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Forskolin and cAMP
Wide-Ranging
Benefits
From an Ayurvedic Herb
By Ward Dean, MD
NaturoDoc Note: Forskolin is an extract from the plant Coleus
forskohli, a member of the mint family that grows
natively in subtropical areas of India, Burma, and Thailand. Forskolin
has been extensively researched in the medical field for use in the
treatment of allergies, respiratory problems, cardiovascular diseases,
glaucoma, psoriasis, hypothyroidism and weight loss. Recently, it
has made medical news as a natural remedy for Urinary Tract Infections
(UTI) by
enhancing the ability of antibiotics to kill the bacteria that cause 90
percent of infections in the bladder. As such, it can
greatly reduce recurrence of urinary tract infections, according to a
new study published online April 8, 2007, in the journal Nature
Medicine.
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.
This article contains the following sections:
How Forskolin Works
Effects of Cyclic AMPP
Asthma and Allergies
Cardiovascular Effects of Forskolin
Glaucoma and Increased Intraocular Pressure
Psoriasis
Depression
Weight Loss
Hypothyroidism
Cancer
Metastases
Immune
Enhancement
Dosage
References
Related Products
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.
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.
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
ability to act 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,
which are important indicators of pulmonary function (Fig 2). Forskolin also
has tremendous antispasmodic action on various smooth muscles in the body,
making it useful to relieve intestinal colic, uterine cramps, painful
urination, angina, and hypertension.
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 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
such as the amino acids L-Phenylalanine or L-Tyrosine, or monoamine oxidase
inhibitors such as 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."
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.
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.
9. Laurenza, A., Sutkowski, E.M., and Seamon, K.B. Forskolin: A 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. T he
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 morbidly
obese humans. Surgery, 1990, 108: 228-235.
12. Okuda, H., Morimoto, C., and Tsujita, T. Relationship between cyclic AMP
production and lipolysis induced by Forskolin in rat fat cells. J Lipid
Research, 1992, 33: 225-231.
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, 1985,
102: 1009.
16. Wachtel, H., and Loschmann, P.-A. Effects of
Forskolin and cyclic
nucleotides in animal models predictive of antidepressant activity:
interactions with rolipram. Psychopharmacology, 1986, 90: 430-435.
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 by Vitamin Research Products, Inc. Used by permission.
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