Coleus Forskolin is a blood-vessel-dilating compound that stimulates increased production of thyroid hormones T4 and T3 greatly assisting in overcoming sluggish thyroid activity. It also increases the activity of an enzyme Adenylate Cyclase (AC) that resides in the membrane of all cells, enabling greater cAMP production and activity within the cell. It is of note that there are at least 3 different opioid receptors—mu, delta, and kappa. When an opioid molecule attaches to a receptor in which it “fits”, adenylate cyclase is inactivated, leading to a decrease in intracellular cAMP. If intracellular cAMP levels have been lowered because of constant (inappropriate) stimulation of opioid receptors on the cell surface, less tryptophan hydroxylase is phosphorylated, and therefore more of the enzyme is inactive. When this happens, tryptophan is not converted into serotonin, but is shunted down alternate pathways, eventually leading to urinary IAG (indolyl acryloyl glycine) and 3-indoleacetate. In the pancreas, studies show forskolin increased amylase secretion that is often low in these kids. In fact, it increased AC pancreatic activity 26-fold, and potentiated the increase induced by Secretin. Its activity is weak compared to that of Secretin, but forskolin also potentiates the activity of CCK-8 that affects the redistribution of cellular calcium. It would seem that forskolin could offset some of the effects of casein and gluten produced opioids, but is this an appropriate route?
In one study, Secretin increased cAMP activity up to 10-fold, which mediated the enzyme Tyrosine Hydroxylase (TH) activity up to three-fold. Forskolin also increased cAMP and TH activity. In fact, forskolin stimulates TH activity in the hypothalamus, hippocampus, and frontal cortex of the brain, whereas Secretin activated TH only in the hypothalamus and hippocampus. Use of forskolin (2 mg twice a day) improved speech and induced sleep more quickly in one child. Additional dosage may be needed, and seems to be dependent on body weight. A small, 4-year-old child with distinct hypothyroidism, using 10 mg daily, had adverse reactions, regressing into stimming and screaming.
Forskolin, especially in conjunction with lecithin, phosphatidylcholine, or choline supplementation, may greatly improve the action and effectiveness of vitamin A from cod-liver oil, in the fashion that Dr. Megson has used the drug, Urecholine™ (Bethanechol), by supplying a constant and adequate supply of acetylcholine to the brain. She talks about a problem in absorbing CoA. (Truss says CoA is depleted by the yeast toxin acetaldehyde.) However, Dr. Megson asks this question: “Mucosal cell integrity is also important for absorption of CoA. That is the critical enzyme when choline is converted to acetylcholine. The precursor for this reaction is s-adenosyl methionine (SAMe)…If the CoA pathway is blocked, choline is diverted to production of homocysteine. Are we effectively blocking G-alpha inhibitor of G-stimulatory alpha pathways increasing cAMP cells causing lipolysis, and blocking production of acetylcholine?” To increase the effectiveness of vitamin A, our desire is to increase acetylcholine, however, this may be contraindicated for children struggling under the burden of a PST/sulfoxidation disorder. Kane found choline and inositol were disturbing to children with autism due to their stimulation of nitric oxide (autoimmune response) and the Arachidonic Acid cascade. “Furthermore, the mineral endings contained in many multiples were worthless (Mg oxide), or irritating to the CNS (aspartates) or urea cycle (picolinates). The children responded beautifully to alkaline salts such as Buffered C, and to the glandular pancreas (porcine derivative), or digestive support,” she says.
Michael Murray, prominent naturopath, has this to say about forskolin:
It has a long history of use in Ayruvedic medicine for treatment of cardiovascular disease, eczema, abdominal colic, respiratory disorders, painful urination, insomnia, and convulsions. The basic mechanism of action of forskolin is the activation of an enzyme, adenylate cyclase, that increases the amount of cyclic adenosine monophosphate (cAMP) in cells. Cyclic AMP is perhaps the most important cell-regulating compound. Once formed it activates many other enzymes involved in diverse cellular functions.
Under normal conditions, cAMP forms when a stimulatory hormone (e.g., epinephrine, or Secretin) binds to a receptor site on the cell membrane and stimulates the activation of adenylate cyclase. This enzyme is incorporated into all cellular membranes, and only the specificity of the receptor determines which hormone will activate it in a particular cell. Forskolin appears to bypass the need for direct hormonal activation of adenylate cyclase via transmembrane activation. As a result of this non-specific activation of adenylate cyclase, intracellular cAMP levels rise.
The physiological and biochemical effects of a raised intracellular cAMP level include the following: inhibition of platelet activation and degranulation, inhibition of mast cell degranulation and histamine release, increased force of contraction of heart muscle, relaxation of the arteries and other smooth muscles, increased insulin secretion, increased thyroid function, and increased lipolysis (fat burning).
Recent studies have found forskolin to possess additional mechanisms of action independent of its ability to stimulate adenylate cyclase and cAMP dependent responses directly. Specifically, forskolin inhibits a number of membrane transport proteins and channel proteins through a mechanism that does not involve the production of cAMP. The result, once again, is a transmembrane signal that results in activation of other cellular enzymes.
Forskolin also antagonizes the action of platelet activating factor (PAF) by interfering with the binding of PAF to receptor sites on cells. PAF plays a central role in many inflammatory and allergic processes, including neutrophil activation, increasing vascular permeability, smooth muscle contraction (including bronchoconstriction), and reduction in coronary blood flow. After treatment of platelets with forskolin prior to PAF binding, a 30-40% decrease in PAF binding was observed. The decrease in PAF binding caused by forskolin was concomitant with a decrease in the physiological responses of platelets induced by PAF. However, this forskolin induced decrease in PAF binding was not a consequence of cAMP formation, as the addition of a cAMP analog could not mimic the action of forskolin. In addition, the inactive analog of forskolin, dideozyforskolin, which does not activate adenylate cyclase, also reduced PAF binding to its receptor. Researchers speculate that the action of forskolin on PAF binding is due to a direct effect of this molecule and its analog on the PAF receptor itself, or to components of the postreceptor signaling for PAF.
These are some of the things they say forskolin may be helpful and useful for: eczema, psoriasis, asthma, hypertension, congestive heart failure, angina, cerebral vasodilator indicating that it may prove to be useful in cerebral vascular insufficiency and post stroke recovery, increasing intraocular blood flow, weight loss programs (due to its lipolysis stimulation), hypothyroidism, malabsorption and digestive disorders, depression, prevention of cancer metastasis, and immune system enhancement.
This is what
Hypothyroidism—forskolin increases thyroid hormone production and stimulates thyroid hormone release. Malabsorption and digestive disorders—forskolin stimulates digestive secretions including the release of hydrochloric acid, pepsin, amylase, and pancreatic enzymes. Forskolin has been shown to promote nutrient absorption in the small intestine. Coleus forskohlii extracts may prove useful in treating dry mouth, as forskolin increases salivation. Immune system enhancement—forskolin exhibits potent immune system enhancement (primarily through activation of macrophages and lymphocytes) in several models.
My reservations, and that of others more qualified than
I, is that forskolin bypasses the G-protein “switch” to activate adenylate
cyclase and raise cAMP levels. Apparently, since there is no “off” switch,
this will keep these cells running “full bore” without a brake. This seems
to stimulate the sympathetic nervous system to greater activity. This would
not be desirable, obviously, for those with an overactive sympathetic system
(most autists). Conversely, in low dose, it would probably be beneficial to
one with a sluggish sympathetic nervous system (while one gives the
sympathetic glands—the thyroid, adrenal medulla, anterior pituitary, and
andric [male] hormones—needed nutritional support), and possibly to one with
the G-protein dislocated from its retinoid receptors by the DPT vaccine as
postulated by Dr. Mary Megson, however, she asked if increasing cAMP cells
could be causing lipolysis, and blocking production of acetylcholine needed
to enhance the activity of vitamin A. (See my paper “Notes on pH Balance and
Metabolic Types”). Increasing