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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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