Obesity Supplements

Earn CME/CE in your profession:


Continuing Education Activity

Over 70% of adults in the United States are overweight or obese. This significantly increases the risk of developing several chronic diseases and levies an enormous cost to the healthcare system. While a nutritious diet and active lifestyle are the foundation of optimal weight and good health, the appeal of a quick fix is strong. Approximately one-third of adults in the United States have used dietary weight-loss supplements. While a nutritious diet and active lifestyle are the foundation of optimal weight and health, the appeal of a quick fix is strong. This activity reviews the types, indications, contraindications, actions, and adverse effects of available non-prescription weight-loss supplements and highlights the role of the interprofessional team in managing patients with overweight and obesity.

Objectives:

  • Review data on the efficacy of various dietary weight-loss supplements.
  • Explain the mechanisms of action for dietary weight-loss supplements.
  • Identify contraindications to common dietary weight-loss supplements.
  • Summarize the risks associated with dietary weight-loss supplements and key patient counseling points.

Introduction

Over 70% of adults in the United States are overweight or obese.[1] This significantly increases the risk of developing several chronic diseases and levies an enormous cost to the healthcare system. While a nutritious diet and active lifestyle are the foundation of optimal weight and good health, the appeal of a quick fix is strong. About one-third of adults in the United States attempting to lose weight have utilized dietary supplements.[2] Despite promising mechanistic data, evidence that these supplements are safe and effective is lacking, limiting their clinical usefulness.

Function

Beta-Glucans

Beta-glucans are soluble fibers found in bacteria, yeast, fungi, and grains such as oat bran and barley. They are glucose polysaccharides fermented by the gut microbiota.[3] Weight loss effects may be due to increased satiety and decreased food intake. A meta-analysis published in 2019 showed that most trials reported non-significant or no weight loss from beta-glucans administered at a dose of three to ten grams per day for four to twelve weeks.[4] Data does not currently support their use for the treatment of obesity. Adverse effects include increased flatulence.[5]

Camellia Sinensis

Camellia sinensis is the active ingredient found in the green tea plant. This popular plant is thought to aid in weight loss through anti-lipidemic effects.[6] The data for weight loss in humans have been mixed, generally showing a modest effect. In a 2012 Cochrane systematic review, green tea was associated with a slight, statistically non-significant decrease in weight among overweight and obese adults. The mean difference in weight loss ranged from 0.2 kg to 3.5 kg compared with a placebo.[7] A more recent meta-analysis found a statistically significant but modest decrease in body mass index (BMI) with green tea consumption.[8] 

Consumption of green tea as a beverage is generally regarded as safe in moderate amounts, and the extract appears to be well-tolerated when used for prolonged periods.[9] However, green tea extract may inhibit iron absorption and should be used cautiously in iron-deficient patients. Patients with low bone density should be careful about excessive use since large quantities of green tea extract contain high doses of caffeine that can contribute to urinary calcium losses.[10] In addition, caffeinated green tea may worsen symptoms in patients with anxiety, diarrhea, and dysrhythmias and increase intraocular pressure in glaucoma.[11][12] Patients with liver disease should use supplements containing green tea extract with caution, as there have been isolated cases of associated hepatotoxicity.[13]

Chromium Picolinate

Chromium is an essential mineral associated with reduced hunger levels and food intake, likely via its action on insulin-sensitive signaling pathways in the brain.[14] Chromium is often combined with picolinic acid to aid absorption, and the resulting chromium picolinate compound has been marketed as a diet aid. A 2013 Cochrane systematic review and meta-analysis found that it decreased body weight an average of 1.1 kg more than the placebo, a statistically significant finding but of questionable clinical significance.[15] Furthermore, there have been safety concerns, with reports of nephrotoxicity.[16][17][18] Chromium can cause hypoglycemia, so patients taking diabetes medications must monitor their blood glucose. Adverse events, including urticaria, vertigo, nausea, vomiting, fatigue, abdominal cramps, and bloating, are generally mild and self-limited.

Citrus Aurantium 

Citrus aurantium, also known as bitter orange, is derived from a fruit-bearing tree indigenous to Southeast Asia. Due to its sympathomimetic properties, bitter orange gained popularity as a weight-loss supplement after ephedra was banned because of adverse cardiovascular effects.[19] Like ephedra, Citrus aurantium has alpha and beta-adrenergic effects and is purported to increase metabolic rate and lipolysis.[20] Several studies have examined multi-ingredient products containing bitter orange. They have found these products to have beneficial effects on weight loss, but the individual effect of bitter orange itself is difficult to ascertain.[21] When studied alone, bitter orange increases basal metabolic rate in adults.[22] A review of published and unpublished studies concluded that bitter orange extract and p-synephrine increase metabolism and energy expenditure, but there is a need for long-term efficacy studies in humans.[23] 

There are safety considerations regarding this supplement when used for weight loss. In patients taking diabetes medications, concurrent use of bitter orange may have an additive hypoglycemic effect, and blood glucose should be monitored closely. Bitter orange inhibits CYP3A4 metabolism, and patients taking medications that are CYP3A4 substrates should use the supplement with caution.[24] Bitter orange, especially in combination with caffeine, may increase blood pressure and heart rate, and patients with cardiovascular disease or hypertension should avoid its use.[25] CNS stimulant medications and monoamine oxidase inhibitors can increase the hypertensive and cardio-stimulatory effects of bitter orange, and concurrent use should be avoided. However, there is a lack of direct evidence to support this conservative approach, and randomized controlled studies would be helpful.

Coleus Forskohlii

Coleus forskohlii is a member of the mint family and has been used for centuries for its medicinal properties. Forskolin is derived from the roots of the Coleus forskohlii plant and promotes the release of fatty acids from adipose tissue by stimulating cyclic AMP.[26] Cyclic AMP increases the utilization of body fat and regulation of the body’s thermogenic response to food, which is purported to cause an increase in lean tissue and a loss of body fat. Human studies on forskolin extract have shown inconsistent results. One double-blind placebo-controlled study of 15 obese men administered 500 mg a day of 10 percent forskolin extract for twelve weeks showed promising results with decreased body fat and increased lean body mass.[27] A similar study of 19 moderately overweight women assigned to receive 500 mg per day of 10 percent forskolin extract for twelve weeks showed some appetite reduction but no significant changes in food intake or weight.[28] More clinical data and more extensive studies are needed. No significant side effects or adverse events were reported with C. forskohlii supplementation.

Conjugated Linoleic Acid

Conjugated linoleic acid (CLA) is found in dairy and meat products. In supplement form, it is usually synthesized from safflower and sunflower oils. Animal studies suggest that CLA promotes lipolysis, increases apoptosis in adipose tissue, inhibits lipogenesis, and reduces food intake.[29][30][31] In humans, CLA appears to have a minimal to modest weight-reducing effect. A 2007 meta-analysis showed that CLA was associated with a weight loss of 0.09 kg per week. In a 2012 meta-analysis, overweight and obese individuals who took CLA lost an average of 0.7 kg more than those who received a placebo.[32][33] 

Adverse effects are generally mild, such as constipation and diarrhea. There are concerns that CLA may worsen insulin sensitivity and cholesterol levels, which are often already abnormal in overweight and obese individuals.[34] In addition, CLA may reduce platelet aggregation, so care should be taken if used concurrently with anticoagulants or antiplatelet therapies.[35]

Fucoxanthin

Fucoxanthin is a carotenoid found in brown seaweed and other algae. Preclinical data suggest that fucoxanthin might be effective for treating obesity through its anti-lipidemic properties. Only two clinical trials have been conducted using fucoxanthin. In a 16-week double-blind placebo-controlled trial, 151 non-diabetic, obese, pre-menopausal women with and without non-alcoholic fatty liver disease were given a combination of fucoxanthin with pomegranate seed oil (PSO) at different doses (300 mg algae containing 2.4 mg fucoxanthin plus 300 mg PSO versus 200 mg algae containing 1.6 mg fucoxanthin plus 200 mg PSO).[36] The group taking the higher dose of combined fucoxanthin plus PSO had a statistically significant reduction in body weight, waist circumference, and other metabolic parameters. In a double-blind, placebo-controlled trial of 31 obese participants receiving 0.8 mg fucoxanthin plus 100 mg of PSO versus placebo for sixteen weeks, no significant differences in body fat or weight loss were observed. Toxicological assessments of the combined fucoxanthin and PSO extract administered to rats found no teratogenic or toxic effects.[37] Of note, a statistically significant decrease in body weight and food intake occurred in the treated rats. Based on the results of the published data, no recommendations can be made about the efficacy of fucoxanthin for overweight and obesity treatment in humans, but preclinical and clinical data show promise.

Garcinia Cambogia

Garcinia cambogia is a fruit-bearing tree native to Southeast Asia and India. The plant’s active compound, hydroxy citric acid (HCA), has several potential mechanisms for mediating weight loss. HCA is thought to decrease fatty acid synthesis and lipogenesis, suppress appetite by increasing serotonin availability in the brain and increase hepatic glycogen synthesis, thus increasing satiety. In a 2011 meta-analysis, HCA decreased weight by 0.88 kg on average compared to a placebo.[38] While this finding did reach statistical significance, its clinical significance is questionable. Subsequent randomized controlled trials have failed to find a benefit.[39][40] 

Furthermore, safety has been questioned due to reports of associated liver toxicity. While most of these cases occurred in patients taking combination products, three have occurred with Garcinia cambogia alone, and patients with liver disease should be cautioned.[41][42]

Glucomannan

Glucomannan is a soluble fiber commonly derived from the Amorphophallus konjac root. Because human salivary and pancreatic amylase cannot split β-1,4 linkages, glucomannan passes relatively unchanged into the colon, where the gut microbiota ferment it.[43] While it may be an ingredient in weight-loss products, it is more commonly used to treat constipation or elevated glucose and cholesterol. The compound reportedly promotes satiety, slows gastrointestinal transit, and reduces fat and protein absorption through fecal loss. In animal studies, glucomannan suppressed hepatic cholesterol synthesis and increased the fecal excretion of bile acids and cholesterol.[44] In a 2008 systematic review and meta-analysis, glucomannan significantly lowered total cholesterol, low-density lipoprotein cholesterol, triglycerides, body weight, and fasting blood glucose. This led to a statistically significant, albeit unlikely clinically significant, weight loss of 0.79 kg.[45] However, two recent reviews showed no statistically significant change in weight compared to a placebo, contradicting the earlier meta-analysis.

Glucomannan appears to be well tolerated for short-term use. Minor adverse gastrointestinal effects include belching, bloating, frequent loose stools, flatulence, constipation, and abdominal discomfort.[46] There have been reports of esophageal obstruction following the consumption of glucomannan-containing compounds, specifically with the tablet formulation and in patients with esophageal pathology. The capsule form of the supplement has not been associated with this effect.[47]

Green Coffee Extract

Green coffee beans are unroasted mature or immature coffee beans. They are high in polyphenols, which have purported positive biologic effects, including anti-inflammatory activities and anti-diabetic, anti-lipidemic, and anti-hypertensive effects.[48][49] While earlier studies showed inconsistent benefits of green coffee bean extract on weight and body mass, more recent studies have been more promising. A meta-analysis published in 2011 assessing the efficacy of green coffee extract on weight loss analyzed three human studies and found an overall moderate benefit in favor of green coffee extract versus placebo, with a mean weight loss of 2.5 kg after four to twelve weeks.[50] A study published in 2017 examined 64 obese women randomized to receive 400 mg of green coffee extract per day for eight weeks and found significant reductions in body weight, body mass, and fat mass.[48] The safety of green coffee extract is difficult to assess due to the small sample size and duration of published studies. While none reported adverse events, more research is needed to detail a full safety profile. Given these promising early findings, green coffee extract is a topic for more extensive controlled clinical trials.

Guar Gum

Guar Gum is a soluble fiber supplement derived from the Indian bean Cyamopsis tetragonolobus and is generally found in food products as a thickening agent. Guar gum is purported to promote weight loss by acting as a bulking agent in the gut, which results in delayed gastric emptying and increased satiety. Several studies have evaluated the effect of guar gum on weight reduction. A meta-analysis of 11 randomized, double-blind, placebo-controlled clinical trials of guar gum at dosages of nine to thirty grams daily for three weeks to six months found no significant difference in weight loss compared to placebo.[51] More recently, a clinical trial in 44 patients with type 2 diabetes evaluated the effects of ten grams per day of guar gum on metabolic syndrome parameters and found a significant reduction in waist circumference but no effect on weight loss.[52] 

Reported adverse effects include gastrointestinal complaints, such as abdominal pain, flatulence, diarrhea, nausea, and cramps. More research is needed to support the use of guar gum as a weight-loss supplement.

Hoodia Gordonii

Hoodia gordonii is a succulent plant native to Africa. It contains a steroidal glycoside that acts centrally on the hypothalamus to suppress appetite.[53] While this popular supplement has been used for weight loss, the one randomized, double-blind, placebo-controlled study examining H. gordonii found no significant improvement in energy intake, body weight, or fat percentage compared with a placebo.[54] Furthermore, adverse events were more common among those receiving H. gordonii, with altered skin sensation, headache, dizziness, and nausea among the most commonly reported symptoms. [54]

Irvingia Gabonensis

Irvingia gabonensis, also known as African mango, is a fruit native to Africa and commonly consumed in African cuisine.[55] The plant has many advantageous properties, including high fiber content and anti-diabetic and anti-lipidemic effects. Several studies have examined different formulations of I. gabonensis on weight and found beneficial results. A 2013 systematic review of the efficacy of I. gabonensis for weight management reported significant reductions in body weight, waist circumference, and total cholesterol.[56] An article published in 2018 studied the effect of 150 mg (milligrams) of I. gabonensis taken twice a day over 90 days and found improved and statistically significant differences in waist circumference, serum glucose, and triglycerides.[57] While multiple studies have reported beneficial results on metabolic disease markers, small sample sizes and mixed methods make it difficult to extrapolate a true clinical benefit. Overall, I. gabonensis appears to be safe and well-tolerated. The most common side effects include headache, flatulence, and difficulty sleeping.[58][59] Further studies are needed to determine efficacy, dosing, and safety.

Phaseolus Vulgaris/White Kidney Bean

Phaseolus vulgaris is a legume cultivated worldwide and marketed as a weight-loss supplement for its carbohydrate-blocking effects. Studies show that Phaseolus vulgaris inhibits pancreatic amylase, which decreases the gastrointestinal absorption of dietary starches. There have been several published clinical trials and reviews that show mixed results regarding weight loss efficacy.[60][61] The authors of a 2011 systematic review of six trials found that 445 to 1,500 mg per day of P. vulgaris for four to thirteen weeks significantly reduced body fat but not body weight.[62] A 2014 clinical trial of 123 overweight and obese participants consuming 3,000 mg a day of P. vulgaris with a hypocaloric diet over twelve weeks showed a modest yet significant reduction in body fat and body weight. This indicates that P. vulgaris has a possible modest effect on body fat and weight, but more data is needed to confirm this benefit.

Reported adverse effects of P.vulgaris include headaches, soft stools, flatulence, and constipation.[63] No serious adverse effects of P.vulgaris have been reported. The long-term effects are unknown.

Probiotics

Probiotics are bacteria and yeasts that have historically been used to confer a beneficial effect on gastrointestinal health. Since manipulation of the intestinal microbiome has been linked to changes in energy balance and metabolism, probiotics have garnered interest in their potential role in promoting weight loss. The data, however, have been underwhelming. In one systematic review and meta-analysis, probiotics were associated with a significant but small weight loss compared with placebo (weighted mean difference of 0.6 kg). Subsequently, a 2021 systematic review found no significant decrease in body weight with probiotic supplementation.[64] 

Probiotics have a very good safety profile in healthy individuals. However, they should be used cautiously in patients with central venous catheters or immunodeficiency since there have been rare reports of fungemia and pathogenic colonization.[65][66] Similarly, care should be taken in patients with valvular heart disease who plan to undergo dental surgery, endoscopy, or colonoscopy, as rare cases of lactobacillus endocarditis have occurred in patients taking lactobacillus-containing probiotics.[67][68]

Psyllium

Psyllium seed is a soluble fiber supplement derived from the husk of Plantago psyllium. Psyllium is purported to promote weight loss by acting as a bulking agent in the gut, which results in delayed gastric emptying and increased satiety. Fiber-enriched meals decrease the hunger hormone ghrelin and increase the satiety hormone peptide YY.[69] This finding suggests that fiber-rich meals might reduce appetite and increase satiety, although the data are inconsistent. Many human studies show no improvement in body weight and composition after psyllium consumption. One early study of psyllium supplementation showed improved glucose and lipid control compared to placebo in 125 overweight patients with type 2 diabetes, although no weight loss occurred.[70] Recent studies have demonstrated similar results with improved metabolic parameters without statistically significant weight reduction. A study in overweight and obese individuals noted a dose-response relationship with psyllium supplementation, with a dose greater than 30 g of fiber per day leading to the most robust weight loss effect compared to a placebo.[71] A more recent trial in patients with type 2 diabetes supported these positive findings, demonstrating that 10.5 g of psyllium supplementation daily for eight weeks was associated with a significant reduction in body weight, waist circumference, and hip circumference.[72] 

Psyllium is less readily fermented and does not cause as much flatulence and abdominal distension as other fiber supplements. Still, the most commonly reported side effects are gastrointestinal, including flatulence, abdominal pain, diarrhea, constipation, and nausea. Generally, psyllium is well tolerated for short-term use without serious adverse effects.[73]

Raspberry Ketone

Raspberry ketone is the natural aromatic substance found in red raspberries and is used by the food industry for flavoring. Animal studies have found that raspberry ketone down-regulates key genes responsible for adipogenesis while up-regulating genes that regulate fatty acid oxidation.[74][75] In-vitro studies in adipocytes have shown promising results, including an increase in fatty acid oxidation and suppression of lipid accumulation. One randomized controlled trial of 70 participants with a BMI greater than 27 examined the effects of supplementation with a proprietary blend of raspberry ketone, caffeine, bitter orange, ginger, garlic, cayenne, L-theanine, and pepper extract along with B vitamins and chromium versus placebo over eight weeks.[76] Participants also followed a calorie-restricted diet and engaged in moderate physical activity. Compared to the placebo group, those receiving the raspberry ketone supplement lost significantly more weight and fat mass. However, the data are difficult to interpret given that 25 participants dropped out of the study and an intention-to-treat analysis was not performed. Furthermore, the product contained multiple ingredients, rendering the effects of the single raspberry ketone compound impossible to determine. While typical diets only contain a few milligrams of raspberry ketones daily, dietary supplements contain 100 to 1000mg, leading to concerns about possible cardiotoxic and teratogenic effects.[77]

Issues of Concern

Weight-loss dietary supplements are regulated by the U.S. Food and Drug Administration (FDA). Unlike over-the-counter and prescription medications, the FDA does not classify dietary supplements as drugs. Therefore, these supplements do not require FDA approval before marketing, and the manufacturer determines the product's safety and efficacy. However, the FDA does not allow supplements containing pharmaceutical ingredients or those that claim to diagnose, treat, cure, or prevent disease.[78] The FDA has the authority to remove any supplement deemed unsafe from the market and can act against manufacturers if necessary.

When evaluating the evidence for dietary weight-loss supplements, additional data are needed to more clearly understand the efficacy, dosing, and safety of each ingredient. Human studies are limited, and data are often extracted from animal and laboratory research. Most human trials are small and of questionable quality, limiting interpretation. Many supplements marketed for weight loss contain multiple ingredients, making it impossible to isolate each ingredient's effect. Studies often use different formulations, combinations of ingredients, and variable dosages, all of which complicate the analysis of the supplement's safety and efficacy.

Clinical Significance

Americans spend over $2 billion a year on weight-loss dietary supplements. These supplements are costly and can contain dozens of ingredients, including plant components, herbs, dietary fiber, caffeine, and minerals. The proposed mechanisms of action vary for each supplement. These include blocking the absorption of fats and carbohydrates, reducing appetite and increasing satiety, increasing thermogenesis, and changing metabolism to improve body composition. There are concerns over the efficacy, safety, and purity of the compounds in supplements, which are usually marketed without substantiating data. The FDA regulates dietary supplements as foods, not drugs. 

People considering using weight-loss supplements should talk with their healthcare providers to discuss potential benefits and risks. This is especially important for patients with comorbid conditions who are taking prescription medications. Yet fewer than one-third of U.S. adults who use weight-loss dietary supplements discuss this with a clinician.[79] Healthcare providers should inquire about weight-loss supplements to facilitate open discussion.

The evidence supporting the use of weight-loss dietary supplements is limited, inconclusive, and unconvincing.[80][81] The benefits reported are often neither reproducible nor clinically significant. The safest, most effective way to lose weight is by choosing a healthy diet of whole foods and obtaining regular physical activity. Clinicians can consider FDA-approved pharmaceuticals and bariatric procedures for patients requiring additional measures.

Enhancing Healthcare Team Outcomes

Weight-loss dietary supplements are widely used and available worldwide. Patients considering these supplements should talk to their healthcare providers. The entire healthcare team must understand the ingredients, risks, and potential benefits of supplements and assess patients accordingly. 

Healthcare providers must consider what is known and unknown about each ingredient in a product before recommending its use. Manufacturers market supplements with a variety of claims, many of which have not been substantiated. Some preparations contain multiple ingredients that can cause harm by interacting with medications or causing organ dysfunction. Patients with hypertension, diabetes, cardiac, renal, and liver disease should consult their physicians before using any supplement, especially those marketed for weight loss.

Clinicians should complete a thorough history of prescription and over-the-counter medications and dietary supplements at all patient encounters. This list should be updated regularly and documented in the medical record. Patients should be encouraged to lead a healthy lifestyle with nutritious dietary choices and regular exercise to enhance their weight loss efforts. The interprofessional healthcare team should support the patient's weight loss journey to improve clinical outcomes. [Level 2]


Article Details

Article Author

Amy J. Sheer

Article Editor:

Marika Alois

Updated:

1/20/2023 11:20:07 PM

References

[1]

Hales CM,Carroll MD,Fryar CD,Ogden CL, Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS data brief. 2020 Feb;     [PubMed PMID: 32487284]

[2]

Pillitteri JL,Shiffman S,Rohay JM,Harkins AM,Burton SL,Wadden TA, Use of dietary supplements for weight loss in the United States: results of a national survey. Obesity (Silver Spring, Md.). 2008 Apr;     [PubMed PMID: 18239570]

[3]

Ríos-Hoyo A,Gutiérrez-Salmeán G, New Dietary Supplements for Obesity: What We Currently Know. Current obesity reports. 2016 Jun;     [PubMed PMID: 27053066]

[4]

Rahmani J,Miri A,Černevičiūtė R,Thompson J,de Souza NN,Sultana R,Kord Varkaneh H,Mousavi SM,Hekmatdoost A, Effects of cereal beta-glucan consumption on body weight, body mass index, waist circumference and total energy intake: A meta-analysis of randomized controlled trials. Complementary therapies in medicine. 2019 Apr;     [PubMed PMID: 30935520]

[5]

Queenan KM,Stewart ML,Smith KN,Thomas W,Fulcher RG,Slavin JL, Concentrated oat beta-glucan, a fermentable fiber, lowers serum cholesterol in hypercholesterolemic adults in a randomized controlled trial. Nutrition journal. 2007 Mar 26;     [PubMed PMID: 17386092]

[6]

Huang J,Wang Y,Xie Z,Zhou Y,Zhang Y,Wan X, The anti-obesity effects of green tea in human intervention and basic molecular studies. European journal of clinical nutrition. 2014 Oct;     [PubMed PMID: 25074392]

[7]

Jurgens TM,Whelan AM,Killian L,Doucette S,Kirk S,Foy E, Green tea for weight loss and weight maintenance in overweight or obese adults. The Cochrane database of systematic reviews. 2012 Dec 12;     [PubMed PMID: 23235664]

[8]

Li X,Wang W,Hou L,Wu H,Wu Y,Xu R,Xiao Y,Wang X, Does tea extract supplementation benefit metabolic syndrome and obesity? A systematic review and meta-analysis. Clinical nutrition (Edinburgh, Scotland). 2020 Apr;     [PubMed PMID: 31174941]

[9]

Dostal AM,Samavat H,Bedell S,Torkelson C,Wang R,Swenson K,Le C,Wu AH,Ursin G,Yuan JM,Kurzer MS, The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2015 Sep;     [PubMed PMID: 26051348]

[10]

Wikoff D,Welsh BT,Henderson R,Brorby GP,Britt J,Myers E,Goldberger J,Lieberman HR,O'Brien C,Peck J,Tenenbein M,Weaver C,Harvey S,Urban J,Doepker C, Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2017 Nov;     [PubMed PMID: 28438661]

[11]

Cannon ME,Cooke CT,McCarthy JS, Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products. The Medical journal of Australia. 2001 May 21;     [PubMed PMID: 11419773]

[12]

Avisar R,Avisar E,Weinberger D, Effect of coffee consumption on intraocular pressure. The Annals of pharmacotherapy. 2002 Jun;     [PubMed PMID: 12022898]

[13]

Isomura T,Suzuki S,Origasa H,Hosono A,Suzuki M,Sawada T,Terao S,Muto Y,Koga T, Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials. European journal of clinical nutrition. 2016 Nov;     [PubMed PMID: 27805619]

[14]

Anton SD,Morrison CD,Cefalu WT,Martin CK,Coulon S,Geiselman P,Han H,White CL,Williamson DA, Effects of chromium picolinate on food intake and satiety. Diabetes technology     [PubMed PMID: 18715218]

[15]

Tian H,Guo X,Wang X,He Z,Sun R,Ge S,Zhang Z, Chromium picolinate supplementation for overweight or obese adults. The Cochrane database of systematic reviews. 2013 Nov 29;     [PubMed PMID: 24293292]

[16]

Cerulli J,Grabe DW,Gauthier I,Malone M,McGoldrick MD, Chromium picolinate toxicity. The Annals of pharmacotherapy. 1998 Apr;     [PubMed PMID: 9562138]

[17]

Wasser WG,Feldman NS,D'Agati VD, Chronic renal failure after ingestion of over-the-counter chromium picolinate. Annals of internal medicine. 1997 Mar 1;     [PubMed PMID: 9054292]

[18]

Wani S,Weskamp C,Marple J,Spry L, Acute tubular necrosis associated with chromium picolinate-containing dietary supplement. The Annals of pharmacotherapy. 2006 Mar;     [PubMed PMID: 16492795]

[19]

Preuss HG,DiFerdinando D,Bagchi M,Bagchi D, Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview. Journal of medicine. 2002;     [PubMed PMID: 12939122]

[20]

Haaz S,Fontaine KR,Cutter G,Limdi N,Perumean-Chaney S,Allison DB, Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2006 Feb;     [PubMed PMID: 16436104]

[21]

Suntar I,Khan H,Patel S,Celano R,Rastrelli L, An Overview on {i}Citrus aurantium{/i} L.: Its Functions as Food Ingredient and Therapeutic Agent. Oxidative medicine and cellular longevity. 2018;     [PubMed PMID: 29854097]

[22]

Stohs SJ, Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p-Synephrine. Phytotherapy research : PTR. 2017 Oct;     [PubMed PMID: 28752649]

[23]

Stohs SJ,Preuss HG,Shara M, A review of the human clinical studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine. International journal of medical sciences. 2012;     [PubMed PMID: 22991491]

[24]

Malhotra S,Bailey DG,Paine MF,Watkins PB, Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clinical pharmacology and therapeutics. 2001 Jan;     [PubMed PMID: 11180034]

[25]

Penzak SR,Jann MW,Cold JA,Hon YY,Desai HD,Gurley BJ, Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. Journal of clinical pharmacology. 2001 Oct;     [PubMed PMID: 11583473]

[26]

Litosch I,Hudson TH,Mills I,Li SY,Fain JN, Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes. Molecular pharmacology. 1982 Jul;     [PubMed PMID: 6289066]

[27]

Godard MP,Johnson BA,Richmond SR, Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese men. Obesity research. 2005 Aug;     [PubMed PMID: 16129715]

[28]

Henderson S,Magu B,Rasmussen C,Lancaster S,Kerksick C,Smith P,Melton C,Cowan P,Greenwood M,Earnest C,Almada A,Milnor P,Magrans T,Bowden R,Ounpraseuth S,Thomas A,Kreider RB, Effects of coleus forskohlii supplementation on body composition and hematological profiles in mildly overweight women. Journal of the International Society of Sports Nutrition. 2005 Dec 9;     [PubMed PMID: 18500958]

[29]

Park Y,Albright KJ,Liu W,Storkson JM,Cook ME,Pariza MW, Effect of conjugated linoleic acid on body composition in mice. Lipids. 1997 Aug;     [PubMed PMID: 9270977]

[30]

Miner JL,Cederberg CA,Nielsen MK,Chen X,Baile CA, Conjugated linoleic acid (CLA), body fat, and apoptosis. Obesity research. 2001 Feb;     [PubMed PMID: 11316347]

[31]

Brown JM,Halvorsen YD,Lea-Currie YR,Geigerman C,McIntosh M, Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates lipogenesis in primary cultures of stromal vascular cells from human adipose tissue. The Journal of nutrition. 2001 Sep;     [PubMed PMID: 11533273]

[32]

Whigham LD,Watras AC,Schoeller DA, Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. The American journal of clinical nutrition. 2007 May;     [PubMed PMID: 17490954]

[33]

Onakpoya IJ,Posadzki PP,Watson LK,Davies LA,Ernst E, The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials. European journal of nutrition. 2012 Mar;     [PubMed PMID: 21990002]

[34]

Risérus U,Smedman A,Basu S,Vessby B, Metabolic effects of conjugated linoleic acid in humans: the Swedish experience. The American journal of clinical nutrition. 2004 Jun;     [PubMed PMID: 15159248]

[35]

Sofi F,Buccioni A,Cesari F,Gori AM,Minieri S,Mannini L,Casini A,Gensini GF,Abbate R,Antongiovanni M, Effects of a dairy product (pecorino cheese) naturally rich in cis-9, trans-11 conjugated linoleic acid on lipid, inflammatory and haemorheological variables: a dietary intervention study. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2010 Feb;     [PubMed PMID: 19473822]

[36]

Abidov M,Ramazanov Z,Seifulla R,Grachev S, The effects of Xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat. Diabetes, obesity     [PubMed PMID: 19840063]

[37]

López-Rios L,Vega T,Chirino R,Jung JC,Davis B,Pérez-Machín R,Wiebe JC, Toxicological assessment of Xanthigen{sup}®{/sup} nutraceutical extract combination: Mutagenicity, genotoxicity and oral toxicity. Toxicology reports. 2018;     [PubMed PMID: 30386730]

[38]

Onakpoya I,Hung SK,Perry R,Wider B,Ernst E, The Use of Garcinia Extract (Hydroxycitric Acid) as a Weight loss Supplement: A Systematic Review and Meta-Analysis of Randomised Clinical Trials. Journal of obesity. 2011;     [PubMed PMID: 21197150]

[39]

Kim JE,Jeon SM,Park KH,Lee WS,Jeong TS,McGregor RA,Choi MS, Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial. Nutrition journal. 2011 Sep 21;     [PubMed PMID: 21936892]

[40]

Vasques CA,Schneider R,Klein-Júnior LC,Falavigna A,Piazza I,Rossetto S, Hypolipemic effect of Garcinia cambogia in obese women. Phytotherapy research : PTR. 2014 Jun;     [PubMed PMID: 24133059]

[41]

Corey R,Werner KT,Singer A,Moss A,Smith M,Noelting J,Rakela J, Acute liver failure associated with Garcinia cambogia use. Annals of hepatology. 2016 Jan-Feb;     [PubMed PMID: 26626648]

[42]

Lunsford KE,Bodzin AS,Reino DC,Wang HL,Busuttil RW, Dangerous dietary supplements: {i}Garcinia cambogia{/i}-associated hepatic failure requiring transplantation. World journal of gastroenterology. 2016 Dec 7;     [PubMed PMID: 28018115]

[43]

Devaraj RD,Reddy CK,Xu B, Health-promoting effects of konjac glucomannan and its practical applications: A critical review. International journal of biological macromolecules. 2019 Apr 1;     [PubMed PMID: 30586587]

[44]

Hozumi T,Yoshida M,Ishida Y,Mimoto H,Sawa J,Doi K,Kazumi T, Long-term effects of dietary fiber supplementation on serum glucose and lipoprotein levels in diabetic rats fed a high cholesterol diet. Endocrine journal. 1995 Apr;     [PubMed PMID: 7627263]

[45]

Sood N,Baker WL,Coleman CI, Effect of glucomannan on plasma lipid and glucose concentrations, body weight, and blood pressure: systematic review and meta-analysis. The American journal of clinical nutrition. 2008 Oct;     [PubMed PMID: 18842808]

[46]

Zalewski BM,Chmielewska A,Szajewska H, The effect of glucomannan on body weight in overweight or obese children and adults: a systematic review of randomized controlled trials. Nutrition (Burbank, Los Angeles County, Calif.). 2015 Mar;     [PubMed PMID: 25701331]

[47]

Vanderbeek PB,Fasano C,O'Malley G,Hornstein J, Esophageal obstruction from a hygroscopic pharmacobezoar containing glucomannan. Clinical toxicology (Philadelphia, Pa.). 2007;     [PubMed PMID: 17357389]

[48]

Haidari F,Samadi M,Mohammadshahi M,Jalali MT,Engali KA, Energy restriction combined with green coffee bean extract affects serum adipocytokines and the body composition in obese women. Asia Pacific journal of clinical nutrition. 2017;     [PubMed PMID: 28917230]

[49]

Roshan H,Nikpayam O,Sedaghat M,Sohrab G, Effects of green coffee extract supplementation on anthropometric indices, glycaemic control, blood pressure, lipid profile, insulin resistance and appetite in patients with the metabolic syndrome: a randomised clinical trial. The British journal of nutrition. 2018 Feb;     [PubMed PMID: 29307310]

[50]

Onakpoya I,Terry R,Ernst E, The use of green coffee extract as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials. Gastroenterology research and practice. 2011;     [PubMed PMID: 20871849]

[51]

Pittler MH,Ernst E, Guar gum for body weight reduction: meta-analysis of randomized trials. The American journal of medicine. 2001 Jun 15;     [PubMed PMID: 11403757]

[52]

Dall'Alba V,Silva FM,Antonio JP,Steemburgo T,Royer CP,Almeida JC,Gross JL,Azevedo MJ, Improvement of the metabolic syndrome profile by soluble fibre - guar gum - in patients with type 2 diabetes: a randomised clinical trial. The British journal of nutrition. 2013 Nov 14;     [PubMed PMID: 23551992]

[53]

MacLean DB,Luo LG, Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside. Brain research. 2004 Sep 10;     [PubMed PMID: 15312781]

[54]

Blom WA,Abrahamse SL,Bradford R,Duchateau GS,Theis W,Orsi A,Ward CL,Mela DJ, Effects of 15-d repeated consumption of Hoodia gordonii purified extract on safety, ad libitum energy intake, and body weight in healthy, overweight women: a randomized controlled trial. The American journal of clinical nutrition. 2011 Nov;     [PubMed PMID: 21993434]

[55]

Martínez-Abundis E,Méndez-Del Villar M,Pérez-Rubio KG,Zuñiga LY,Cortez-Navarrete M,Ramírez-Rodriguez A,González-Ortiz M, Novel nutraceutic therapies for the treatment of metabolic syndrome. World journal of diabetes. 2016 Apr 10;     [PubMed PMID: 27076875]

[56]

Onakpoya I,Davies L,Posadzki P,Ernst E, The efficacy of Irvingia gabonensis supplementation in the management of overweight and obesity: a systematic review of randomized controlled trials. Journal of dietary supplements. 2013 Mar;     [PubMed PMID: 23419021]

[57]

Méndez-Del Villar M,González-Ortiz M,Martínez-Abundis E,Pérez-Rubio KG,Cortez-Navarrete M, Effect of Irvingia gabonensis on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion. Journal of medicinal food. 2018 Jun;     [PubMed PMID: 29336718]

[58]

Oben JE,Ngondi JL,Momo CN,Agbor GA,Sobgui CS, The use of a Cissus quadrangularis/Irvingia gabonensis combination in the management of weight loss: a double-blind placebo-controlled study. Lipids in health and disease. 2008 Mar 31;     [PubMed PMID: 18377661]

[59]

Egras AM,Hamilton WR,Lenz TL,Monaghan MS, An evidence-based review of fat modifying supplemental weight loss products. Journal of obesity. 2011;     [PubMed PMID: 20847896]

[60]

Celleno L,Tolaini MV,D'Amore A,Perricone NV,Preuss HG, A Dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women. International journal of medical sciences. 2007 Jan 24;     [PubMed PMID: 17299581]

[61]

Udani J,Hardy M,Madsen DC, Blocking carbohydrate absorption and weight loss: a clinical trial using Phase 2 brand proprietary fractionated white bean extract. Alternative medicine review : a journal of clinical therapeutic. 2004 Mar;     [PubMed PMID: 15005645]

[62]

Onakpoya I,Aldaas S,Terry R,Ernst E, The efficacy of Phaseolus vulgaris as a weight-loss supplement: a systematic review and meta-analysis of randomised clinical trials. The British journal of nutrition. 2011 Jul;     [PubMed PMID: 22844674]

[63]

Grube B,Chong WF,Chong PW,Riede L, Weight reduction and maintenance with IQP-PV-101: a 12-week randomized controlled study with a 24-week open label period. Obesity (Silver Spring, Md.). 2014 Mar;     [PubMed PMID: 24006357]

[64]

Perna S,Ilyas Z,Giacosa A,Gasparri C,Peroni G,Faliva MA,Rigon C,Naso M,Riva A,Petrangolini G,A Redha A,Rondanelli M, Is Probiotic Supplementation Useful for the Management of Body Weight and Other Anthropometric Measures in Adults Affected by Overweight and Obesity with Metabolic Related Diseases? A Systematic Review and Meta-Analysis. Nutrients. 2021 Feb 19;     [PubMed PMID: 33669580]

[65]

Lherm T,Monet C,Nougière B,Soulier M,Larbi D,Le Gall C,Caen D,Malbrunot C, Seven cases of fungemia with Saccharomyces boulardii in critically ill patients. Intensive care medicine. 2002 Jun;     [PubMed PMID: 12107689]

[66]

MacGregor G,Smith AJ,Thakker B,Kinsella J, Yoghurt biotherapy: contraindicated in immunosuppressed patients? Postgraduate medical journal. 2002 Jun;     [PubMed PMID: 12151695]

[67]

Kato K,Funabashi N,Takaoka H,Kohno H,Kishimoto T,Nakatani Y,Matsumiya G,Kobayashi Y, Lactobacillus paracasei endocarditis in a consumer of probiotics with advanced and severe bicuspid aortic valve stenosis complicated with diffuse left ventricular mid-layer fibrosis. International journal of cardiology. 2016 Dec 1;     [PubMed PMID: 27657466]

[68]

Aaron JG,Sobieszczyk ME,Weiner SD,Whittier S,Lowy FD, {i}Lactobacillus rhamnosus{/i} Endocarditis After Upper Endoscopy. Open forum infectious diseases. 2017 Spring;     [PubMed PMID: 28695143]

[69]

Karhunen LJ,Juvonen KR,Flander SM,Liukkonen KH,Lähteenmäki L,Siloaho M,Laaksonen DE,Herzig KH,Uusitupa MI,Poutanen KS, A psyllium fiber-enriched meal strongly attenuates postprandial gastrointestinal peptide release in healthy young adults. The Journal of nutrition. 2010 Apr;     [PubMed PMID: 20147463]

[70]

Ziai SA,Larijani B,Akhoondzadeh S,Fakhrzadeh H,Dastpak A,Bandarian F,Rezai A,Badi HN,Emami T, Psyllium decreased serum glucose and glycosylated hemoglobin significantly in diabetic outpatients. Journal of ethnopharmacology. 2005 Nov 14;     [PubMed PMID: 16154305]

[71]

Pal S,Khossousi A,Binns C,Dhaliwal S,Ellis V, The effect of a fibre supplement compared to a healthy diet on body composition, lipids, glucose, insulin and other metabolic syndrome risk factors in overweight and obese individuals. The British journal of nutrition. 2011 Jan;     [PubMed PMID: 20727237]

[72]

Abutair AS,Naser IA,Hamed AT, Soluble fibers from psyllium improve glycemic response and body weight among diabetes type 2 patients (randomized control trial). Nutrition journal. 2016 Oct 12;     [PubMed PMID: 27733151]

[73]

Anderson JW,Allgood LD,Lawrence A,Altringer LA,Jerdack GR,Hengehold DA,Morel JG, Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials. The American journal of clinical nutrition. 2000 Feb;     [PubMed PMID: 10648260]

[74]

Park KS, Raspberry ketone increases both lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Planta medica. 2010 Oct;     [PubMed PMID: 20425690]

[75]

Park KS, Raspberry ketone, a naturally occurring phenolic compound, inhibits adipogenic and lipogenic gene expression in 3T3-L1 adipocytes. Pharmaceutical biology. 2015 Jun;     [PubMed PMID: 25429790]

[76]

Lopez HL,Ziegenfuss TN,Hofheins JE,Habowski SM,Arent SM,Weir JP,Ferrando AA, Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women. Journal of the International Society of Sports Nutrition. 2013 Apr 19;     [PubMed PMID: 23601452]

[77]

Bredsdorff L,Wedebye EB,Nikolov NG,Hallas-Møller T,Pilegaard K, Raspberry ketone in food supplements--High intake, few toxicity data--A cause for safety concern? Regulatory toxicology and pharmacology : RTP. 2015 Oct;     [PubMed PMID: 26160596]

[78]

White CM, Dietary Supplements Pose Real Dangers to Patients. The Annals of pharmacotherapy. 2020 Aug;     [PubMed PMID: 31973570]

[79]

Blanck HM,Serdula MK,Gillespie C,Galuska DA,Sharpe PA,Conway JM,Khan LK,Ainsworth BE, Use of nonprescription dietary supplements for weight loss is common among Americans. Journal of the American Dietetic Association. 2007 Mar     [PubMed PMID: 17324663]

[80]

Pittler MH,Ernst E, Dietary supplements for body-weight reduction: a systematic review. The American journal of clinical nutrition. 2004 Apr     [PubMed PMID: 15051593]

[81]

Dwyer JT,Allison DB,Coates PM, Dietary supplements in weight reduction. Journal of the American Dietetic Association. 2005 May     [PubMed PMID: 15867902]