Introduction

One of the most common issues troubling the modern human race is weight loss. To put this in perspective, it has to be said, that our obsession with weight loss is unique to the first world and our way of living. We already know that eating less and expending more calories can help us lose weight. However, that is not really what we are after.

Ideally, we do not want to change our ways and yet lose weight. We are human after all.

Mankind (and womankind) has been on the hunt for a weight loss hack for a very long time. A hack like this would also be a very viable commercial market.  For some people, the ideal weight loss agent would be a pleasant tasting pill which we could order online and have delivered to our door.

To be really cynical, I would add that it would be even better if the weight loss pill came originally from some exotic part of the world.

How do I know? Not just because I have been a doctor for decades, but because I too am a fatally flawed human who often times does not feel like exercising and likes to eat great French bread.

May I present forksolin. Promoted and sold by Jeff Bezos’ very successful company as a weight loss agent. Before I order some, may I check if it works?

What Is Forskolin?

Forskolin is a plant which is native to the Indian subcontinent from the Himalayas to Southern India and is also found in Nepal and Thailand. It is also known as makandi and colforsin. It comes from the roots of the Coleus forskohlii plant which is a perennial herb with fleshy fibrous roots and belongs to the mint family of plants. The tuber is known as ‘garmar’ in Gujrat and is very popular in pickles.

Initially, forskolin was positioned as a vasodilator and was investigated for use in a number of cardiovascular conditions. More recently, interest in forksolin has shifted to its role as a potential weight loss agent. Hmmmmm, an exotic weight loss agent that is a first cousin of mint, I am really interested now.

It is classified as a labdane diterpene (1). This means that its chemical structure has two joined rings which occur naturally. It has a chemical structure of 7β-acetoxy-8,13-epoxy-1α,6β,9α-trihydroxy-labd-14-en-11-one (C22H34O7).

It has played an important role in Ayurvedic traditional Indian medicine for centuries. It is used for a wide range of conditions including cancer, obesity, glaucoma, asthma, and heart failure. Modern science is starting to investigate what the ancients perscribed and science is now beginning to codify the science behind forksolin.

We now know that forsksolin increases the levels of a small molecule called cyclic adenosine monophosphate (cAMP) which comes from adenosine triphosphate (ATP) (2). cAMP is an important biological messenger which means that it is biologically plausible that it has therapeutic effects.

Based on this science, if I were in the business of guessing, I would guess that forksolin might have some effects on blood vessels and the bronchial tree which interestingly enough actually does correlate with its use in traditional Indian medicine.

There are 106 forksolin related products for sale on Amazon. There is a huge price (inexplicable) difference in the price range ( from ten cents to one USD per tablet).

Is There Any Research?

There are 22,000 publications on forksolin which includes 57 clinical trials. To put this into context, there are 130,000 publications on weight loss which include 11,000 clinical trials.

Does it Help Treat Cancer?

cancer ribbon

As mentioned, forskolin directly activates an enzyme called adenylate cyclase enzyme which converts cAMP from ATP. This has the effect of raising cAMP levels in cells. In turn, cAMP modulates protein kinase A which plays a key role in cancer cell regulation (3).

There are no human clinical trials looking at the effects of forksolin as an anti-cancer agent. There are, however, a number of relevant and interesting studies.

A study from 1983 looked at the effect of forksolin on B16 murine melanoma, B16-F10 which is a lung cancer cell line that likes to metastasize to lungs (cause lung cancer secondaries) in lungs (4). The researchers injected forksolin into the tail of mice and then injected the B16-F10 cells. They found that forksolin reduced lung metastases by 70% in three different experiments.

A number of studies show that forksolin may reduce the side effects of chemotherapy in cell lines (5).

Bottom Line

There is no evidence to support forksolin as an agent in cancer treatment or prevention.

Does It Help Manage Asthma Attacks?

As mentioned earlier, there is biological plausibility that forksolin could help with asthma. cAMP helps dilate the bronchial tree.

There are two studies looking at forksolin for prevention of acute asthma.

The first study compared sodium cromoglycate to forksolin (6). Sodium cromoglyacte is widely used to prevent asthma.

Mexican researchers assigned 40 adults with mild-moderate asthma to forskolin at 10 mg/day orally (capsules) or with two inhalations of sodium cromoglycate every 8 h, i.e. three times a day for six months. The results showed that 40% of people in the forksolin arm versus 85% in the cromoglycate arm had asthma attacks.

The difference was statistically significant in favor of forksolin. Two things strike me about this study. Firstly, it was single blinded and not double blinded. This is understandable as forksolin was taken orally while the cromoglycate was inhaled. However, this is a weakness in the study design.

Secondly, an attack rate of 85% seems very high suggesting either that the definition of an asthmatic episode was very lax or that these people needed better control of their asthma. Either way, this high rate of asthma makes me nervous.

The same Mexican study group looked at forskolin (one 10-mg capsule orally per day) or the steroid, beclomethasone (two 50 microg inhalations every 12 h) in 60 patients for 2 months (7). There was no statistically significant difference in lung function or asthma episodes between the study groups.

Bottom Line

There is some very limited but questionable evidence to suggest that forksolin may help prevent asthma in mild to moderate asthmatics. However, from my perspective, there is too little evidence to recommend forksolin for this indication. Poorly controlled asthma can kill. There are already well-established prevention strategies in asthma which should be used.

There are no studies looking at forksolin in acute asthma or during an attack and there is no way that forksolin should be tried out during this potentially life threatening emergency. No way. Ever.

Is it useful in Alzheimer’s Disease?

We already know that forksolin affects cAMP. Via the cAMP pathway, it inhibits cholinesterase which plays a key protective role in Alzheimer’s disease (8).

There are no human clinical trials studying forksolin in Alzheimer’s disease. There are 58 pre-clinical studies which suggest that it may be worthwhile studying forksolin in this population

A 1998 study showed that increasing cAMP can help aid memory loss in mice (9). This study did not use forksolin as the agent to increase cAMP but used another agent called rolipram. The importance of this study is that it provides a biological basis for a mechanism by which forksolin could help with memory.

I agree that this is not ideal. However, in the absence of clinical data, we have to work with what we have.

A 2017 study showed that forksolin could reverse memory deficits in mice who had been treated with streprozocin to induce dementia (8).

A 2018 study showed that forksolin can affect a protein called tau and as such may (possibly) have beneficial effects in Alzheimer’s disease (10). This is all very theoretical and based on test tube style research.

There is one study in humans which I would like to mention here. It relates to brain health but not via an anti-Alzheimer’s effect. However, as the results of the study were positive and it was an actual human clinical trial, I think it fits perfectly here. Subarachnoid hemorrhage can happen out of the blue whereby people bleed into the subarachnoid space (space around the brain).

As such, it is classified as a form of stroke. Usually people who present with strokes are middle aged to elderly but subarachnoid hemorrhage is often seen in a much younger age group. Following the bleed, the vessels in the brain can go into spasm which can cause significant disability and even death.

Colforsin which is a water soluble from of forksolin was injected directly into the cerebral arteries of 29 patients with subarachnoid hemorrhage (11). The 29 patients underwent a total of 53 procedures. Of these procedures, clinical improvement was seen in 86% of cases and 66% of patients were noted to have a good recovery or just a moderate disability at 3 months of follow up.

The Japanese team of investigators concluded that the forksolin derivative was effective in managing the complications of subaracnhoid hemorrhage.

Bottom Line

There is no clinical proof that forksolin can help with Alzheimer’s Disease.

Does It Reduce High Blood Pressure?

As a cAMP modulator, it is biologically plausible that forksolin can affect blood pressure via vasodilation. We have already seen that forksolin can dilate cerebral arteries which have gone into spasm following a subarachnoid hemorrhage.

There is a really interesting study to look at here. Indian researchers compared the effect of forksolin tuber to forksolin tablets in 49 adults with high blood pressure (12). The researchers explained the study design as follows.

In Ayurvedic or traditional Indian medicine, it is believed that whole plants are preferable to plant extracts. It is believed that the whole plant contains fractions that balance the active agents and as such minimize side effects. Selecting out compounds from plants for use in pills is believed to reduce this in-built safety check that nature has designed.

The study showed that both the tuber and the pills reduced blood pressure. The study took place over 2 months. All study participants received lifestyle advice. Both groups were noted to have statistically significant improvements in blood pressure.

There was a non-significant greater improvement in the tuber treated arm of the study. No differences were noted in the safety profile between the two arms of the study.

Bottom Line

There is limited clinical evidence which does support a role for forksolin as an antihypertensive agent.

Do Forskolin Supplements Help Reduce Weight?

reduce weight

Ah, that is the real question.

US based researchers randomized 30 men to either twice daily forksolin or placebo for 12 weeks (13). All study participants met the criteria for obese or overweight. There was a statistically significant decrease in body fat in the forksolin arm of the study which was accompanied by a non statistically significant trend towards an increase in lean body mass in this arm of the study.

These changes in body composition did not translate into actual weight loss. The study took place over 12 weeks.

A second study with a similar design compared twice daily forksolin or placebo for 12 weeks (14). The study participants were 19 women who were moderately overweight. The study found that the forksolin did not help with weight loss but may have helped prevent weight gain. The study participants were described as ‘free living’.

‘Free living’ means that any number of variables could have affected the study results and indeed that seems to be the case (like French bread in my case). The study team noticed that both arms of the study reduced their calorie intake during the study which was thought to be due to an effort by study participants to help the study. Obviously this can affect the study results.

Next a study from Johnson and Johnson looked at a topical slimming aid containing tetrahydroxypropyl ethylenediamine, caffeine, carnitine, forskolin and retinol (15). The study found that improvements in orange peel and cellulite in 78 women who took part in the study over 12 weeks. With the best will in the world, it is difficult to take industry conducted or sponsored studies seriously.

Finally, a study by Belgian researchers (that I would highly recommend reading but only if you have problems sleeping) showed that forksolin reduces inflammation from fat cells by an effect on a molecule known as NFkB (16).

While the details of this study are complex (and could lull you to sleep) and are based on in vitro tests, the take home message is that there is some emerging evidence to support a mechanism by which forksolin can effect fat cells and obesity.

Bottom Line

This is a really tough one. There is no evidence that forksolin makes you gain weight. It is biologically possible that it could help you loose weight. But, the available studies are not exactly slam dunks. Certainly, no one peeled away kilograms. Sorry, I would have been very happy to report on a statistically significant difference in a large, long term clinical trial. But this is not the case.

Does It Lower Blood Sugar Levels?

Again, there are no human clinical trials to guide us here. We do have some rodent data.

A study in 27 rats (19 of whom had streptozocin induced diabetes and 8 of whom were health) looked at the effects of forksolin on blood sugar metabolism (17). The study had four groups:

  • diabetic without forksolin
  • diabetic with forksolin
  • healthy with forksolin and
  • healthy without forksolin.

The study found that forksolin significantly reduced serum levels of fasting glucose in healthy rats and significantly decreased the severity of fasting hyperglycemia in diabetic male rats. The study authors point out the obvious limitation of the study.

Streptozocin induces diabetes in rats faster than would occur in humans and as such is only a poor proxy for human diabetic subjects.

Bottom Line

There is no proof that forksolin helps with diabetes in humans.

Other Possible Uses

There is an interesting study from US based melanoma researchers who found that forksolin cream could cause tanning in fair skinned individuals which in turn could theoretically protect against UV damage (18). This theory has not yet been tried out in humans but is interesting nonetheless.

One Last Thing

When I read the above articles on forksolin, I was surprised that there was no mention of erectile dysfunction. Why do I say that? Erectile dysfunction is not just one of the few things that could compete with a weight loss agent from a commercial perspective, it is also biologically plausible that forksolin could help with erectile dysfunction.

Smooth muscle relaxation and vasodilation is the answer to erectile dysfunction.

I found a 2007 paper which reviewed possible natural remedies for erectile dysfunction which suggested yohimbine and forksolin (19).

The following is definitely not a home remedy that you should try for yourself. A study in a white rabbit model found that injection of forksolin resulted in changes (relaxation of smooth muscle) which could help with erectile dysfuntion (20). The same team then injected forksolin into the blood vessels of the penis of 31 men with erectile dysfunction.

They found that there was a 61% reported improvement in rigidity and/or erection duration using intracavernosal forskolin (98 micrograms./ml.). Ouch.

Is Forskolin Supplement Safe?

The optimal dose of forksolin has not been established. Nor has the safe dosing range for forksolin been identified.

A 2015 study from India looked at the effect of forksolin in an Allium cepa (onion) model (21). This study was done to look at the effect of forksolin on genotoxicity. As such, it is a highly investigational model but it does give us useful information. Overall, it was noted that ‘ Forskolin may cause genotoxic effects and further toxicological evaluations should be conducted to ensure its safety’.

There is one human safety study looking at forksolin  (22). Forksolin was shown to be safe in a study of 90 adults who used forksolin drops for glaucoma for four weeks. There are two main problems with this study. Firstly, the dose of forksoilin in eye drops would be way lower than that when forksolin is taken orally. Secondly, this study was too short to be reassuring.

Kidney cysts growth is stimulated by cAMP. On study found a forksolin like compound in people with polycystic kidney disease and cautioned that forksolin may promote kidney cyst growth in these patients and should be avoided.(23).

in 2005, a number of cases of acute poisoning relating to forksolin were reported (24). The affected patients were noted to have tremor, agitation, hallucination and confusion. It was thought that the forksolin batch had been contaminated with a member of the deadly nightshade, Atropa Belladona which is a member of the Solanaceae family.

As forksolin can cause a drop in BP, care should be taken by people who have low blood pressure or who are taking medication for lowering blood pressure.

Like many herbal medications, care should be taken in people who are taking any blood thinning medication.

Conclusions

Just imagine for a moment that there were a product that could help you lose weight, manage your blood sugar, prevent Alzheimer’s and reverse erectile dysfunction. That would be a multi-billion dollar product for sure. In fact, I suspect that it would be a premium product as demand would likely far outstrip demand.

Sadly, we have to say forksolin is not that product. In fairness, we have looked at forksolin in the tail of rats, the penis of white rabbits and available studies in humans to come up with this conclusion. At best, it may help with lowering blood pressure and may possibly help with preventing weight gain. The limited available studies come with lots of caveats which always makes me suspicious.

Dear customer support at Amazon, may I please cancel my order for forksolin and order a skipping rope instead?.

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