Retinol / vitamin A is a well-established anti-ageing and anti-acne natural chemical. It's more powerful metabolite, all trans retinoic acid (ATRA), is also used for anti-ageing, and especially for acne reduction. However, retinoic acid has quite a few side effects, so it would be interesting to know if retinol, which has a much safe profile, is equally effective or not.
In this study, after four weeks of topical application, patients experienced increased skin firmness, increased collagen type I and collagen type III with both products, and also significant reduction of wrinkles after 12 weeks of treatment with retinol.
Predictably, retinol was found to be somewhat less effective than retinoic acid, but nevertheless the results were classed as "significant" by the researchers. So the use of retinol creams for anti-ageing, skin firming and wrinkle reduction is warranted, based on the results of this study.
Source: A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin.
Abstract: BACKGROUND: All-trans retinol, a precursor of retinoic acid, is an effective anti-aging treatment widely used in skin care products. In comparison, topical retinoic acid is believed to provide even greater anti-aging effects; however, there is limited research directly comparing the effects of retinol and retinoic acid on skin. OBJECTIVES: In this study, we compare the effects of retinol and retinoic acid on skin structure and expression of skin function-related genes and proteins. We also examine the effect of retinol treatment on skin appearance. METHODS: Skin histology was examined by H&E staining and in vivo confocal microscopy. Expression levels of skin genes and proteins were analyzed using RT-PCR and immunohistochemistry. The efficacy of a retinol formulation in improving skin appearance was assessed using digital image-based wrinkle analysis. RESULTS: Four weeks of retinoic acid and retinol treatments both increased epidermal thickness, and upregulated genes for collagen type 1 (COL1A1), and collagen type 3 (COL3A1) with corresponding increases in procollagen I and procollagen III protein expression. Facial image analysis showed a significant reduction in facial wrinkles following 12 weeks of retinol application. CONCLUSIONS: The results of this study demonstrate that topical application of retinol significantly affects both cellular and molecular properties of the epidermis and dermis, as shown by skin biopsy and noninvasive imaging analyses. Although the magnitude tends to be smaller, retinol induces similar changes in skin histology, and gene and protein expression as compared to retinoic acid application. These results were confirmed by the significant facial anti-aging effect observed in the retinol efficacy clinical study.
The natural anti-aging chemical resveratrol was shown in this study to inhibit the growth of new fat tissue - and consequently the growth of cellulite - by activating a protein called Wnt/β-catenin. Pterostilbene, which also activates SIRT1 and is more bioavailable should exert the same effect.
In combination with other anti-cellulite actives, resveratrol and pterostilbene can be a valuable component of anti-cellulite creams
On the other hand, nicotinamide / vitamin B3, which is erroneously used in anti-cellulite creams, was shown in the same study to actually stimulate the growth of fat tissue
Technical summary: Resveratrol, via SIRT1 activation, inhibits adipogenesis by regulating Wnt/β-catenin signalling
Source: SIRT1 inhibits adipogenesis and promotes myogenic differentiation in C3H10T1/2 pluripotent cells by regulating Wnt signaling
Abstract: BACKGROUND: The directed differentiation of mesenchymal stem cells (MSCs) is tightly controlled by a complex network. Wnt signaling pathways have an important function in controlling the fate of MSCs. However, the mechanism through which Wnt/β-catenin signaling is regulated in differentiation of MSCs remains unknown. SIRT1 plays an important role in the regulation of MSCs differentiation. RESULTS: This study aimed to determine the effect of sirtuin 1 (SIRT1) on adipogenesis and myogenic differentiation of C3H10T1/2 cells. First, the MSC commitment and differentiation model was established by using 5-azacytidine. Using the established model, C3H10T1/2 cells were treated with SIRT1 activator/inhibitor during differentiation. The results showed that resveratrol inhibits adipogenic differentiation and improves myogenic differentiation, whereas nicotinamide promotes adipogenic differentiation. Notably, during commitment, resveratrol blocked adipocyte formation and promoted myotubes differentiation, whereas nicotinamide enhanced adipogenic potential of C3H10T1/2 cells. Furthermore, resveratrol elevated the expression of Cyclin D1 and β-catenin in the early stages. The luciferase assay showed that knockdown SIRT1 inhibits Wnt/β-catenin signaling, while resveratrol treatment or overexpression SIRT1 activates Wnt/β-catenin signaling. SIRT1 suppressed the expression of Wnt signaling antagonists sFRP2 and DACT1. Knockdown SIRT1 promoted adipogenic potential of C3H10T1/2 cells, whereas overexpression SIRT1 inhibited adipogenic differentiation and promoted myogenic differentiation. CONCLUSIONS: Together, our results suggested that SIRT1 inhibits adipogenesis and stimulates myogenic differentiation by activating Wnt signaling.
SIRT1 activation can inhibit NF-κB, and thereby inflammation, in adipose tissue, via multiple pathways.
Low grade inflammation is a major component of the metabolic syndrome, diabetes, and of course cellulite.
Pterostilbene and resveratrol activate SIRT1 expression in adipose tissue, which in turn inhibits inflammation, and thereby can help treat cellulite, via either oral or local application, as components of a cellulite cream.
Source: Molecular Mechanisms of Latent Inflammation in Metabolic Syndrome. Possible Role of Sirtuins and Peroxisome Proliferator-Activated Receptor Type γ.
Abstract: The problem of metabolic syndrome is one of the most important in medicine today. The main hazard of metabolic syndrome is development of latent inflammation in adipose tissue, which promotes atherosclerosis, non-alcoholic fatty liver disease, myocarditis, and a number of other illnesses. Therefore, understanding of molecular mechanisms of latent inflammation in adipose tissue is very important for treatment of metabolic syndrome. Three main components that arise during hypertrophy and hyperplasia of adipocytes underlie such inflammation: endoplasmic reticulum stress, oxidative stress, and hypoxia. Each of these components mediates activation in different ways of the key factor of inflammation - NF-κB. For metabolic syndrome therapy, it is suggested to influence a number of inflammatory signaling components by activating other cell factors to suppress development of inflammation. Such potential factors are peroxisome proliferator-activated receptors type γ that suppress transcription factor NF-κB through direct contact or via kinase of a NF-κB inhibitor (IKK), and also the antiinflammatory transcription factor AP-1. Other possible targets are type 3 NAD+-dependent histone deacetylases (sirtuins). There are mutually antagonistic relationships between NF-κB and sirtuin type 1 that prevent development of inflammation in metabolic syndrome. Moreover, sirtuin type 1 inhibits the antiinflammatory transcription factor AP-1. Study of the influence of these factors on the relationship between macrophages and adipocytes, macrophages, and adipose tissue-derived stromal cells can help to understand mechanisms of signaling and development of latent inflammation in metabolic syndrome.
"As current aesthetic surgical techniques become more standardised and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results"
Indeed scar tissue management is an important aspect of cosmetic surgery and natural actives that can help scar wound healing and prevent hypertrophic scars are very welcome.
Centella asiatica is well-known for it's wound healing properties, due to it's action on connective tissue restructuring, repair and balanced growth, helping avoid extremes such as hypertrophic wounds or slow healing wounds.
This paper describes how tension is the initiating factor of hypertrophic scar formation or incomplete healing and also how the principal extracts of the centella asiatica plant (asiatic acid, madecassic acid and asiaticoside) have been documented in a large number of scientific reports to:
aid wound healing
stimulate scar maturation
produce collagen type I
reduce myofibroblast differentiation
Centella asiatica extract is well established as an effective skin tightening / skin repair / would healing natural chemical, and for this reason it is an ideal ingredient in anti-ageing, skin firming, wound healing, post-liposuction scar management creams.
Given that skin looseness and connective tissue deformity are important components of cellulite, the combination of asiatic acid, madecassic acid and asiaticoside is also ideal components in anti-cellulite creams, especially when included in high concentrations and combined with similar synergistic natural actives.
Source: New innovations in scar management.
Abstract: As current aesthetic surgical techniques become more standardized and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results. With this in mind, a scar management program has been adopted based on the modalities of wound support, hydration, and hastened maturity, all factors gleaned from scientific evidence published over the past 25 years. Tension on a scar in one axis will result in a stretched scar, probably initiated by neutrophils and their neutral proteases [18,26]. Tension on a scar from many directions or intermittently will result in a hypertrophic scar, possibly initiated by lymphocytes but definitely related to a prolongation of the inflammatory process, with increased fibroblast activity and overabundant extracellular matrix secretion [24,26]. The common initiating factor is the tension on the scar, and the critical element needed to counteract this tension is scar support. Clinical experience has shown us that the most reliable way to support a scar is by using microporous tape. Hydration is a second beneficial influence on scar control and is the basis of the use of silicone sheeting and gel [7,29,36]. Alpha Centella cream has two main components. The first is an extract from the plant Bulbine frutescens. This increases hydration under the tape by leaving a layer of fatty vesicles of glycoprotein on the skin surface. This also has antibacterial properties. The second component is the principal terpenoids extracted from the Centella asiatica plant. These include asiatic acid, madecassic acid, and asiaticoside. Centella asiatica has been documented to aid wound healing in a large number of scientific reports [5,12,21,22,33,34,40]. The most beneficial effect appears to be the stimulation of maturation of the scar by the production of type I collagen [4,19] and the resulting decrease in the inflammatory reaction and myofibroblast production. Thus these components have been incorporated into the formulation of a scar management program. This publication reviews much of the available literature relating to scar management and describes the formulation and use of a scar management program based on this information.
Gotu kola / centella asiatica is well known for it's connective tissue repair and vein protective action. In fact, one reason centella asiatica protects blood vessels is by maintaining blood vessel connective tissue integrity.
Patients who suffer from phlebitis (vein inflammation), chronic vein thrombosis and especially post-thrombotic syndrome have "an increased number of circulating endothelial cells in comparison to normal subjects (3.8 cells versus 1.5, per counting chamber)".
Basically, in the post-phlebitic syndrome, endothelial cells, i.e. cells that line the inside of blood vessels get unattached from the blood vessels and are shed into the blood stream. Endothelial cells normally line blood vessels to maintain vascular integrity and permeability, but when these cells enter into the circulation, this is a reflection of vascular damage.
By preserving the integrity of the connective tissue to which endothelial cells are attached, centella asiatica should reduce endothelial cell shedding.
In a study assessing the effectiveness of concentrated gotu kola extract, containing only triterpenes (such as asiatic acid, madecassic acid and asiaticoside), it was found that treatment for three weeks with this extract caused a statistically significant reduction of circulating endothelial cells (1.80 cells per counting chamber), bringing endothelial cells to almost normal levels.
Clearly centella asiatica triterpenes are ideal for the complementary treatment of vascular disorders, especially when combined with similar vasoprotective actives, such as ruscogenin, hesperidin, escin and esculoside, among others.
Given that vascular integrity and good circulation are important in preventing water retention and cellulite, gotu kola / centella asiatica triterpenes are ideal natural actives for creams against cellulite and puffiness / water retention.
Source: Centella Asiatica Triterpenic Fraction (CATTF) reduces the number of circulating endothelial cells in subjects with post phlebitic syndrome.
Abstract: Here we report a study performed in order to assess the number of circulating endothelial cells (EC) in normal subjects and in patients with post-phlebitic syndrome (PPS), and the effect of treatment with Centella Asiatica Triterpenic Fraction (CATTF), a drug which has been demonstrated to be effective in promoting wound healing in vivo. EC counts were determined by means of differential centrifugation and phase contrast microscopy. Patients with PPS showed an increased number of circulating EC in comparison to normal subjects (3.8 +/- 1.2 cells versus 1.5 +/- 0.6 per counting chamber). Treatment for three weeks with CATTF caused a statistically significant reduction of circulating EC (1.80 +/- 0.6 cells per counting chamber).
Retinol, caffeine and ruscogenin (butcher's broom extract) are well-known natural anti-cellulite chemicals, which are used, in lower or higher concentrations, in many anti-cellulite creams.
In this study, the efficacy of a cream containing the combination of all three actives was tried on a group of 46 women for 84 days.
Skin texture, dermal and hypodermal structures, mechanical characteristics and superficial blood circulation were assessed using several non-invasive methods.
At the end of the study the researchers concluded that both the orange peel appearance as well as circulation were significantly improved, in relation to placebo: "The association of the three tested active ingredients was significantly active on the 'orange peel' appearance of the skin, which is the most apparent manifestation of cellulite (53.1% at T84 versus 14.1% for the placebo)"
"This combination of different evaluation methods resulted in the demonstration of significant activity of the anti-cellulite product versus baseline and showed its superiority versus the placebo in skin macrorelief (decrease of the "orange peel" effect) and an increase in cutaneous microcirculation"
Clearly, cellulite creams do get absorbed (contrary to the urban myth that creams do not get absorbed) and they do work, especially if multiple natural actives are combined - especially in high concentrations.
Source: A double-blind evaluation of the activity of an anti-cellulite product containing retinol, caffeine, and ruscogenin by a combination of several non-invasive methods.
Abstract: A double-blind, randomized, placebo-controlled study was conducted with 46 healthy female volunteers in order to test an anti-cellulite product containing retinol, caffeine and ruscogenine. An evaluation of different parameters related to cellulite appearance, i.e. the skin macrorelief, the dermal and hypodermal structures, the skin mechanical characteristics, and the cutaneous flowmetry was assessed using several non-invasive methods. This combination of different evaluation methods resulted in the demonstration of significant activity of the anti-cellulite product versus baseline and showed its superiority versus the placebo in skin macrorelief (decrease of the "orange peel" effect) and an increase in cutaneous microcirculation. By using a combination of methods, it was possible to detail the activity of an anti-cellulite product and to show superiority of the product in comparison with the placebo.
The combination of Ruscus aculeatus (butcher's broom), hesperidin methyl chalcone (HMC) and ascorbic acid has been tested before on patients with lower limb chronic venous insufficiency and was found effective in reducing water retention and improving vein tone.
In this study patients with chronic venous disorders (CVD) were assessed after 12 weeks of taking a nutritional supplement comprising of the three actives mentioned above.
At the conclusion of the study it was found that "all clinical symptoms significantly improved with treatment, especially for patients with higher body mass index and heavier pathology. Ankle circumference, which reveals the extension of water retention decreased over time, gradually decreased and both the physical and psychological dimensions of quality of life significantly increased over time and improved in all types of patients.
The researchers concluded that" "A 12-week treatment with ruscus aculeatus, HMC and ascorbic acid showed a significant decrease in clinical symptoms and a significant improvement in the quality of life of patients with chronic venous disorder".
The results are unsurprising, given the well-studied circulation-enhancing and blood vessel-protecting effects these separate actives have on their own.
Given that poor circulation is an important aspect of cellulite, this combination is also ideal for the treatment of cellulite, both when taken orally (food supplement) or applied locally (cellulite cream). Other active ingredients, in addition to the above three, would offer enhanced synergy and maximum results.
Source: Quality of life improvement in Latin American patients suffering from chronic venous disorder using a combination of Ruscus aculeatus and hesperidin methyl chalcone and ascorbic acid (quality study).
Abstract: AIM: The present study assessed the effect of Ruscus aculeatus, hesperidin methyl-chalcone and ascorbic acid (HMC-AA), in the treatment of chronic venous disorders (CVD) in Latin American patients. METHODS: This study is an observational, single arm, multicentric and prospective trial. Patients suffering from CVD and belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological (CEAP) classes were included. Patient profiles, risk factors, clinical symptomatology and quality of life (QoL) assessed by SF-12 and CIVIQ questionnaires were evaluated at inclusion and after 12-week treatment. RESULTS: The main factors influencing the previous management of patients were age, gender, body mass index (BMI), familial history, physical activity, exposure to heat, heavy loads lifting, profession and clinical characteristics. All clinical symptoms significantly improved with treatment and, as BMI and CEAP classes increased. Ankle circumferences decreased over time, correlating with BMI and CEAP classes. The physical and psychological dimensions of the SF-12 score significantly increased over time and improved within each CEAP class. The CIVIQ score significantly improved over time, correlating with age and CEAP classes. CONCLUSION: A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant decrease in the clinical symptoms and a significant improvement in the QoL of patients with CVD.
The centella asiatica (gotu kola) extract asiaticoside, is well-known to promote skin connective tissue repair and wound healing.
In a study assessing the exact biology of this action of asiaticoside on skin and connective tissue repair, it was found that asiaticoside affected the expression of 54 genes related to connective tissue function!
Specifically, asiaticoside upregulated the expression of genes related to fibroblast "cell proliferation, cell-cycle progression and synthesis of the extracellular matrix".
This, in simple terms, means that collagen cells mature and multiply faster and produce more collagen and other connective tissue proteins.
In the same study it was found that asiaticoside boosted the secretion of collagen type I (the hard collagen that gives firmness to skin and connective tissue) and collagen type III (the softer, "baby collagen", which is produced before collagen type I and helps with connective tissue repair and regeneration).
Asiaticoside is one of four chemicals, all equally important, that are found in centella asiatica plant and which possess similar connective tissue strengthening and repair action.
Because of this action on connective tissue, and also blood circulation, we believe that centella asiatica extract is the most important skin tightening an anti-cellulite active for use in cellulite creams and also in nutritional supplements to support connective tissue and help prevent cellulite.
Source: Asiaticoside induction for cell-cycle progression, proliferation and collagen synthesis in human dermal fibroblasts.
Abstract: Asiaticoside, isolated from Centella asiatica, promotes fibroblast proliferation and extracullar matrix synthesis in wound healing. The precise mechanism, however, in molecular and gene expression levels still remains partially understood. Using cDNA microarray technology, the alternation of genes expression profiles was determined in a human dermal fibroblast in vitro in the presence of asiaticoside (30 microg/ml). Fifty-four genes, with known functions for cell proliferation, cell-cycle progression and synthesis of the extracellular matrix, were significantly up-regulated in our "whole-genes nest" expression profile at various timepoints. Furthermore, mRNA levels and protein productions of certain genes responsible for extracellular matrix (ECM) synthesis (e.g. encoding type I and type III collagen proteins) were evaluated by Northern blot and radioimmunoassay, respectively. As a result, there is a close correlation among the gene profile, mRNA and protein production in the cells response to asiaticoside stimulation. This information could be used for exploring the target genes in response to asiaticoside in fibroblasts.
Ruscus aculeaus (butcher's broom) extract is well known for it's action on circulation improvement and chronic vein insufficiency. The flavonoid hesperidin and Vitamin C are also well established vein toning natural chemicals.
In a study asessing the effectiveness of the combination of these three venotonic chemicals, it was found that patients with chronic venous insufficiency that took 2 capsules a day for 60 days, experienced "significant decrease and regression of clinical symptoms and a reduction in lower limb circumference measured at the ankle were observed."
Ruscogenin and neoruscogenin, found in butcher's broom extract, are important actives against poor circulation and, as expected, work better in combination with other circulation-enhancing actives. Local application, in the form of microcirculation-boosting or anti-cellulite creams and food supplements is warranted.
Source: A Study of the Efficacy and Tolerability of a Preparation Containing Ruscus aculeatus in the Treatment of Chronic Venous Insufficiency of the Lower Limbs
Abstract: Objective: The objective of the study was to assess the efficacy and tolerability of an extract of Ruscus aculeatus combined with hesperidin methyl chalcone and ascorbic acid (Cyclo 3 Fort®) in the treatment of uncomplicated chronic venous insufficiency. Design and Methods: A randomised, double-blind, placebo-controlled study was conducted in 60 patients with uncomplicated chronic venous insufficiency. The patients received two daily capsules of a Ruscus extract combination formulation or placebo for a period of 60 days. Results: During the period of treatment with the Ruscus extract combination formulation, a significant decrease and regression of clinical symptoms and a reduction in lower limb circumference measured at the ankle were observed. The overall assessment of efficacy in the 30 patients receiving the active drug combination showed an excellent result in 15 patients, good in 13 and moderate in two. Of the 30 patients receiving placebo, the results were excellent in four, good in 17, moderate in eight and insufficient in one. Tolerability was considered excellent in 23 cases, good in five and poor in two. Conclusion: It was concluded that Ruscus extract combined with hesperidin methyl chalcone and ascorbic acid is effective and well tolerated in the treatment of patients with uncomplicated venous-lymphatic insufficiency of the lower limbs.
The botanical extract of ruscus aculeatus (butcher's broom), comprising the steroidal sapogenins ruscogenin and neoruscogenin, is used against haemorrhoids, chronic venous insufficiency, improvement of venous tone and stimulation of lymphatic drainage.
Among other studies, a double-blind study on healthy volunteers showed a significant decrease in venous capacity and tissue volume.
Due to it's effect on circulation improvement and lymph drainage, ruscogenins from butcher's broom are important actives in circulation-assisting and anti-cellulite creams and nutritional supplements, - ideally in combination with multiple similar natural actives, such as escin and rutin, for enhanced synergy.
Source: Der stechende Mäusedorn - Ruscus aculeatus L.
Abstract: Ruscus aculeatus is a medicinal plant of the Mediterranean region. This review covers its botany, composition, pharmacology, pharmacokinetics, toxicity and clinical use. Extracts of the underground parts are mainly used to treat chronic venous insufficiency, while the isolated steroidal sapogenins, ruscogenin and neoruscogenin, are applied against haemorrhoids. Increase of the venous tone and stimulation of the lymphatic transport are evident from pharmacological data. Several uncontrolled studies indicate efficacy of the isolated sapogenins in the treatment of haemorrhoids. A double-blind study on healthy volunteers showed a significant decrease in venous capacity and tissue volume. The efficacy of Ruscus aculeatus in the treatment of chronic venous insufficiency has not yet been proven in controlled clinical trials, as it has always been studied in combination with other active principles.
Centella asiatica / gotu kola is well established as a potent natural active for skin firming / skin repair.
The main active chemicals in centella asiatica extract are the triterpenes madecassoside, asiaticoside, madecassic acid and asiatic acid.
In this study it was found that gotu kola extract comprising the above phytochemicals significantly stimulated collagen synthesis (better than vitamin C) and lipolysis (better than that of caffeine), and exhibited potent antioxidant / free radical scavenging activity (equal to that of grape seed extract) and protection from UVB damage.
The sum of all these properites determined in this study (antioxidant, firming, lipolytic) and others determined in other studies (anti-glycation, skin restructuring) make centella / gotu kola the ideal anti-cellulite active for use in anti-cellulite creams also nutritional supplements.
Source: Triterpene Composition and Bioactivities of Centella asiatica
Abstract: Leaves of Centella asiatica (Centella) were analysed for their triterpene composition and bioactivity such as collagen enhancement, antioxidant, anticellulite and UV protection capacity properties. Triterpenes of Centella were measured using HPLC- PAD on an Excil ODS 5 μm (C18) column for the simultaneous determination of asiatic acid, madecassic acid, asiaticoside and madecassoside. Centella was found to contain significant amounts of madecassoside (3.10 ± 4.58 mg/mL) and asiaticoside (1.97 ± 2.65 mg/mL), but was low in asiatic and madecassic acid. The highest collagen synthesis was found at 50 mg/mL of Centella extracts. The antioxidant activity of Centella (84%) was compared to grape seed extract (83%) and Vitamin C (88%). Its lipolytic activity was observed by the release of glycerol (115.9 μmol/L) at 0.02% concentration. Centella extracts exhibited similar UV protection effect to OMC at 10% concentration. In view of these results, the potential application of Centella in food and pharmaceutical industries is now widely open.
Centella extract exhibited several potential bioactivities which could be of potential commercial interest in the food and pharmaceutical industries. Evaluation on Centella has found its chemical composition consist of four triterpenes, namely madecassoside, asiaticoside, madecassic acid and asiatic acid. The extract significantly stimulated collagen synthesis, better than vitamin C, and the lipolysis activity was found to be better than that of caffeine. The extract also showed an inhibitory effect with regards to free radical scavenging activity, comparable to grape seed extract. This preliminary UV study suggested that the Centella extract could be a potential natural protection against UVB damage and this activity might be due to its triterpene component(s). Therefore, further experiments are required to identify the component(s) responsible.
Forskolin is a well-known natural chemical from the Coleus Forkohlii plant, used in hundreds of studies because of it's lipolytic (fat reducing) properties. Forskolin stimulates the release of cAMP which is the most important step towards lipolysis.
In this study forskolin was used on it's own and also in combination with rolipram, a PDE4 inhibitor. PDE4 is an enzyme that inhibits the lipolytic process, by blocking the release of cAMP. As forskolin stimulates cAMP release / lipolysis, it makes sense to combine it with a PDE4 (phosphodiesterase-4) inhibitor, to ensure that cAMP release / lipolysis is maximised.
In regard to PDE4 inhibition, rolipram is similar to caffeine, a natural, widely consumed PDE4 inhibitor, which does not have the side-effects of drugs such as rolipram.
At the end of the study it was shown that forskolin and rolipram on their own were effective in reducing fat levels. As expected, the synergistic combination of forskolin and rolipram yielded better results than the two chemicals alone.
This study shows that when cAMP stimulation is combined with PDE4 inhibition, lipolysis is maximised.
Although rolipram is only used experimentaly (due to it's narrow therapeutic window), caffeine, it's PDE4 inhibiting analog, is used widely and makes an excellent partner with forskolin for maximum cAMP release, lipolysis and fat reduction.
Due to it's lipolytic action, forskolin is an ideal anti-cellulite cream active ingredient, especially if combined with caffeine, raspberry ketone or other cAMP-boosting / lipolytic actives.
Source: The effects of forskolin and rolipram on cAMP, cGMP and free fatty acid levels in diet induced obesity
Abstract: Obesity is a major health problem. We investigated the effects of forskolin and rolipram in the diet of animals in which obesity had been induced. We used 50 female albino Wistar rats that were assigned randomly into five groups as follows: group 1, control; group 2, high fat diet; group 3, high fat diet + forskolin; group 4, high fat diet + rolipram; and group 5, high fat diet + rolipram + forskolin. The rats were fed for 10 weeks and rolipram and forskolin were administered during last two weeks. The animals were sacrificed and blood samples were obtained. Serum cAMP, cGMP and free fatty acids (FFA) levels were measured using ELISA assays. We also measured weight gain during the 10 week period. cAMP and FFA levels of groups 3, 4 and 5 were significantly higher than those of groups 1 and 2. We found no significant differences in serum cGMP levels among the groups. The weight gain in groups 3, 4 and 5 was significantly less than for group 2. We also found that the weight gain in group 5 was significantly less than in groups 3 and 4. We found that both forskolin and rolipram stimulated lipolysis and inhibited body weight increase by increasing cAMP levels. Also, combination therapy using the two agents may be more effective in preventing diet induced obesity than either agent alone. We found also that these agents did not effect cellular cGMP levels in diet induced obesity.
This is yet another placebo controlled study to show that centella asiatica / gotu kola extract helps with venous hypertension (high blood pressure in veins) and oedema (water retention reduction).
In this study 20 patients with venous hypertension and an average age of 42 were given 60mg of purified gotu kola extract twice daily for six weeks, with another 20 given placebo and acting as a control.
At the end of the trial circulation at rest (resting flux) was improved by 29% and small blood vessel function (venoarterioal response) was increased by 59%! Leg volume (puffiness) also decreased.
In conclusion, the researchers stated that these "parameters were significant and clinically important at 6 weeks in the treatment group" and that "TTFCA improves microcirculation and leg volume in venous hypertension."
Other studies on purified centella asiatica (one that contains 100% of asiatic acid, madecassic acid, asiaticoside and madecassoside) have reported similar results.
Gotu kola / centella asiatica TTFCA extract is an ideal active against water retention and poor circulation, and it is used both in oral form (nutritional supplement) or as a circulation-aiding / anti-cellulite cream active ingredient.
Source: Microcirculatory effects of total triterpenic fraction of Centella asiatica in chronic venous hypertension: measurement by laser Doppler, TcPO2-CO2, and leg volumetry.
Abstract: The aim of this prospective, randomized study was to demonstrate whether an oral preparation of TTFCA was effective in improving the microcirculation and edema (leg volume) in venous microangiopathy. Forty patients with venous hypertension were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice daily). Patients were randomized into a treatment and a placebo group. There were 20 patients in each group. In the treatment group the mean age was 42 (SD 7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10). Tolerability and compliance were very good; there were no dropouts. At inclusion there were no differences between placebo and treatment group. After treatment there was a decrease in resting flux (29%) and an improvement (increase) in venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased (9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3% volume variation). The difference in flux, O2-CO2 and volume parameters were significant and clinically important at 6 weeks in the treatment group. In conclusion, TTFCA improves microcirculation and leg volume in venous hypertension. The effects of TTFCA are observed even in a limited sample of patients.
Polyphenols comprise a large class of plant/fruit-derived molecules with multiple benefits for human health. Resveratrol has been extensively studied for its anti-diabetic, neuroprotective, skimming, heart-protective and anti-cancer properties.
However its low bioavailability strongly limits it's potential. On the other hand, resveratrol's sister compound, pterostilbene, has shown similar or even more potent antitumor activities than resveratrol, due to pterostilbene's 7.5 times higher bioavailability.
In this study on mice, pterostilbene was found to "induce tumor cell cycle arrest and autophagy activation at bioavailable concentrations", i.e. on concentrations achievable by oral or intervenors administration.
On the other hand, resveratrol could not induce cancer cell death at biologically achievable concentrations.
Source: Pterostilbene, a natural polyphenol with anticancer activity, induces tumor cell death through autophagy activation
Abstract: Polyphenols (PFs) conform a large class of plants/fruits-derived molecules with potential benefits for human health. Resveratrol (Resv) (3,4′,5-trihydroxy-trans-stilbene), has been extensively studied for its anti-diabetic, neuroprotective, anti-adipogenic, cardioprotective and anti-tumoral properties. However its low bioavailability (half-life in blood was 10.2 minutes after i.v. adm. of 20 mg/kg to mice) strongly limits Resv potential in vivo. Thus, compounds that may mimic Resv effects, but showing more bioavailability, may improve health benefits and should be investigated. Pterostilbene (Pter) (3,5-dimethoxy-4′-hydroxystilbene, another natural phytoalexin), has shown similar or even more potent antitumor activities than Resv. However, Pter's half-life in mouse blood (77.9 min) is approx. 7.5 times higher. Pter causes cancer cell death in vitro at bioavailable concentrations, and decreases tumor growth in mice. The aim of our present study was a) to determine whether Pter causes cytotoxicity in human tumors at concentrations that are reliable under in vivo conditions; and b) identify which death-related molecular mechanisms are activated by Pter. For these purposes we used a panel of different human tumors: melanoma, breast cancer, lung cancer, and colon cancer. Resv and Pter were assayed in a μM range, between 10 μM (below the IC50 for all cell lines) and 200 μM (an unachievable in vivo concentration). Cell cycle and death induction were determined by flow cytometry. The effects observed in the presence of Resv or Pter, under in vitro conditions, were concentration and exposure time dependent. In fact, an increase in PF concentration switched the type tumor cell death. Resv or Pter induced inhibition of tumor cell division and autophagy activation, although no caspase 3 activation was detected within a 24 h-period in the presence of either PF. On the other hand by further increasing Resv or Pter concentration, apoptosis and necrosis were progressively activated as shown by flow cytometry, caspase 3 activity and lactate dehydrogenase activity released to the culture medium. The main difference between Resv and Pter is the effective concentration, much lower for Pter and thus close to bioavailable levels. Whereas bioavailable levels of Resv do not cause tumor cell death. Different molecular events associated Pter with autophagy activation: a) an increase of LC3-II form, indicating the processing of LC3 protein to its lipidated form; b) an increase in P62 bands and GFP-LC3 punctation were observed thus indicating P62 accumulation and translocation of LC3 to autophagic membranes, respectively. Besides low levels of Pter, in addition of activating autophagy, also cause a rapid loss of tubulin organization as detected by immunochemistry. Therefore our results demonstrate that Pter induces tumor cell cycle arrest and autophagy activation at bioavailable concentrations.
The botanical extract of centella asiatica / gotu kola is well-known for strengthening blood vessel walls. This as a results reduces leaky blood vessels (capillary premeability), high blood pressure in veins (venous hypertension) and oedema (puffiness / water retention), and improves circulation in small blood vessels (microcirculation) and tissue nourishment and oxygenation.
In a study involving people with mild and severe venous hypertension, it was shown that in just two weeks of treatment with purified gotu kola extract, there was a significant decrease of ankle and foot oedema in limbs with superficial and with deep venous incompetence.
Specifically it was shown that with 60mg of total triterpenic fraction of centella asiatica (TTFCA) there was a significant reduction in both superficial and deep venous incompetence. "The improvement (decrease) of the abnormally increased capillary permeability was associated with a significant improvement of the microcirculation and symptoms", as the authors of the study stated.
The purified extract used of the study comprised 100% asiatic acid, madecassic acid, asiaticoside and madecassoside, i.e. all four important triterpenes found in centella asiatica. Unfortunately most nutritional supplements only contain 20% of those triterpenes and many anti-cellulite creams contain as little as 1%...
Centella asiatica extract has been proven time and again ideal in microcirculation enhancement and water retention reduction with both oral intake (as a nutritional supplement) and topical application (as an anti-cellulite cream ingredient).
Gotu kola, also known as hydrocotyle, asiatic pennywort and indian pennywort, is also traditionally used in teas, curries, juice drinks and other foods throughout south and southeast Asia, including Thailand, India, Sri Lanka and Vietnam - my local Thai shop in London, for example, sells fresh centella for use in foods :)
Source: Improvement of capillary permeability in patients with venous hypertension after treatment with TTFCA.
Abstract: The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, was used with laser Doppler flowmetry to study variations of permeability and of the microcirculation in 10 normal subjects; in 22 patients with moderate, superficial venous hypertension; and in 12 patients with postphlebitic limbs and severe venous hypertension. All these patients had distal (ankle and foot) oedema in the evening. After a first assessment these subjects were studied again after two weeks without treatment and after two weeks' treatment with total triterpenic fraction of centella asiatica (TTFCA), tablets, 60 mg, tid. The VSC produces a wheal on the skin of the perimalleolar region that disappears (in average) in less than sixty minutes in normal subjects. The disappearance time (DT) is greater in conditions of increased capillary filtration and permeability. The three groups of subjects (normal and those with superficial and severe venous hypertension) had significantly different, increasing disappearance time of the wheals at the first observation. There were no significant changes after two weeks' observation, but after 2 weeks' treatment with TTFCA, there was a significant decrease of DT both in limbs with superficial and with deep venous incompetence. The improvement (decrease) of the abnormally increased capillary permeability was associated with a significant improvement of the microcirculation and symptoms (studied by an analogue scale line). In conclusion this study showed a combined improvement of the microcirculation and capillary permeability after treatment with TTFCA and the possibility of using the VSC to evaluate the effects of drugs (or other treatment) on local capillary permeability in patients with venous hypertension.
High-intensity interval training (HIIT) has become popular because it is a time-efficient way to increase endurance.
An intriguing and so-far-unanswered question is how a few minutes of HIIT can be that effective.
New research has now shown that interval training (as little as 10 sets of 30" full-intensity cycling alternated by 4' of rest between sets!) causes free radical damage on a muscle cell protein called ryanodine receptor 1 (RyR1).
This ultimately causes "mitochondrial biogenesis", i.e. the creation of new mitochondria (mitochondria are the powerhouses of the cell, the place where most of cell energy production occurs).
In summary: high intensity interval training > more mitochondria > more energy production > more fitness!
As these changes depend on free radical damage, taking antioxidants (such as Vitamin C, Vitamin E, CoQ10, Alpha Lipoic Acid, polyphenols etc.) stops this process, and this has been proven experimentally.
So practically you should not take antioxidants one day before, on the same day and one day after doing HIIT training.
Furthermore these adaptations to HIIT did not occur on elite athletes, because they are fully adapted to high intensity training due to their daily gruelling training regime.
This practically means that interval training is ideal for unfit or moderately fit people. The only limitation is that you need to have generally good cardiovascular health.
Interval training is not a good idea for people with cardiovascular problems, as high intensity training puts a lot of pressure on the heart and may lead to too high or too low blood pressure.
Source: Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise, http://m.pnas.org/content/early/2015/10/28/1507176112
The natural lipolytic active forskolin was found to reduce thigh girth by 1cm in 4 weeks, in relation to the untreated thigh (placebo), in females who were placed on a 800 calorie diet.
This was achieved with an extremely low forskolin concentration in the cream of about 0.01% and without any synergistic ingredients, such as caffeine etc.
With synergistic ingredients and at higher concentrations results are even more pronounced. In this study, the combination of forskolin aminophylline and yohimbine (in equally low concentrations) produced a fat loss of 2cm in relation to placebo and exactly the same results as the injections, but without the pain, bruising and dangers of injections.
12 multiple injections of isoproterenol over 4 weeks also produced a 2cm girth reduction. Isoproterenol is an analog of adrenaline and the strongest lipolytic chemical known (stronger even than adrenaline itself). it is only allowed to be used for experiments.
The main objective of this trial was to assess tigh girth / deep fat reduction. Cellulite being more superficial also improves more significantly to local lipolytic actives.
The controversial ingredients aminophylline and yohimbine were also found to be effective. However, these ingredients have a poor safety profile so they are not used as widely any more.
Being on a diet is essential for maximum spot fat reduction as being on a weight loss phase always accelerates topical fat loss
Source 1: Regional fat loss from the thigh in obese women after adrenergic modulation, http://www.ncbi.nlm.nih.gov/pubmed/2894247
Abstract: Eighteen women (mean weight, 197 lb) who were more than 20% above desirable body weight and wished to lose weight from the thighs were recruited and placed on a liquid formula diet of 800 kcal daily and encouraged to engage in a walking program. They were seen five days per week for four weeks. At each visit, warm wraps of 600 to 900 mosm/L of magnesium sulfate solution were applied to each thigh for 30 minutes, followed by cream application. One thigh was treated in each patient with one of the three creams in xipamide: forskolin, 25 X 10-5 mol/L (six patients); yohimbine, 5 X 10-4 mol/L (six patients); or aminophylline, 1.3 X 10-2 mol/L (six patients). The other thigh in each subject was treated with xipamide only, in a double-blind design.
Abstract: The fat on women's thighs is more difficult to mobilize due to increased alpha-2 adrenergic receptor activity induced by estrogen. Lipolysis can be initiated through adipocyte receptor stimulation (beta adrenergic) or inhibition (adenosine or alpha-2 adrenergic) or by inhibition of phosphodiesterase. Since many women desire regional thigh fat loss, a series of clinical trials were initiated using one thigh as a double-blinded control. Trial #1: Five overweight women had injections of isoproterenol at intervals around the thigh three times a week for 4 weeks with diet and walking. Trial #2: Five overweight woman had ointment containing forskolin, yohimbine and aminophylline applied to the thigh five times a week for 4 weeks after hypertonic warm soaks with a diet and walking. Trial #3: Eighteen overweight women were divided into three groups of six and trial #2 was repeated with each agent alone vs. placebo using forskolin, yohimbine or aminophylline in separate ointments. Trial #4: Thirty overweight women had 10% aminophylline ointment applied to the thigh five times a week for 6 weeks with diet and walking. Chemistry panel, theophylline level and patch testing were performed. Trial #5: Twelve women had trial #4 repeated with 2% aminophylline cream without a diet or walking. Trial #6: Trial #5 was repeated with 0.5% aminophylline cream. All trials except yohimbine ointment gave significantly more girth loss from the treated thigh (p < 0.05 to p < 0.001). Chemistry panel showed no toxicity. Theophylline was undetectable and patch testing was negative. We conclude that topical fat reduction for women's thighs can be achieved without diet or exercise.
Many people today follow a low carb diet, refraining from starch-rich foods (what most people call "carbs"), such as potatoes, rice, pasta, bread, corn etc.
This is because those foods have a low ratio of nutrients versus calories and quite often a high glycaemic index (they raise insluin levels too fast and too much). This does not help at all with weight maintenance, fat loss or cellulite reduction.
However, there is one complex "carb" with high nutrient to calorie ratio: black rice.
Black rice (also known as purple rice) is very high in antioxidants (more than in blueberries). It's bran hull (outermost layer) contains one of the highest levels of anthocyanin antioxidants found in food. It also has a similar amount of fiber to brown rice, which means that it has a low glycaemic index and that it helps digestion and regularity.
Like brown rice, black rice has a mild, aromatic, nutty taste, and a deep black color which turns deep purple when cooked. To cook, simply use one part of black rice and four parts of black rice and simmer until all water is absorbed.
Black rice can be used in place of white rice (one of the highest GI carbs available and not very good for you at all) or brown rice (low GI, high in fibre, but no antioxidants).
In summary, if there is one "carb" food I would recommend, it would be black rice, due to the very high anthocyanin / antioxidant content. Anthocyanins, like most polyphenols, are well-known for their beneficial effect on cardiovascular health, anti-ageing, diabetes prevention and cellulite prevention.
A second best would be wild rice (which is also dark brown / black, but does not have nearly as many antioxidants).
A third best would be red (camargue) rice and red quinoa (yes, quinoa is a carb-rich food and contains very ittle protein, contrary to the urban myth).
Of course, the absolute best carb-containing foods are berry fruits (blueberries, blackberries, strawberries, raspberries etc.) , which have a very high antioxidant content and very, very few carbohydrates and calories. This means that berry fruits have an extremely high nutrient to calorie ratio.
Black rice is superior to black or dark red beans, in terms antioxidant content, as no water is thrown away after cooking black rice, while after boiling / steaming beans some water has to be thrown away, with all the antioxidants contained in it.
Note: there are two types of black rice: glutinous (sticky) and non-glutinous. It is better to prefer the non-glutinous, as it has a higher fibre content and lower GI.
Like all surgery, some aftercare treatments are essential after all types of liposuction, even if is performed by a very skilled surgeon. This is because pain and swelling always follow any intrusive procedure. However, more often than not, the following side effects typically occur:
Loose skin (with plain lipo)
Excessive hardening of the skin (with vaser / smart lipo / bodytite)
Scar tissue formation / bumps (with all procedures)
Lumps of fat left unremoved (with all proceudrs)
Sticking of the skin onto the underlying tissues that leads to movement restriction (with all procedures but especially so with vaser / smart lipo / bodytite)
The recommended treatments differ depending on the timeline after surgery. Here is a short list:
Day 3-20: Focusing on pain, swelling and tissue healing. During the first 2-3 weeks post-lipo aftercare treatments are very gentle and aim to minimise pain and swelling and prevent excessive scar tissue from forming. Mild lymphatic drainage massage by hand or with special lymphatic drainage equipment is needed in the first few days after vaser surgery.
Day 21+: Focusing on scar tissue breakdown and cellulite reduction. From the third week onwards treatment can become progressively more vigorous: stronger lymphatic stimulation massage is preferred to the lighter variety used the first three weeks, which in addition to reduving water retention also helps with the break down of scar tissue / hard bumps that typically form, remove fatty lumps, reduce cellulite (which liposuction of course does not remove) and uncouple the stuck skin from underlying tissue and increase range of movement.
A good anti-cellulite, i.e. a cream that contains anti-inflammatory and circulation/lymph drainage-enhancing ingredients, among others, should offer valuable help both through the different stages of recovery and later, with cellulite and residual fat removal. Cream application can start immediately - just make sure you avoid the portals (cannula insertion points).
Laser / ultrasound / radiofrequency assisted liposuction is used to remove fat and tighten the skin at the same time, thereby attempting to solve the problem of loose, saggy skin left after the removal of fat
The special laser / ultrasound / radiofrequency cannula tips used for these procedures burn (coagulate) the skin internally, thereby hardening it. However, this coagulation also literally sticks the skin to the underlying tissues, which leads to difficulty with movement, pain and discomfort for a few weeks or months, until all tissue adhesions are broken down. Strong massage helps with adhesion removal.
To be honest, I would not call the skin hardening that occurs with the procedures skin tightening, because you do not gain a nice firm feel on your skin, but thick hardened skin.
Furthermore, in the same manner unwanted adhesions are gradually broken down by the body, so are the ones that led to skin hardening: the body gradually rejects the denatured coagulated collagen fibres, thereby reverting to the saggy appearance in a few months to a year.
So the skin hardening effect caused by the laser / ultrasound / radiofrequency tips is usually short lived.
On the other hand, the "burning from the inside" caused by the laser / ultrasound / radiofrequency tips typically causes excessive hardening on some skin spots here and there, leading to the appearance of several hard lumps and bumps made up of scar tissue / fibrosis. As these bumps are basically balls of scar tissue, they take much more time to be dissolved by the body, leaving you with both loose skin AND unsightly hard bumps.
During the last decade I have seen hundreds of clients who had different types of lipo before, and in my experience, most hard bumps are caused by laser-assisted liposuction, although I have seen bad cases with ultrasound and radiofrequency assisted lipolysis. Of course, I have seen some amazing results too and loads of average ones. Results depend on both the skill of the surgeon and also on how your body reacts to the coagulation.
Strong massage can help with the breaking down of those hard bumps, but that can only be initiated six weeks after surgery, as before that time tissues are too sensitive / painful for any strong treatment.
In summary, if you really need to have these kind of procedures, pick the best doctor possible (not necessarily the most expensive) and if you end up with some hard bumps have plenty of strong massages, starting six weeks after surgery.