Summary
Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.
Keywords: Weight loss in lipedema, Dietary supplements, Fat burning supplements, Fat burners
Citation
How to cite this article: Bonetti G, Herbst KL, Dhuli K, Kiani AK, Michelini S, Michelini S, Ceccarini MR, Michelini S, Ricci M, Cestari M, Codini M, Beccari T, Bellinato F, Gisondi P, Bertelli M. Dietary supplements for Lipedema. J Prev Med Hyg 2022;63(suppl.3):E169-E173. https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2758
Introduction
Lipedema is a chronic and progressive disease that is characterized by the abnormal distribution of subcutaneous adipose connective tissue causing disproportionate and painful limbs [1]. Usually, it develops in females during their time of puberty or other times of hormonal, shape and weight change, including menopause or childbirth. Lipedema is characterized by the symmetrical enhancement of nodular subcutaneous adipose connective tissue on the lower body and arms, while leaving the upper trunk, hands, and feet unaffected. Lipedema tissue often affects the lower abdomen, thighs, buttocks, and calves. In about 80% of cases, lipedema can also affect the arms, whereas the hands and feet are not affected [2]. Although lipedema greatly affects women’s health around the world, it remains either undiagnosed or misdiagnosed as other similar diseases, such as obesity or lymphedema [3]. Polygenic susceptibility along with lymphatic, hormonal and microvascular disorders might be at least partially responsible for the development of lipedema. Moreover, lipedema can progress to the point where lymphedema develops. The major causes for the onset of lymphedema include genetic susceptibility, lymphatic vessel malformations, surgery and trauma [4]. Lipedema does not respond well to restrictive diets, contrary to usual forms of obesity. Thus, lipedema leads to a disproportionate increase in lower body tissue that stubbornly retains its shape (waist to ankles) after diets or bariatric surgery. Lipedema is not restricted to just subcutaneous adipose connective tissue, in fact, women with lipedema had significantly lower muscle strength and a non-significant, but clinically relevant lower exercise-endurance capacity than women with obesity [5]. Excess subcutaneous adipose connective tissue and lower muscle function results in later stages, patients with lipedema with an elevated body mass index, increasing the risk of developing severe obesity with metabolic complications, which in turn worsens the symptoms of lipedema [1, 6-8]. The Mediterranean diet and ketogenic diet have been proposed for lipedema treatment, showing weight loss in both cases but failure to reduce pain with either intervention, and failure to reduce percent fat after the Mediterranean diet. [9, 10] The ketogenic diet trial was small; hence no evidence-based diet has been recommended for the treatment of lipedema. It is suggested that hypocaloric nutrition should be accompanied by suitable dietary supplements and exercise to overcome diet resistance and to manage weight gain in lipedema [8].
If a patient with lipedema develops obesity, it can cause similar serious health issues as in individuals with obesity but without lipedema. For example, it could trigger insulin resistance [2] resulting in hyperglycemia leading to the development of type 2 diabetes, which could further damage organs of the body as well as reduce quality of life. Moreover, obesity increases the risk of developing high blood pressure, hypercholesterolemia and increased blood clotting tendency that leads to higher risk of stroke and heart attacks [11-14].
In order to define an effective treatment option for lipedema, knowing the physiological process of subcutaneous adipose connective tissue deposition and reduction of muscle function and energy utilization is of outmost importance. Excess protein, fat and carbohydrates that are consumed daily can be converted into stored or ectopic fat though the process of lipogenesis in adipose tissue and the liver, and normally stored in adipose tissue as triacylglycerol [15-17]. When consumption of macronutrients, especially fat and carbohydrates, is in excess, fat can also be stored ectopically in muscle, liver, and other depots in the body [18]. Fat must be released from adipocytes through complex enzymatic/hormonal pathways in order to be utilized for energy production. When adipocytes are stimulated, they release triacylglycerol into the bloodstream as free fatty acids (FFA) via lipolysis. Then, FFA are transported by the blood stream to energy requiring tissues, especially muscles, and finally enter mitochondria where they are utilized for energy production [15, 19].
Dietary supplements that reduce adipose tissue and increase muscle (lean mass) could be an effective ally in the management of lipedema. Reduction of adipose tissue and increase in lean mass could improve body image, reduce pain, and improve mobility for patients with lipedema. The use of specific dietary supplements could help in reducing body fat and increasing lean mass thus preventing the invasive practice of microcannular tumescent lipedema reduction surgery including suction lipectomy, which is currently the most effective treatment for lipedema [20].
Fat-burning supplements
Fat-burning supplements are a specific type of dietary supplement that stimulates the fat burning process by several mechanisms. They can boost energy expenditure, increase fat metabolism, increase weight loss, increase oxidation of fats during exercise, as well as make long-term adjustments in metabolic pathways that enhance fat metabolism. Indeed, a good fat burner supplement should [15, 21, 22]:
stimulate conversion of stored fats into energy;
stimulate mobilization and break down of stored triacylglycerol from adipocytes;
increase metabolism to burn stored fats;
inhibit adipocyte enlargement via lipogenesis.
The efficacy of fat-burning supplements is supported by several studies. Indeed, weight loss induced by supplementation and diet together can be significantly higher than weight loss from diet alone [23]. In a study by Falcone et al., addition of thermogenic supplements containing caffeine, conjugated linoleic acid (CLA), multi-vitamins, and protein, to a hypocaloric diet with high-protein content for a period of 3 weeks resulted in 97% additional reduction in body weight and 35% additional fat loss when compared with the same diet alone. Thus, dietary supplements can increase overall weight loss, including fat loss [23].
CLASSES OF FAT-BURNING SUPPLEMENTS
As described by El-Zayat et al., fat burners may be divided into several classes based on their mechanism of action: energy enhancers, protein and amino acids supplements, adrenergic enhancers, and lean mass enhancers [15]. Moreover, they can be comprised of several ingredients, each of which has its own mechanism of action. The main ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and CLA. They can also include herbal stimulants such as ephedrine, pyruvate, yohimbine, and chitosan. Fat-burning supplements stimulate weight loss through several molecular mechanisms, mainly boosting metabolism and suppressing appetite [22, 24-26].
Energy enhancers
Fat-burning energy enhancers are usually caffeine or catechins. Caffeine is found in coffee, soft drinks, tea, cola nuts, and cocoa, and it can act as an energy enhancer and an exercise performance booster. Caffeine has the ability to increase stored fat release and the rate of calorie burn [15, 27-29]. Caffeine stimulates fat loss at the level of adipocytes and myocytes, mainly acting synergistically with beta-adrenergic drugs and neurotransmitters. Indeed, beta-adrenergic receptors stimulate fat loss and increase calorie burning, while alpha2-adrenergic receptors have the opposite function [30, 31].
Catechins are often derived from green tea. They have anti-obesity effects and their effect in weight loss is sustained by several human studies [32, 33]. Indeed, they stimulate fat oxidation and energy expenditure, decreasing dietary fat-induced weight gain. Their action is probably due to an increase in sympathetic neuronal activity, which in turn activates hepatic fat oxidation [34].
Protein and amino acids supplements
Protein supplements are utilized to create and maintain a positive nitrogen balance during the day without severely elevating caloric intake. They include whey protein and casein [15]. Whey protein is reported to help in building muscles, increasing strength, controlling appetite, improving endurance, aiding in weight loss, and boosting energy levels [35]. Casein provides all the essential amino acids required for exercise-induced growth of tissue. Casein also forms a gel within the stomach that causes it to slowly digest so that the amino acids/peptides are steadily absorbed over a longer period of time [36].
Adrenergic enhancers
Estrogens are thought to play a key role in the development of lipedema. Aromatase, produced by adipocytes, is an enzyme that converts androgens to estrogen. When mice had the aromatase gene knocked out, body weight gain and obesity-related metabolic complications occurred in both genders. This suggests that an optimal estrogen to testosterone ratio is important, and with increased lipedema tissue, this ratio may be high [37]; thus, dietary supplements that modify hormonal levels could be an effective strategy for lipedema treatment. Testosterone is a key molecule in the pathophysiology of weight gain and obesity. Indeed, it increases lean mass and decreases fat mass, where low testosterone levels are associated with energy imbalance, insulin resistance and dyslipidemia [38]. Supplementation of molecules that act on adrenergic receptors might help in increasing metabolic rate and fat burning, and in accelerating weight loss in women with lipedema. Adrenergic enhancers comprise 7-Keto dehydroepiandrosterone (DHEA) and yohimbine. 7-Keto-DHEA causes long-term changes in body levels of epitestosterone, testosterone, estradiol as well as other steroid hormones. It stimulates thermogenesis, diverting store fats in ATP and heat production [39, 40]. Yohimbe derives from the bark of Pausinystalia yohimbe. It is an alpha-2 receptor antagonist, and it accelerates weight loss, increasing testosterone levels, blood flow, thermogenesis, and fatty acid oxidation [15, 41-43].
Lean mass enhancers
The wide class of lean mass enhancers comprise several molecules that stimulate lean mass production through different molecular mechanisms. A non-exhaustive list, comprising their mechanism of action, is reported below in Table I [15]. Further studies will be needed to confirm their effects in humans, considering that a systematic review by Pittler & Ernst doubted the efficacy of several molecules, such as chitosan and pyruvate, in reducing body weight [41].
Fat-burning foods
Certain foods can help in the fat burning process by enhancing metabolism and suppressing appetite. Indeed, food consumption normally increases body weight, but certain foods stimulate lipolysis if coupled with regular exercise and sufficient water intake [15]. Fat-burning foods comprise good fats, medium chain triglycerides, and meat and dairy proteins. Good fats are lipids from several sources, among which are avocados, nuts, fish and vegetable oils [15]. These foods are rich in beta-sitosterol, oleic acids and omega-3 polyunsaturated fatty acids, and they accelerate fat burning and decrease triglycerides and LDL cholesterol levels [52, 53]. Medium chain triglycerides are found in cow butter, palm oil and coconut oil. They are easily digested and absorbed and are directly used for energy. Thus, foods rich in medium chain triglycerides suppress appetite and stimulate body fat loss [54]. Finally, meat and dairy proteins require a complex digestion and absorption processes, which burns energy. They stimulate satiety and use energy for their conversion and storage as fats, therefore meat and dairy they are excellent fat-burning foods [15, 55].
Conclusion
Lipedema is a chronic disease that results in the abnormal distribution of subcutaneous adipose tissue but also the loss of function of muscle. In some cases, obesity arises in later lipedema stages, leading to serious health issues. Lipedema adipose tissue is usually not responsive to diet and exercise, thus invasive techniques such as suction lipectomy are usually required. The use of fat-burning supplements and lean mass enhancers could improve the process of weight loss and but also increase muscle mass and possibly muscle function. Indeed, these supplements are known to increase fat mass loss boosting energy expenditure, increasing fat metabolism, and impairing fat absorption, which may in turn improve muscle function indirectly. Therefore, the use of dietary supplements could be a valid alternative to invasive techniques for the reduction of adipose tissue and related issues in lipedema patients. Human studies are needed to confirm their effectiveness in lipedema and to select the most effective dietary supplements.
Acknowledgements
This research was funded by the Provincia Autonoma di Bolzano in the framework of LP 15/2020 (dgp 3174/2021).
Conflicts of interest statement
Authors declare no conflict of interest.
Author's contributions
Gabriele Bonetti, Karen L. Herbst: These authors contributed equally to this work. MB: study conception, editing and critical revision of the manuscript; GB, KLH, KD, AKK, Serena M, Silvia M, MRC, Sandro M, MR, Marina C, Michela C, TB, FB, PG: literature search, editing and critical revision of the manuscript. All authors have read and approved the final manuscript.
Figures and tables
Tab. I.
Sources and mechanism of action of lean body enhancers.
Molecule | Source | Mechanism of action | References |
---|---|---|---|
Chitosan | Crustaceans | Reduces fat absorption | [40,41] |
L-Carnitine | Chemical catalyst that is synthesized by human kidneys, brain, and liver | Participates in fatty acid transport into mitochondria during the breakdown of fats | [44,45] |
Chromium | Trace mineral found in meat, grain, nuts | Reduces insulin resistance | [41,46] |
Ephedrine | The plant Ephedra sinica | Stimulates sympathetic neuronal action | [47] |
Synephrine | Citrus fruits | Stimulates thermogenesis | [48,49] |
Pyruvate | Intermediate of glycolysis | Reduces appetite and fatigue, increases energy levels and muscle glycogen stores | [24,41] |
Conjugated Linoleic Acid | Meat & dairy products | Transports dietary fats to cells for lipolysis | [50,51] |
References
- [1].Buso G, Depairon M, Tomson D, Raffoul W, Vettor R, Mazzolai L. Lipedema: a call to action! Obesity 2019;27:1567-76. https://doi.org/10.1002/oby.22597 10.1002/oby.22597 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [2].la Torre YS-D, Wadeea R, Rosas V, Herbst KL. Lipedema: friend and foe. Horm Mol Biol Clin Investig 2018;33. https://doi.org/10.1515/hmbci-2017-0076 10.1515/hmbci-2017-0076 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [3].Michelini S, Herbst KL, Precone V, Manara E, Marceddu G, Dautaj A, Maltese PE, Paolacci S, Ceccarini MR, Beccari T, Sorrentino E, Aquilanti B, Velluti V, Matera G, Gagliardi L, Miggiano GAD, Bertelli M. A multi-gene panel to identify lipedema-predisposing genetic variants by a next-generation sequencing strategy. J Pers Med 2022;12. https://doi.org/10.3390/jpm12020268 10.3390/jpm12020268 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Bonetti G, Paolacci S, Samaja M, Maltese PE, Michelini S, Michelini S, Michelini S, Ricci M, Cestari M, Dautaj A, Medori MC, Bertelli M. Low efficacy of genetic tests for the diagnosis of primary lymphedema prompts novel insights into the underlying molecular pathways. Int J Mol Sci 2022;23:7414. https://doi.org/10.3390/ijms23137414 10.3390/ijms23137414 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].van Esch-Smeenge J, Damstra RJ, Hendrickx AA. Muscle strength and functional exercise capacity in patients with lipoedema and obesity: a comparative study. J Lymphoedema 2017;12:27-31. [Google Scholar]
- [6].Paolacci S, Precone V, Acquaviva F, Chiurazzi P, Fulcheri E, Pinelli M, Buffelli F, Michelini S, Herbst KL, Unfer V, Bertelli M. Genetics of lipedema: new perspectives on genetic research and molecular diagnoses. Eur Rev Med Pharmacol Sci 2019;23:5581-94. https://doi.org/10.26355/eurrev_201907_18292 10.26355/eurrev_201907_18292 [DOI] [PubMed] [Google Scholar]
- [7].Michelini S, Chiurazzi P, Marino V, Dell'Orco D, Manara E, Baglivo M, Fiorentino A, Maltese PE, Pinelli M, Herbst KL, Dautaj A, Bertelli M. Aldo-Keto Reductase 1C1 (AKR1C1) as the first mutated gene in a family with nonsyndromic primary lipedema. Int J Mol Sci 2020;21. https://doi.org/10.3390/ijms21176264 10.3390/ijms21176264 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Kruppa P, Georgiou I, Biermann N, Prantl L, Klein-Weigel P, Ghods M. Lipedema–pathogenesis, diagnosis, and treatment options. Dtsch Arztebl Int 2020;117:396-403. https://doi.org/10.3238/arztebl.2020.0396 10.3238/arztebl.2020.0396 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Cannataro R, Michelini S, Ricolfi L, Caroleo M, Gallelli L, de Sarro G, Onorato A, Cione E. Management of lipedema with Ketogenic Diet: 22-Month Follow-Up. Life 2021;11:1402. https://doi.org/10.3390/life11121402 10.3390/life11121402 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Di Renzo L, Cinelli G, Romano L, Zomparelli S, Lou De Santis G, Nocerino P, Bigioni G, Arsini L, Cenname G, Pujia A, Chiricolo G, De Lorenzo A. Potential effects of a modified Mediterranean Diet on body composition in lipoedema. Nutrients 2021;13:358. https://doi.org/10.3390/nu13020358 10.3390/nu13020358 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Vettori A, Paolacci S, Maltese PE, Herbst KL., Cestari M, Michelini S, Michelini S, Samaja M, Bertelli M. Genetic determinants of the effects of training on muscle and adipose tissue homeostasis in obesity associated with lymphedema. Lymphat Res Biol 2021;19:322-33. https://doi.org/10.1089/lrb.2020.0057 10.1089/lrb.2020.0057 [DOI] [PubMed] [Google Scholar]
- [12].Vettori A, Pompucci G, Paolini B, del Ciondolo I, Bressan S, Dundar M, Kenanoğlu S, Unfer V, Bertelli M. Geneob project genetic background, nutrition and obesity: a review. Eur Rev Med Pharmacol Sci 2019;23:1751-61. https://doi.org/10.26355/eurrev_201902_17137 10.26355/eurrev_201902_17137 [DOI] [PubMed] [Google Scholar]
- [13].Dhuli K, Ceccarini MR, Precone V, Maltese PE, Bonetti G, Paolacci S, Dautaj A, Guerri G, Marceddu G, Beccari T, Michelini S, Bertelli M. Improvement of quality of life by intake of Hydroxytyrosol in patients with lymphedema and association of lymphedema genes with obesity. Eur Rev Med Pharmacol Sci 2021;25:33-42. https://doi.org/10.26355/eurrev_202112_27331 10.26355/eurrev_202112_27331 [DOI] [PubMed] [Google Scholar]
- [14].Camilleri G, Kiani AK, Herbst KL, Kaftalli J, Bernini A, Dhuli K, Manara E, Bonetti G, Stuppia L, Paolacci S, Dautaj A, Bertelli M. Genetics of fat deposition. Eur Rev Med Pharmacol Sci 2021;25:14-22. https://doi.org/10.26355/eurrev_202112_27329 10.26355/eurrev_202112_27329 [DOI] [PubMed] [Google Scholar]
- [15].El-Zayat SR, Sibaii H, El-Shamy KA. Physiological process of fat loss. Bull Natl Res Cent 2019;43:208. https://doi.org/10.1186/s42269-019-0238-z 10.1186/s42269-019-0238-z [DOI] [Google Scholar]
- [16].Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2001;2:282-6. https://doi.org/10.1093/embo-reports/kve071 10.1093/embo-reports/kve071 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].Wood JD, Enser M, Fisher AV, Nute GR, Sheard PR, Richardson RI, Hughes SI, Whittington FM. Fat deposition, fatty acid composition and meat quality: a review. Meat Sci 2008;78:343-58. https://doi.org/10.1016/j.meatsci.2007.07.019 10.1016/j.meatsci.2007.07.019 [DOI] [PubMed] [Google Scholar]
- [18].Trouwborst I, Bowser SM, Goossens GH, Blaak EE. Ectopic fat accumulation in distinct insulin resistant phenotypes; targets for personalized nutritional interventions. Frontiers Nutr 2018;5. https://doi.org/10.3389/fnut.2018.00077 10.3389/fnut.2018.00077 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Manore MM. Dietary supplements for improving body composition and reducing body weight: where is the evidence? Int J Sport Nutr Exerc Metab 2012;22:139-54. https://doi.org/10.1123/ijsnem.22.2.139 10.1123/ijsnem.22.2.139 [DOI] [PubMed] [Google Scholar]
- [20].Aksoy H, Karadag AS, Wollina U. Cause and management of lipedema-associated pain. Dermatol Ther 2021;34. https://doi.org/10.1111/dth.14364 10.1111/dth.14364 [DOI] [PubMed] [Google Scholar]
- [21].Jeukendrup AE, Randell R. Fat burners: nutrition supplements that increase fat metabolism. Obes Rev 2011;12:841-51. https://doi.org/10.1111/j.1467-789X.2011.00908.x 10.1111/j.1467-789X.2011.00908.x [DOI] [PubMed] [Google Scholar]
- [22].Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Addit Contam 2003;20:1-30. https://doi.org/10.1080/0265203021000007840 10.1080/0265203021000007840 [DOI] [PubMed] [Google Scholar]
- [23].Falcone PH, Tai CY, Carson LR, Joy JM, Mosman MM, Vogel RM, McCann TR, Crona KP, Griffin JD, Kim MP, Moon JR. Subcutaneous and segmental fat loss with and without supportive supplements in conjunction with a low-calorie high protein diet in healthy women. PLOS ONE 2015;10:e0123854. https://doi.org/10.1371/journal.pone.0123854 10.1371/journal.pone.0123854 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Onakpoya I, Posadzki P, Ernst E. Chromium supplementation in overweight and obesity: a systematic review and meta-analysis of randomized clinical trials. Obes Rev 2013;14:496-507. https://doi.org/10.1111/obr.12026 10.1111/obr.12026 [DOI] [PubMed] [Google Scholar]
- [25].Onakpoya I, Hunt K, Wider B, Ernst E. Pyruvate supplementation for weight loss: a systematic review and meta-analysis of randomized clinical trials. Crit Rev Food Sci Nutr 2014;54:17-23. https://doi.org/10.1080/10408398.2011.565890 10.1080/10408398.2011.565890 [DOI] [PubMed] [Google Scholar]
- [26].Cohen PA, Wang Y, Maller G, DeSouza R, Khan IA. Pharmaceutical quantities of yohimbine found in dietary supplements in the USA. Drug Test Anal 2016;8:357-69. https://doi.org/10.1002/dta.1849 10.1002/dta.1849 [DOI] [PubMed] [Google Scholar]
- [27].Acheson KJ, Gremaud G, Meirim I, Montigon F, Krebs Y, Fay LB, Gay L-J, Schneiter P, Schindler C, Tappy L. Metabolic effects of caffeine in humans: lipid oxidation or futile cycling? Am J Clin Nutr 2004;79:40-6. https://doi.org/10.1093/ajcn/79.1.40 10.1093/ajcn/79.1.40 [DOI] [PubMed] [Google Scholar]
- [28].Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin Nutr 1989;49:44-50. https://doi.org/10.1093/ajcn/49.1.44 10.1093/ajcn/49.1.44 [DOI] [PubMed] [Google Scholar]
- [29].Shekelle PG. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003;289:1537-45. https://doi.org/10.1001/jama.289.12.1537 10.1001/jama.289.12.1537 [DOI] [PubMed] [Google Scholar]
- [30].Onslev J, Jacobson G, Narkowicz C, Backer V, Kalsen A, Kreiberg M, Jessen S, Bangsbo J, Hostrup M. Beta2-Adrenergic stimulation increases energy expenditure at rest, but not during submaximal exercise in active overweight men. Eur J Appl Physiol 2017;117:1907-15. https://doi.org/10.1007/s00421-017-3679-9 10.1007/s00421-017-3679-9 [DOI] [PubMed] [Google Scholar]
- [31].Lafontan M, Berlan M, Galitzky J, Montastruc JL. Alpha-2 adrenoceptors in lipolysis: α2 antagonists and lipid-mobilizing strategies. Am J Clin Nutr 1992;55:219S-227S. https://doi.org/10.1093/ajcn/55.1.219s 10.1093/ajcn/55.1.219s [DOI] [PubMed] [Google Scholar]
- [32].Johnson R, Bryant S, Huntley AL. Green tea and green tea catechin extracts: an overview of the clinical evidence. Maturitas 2012;73:280-7. https://doi.org/10.1016/j.maturitas.2012.08.008 10.1016/j.maturitas.2012.08.008 [DOI] [PubMed] [Google Scholar]
- [33].Ha E, Zemel MB. Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (Review). J Nutr Biochem 2003;14:251-8. https://doi.org/10.1016/S0955-2863(03)00030-5 10.1016/S0955-2863(03)00030-5 [DOI] [PubMed] [Google Scholar]
- [34].Maki KC, Reeves MS, Farmer M, Yasunaga K, Matsuo N, Katsuragi Y, Komikado M, Tokimitsu I, Wilder D, Jones F, Blumberg JB, Cartwright Y. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J Nutr 2009;139:264-70. https://doi.org/10.3945/jn.108.098293 10.3945/jn.108.098293 [DOI] [PubMed] [Google Scholar]
- [35].Dangin M, Boirie Y, Guillet C, Beaufrère B. Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr 2002;132:3228S-3233S. https://doi.org/10.1093/jn/131.10.3228S 10.1093/jn/131.10.3228S [DOI] [PubMed] [Google Scholar]
- [36].Delbeke FT, van Eenoo P, van Thuyne W, Desmet N. Prohormones and sport. J Steroid Biochem Mol Biol 2002;83:245-51. https://doi.org/10.1016/S0960-0760(02)00274-1 10.1016/S0960-0760(02)00274-1 [DOI] [PubMed] [Google Scholar]
- [37].Jones ME, Thorburn AW, Britt KL, Hewitt KN, Wreford NG, Proietto J, Oz OK, Leury BJ, Robertson KM, Yao S, Simpson ER. Aromatase-Deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci USA 2000;97:12735-40. https://doi.org/10.1073/pnas.97.23.12735 10.1073/pnas.97.23.12735 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [38].Kelly DM, Jones TH. Testosterone and obesity. Obes Rev 2015;16:581-606. https://doi.org/10.1111/obr.12282 10.1111/obr.12282 [DOI] [PubMed] [Google Scholar]
- [39].Worrel ME, Gurkovskaya Ov, Leonard ST, Lewis PB, Winsauer PJ. Effects of 7-Keto dehydroepiandrosterone on voluntary ethanol intake in male rats. Alcohol 2011;45:349-54. https://doi.org/10.1016/j.alcohol.2010.08.020 10.1016/j.alcohol.2010.08.020 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [40].Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-Acetyl-7-Oxo-Dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem 2007;18:629-34. https://doi.org/10.1016/j.jnutbio.2006.11.008 10.1016/j.jnutbio.2006.11.008 [DOI] [PubMed] [Google Scholar]
- [41].Pittler MH, Ernst E. Dietary supplements for body-weight reduction: a systematic review. J Clin Nutr 2004;79:529-36. https://doi.org/10.1093/ajcn/79.4.529 10.1093/ajcn/79.4.529 [DOI] [PubMed] [Google Scholar]
- [42].Ylitalo R, Lehtinen S, Wuolijoki E, Ylitalo P, Lehtimäki T. Cholesterol-Lowering properties and safety of Chitosan. Arzneimittelforschung 2011;52:1-7. https://doi.org/10.1055/s-0031-1299848 10.1055/s-0031-1299848 [DOI] [PubMed] [Google Scholar]
- [43].Zahorska-Markiewicz B, Krotkiewski M, Olszanecka-Glinianowicz M, Zurakowski A. Effect of Chitosan in complex management of obesity. Pol Merkur Lekarski 2002;13:129-32. [PubMed] [Google Scholar]
- [44].Anton SD, Morrison CD, Cefalu WT, Martin CK, Coulon S, Geiselman P, Han H, White CL, Williamson A. Effects of Chromium Picolinate on food intake and satiety. Diabetes Technol Ther 2008;10:405-12. https://doi.org/10.1089/dia.2007.0292 10.1089/dia.2007.0292 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [45].Pooyandjoo M, Nouhi M, Shab-Bidar S, Djafarian K, Olyaeemanesh A. The Effect of (L-)Carnitine on weight loss in adults: a systematic review and meta-analysis of randomized controlled trials. Obes Rev 2016;17:970-6. https://doi.org/10.1111/obr.12436 10.1111/obr.12436 [DOI] [PubMed] [Google Scholar]
- [46].Tian H, Guo X, Wang X, He Z, Sun R, Ge S, Zhang Z. Chromium Picolinate supplementation for overweight or obese adults. Cochrane Database Syst Rev 2013. https://doi.org/10.1002/14651858.CD010063.pub2 10.1002/14651858.CD010063.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [47].Yoo H-J, Yoon H-Y, Yee J, Gwak H-S. Effects of ephedrine-containing products on weight loss and lipid profiles: a systematic review and meta-analysis of randomized controlled trials. Pharmaceuticals 2021;14:1198. https://doi.org/10.3390/ph14111198 10.3390/ph14111198 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [48].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? Regul Toxicol Pharmacol 2015;73:196-200. https://doi.org/10.1016/j.yrtph.2015.06.022 10.1016/j.yrtph.2015.06.022 [DOI] [PubMed] [Google Scholar]
- [49].Stohs SJ. Safety, efficacy, and mechanistic studies regarding Citrus Aurantium (Bitter Orange) Extract and p -Synephrine. Phytotherapy Research 2017;31:1463-74. https://doi.org/10.1002/ptr.5879 10.1002/ptr.5879 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [50].Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, Higenbottam T, Oakley C, Wouters E, Aubier M, Simonneau G, Bégaud B. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996;335:609-16. https://doi.org/10.1056/NEJM199608293350901 10.1056/NEJM199608293350901 [DOI] [PubMed] [Google Scholar]
- [51].Kamphuis MMJW, Lejeune MPGM, Saris WHM, Westerterp-Plantenga MS. Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects. Eur J Clin Nutr 2003;57:1268-74. https://doi.org/10.1038/sj.ejcn.1601684 10.1038/sj.ejcn.1601684 [DOI] [PubMed] [Google Scholar]
- [52].Sandhya VG, Rajamohan T. Beneficial effects of coconut water feeding on lipid metabolism in Cholesterol-fed rats. J Med Food 2006;9:400-7. https://doi.org/10.1089/jmf.2006.9.400 10.1089/jmf.2006.9.400 [DOI] [PubMed] [Google Scholar]
- [53].Wanten G, Naber A. Cellular and physiological effects of medium-chain Triglycerides. Mini Rev Med Chem 2004;4:847-57. https://doi.org/10.2174/1389557043403503 10.2174/1389557043403503 [DOI] [PubMed] [Google Scholar]
- [54].Maher T, Sampson A, Goslawska M, Pangua-Irigaray C, Shafat A, Clegg ME. Food intake and satiety response after medium-chain Triglycerides ingested as solid or liquid. Nutrients 2019;11:1638. https://doi.org/10.3390/nu11071638 10.3390/nu11071638 [DOI] [PMC free article] [PubMed] [Google Scholar]
- [55].Soerensen Kv, Thorning TK, Astrup A, Kristensen M, Lorenzen JK. Effect of dairy calcium from cheese and milk on fecal fat excretion, blood lipids, and appetite in young men. Am J Clin Nutr 2014;99:984-91. https://doi.org/10.3945/ajcn.113.077735 10.3945/ajcn.113.077735 [DOI] [PubMed] [Google Scholar]