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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
1. Agarwal, K.C., and Parks, R.E. Forskolin: A potential antimetastatic
agent. Int J Cancer, 1983, 32: 801-804.
2. Allen, D.O., Ahmed, B., and Naseer, K. Relationships between
cyclic AMP levels and lipolysis in fat cells after isoproterenol
and forskolin stimulation, J Pharmacol and Exp Therapeutics, 1986,
238: 2, 659-238.
3. Badmaev, V., Majeed, M., Conte, A., and Parker, J. Diterpene
Forskolin: A possible new compound for reduction of body weight
by increasing lean body mass. Townsend Letter for Doctors and Patients,
2001, June, 115.
4. Bartels, S.P., Lee, S.R., and Nuefeld, A.H. Forskolin stimulates
cyclic AMP synthesis, lowers intraocular pressure and increases
outflow facility in rabbits, Current Eye Research, 1983, 2: 10,
673-681)
5. Caprioli, J., and Sears, M. Forskolin lowers intraocular pressure
in rabbits, monkeys and man. The Lancet, 1983, April 30, 958-960.
6. Haye, B. Chronic and acute effects of forskolin on isolated thyroid
cell metabolism Mol Cell Endocrinol, 1990, 43: 41-50.
7. Kramer, W. Effects of forskolin on left ventricular function
in dilated cardiomyopathy. Arzneim Forsch, 1987, 37: 364-367.
8. Kreutner, W. Bronchodilatory and antiallergy activity of forskolin.
European J Pharmacology, 1985, 111: 1-8.
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specific stimulator of adenylyl cyclase or a diterpene with multiple
sites of action? TIPS, 1989, November, 101: 442-446.
10. Lichey, J., Friedrich, T., Priesnitz, M., et al. Effect of forskolin
on methacholine-induced bronchoconstriction in extrinsic asthmatics.
The Lancet, 1984, July 21, 167.
11. Martin, L.F., Klim, C.M., Vannucci, S.J., et al. Alterations
in adipocyte adenylate cyclase activity in morbidly obese and formerly
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12. Okuda, H., Morimoto, C., and Tsujita, T. Relationship between
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13. Roger, P.P., Servais, P., and Dumont, J.E. Regulation of dog
thyroid epithelial cell cycle by forskolin, and adenylate cyclase
activator. Exp Cell Res, 1990, 172: 282-292.
14. Saunier, B. Cyclic AMP regulation of Gs protein. Thyrotropin
and forskolin increase the quantity of stimulatory guanine nucleotide-binding
proteins in cultured thyroid follicles. J Biol Chem, 1990. 265:
19942-6.
15. Schorlemmer, H.U. Forskolin for immune stimulation. Chem Abstr,
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16. Wachtel, H., and Loschmann, P.-A. Effects of forskolin and cyclic
nucleotides in animal models predictive of antidepressant activity:
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17. Wysham, D.G., Brotherton, A.F., and Heistad, D.D. Effects of
forskolin on cerebral blood flow: Implications for a role of adenylate
cyclase. Stroke, 1986, 17: 1299-1303.
The information
in this article is not intended to provide personal medical advice,
which should be obtained from a medical professional, and has not
been approved by the U.S. FDA.
Copyright 2004
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