Caffeine and your skin

Lipolysis, water retention, fat/cellulite reduction

Caffeine, found in coffee berries (coffea arabica and coffea robusta), tea leaves (camellia sinensis), mate leaves (ilex paraguayensis) and guarana berries (paullinia cupana), among other plants, is the most widely established natural lipolytic chemical, and also enhances blood circulation (caffeine enhances the lipolytic process and boosts circulation via phosphodiesterase and adenosine inhibition on fat cells and blood vessels).

 

CAFFEINE CREAM

For these reasons, caffeine is one of the most popular actives in anti-cellulite, leg wellnesscontouring and under-eye creams [the Celluence® cellulite creams are the only creams in the world with pure caffeine contained in liposome form for easy absorption, plus 39 synergistic natural actives for maximum results with cellulite reduction and leg wellness].

 


Caffeine: The science

 

 

The combination of caffeine, Esculoside, centella asiatica and L-carnitine maximise lipolysis by inhibiting alpha-2 adrenoreceptors

 In vitro tests demonstrated (a) a dramatic increase in the cyclic adenosine monophosphate (cAMP) content in human adipocytes, with a subsequent rise in the nonesterified fatty acids (NEFA) content of human adipocyte incubation medium, and (b) in vivo studies showed an actual potent slimming effect on human volunteers. Moreover, the combination antagonises the alpha(2)-adrenergic receptor that is known to reduce intracellular AMPc content and, subsequently, to down-regulate lipolysis.

[Source: An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of slimming liposomes: an unexpected alpha(2)-adrenergic antagonism]

 

 

Forskolin, alone or in combination with a PDE4 inhibitor, such as caffeine, stimulates lipolysis and reduces fat

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.

 

 

Effectiveness evaluation of an anti-cellulite cream containing retinol, caffeine and ruscogenin

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.

 

 

EFFECTS OF CAFFEINE AND SILOXANETRIOL ALGINATE CAFFEINE, AS ANTICELLULITE AGENTS, ON FATTY TISSUE: HISTOLOGICAL EVALUATION.

  • Journal: Journal of cosmetology and dermatology
  • Abstract: BACKGROUND: Cellulite is a physiological condition that presents etiologic plurality. Caffeine and its derivatives are used in anticellulite cosmetics due to their lipolytic activity on fatty cells. Siloxanetriol alginate caffeine (SAC) is a silanol derived from organic silicon. Radicals primarily from SAC are caffeine and the mannuronic acid. AIMS: This study aims to analyze the effects of caffeine and siloxanetriol alginate caffeine on fatty tissue by histological evaluation. METHODS: Formulations were developed with caffeine, caffeine + sodium benzoate or SAC and were applied topically for 21 days on Wistar female mice. The study regarded the histological aspects by determination of diameter and number of fatty cells with a light microscope. RESULTS: Emulsion with caffeine caused a reduction of 17% on the diameter of the fatty cells compared with the control. The emulsion with caffeine + sodium benzoate did not cause alterations on cell diameter. Emulsion with SAC provoked reduction on fatty cell diameters of 16%. No significant alterations were observed on the diameter of the fatty cells treated with gels, although it was noticed that gel with SAC promoted a reduction of 26% on the number of fatty cells. CONCLUSIONS: Emulsion with SAC was considered more indicated to promote the lipolytic action on fatty tissue, acting as a complement to treat cellulite. When sodium benzoate was added to the preparations, it inhibited the caffeine efficiency. Gel was not an adequate vehicle to be incorporated with caffeine and SAC.
  • Link: http://onlinelibrary.wiley.com/doi/10.1111/j.1473-2165.2008.00357.x/abstract

 

 

CAFFEINE'S MECHANISMS OF ACTION AND ITS COSMETIC USE

  • Journal: Skin pharmacology and physiology
  • Abstract: Caffeine is being increasingly used in cosmetics due to its high biological activity and ability to penetrate the skin barrier. This alkaloid is frequently used as a hydrophilic model substance in human and animal skin penetration as well as different synthetic membrane using Franz diffusion cell experiments. The commercially available topical formulations of caffeine normally contain 3% caffeine. As for a cosmetic purpose, caffeine is used as an active compound in anti-cellulite products because it prevents excessive accumulation of fat in cells. This alkaloid stimulates the degradation of fats during lipolysis through inhibition of the phosphodiesterase activity. Caffeine has potent antioxidant properties. It helps protect cells against the UV radiation and slows down the process of photoaging of the skin. Moreover, caffeine contained in cosmetics increases the microcirculation of blood in the skin and also stimulates the growth of hair through inhibition of the 5-α-reductase activity.
  • Link: http://www.karger.com/Article/FullText/343174

 

 

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.

  • Journal:  Journal of Cosmetic Dermatology
  • 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.
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/11479653

 

 

INHIBITORY EFFECTS OF CAFFEINE AND ITS METABOLITES ON INTRACELLULAR LIPID ACCUMULATION IN MURINE 3T3-L1 ADIPOCYTES.

  • Journal: Biofactors
  • Abstract: To understand the mechanisms of the anti-obesity effects of dietary caffeine, the effects of caffeine and its metabolites on adipocyte differentiation and insulin-stimulated glucose uptake in murine 3T3-L1 adipocytes were investigated. Caffeine did not inhibit the differentiation of 3T3-L1 pre-adipocytes to mature adipocytes, but it did suppress the intracellular lipid accumulation after complete differentiation in a dose-dependent manner (0.125-1.0 mM). This effect was also observed in 1,3,7-trimethyluric acid- 3,7-dimethyluric acid- and 5-acetylamino-6-formylamino-3-methyluracil-treated cells. Caffeine also inhibited insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes in a dose-dependent manner. Treatment with theophylline, paraxanthine, 1-methylxanthine (MX), 3-MX, or 7-MX also inhibited glucose uptake in differentiated adipocytes. These results suggest that the anti-obesity activity of dietary caffeine is due to the additive and/or synergistic inhibitory effects of caffeine and its metabolites on intracellular lipid accumulation and that caffeine does not affect adipocyte differentiation.
  • Link: http://onlinelibrary.wiley.com/doi/10.1002/biof.5520340405/abstract

 

 

INHIBITORY MECHANISM OF CAFFEINE ON INSULIN-STIMULATED GLUCOSE UPTAKE IN ADIPOSE CELLS.

  • Journal: Biochemical Pharmacology
  • Abstract: Caffeine inhibits insulin-induced glucose uptake in rat adipocytes and also decreases insulin sensitivity, including whole-body glucose disposal and glucose uptake in skeletal muscle, during a euglycemic-hyperinsulinemic clamp in human. However, the mechanism by which caffeine decreases the insulin sensitivity is not still clear. We found that pre-treatment with caffeine inhibited the insulin-induced 2-deoxy-D-[1-(3)H]glucose uptake in a concentration-dependent manner in mouse preadipose MC-3T3-G2/PA6 cells differentiated into mature adipose cells. Caffeine also suppressed insulin-induced GLUT4 translocation in the differentiated cells. Although caffeine did not alter insulin-induced activation of PI3K and protein kinase C-zeta (PKCzeta), an isoform of atypical PKC, which is reported to have an important role in insulin-induced GLUT4 translocation, we found that insulin-induced phosphorylation and activation of Akt were blocked by pre-treatment with caffeine. Inhibition of insulin-induced 2-deoxy-D-[1-(3)H]glucose uptake by caffeine was also observed in primary cultured brown adipocytes in a concentration-dependent manner. These results may, in part, explain the ability of caffeine to decrease insulin sensitivity.
  • Link: http://www.sciencedirect.com/science/article/pii/S000629520400557X

 

 

XANTHINES AS ADENOSINE RECEPTOR ANTAGONISTS

  • Journal: Handbook of Experimental Pharmacology
  • Abstract: The natural plant alkaloids caffeine and theophylline were the first adenosine receptor (AR) antagonists described in the literature. They exhibit micromolar affinities and are non-selective. A large number of derivatives and analogues were subsequently synthesized and evaluated as AR antagonists. Very potent antagonists have thus been developed with selectivity for each of the four AR subtypes.
  • Link: http://link.springer.com/chapter/10.1007%2F978-3-642-13443-2_6

 

 

THE EFFECTS OF CHRONIC CAFFEINE ADMINISTRATION ON PERIPHERAL ADENOSINE RECEPTORS

  • Journal: The journal of pharmacology and experimental therapeutics
  • Abstract: Rat platelets and adipocytes were used as models to investigate alterations of the A2- and of the A1-adenosine receptor-adenylate cyclase system of peripheral cells caused by chronic caffeine administration. The maximum effects of 5'-N-ethylcarboxamidoadenosine (NECA) to stimulate adenylate cyclase activity in suspensions of platelet membranes and to inhibit aggregation were significantly greater with platelets from caffeine-treated rats than from control rats. The effects of 1 to 100 nM prostaglandin E1 to inhibit platelet aggregation and to stimulate adenylate cyclase activity in platelet membranes were also significantly greater with caffeine-treated than with control rats. These data suggest that the increased ability of NECA to inhibit platelet aggregation after chronic caffeine ingestion was a result of increased cyclic AMP accumulation induced by this agonist. The increased stimulatory effect of NECA on adenylate cyclase in platelet membranes could be due to an increased A2-adenosine receptor number and/or an increased functional coupling between A2-adenosine receptor and stimulatory guanine nucleotide binding proteins. In contrast, although A1-receptor number was 37% higher in fat cell membranes from caffeine-treated rats than in those from control rats, increased A1-adenosine receptor-mediated inhibition of lipolysis and of adenylate cyclase was not detected. Thus, chronic caffeine consumption causes alterations in the response of some but not all peripheral cell types to agonists of adenosine receptors.
  • Link: http://jpet.aspetjournals.org/content/254/3/757.abstract?sid=c881228b-76a7-4933-914f-735c34522c5b

 

 

INTERACTIONS BETWEEN CATECHOLAMINES, METHYL XANTHINES AND ADENOSINE IN REGULATION OF CYCLIC AMP ACCUMULATION IN HAMSTER ADIPOCYTES

  • Journal: Biochimica et Biophysica Acta (BBA) - General Subjects
  • Abstract: In the presence of either methyl xanthines or adenosine deaminase, isoproterenol elicited large dramatic increases in accumulation of cyclic AMPP. In contrast, cyclic AMP accumulation in response to epinephrine or norepinephrine was not potentiated by either methyl xanthines or by adenosine deaminase. Blocking the alpha adrenergic activity of norepinephrine and epinephrine with phentolamine established synergism between these catecholamines and methyl xanthines and adenosine deaminase. The activity of the particulate phosphodiesterase was not influenced by norepinephrine suggesting that the lack of synergism between the catecholamines norepinephrine and epinephrine and methyl xanthines is unrelated to this enzyme. The data are interpreted to suggest that the alpha adrenergic activity of catecholamines prevents the potentiation of cyclic AMP accumulation that occurs when the action of endogenously produced adenosine is interfered with, either by its degradation with adenosine deaminase or by receptor blockade with methyl xanthine. Because a major action of adenosine on fat cells is to inhibit adenylate cyclase it is suggested that alpha adrenergic receptor activation limits the extent to which the enzyme adenylate cyclase can be activated in a fashion similar to that of adenosine.
  • Link: http://www.sciencedirect.com/science/article/pii/0304416580902676

 

 

GREEN TEA CATECHINS, CAFFEINE AND BODY-WEIGHT REGULATION

  • Journal: Physiology & Behavior
  • Abstract: The global prevalence of obesity has increased considerably in the last decade. Tools for obesity management including caffeine, and green tea have been proposed as strategies for weight loss and weight maintenance. These ingredients may increase energy expenditure and have been proposed to counteract the decrease in metabolic rate that is present during weight loss. Positive effects on body-weight management have been shown using green tea mixtures. Green tea, by containing both tea catechins and caffeine, may act through inhibition of catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here the mechanisms may also operate synergistically. A green tea–caffeine mixture improves weight maintenance, through thermogenesis, fat oxidation, and sparing fat free mass. The sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general. Taken together, these functional ingredients have the potential to produce significant effects on metabolic targets such as thermogenesis, and fat oxidation. An ethnic or genetic effect, and habitual caffeine or green tea catechin intake may act as confounders; this remains to be revealed.
  • Link: http://www.sciencedirect.com/science/article/pii/S0031938410000703

 

 

EFFECT OF CAFFEINE ON THE BODY FAT AND LIPID METABOLISM OF RATS FED ON A HIGH-FAT DIET

  • Journal: Bioscience, biochemistry and biotechnology
  • Abstract: The intake of caffeine (CF) at 0.025, 0.05 or 0.1% for 21 days progressively reduced the body fat mass and body fat percentage in Sprague-Dawley (SD) rats fed on a high-fat diet with increasing administration level. Moreover, CF increased the serum concentrations of catecholamines and free fatty acids in SD rats orally administered with CF (5 mg/kg). These results suggest that the intake of CF reduced body fat by lipolysis via catecholamines. CF has potential as a functional food ingredient with an anti-obesity action.
  • Link: https://www.jstage.jst.go.jp/article/bbb/69/11/69_11_2219/_article

 

 

METABOLIC EFFECTS OF CAFFEINE IN HUMANS: LIPID OXIDATION OR FUTILE CYCLING?

  • Journal: The American Journal for Clinical Nutrition
  • Abstract: Background: Caffeine ingestion stimulates both lipolysis and energy expenditure.
  • Objectives: Our objectives were to determine whether the lipolytic effect of caffeine is associated with increased lipid oxidation or futile cycling between triacylglycerol and free fatty acids (FFAs) and whether the effects of caffeine are mediated via the sympathetic nervous system. Design: Respiratory exchange and [1-13C]palmitate were used to trace lipid oxidation and FFA turnover in 8 healthy, young men for 90 min before and 240 min after ingestion of placebo, caffeine (10 mg/kg), or caffeine during β-adrenoceptor blockade. Results: During fasting conditions, there were few differences in measured variables between the 3 tests. During steady state conditions (last hour of the test) after ingestion of caffeine, lipid turnover increased 2-fold (P < 0.005), and the mean (±SEM) thermic effect was 13.3 ± 2.2% (P < 0.001), both of which were greater than after ingestion of placebo or caffeine during β-adrenoceptor blockade. After ingestion of caffeine, oxidative FFA disposal increased 44% (236 ± 21 to 340 ± 16 μmol/min), whereas nonoxidative FFA disposal increased 2.3-fold (455 ± 66 to 1054 ± 242 μmol/min; P < 0.01). In postabsorptive conditions, 34% of lipids were oxidized and 66% were recycled. Caffeine ingestion increased energy expenditure 13% and doubled the turnover of lipids, of which 24% were oxidized and 76% were recycled. β-Adrenoceptor blockade decreased, but did not inhibit, these variables. Conclusions: Many, but not all, of the effects of caffeine are mediated via the sympathetic nervous system. The effect of caffeine on lipid mobilization in resting conditions can be interpreted in 2 ways: lipid mobilization alone is insufficient to drive lipid oxidation, or large increments in lipid turnover result in small increments in lipid oxidation
  • Link: http://ajcn.nutrition.org/content/79/1/40.long

 

 

EVALUATION OF THE EFFECTS OF CAFFEINE IN THE MICROCIRCULATION AND EDEMA ON THIGHS AND BUTTOCKS USING THE ORTHOGONAL POLARIZATION SPECTRAL IMAGING AND CLINICAL PARAMETERS.

  • Journal: Journal of Cosmetic Dermatology 
  • Abstract: Gynoid lipodystrophy, also known as cellulite, is a common multifactorial entity that affects millions of women around the world. There have been few scientific articles dealing with its physiology and treatment in the past few years, and vascular changes seem to play an important role in its pathophysiology. Skin microvascular alterations can be observed noninvasively with a new method called orthogonal polarization spectral imaging, which was used to evaluate the effectiveness of an anticellulite drug composed mainly of a 7% caffeine solution. Microcirculatory parameters evaluated were functional capillary density (FCD; number of flowing capillaries per unit area), diameter of the dermic papilla (DPD), and capillary diameter (CD). The clinical parameters analyzed were centimetrical measurements of thighs and hips and the influence of tobacco, alcohol, and physical activities on the efficacy of the treatment. After 1 month of treatment, statistical application of chi-squared and Z approximation tests showed, in treated patients, statistically significant reduction of thigh circumferences in more than 80% of the cases and reduction of hip circumference in 67.7%. FCD, DPD, and CD did not change significantly after treatment. Smoking as well as alcohol consumption and regular physical activity were not significantly related to the centimetrical reduction observed in treated thighs and hips.
  • Link: http://onlinelibrary.wiley.com/doi/10.1111/j.1473-2165.2007.00304.x/abstract

 

 

THE EFFECT OF ALKYLXANTHINES AND OTHER PHOSPHODIESTERASE INHIBITORS ON ADENOSINE-RECEPTOR MEDIATED DECREASE IN LIPOLYSIS AND CYCLIC AMP ACCUMULATION IN RAT FAT CELLS

  • Journal: Basic and clinical pharmacology and toxicology
  • Abstract: Cyclic AMP accumulation and glycerol release were studied in isolated rat fat cells. Both processes were inhibited by R-site specific adenosine analogues (L-PIA greater than NECA greater than 2-chloro-adenosine greater than D-PIA), but poorly or not at all by the P-site selective analogue SQ 22,536. The effect of a series of xanthine derivatives and of some structurally unrelated phosphodiesterase inhibitors as inhibitors of 2-chloro-adenosine induced inhibition of NA stimulated cyclic AMP accumulation and lipolysis was subsequently examined. The 2-chloroadenosine effect on cyclic AMP accumulation was antagonized by the xanthines with the following order of potency: DPX greater than 8-phenyl-theophylline greater than 8-p-sulpho-phenyl-theophylline greater than verrophylline greater than IBMX greater than theophylline greater than HWA 285 greater than pentoxiphylline greater than caffeine greater than 7-benzyl IBMX greater than theobromine greater than enprofylline greater greater than ZK 62,711. The rank order potency of xanthines against the antilipolytic effect of 2-chloro-adenosine was the same with two notable exceptions: the two potent phosphodiesterase inhibitors 7-benzyl-IBMX and ZK 62,711 were more than 20 times more potent as inhibitors of the antilipolytic effect of 2-chloro-adenosine. The results show that antagonism of adenosine analogue-induced antilipolytic effects is a convenient assay for adenosine antagonistic potency of drugs, except for drugs with a high potency as phosphodiesterase inhibitors. The lipolytic potency of the xanthine derivatives was also studied. The ability of the xanthines to stimulate basal and noradrenaline stimulated lipolysis was generally in agreement with their potency as adenosine antagonists. Adenosine deaminase induced lipolysis was stimulated by potent phosphodiesterase inhibitors.
  • Link: http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0773.1984.tb01896.x/abstract