Forskolin: Everything There is to Know About This Powerful Substance

Introduction to Forskolin

Forskolin is a popular supplement, therapeutic drug and research tool that entered medical practice from ayurvedic medicine [R1].

It is obtained from an Indian plant known as Plecthranthus barbatus or Coleus forskohli [R2].

Forskolin has many potentially useful properties:

The following article will discuss potential uses and side effects of cyclic AMP, forskolin and forskolin derivatives.

Where Does Forskolin Come From?

As was mentioned earlier, forskolin is a plant-derived substance

It is produced in the root-cells of Plecthranthus barbatus/Coleus forskohli [R3R4].

Forskolin is obtained primarily from dried root [R5].

Wider-spectrum extracts such as teas and powders are also used [R6, R7, R8].

Analogues of forskolin have also been investigated:

  • colforsin daropate [R9]
  • NKH477 [R10]
  • FSK88 [R11]

All of those substances have the common ability to activate adenylate cyclase, which produces cyclic adenosine monosphate (cAMP) [R12].

cAMP is crucially important to all cells [R13].

Forskolin also influences a number of processes independent of cAMP [R14, R15, R16]

Why Is cAMP So Important?

Cyclic adenosine monophosphate or cAMP is a molecule derived from adenosine – a nucleotide that is also a part of DNA and RNA [R17].

It activates several proteins, including protein kinase A, exchange protein activated by cAMP (Epac) and AMP-activated protein kinase (AMPKA) [R18]

Through these proteins cAMP determines the reaction of the cells to hormones and maintains energy balance [R19].

It was also reported to be involved in immune reactions [R20].

It is a part of extremely complex processes, most of which are not fully understood [R21]. Forskolin plays an important role in investigating these processes [R12]

It is also because of cAMP that forskolin has such diverse effect on the organism and is a promising therapy for many diseases.

Where to Buy Forskolin

Health Benefits of Forskolin

Forskolin Helps To Lose Weight

Both Coleus forskohli extract and pure forskolin supplement help fight obesity and weight gain [R22, R23].

It was shown in the clinical trial that an extract of the plant Coleus forskohli together with the low-calorie diet can be useful for counteracting weight-gain due to metabolic issues [R22].

Patients that were practicing low calorie diet and took the plant extract had lower weight and improved insulin resistance [R22].

In overweight women, C. forskohli extract did not cause weight-loss directly, but prevented weight gain and did not have the side effects of other weight-loss supplements [R24].

Forskolin supplement taken for obesity in obese and overweight men not only led to a decrease in body fat, but also increased testosterone levels and improved bone structure [R23]

It was also shown that forskolin taken together with rolipram induced fat destruction and prevented weight gain [R25].

The latter study has also shown that these effects were connected to the increase of cAMP levels [R25].

Taken together with isoprenalin, forskolin improves blood flow and helps to destroy fat [R26]. This is likely because cAMP levels control rates of lipolysis [R18].

cAMP also influences fat storage R27].

On the other hand, the mechanisms activated by cAMP lead to a decrease in leptin – a hormone that suppresses appetite [R28].

It was also established that the absence of a cAMP activated protein, CREB, in the brain can lead to obesity [R29]

Thus we can conclude that forskolin and forskolin-containing extract are scientifically proven to help fight obesity.

Forskolin Can Be Used To Treat Diabetes

Forskolin may have some role in treating conditions associated with diabetes. As mentioned above, forskolin improves cellular insulin response [R22].

It is also good for suppressing inflammation, which often worsens the condition in diabetic patients and helps decrease the level of sugar in the blood in rats [R30].

Though there is no data that directly shows that forskolin helps in diabetic conditions, it was proposed as a drug to help treat one of the complications of diabetesdiabetic retinopathy [R31].

Diabetic retinopathy is caused by high levels of sugar that damage small eye vessels and cause blood to leak into the eye and damage vision [R32].

Forskolin blocks two proteins responsible for glucose transport – GLUT1 and GLUT 4, thus helping to decrease blood sugar levels [R32, R33].

Forskolin Influences Immune System

There are several articles showing the influence of forskolin on different parts of immune system.

It was recently found that forskolin helps killer immune cell development [R34].

Other studies however show completely opposite findings – that forskolin blocks immune T cell development and immune protein IL-2 [R35].

Forskolin does not act by blocking IL-2 directly, as cAMP is actually increasing the level of this protein [R36].

It is known to destroy the relationship between proteins that carry information into the cell and activate the development of appropriate changes [R36].

It is also known that cAMP can reduce inflammation by suppressing RAGE protein, which initiates the development of inflammation [R37].

There is also a report showing that cAMP elevating drugs, including forskolin, are able to block production of potentially inflammatory protein GM-CSF [R38].

There is also evidence that forskolin induces immune cell production of a number of substances beneficial in treating chronic inflammation [R39].

It should be noted that while the immune cells produce some useful proteins, their activity is partly blocked by forskolin [R40].

The dual effect of forskolin may be explained by the fact that cAMP selectively drives the development of immune cells in favour of certain types, blocking other types of cells and reactions [R41]

Forskolin Kills Cancer Cells

Forskolin can influence cancer cells through a number of mechanisms and is now viewed as a promising assisting drug in cancer therapy.

First of all, forskolin activates protein phosphatase 2A (PP2A), that is blocked in some cancers especially leukemias – cancers of blood cells [R42].

PP2A is an important protein that activates many enzymes in the cell [R43].

Restoration of PP2A activity with forskolin blocks cancer cell development and induces cancer cell death [R43].

It can also enhance the effect of standart anti-cancer drugs such as Idarubicin and Ara-c [R43].

Activation of PP2A also causes cell death in cancer of the prostate [R44].

Forskolin also enhances the action of chemotherapy drugs 5-fluorouracil and oxaliplatin when treating colon cancer and causes cancer cell death due to the same mechanism [R45].

Forskolin is also know to block Hedgehog – a protein crucially important in early development, as it determines the fate of all the organs in the newly formed embryo [R45].

In a grown organism Hedgehog can help cancer cells move to other locations and form metastases [R46].

By inhibiting hedgehog forskolin prevents development of new cancer cells and tumour growth [R46].

It also prevents the invasion of cancer cells into other organs [R47].

It was also shown that by increasing the level of cAMP and activating PKA forskolin blocks a gene called gli1 besides Hedgehog [R48].

Through this mechanism cancer growth in the brain can be prevented [R48, R49].

Research on brain cancer cell lines also shows that forskolin block editing of gene products thus preventing the development of new cancer cells from brain cells [R50].

This drug also increases the benefits of other cancer drugs such as dexamethasone [R51].

Forskolin can also cause changes in cancer cells of leukemia and myeloma that make them sensitive to glucocorticoids [R52].

This makes glucocorticoid cancer therapy more effective [R52].

Forskolin Is Good For The Heart

According to recent research, forskolin can be used to treat heart disease.

First of all, forskolin blocks movement of Ca2+ into muscle cells, thus preventing contraction of muscle cells in the heart and blood vessels [R53].

Muscle relaxation is very important in preventing heart attacks [R53].

It was also proposed that new forskolin derivative, NKH477, can reverse damage to the heart in rats with heart attack [R54].

NKH477 at present is viewed as a promising drug that can make the heart to work at a proper pace [R55]

It was also shown in experiments on heart cells that forskolin reverses some defects associated with a type of heart failure called mitral deficiency, which may improve outcomes after heart operations for this type of problem [R56].

NKH477 can be also useful as preventive measure during surgery as it prevents heart failure by narcotic drugs used in anaesthesiology [R57].

Forskolin derivatives NKH77 and DMAPD increase the level of cAMP in heart cells better than forskolin itself and are more effective for heart therapy [R58].

Forskolin Relaxes Muscles In Blood Vessels

It was known since the 80-s that forskolin helps muscles in blood vessels relax, thus helping the blood flow [R59, R60].

The same effect was observed a decade later for forskolin derivative, NKH477 [R61].

Coleus forskohli extract is shown to lower blood pressure in older patients due to forskolin ability to relax muscle cells in blood vessels [R62].

Forskolin Can Prevent Different Types Of Surgical Complications

Drugs used during surgery can cause problems with the heart, breathing and kidney. Using forskolin before operations can prevent such complications, as is shown below.

As it was said earlier, NKH477 reverses the heart failure caused by narcotic drugs used in surgery such as pentobarbital, propranolol or verapamil, thus preventing heart arrest [R57].

Pretreatment of sheep before surgery with forskolin prevents the blockage of blood vessels and relaxes vessel muscles, thus improving blood flow [R63].

Another forskolin derivative, colforsin daropate, prevents complications by improving blood flow when taken before undergoing surgery for blood vessel transplants [R64].

Also synthetic blood vessel grafts coated with forskolin are better accepted into patients organism as there is no immune cell attachment on their surface and they do not get rejected by the patient’s immune system [R65].

Both forskolin and colforsin daropate also improve blood flow in the kidney, which prevents complications caused both by narcotics and drugs taken for heart failure [R66, R67]

Forskolin Helps Breathing

Forskolin also relaxes muscles in the lung, helping breathing. Injection or inhalation of forskolin derivative NKH477 prevents the constriction of lungs during surgery and may be also used against asthma [R67].

It also lowers blood pressure during surgery, which may prevent bleeding [R68].

Colforsin daropate, a forskolin derivative, prevents tightening of the lungs in humans, which is useful for asthma attacks [R69].

Forskolin was actually compared in efficacy to two asthma drugs, sodium chromoglycate and beclomethasone [R70, R71].

It was found to be more effective than sodium chromoglycate [R70].

As for beclomethasone, no significant differences were found [R71].

It should be noted, that cAMP alone actually can cause asthma attacks [R72].

Forskolin Is Used For Skin Treatment

Forskolin and C. forskohli extract is often used for skin treatments.

For example, it was shown that forskolin can induce migration of skin cells to the place of the wound helping its healing [R73].

Certain types of ultraviolet rays emitted by the sun are actually dangerous, damaging the genetic information in the skin cells [R74].

Application of forskolin to skin cell culture repairs such damage and prevents skin cell death [R74]

Also forskolin treatment makes skin thicker and resistant to UV light [R75].

It was shown in the lab setting that in animals that do not possess an active melanin gene, forskolin increases production of a protein similar to melanin-eumelanin, thus activating an alternative mechanism of protection [R76].

Forskolin can also prevent aging by counteracting damage to the genes and eliminating destructive types of oxygen [R77].

Comparison of skin treatment with forskolin and C.forskohli extract has shown that forskolin gets into the skin faster if it a part of the plant extract [R78].

Forskolin Influences Egg Cells And Sperm

Forskolin can also influence reproductive cells both in men and women.

In case of women, forskolin in combination with ciclostamide improved the development of human egg cells [R79].

Even without the presence of other drugs forskolin increases the rate of egg cell division and makes them more likely to be fertilized and develop into an embryo [R80].

In course of laboratory research on pig egg cells it was found that forskolin is able to control the development of pig oocytes and increases production of progesterone, a protein important for development of the embryo [R81].

Forskolin can also play a role in male reproduction. Forskolin in low doses can increase testosterone production by testes cells as well as production of cAMP, but in high doses it can block the same processes [R82, R83].

Also forskolin is able to increase the level of cAMP in appropriate part of the sperm cell and make the cell more likely to get inside the egg cell [R84]. ]

Forskolin Is Good For Nerve Cells

There is a number of research reports that show the influence of forskolin and P.barbatus/C.forskohli extract on nerve cells in different conditions.

P.barbatus herbal tea can protect nerve cells enzyme acetylcholinesterase [R85].

This protein can be toxic for the organism, so P. barbatus tea is a potential antidote against this type of poisoning [R85].

It was also discovered in rats with brain injury that forskolin derivative NKH477 prevents complications in affected animals by elevating cAMP [R86].

cAMP is involved in many other processes of nerve cell development and protection. For example, cAMP can be used to protect nerve cells from toxic proteins in some diseases that involve nerve cells destruction by initiating ubiquitin protein production [R87].

cAMP is also important for the activity of pituitary gland, which is a part of the brain. Pituitary gland controls a wide array of processes, mainly those controlled by hormones [R88].

The ability of pituitary gland cells to react to the changes in the organism and in the surrounding depends on cyclic nucleotides, including cAMP [R88] .

By increasing cAMP level, forskolin makes nerve cells of pituitary gland produce electrical impulses and regulatory chemical substances [R88].

Among other necessary substances, cAMP increases the production of prolactin by certain specialized cells in the pituitary gland [R89].

Prolactin is mainly known as a hormone that stimulates production of milk for feeding in mothers, but also controls many other processes that are crucial for well being and even mood [R89].

cAMP can be also used in therapy after nerve injuries. For instance, combination of drugs promoting cell growth together with cAMP injections promote nerve cell growth and regeneration after injury [R90].

Forskolin can even reprogram cancer cells into the certain type of nerve cells called astrocytes [R91].

cAMP is so crucial in nerve development, that normal development of the eye retina depends on regulation of cAMP level inside the cell [R92].

Forskolin is also found to be influencing the activity of the nerve cells responsible for hearing in the brain [R93].

Besides general nerve condition and nerve cells responsible for senses, forskolin also increases the level of protein TrkB in rats, helping the animals recover lost memories after trauma [R94].

Forskolin can be also used indirectly for treating nerve disorders such as autism, epilepsy and schizophrenia, as it is used together with a protein Ascl1 to reprogram connective tissue cells into certain type of neurons [R95].

Forskolin Is Used To Treat Glaucoma

Forskolin and cAMP influence on the eye nerve cells is so profound that forskolin – containing substances are actively reviewed for treatment of glaucoma and other eye diseases.

Here it was already mentioned that forskolin can be used for treatment of diabetic retinopathy [R31].

cAMP is also known to be very important in the retina development [R92].

It is known that soluble adenylyl cyclase, an enzyme directly making cAMP, active in different parts of the eye and plays an important role in their function [R96].

Food supplements containing forskolin and other useful substances have improved the condition of patients with glaucoma [R97].

It is also proposed that forskolin taken together with vitamins such as B1 and B2 andrutin lowers blood pressure in the eye, which is the main problem in glaucoma [R98].

In case of injuries to the eye blood vessels, complex injections into the eye with forskolin, homotaurine, and L-carnosine prevents nerve cell death in the eye after elevating of the intraocular blood pressure [R99].

Forskolin Can Be Used For Treatment Of X-Adrenoleukodystrophy

x-ALD or x-adrenoleukodystrophy is a disease caused by faulty transformation of molecules called long chain fatty acids [R100].

cAMP helps lower the level of such acids and also blocks a number of cytokines driving the disease progress [R100].

Forskolin Can Help With HIV Infection

There is one experimental report indicating that P. barbatus extract blocks the activity of proteins derived from HIV virus [R101].

Unfortunately, there are no more reports that corroborate or refute this statement.

Forskolin Can Be Toxic And Can Interfere With Other Drugs

There are several online videos and articles that state – forskolin can have powerful side effects [R102, R103, R104].

Here is the review of literature concerning this topic.

C. forskohli extract can potentially damage the liver [R105]. It was shown on laboratory animals that Coleus forskohli extract increases the level of a number of proteins in the liver which may result in damage to the organ [R105].

It should be noted that forskolin itself has negligible effect in the worsening of liver condition [R106].

It also should be said that the diet of the patient is of importance. C. forskohli extract was shown to be most toxic in cases where the animals were fed products with the high level of starch (is present in high quantities in grain and potatoes) [R107].

C. forskohli extract also interacts badly with tolbutamide that lowers the level of sugar in the blood [R108].

The plant extract increases the level of a protein called cytochrome P450 and prevents tolbutamide from lowering blood sugar levels [R108].

The same cytochrome P450, increased by C. forskohli extract, blocks the action of warfarin, a drug preventing blood flow blockages [R109].

Besides activating potentially damaging proteins in the liver, C.forskohli also leads to the increase in the size of the liver and quantity of fat it contains [110].

Considering contradictory effects of forskolin described above, it is understandable that both the dietary plant extract and forskolin itself should be taken carefully.

There Are Novel Ways Of Forskolin Synthesis

Due to wide use of the compound, difficulties inherent to terpene synthesis and potential hepatotoxicity of natural sources there is a demand for new methods of production [R105110].

There are two new methods of forskolin synthesis that do not involve plant extraction [R111, R112].

One method uses genetically engineered yeast to make 11β-hydroxy-manoyl oxide, a similar copound which can be used to make forskolin [R111].

Another biosynthetic method introduces C. forskholi genetic material to E.coli in order to produce manoyl oxide, another forskolin precursor  [R112].

Conclusion

The wide array of forskolin properties already known makes it a certainty more ways of forskolin applications are to be discovered in the nearest future: new, safer and more effective derivatives would be made and the laboratory successes would be used in real therapy, especially in case of cancer. But the very same reasons for forskolin research and success make the drug also dangerous when taken indiscriminately. Please consult your doctor even about taking forskolin containing extracts or dietary supplements.

Comments

  1. np

    Processes like cAMP are not meant to be activated All.The.Time as there are side effects. Unfortunately this article lists none other than potential asthma (which thankfully is counteracted by other substances in forskolin)

    One big side effect is catabolism. You will loose muscle and have slower recovery after intense, muscle tearing exercise if it is kept activated.

    There is a reason cAMP is heavily modulated, and occurs only in specific situations for healthy individuals, such as fasting or for a short time after an equivalent calorie defecit from exercise

  2. Andy

    Hi Joe, have you ever experienced neck and headache after taking Forskolin? I have taken 250mg Forskolin standardised at 20% twice and both times I have suffered with neck and head ache. Do you know why this could be?

    • John A

      I would suggest supplementing with a choline source. Because of its effect on AChE, many people suggest taking it along with Acetyl-L-Carnitine.

      Personally, I’m looking at Forskolin for the primary purpose of lowering ACh to restore balance, but – as with many things – I’m an anomaly. Many people need more choline, or are already nicely balanced. Where with me, any small addition of a choline source throws me out of wack.

      Try a google search for Forskolin + ALCAR. You’ll find a lot of great info and some recommendations for dosing.

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