t prescribe urgent action that fails to account for the consequences—which is where the headlong rush toward Ozempic raises concern.
Its active component, and that of similar drugs, is semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist that upregulates the effects of this naturally occurring hormone.
Those effects include increased insulin production and a subsequent decrease in circulating levels of blood glucose, as well as inhibited production of the hormone glucagon—which, as yin to insulin’s yang, increases the breakdown of liver glycogen and the synthesis of new glucose, thereby boosting blood-glucose levels.
Combined, these reciprocal actions help explain why Ozempic and other semaglutide drugs are potent diabetes treatments. But what makes semaglutide relevant for weight management are its actions on the brain’s hypothalamic hunger centers and its ability to slow stomach emptying and thus extend postprandial feelings of fullness.
The net effects there amount to greater satiety, less hunger, and fewer food cravings—all of which stack the odds in favor of eating less and shifting the body’s energy balance toward caloric deficit. And that, as the laws of thermodynamics predict, shifts the scale downward.
Not So Fast
So far so good, right?
Not necessarily. As Zangara sees it, the drug’s “sudden popularity demonstrates how quickly information can spread and influence public opinion, especially when it comes to weight loss.” And while he acknowledges that medications like Ozempic “aren’t bad starting points” for obese individuals, he’s hardly alone in noting that “it has its limitations.”
Shaheen Majeed, CEO of BGG Americas, Algae Health Sciences, and HBNI North America (Irvine, CA), also sees drawbacks. “I’m not an expert on Ozempic by any means,” Majeed says, “but historically, most pharmaceutical weight-loss drugs have had serious side effects.” One need only visit Ozempic’s own website, he notes, to review its litany of possible complications—from nausea and abdominal pain to pancreatitis, thyroid tumors, and kidney failure. “Plus,” Majeed says, “the drug is an injectable, so I’d certainly not consider it convenient.”
Michael Chernyak, president, CK Nutraceuticals (Oakville, ON, Canada), adds that cravings may resume once use of the drug stops. And indeed, he says, “Weight gains of around 10%-15% have been observed in obese subjects who discontinued use.”
And as far as Gary Troxel, CEO, Gateway Health Alliances (Fairfield, CA), is concerned, the drug’s apparent vogue is “unfortunate for several reasons.”
First, he laments the supply bottlenecks that impeded diabetics’ access. Besides that, he says, “Hollywood and some media are normalizing the use of a powerful medicine that’s not intended for healthy individuals. For people who don’t have the serious medical issues for which these drugs were intended, taking them as shortcuts to weight management is ill advised and possibly dangerous. And it perpetuates the myth that there’s a ‘magic bullet’ for weight loss.”
Of course, Troxel gets that myth’s allure. “It’s human nature to seek easy solutions,” he concedes. “Maintaining healthy body weight and composition requires work and discipline around eating healthily, exercising, and making smart lifestyle choices.” And staying on those wagons isn’t easy in our distracted, hyper-caloric age.
Chernyak also sees the desire for easy weight loss as “human nature at its finest.” But, he continues, “The fact that obesity and other metabolic indications are still so prevalent means that quick fixes simply don’t exist—at least not in a sustainable fashion. So even though busy, tired consumers will always ‘bite’ on the next big promise or ‘miracle’ product, permanent diet and lifestyle changes are the answers long-term.”
That makes common sense to Majeed. “Anything that seems too good to be true usually is,” he concludes. “Weight loss isn’t rocket science and doesn’t have to be risky. The best formula for safe weight management is maintaining caloric intake at normal levels and eating a healthy diet—combined with regular aerobic exercise and a good weight-loss supplement.”
And lest anyone worry: Ozempic may have dominated recent news cycles, but “health-conscious consumers who prefer natural ways of addressing wellness will continue to gravitate toward clinically validated weight-loss supplements,” Majeed predicts.
Increasingly, that clinical validation shows that contemporary weight-management supplements achieve their benefits via multiple mechanisms of action.
The word Zangara uses to describe this is pleiotropic, or producing more than one effect, and he sees it as a signature advantage of today’s weight-management supplements relative to their predecessors.
“These innovations reflect a deeper understanding of the relationship between nutritional supplementation and weight management,” Zangara argues, “and they offer a more comprehensive approach by targeting multiple mechanisms rather than focusing on a single aspect of weight loss.”
For example, Zangara notes that the pomegranate polyphenols punicalagin and urolithin can influence satiety signaling via hormones like leptin and ghrelin—which affect hunger and fullness—while also improving metabolic health by reducing insulin resistance, blood pressure, and stress-hormone levels.
They may also increase levels of adiponectin, a hormone produced in fat cells that improves insulin sensitivity while attenuating inflammation—all of which Zangara says “may affect fat metabolism and positively influence the gut microbiome, potentially affecting the gut/brain axis through modulation of gut peptides involved in satiety signaling.”
Thus Euromed standardized its Pomanox pomegranate extract to 30% punicalagins, and a recent study2 on the product found that subjects who supplemented with it daily for three weeks felt less hungry, more satisfied, and fuller relative to those in the placebo group. Another study3 found that supplementation yielded significant increases in urinary total phenolics excretion, antioxidant capacity, and lean body mass while reducing blood pressure, fat mass, body fat, and salivary cortisol levels.
Calling it the “stress hormone,” Zangara notes that cortisol can promote fat storage and muscle breakdown, hamper metabolism, and disrupt sleep, “which itself can affect appetite regulation and metabolism,” he says.
Euromed also explored the metabolic effects of abscisic acid (ABA), a phytohormone present in figs, with research4 on its ABAlife fig extract standardized to various ABA concentrations showing that it regulates blood glucose and insulin levels while lowering the glycemic and insulinemic indexes of high-glycemic-index foods.
Interestingly, Zangara says, the compound may bind to LANCL2 receptors to initiate cellular signaling that enhances glucose uptake and increases expression and membrane translocation of a glucose-transport protein, thereby improving glucose homeostasis via a mechanism not unlike semaglutide’s. “Given the similarities in how they work,” he concludes, “ABAlife may offer weight-management benefits with fewer potential side effects than synthetic weight-management drugs like Ozempic.”
Turmeric to the Rescue
Also turning to the plant kingdom, scientists at Sabinsa Corp. (East Windsor, NJ) developed the company’s CurCousin supplement based on “a minor plant metabolite occurring in Curcuma longa,” or turmeric root, explains Kalyanam Nagabhushanam, PhD, Sabinsa’s president of R&D.
In a recent clinical trial5, twice-daily supplementation with 25 mg over the study’s 90-day duration yielded statistically significant drops in bodyweight, body-mass index, and waist circumference in obese participants, with additional benefits appearing in the supplement group’s lipid profiles, he says, including a detectable increase in HDL. Increases also emerged in levels of adiponectin, Nagabhushanam adds.
“Obesity is always underlined with chronic inflammation,” he continues, “and a reduction of that was observed in subjects receiving CurCousin.”
Finally, an animal study6 published this year associated the supplement with benefits around thermogenesis and modulation of the gut microbiota, leading Nagabhushanam to conclude that, “Clearly, CurCousin combines several advantages and acts on various pathways.”
Approaching wellness via the microbiome is a specialty at OptiBiotix Health Plc (York, UK), and as CEO Stephen O’Hara says, “The challenge with weight management is to steer the conversation in a new direction with alternatives that offer no reported side effects but that deliver the same results” as do pharmaceuticals like Ozempic.
For example, the company’s SlimBiome, a patented, mineral-enriched prebiotic fiber complex, “gently expands in the stomach to help consumers feel fuller longer,” O’Hara claims. The ingredient also attenuates blood-glucose levels and reduces craving—all actions seen with semaglutide.
But the fiber complex actually modifies the microbiome, O’Hara says, “to increase the number of microbes associated with lean body shape.”
According to one double-blind, placebo-controlled study carried out by Oxford Brookes University7, SlimBiome reduced hunger by 10%, food cravings by 11%, and food intake by 49%. “A second study8 by the University of Roehampton demonstrated a 21% reduction in food cravings and a 26% improvement in mood,” O’Hara adds. “It also showed that 90% of volunteers lost weight, reduced their body fat, and exhibited reductions in hip and waist circumferences.”
In comparison to injectable drugs, SlimBiome generated no side effects in either study, and it appears to spare muscle even at the expense of body fat—a hedge against reported cases of muscle loss and wastage associated with semaglutide use, O’Hara notes. “So while there’s no simple path to weight loss,” he concludes, “there are safe, effective, and sustainable alternatives that help consumers help themselves.”
Out of Africa
Gateway Health has looked to Africa for clues about how to formulate safe and effective weight-management supplements, and one of the trails it followed led to African mango, or Irvingia gabonensis.
Used traditionally, this botanical is now the subject of research for its apparent ability to modulate hormones linked to appetite, satiety, insulin sensitivity, and energy metabolism, Troxel notes.
And in five peer-reviewed, double-blind, placebo-controlled clinical studies involving more than 400 subjects9-13, supplementation with IGOB131, the company’s Irvingia gabonensis product standardized to an aqueous-ethanol-extracted minimum of 10% albumins and 1% ellagic acid, has led to significantly lower bodyweight and body-fat percentage, as well as significantly lower levels of LDL cholesterol and the inflammatory biomarker C-reactive protein.
And while initial observations suggested that the extract’s beneficial metabolic effects owed to its high fiber content, Troxel says that “subsequent analysis suggests additional and unidentified bioactive components have contributory effects.”
Also out of African tradition is Dyglomera, Gateway Health’s patented extract of Dichrostachys glomerata standardized to an aqueous ethanol–extracted minimum of 10% polyphenols. According to Troxel, the supplement doesn’t just restore sensitivity to insulin, leptin, and adiponectin to improve blood sugar, satiety, and appetite; it also “favorably modulates various metabolic pathways and reduces oxidative stress linked to cell damage and that contributes to obesity and a high body-mass index.”
A randomized, double-blind, placebo-controlled clinical study of 297 subjects14 found that after eight weeks of supplementation, participants in the Dyglomera group lost an average of 24.5 lb compared to 1.16 lb for the control group. The Dyglomera subjects also saw significant improvements in blood glucose and lipid parameters and reduced insulin resistance and circulating markers of inflammation.
Heartened by such results, Troxel has no doubt about weight-management supplements’ prospects even in the face of blockbuster drugs. “In fact, supplements’ role in weight management routines may actually increase as ingredient science expands through well-designed clinical studies.”
Yes, Ozempic and its ilk may exert a “short-term impact,” he allows. “But we think off-label use will fizzle once the public becomes more aware of the potential serious side effects of drugs like these. Healthy consumers will follow their traditional preferences for natural solutions over pharmaceuticals.”