Forskolin and cAMP
Wide-Ranging Benefits From Ayurvedic Herb
Ward Dean, MD
Forskolin is an extract from the plant, Coleus
forskohli. Coleus has been traditionally used in Ayurvedic medicine for
a variety of conditions, including hypertension, asthma, eczema,
psoriasis, congestive heart failure, and angina. The effects of
forskolin have been intensively researched in in vitro, animal, and
human clinical studies.
Mechanism(s) of Action
Forskolin acts primarily by activating the enzyme adenylate cyclase,
which results in increased cyclic adenosine monophosphate (cAMP) in
cells. Cyclic AMP belongs to a class of substances known as "second
messengers," and is one of the most important cell-regulating compounds.
Among its many roles, cAMP activates numerous other enzymes involved in
diverse cellular functions. Hormones and neurotransmitters also activate
adenylate cyclase—but forskolin appears to be able to activate adenylate
cyclase by itself. Thus, forskolin can increase cyclic AMP without the
assistance of hormones or neurotransmitters.
Effects of Cyclic AMP
Increased cellular cyclic AMP results in a broad range of physiological
and biochemical effects, including inhibition of platelet activation
(resulting in decreased likelihood of blood clots), reduced release of
histamine (resulting in decreased allergy symptoms), increased force of
contraction of the heart, relaxation of the arteries and other smooth
muscles, increased thyroid function, and increased lipolysis (fat
burning) (Fig. 1).
A number of diseases are characterized, in part, by decreased
intracellular levels of cyclic AMP. These include: asthma, eczema,
psoriasis, angina, obesity and hypertension. In addition to its adenylyl
cyclase-stimulating actions, forskolin also appears to have actions that
are not due to this mechanism, but are due to its ability to alter a
number of membrane transport proteins.
Asthma and Allergies
Many drugs used to treat asthma and allergies are designed to increase
cAMP levels. Usually they inhibit the enzyme (phosphodiesterase) that
breaks down cAMP. This mechanism is the "flip side" of forskolin's,
which acts directly to increase cAMP. Thus, forskolin can be used by
itself, or in addition to phosphodiesterase-inhibiting drugs in the
prevention and treatment of many allergic conditions, including asthma.
Forskolin is an effective smooth muscle relaxer, resulting in
bronchodilation, decreased airway resistance, and increased vital
capacity and forced expiratory volume (important indicators of pulmonary
function) (Fig 2). Forskolin also has tremendous anti-spasmodic action
on various smooth muscles in the body, making it useful to relieve
intestinal colic, uterine cramps, painful urination, angina, and
Cardiovascular Effects of Forskolin
Coleus forskohli has traditionally been used to treat hypertension,
congestive heart failure, and angina. Treating these conditions may be
among the most useful uses for forskolin. Forskolin's basic
cardiovascular action is to lower blood pressure, while simultaneously
increasing the contractility of the heart. This is believed to be due to
forskolin's cAMP-elevating ability, which results in relaxation of the
arteries, and increased force of contraction of the heart muscle. One
study involved seven patients with dilated cardiomyopathy—a particularly
difficult condition to treat. Forskolin administration dramatically
improved left ventricular function and overall cardiovascular
Forskolin also increases cerebral blood flow, indicating that it may be
beneficial in cerebral vascular insufficiency, and in enhancing
post-stroke recovery. The platelet aggregation-inhibiting effects of
forskolin also add to its value in cardiovascular disorders.
Glaucoma and Increased Intraocular Pressure
Glaucoma is a cause of visual loss characterized by nerve damage
(usually associated with increased intraocular pressure), loss of visual
field, glare, and sometimes pain. It is one of the leading causes of
blindness in the elderly. Unfortunately, there is very little in the
armamentarium of alternative health care practitioners that is effective
in preventing or treating this poorly understood condition. However, a
number of studies have shown that topical application of one percent
forskolin eye drops resulted in significant decreases in intraocular
pressure for up to five hours (Fig. 3). Researchers believe that it is
the cAMP-elevating effects of forskolin that result in this significant
improvement. Unfortunately, no commercial forskolin eye drops have been
developed at this time. Although clinical experience is limited, oral
forskolin appears to offer significant potential for sufferers of
glaucoma or intraocular hypertension, and may be a major advance in the
non-drug treatment of this condition.
Psoriasis is characterized by a relative decrease in cAMP compared to
another second messenger, cyclic guanine monophosphate (cGMP). This
imbalance results in a tremendous increase in cell division. In
psoriasis, cells divide about 1,000 times faster than normal. Forskolin
helps to alleviate psoriasis by normalizing the cAMP /cGMP ratio. (It
should be noted that Fumaric Acid, by itself, is highly effective in the
prevention and treatment of psoriasis. However, forskolin and Evening
Primrose Oil may both be considered as additional substances to be added
to a regimen to treat this particularly vexatious disease.)
Depression is believed to be due to an imbalance of neurotransmitters in
the brain — most commonly either serotonergic (inhibitory) or
dopaminergic (stimulatory). The response to various antidepressants
depends on which neurotransmitter system has deviated farthest from the
"norm." If the serotonergic neurotransmitters are most deficient,
serotonin precursors like 5-HTP or L-tryptophan, or the selective
serotonin reuptake inhibitors (SSRI) like Paxil, Prozac, or Zoloft are
most likely to be of help. If the dopaminergic (i.e., catecholamines
like epinephrine or noradrenaline) neurotransmitters are deficient,
catecholamine precursors like the amino acids L-Phenylalanine or
L-Tyrosine, or monoamine oxidase inhibitors like GeroVital (GH3) or
Deprenyl are most likely to help.
German scientists have been working with a different approach to
elevating catecholamines, using a class of drugs that stimulate both the
presynaptic as well as the postsynaptic components of catecholamanergic
transmission. This novel approach uses a drug, rolipram, which acts by
increasing cAMP (an action similar to that of forskolin), and inhibiting
Although the researchers stopped short of recommending forskolin for the
treatment of depression, they stated clearly that "elevated brain cAMP
levels are closely linked to antidepressant activity in animal models of
In vitro studies show that forskolin stimulates lipolysis (breaking down
of fats) in fat cells. Additionally, scientists at the Penn State
University College of Medicine have found that many obese people have
lower than normal cAMP production. Based on these findings and in vitro
studies, scientists theorized that forskolin might be an effective
weight loss agent, especially for those with impaired cAMP production. A
recent small study appeared to confirm this conjecture. Six overweight
women took 25 mg of forskolin (250 mg capsules of 10% standardized
forskolin extract) twice daily for eight weeks. At the end of the
eight-week trial, the participants lost a mean of ten pounds, and
reduced their percentage of body fat by nearly 8% (Fig. 4). Blood
pressure levels also trended lower during the trial. These preliminary
results indicate that forskolin may be a safe, useful adjunct to losing
weight and maintaining normal body composition.
Forskolin also has demonstrated the ability to increase thyroid hormone
production and stimulate thyroid hormone release. This mechanism of
stimulating the thyroid to enhance metabolism may be one way in which
forskolin promotes normal body weight. Forskolin's effects in
normalizing thyroid function may also contribute to its antidepressant
effects, as depression is a common feature of hypothyroidism.
Scientists at Brown University confirmed that forskolin is a potent
inhibitor of platelet aggregation, as well as being a potent inhibitor
of tumor colonization in mice. They suggested that forskolin could find
a place in the prevention of tumor metastases.
Forskolin also exhibits potent immune system enhancement by activating
macrophages and lymphocytes.
Based on the human studies for weight loss, 50 to 100 mg of forskolin
taken in divided doses during the day appears to be a safe, effective
dose for the conditions discussed above.
source of nutrients and supplements.
did we qualify them ?
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