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 is therefore of great importance as an active ingredient in anti-cellulite, contouring 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.
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.
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.
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
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.