forskolin and your skin

Lipolysis, circulation enhancement, cellulite

Forskolin, found in the Indian coleus plant (also known as coleus forskohlii, coleus barbatus, plectranthus barbatus) is probably the most potent natural lipolytic chemical available (stimulates fat release), and also a vasodilator.

 

Forskolin cream

Forskolin is therefore of great importance as an active ingredient in anti-cellulitecontouring and under-eye creams [the Celluence® cellulite / leg wellness creams are the only creams in the world to contain 95% pure forskolin plus another 39+ natural, highly purified anti-cellulite actives; normally, due to it's very expensive price, forskolin is not widely used in anti-cellulite creams, and when it is used, it is quite often either of low purity or in minute concentrations].

 


Forskolin: the science

 

 

Forskolin stimulates lipolysis in fat cells (via excessive cAMP release)

The natural lipolytic chemical forskolin, was found in this study to release fat from adipocytes, via excessive cAMP production in fat cells

This excessive cAMP production should normally stimulate much more fat release than evidenced by the experiment, but nevertheless the lipolytic effect of forskolin was found to be impressive, as it compared well to the very strong adrenaline analogue isoproterenol.

Forskolin is clearly a very strong lipolytic nature active and it is an ideal anti-cellulite / topical fat reduction cream ingredient, used on it's own and in combination with caffeine and other actives.

Source: Rate-limiting steps in isoproterenol and forskolin stimulated lipolysis, http://www.ncbi.nlm.nih.gov/pubmed/2983738

Abstract: Using the flask-incubated fat cell system, effects of isoproterenol and forskolin on glycerol release, cyclic AMP levels and protein kinase were studied. Isoproterenol increased cyclic AMP levels, protein kinase activity and glycerol release over the same concentration range (10(-9) M to 10(-6) M). Forskolin also increased all three variables in a concentration-dependent manner (10(-7) M to 10(-4) M). The maximum response for each variable was significantly greater with forskolin than with isoproterenol. A combination of isoproterenol and forskolin resulted in an additional increase in cyclic AMP over forskolin alone, but no significant increase in protein kinase activity or glycerol release. These results support the concepts that the maximum lipolytic response to isoproterenol is limited by the accumulation of cyclic AMP and the maximum lipolytic response to forskolin is limited by some step distal to cyclic AMP production, possibly activation of protein kinase. At high concentrations of forskolin or with a combination of forskolin and isoproterenol, cyclic AMP levels were in excess of those needed to maximally activate protein kinase and lipolysis.

 

 

Forskolin stimulates fat release from fat cells (but is inhibited by alpha-2 adrenoreceptor activation)

Forskolin is the strongest natural lipolytic chemical known today

In this paper forskolin was shown to increase glycerol release from adipocytes by 600% than without, proving the lipolytic effects of forskolin

Adenylate cyclase, a kew enzyme in the lipolytic process was increased by 100x times (10,000%), showing that forskolin needs to release a lot of adenylate cyclase in order to produce lipolysis, in comparison to adrenaline.

The lipolytic effect of forskolin has been enhanced by adrenaline, which is normally produced when we exercise. This practically means that combining forskolin application in combination with exercise (as in applying a forskolin-rich anti-cellulite cream before and after exercise when adrenaline levels are high) will offer maximum results.

On the other hand, alpha-2 adrenoreceptor activation reduced the lipolytic response of forskolin. This practically means that we need to combine forskolin with an alpha-2 antagonist (such as golden chamomile extract or yohimbine), for maximum results.

Forskolin is ideal as an anti-cellulite / topical fat loss active in cellulite / contouring creams, especially if combined with golden chamomile, caffeine and other synergistic actives.

Source: Alpha-2 adrenergic activation inhibits forskolin-stimulated adenylate cyclase activity and lipolysis in human adipocytes, http://www.ncbi.nlm.nih.gov/pubmed/6127588

Abstract: Forskolin at 10 muM caused a 100-fold increase in the intracellular concentration of cyclic AMP and a 6-fold increase in glycerol release in the human adipocyte. These responses are comparable to those prompted by 10 muM isoproterenol. The effects of forskolin on cyclic AMP and lipolysis were dose-dependent. Alpha-2 adrenergic activation, achieved with 10 muM epinephrine and 30 muM propranolol, significantly inhibited forskolin-stimulated cyclic AMP accumulation and glycerol release, shifting the dose-response curves to the right. Forskolin at 10 muM caused a 4.5-fold increase in the adenylate cyclase activity of human adipocyte membranes. When either isoproterenol or epinephrine (0.1 mM) was combined with forskolin, the magnitude of response was substantially greater than the sum of responses achieved by each agent incubated alone.

 

 

Forskolin cream produces spot fat reduction on the thighs

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 research.

The main objective of this trial was to assess thigh girth / deep fat reduction. Cellulite, being more superficial, responds 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 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

Abstract 1: 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.

Source 2: Topical fat reduction

Abstract 2: 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.

 

 

STIMULATION OF CAMP ACCUMULATION AND LIPOLYSIS IN HAMSTER ADIPOCYTES WITH FORSKOLIN.

Journal: American journal of physiology

Abstract: This study compares the effects of forskolin and isoproterenol on lipolysis and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in hamster white adipocytes. Rates of lipolysis in forskolin-stimulated cells were equivalent to those in cells incubated with isoproterenol, but cAMP levels were more than 10-fold greater in the presence of forskolin. The stimulatory effects of forskolin were partially inhibited by N6-phenylisopropyl adenosine but not by 2',5'-dideoxyadenosine. In other experiments, cells were exposed to forskolin in combination with either isoproterenol or adenosine deaminase. A concentration of forskolin that caused only a small increase in lipolysis was used. When isoproterenol or adenosine deaminase were added withforskolin, lipolysis increased dramatically, but cAMP content either did not change, as occurred with isoproterenol, or increased only slightly with adenosine deaminase. Isoproterenol potentiation of forskolin's lipolytic action persisted in the absence of extracellular K+, even though the lipolytic response to isoproterenol alone was absent in K+-free media. These data demonstrate that the lipolytic responses of adipose tissue are more complex than are responses simply in proportion to cellular concentration of cAMP. Such complexity could arise if lipolytic regulatory factors other than cAMP existed or if cAMP and protein kinase were functionally segregated within adipocytes.

Link: http://ajpcell.physiology.org/content/246/1/C63.full.pdf

 

 

QUANTITATIVE DIFFERENCES IN THE CYCLIC AMP-LIPOLYSIS RELATIONSHIPS FOR ISOPROTERENOL AND FORSKOLIN.

Journal: Journal of pharmacology and experimental therapeutics

Abstract: The relationships between cyclic AMP (cAMP) levels and glycerol release (lipolysis) were determined for isoproterenol and forskolin under varied conditions in the isolated fat cell of the rat. Prevention of the inhibitory action of endogenous adenosine [by adenosine deaminase (100 mU/ml) or theophylline (3.3 X 10(-4) M)] resulted in increased levels of cAMP and increased rates of lipolysis with forskolin. However, the relationship between cAMP levels and rates of lipolysis remained the same under all conditions. N6-phenylisopropyladenosine (PIA; an analog of adenosine) abolished the increase in cAMP level produced by isoproterenol (10(-7) M) or forskolin (10(-6) M) and the lipolytic response to forskolin. However, PIA failed to inhibit completely the lipolytic response to isoproterenol. Dose-response curves to isoproterenol were determined in the presence and absence of adenosine deaminase. PIA (10(-6) M) inhibited the increase in cAMP levels under both conditions. PIA also inhibited the lipolytic responses that were associated with increases in cAMP levels, i.e., high concentrations of isoproterenol alone and isoproterenol with adenosine deaminase. A plot of cAMP levels against corresponding rates of lipolysis for all conditions agreed with previous observations that the relationship for isoproterenol differs from that for forskolin. At any concentration of cAMP the corresponding lipolytic response was greater for isoproterenol than for forskolin. The possibility of a cAMP-independent lipolytic response was discussed.

Link: http://jpet.aspetjournals.org/content/244/3/852.abstract

 

 

INSULIN SENSITIZES BETA-AGONIST AND FORSKOLIN-STIMULATED LIPOLYSIS TO INHIBITION BY 2',5'-DIDEOXYADENOSINE

American journal of physiology

In isolated rat adipocytes incubated in the absence of insulin, 2',5'-dideoxyadenosine blocked the increase in total adenosine 3',5'-cyclic monophosphate (cAMP) accumulation due to beta 1- or beta 3-catecholamine agonists and forskolin without affecting their stimulation of lipolysis. The inhibition of cAMP accumulation by 2',5'-dideoxyadenosine was not reflected in the total cytosolic cAMP-dependent protein kinase A activity, suggesting that the inhibition of cAMP occurred in cellular compartments distinct from those involved in the regulation of bulk protein kinase A activity. However, there was a good correlation between effects of lipolytic agents on cytosolic protein kinase A activity in fat cell extracts and lipolysis. Furthermore, it was possible to see an inhibition of the increase due to beta-agonists in cAMP accumulation, protein kinase A activity, and lipolysis by 2',5'-dideoxyadenosine in the presence of insulin. These data suggest that the readily measurable accumulation of cAMP seen with catecholamines in the absence of insulin is in a compartment separate from that involved in protein kinase A activation.

http://ajpcell.physiology.org/content/270/2/C562

 

 

EFFECT OF COLEUS FORSKOHLII EXTRACT ON CAFETERIA DIET-INDUCED OBESITY IN RATS

Journal: Pharmacognosy Research

Abstract: Background: Obesity is a metabolic disorder that can lead to adverse metabolic effects on blood pressure, cholesterol, triglycerides and insulin resistance and also increases the risk of coronary heart disease, ischemic stroke and type 2 diabetes mellitus. This study was designed to determine the effect of Coleus forskohlii on obesity and associated metabolic changes in rats fed with cafeteria diet. Objective: The aim of this study was to evaluate antiobesogenic and metabolic benefits of C. forskohlii in cafeteria diet induced obesity rat model. Materials and Methods: Rats were randomly divided into five groups of six animals in each group and as follows: Normal pellet diet group; cafeteria diet group; cafeteria diet followed by 50 mg/kg/d Coleus forskohlii extract (CFE), 100 mg/kg/d CFE and 45 mg/kg/d orlistat groups, respectively. Indicators of obesity such as food intake, body weight and alteration in serum lipid profiles were studied. Results: Feeding of cafeteria diet induced obesity in rats. Administration of CFE significantly halted increase in food intake and weight gain associated with cafeteria diet. Development of dyslipidemia was also significantly inhibited. Conclusion: The observed effects validate that supplementation of CFE with cafeteria diet could curb the appetite and mitigate the development of dyslipidemia.

 

 

BODY COMPOSITION AND HORMONAL ADAPTATIONS ASSOCIATED WITH FORSKOLIN CONSUMPTION IN OVERWEIGHT AND OBESE MEN

Journal: Obesity

Abstract: Objective: This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese (BMI ≥ 26 kg/m2) men. Research Methods and Procedure: Thirty subjects (forskolin, n = 15; placebo, n = 15) were studied in a randomized, double-blind, placebo-controlled study for 12 weeks. Results: Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage (BF%) and fat mass (FM) as determined by DXA compared with the placebo group (p ≤ 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12-week trial compared with the placebo group (p ≤ 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p = 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p ≤ 0.05). The actual change in serum total testosterone concentration was not significantly different among groups, but it increased 16.77 ± 33.77% in the forskolin group compared with a decrease of 1.08 ± 18.35% in the placebo group. Discussion: Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12-week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.

Link: http://onlinelibrary.wiley.com/doi/10.1038/oby.2005.162/abstract

 

 

Forskolin stimulates cAMP production (and consequently fat release) in fat cells - ideal for cellulite / leg wellness creams

Forskolin stimulates cAMP production in fat cells, which consequently leads to fat release and fat reduction. Due to it's cAMP and fat releasing properties, forskolin is one of the most important anti-cellulite actives.

Source: Comparative effects of forskolin and isoproterenol on the cyclic AMP content of human adipocytes

Abstract: Alterations in adipocyte cyclic AMP concentrations in response to 100 microM forskolin and 10 microM isoproterenol over a 4 hour period were found to be similar; with each agent, a peak response was noted within 30 minutes. In general, the greater the magnitude of peak response, the more rapid the decline of cyclic AMP concentration during the ensuing 3 1/2 hours. Alpha-2 adrenergic activation, achieved with 10 microM clonidine or 10 microM epinephrine, substantially reduced the cyclic AMP concentrations in cells stimulated by 100 microM forskolin or 10 microM isoproterenol. Isoproterenol-stimulated cells appeared to be more sensitive to alpha adrenergic inhibition than did forskolin-stimulated cells. Cells preincubated for 3 hours with 100 microM forskolin were markedly less responsive to a second exposure to the diterpine. Cells exposed to forskolin for 3 hours also had a reduced response when incubated with isoproterenol; thus, desensitization to forskolin appears to be heterologous. Forskolin desensitization did not appear to be dependent on cellular ATP depletion since cells mildly stimulated during preincubation were as severely desensitized as those adipocytes strongly stimulated. Maximum desensitization required a preincubation time of 1-2 hours with either isoproterenol or forskolin.

 

 

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.

 

 

Forskolin stimulates both cAMP and lipolysis in an independent manner - making it an ideal anti-cellulite cream active

Forskolin is well known to stimulate the release of both cAMP and lipolysis. However, this (older) study showed that forskolin stimulates lipolysis without the intermediate cAMP step = previously thought essential for lipolysis, but acts directly on the lipid droplet in fat cells - most probably on perilipin (unknown when that paper was published). In any case, forskolin is well established as a lipolytic and cAMP-releasing natural molecule, and both of those properties make it an essential cellulite cream active ingredient.

Source: Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells

Abstract: Forskolin (7 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxy-labd-14-ene-11-one) induced both cyclic AMP production and lipolysis in intact fat cells, but stimulated lipolysis without increasing cyclic AMP at a concentration of 10(-5) M. Homogenization of fat cells elicited lipolysis without elevation of cyclic AMP. Forskolin did not stimulate lipolysis in the homogenate. Forskolin stimulated both cyclic AMP production and lipolysis in a cell-free system consisting of endogenous lipid droplets and a lipoprotein lipase-free lipase fraction prepared from fat cells. However, at a concentration of 10(-6) M, it induced lipolysis without increase in the cyclic AMP content in this cell-free system. In the cell-free system, homogenization of the lipid droplets resulted in marked increase in lipolysis to almost the same level as that with 10(-4) M forskolin without concomitant increase in cyclic AMP. Addition of forskolin to a cell-free system consisting of homogenized lipid droplets and lipase did not stimulate lipolysis further. Phosphodiesterase activities were found to be almost the same both in the presence and absence of forskolin in these reaction mixtures. Although 10(-3) M forskolin produced maximal concentrations of cyclic AMP: 6.7 x 10(-7) M in fat cells and 2.7 x 10(-7) M in the cell-free system, 10(-4) M cyclic AMP did not stimulate lipolysis in the cell-free system. In a cell-free system consisting of lipid droplets and the lipase, pyrophosphate inhibited forskolin-induced cyclic AMP production, but decreased forskolin-mediated lipolysis only slightly. Based on these results, mechanism of lipolytic action of forskolin was discussed.

 

 

Fat release declines with age due to increased PGE1 and adenosine; forskolin reverses those effects and allows maximum lipolysis and cAMP release!

Stimulation and inhibition of lipolysis in isolated rat adipocytes: evidence for age-related changes in responses to forskolin and PGE1

The ability of a number of hormones to activate cellular responses in a variety of cells declines with age. The mechanisms responsible for these alterations are complex and incompletely understood. Rat adipocytes have served as an important model to study blunted responses to stimulatory hormones which function by activating cAMP accumulation. We have previously found that the blunted lipolytic response of adipocytes from older rats to the beta adrenergic receptor agonist isoproterenol appeared to be due to a lessened ability of isoproterenol to activate cAMP accumulation. Further, the blunted response to isoproterenol was apparently caused by an accentuated inhibition of lipolysis mediated by adenosine receptors activated by endogenously released adenosine. The present studies were designed to test and extend those conclusions. We have utilized forskolin to augment the cAMP accumulation that occurs in the presence of isoproterenol. Isoproterenol-activated lipolysis was greater in adipocytes from 2 month old rats compared with those from 12 month old rats (603±32 vs 450±29 nmol/105 cells/hr, P < 0.01). However, in the presence of forskolin (10-6 M), there was no significant difference in the response to isoproterenol between the two groups (646±23 vs 615±29 nmoles/105 cells/hr). As we had seen previously, the adenosine receptor agonist phenylisopropyladenosine more effectively inhibited lipolysis in the adipocytes from older rats. We now also find that PGE1 more efficaciously inhibits lipolysis in the cells from older rats. These data confirm that diminished cAMP accumulation in adipocytes from older rats appears to be a ratelimiting alteration in the regulation of lipolysis. Also, enhanced inhibition of lipolysis in these cells is mediated by both adenosine and PGE1 receptors.

 

 

Forskolin stimulates fat release as potently as adrenergic stimulation, with the combination of both producing maximum results

Forskolin is a natural chemical which is used as supplement and cellulite cream ingredient for it's lipolytic (fat releasing) action on fat cells. In this study forskolin was found to stimulate lipolysis as well as an adrenaline / noradrenaline analog, but it stimulates the production of 10 times more cAMP in the cell (cAMP stimulates energy production / fat burning in fat cells and vasodilation in blood vessels). Adrenaline and noradrenaline are produced during exercise and are the most potent fat release chemicals in the body, so forskolin has a similar effect on fat cells as exercise. On the other hand, in the same study it was shown that forskolin's fat release effect was potentiated by:

  • the adrenaline / noradrenaline analog (so we should practically expect that forskolin + exercise would have even stronger lipolytic effect than either exercise or forskolin alone)
  • an adenosine inhibitor (so we should practically expect that forskolin + caffeine would have even stronger lipolytic effect than either caffeine or forskolin alone)
  • In practice, the results of this and other similar studies show that forskolin works better when combined with caffeine (an adenosine inhibitor), and these two ingredients should be together in anti-cellulite creams and for spot fat reduction treatments / creams.

Furthermore, exercise (an adrenaline / noradrenaline stimulator) could potentially maximise the effect of forskolin, or forskolin combined with caffeine.

Source: Stimulation of cAMP accumulation and lipolysis in hamster adipocytes with forskolin.

Abstract: This study compares the effects of forskolin and isoproterenol on lipolysis and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in hamster white adipocytes. Rates of lipolysis in forskolin-stimulated cells were equivalent to those in cells incubated with isoproterenol, but cAMP levels were more than 10-fold greater in the presence of forskolin. The stimulatory effects of forskolin were partially inhibited by N6-phenylisopropyl adenosine but not by 2',5'-dideoxyadenosine. In other experiments, cells were exposed to forskolin in combination with either isoproterenol or adenosine deaminase. A concentration of forskolin that caused only a small increase in lipolysis was used. When isoproterenol or adenosine deaminase were added with forskolin, lipolysis increased dramatically, but cAMP content either did not change, as occurred with isoproterenol, or increased only slightly with adenosine deaminase. Isoproterenol potentiation of forskolin's lipolytic action persisted in the absence of extracellular K+, even though the lipolytic response to isoproterenol alone was absent in K+-free media. These data demonstrate that the lipolytic responses of adipose tissue are more complex than are responses simply in proportion to cellular concentration of cAMP. Such complexity could arise if lipolytic regulatory factors other than cAMP existed or if cAMP and protein kinase were functionally segregated within adipocytes.

 

 

Forskolin stimulates lipolysis irrespectively of it's cAMP production in fat cells

Comment: Forskolin is very well know for it's cAMP production, which normally leads to lipolysis, and also lipolysis itself. This study has found that the lipolytic effect of forskolin is not necessarily based on cAMP production. In fact forskolin stimulates a disproportionate amount of cAMP in relation to lipolysis. However, both cAMP itself as well as lipolysis have applications in the fight against cellulite, so forskolin remains one of the top 5 anti-cellulite actives.

Source: Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells

Abstract: Forskolin (7 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxy-labd-14-ene-11-one) induced both cyclic AMP production and lipolysis in intact fat cells, but stimulated lipolysis without increasing cyclic AMP at a concentration of 10(-5) M. Homogenization of fat cells elicited lipolysis without elevation of cyclic AMP. Forskolin did not stimulate lipolysis in the homogenate. Forskolin stimulated both cyclic AMP production and lipolysis in a cell-free system consisting of endogenous lipid droplets and a lipoprotein lipase-free lipase fraction prepared from fat cells. However, at a concentration of 10(-6) M, it induced lipolysis without increase in the cyclic AMP content in this cell-free system. In the cell-free system, homogenization of the lipid droplets resulted in marked increase in lipolysis to almost the same level as that with 10(-4) M forskolin without concomitant increase in cyclic AMP. Addition of forskolin to a cell-free system consisting of homogenized lipid droplets and lipase did not stimulate lipolysis further. Phosphodiesterase activities were found to be almost the same both in the presence and absence of forskolin in these reaction mixtures. Although 10(-3) M forskolin produced maximal concentrations of cyclic AMP: 6.7 x 10(-7) M in fat cells and 2.7 x 10(-7) M in the cell-free system, 10(-4) M cyclic AMP did not stimulate lipolysis in the cell-free system. In a cell-free system consisting of lipid droplets and the lipase, pyrophosphate inhibited forskolin-induced cyclic AMP production, but decreased forskolin-mediated lipolysis only slightly. Based on these results, mechanism of lipolytic action of forskolin was discussed.

 

 

Forskolin boosts fat release, especially if used in high concentrations and if combined with caffeine, exercise and dieting

In this study it was found that:

  • forskolin boosts fat release due to adrenergic stimulation (this suggests that combining exercise and forskolin would produce maximum results)
  • that adrenergic stimulation is stronger than forskolin in stimulating lipolysis (this means that higher concentrations of forskolin are needed than adrenergic stimulation, in order to produce the same lipolytic result)
  • that insulin and adenosine inhibit the effect of forskolin (thus suggests that caffeine should boost the effect of forskolin)

Taken together, these three results practically mean that as an active ingredient in anti-cellulite creams, forskolin can boost both cAMP and fat release from fat cells, especially if combined with exercise (adrenergic response), dieting (insulin inhibition) and caffeine (PDE inhibition) and if used in high concentrations.

Source: Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes

Abstract: Forskolin increased cyclic AMP accumulation in isolated adipocytes and markedly potentiated the elevation of cyclic AMP due to isoproterenol. In adipocyte membranes, forskolin stimulated adenylate cyclase activity at concentrations of 0.1 microM or greater. Forskolin did not affect the EC50 for activation of adenylate cyclase but did increase the maximal effect of isoproterenol. Neither the soluble nor particulate low-Km cyclic AMP phosphodiesterase activity was affected by forskolin. Low concentrations of forskolin (0.1-1.0 microM), which significantly elevated cyclic AMP levels, did not increase lipolysis, whereas similar increases in cyclic AMP levels due to isoproterenol elevated lipolysis. Forskolin did not inhibit the activation of triacylglycerol lipase by cyclic AMP-dependent protein kinase or the subsequent hydrolysis of triacylglycerol. Higher concentrations of forskolin (10-100 microM) did increase lipolysis. Both the increased cyclic AMP production and lipolysis due to forskolin were inhibited by the antilipolytic agents insulin and N6-(phenylisopropyl)adenosine. Hypothyroidism reduced the ability of forskolin to stimulate cyclic AMP production and lipolysis. These results indicate that forskolin increases cyclic AMP production in adipocytes through an activation of adenylate cyclase. Lipolysis is activated by forskolin but at higher concentrations of total cyclic AMP than for catecholamines.

 

 

Forskolin reduces fat and improves body composition, bone mass and testosterone in overweight men

Body Composition and Hormonal Adaptations Associated with Forskolin Consumption in Overweight and Obese Men

Abstract: Objective: This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese (BMI ≥ 26 kg/m2) men. Research Methods and Procedure: Thirty subjects (forskolin, n = 15; placebo, n = 15) were studied in a randomized, double-blind, placebo-controlled study for 12 weeks. Results: Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage (BF%) and fat mass (FM) as determined by DXA compared with the placebo group (p ≤ 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12-week trial compared with the placebo group (p ≤ 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p = 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p ≤ 0.05). The actual change in serum total testosterone concentration was not significantly different among groups, but it increased 16.77 ± 33.77% in the forskolin group compared with a decrease of 1.08 ± 18.35% in the placebo group. Discussion: Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12-week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.

 

 

Forskolin may reduce body weight and fat accumulation in menopause

Source: Effects of Coleus forskohlii on fat storage in ovariwctomized rats

Abstract: The antiobesity effects of Coleus forskohlii were investigated in ovariectomized (ovx) rats. Eight-week-old female Wistar rats were assigned to four groups: a sham-operated group fed the control diet (MF, sham-m) ; an ovx-m group fed the control diet; a sham-operated group fed the control diet containing 50 g/kg of Coleus forskohlii extract (sham-c) ; and an ovx-c group fed the control diet containing 50 g/kg of Coleus forskohlii extract. The body weight, adipose tissues, and cell diameter were investigated in ovx rats after Coleus forskohlii extract treatment. Administration of Coleus forskohlii extracts reduced body weight, food intake, and fat accumulation in ovx rats. Our results suggest that Coleus forskohlii may be useful in the treatment of obesity.

 

 

 

The lipolytic herbal extract forskolin inhibits fat tissue inflammation, may help fight obesity and overweight complications

In a study published last week it was shown that forskolin, one of the most important lipolytic natural chemicals, also inhibits fat tissue inflammation, making it a valuable anti-obesity and anti-cellulite natural agent. Fat tissue inflammation is the major cause of obesity's adverse health complications, so fighting fat tissue inflammation is an important step in restoring health in obese and overweight individuals. Previous studies have also shown that, in addition to its widely recognised slimming properties, and the newly discovered anti-inflammatory action, forskolin also boosts local circulation, thereby  helping maintain leg wellness and fight cellulite in three fronts: fat tissue inflammation, fat reduction  and circulation enhancement. Forskolin works best topically and in combination with caffeine, raspberry ketone and other natural phytochemicals as actives in a high concentration leg wellness cream formulation.

Paper: Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB.

Abstract: In an obese state, Toll-like receptor-4 (TLR-4) upregulates proinflammatory adipokines secretion including monocyte chemotactic protein-1 (MCP-1) in adipose tissue. In contrast, G-protein coupled receptor 120 (GPR120) mediates antiobesity effects. The aim of this study was to determine the signaling pathway by which Forskolin (FK), a cyclic adenosine monophosphate- (cAMP-) promoting agent causing positive changes in body composition in overweight and obese adult men, affects MCP-1 and GPR120 expression during an inflammatory response induced by lipopolysaccharide (LPS) in adipocytes, such as in an obese state. 3T3-L1 cells differentiated into adipocytes (DC) were stimulated with LPS in the absence or presence of FK and inhibitors of TLR-4 and inhibitor of kappa B (IκBα). In DC, LPS increased MCP-1, TLR-4, and nuclear factor-κB1 (NFκB1) mRNA levels, whereas it decreased GPR120 mRNA levels. In DC, FK inhibited the LPS-induced increase in MCP-1, TLR-4, and NFκB1 mRNA levels and the LPS-induced decrease in GPR120 mRNA. BAY11-7082 and CLI-095 abolished these LPS-induced effects. In conclusion, FK inhibits LPS-induced increase in MCP-1 mRNA levels and decrease in GPR120 mRNA levels in adipocytes and may be a potential treatment for inflammation in obesity. Furthermore, TLR-4-induced activation of NFκB may be involved in the LPS-induced regulation of these genes.