Globally, the struggle with obesity is a widespread concern, leading many to seek effective, non-conventional weight reduction methods, including herbal and natural dietary supplements. Among these, fat burners are popular, with the belief that they can accelerate fat loss by raising metabolism and burning more calories. However, it's crucial to recognize that despite the perception that herbal remedies are free of adverse effects, some supplements have been linked to severe health issues, such as hepatotoxicity.
The Appeal of Weight Loss Supplements
In recent years, the alarming increase in obesity worldwide has driven a growing number of individuals to find the best ways to lose weight. This demand has fueled a massive industry for weight loss and related health products. Herbal remedies, in particular, remain a popular choice due to their perceived safety and easy availability, especially since they are not subject to regulatory testing by the United States Food and Drug Administration (FDA). Among these remedies, "fat burners" are heavily marketed for their ability to increase thermogenesis and the basal metabolic rate, mimicking the effects of exercise.
The Dark Side of "Fat Burners": A Case Study
Several slimming aids and herbal medications have been associated with severe hepatotoxicity, as reported in medical literature. One case involved a previously healthy 28-year-old female bodybuilder with no risk factors for liver disease who presented with fatigue, malaise, inability to exercise, and new-onset jaundice. Her symptoms worsened over a span of one week before hospitalization.
The patient was taking a multi-ingredient, nonstimulant health supplement and fat burner (Somalyz and Lipolyz, Species Nutrition, USA). Somalyz contains usnic acid (4 mg), propionyl-L-carnitine (167 mg), phosphatidylcholine/phosphatidylethanolamine (50 mg), gamma-aminobutyric acid (667 mg) and vitamin E (27 IU) per capsule. Lipolyz contains usnic acid (12 mg), propionyl-L-carnitine (500 mg), green tea extract (300 mg), guggulsterone Z and guggulster-one E (10 mg), cyclic adenosine monophosphate (2 mg) and vitamin E (20 IU) per capsule. She was taking one to two capsules of Somalyz at bedtime and one capsule of Lipolyz with meals three times a day as recommended for one month before illness.
On evaluation at The Mount Sinai Medical Center, there were no stigmata of chronic liver disease. Blood work revealed a total serum bilirubin level of 82.08 mmol/L (normal range 1.71 mmol/L to 20.5 mmol/L), a direct bilirubin level of 47.88 mmol/L (1.71 mmol/L to 13.6 mmol/L), a serum alanine aminotransferase level of 1220 U/L (1 U/L to 53 U/L), a serum aspartate aminotransferase level of 577 U/L (1 U/L to 50 U/L), an alkaline phosphatase level of 111U/L (30 U/L to 110 U/L), a gamma-glutamyl transferase level of 125 U/L (8 U/L to 35 U/L), an international normalized ratio of 2.6 and a serum creatinine level of 53.04 μmol/L (44.2 μmol/L to 106.2 μmol/L). Etiological workup included the following: negative viral serology (hepatitis A virus immunoglobulin M, hepatitis B virus surface antigen and core antibody, hepatitis C virus antibody [polymerase chain reaction assay], cytomegalovirus DNA and Epstein-Barr virus immunoglobulin M); negative syphilis rapid plasma regain; negative autoimmune markers (antinuclear antibody, antiliver kidney muscle antibody, antimitochondrial antibody and antismooth muscle antibody); and normal serum gamma globulins. Extensive toxicology screening was negative, with no features of acetaminophen toxicity (acidosis, high lactate or renal failure). She had normal levels of ferritin, ceruloplasmin and alpha-1 antitrypsin. A pregnancy test was negative. A computed tomography scan of her abdomen revealed a normal size liver with a patent portal vein, hepatic artery, hepatic vein and normal biliary anatomy. The patient’s encephalopathy worsened and she remained unresponsive. A computed tomography scan of her head was normal. An intracranial pressure monitor was placed, which measured an intracranial pressure of 19 mmHg and a cerebral perfusion pressure of 77 mmHg to 82 mmHg. She underwent successful cadaveric orthotopic liver transplantation on hospital day 2. By postoperative day 4, she was awake and alert.
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Histology of the native explanted liver. A Low-power magnification showing confluent necrosis resulting in parenchymal collapse (hematoxylin and eosin stain, original magnification ×40). B Reticulin stain confirming the extensive parenchymal collapse (original magnification ×40). C High-power magnification showing the formation of ductular hepatocytes in periportal areas (arrow) (hematoxylin and eosin stain, original magnification ×100).
Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects.
The Role of Specific Ingredients
Based on the temporal relationship between the use of the dietary supplements and onset of liver failure, literature supporting reports of hepatotoxicity associated with dietary supplements and exclusion of other causes, it is fair to assume that the patient developed fulminant hepatic failure due to dietary supplements. In view of the bulk of the literature, of all the ingredients, usnic acid may have been predominantly responsible for the hepatoxicity.
Usnic Acid
Usnic acid is a component of nutritional supplements that are promoted for weight loss and have been associated with liver-related adverse events including mild hepatic toxicity, chemical hepatitis and liver failure requiring liver transplantation. Usnic acid is derived from a lichen species of the genus Usnea. It has been investigated for diverse uses as an antimicrobial, an anti-inflammatory, an antioxidant, an analgesic/antipyretic, an antiproliferative and as a natural supplement for weight loss. Several previous reports described liver failure associated with the use of LipoKinetix, a multi-ingredient preparation containing usnic acid (6-8). In 2002, Favreau et al (6) reported on seven patients who developed acute hepatitis after using LipoKinetix. This dietary supplement contains sodium usniate, norephedrine, yohimbine, 3-5-diiodothyronine and caffeine; both usnic acid and ephedra alkaloids have been associated with severe hepatotoxicity. Sanchez et al (8) reported severe hepatotoxicity in a husband and wife (both 38 years of age) who were bodybuilders taking the multi-ingredient health supplement UCP-1 (BDC Nutrition, USA) for three months. UCP-1 contains usnic acid (150 mg), L-carnitine (525 mg) and calcium pyruvate (1050 mg) per capsule. The wife developed fulminant hepatic failure requiring liver transplantation. The husband experienced submassive necrosis but did not require liver transplantation. Another herbal remedy containing usnic acid - well known to be hepatotoxic - is kombucha tea. Usnic acid has been shown to uncouple oxidative phosphorylation in a murine model, with resultant loss of mitochondrial respiratory control and inhibition of ATP synthesis. A direct hepatotoxic effect analogous to carbon tetrachloride-induced liver toxicity has also been described (10). Usnic acid is a weak inhibitor of cytochrome CYP2D6 and a potent inhibitor of cytochrome CYP2C19. Based on potent inhibition of CYP2C enzymes, usnic acid has significant potential to interact with other medications (5).
Green Tea Extract
Chinese green tea extracts are derivatives of the leaves of Camellia sinensis, which belongs to the aceae family. Green tea extracts have been marketed as effective weight-loss supplements, and for the prevention and cure of solid tumours. Although there is little scientific evidence supporting the effectiveness of green tea extracts, serious side effects, including acute liver failure, are increasingly being reported (13,14). Similar cases have been reported from France and Spain resulting in the removal of the green tea extract ‘Exolise’ from the market (15). Two cases of fulminant hepatic failure associated with green tea extracts have been reported (16,17). Mitochondrial toxicity and the formation of reactive oxygen species have been demonstrated with epigallocatechin-3-gallate, a key constituent of green tea extracts.
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Gum Guggul
Gum guggul and its constituents are increasingly being used as dietary supplements. Gum guggul is the oleoresin of Commiphora mukul, a plant native to India. Its extracts include compounds known for their hypolipidemic properties - the Z and E isomers of guggulsterone and its regulated guggulsterols. Human exposure to gum guggul most often occurs from ingesting herbal remedies or pharmaceuticals, and from the use of cosmetics. Side effects include skin rashes, irregular menstruation, diarrhea, headache, mild nausea and, with very high doses, liver toxicity.
Regulatory Landscape and Consumer Awareness
According to the Dietary Supplement Health and Education Act of 1994, dietary supplements are regulated as foods and are not subject to regulation as drugs by the FDA; manufacturers are not compelled to provide safety data to the FDA. However, increasing reports of liver failure due to usnic acid have triggered a regulatory warning and one voluntary product withdrawal (LipoKinetix) (20). Despite this, usnic acid is still available and advertised on the Internet as an ingredient in various other dietary supplements and fat burners.
Bravenly Global: A Wellness Brand
At Bravenly Global, we are a family-owned wellness brand built on courage, integrity, and authenticity. We believe wellness is a lifestyle, not just a product. One rooted in trust and bold living. Our clean supplements are crafted with the highest-quality ingredients for purity, potency, and sustainability. From energy support to holistic health, we make wellness simple, effective, and accessible. Proudly based in Florida yet reaching worldwide, we partner with communities to inspire vitality, confidence, and positive change.
Plexus: An Overview
Plexus is a dietary supplement company that’s best known for its “pink drinks,” such as Plexus Slim Hunger Control or Plexus Slim Microbiome Activating. They are sold as powdered supplements meant to suppress appetite and help you lose weight. Over the past few years, the company’s product line has greatly expanded to include items like the Plexus Block, which is purported to help metabolize carbohydrates, and Plexus MetaBurn, which claims to boost metabolism and burn fat.
The MLM Model
Plexus operates using a multilevel marketing (MLM) structure. This means that products are largely marketed and sold by brand ambassadors. Like many other MLMs, the company makes extravagant claims about brand ambassadors’ profit-making capability. This can be dangerous, as brand ambassadors often recommend products to new customers despite lacking proper education on nutrition and supplements. The company is also known to make bold claims regarding the effectiveness of its products without clinical evidence or third-party testing to support them.
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Furthermore, in 2020, Plexus received a letter of warning from the Federal Trade Commission (FTC) in regards to social media posts that claimed that Plexus products could help treat or prevent COVID-19 (2).
The Pivotal Program
According to Plexus, participants will receive weekly content that educates them on building healthy habits. The program could be helpful for someone who is independent and feels confident tackling weight loss on their own or has already sought other support. However, research shows that strategies such as keeping a food diary, maintaining a good support system, and setting goals are some of the most effective methods for successful weight loss. So, for someone just getting started, this program may not be enough (3).
Additionally, diet and lifestyle sustainability are important for success. Research shows that adherence to a diet, rather than the specific diet itself, is important for success (4).
Cost and Long-Term Feasibility
Anyone considering Plexus should also consider whether it’s financially feasible long-term. The packages are relatively costly, and the company provides few guidelines on how long to take the products. Therefore, you may find this weight loss approach difficult to maintain over time.
The cost varies depending on which combination package you purchase and whether you’re a VIP customer. Plexus weight management combos are designed to provide 30-days-worth of product and vary in the types of products included. Here’s an overview of the price and what’s included for each weight management combo:VIP customers pay a $9.95 sign-up fee along with an annual $19.95 annual fee in order to receive up to 25% off products. Additionally, all customers have the option to sign up for a monthly subscription with a 10% discount after the first two consecutive subscription orders.
Plexus offers three weight management product combinations, including Weight Loss Basics, Weight Loss Plus, and Weight Loss Advanced.Here are the products found in various weight loss combos:Plexus Lean. Lean is a protein powder that comes in both chocolate and vanilla flavors, as well as either whey or vegan protein. These powders come in a variety of flavors and are recommended to be mixed with water and consumed 30-60 minutes before a meal twice a day. Slim Hunger Control is purported to suppress appetite, while the Microbiome Activating powder claims to support gut health. MetaBurn. These capsules claim to support fat burning and boost energy levels. Individuals are encouraged to take one capsule, twice a day.Active or Hydrate. These drink mixes are included in the Plus and Advanced combos and are claimed to help boost either hydration (Hydrate) or energy levels (Active). They’re designed to be mixed with water and be consumed at any time. BioCleanse. These capsules are included in the Advanced combo and claim to help reduce gas, bloating, and stomach discomfort. Individuals are instructed to take 2 capsules with 8 ounces (236.6 mL) of water twice daily between meals.The ProBio 5. These capsule are also included in the Advanced combo. While there are instructions on how to take each of the products, and even recommendations for decreasing meal replacement shakes once you reach your weight goal, there are no guidelines for how long to continue taking these products for.
Lack of Safety Research and Third-Party Testing
Finally, no specific research supports the safety of Plexus supplements, and they are not third-party tested. It’s best for certain individuals, such as children and people who are pregnant or nursing, to avoid these products.
A Closer Look at Plexus Ingredients and Nutrition
Here’s a closer look at the ingredients and nutrition facts of the main Plexus weight management products, including Plexus Lean, Slim Hunger Control and Microbiome Activating, MetaBurn, and Block. Plexus Lean is designed to be used as a meal replacement for 2 meals per day for weight loss, or for 1 meal per day for weight maintenance.
Plexus Lean
The nutritional information for 2 scoops (40 grams) of the chocolate Lean Whey is as follows (5):Calories: 140Fat: 3 gramsSaturated fat: 1.5 gramsCarbohydrates: 12 gramsFiber: 5 gramsSugar: 3 grams (includes 1 gram of added sugar)Protein: 21 grams
The vanilla Lean Whey is slightly different in terms of nutritional information (6):Calories: 140Fat: 3.5 gramsSaturated fat: 1 gramCarbohydrates: 11 gramsFiber: 5 gramsTotal sugars 3 grams (includes 1 gram of added sugar)Protein: 21 grams
The nutritional information for 2 scoops (48 grams) of the chocolate Lean Vegan prepared with water is as follows (7):Calories: 140Fat: 3.5 gramsSaturated fat:.5 gramsCarbohydrates: 11 gramsFiber: 7 gramsSugar: 2 gramsProtein: 21 grams
The vanilla Lean Vegan is nearly identical (8).Calories: 140Fat: 3 gramsSaturated fat:.5 gramsCarbohydrates: 12 gramsFiber: 7 gramsSugar: 1 gramsProtein: 21 grams
Below is an overview of the ingredients found in the Lean shakes.
rBGH-Free Whey Protein
The Lean Whey shakes are made with a combination of whey concentrate and whey isolate proteins and are meant to support lean muscle growth. Research supports the use of whey protein, or other complete sources of protein, like chicken or beef, for supporting muscle mass and benefits in body composition (9).
Vegan Protein Blend
The vegan variety of the Lean shake contains a protein blend made from pea and almond proteins, rather than whey protein, which is derived from cows. Research shows pea protein to be beneficial for supporting lean muscle mass, and some studies have found it to be comparable to whey protein for improving body composition (10). Research shows that some individuals, such as those with a lactose intolerance or cystic fibrosis, may benefit from digestive enzymes (15). However, it’s unclear if digestive enzymes offer the same effect in those without lactose intolerance or another gastrointestinal condition.
Other Ingredients
Lean also contains 21 vitamins and minerals. Flax seeds are rich in omega-3 fatty acids, which may help reduce the risk of some disease, such as heart disease, cancer, and some neurological disorders (16). Both the whey and vegan Lean products are sweetened with coconut sugar and stevia leaf extract.
Plexus Slim Hunger Control and Microbiome Activating
All weight loss combos come with a choice of either Plexus Slim Hunger Control or Microbiome Activating powder. The main difference between the two is that the Hunger Control contains polydextrose, a type of soluble fiber, while Microbiome Activating contains prebiotics called xylooligosaccharides (XOS).
The nutritional information for 1 packet of Plexus Slim Hunger Control (17):Calories: 15Fat: 0 gramsSaturated fat: 0 gramsCarbohydrates: 8 gramsFiber: 6 gramsSugar: 0 gramsProtein: 0 grams
The nutritional information for 1 packet of Plexus Microbiome Activating (18):Calories: 5Fat: 0 gramsSaturated fat: 0 gramsCarbohydrates: 2 gramsFiber: 0 gramsSugar: 0 gramsProtein: 0 grams
Slim Hunger Control (Polydextrose)
Plexus claims that Slim Hunger Control is designed to help individuals feel full, thanks to its polydextrose content. Polydextrose is a soluble fiber that’s commonly used as a bulking agent and thickener in commercial food products (19). Some research suggests that polydextrose may improve postprandial blood sugar levels (blood sugar levels after a meal), decrease overall caloric intake by enhancing satiety, and improve overall bowel function (19). However, the review includes both animal and human studies. Furthermore, there’s currently no research supporting the company’s claim that green coffee bean extract decreases the body’s absorption of sugars.
Chromium Polynicotinate
Chromium is an essential mineral that plays an important role in breaking down carbs, fat, and protein, making it a popular ingredient in weight loss supplements. One review found that taking chromium supplements was linked to weight loss and reductions in body fat percentages in people with overweight and obesity.
Plexus Block
Plexus Block is marketed as supplement that can lower the glycemic index of food and reduce the absorption of carbohydrates. Plexus recommends taking two capsules a day, ideally before your highest carbohydrate meal.
Brown Seaweed Blend and White Kidney Bean Extract
Plexus claims the brown seaweed blend and white kidney bean extract in Plexus Block reduces the glycemic index of foods, thereby helping reduce blood sugar spikes after eating. Some test-tube studies suggest that brown seaweed may help in the prevention and management of metabolic syndrome, as well as other diseases, by aiding in blood sugar management. However, human clinical trials are lacking in quality and have shown varied results (34, 35). White kidney bean extract contains alpha-amylase inhibitor, which blocks the absorption of carbohydrates. However, it’s unclear whether white kidney bean extract has a significant effect on carbohydrate absorption and weight loss (36, 37). Lastly, it’s important to note that this is a proprietary blend, which means the exact amounts of ingredients are not disclosed.
Chromax Chromium Picolinate
Also present in Slim Hunger Control and Microbiome Activating, chromium picolinate is an ingredient that’s often found in weight loss supplements due to its role in nutrient metabolism. While some research supports the use of chromium supplements for aiding weight loss, more studies are needed (24).
Potential Effectiveness and Side Effects of Plexus
Plexus may be effective for weight loss, particularly because it encourages you to consume fewer calories each day. However, it’s likely too low in calories for adults. Most adults should consume at least 1,500 calories per day, and prolonged low calorie intake can harm your metabolism (38, 39). Even if you see initial weight loss on this type of diet, it’s most likely from water loss and you’ll likely gain the weight back once the diet ends.
Some customers complain of side effects after taking Plexus products, including bloating, gas, nausea, stomach ache, and constipation. There have also been reports of more serious negative outcomes, including one person who developed a blood disorder known as secondary immune thrombocytopenic purpura (ITP) after consuming Plexus Slim (41). However, Plexus products haven’t officially been proven to be the cause of more serious side effects, such as ITP.
Precautions and Recommendations
Due to a lack of research on the safety of the products, Plexus supplements shouldn’t be consumed by children or people who are pregnant or breastfeeding. It’s also important to consult a healthcare professional before trying any new supplement.
If you’ve been trying to lose weight without success, you might consider seeking the opinion of a healthcare professional, such as your doctor, or a registered dietitian. Because no research-based evidence supports the use of Plexus supplements for weight loss, you may have more success working with a professional who can help you set realistic goals and build sustainable habits informed by your needs and dietary restrictions.
Additionally, some individuals have reported experiencing side effects after using Plexus supplements. If you’ve been using the products and are noticing any side effects, such as gas, nausea, or other stomach discomfort, it’s a good idea to stop using the supplements immediately and consult a healthcare professional.
FDA Regulation of Supplements
The FDA regulates supplements differently from foods and medicines. Foods and medicines must be proven safe before manufacturers can make them available to consumers. However, the FDA does not have the authority to approve supplements for safety before they are widely sold. This is true of all supplements, not just Plexus products (42). This is because there are no legal provisions for the FDA to approve supplements before they reach consumers.
The "Pink Drink" Explained
The Plexus pink drink is officially called Plexus Slim Hunger Control. It’s a powdered supplement designed to suppress appetite when mixed with water and consumed 30-60 minutes before a meal. The powder is made of polydextrose, a soluble fiber. In preliminary studies on animals, researchers found that the fiber may help lower overall food intake by increasing fullness. However, more research is needed (43).
Is Plexus Safe for Weight Loss?
It’s unclear whether Plexus products are safe for weight loss because they have not been explicitly tested or certified by third-party agencies. It’s also worth noting that there have been anecdotal complaints of side effects and some reports of more serious complications from taking the products (44).