Forskohlii Root (Coleus forskohlii / Plectranthus barbatus): A Comprehensive Reference
1. Identity, Nomenclature, and Natural Source
Botanical Names and Taxonomy
Coleus forskohlii auct. is a perennial plant of the Lamiaceae (mint) family and is native to Nepal, Thailand, and India. The plant is now widely accepted under its modern taxonomic synonym Plectranthus barbatus, and its primary bioactive molecule is the labdane diterpene forskolin (C22H34O7). Coleus forskohlii is a small, perennial member of the mint (Labiatae) family that grows on sun-exposed, dry hill slopes between an altitude of 1,000 and 6,000 feet in subtropical, temperate climatic zones, and is thus found in India, Nepal, Sri Lanka, and Thailand.
Common Names and Synonyms
Alternative names include Coleus forskohlii extract, Plectranthus barbatus extract, Indian coleus, makandi (Ayurvedic name), coleonol, and forskolin (for the isolated diterpene).
Localization of Active Compounds Within the Plant
Forskolin is found exclusively in the root of Coleus forskohlii, which is native to India and South-East Asia. It is stored inside cells within the bark of the root in structures called oil bodies, which are similar to oil drops. There are approximately 20 constituents in different parts of the Coleus plant, but forskolin and coleonols are found specifically in the root part of the plant.
Chemical Identity of Forskolin
Forskolin (7-β-acetoxy-8,13-epoxy-1β,6β,9β-trihydroxy-labd-14-ene-11-one) is a labdane diterpene with the chemical formula C22H34O7, and it is the primary active ingredient present in the root cork tissue of Coleus forskohlii. It is a labdane diterpene that was first isolated from the plant in 1974.
Related Diterpenoid Constituents
Forskolin, 1-deoxyforskolin, and 1,9-dideoxyforskolin are structurally related bioactive diterpenoids from C. forskohlii. Other plant constituents include volatile oils, diterpenoids, and coleonols. The leaf extract of Coleus contains significantly high amounts of polyphenols, flavonols, and flavones with high antioxidant activity.
Commercial Forms and Preparations
Commercial extracts are commonly standardized to 10–20% forskolin and are dosed in supplements at approximately 25–100 mg forskolin per day, equivalent to approximately 250–1,000 mg extract depending on standardization. In research settings, the extract is obtained from the sun-dried tuberous roots of the plant by ethanol-grade extraction and standardized to contain 10% forskolin; once extracted, it is typically blended with excipients and packaged into capsules. In ophthalmic research, the compound has been formulated as a 1% topical eye drop. Intravenous formulations of the compound (or its water-soluble analog colforsin daropate) have been studied in clinical cardiac settings but the intravenous form of forskolin is not available in the United States.
2. Traditional and Historical Use
Ayurvedic Medicine
A compound called forskolin has been used since ancient times in traditional Indian medicine to treat conditions such as high blood pressure, asthma, and heart complications. Coleus forskohlii Briq. (family: Lamiaceae) has a very long history of use in many traditional herbal medicines, with special reference to Ayurveda. It is a diterpene derived from the root of Coleus forskohlii, and it has been used for centuries in Ayurvedic medicine to treat a variety of conditions including heart disease, respiratory disorders, and hypothyroidism.
In Ayurveda, Coleus has been used to treat heart disease, spasmodic pain, painful urination, and convulsions. Historically, it has also been used to treat hypertension, congestive heart failure, eczema, colic, respiratory disorders, insomnia, and convulsions.
Geographic and Cultural Range
Since ancient times, plants of the Coleus species have been used as herbal medicines to treat various disorders of the cardiovascular, respiratory, gastrointestinal, and central nervous systems. Beyond internal medicine, Coleus forskohlii has also been used in food industries, with edible tubers being used, for example, in pickles.
Traditional Preparation of the Root
Traditional preparations of the root of Coleus forskohlii (known as Makandi in Ayurveda) have included Ghana vati (concentrated aqueous extract tablets) and churna tablets (powdered herb tablets). These preparations were used for conditions including hypertension in older adults.
3. Key Constituents and Mechanisms of Action
Forskolin as Adenylyl Cyclase Activator
As initially shown by Seamon and Daly, the diterpene forskolin directly activates adenylyl cyclase (AC) and raises cyclic AMP (cAMP) levels in a wide variety of cell types. Forskolin is a cell-permeable activator of adenylyl cyclase that interacts directly with the catalytic subunit of the enzyme to increase intracellular cAMP levels. This mechanism of action is receptor-independent: forskolin is a receptor-independent adenylyl cyclase activator that increases intracellular cAMP; it has been shown to decrease intraocular pressure (IOP) after topical application by a mechanism not shared by other drug classes.
Adenylyl Cyclase Isoform Selectivity
Adenylyl cyclase (AC) isoforms 1 to 9 are differentially expressed in tissues and constitute an interesting drug target; ACs 1 to 8 are activated by the diterpene forskolin. Diterpenes show the highest potencies at AC1 and the lowest potencies at AC2. Full agonists, partial agonists, antagonists, and inverse agonists can be identified among forskolin analogs, and each AC isoform exhibits a distinct pharmacological profile.
G-Protein Synergy
Response to forskolin is strongly influenced by the activation of AC by the heterotrimeric G-protein, Gs. Gs-promoted enhancement of AC activity in response to forskolin occurs not only when cells are incubated with exogenously administered agonists that activate G-protein-coupled receptors, but also by agonists that can be endogenously released by cells.
Downstream Effects of Elevated cAMP
Forskolin acts as an adenylate cyclase activator; adenylate cyclase is involved in the production of cyclic adenosine monophosphate (cAMP), a significant biochemical agent in metabolic processes. cAMP induces biochemical events that trigger metabolic processes and diet-induced thermogenesis, increase lean body mass, and stimulate the loss of body fat.
The downstream consequences of cAMP elevation are broad and tissue-specific:
- Lipolysis: Elevated cAMP plays a role in numerous cellular processes, including the stimulation of hormone-sensitive lipase — an enzyme involved in the breakdown of stored fat (lipolysis).
- Smooth muscle relaxation: Forskolin exhibits positive inotropic, platelet antiaggregatory, and antihypertensive actions in vivo.
- Platelet and gastric effects: Increased cAMP tends to inhibit platelet activation (creating a possible bleeding risk with high doses or in combination with anticoagulants) and stimulate gastric acid secretion, explaining reports of heartburn or loose stools.
- Intraocular pressure: Intraocular pressure depends partly on aqueous humor dynamics; forskolin's cAMP effect can reduce aqueous humor production, which helps explain its presence in 1% ophthalmic solutions studied for open-angle glaucoma.
- Mast cell stabilization: Forskolin's activation of cAMP inhibits human basophil and mast cell degranulation, resulting in subsequent bronchodilation.
Steroidogenesis and Endocrine Effects
Forskolin has been shown in recent studies to stimulate cAMP-mediated acute steroidogenesis and likely up-regulate the transcriptional levels of aromatase in vitro in a dose-dependent manner. A general increase in the production of 17β-estradiol has also been reported for cells upon forskolin exposure. The clinical significance of these in vitro findings for humans taking oral supplemental doses has not been established.
4. Scientific Evidence by Area of Use
4.1 Body Composition and Obesity
Overview of Evidence
Limited studies have shown that Coleus forskohlii extract may aid in weight management. A comprehensive review of the literature identified 7 clinical studies, of which 4 were randomized, double-blind, placebo-controlled studies and the others were open-label studies. Only a handful of clinical trials have looked at the effects of Coleus forskohlii in humans; most of these trials have administered 250 mg of Coleus forskohlii extract standardized to contain 10% forskolin twice per day, for a total daily dose of 500 mg of extract (equivalent to 50 mg of forskolin).
Godard et al. (2005) — Men
The most-cited clinical trial in this area enrolled overweight and obese men. Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage and fat mass 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 primary objective of this study was to determine whether forskolin administration (250 mg of 10% forskolin extract twice a day) results in fat loss and muscle gain, higher endogenous testosterone levels, a positive effect on resting metabolic rate (RMR), and lower systemic blood pressure. The study enrolled only 30 men; the most-cited human trial involved only 30 men over 12 weeks and showed modest body composition changes but no significant absolute weight loss; no large-scale RCTs have confirmed efficacy.
Henderson et al. (2005) — Women
A study investigating the effects of Coleus forskohlii (CF) on body composition determined the safety and efficacy of supplementation. In a double-blind, randomized manner, 23 females supplemented their diet with ForsLeanâ„¢ (250 mg of 10% CF extract, n = 7) or a placebo (n = 12) two times per day for 12 weeks. Body composition (DEXA), body weight, and psychometric instruments were obtained at 0, 4, 8, and 12 weeks of supplementation. It was suggested that CF does not appear to promote weight loss but may help mitigate weight gain in overweight females with apparently no clinically significant side effects. There was no significant interaction (p > 0.05) among the groups in body composition, though group trends occurred in total mass (p = 0.08).
Loftus et al. (2015) — Mixed-Sex RCT with Hypocaloric Diet
This randomized, double-blind, placebo-controlled clinical study assessed the effects of supplementation with C. forskohlii extract on key markers of obesity and metabolic parameters in overweight and obese individuals. Thirty participants completed the trial and were randomly assigned to receive either 250 mg of C. forskohlii extract (n = 15) or a placebo twice daily for 12 weeks, with all participants advised to follow a hypocaloric diet throughout the study. Body weight, BMI, waist and hip circumference, and waist-to-hip ratio were monitored fortnightly, and blood samples were analyzed for plasma lipids, ghrelin, leptin, glucose, and insulin at baseline and end of the intervention. Significant reductions to waist and hip circumference (p = 0.02; p = 0.01, respectively) were recorded in both the experimental and placebo groups after the 12-week intervention — meaning these reductions were not attributed exclusively to the supplement. Findings suggest that C. forskohlii extract in conjunction with a hypocaloric diet may be useful in the management of metabolic risk factors.
Evidence Strength Summary
An NIH Office of Dietary Supplements review notes that Coleus forskohlii (forskolin) has only been studied in a few short-term clinical trials, with current evidence showing no clear effect on body weight and limited safety data, underscoring the need for more rigorous research. Of the 7 clinical studies identified in one comprehensive review, 4 were randomized, double-blind, placebo-controlled studies, and the evidence indicated that C. forskohlii extract had a significant benefit on body composition in overweight/obese subjects, though sample sizes across all these studies were small and study duration was uniformly short (12 weeks). The mechanistic rationale does not establish clinical efficacy for weight loss in humans; a plausible biological pathway is not the same as proven benefit in clinical trials.
4.2 Intraocular Pressure and Glaucoma
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.
An open-label clinical study published in the Saudi Journal of Ophthalmology (2015) and indexed in PubMed (PMID 26155078) enrolled 90 adult patients suffering from open-angle glaucoma with an IOP of more than 24 mmHg. Ninety adult male/female patients aged 18–60 years suffering from open-angle glaucoma with an IOP of more than 24 mmHg were enrolled. Patients were advised to instill 2 drops thrice a day (at 8:00, 14:00, and 20:00 hours) and tonometric readings were recorded at baseline and at the end of weeks 1, 2, 3, and 4. After administration of the first dose (two drops) of forskolin 1% eye drops, a decrease in IOP was observed at the first reading (30 minutes after administration), reached statistical significance from 1 hour onward, and IOP continued to drop until 4 hours and then remained at a plateau for the next 2 hours. The study concluded that forskolin 1% eye drops can be a safe alternative to beta-blockers in glaucoma patients having concomitant asthma.
A registered clinical trial (NCT00864578) assessed whether an oral supplement containing forskolin combined with rutin and vitamins (KRONEK) had any additional effect on IOP in patients with primary open-angle glaucoma already under maximum tolerated medical therapy. Forskolin is a receptor-independent adenylyl cyclase activator that increases intracellular cAMP and has been shown to decrease IOP after topical application by a mechanism not used by other drugs; the trial aimed to see whether a food supplement containing forskolin has any effect on the IOP of primary open-angle glaucoma patients who cannot reach their target pressure. Studies in humans have produced conflicting results for glaucoma use overall.
4.3 Asthma and Respiratory Function
Forskolin's activation of cAMP inhibits human basophil and mast cell degranulation, resulting in subsequent bronchodilation. When administered intravenously or inhaled, forskolin produced a bronchodilation effect in clinical studies.
A single-blind clinical trial (Huerta et al., 2010; Journal of International Medical Research, 38(2):661–668) compared forskolin with the inhaled corticosteroid beclomethasone for prevention of asthma attacks. Limited preliminary clinical research suggests that supplementation with Coleus forskohlii extract or forskolin may reduce the number of asthma attacks in children and protect against methacholine-induced airway restriction in healthy adults. However, much more evidence is needed in these research areas before firm conclusions can be drawn. Overall, smooth-muscle relaxation may translate to easier breathing for some users, although modern, well-controlled human trials are sparse for asthma.
4.4 Cardiovascular Effects and Blood Pressure
Two clinical trials found positive effects with intravenous forskolin for heart disease, but overall support for this use is not strong. In addition, oral forms have not been tested in human clinical trials for cardiac endpoints. Forskolin is known to cause cellular changes that lead to blood vessel dilation, which should lower blood pressure, but there is no proof from clinical trials that this effect occurs in humans.
An Ayurvedic clinical study (Jagtap et al., 2011; Ayu, 32(1):59–65) examined the effect of Makandi (Coleus forskohlii) preparations in a geriatric hypertensive population. A total of 49 hypertensive patients fulfilling the diagnostic criteria were registered in two groups — Group I (Ghana vati) and Group II (Churna tablet). Out of 27 enrolled patients in Group I, 21 completed treatment; in Group II, out of 22 registered patients, 20 completed treatment. This trial used traditional Ayurvedic preparations and lacked a placebo control, limiting its applicability to standardized supplement forms.
Preliminary findings also suggest intraoperative infusion of forskolin may benefit cardiovascular health due to anti-inflammatory effects, or that intraarterial forskolin daropate may improve cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. These represent investigational, not established, uses.
4.5 Testosterone and Bone Mineral Density
In the Godard et al. (2005) trial, 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. Additionally, forskolin administration resulted in a change in bone mass for the 12-week trial compared with the placebo group (p ≤ 0.05). These findings were in a small sample of men and have not been independently replicated in larger RCTs. A bone-conserving effect was also reported to involve osteogenic and anti-resorptive mechanisms resulting in the maintenance of bone mass, microarchitecture, material, and strength.
4.6 Psoriasis
Ammon et al. reported an improvement in symptoms of psoriasis in four patients treated with forskolin. The ability of forskolin to regulate cAMP levels in skin cells has been shown to have therapeutic benefit for sufferers of psoriasis. This represents preliminary, very small-scale human evidence and is insufficient to draw clinical conclusions.
4.7 Antiviral Properties
Researchers evaluated the antiviral potential of forskolin against herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), hepatitis A virus (HAV), and coxsackievirus B4 (COX-B4). Forskolin displayed antiviral activity against HAV, COX-B4, HSV-1, and HSV-2 with IC50 values of 62.9, 73.1, 99.0, and 106.0 μg/mL, respectively. These findings are purely in vitro; no human clinical trials on antiviral efficacy have been conducted.
4.8 Metabolic Syndrome Risk Factors
The Loftus et al. (2015) double-blind RCT (discussed above) specifically examined metabolic syndrome risk factors alongside anthropometric parameters. Researchers concluded that C. forskohlii extract in conjunction with a hypocaloric diet may be useful in the management of metabolic risk factors. In the randomized trial with a hypocaloric diet, the forskolin group showed improved fasting insulin and insulin resistance, while anthropometric changes were small and similar between groups.
5. Body Systems Associated With Forskohlii Root
Based on available evidence, Coleus forskohlii is considered to possess antianaphylactic, antiobesity, amebicidal, gastroprotective, bronchodilating, antiaging, antioxidant, anti-inflammatory, and anticancer activities. The body systems most directly associated with its mechanism-of-action (cAMP elevation) include:
- Adipose tissue / metabolic: Activation of hormone-sensitive lipase and promotion of lipolysis.
- Cardiovascular: Smooth muscle relaxation in vasculature, positive inotropy, platelet inhibition.
- Respiratory: Smooth muscle relaxation in bronchi, mast cell stabilization.
- Ophthalmic: Reduction of aqueous humor formation, lowering of intraocular pressure.
- Endocrine / reproductive: Stimulation of steroidogenesis and possible effects on testosterone and aromatase.
- Skeletal: Possible osteogenic / anti-resorptive effects on bone mineral density.
- Gastrointestinal: Stimulation of gastric acid secretion (a side effect, not a therapeutic target).
- Hepatic: Animal studies indicate induction of hepatic cytochrome P450 enzymes, particularly CYP2B, CYP2C, and CYP3A subtypes, and increased relative liver weight at high doses.
6. Dosage Forms and Doses Reported in Clinical Studies
The following dosages are drawn exclusively from clinical studies reported in the indexed literature:
- Oral capsules (body composition / metabolic studies): Most clinical trials have administered 250 mg of Coleus forskohlii extract standardized to contain 10% forskolin twice per day, for a total daily dose of 500 mg of extract, equivalent to 50 mg of forskolin.
- Oral capsules (metabolic syndrome RCT): Capsules containing 250 mg of C. forskohlii extract (standardized to 10% forskolin) were taken once twice daily 30 minutes before main meals for 12 weeks; placebo capsules contained 250 mg of maltodextrin.
- Ophthalmic drops (glaucoma): In the open-label glaucoma study, 90 adult patients were instructed to instill 2 drops of a 1% forskolin solution thrice daily.
- Aerosolized / inhaled (asthma, investigational): A dose of 10 mg of forskolin has been incorporated for asthma in clinical use.
- Post-marketing safety data: Coleus extract is assessed as possibly safe when used in doses of 500 mg or less daily for up to 3 months; larger doses may cause side effects including diarrhea, constipation, and vomiting.
7. Safety Considerations and Drug Interactions
Gastrointestinal Adverse Events
A post-marketing nationwide online survey in Japan found that 10.5% of users experienced adverse events; gastrointestinal symptoms accounted for 92.0% of all adverse events, and diarrhea alone accounted for 81.3%. One controlled study reported that increased bowel motions and loose stools were plausibly due to an initial increase in gastric acid secretion following supplementation with C. forskohlii extract, as forskolin has been shown to increase acid formation. The reported gastrointestinal side effects were mild in nature and did not lead to discontinuation of the intervention, and the symptoms subsided within four weeks of use.
Cardiovascular Risks
Coleus forskohlii may cause side effects such as headaches, low blood pressure, and increased heart rate; interactions with certain medications can occur, necessitating caution, especially in patients with cardiovascular diseases.
Warfarin / Anticoagulant Interaction
A study determined whether Coleus forskohlii extract (CFE) influences the anticoagulant action of warfarin in mice in vivo. Mice were fed various doses of CFE standardized with 10% forskolin, then administered warfarin, and blood coagulation parameters as well as hepatic CYP were analyzed. CFE dose-dependently increased hepatic total CYP content and S-warfarin 7-hydroxylase activity at a dietary level of ≥0.05%; warfarin-induced anticoagulation was attenuated by CFE in parallel with CYP induction. CFE attenuates the anticoagulant action of warfarin by inducing hepatic CYP2C; thus, caution is required with the combination of warfarin and dietary supplements containing CFE. This finding was in an animal model; direct human pharmacokinetic data on this interaction are not yet available in the published clinical literature.
Cytochrome P450 Enzyme Induction
Investigation of the influence of standardized CFE containing 10% active component forskolin on the hepatic drug-metabolizing system found that mice fed diets containing various doses of CFE showed significantly increased relative liver weight, total content of hepatic CYP, and induced CYPs (especially 2B, 2C, and 3A types) and glutathione S-transferase activities. Importantly, unlike the full CFE, intake of pure forskolin was found to be associated with only weak induction in CYP3A and GST activities with no significant increases in relative liver weight, total hepatic content, or other CYP activities. This implies that the induction potential on CYPs was predominantly due to other, as yet unidentified constituents of CFE, and not to forskolin contained in CFE. As CYP3A4 is involved in the metabolism of many pharmaceutical drugs, this interaction is of clinical relevance for patients on polypharmacy, though confirmatory human data are lacking.
Hepatic Effects
CFE has been shown to induce fatty liver in mice, with components other than forskolin playing a part in this effect. Mice fed a diet containing 1% CFE clearly developed fatty liver, as demonstrated by histological examination and confirmed by increases in triglyceride concentrations in liver. In the nationwide Japanese survey, one participant reported a worsening of liver function test, but continued to take supplements with a reduced amount/frequency; there was no severe liver damage in the collected reports. These liver findings were observed at high doses in animal models; their relevance to typical human supplemental doses is unresolved.
Polycystic Kidney Disease
Forskolin preparations should not be used by patients with polycystic kidney disease.
Platelet Function and Bleeding Risk
Safety concerns include hypotension and increased bleeding risk when combined with anticoagulants or antiplatelet drugs. Increased cAMP tends to inhibit platelet activation, creating a possible bleeding risk with high doses or in combination with anticoagulants.
Endocrine and Hormonal Considerations
In vitro studies have found that forskolin stimulates cAMP-mediated acute steroidogenesis and likely up-regulates the transcriptional levels of aromatase in a dose-dependent manner, and a general increase in the production of 17β-estradiol has been reported for cells upon exposure. Whether these effects are clinically meaningful at supplemental doses in humans has not been determined.
Evidence-Based Overview of Safety
Of the 7 clinical studies identified in one comprehensive review — including 4 double-blind, placebo-controlled studies — the extract had a significant benefit on body composition in overweight/obese subjects, and no major adverse events were reported. The most commonly reported side effects across human trials were gastrointestinal in nature and transient.
References
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