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Wide-Ranging Benefits From Ayurvedic Herb
Forskolin and cAMP
by 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.1
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 hypertension.
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 performance.
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
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
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 phosphodiesterase. 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 depression.”
Weight Loss
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.
Hypothyroidism
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.
Cancer Metastases
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.
Immune Enhancement
Forskolin also exhibits potent immune system enhancement by
activating macrophages and lymphocytes.
Dosage
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.
Reference
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cyclic AMP levels and lipolysis in fat cells after isoproterenol and
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