Research Perspectives in Asthma: A Rationale for the Therapeutic Application of Magnesium, Pyridoxine, Coleus forskholii and Ginkgo biloba in the Treatment of Adult and Pediatric Asthma
 
   

Research Perspectives in Asthma: A Rationale for
the Therapeutic Application of Magnesium,
Pyridoxine, Coleus forskholii and Ginkgo biloba
in the Treatment of Adult and Pediatric Asthma

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:
   Frankp@chiro.org
 
   

The Internist 1998 (Sept);    5 (3):   1416 ~ FULL TEXT

by Mitchell Chavez, BS CN


Thanks to the ACA's Council On Family Practice for their permission to reprint this article exclusively at Chiro.Org


Asthma affects approximately 10 million people in the U.S.A.   The most common populace is children under the age of ten. This disease has had an increased occurrence of over 29% within the last twelve years. United States mortality rates have also increased by a staggering 31%, with blacks requiring hospitalization twice as often as whites.

The pathophysiology of asthma generally includes, but is not limited to:

(1) bronchial spasm and/or constriction of smooth muscle tissue due to a reduced production of cyclic adenosine monophosphate (cAMP) resulting in a reduction of airways diameter;

(2) inflammation, via edema, of bronchial mucosa;

(3) increased mucus production (this is a precursing symptom to bacterial infection, often resulting in bronchitis or bacteria pneumonia); and

(4) cellular allergic factors such as eosinophilia, results in inflammation of airways. This allergic mechanism is almost always mediated by platelet activating factor (PAF) and histamine (to a lesser extent) and will often result in bronchial hyperresponsiveness.


At Last, An Alternative's Alternative

The compounds in this "alternative protocol" apply to the four major aspects of the disease as described above; without the side-effects of orthodox treatments.

Other alternative treatments often implement and/or advocate the usage of botanical compounds such as ma huang (Ephedra sinensis and its subspecies), cola nut (also known as bissy nut), and green tea.   These botanicals are rich sources of sympathetic amines such as ephedrine, and methylxanthines such as caffeine and theophylline.   Side-effects such as hyperactivity, hypertension, reduction in peripheral circulation, diuresis, and tachycardia have all been demonstrated by these indigenous plant constituents.

The efficacy of magnesium, pyridoxine, cobalamin, Coleus forskholii, and Ginkgo biloba have all been established and validated many times over, by multiple studies via peer-reviewed journals.   These anti-asthmatic compounds are completely free of any hidden source of potentially stimulating alkaloids such as: caffeine, theophylline and ephedrine.


Magnesium: An Unsung Hero

Magnesium is extremely effective in the relaxation of bronchial smooth muscle tissue, resulting in a reduction of bronchospasm and increased airways diameter.   Magnesium is a critical cofactor in cellular biochemistry areas such as production of adenosine triphosphate (ATP) and cyclic adenosine monophosphate (cAMP) are mediated by magnesium status.   By competitive inhibition of ionized calcium (which induces smooth muscle tissue constriction via the elevation of cyclic guanine monophosphate), magnesium has been shown to relax bronchial smooth muscle tissue.

Magnesium has also been demonstrated to reduce the histamine response.   Patients who suffer from allergy related asthma often show excessive eosinophilic and basophilic histamine release which ultimately results in bronchoconstriction.   The "dulling" of magnesium to the histamine response might be due to a correction and/or increase in tryptophan metabolism, via the pyridoxine pathway.

Various nutritional and lifestyle practices have been shown to have a negative effect on cellular magnesium levels.   Factors include: chronic caffeine and alcohol consumption, dieting, and prescription diuretics such as hydrochlorothiazide, furosemide, and bumetanide.   Ironically, studies have shown asthma medications such as theophylline and the beta agonists (such as albuterol and metaproterenol) can cause magnesium wasting. This may result in exacerbation of the overall condition.


Vitamin B6: The Critical Catalyst

Pyridoxine, commonly refered to as vitamin B6, is a critical co-enzyme in human biochemistry, areas such as production of adenosine triphosphate (ATP) and cyclic adenosine monophosphate (cAMP) are mediated by cellular pyridoxal and magnesium status.   ATP and cAMP have been shown to promote relaxation of bronchial smooth muscle tissue, resulting in an increase of airways diameter.   Vitamin B6 also plays a critical role in the utilization of various amino-acids such as L-tryptophan and L-tyrosine and is therefore the key co-enzyme in the synthesis of neurotransmitters such as: serotonin, adrenaline, and norepinephrine.

Unfortunately, most medications commonly prescribed have been demonstrated to potentially induce pyridoxine deficiency, again exacerbating the asthma.   Some of these pharmaceutical agents include: theophylline (an oral methylxanthine), albuterol (an inhaled beta-adrenergic agonist) and prednisone (an oral steriod form of cortisone).

In one study, patients were given 50 mg of vitamin B6 twice daily and reported a dramatic decrease in frequency and severity of asthma attacks.


Vitamin B-12: The Anti-Sulfite Agent

In several clinical trials, supplementation with cobalamin (vitamin B12) has been demonstrated to improve the overall asthma condition by reducing its severity and frequency.

This is especially true with pediatric asthma, which is often a result of sulfite-sensitivity.   Jonathan V. Wright, MD of Kent, Washington, believes "B12 therapy is the mainstay in childhood asthma".

Vitamin B12 has been shown to induce the production of a sulfite-cobalamin complex, which blocks the allergic effects of sulfites.   It has also been proposed that the oxidative action of vitamin B12 is able to block the sulfite-induced bronchospasm associated with chronic allergy related asthma.


Coleus Forskholii: Bronchodilation Ayurvedic Style

As an Ayurvedic herb used for centuries, Coleus forskholii has been traditionally used for respiratory disorders, painful urination, and various heart conditions.   This botanical medicine has been scientifically demonstrated to be a rich source of biologically active compounds including a diterpene molecule known as forskolin.

Forskolin has been demonstrated by many studies to potentiate and activate the enzyme adenyl cyclase.   This enzyme is the critical catalyst in the production and conversion of magnesium mediated adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) and is also antagonistic to the production of guanyl cyclase.

Calcium has been shown to increase levels of guanine triphosphate and cyclic guanine monophosphate (cGMP) (via guanyl cyclase), thus resulting in smooth muscle tissue constriction.   Studies have shown that relaxation of bronchial smooth muscle tissue is dependent on intra-cellular cAMP production.

Since forskolin is not a sympathomimetic amine or central nervous system stimulant (e.g. ephedrine and theophylline), it's mechanism of action is free of the side-effects (e.g. tachycardia, hypertension, anorexia, etc.) common to sympathetic agents generally prescribed.


Ginkgo Biloba For Intelligent Breathing

Commonly referred to as the plant kingdom's oldest living fossil, Ginkgo biloba's existence can be traced back over 200 million years.   The Ginkgo tree is planted throughout the United States primarily as an ornament, often as city landscape along roadsides.   A single tree may easily reach the age of one thousand years with great resistance to insects, disease, and pollution.   The traditional use of Ginkgo, in China, has almost always been related to lung function, blood circulation, longevity, and/or mental performance.

To date, Ginkgo biloba is the most widely prescribed phyto-pharmaceutical in the world, with over two hundred published studies and abstracts validating the herb's efficacy.   Clinical indications include cerebral vascular insufficiency, Raynaud's Phenomenon, and asthma. All of these diseases have common components: a physiological need for an increase in micro-circulation and reduction or inhibition of platelet-activating factor.

The biologically active compounds occur primarily in the leaves of the Ginkgo tree and are classified as ginkgo-flavoneglycosides and terpenoids.   The flavonoid (ginkgo-flavoneglycoside) class includes: the molecules kaempferol, isohamnetin, and quercitin.   The terpenoid class is further broken down into two subclasses as ginkgolides and bilobalides.   The major ginkgolide factors are A, B, and C.

The terpenoids have been demonstrated in a multitude of research to be potent inhibitors of PAF, resulting in increased micro-circulation and reduction of the inflammatory response.   Other constituents such as the ginkgo-flavoneglycosides, have been shown to improve capillary integrity and strengthen collagen tissues.

Studies have demonstrated maximum efficacy is achieved at 120 mg. total per day as 24% ginkgo-flavoneglycosides and 6% terpenoids.


Review and Conclusion

Combination therapy utilizing the compounds previously discussed could be the best approach for the chronic asthmatic patient; especially pediatric situations where stimulating modalities (eg. theophylline and ephedrine) may cause a range of side-effects.   Implementing magnesium, pyridoxine, cobalamin, Coleus forskholii, and Ginkgo biloba as long-term therapy could not only provide prophylactic benefits, but would also yield a multi-faceted approach.

Bronchodilation, increased production of cAMP, reduction of the histamine response, and the blocking of sulfite sensitivity, have all been demonstrated to minimize the frequency and severity of asthma attacks.   Magnesium, pyridoxine, cobalamin, Coleus forskholii, and Ginkgo biloba; a novel, unique, and non-invasive therapy for the asthma patient.


SELECTED REFERENCES

1.   Brunner, E.H. et al.   "Effect of parenteral magnesium on pulmonary function, plasma cAMP, and histamine in bronchial asthma."
Journal of Asthma, 22:3-11, 1985.

2.   Wright, J.V.   "Treatment of childhood asthma with parenteral vitamin B12, gastric reacidification, and attention to food allergy, magnesium and pyridoxine: Three case reports with background, and integrated hypothesis."
Journal of Nutritional Medicine, 1:277-282, 1990.

3.   Mathew, R. et al.   "The role of magnesium in lung diseases: Asthma and Allergy."
Magnesium and Trace Elements, 10(24):220-228, 1991-1992.

4.   Khilnani, G. et al.   "Hypomagnesemia due to beta 2-agonist use in bronchial asthma."
Journal of the Association of Physicians of India, 40(5):346, 1992.

5.   Rolla, G. et al.   "Reduction of histamine-induced bronchoconstriction by magnesium in asthmatic patients."
Allergy, 42(3):186-188, 1987.

6.   Collip, P.J. et al.   "Pyridoxine treatment of childhood asthma."
Annals of Allergy, 35:93-97, 1975.

7.   Ubbink, J.B. et al.   "The relationship between vitamin B6 metabolism and asthma."
Annals of the New York Academy of Sciences, 585:285-294, 1990.

8.   Weir, M.R. et al.   "Depression of vitamin B6 levels to theophylline."
Annals of Allergy, 65:59-62, 1990.

9.   Simon, S.W.   "Vitamin B12 therapy in allergy and chronic dermatoses."
Journal of Allergy, 2:183-185, 1951.

10.   Anibarro, B. et al.   "Asthma with sulfite intolerance in children: A blocking study with cyanocobalamin."
Journal of Allergy and Clinical Immunology, 90(1):103-109, 1992.

11.   Kreutner, W. et al.   "Bronchodilation and antiallergy activity of forskolin."
European Journal of Pharmacology, 111:1-8, 1985.

12.   Lichey, J. et al.   "Effect of forskolin on methacholine-induced bronchoconstriction in extrinsic asthmatics."
Lancet ii, p.167, 1984.

13.   Braquet, P.   "The ginkgolides: Potent platelet-activating factor antagonists from Ginkgo biloba. Chemistry, pharmacology, and clinical applications."
Drugs of the Future, 12:643-699, 1987.

14.   V Klein, P. V "Study on the inhibitory activity of Ginkgo biloba extract. PAF-induced platelet aggregation."
Therapiewoche, 38:2379-2383, 1988.

15.   V Kleijen, J. and Knipschild, P. V   "Ginkgo biloba."
Lancet, 340:1136-1139, 1992.



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