What is forskolin
Forskolin is also known as Colforsin, Boforsin or Coleonol, is a pharmaceutical drug 7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one. Forskolin is the first main labdane diterpenoid isolated from the roots of Coleus forskohlii (Lamiaceae) or the Indian Plectranthus barbatus ANDREWS plant 1. Detailed analysis reveals approximately 20 constituents in various parts of the Coleus forskohlii plant, but forskolin and other coleonols are present only in the root portion 2. Forskolin is the primary constituent of clinical interest in Coleus forskohlii. It was discovered by Western scientists in 1974. Initially it was referred to as coleonol.  The name was changed to forskolin as other coleonols and diterpenoids have been identified later. All pharmacological activities related to Coleus forskohlii are due to the active constituent named forskolin. Forskolin’s molecular weight is 410.5 g/mole (anhydrous) and molecular formula is C 22 H 34 O 7 3. Coleus forskohlii is a perennial member of the mint or Lamiaceae (also known as Labiatae) family that was first discovered in the mountainous region of India. Forskolin is a lipid-soluble compound that can penetrate cell membranes and stimulates the enzyme adenylate cyclase which, in turn, stimulates ciliary epithelium to activate cyclic adenosine monophosphate, which decreases intraocular pressure (antiglaucoma potential) by reducing aqueous humor inflow. The topical application of forskolin is capable of reducing intraocular pressure in rabbits, monkeys, and humans. In its drug interactions, forskolin may act synergistically with epinephrine, ephedrine and pseudoephedrine. Whereas the effects of anti-clotting medications like warfarin, clopidogre, aspirin, anoxaparin, etc., may be enhanced by forskolin. Forskolin is contraindicated in the medications for people with ulcers as forskolin may increase acid level. Forskolin has a very good shelf-life of five years. Recently, its ophthalmic inserts and in situ gels for sustained and delayed-release drug delivery systems were tested in New Zealand Albino Rabbits for its antiglaucoma efficacy.
In Hindu and Ayurvedic traditional medicine, coleus forskohlii is used for the treatment of digestive disorders (stomach ache, gastric and intestinal spasm, nausea, as a purgative), skin (burns, wounds, insect bites, allergies), infections (eg, syphilis, ringworm), and other conditions, including neck stiffness, and rheumatism, and to induce menstruation and as an oral contraceptive 4. Forskolin has also been used to treat heart, blood, and circulation conditions, hypertension, congestive heart failure, eczema, colic, respiratory disorders, painful urination, insomnia, convulsions, asthma, angina, psoriasis and for prevention of cancer metastases 5, 6. In the 1970s, the plant’s cardiovascular activity was investigated. Forskolin is a vasodilator, hypotensive agent. Forskolin activates Adenylate Cyclase, thus increasing the cyclic AMP intra-cellular concentration. Forskolin is commonly used to raise levels of cyclic AMP (cAMP) in the study and research of cell physiology 2. Quality clinical trials are lacking to support claims made of the weight loss properties of forskolin, and clinical studies conducted with oral and inhaled forskolin in patients with asthma are limited.
Forskolin is an active constituent of Coleus forskohlii. Unlike the other coleus species Coleus forskohlii is used for health purposes 6. Forskolin is a diterpene that acts directly on adenylate cyclase 7. Adenylate Cyclase is an enzyme that activates cyclic adenosine monophosphate (cAMP) in the cell. Cyclic adenosine monophosphate (cAMP) promotes the breakdown of stored fats in rat fat cells 8. Forskolin regulates the body’s thermogenic response to food, increases the body’s basal metabolic rate, and increases utilization of body fat 9. Forskolin may also release fatty acids from adipose tissue, which results in increased thermogenesis, loss of body fat, and theoretically increased lean body mass 9. Forskolin increases cAMP accumulation, and therefore stimulates lipolysis in rats. So, with high concentrations of forskolin, cAMP and lipolysis increase 10. Enhanced lipolysis increases fat degradation and fat usage as a fuel in the body 11. This may promote fat and weight loss. It is thought that supplementing with forskolin may enhance fat loss without loss of muscle mass 12.
Forskolin has been shown to increase cAMP formation in all eukaryotic cells except sperm, without hormonal activation of adenylate cyclase 13. Forskolin’s potentiation of cyclic adenosine monophosphate (cAMP) in turn inhibits basophil and mast cell degranulation and histamine release 14, lowers blood pressure 15 and intraocular pressure 16, inhibits platelet aggregation 17, promotes vasodilation 18, bronchodilation 19 and thyroid hormone secretion 20 and stimulates lipolysis in fat cells 21. Forskolin also has a positive inotropic action on cardiac tissue via increased cAMP levels 22.
In addition to its cAMP-stimulating activity, forskolin inhibits the binding of platelet-activating factor, independently of cAMP formation. This may be a result of forskolin’s direct effect on platelet-activating factor or via interference with platelet-activating factor binding to receptor sites 17. Forskolin also appears to have an effect on several membrane transport proteins, and inhibits glucose transport in erythrocytes, adipocytes, platelets, and other cells 23.
Forskolin for weight loss
Forskolin is a diterpene of the labdane family that is produced by the Indian Coleus plant, Coleus forskohlii. Forskolin is often used to raise levels of cyclic adenosine monophosphate (cAMP) in the study and research of cell physiology. The effects of forskolin on cAMP have been described in detail as early as the 1980s and can be observed in isolated cell preparations as well as in intact tissue. If this mechanism is also active in vivo in humans after forskolin ingestion, it could result in an activation of hormone-sensitive lipase, and increase lipolysis enabling greater fat oxidation.
It has been demonstrated that forskolin can stimulate lipolysis in adipose tissue in rats 24, 25. There is only one study that investigated the effects of forskolin on body composition and metabolic rate in humans 26. In a study conducted by Godard and colleagues 26, 30 obese men were supplemented with forskolin (250 mg of a 10% forskolin extract twice a day) for 12 weeks. The authors concluded that forskolin ingestion resulted in favourable changes in body composition determined by dual-emission x-ray absorptiometry. Following forskolin supplementation body fat mass was significantly decreased by -11.23%, compared to 1.73% in the placebo group. This reduction in body fat mass, with forskolin ingestion, was accompanied with a significant reduction in body fat percentage from baseline (35.17 8.03% to 31.03 7.96%). Unfortunately, no measurements of fat metabolism were reported, although the authors did report that energy expenditure was not different between the forskolin-supplemented group and the placebo group. So although there is a theory that is promising, there is only one study at the present time and more work is required before forskolin can be recommended as a fat metabolism enhancing substance.
Henderson et al. 9 conducted a double blind and randomized study with 19 moderately overweight (BMI of 25 – 35 kg/m²) female subjects between the ages of 18 and 40. The female subjects took Coleus Forskohlii supplementation (250 mg of a 10% Coleus Forskohlii extract taken two times per day) for 12 weeks. The major findings of that study were 9: 1.) 12-weeks of Coleus Forskohlii supplementation (250 mg of a 10% Coleus Forskohlii extract taken two times per day) did not promote weight loss but may have helped mitigate weight gain in free-living overweight females; and, 2.) Coleus Forskohlii supplementation did not adversely affect markers of health status. However, the results of their analysis showed that forskolin supplementation had no significant effect on either heart rate and blood pressure. Blood samples collected from the female subjects were assayed for muscle and liver enzymes, lipid profile, electrolytes, protein status, thyroid hormones, fasting insulin, and whole blood cell counts. Significant changes were observed from Week 0 to Week 12 in Group Coleus Forskohlii in white blood cell count, absolute lymphocyte count, absolute neutrophil count, calcium levels, alanine aminotransferase (ALT), and uric acid levels 9. Forskolin supplementation resulted in an increase in calcium, white blood cell, absolute lymphocyte, and absolute neutrophil counts 9. Decreases were observed in ALT (alanine aminotransferase) and uric acid levels. These variables contribute to muscle, immune, liver, and protein functions, respectively, in the body. Even though these changes occurred, the values remained within normal ranges and were relatively small. Additionally, no significant adverse events were reported during the study that could be attributed to the supplementation protocol 9. The findings suggest that 12-weeks of Coleus Forskohlii supplementation in free-living subjects have limited effects on body composition and no apparent clinically significant side effects.
Forskolin for asthma
This single-blind study 27 compared the efficacy of oral forskolin versus inhaled beclomethasone for mild or moderately persistent adult asthma. Patients were randomly assigned to receive forskolin (one 10-mg capsule orally per day; n = 30) or beclomethasone (two 50 μg inhalations every 12 h; n = 30) for 2 months. No statistically significant improvement occurred in any lung function parameter in the forskolin-treated patients. Subjects in the beclomethasone-treated group presented a slight but statistically significant improvement in percentage forced expiratory volume in 1 s (FEV1), percentage forced expiratory flow in the middle (25–75%) expiratory phase (FEF25–75%) and percentage forced vital capacity (FVC) after 2 months of treatment, though the improvement in absolute values for FEV1, FEF25–75%, FVC and FEV1:FVC did not reach statistical significance. There was no statistically significant difference between the forskolin and beclomethasone treatment groups for any lung function parameter at baseline or after treatment. None of the beclomethasone-treated patients had an asthma attack and one forskolin-treated patient had a mild asthma attack during the 2-month study period. More studies are needed in adult asthma patients to confirm whether forskolin may be a useful preventive treatment for mild or moderately persistent adult asthma.
To determine the efficacy of forskolin in preventing asthma attacks, another single-blinded clinical study 28 in children and adult out-patients at a public hospital in Mexico. Forty patients of either sex with mild persistent or moderate persistent asthma were assigned randomly to 6 months of treatment with forskolin at 10 mg/day orally (capsules) or with two inhalations of sodium cromoglycate every 8 hours, i.e. three times a day. The study authors found that the use of forskolin allowed 60% (n = 12) of treated patients to remain free of asthma attacks during the 6 months of treatment, whereas only 15% of the patients treated with sodium cromoglycate stayed free of asthmatic attacks during the same period of treatment, giving a relative risk reduction of 52.9% 28. The number of patients who had asthma attacks during the treatment period was significantly lower among those receiving forskolin (8/20, 40%) than among those receiving sodium cromoglycate (17/20, 85%) 28. Values of forced expiratory volume in 1 second and forced expiratory flow, mid-phase, were similar in the two groups during the treatment period. The study authors concluded that important to perform more studies in patients with asthma to confirm their results.
Forskolin for glaucoma
Glaucoma is characterized by elevated intraocular pressure (IOP). Several animal and human studies have demonstrated the ability of forskolin to lower intraocular pressure (IOP), possibly via cAMP activation and a reduction in aqueous flow 29.
Caprioli et al 16 demonstrated a significant decrease in intraocular pressure in rabbits, monkeys, and humans administered a topical forskolin suspension (1% forskolin). This effect was present at one hour post application and remained significant for at least five hours. In one clinical trial of 20 young, healthy Japanese volunteers 30, two 50 μL topical instillations of one-percent forskolin were applied to one eye while the other eye served as control, receiving only the topical vehicle. At one-hour post instillation, the IOP fell 2.4 ± 1.3 mmHg and aqueous flow rate was reduced by 13 percent in the treatment eye compared to the control. Both results were statistically significant.
In a randomized, double-blind, placebo-controlled, cross-over trial with two separate arms, 10 healthy, non-smoking men were given a forskolin (1%) suspension in one eye and placebo in the other eye; proxymetacaine (0.5%) was the local anesthetic. The forskolin suspension resulted in decreases in intraocular pressure (IOP), but the differences between the forskolin treatment and placebo treatment at eight hours post application were statistically insignificant. Six men articipated in a second arm of the study and a different local anesthetic (0.4% oxybuprocaine) was used. In this study arm a highly significant 25-percent reduction of intraocular pressure (IOP). was observed at six hours post application. The different results in the two arms may be attributable to the different topical anesthetics used prior to forskolin application 29. These results suggest forskolin may be of benefit in reducing IOP in glaucoma patients.
Other Clinical Indications
Research has shown forskolin stimulates thyroid hormone release and increases thyroid hormone production 20. Forskolin has been shown to stimulate digestive secretions, including hydrochloric acid, pepsin, amylase, and pancreatic enzymes 31, suggesting clinical benefit in digestive disorders and malabsorption. Animal research indicates forskolin exerts an antidepressant action via activation of cAMP 32. In vitro research indicates forskolin has potent immunestimulating properties 33.
Forskolin side effects
Coleus forskohlii and forskolin extracts are generally without toxicity or side effects at the recommended dosage.
However, caution should be used in a patient with ulcers as forskolin can increase stomach acid levels 13. Caution should also be used in a patient with low blood pressure due to forskolin’s hypotensive effects 15. Adverse events reported with the use of colforsin (a forskolin derivative) include tachycardia and arrhythmias. Forskolin should be avoided in patients with polycystic kidney disease. Because of forskolin’s effect on platelet aggregation, Coleus forskohlii should be used with caution or avoided in patients with bleeding disorders or on blood-thinning medication 34. Coleus forskohlii extracts have not been studied in pregnant or lactating women.References
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