Life Extension Magazine August 2008
A Scientific Solution to Unsightly Cellulite
By Laurie Barclay, MD
Cellulite affects nearly every woman as she gets older. The skin dimpling and bumps typically seen on the thighs, hips, and buttocks is a condition that women have endured for centuries.
While purported “cures” for cellulite abound, the billions of dollars spent on specialized creams, diets, and massage therapies have not overcome the problem. The reason why these methods have failed is because they have approached cellulite as purely a cosmetic problem and neglected to address its underlying causes.
Fortunately, major scientific discoveries have uncovered the factors that cause cellulite.
Dermatology experts have taken these new data to develop powerful topical agents that target cellulite by correcting the underlying abnormalities involved in its formation. These active botanicals have been shown to help restore smooth and youthful body contours to the hips and thighs.
How Females Develop Cellulite
Why are women prone to cellulite as soon as they begin menstruation, whereas men are spared? Many experts believe that the primary culprits are hormonal influences on fat deposits over the buttocks, thighs, and hips, as well as anatomical differences in how this fat is stored.1,2
Although there are three layers of fat under the skin, only the top layer is involved in cellulite. Imagine that the skin in this top layer is like a down quilt. The stitches in the quilt represent columns of collagen fibers that give the skin its structure. Adding feathers into the compartments between the stitches is analogous to how fat globules accumulate between the skin’s collagen columns. As more fat globules are added, the compartments fill up, causing fat to bulge out from the compartments resulting in the characteristic dimpled appearance of cellulite.
Scientists have discovered how changes in the connective tissue structure in this top fat layer trigger the formation of cellulite. Magnetic resonance imaging studies have shown that women with cellulite have pillar-like columns separating the fat chambers, which are larger and deeper than those in men.3
What makes women more vulnerable to cellulite is that these large vertical chambers can store an abundance of fat. Collagen supporting tissue of men, on the other hand, is more like a criss-cross net that is organized into small diagonal chambers, which hold only small amounts of fat.4
These longer supportive columns in women are more easily weakened by hormonal, structural, and vascular changes that affect the skin’s support structure, allowing fat to protrude deeply into the dermis (the layer of skin beneath the outermost layer), which gives rise to the characteristic lumpy appearance of cellulite.1
Pregnancy and other hormonal changes in women affect the formation of cellulite, as do genetics and aging. These factors adversely affect adipose tissue and the supporting connective tissue.1 Hormones secreted in response to stress, particularly cortisol, also encourage fat deposition in problem areas.5
“The adipose tissue in the thighs and buttocks [in women] is special in that it is reserved for nutrition of a fetus in bad times,” Peter T. Pugliese, MD, founder of Circadia Skin Care Institute in Reading, PA, tells Life Extension. “So this fat does not move with normal dietary restriction or with exercise.”
These differences highlight the fact that cellulite is not purely a cosmetic problem, but involves a number of physiological factors. “Cellulite is multifactorial but mostly related to the underlying structure or framework and relationship of adipose tissue to connective tissue in women,” Adam M. Rotunda, MD, a clinical instructor of dermatology at the David Geffen School of Medicine, UCLA, tells Life Extension.
Connective Tissue Structure Abnormalities in Cellulite
Connective tissue structure in women increases vulnerability to cellulite, with the result that female skin becomes loose and more wrinkled with age.
“Cellulite-affected skin demonstrates biomechanical properties of increased laxity in contrast to skin without cellulite,” Gordon H. Sasaki, MD, FACS, a surgeon at the Sasaki Advanced Aesthetic Medical Center in Pasadena, CA, says.
Other factors compromise the underlying connective tissue such as the enzyme collagenase that is released before a woman’s menstrual cycle. This enzyme breaks down collagen, which is a key structural protein within connective tissues.6 Fibrous tissue, similar to that seen with scarring, may fill in the gaps caused by degraded collagen. This results in the formation of fibrotic stiff bands that can worsen the appearance of cellulite.
“Cellulite is a disease of the connective tissue initiated by cyclic hormones of the menstrual cycle,” Dr. Pugliese says. “The characteristic undulating surface one sees with cellulite is the product of extensive connective tissue destruction.”
Poor Circulation Aggravates Cellulite
As well as connective tissue abnormalities, poor circulation and lymph drainage can also aggravate cellulite. Fat, or adipose tissue, is relatively rich in blood vessels. Decreased blood flow, swelling from fluid accumulation (edema), and local inflammation can aggravate the female propensity to skin looseness and hasten the development of cellulite through a domino effect.
When small blood vessels become fragile, they leak excess fluid that accumulates in the compartments between the fat chambers. This effect increases pressure within the tissues, resulting in poor lymphatic drainage. As excess fluid is retained in dermal tissues, fat globules cluster together and inhibit venous return. This vascular damage results in decreased collagen synthesis and an inability to repair tissue damage, which weakens the dermis. Over time, clumps of hardened collagen contribute to the formation of fibrotic collagen bands, which become deposited around fat globules beneath the skin. The tightening of these bands causes a vicious cycle that worsens cellulite and impairs blood flow even more.6 These changes have been seen in ultrasound imaging of skin affected by cellulite, which reveals thinning of the dermis with fat pushing upward.6
As a result of compromised circulation and lymphatic drainage, cellulite may appear and worsen in predisposed areas.1 “One of the major factors inducing cellulite is venous insufficiency and congestion,” Carl R. Thornfeldt, MD, FAAD, founder and CEO of Episciences, Inc., tells Life Extension. “Non-prescription and/or herbal therapies have rarely been studied in this condition. Several are reported to be effective in the literature, but only horse chestnut [Aesculus hippocastanum] and gotu kola [Centella asiatica] have documented efficacy in reversing venous insufficiency.” Leslie Baumann, MD, professor of dermatology at the University of Miami, agrees that, “Horse chestnut and gotu kola seem to improve circulation.”
“Increasing circulation may help by increasing lymph flow,” Dr. Baumann tells Life Extension. “Lymph builds up and makes cellulite appear worse. By increasing circulation this may increase lymph flow and help the appearance of cellulite.”
Zeroing in on Anti-Cellulite Compounds
Ideally, an herbal cream to combat cellulite should target the three main causes of cellulite that have been identified. These are excess fat deposition, weakened connective tissue support structure, and poor circulation.1,7,8
Life Extension has identified seven compounds that may be especially promising as a multi-modal approach to correct the underlying causes of cellulite. Glycyrrhetinic acid, for example, is a compound derived from licorice root that targets fat storage in response to stress. Horse chestnut and gotu kola improve circulation, while also supporting connective tissue integrity. All three compounds have additional benefits that may improve the appearance of cellulite-prone skin, including antioxidant and anti-inflammatory activity. For readers interested in technical descriptions of these anti-cellulite nutrients, please see the information outlined in the boxes throughout this article.
While the combination of glycyrrhetinic acid, horse chestnut, and gotu kola has demonstrated favorable anti-cellulite effects, scientists have discovered four additional nutrients that have demonstrated profound fat-reducing benefits. As you will read, these anti-fat ingredients provide a key missing link to resolving cellulite.
Enzymatic Breakdown of Body Fat
Fat storage and breakdown are controlled by two sets of special receptors called alpha and beta receptors on the surface of each fat cell, or adipocyte. Regulated by the hormone epinephrine, beta-adrenergic receptors promote fat breakdown (lipolysis), whereas alpha-adrenergic receptors prevent fat breakdown and promote fat storage.9,10 “In the case of cellulite fat, the alpha receptors outnumber the beta receptors,” Dr. Pugliese says. Women also tend to have more fat-storage alpha receptors than fat-breakdown beta receptors in the hips and thighs9 so that storage exceeds breakdown in these areas, causing swelling of the stored fat within cells.
Stimulation of these receptors also leads to changes in a crucial lipolytic (fat-breakdown) enzyme called hormone-sensitive lipase.11 This enzyme is located directly in the fat cell and is activated when beta receptors are stimulated, breaking down triglycerides in fat to release free fatty acids and glycerol into the bloodstream. Conversely, alpha-receptor stimulation inhibits this enzyme and promotes fat storage.
Aerobic exercise improves the ability to mobilize and break apart triglycerides for energy use, whereas obesity makes the fat-breakdown enzyme hormone-sensitive lipase less sensitive to epinephrine.11 This may help explain why, to some degree, exercise, which is associated with epinephrine release by the sympathetic nervous system, is helpful in improving the appearance of cellulite, whereas obesity aggravates its appearance.
Another enzyme called lipoprotein lipase that is found in large amounts in adipose tissue and in the liver acts on triglycerides within lipoproteins, breaking them down into free fatty acid molecules to be either burned for energy or stored as fat. Lipoprotein lipase is also responsible for the uptake of fat into the adipocytes. Women tend to have higher concentrations and activity of this enzyme in the hips and thighs, favoring fat storage in this region particularly if they are not physically active.9
To overcome these adverse enzymatic changes that make women vulnerable to cellulite formation, scientists have identified two unique marine extracts known as Phycoboreane™ and Rhodysterol™ that are showing promise for their effects in promoting lipolysis and liberating fat.
These compounds appear to stimulate an enzyme called protein kinase A, which in turn activates hormone-sensitive lipase to break down fat, releasing fatty acids and glycerol. These compounds also contain sulfated polysaccharides, which can bind to fatty acids and facilitate their elimination. Studies in all types of cellulite are underway to determine the effects of Phycoboreane™ and Rhodysterol™ on edema, fibrosis, skin suppleness, and tonicity.
The Two Most Exciting Fat-Reducing Ingredients
Scientists in Europe have developed two new breakthrough formulations called Adiposlim™ and Adipoless™. Both of these compounds work in synergy to help reduce stubborn cellulite and prevent its formation.12 Adiposlim™ shrinks adipocytes by activating the fat-burning beta receptors while simultaneously turning off alpha receptors that inhibit fat burning.12 It also boosts fat oxidation, ensuring fat is burned as cellular energy, and inhibits the enzyme lipoprotein lipase to prevent fat storage.12
A clinical trial in adults using Adiposlim™ on the thigh area showed 12% cellulite reduction after only one month, compared with only 6% for a control group, as well as visual cellulite improvement in 71% of treated subjects.12
Adipoless™, meanwhile, blocks the formation of blood vessels needed to transform pre-adipocytes into fully formed fat cells, thereby inhibiting the formation of new fat.12
Doctors interviewed by Life Extension emphasized the importance of reducing fat storage in the regions of the body prone to cellulite. According to Dr. Rotunda, once an anti-cellulite cream is discontinued, it is conceivable any regional benefit at the site of application would be lost unless fat cells are destroyed or removed.
With the advent of these four new topical fat-altering compounds (Adiposlim™, Adipoless™, Phycoboreane™, and Rhodysterol™), a sustainable anti-cellulite program is now a reality.
A Multi-Pronged Approach
Effective cellulite therapy may ultimately require a multi-pronged approach: mobilizing and reducing fat, preventing breakdown of support structures within the skin by promoting collagen synthesis, and preventing capillary leakage, while inhibiting inflammation and edema.
Glycyrrhetinic acid, horse chestnut, gotu kola, Phycoboreane™, Rhodysterol™, Adiposlim™, and Adipoless™ are well poised to facilitate this strategy, ideally in combination with healthy lifestyle changes and use of adjunctive measures.
“Since cellulite is the visible manifestation of multiple pathologic processes, one cannot reasonably expect a single agent to effectively treat this disease,” Dr. Thornfeldt concludes.
If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.
1. Rotunda AM, Rao J, Goldman M. Treatments for cellulite. In Lasers and Lights, Volume II, 2nd Edition. Goldberg D, Ed; Elsevier 2007.
2. Wollina U, Goldman A, Berger U, bdel-Naser MB. Esthetic and cosmetic dermatology. Dermatol Ther. 2008 Mar;21(2):118-30.
3. Querleux B, Cornillon C, Jolivet O, Bittoun J. Anatomy and physiology of subcutaneous adipose tissue by in vivo magnetic resonance imaging and spectroscopy: relationships with sex and presence of cellulite. Skin Res Technol. 2002 May;8(2):118-24.
4. Nurnberger F, Muller G. So-called cellulite: an invented disease. J Dermatol Surg Oncol. 1978 Mar;4(3):221-9.
5. Stewart PM, Tomlinson JW. Cortisol, 11 beta-hydroxysteroid dehydrogenase type 1 and central obesity. Trends Endocrinol Metab. 2002 Apr;13(3):94-6.
6. Draelos ZD. The disease of cellulite. J Cosmet Dermatol. 2005;4:221-2.
7. Avram MM. Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther. 2004 Dec;6(4):181-5.
8. Pavicic T, Borelli C, Korting HC. Cellulite—the greatest skin problem in healthy people? An approach. J Dtsch Dermatol Ges. 2006 Oct;4(10):861-70.
9. Blaak E. Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care. 2001 Nov;4(6):499-502.
10. Richelsen B, Pedersen SB, Moller-Pedersen T, Bak JF. Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2. Metabolism. 1991 Sep;40(9):990-6.
11. Rasmussen BB, Wolfe RR. Regulation of fatty acid oxidation in skeletal muscle. Annu Rev Nutr. 1999;19:463-84.
12. SEPPIC. Data on file. 2008.
13. Quinkler M, Oelkers W, Diederich S. Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues. Eur J Endocrinol. 2001 Feb;144(2):87-97.
14. Stewart PM, Krozowski ZS. 11 beta-Hydroxysteroid dehydrogenase. Vitam Horm. 1999;57:249-324.
15. Armanini D, Nacamulli D, Francini-Pesenti F, et al. Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application. Steroids. 2005 Jul;70(8):538-42.
16. Armanini D, Mattarello MJ, Fiore C, et al. Licorice reduces serum testosterone in healthy women. Steroids. 2004 Oct;69(11-12):763-6.
17. Nam C, Kim S, Sim Y, Chang I. Anti-acne effects of Oriental herb extracts: a novel screening method to select anti-acne agents.
Skin Pharmacol Appl Skin Physiol. 2003 Mar;16(2):84-90.
18. Friis-Moller A, Chen M, Fuursted K, Christensen SB, Kharazmi A. In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots. Planta Med. 2002 May;68(5):416-9.
19. Anon. Glycyrrhiza glabra. Monograph. Altern Med Rev. 2005 Sep;10(3):230-7.
20. Okimasu E, Moromizato Y, Watanabe S, et al. Inhibition of phospholipase A2 and platelet aggregation by glycyrrhizin, an antiinflammation drug. Acta Med Okayama. 1983 Oct;37(5):385-91.
21. Shibata S, Inoue H, Iwata S, et al. Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice. Planta Med. 1991 Jun;57(3):221-4.
22. Abe K, Ikeda T, Wake K, et al. Glycyrrhizin prevents of lipopolysaccharide/D-galactosamine-induced liver injury through down-regulation of matrix metalloproteinase-9 in mice. J Pharm Pharmacol. 2008 Jan;60(1):91-7.
23. Sato I, Kofujita H, Suzuki T, Kobayashi H, Tsuda S. Antiinflammatory effect of Japanese horse chestnut (Aesculus turbinata) seeds. J Vet Med Sci. 2006 May;68(5):487-9.
24. Guillaume M, Padioleau F. Veinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extract. Arzneimittelforschung. 1994 Jan;44(1):25-35.
25. Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 2006;(1):CD003230.
26. Pittler MH, Ernst E. Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review. Arch Dermatol. 1998 Nov;134(11):1356-60.
27. Bisler H, Pfeifer R, Kluken N, Pauschinger P. Effects of horse-chestnut seed extract on transcapillary filtration in chronic venous insufficiency. Dtsch Med Wochenschr. 1986 Aug 29;111(35):1321-9.
28. Diehm C, Trampisch HJ, Lange S, Schmidt C. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet. 1996 Feb 3;347(8997):292-4.
29. Sato I, Suzuki T, Kobayashi H, Tsuda S. Antioxidative and antigenotoxic effects of Japanese horse chestnut (Aesculus turbinata) seeds. J Vet Med Sci. 2005 Jul;67(7):731-4.
30. Facino RM, Carini M, Stefani R, Aldini G, Saibene L. Anti-elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency. Arch Pharm (Weinheim). 1995 Oct;328(10):720-4.
31. Sirtori CR. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol Res. 2001 Sep;44(3):183-93.
32. Fujimura T, Tsukahara K, Moriwaki S, et al. A horse chestnut extract, which induces contraction forces in fibroblasts, is a potent anti-aging ingredient. J Cosmet Sci. 2006 Sep;57(5):369-76.
33. Ortonne JP, Zartarian M, Verschoore M, Queille-Roussel C, Duteil L. Cellulite and skin ageing: is there any interaction? J Eur Acad Dermatol Venereol. 2008 Feb 25.
34. Calabrese C, Preston P. Report of the results of a double-blind, randomized, single-dose trial of a topical 2% escin gel versus placebo in the acute treatment of experimentally-induced hematoma in volunteers. Planta Med. 1993 Oct;59(5):394-7.
35. Anon. Centella asiatica. Altern Med Rev. 2007 Mar;12(1):69-72.
36. Lee J, Jung E, Kim Y, et al. Asiaticoside induces human collagen I synthesis through TGFbeta receptor I kinase (TbetaRI kinase)-independent Smad signaling. Planta Med. 2006 Mar;72(4):324-8.
37. Hachem A, Borgoin JY. Eude anatomo-clinique des effects de e’extrait titre de centela asiatica dans la lipodystrophie localisse. LA Med Prat. 12 (Suppl 2): 17-21.
38. Martelli, Berardesca. Topical formulation of a new plant extract complex with refirming properties. Clinical and non-invasive evaluation in a double-blind trial. Int J Cos Sci. 2000 Jun;22(3):201-6.
39. Cesarone MR, Incandela L, De Sanctis MT, et al. Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model. Angiology. 2001 Oct;52 Suppl 2S49-S54.
40. Klovekorn W, Tepe A, Danesch U. A randomized, double-blind, vehicle-controlled, half-side comparison with a herbal ointment containing Mahonia aquifolium, Viola tricolor and Centella asiatica for the treatment of mild-to-moderate atopic dermatitis. Int J Clin Pharmacol Ther. 2007 Nov;45(11):583-91.