Life Extension Magazine July 2011
Shed Pounds by Inhibiting Cellular Fat Storage
By Kirk Stokel
Health authorities are warning about the devastating consequences of obesity, yet doctors remain in the dark about what causes people to accumulate so many fat pounds as they age.
Through a series of well-designed studies, scientists investigating certain plant extracts found they can block fat storage at the cellular level.
In a significant scientific advance, a potent new weapon has been identified to help safely induce weight loss.
This article describes how a novel dual plant extract favorably modulates six pathways that fat cells use to trigger weight gain.
When tested on humans in a placebo-controlled study, those taking this dual plant extract lost 4.05 inches of abdominal fat and dropped 11.4 pounds after eight weeks…with weight loss observed as early as 14 days.1
Cells that store fat are called adipocytes. They are deposited throughout our bodies.2,3
As we age, adipocytes tend to expand and congregate in areas that are cosmetically unsightly and detrimental to our health.
Of greatest concern are the adipocytes that deposit deep in our abdomens. This “visceral fat” represents more than fat stored on our waistlines. Visceral fat is chemically active tissue that churns out a torrent of pro-inflammatory cytokines.4
Those with bulging belly fat suffer constant bombardment from toxic cytokines that trigger the metabolic syndrome and its deadly consequences.5,6
This widespread problem led scientists to seek out plant extracts that specifically interfere with adipocyte fat storage in our abdominal anatomy.
How Unwanted Fat Storage Occurs
Excess calories transform to fat deposits in adipocytes7 through a multi-step process known as adipogenesis.
When fewer calories are consumed, fat is released from adipocytes to meet the body’s energy needs.8,9 This is known as lipolysis.
A dual plant extract has been studied based on its ability to simultaneously inhibit adipogenesis (fat storage) and enhance lipolysis (fat breakdown and release).
Like any other cell, adipocytes develop from undifferentiated stem cells. Premature, developing fat cells are called pre-adipocytes. When you ingest more calories than your body needs, “young” pre-adipocytes respond by maturing into “adult” adipocytes.7,10-12
“Adult” adipocytes take up excess fatty acids from your bloodstream and begin expanding. It is this process of fatty acid uptake and adipocyte expansion that ultimately results in obesity and its pathologic consequences. Every excess calorie contributes to the maturation and growth of fat cells in this way. Past a certain point, adipocytes distend and become bloated, much in the same way your belly does.
Not all adipocytes are the same. While fat cells distribute throughout your body, those that store in your abdomen—producing so-called visceral fat or belly fat—are more than just storage “containers.”
Belly fat cells are chemically active. They form fatty tissue capable of releasing detrimental pro-inflammatory cytokines.4
In obese individuals, the mass of excess visceral fat deposits generates a pro-inflammatory flood of cytokines. This cytokine release then incites a cascade of harmful effects that, if left unchecked, contributes to the onset of multiple degenerative diseases.5,6
So unwanted body fat storage happens when pre-adipocyte stem cells mature in order to store excess dietary fat (adipogenesis) while the ability to break down stored fat (lipolysis) diminishes.
Combating Surplus Body Fat Storage
Searching for natural interventions that would effectively inhibit fat accumulation (adipogenesis) and enhance fat burning (lipolysis), scientists evaluated more than a thousand plants for evidence that would meet this criteria.13
Two plants whose extracts demonstrated significant biological effects were:
In the laboratory, S. indicus and mangosteen extracts powerfully impeded adipogenesis.
When cells were treated with S. indicus alone, fat storage was inhibited by as much as 65%, compared with control cells. Photographs (below) show a markedly visible difference between the two cell groups. The control cells show a bloated, “foamy” appearance, bulging with fat droplets, compared to the smaller, more naturally contoured cells treated with the S. indicus extract.13
Each of these extracts also enhanced lipolysis (or fat burning), by as much as 56% compared to control cells.13
Having identified these unifying properties in the two extracts, the researchers set out to determine if they would exhibit enhanced effects when used in combination.
They found that the S. indicus and mangosteen extracts favorably modulate the activity of six genomic pathways involved in fat cell formation and breakdown.13
Remarkably, these extracts reduced gene expression that promotes adipogenesis while favorably influencing a gene involved in desirable lipolysis.
The box on this page shows how these plant extracts, used alone and in combination, positively modulated the markers involved in unwanted cellular fat accumulation by inhibiting adipogenesis and promoting lipolysis.
Given these observations, researchers recognized that this novel blend of plant extracts could result in significant weight loss via three distinct mechanisms:
The next step was to determine if these plant extracts would induce weight loss in experimental animals and—more importantly—obese humans.
Preventing Obesity in Rodents
When young adult rats are fed a high-fat diet they rapidly gain weight—just as humans often do.
To investigate the effects of the plant extracts that worked in cell studies, scientists fed a group of young adult rats a high-fat diet. Half the rats received the dual plant extract while the other half served as the control group.13
At the end of eight weeks, the control group rapidly gained weight. The rats fed a high-fat diet and given the dual plant extract, on the other hand, reduced body weight gain by an impressive 700%.13
This is not surprising considering these same plant extracts blocked fat accumulation by 48.5% and 65.9% in the cellular model.13
This study demonstrated that these plant extracts decrease diet-induced obesity in young adult rats. The real challenge, however, is whether these same plant extracts are effective in humans who are already obese.
Weight Loss Findings in Humans
Human weight loss studies comprise an active arm that received the potentially effective fat-reducing agent and a similar group that received an inactive placebo.
To evaluate the effects of these two plant extracts, 60 obese adults were recruited and divided into two groups. One arm of 30 patients functioned as the placebo group while a second group of 30 patients received 800 mg per day of a combination of the two plant extracts. Both groups followed a 2,000-calorie- per-day diet and were asked to walk 30 minutes five days a week.
At the end of eight weeks, the group receiving the two plant extracts showed the following improvements:1
This was a randomized, double-blind, placebo-controlled study, the kind the FDA mandates before it approves new drugs. The charts on this page reveal the magnitude of the weight loss and belly fat reduction that occurred in the group receiving the dual plant extract compared to placebo.1 (See Charts 1 and 2)
In addition to the favorable results seen at eight weeks, researchers were impressed with the reduction in waist and hip circumference, as well as lost body weight that occurred within the first 14 days! In fact after only two weeks, the average weight reduction was 4.6 pounds.1
At eight weeks, the dual plant extract group showed reduction in the waist-to-hip ratio that was 2.2 times greater than the placebo group. This is an important improvement as it indicates dangerous visceral belly fat is being lost.
These findings are supported by a second, similarly designed trial involving 60 obese subjects. They were divided into three groups that consisted of a placebo arm, an active arm receiving one plant extract, and another active arm that received a dual plant extract. All participants followed a 2,000-calorie-per-day diet and were asked to walk for 30 minutes five times a week for 8 weeks.13
After eight weeks the group receiving the dual plant extract experienced statistically significant changes in their abdominal circumference, total body weight, and hip circumference similar to those seen in the first study mentioned above.13
These confirmatory findings indicate that this novel dual plant extract may enable aging humans to safely shed unwanted body fat stores. No major adverse events or side effects were reported in either study.
Protection against Coronary Thrombosis
Most sudden death heart attacks occur when a blood clot forms in a coronary artery, choking off oxygenated blood to a portion of the heart muscle.
A protein called plasminogen activator inhibitor-1 (PAI-1) inhibits the normal breakdown of arterial blood clots.29 High levels of PAI-1 are observed in obese individuals and are associated with increased heart attack risk.30,31
When studying the dual plant extract, researchers measured serum levels of plasminogen activator inhibitor-1 (PAI-1). Those receiving the dual plant extract showed a 24.3% reduction in dangerous PAI-1 levels, while the placebo group showed a 2.4% increase.1 (See Chart 3)
Those supplemented with the dual plant extract had a 60% drop in triglyceride levels compared to baseline.1
Subjects given the dual plant extract increased levels of the key metabolic hormone adiponectin.1 Adiponectin regulates how much sugar is in your bloodstream and how quickly your body breaks down fat. In terms of fat loss, high adiponectin levels are desirable. Higher levels of adiponectin are associated with decreased deposits of body fat and a reduced susceptibility to diabetes and metabolic syndrome.42
The dual plant extract group showed trends toward reduced glucose and cholesterol, which are expected to occur in response to loss of belly fat and body weight.1
The loss of visceral fat in the dual extract group— 4.05 inches, amounting to twice the decline observed in the placebo group—is compelling.1 This is important because visceral fat releases a storm of pro-inflammatory cell-signaling molecules. Excess visceral fat is a known risk factor for a number of serious health threats, ranging from systemic inflammation to increased risk of hypertension, atherosclerosis, type 2 diabetes, and coronary artery disease.43-45
Taken together, these findings indicate markedly reduced vascular disease risk in obese individuals taking 800 mg a day of this dual plant extract.
Obesity arises from the increased size of individual adipocytes (fat cells) due to enhanced lipid (fat) accumulation. It worsens as greater numbers of pre-adipocytes transform into dysfunctional, bloated adipocytes.
The novel blend of plant extracts described in this article favorably influences six distinct pathways by which fat cells trigger weight gain.
In cell culture, these plant extracts reduce the ability of progenitor fat cells (pre-adipocytes) to transform into bloated fat cells. These studies also show that components of this dual plant extract reduce the amount of fatty acids taken up by adipocytes (adipogenesis) and facilitate the breakdown (lipolysis) of fat stored in existing adipocytes.
In a placebo-controlled clinical trial involving obese humans, this blend of S. indicus and mangosteen plant extracts safely induced weight loss of 11.4 pounds, along with a decline of 2.05 in body mass index (BMI) and a reduction of 4.05 inches in harmful visceral fat.1
While our medical establishment has failed to offer any safe, long-term, practical solutions for today’s obesity epidemic, natural agents are now available that substantively augment the effects of a sensible weight loss program.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at
1. Lau FC, Golakoti T, Krishnaraju AV, Sengupta K, Bagchi D. Efficacy and tolerability of Merastin™- A randomized, double-blind, placebo-controlled study. FASEB J. April 2011; 25:(Meeting Abstract Supplement) 601.9. Presented at Experimental Biology 2011, Washington, DC. April 10, 2011. Program No. 601.9, Poster No. A278.
2. Bunnell BA, Estes BT, Guilak F, Gimble JM. Differentiation of adipose stem cells. Methods Mol Biol. 2008;456:155-71.
3. Symonds ME, Budge H, Perkins AC, Lomax MA. Adipose tissue development - Impact of the early life environment. Prog Biophys Mol Biol. 2010 Dec 14.
4. Takakura Y, Yoshida T. Beta 3-adrenergic receptor agonists--past, present and future. Nippon Yakurigaku Zasshi. 2001 Nov;118(5):315-20.
5. Xiao L, Zhang J, Li H, Liu J, He L, Zhai Y. Inhibition of adipocyte differentiation and adipogenesis by the traditional Chinese herb Sibiraea angustata. Exp Biol Med (Maywood). 2010 Dec;235(12):1442-9.
6. Bumrungpert A, Kalpravidh RW, Chuang CC, et al. Xanthones from mangosteen inhibit inflammation in human macrophages and in human adipocytes exposed to macrophage-conditioned media. J Nutr. 2010 Apr;140 (4):842-7.
7. Amini Z, Boyd B, Doucet J, Ribnicky DM, Stephens JM. St. John’s Wort inhibits adipocyte differentiation and induces insulin resistance in adipocytes. Biochem Biophys Res Commun. 2009 Oct 9;388(1):146-9.
8. Frayn KN, Fielding BA, Karpe F. Adipose tissue fatty acid metabolism and cardiovascular disease. Curr Opin Lipidol. 2005 Aug;16(4):409-15.
9. Wang S, Soni KG, Semache M, et al. Lipolysis and the integrated physiology of lipid energy metabolism. Mol Genet Metab. 2008 Nov;95(3):117-26.
10. Lee J, Jung E, Huh S, Kim YS, Kim YW, Park D. Anti-adipogenesis by 6-thioinosine is mediated by downregulation of PPAR gamma through JNK-dependent upregulation of iNOS. Cell Mol Life Sci. 2010 Feb;67(3):467-81.
11. Smas CM, Sul HS. Molecular mechanisms of adipocyte differentiation and inhibitory action of pref-1. Crit Rev Eukaryot Gene Expr. 1997;7(4):281-98.
12. Fan B, Ikuyama S, Gu JQ, et al. Oleic acid-induced ADRP expression requires both AP-1 and PPAR response elements, and is reduced by Pycnogenol through mRNA degradation in NMuLi liver cells. Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E112-23.
13. Results based on initial analyses of unpublished research data.
14. Imamura M, Inoguchi T, Ikuyama S, et al. ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. Am J Physiol Endocrinol Metab. 2002 Oct;283(4):E775-83.
15. Grasselli E, Voci A, Canesi L, et al. Direct effects of iodothyronines on excess fat storage in rat hepatocytes. J Hepatol. 2010 Nov 3.
16. Imai Y, Varela GM, Jackson MB, Graham MJ, Crooke RM, Ahima RS. Reduction of hepatosteatosis and lipid levels by an adipose differentiation-related protein antisense oligonucleotide. Gastroenterology. 2007 May;132(5):1947-54.
17. Agardh HE, Folkersen L, Ekstrand J, et al. Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis. J Intern Med. 2011 Feb;269(2):200-10.
18. Aragones G, Ferre R, Lazaro I, et al. Fatty acid-binding protein 4 is associated with endothelial dysfunction in patients with type 2 diabetes. Atherosclerosis. 2010 Nov;213(1):329-31.
19. Cabre A, Lazaro I, Cofan M, et al. FABP4 plasma levels are increased in familial combined hyperlipidemia. J Lipid Res. 2010 May;51(5):1173-8.
20. Cabre A, Lazaro I, Girona J, et al. Plasma fatty acid binding protein 4 is associated with atherogenic dyslipidemia in diabetes. J Lipid Res. 2008 Aug;49(8):1746-51.
21. Chmurzynska A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet. 2006;47(1):39-48.
22. Karakas SE, Almario RU, Kim K. Serum fatty acid binding protein 4, free fatty acids, and metabolic risk markers. Metabolism. 2009 Jul;58(7):1002-7.
23. Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep. 2001 Apr;2(4):282-6.
24. Toruner F, Altinova AE, Akturk M, et al. The relationship between adipocyte fatty acid binding protein-4, retinol binding protein-4 levels and early diabetic nephropathy in patients with type 2 diabetes. Diabetes Res Clin Pract. 2010 Dec 19.
25. Tsai JP, Liou HH, Liu HM, Lee CJ, Lee RP, Hsu BG. Fasting serum fatty acid-binding protein 4 level positively correlates with metabolic syndrome in hemodialysis patients. Arch Med Res. 2010 Oct;41(7):536-40.
26. Li Y, Kang Z, Li S, Kong T, Liu X, Sun C. Ursolic acid stimulates lipolysis in primary-cultured rat adipocytes. Mol Nutr Food Res. 2010 Nov;54(11):1609-17.
27. Nerurkar PV, Lee YK, Nerurkar VR. Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes. BMC Complement Altern Med. 2010;10:34.
28. Tinahones FJ, Garrido-Sanchez L, Miranda M, et al. Obesity and insulin resistance-related changes in the expression of lipogenic and lipolytic genes in morbidly obese subjects. Obes Surg. 2010 Nov;20(11):1559-67.
29. Mutch NJ, Thomas L, Moore NR, Lisiak KM, Booth NA. TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots. J Thromb Haemost. 2007 Apr;5(4):812-7.
30. Trayhurn P, Wood IS. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans. 2005 Nov;33(Pt 5):1078-81.
31. Gnacinska M, Malgorzewicz S, Guzek M, Lysiak-Szydłowska W, Sworczak K. Adipose tissue activity in relation to overweight or obesity. Endokrynol Pol. 2010 Mar-Apr;61(2):160-8.
32. Cock TA, Houten SM, Auwerx J. Peroxisome proliferator-activated receptor-gamma: too much of a good thing causes harm. EMBO Rep. 2004 Feb;5(2):142-7.
33. Jiang HZ, Quan XF, Tian WX, et al. Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostana. Bioorg Med Chem Lett. 2010 Oct 15;20(20):6045-7.
34. Choi JH, Banks AS, Estall JL, et al. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature. 2010 Jul 22;466(7305):451-6.
35. Oben JE, Ngondi JL, Blum K. Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and leptin genes and up-regulation of the adiponectin gene. Lipids Health Dis. 2008;7:44.
36. Tsukahara T, Hanazawa S, Murakami-Murofushi K. Cyclic phosphatidic acid influences the expression and regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 cells. Biochem Biophys Res Commun. 2011 Jan 7;404(1):109-14.
37. An S, Han JI, Kim MJ, et al. Ethanolic extracts of Brassica campestris spp. rapa roots prevent high-fat diet-induced obesity via beta(3)-adrenergic regulation of white adipocyte lipolytic activity. J Med Food. 2010 Apr;13(2):406-14.
38. Hatakeyama Y, Sakata Y, Takakura S, Manda T, Mutoh S. Acute and chronic effects of FR-149175, a beta 3-adrenergic receptor agonist, on energy expenditure in Zucker fatty rats. Am J Physiol Regul Integr Comp Physiol. 2004 Aug;287(2):R336-41.
39. Lima JJ, Feng H, Duckworth L, et al. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism. 2007 Jun;56(6):757-65.
40. Sakura H, Togashi M, Iwamoto Y. Beta 3-adrenergic receptor agonists as anti-obese and anti-diabetic drugs. Nippon Rinsho. 2002 Jan;60(1):123-9.
41. van Baak MA, Hul GB, Toubro S, et al. Acute effect of L-796568, a novel beta 3-adrenergic receptor agonist, on energy expenditure in obese men. Clin Pharmacol Ther. 2002 Apr;71(4):272-9.
42. Ukkola O, Santaniemi M. Adiponectin: a link between excess adiposity and associated comorbidities? J Mol Med. 2002 Nov;80(11):696-702.
43. Koh H, Hayashi T, Sato KK, et al. Visceral adiposity, not abdominal subcutaneous fat area, is associated with high blood pressure in Japanese men: the Ohtori study. Hypertens Res. 2011 Jan 13.
44. Lee YH, Lee SH, Jung ES, et al. Visceral adiposity and the severity of coronary artery disease in middle-aged subjects with normal waist circumference and its relation with lipocalin-2 and MCP-1. Atherosclerosis. 2010 Dec;213(2):592-7.
45. Navarro E, Mijac V, Ryder HF. Ultrasonography measurement of intrabdominal visceral fat in obese men. Association with alterations in serum lipids and insulinemia. Arch Latinoam Nutr. 2010 Jun;60(2):160-7.
46. Galani VJ, Patel BG, Rana DG. Sphaeranthus indicus Linn.: A phytopharmacological review. Int J Ayurveda Res. 2010 Oct;1(4):247-53.
47. Prabhu KS, Lobo R, Shirwaikar A. Antidiabetic properties of the alcoholic extract of Sphaeranthus indicus in streptozotocin-nicotinamide diabetic rats. J Pharm Pharmacol. 2008 Jul;60(7):909-16.
48. Ramachandran S, Asokkumar K, Uma Maheswari M, et al. Investigation of Antidiabetic, Antihyperlipidemic, and In Vivo Antioxidant Properties of Sphaeranthus indicus Linn. in Type 1 Diabetic Rats: An Identification of Possible Biomarkers. Evid Based Complement Alternat Med. 2011;2011.
49. Ghaisas M, Zope V, Takawale A, Navghare V, Tanwar M, Deshpande A. Preventive effect of Sphaeranthus indicus during progression of glucocorticoid-induced insulin resistance in mice. Pharm Biol. 2010 Dec;48(12):1371-5.
50. Shirwaikar A, Prabhu KS, Punitha IS. In vitro antioxidant studies of Sphaeranthus indicus (Linn). Indian J Exp Biol. 2006 Dec;44(12):993-6.
51. Loo AE, Huang D. Assay-guided fractionation study of alpha-amylase inhibitors from Garcinia mangostana pericarp. J Agric Food Chem. 2007 Nov 28;55(24):9805-10.
52. Bumrungpert A, Kalpravidh RW, Chitchumroonchokchai C, et al. Xanthones from mangosteen prevent lipopolysaccharide-mediated inflammation and insulin resistance in primary cultures of human adipocytes. J Nutr. 2009 Jun;139(6):1185-91.
53. Udani JK, Singh BB, Barrett ML, Singh VJ. Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study. Nutr J. 2009;8:48.