That’s So Meta (bolic)!

by Lisa Schofield | November 1, 2024

People are finally seeking to tackle their metabolic health, but there’s still a lot of work to do.

Ballooning waistlines tend to be the factor that opens people’s eyes that there may be something more insidious going on inside them—chiefly, metabolic dysfunction. And unfortunately, those with metabolic dysfunction, metabolic syndrome or pre-diabetes comprise a very large group.

One published analysis generated from the National Health and Nutrition Examination Survey (NHANES) 2009-2016 of 8,721 respondents found that only one in eight adults have optimal metabolic health.

Similarly, a study published in July 2022, that examined data from the NHANES 2017-2018 determined that just 6.8 percent of U.S. adults have optimal cardiometabolic health, down from 1999-2000. “This demonstrates a lack of understanding of risks associated with poor metabolic health,” said Dayna Dye, education content writer, Florida-based Life Extension.

And, pointed out Shawn Manske, ND, assistant director of clinical education, Biocidin Botanicals, California, research indicates that one in three adults now has non-alcoholic fatty liver disease (NAFLD) or what is being termed metabolic dysfunction-associated fatty liver disease (MAFLD). “There is increased promotion of dietary strategies, exercise and the use of supplements to address metabolic health,” he observed. “Additionally, gastric peptide therapeutics such as GLP-1 and GIP agonists are gaining recognition for their ability to promote satiety and weight loss.”

Nicole Avena, PhD, author of the new book Sugarless: A 7 Step Plan to Uncover Hidden Sugar, Curb Your Cravings, and Conquer Your Addiction, explained that approximately two in five American adults in the United States are clinically obese. Research shows that the prevalence of metabolic syndrome and cardiovascular disease is expected to rise along with the obesity epidemic.

“The exact etiology of metabolic syndrome is not fully understood at this time as several factors are interconnected. We do know that an individual’s weight is a major cause of metabolic syndrome. Whenever fat cells accumulate in the abdomen, it can increase the body’s levels of free fatty acids, which can raise other hormones in the body—impacting the way it responds to blood sugar levels. With this, the body’s ability to effectively respond to insulin may become impaired, leading to insulin resistance. Additionally, extra fat cells can increase inflammation and result in plaque build-up in blood vessels. Inflammation can also contribute to insulin resistance.”

Awareness is growing, and as a practitioner, you are likely finding more patients asking about their metabolic health during consultations. But maybe they’re not quite using that term, pointed out Nancy Morrow, MS, CN, clinical product support manager, Standard Process. “While the term ‘metabolic health’ may not be commonly used by the general public, there is a growing understanding that diet and lifestyle factors are foundational aspects of health and wellness,” she commented.

Morrow noted that campaigns launched by the Centers for Disease Control and Prevention (CDC), American Heart Association, American Diabetes Association, and other regional organizations have focused on public awareness of maintaining cardiovascular health have led to a greater understanding of how long-term wellness is impacted by key markers of metabolic health.

Indeed, underscored Dye, education does make a difference.” A 2022 study found that lower health literacy was associated with a higher number of metabolic syndrome-associated conditions that included hypertension, type 2 diabetes and abdominal obesity.

The COVID-19 pandemic had an impact on awareness of metabolic health, according to Joe Brunner, president, Oregon-based Endurance Products Company (EPC). He commented, “One pattern emerging from this collective trauma was hard to miss: Those with poor metabolic health faced more severe illness, longer hospital stays and higher death rates. In other words, the pandemic has transformed a once vague notion about metabolism into something visceral, real and deeply personal. As a result, more consumers than ever are motivated to learn about metabolic health so they can take proactive steps to safeguard their well-being.”

The Berberine Factor

It began on TikTok—berberine as the “natural Ozempic” for weight loss. As of 2023, reported Forbes, the hashtag on X (formerly Twitter) “#berberine” received 84 million views. And unlike previous fad supplement regimens touted for easy weight loss, the “hype” had some scientific support: authors of a 2020 systematic review and meta-analysis “found a significant reduction of body weight, BMI (body mass index), waist circumference and C-reactive protein levels associated with berberine intake, which may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.”

Jared Paulson, natural sales manager for Gaia Herbs Pro (North Carolina) substantiated, “Raspberry ketones and green coffee bean extract may have some beneficial effects but berberine has a mountain of research behind it showing that it is an extremely effective way to improve metabolic health, microbiome balance, and immune health. Berberine has proven to be much more than another fad at this point and continues to be a popular supplement, unlike these other ingredients.”

There is also work showing how it impacts metabolic health and weight. Vanessa Pavey, ND, education scientist, Life Extension, explained that berberine’s metabolic benefits stem from supporting the activation of AMPK (adenosine monophosphate activated protein kinase). AMPK is a fat-burning enzyme that regulates glucose and fat metabolism. AMPK promotes the uptake of glucose and fatty acids to create ATP. Accelerating AMPK activity encourages cells to release fat for use as energy, but aging slows this process, often resulting in “middle-aged spread.” The “spare tire” around the waist tends to increase inflammation, which she noted further impairs metabolic function.

Berberine has a storied past, according to Dr. Manske. He explained that it has been used for hundreds of years, predominantly in traditional Chinese medicine to address gastrointestinal issues. Now it’s used to aid blood sugar control and support insulin sensitivity, maintain healthy body weight and composition, support cardiovascular health, balance blood lipids levels, encourage healthy inflammatory balance and oxidative stress levels, and modify the intestinal microbiome. “All of these actions make berberine a useful adjunctive therapeutic for those who already experience metabolic dysfunction or for those who may be at risk of developing metabolic-related concerns,” he said.

Berberine, described Brunner, “is certainly having a moment thanks to solid research, social media buzz, and a wide variety of available products.” But, he cautioned, berberine products face two challenges. First, berberine is poorly absorbed, so high doses are required, such as 1,500 mg daily, in three 500 mg doses to obtain therapeutic effects. Consuming this high dose can cause digestive upset and make it difficult for a patient to stick to a treatment plan. Second, he added, a healthy gut microbiome is needed to convert berberine into its more absorbable form—dihydroberberine, which is absorbed up to five-fold more than berberine.

EPC’s dihydroberberine SR features GlucoVantage dihydroberberine, a highly bioavailable form of berberine; and the wax-matrix tablet is formulated for a slow, steady release of dihydroberberine over five to seven hours, according to Brunner. He explained that once absorbed, dihydroberberine rapidly converts to berberine in the blood. A growing body of research supports the use of berberine for managing blood glucose, blood lipid profiles, blood pressure and waist circumference, and the sustained-release delivery offers the convenience patients want. Its glycemic action is insulin-independent and mainly attributed to its ability to protect mitochondria, stimulate glycolysis, activate the glucose-transport AMPK pathway, and/or inhibit alpha-glucosidase. Its anti-obesity effect is attributed to its ability to inhibit adipogenesis, promote adipose tissue thermogenesis and energy expenditure, reduce adipose tissue fibrosis and inflammation, and/or regulate the gut microbiota.

Research into berberine’s metabolic effects began to gather steam in the early 2000s, as researchers began to investigate its potential benefits for blood sugar regulation, insulin sensitivity and lipid profiles, according to Morrow. This increase in research has reflected the public’s awareness of metabolic syndrome, she observed. “The last five years have seen an even more significant rise in berberine research output, with many new studies, systematic reviews and meta-analyses emerging, fueling an interest in its use in protocols to support metabolic health.”

Standard Process’ Berberine Active provides 200 mg of berberine per tablet, from Phellodendron amurense stem bark. The compounds in phellodendron are used traditionally in Chinese herbal preparations to help overcome the negative effects of a modern lifestyle and support healthy liver function.

Illinois-based Protocol for Life Balance Berberine “has been a big seller in the past couple years, prompting us to launch a new berberine product to add to this category,” related Celine Torres-Moon, senior scientist.

She explained that a multicenter, double-blind, randomized, placebo-controlled, clinical trial with berberine had compelling results. In the study, adult non-smoking volunteers with mild metabolic dysfunction factors supplemented with berberine (500 mg) or placebo twice daily (at lunch and dinner) for three months. The researchers observed a significant reduction of total and LDL cholesterol from 214 mg/dL to 191 mg/dL and from 157 mg/dL to 133 mg/dL, respectively, in the berberine group vs. baseline and placebo. They also observed that those in the berberine group had a significant reduction in triglycerides from 85 to 67 mg/dL vs. baseline, and a significant increase in HDL cholesterol from 40 to 45 mg/dL vs. baseline.

However, Dr. Pavey pointed out, berberine is not the only plant compound that has been shown to support AMPK activation. Hesperidin, a flavonoid from citrus fruit, and the herb Gynostemma pentaphyllum have also been shown in research to activate AMPK.

In a clinical trial, 24 participants with metabolic syndrome were given 500 mg of hesperidin or placebo daily and after three weeks significant improvements in markers of inflammation, vascular function, and metabolism were seen in the hesperidin group compared to placebo.

Gynostemma pentaphyllum is a botanical that has exhibited AMPK activation in preclinical studies. In a human study, 80 overweight volunteers were randomized to receive 450 mg G. pentaphyllum extract or placebo and all participants were instructed to follow their regular diets. At the end of 12 weeks, the G. pentaphyllum group demonstrated a reduction in total fat by 6.3 percent (compared to 1 percent for placebo) and a reduction in abdominal fat by 11 percent (compared to 3 percent for placebo).

Product Recommendations

Metabol Complex, from Standard Process is influenced by ayurveda, and contains fenugreek, black cumin seed, bitter melon and cinnamon to provide multi-action metabolic support, according to Morrow. The formula supports metabolism of fats and sugars, normal pancreatic and liver function, and also helps relieve occasional indigestion symptoms of the gastrointestinal* tract, such as bloating and gas.

Life Extension’s Waistline Control features Meratrim, a combination of Sphaeranthus indicus flower and Garcinia mangostana (mangosteen) fruit rind extracts. “Clinical studies found Meratrim along with diet and exercise helps promote weight loss and waistline reduction. In-vitro studies have shown this herbal combination reduces the expression of proteins associated with fat production (adipogenesis) and promotes fat breakdown,” said Dr. Pavey.

An RCT involving 57 healthy overweight participants who consumed 400 mg Meratrim twice per day were asked to follow a standardized diet of 2,000 kcal per day with 17 percent protein, 25 percent fat, and 58 percent carbohydrates, in addition to a 30-minute walk five days per week for the 16-weeks of the study. Results showed that body weight decreased 11.2 lbs. (6.7 percent) in Meratrim group and 2.4 lbs. in placebo group. Waist circumference decreased 3.9 inches in Meratrim group and 1.5 inches in placebo group; hip circumference decreased 4.1 inches in Meratrim group and 2.0 inches in the placebo group.

Metabolic health starts in the microbiome as dysbiosis contributes to the development of metabolic disorders, according to Dr. Manske. He explained, “Dysbiosis or pathogen overgrowth in the gastrointestinal tract can lead to increased systemic inflammation, which can impair insulin signaling and lead to blood sugar dysregulation—increasing the risk for developing diabetes, weight gain or obesity, NALFD and the longer-term consequences of these problems.”

And, he continued, metabolic health can be improved through several factors: by removing unwanted organisms and disrupting their biofilms; supporting the elimination of bacterial toxins, endogenous and environmental toxins; and providing probiotic strains and nutrients that support gut barrier function and inflammation management.

Biocidin’s Bioclear Microbiome Detoxification Program, which includes Biocidin, G.I. Detox+, and Proflora 4R, is designed to help to support a healthy microbiome profile. In addition to healthy dietary and lifestyle changes, the Bioclear Microbiome Detoxification program may lead to improvements in blood sugar regulation, effective weight management, healthy blood pressure and healthy blood lipid levels, noted Dr. Manske.

Life Extension’s Glycemic Guard helps manage post-meal blood sugar levels. It combines maqui berry (Aristotelia chilensis) standardized to delphinidins and a water-soluble clove (Syzygium aromaticum) extract to help promote a healthy insulin response and supporting normal HgA1c levels. In an open label study assessing HgA1c every 30 days for 90 days, 31 pre-diabetic overweight/obese participants consumed 180 mg standardized maqui berry extract once daily before breakfast. “Researchers found a statistically significant decrease in HgA1c starting at day 60 of the study,” she reported. HgA1c decreased from 5.65 percent at baseline to 5.35 percent by day 90.

California-based 1MD Nutrition’s GlucoseMD helps maintain healthy blood glucose levels and supports normal glucose uptake, according to cardiologist Heather Shenkman, MD, formulator for the company. “The active ingredients in GlucoseMD, Cinsulin (Cassia cinnamon), berberine bark extract, chromium and lion’s mane work together to promote glucose metabolism,” she explained.

Standard Process’ Glucose Assist is a blend of plant-based carbohydrates and proteins, including all essential amino acids. According to Morrow, it features EnergySMART, a slowly digestible complex carbohydrate complex that provides a slower and more sustained release of glucose. In addition, Glucose Assist provides protein-rich, plant-based nutrition from peas, oats, pumpkin seed and buckwheat that might help further minimize blood glucose spikes. “This can support a reduction of post-prandial glycemic response, which has been demonstrated by recent Standard Process clinical studies,” she commented.

In tandem, naturopaths can augment this supplement with Diaplex contains chromium in a blend of whole foods, enzymes and other ingredients, to manage carbohydrate metabolism.

Gaia Herbs PRO offers Tri-Glycemic and AMPK Activator formulas. Tri-Glycemic is a combination of kimchi ferment, ABAlife fig extract, bitter melon, ginger and BPL-1 postbiotic to support the microbiome’s ability to process sugars and carbohydrates in a healthy manner, according to Paulson. “Our AMPK Activator with InnoSlim (a combination of astragalus and notoginseng), bilberry and resveratrol addresses what occurs once these calories are in the body and focuses on fine-tuning cellular metabolism, from getting glucose into the cells to supporting mitochondrial function.

Blood pressure regulation is not as widely discussed by patients but should be examined and moved to the forefront when talking about metabolic health.

Gaia Herbs PRO’s Systolic Complex, Paulson described, is formulated to address not only healthy blood pressure levels but also vascular health. It contains clinically studied Pomanox pomegranate extract and along with hibiscus, holy basil and olive leaf.

EPC’s MegaNatural-BP Grape Seed Extract is a sustained-release tablet combining a clinically tested extract of grape polyphenols “with our proprietary wax-matrix tablet to promote optimal bioavailability,” Brunner described. “At least three controlled clinical trials involving adults with pre-hypertension or metabolic syndrome indicate that MegaNatural-BP Grape Seed Extract supplementation (150 mg/day or 300 mg/day for four to eight weeks) helps maintain normal blood pressure. Researchers attribute this effect to activating nitric oxide synthase (eNOS) to produce nitric oxide, which has an endothelial-relaxing effect.”

CardioFitMD, from 1MD Nutrition, is a superfood drink that can promote healthy blood pressure, help maintain a healthy weight, and supports energy levels and stamina, according to Dr. Shenkman. Beetroot, the primary ingredient, promotes optimal levels of nitric oxide, which provides circulatory support, as well as promotes stamina, and energy. Broad-spectrum fiber in the beverage nourishes the microbiome for weight-management support and proper bowel function. Further, CardioFitMD contains a prebiotic blend to nourish the good bacteria, and Bacillus coagulans, a probiotic that promotes gut microbiome health and by doing so, supports healthy blood sugar levels and cholesterol.

In summary, Dr. Avena commented, “Behavioral and lifestyle changes are vital in impacting metabolic health and should be emphasized by practitioners. Typically, metabolic syndrome is seen in individuals with abdominal obesity. For these individuals, making necessary diet and lifestyle changes is an important treatment approach.”

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Healthy Take Aways

• Only one in eight adults have optimal metabolic health.
• A study published in July 2022, that examined data from the NHANES 2017-2018 determined that just 6.8 percent of U.S. adults have optimal cardiometabolic health, down from 1999-2000.
• Research indicates that one in three adults now has non-alcoholic fatty liver disease (NAFLD) or what is being termed metabolic dysfunction-associated fatty liver disease (MAFLD).
• As of 2023, reported Forbes, the hashtag on X (formerly Twitter) “#berberine” received 84 million views.