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What is it all about?

The realization that inhibiting the pro-inflammatory enzyme 5-lipoxygenase and its lipid metabolites, the leukotrienes, is essential for the successful management of most illnesses is becoming well established.1 The market for synthetic leukotriene inhibitors (LTI'S) (such as Singulair, Ziflo, etc) in the treatment of asthma and allergies is in the billions of dollars (!), attesting to the need for this class of drugs, their usefulness and not least of all their ease of use. Their applicability is still largely ignored in the treatment of arthritis, colitis, and cancer, etc, to the point that one author calls this a "neglected frontier." 2

With their increased spread has come the awareness of their side effects. This has given pause to the unrestricted enthusiasm for synthetic LTI'S. Liver toxicity, anxiousness, depression and even suicidal tendencies seem to be rare but well established occurrences. 3

Is there an alternative?

Sadly, most doctors and their patients do not seem to be aware of the existence of newer boswellia extracts that are potent 5-lipoxygenase and leukotriene synthesis inhibitors. 4 The gum resin boswellia has been known for a very long time to be anti-inflammatory. 5 However, its most active fraction, the 3-O-acetyl-11-keto-ß-boswellic acid, AKBA, has only recently been offered in 90% pure concentration. This now constitutes a viable natural potential alternative to the leukotriene inhibitors: hopefully all the good results with none of the side effects. The applicability is very large: ranging from arthritis, colitis, asthma, skin diseases and allergic conditions to vascular problems, neurological concerns and cancers (particularly of the prostate, pancreas, breast and bladder). Since all the above conditions entail in their pathophysiology the 5-lipoxygenase pathway, not to treat with AKBA leaves the patient only partially taken care of. With the novel 90% concentration the results are significantly better than in the past.

We will explore how and when to best administer this new Gold Standard LTI's substitute, a nutritional formula called AKBA Plus™, and how to dispense it as a stand alone or in combination with other therapies.

The dosage problem

The commonly available formulations usually give no indication about the actual AKBA fraction content. Saying that the formula has "65% boswellic acids" is meaningless for many reasons (to be discussed elsewhere in more detail) but one of them is that the AKBA content can be anywhere from zero to about 3%. The True Botanica preparation, AKBA Plus™, is standardized to 90% AKBA. Every batch is tested by an independent laboratory. (The product is manufactured in a GMP certified facility).

Each capsule contains 54mg AKBA which compares favorably to the 3 to 9 mg of AKBA present in most other formulations.

This high dosage amount/capsule makes it possible for the first time to achieve the plasma levels that the better clinical and experimental studies indicate are necessary for obtaining optimal results. If one takes into account the known AKBA IC50 for various physiologic events, the distribution volume, pharmacokinetic data, etc. a daily amount of about 150-300 mg AKBA would seem indicated. This means a patient needs in general three to six capsules/day of the AKBA Plus™. This is a reasonable number of capsules to be expected of a patient to take on a daily basis. Compliance is usually very good. To ingest the same daily AKBA amount from the above characterized common market formulas one would need perhaps 18 (!) daily capsules--clearly an impossible task.

How to administer AKBA Plus™

The following comments are based on the experience of over 1 million doses administered so far in several outpatient medical clinics.

In general, starting with one capsule three times daily is adequate.

A common mistake for the patient is to take several capsules at once in order to "get it over with". Considering, however, that the half life is about 5 hours this leads to inadequate blood levels through most of the day. The patient should be encouraged to take one dose every 8 hours as directed.

AKBA Plus™ can be swallowed safely on an empty stomach. Contrary to other preparations we have observed no gastric or digestive irritation following AKBA Plus™.

For better absorption it is best given, however, with a slightly fatty meal, that includes, for example, some oil in the salad dressing, butter, nut butter, eggs, milk, and similar foods.

"Sensitivity" to AKBA

Occasionally, if a greater daily dosage is recommended, f.ex. 6 capsules daily or more, constipation has been noted. This is very rare probably because most patients have an intrinsically inflamed intestinal mucosa which under the influence of AKBA Plus™ then returns to a normal function.

Extremely rarely, especially in female patients, headache has been reported following ingestion of even one single dose. The capsule should then be opened and half the powdery content mixed with a vehicle suitable to the patient's taste- apple sauce, etc- and swallowed. No complete mixing of the powder in water should be expected. (Boswellia gum resin is soluble completely only in alcohol. Water is only a carrier.)

Periodically the situation is encountered where a "universal reactor" patient, a person who reacts sensitively and paradoxically to a large number of substances is given AKBA precisely in order to fight allergies but the person is reacting to this extract as well. In this case the "dot dose" method has worked very well, i.e. having the patient start with literally "a dot's worth" of the powder. Every day the dose can be increased until habituation occurs and the patient can take the ingredient with no ill effects.

Individual paradoxical reactions can occur to AKBA as with any other substances. The patient will then complain of an "allergic reaction" to the ingredient. If one determines that such has in fact occurred- especially in immediate type hypersensitivity- future dosages should not be administered. Most of the time, however, it is an unexpected reaction such as, for example, nausea after a first dose, unpleasant after taste, mild heart palpitations, etc. instead of the desired symptom relief. This is most easily remedied by temporarily suspending or reducing administration of the capsules and restarting again with a lower dosage after a week or so.

Additional examples of dosage suggestions follow based on selected clinical conditions †

Allergies

AKBA Plus™ can be taken continuously throughout the year if needed or only at the outset of an allergic season. Usually even 1 capsule twice a day is sufficient. A loading dose of several additional capsules can be taken when an acute exposure to an allergen has occurred - cat, food, pollen, etc.; moreover, many patients report, that after several months of taking AKBA Plus™ they have been able to reduce the regimen and eventually take only an occasional weekly or less dose when exposed continuously to the offending allergen.

Asthma

AKBA Plus™ is not a replacement for immediate bronchodilators and other asthma controllers. They are meant to create a stable environment where the use of steroids, inhalers and other medications can be reduced or eliminated. Three to four capsules daily are of benefit. Ideally, after an initial time of giving an inhaler together with the AKBA, slowly a reduction or discontinuation of the inhaler can be achieved- under careful monitoring. Other times, when the patient's symptoms were not adequately controlled, as in a particularly severe case, the AKBA Plus™ can be administered concomitantly with the medications.

AKBA Plus™ can also be given in larger amounts, (2-3caps at one time or 2caps x 3 in one day) as a loading dose, before a strenuous activity, such as one leading for example to exercise induced asthma.

AKBA Plus™ can be added to other appropriate modalities in an emergency situation, but not alone, in order to reduce the severity of the emergency. (LTI's in general have been known to shorten the stay in the ED of asthmatics.) 3

Arthritis

Very often giving initially just AKBA Plus™ will suffice to control the symptoms of an arthritic joint. In that case most of the inflammation will have originated from the 5-lipoxygenase pathway. If symptoms persist, however, in all likelihood then additionally the COX enzyme is involved and then an appropriate natural (curcumin, f.ex.) inhibitor needs to be added or a NSAID (like ibuprofen, etc). Very often the more likely situation will be encountered where a patient already taking customary anti-inflammatories will come to one's attention because of inadequate relief asking for another option. Giving them the 5-lipoxygenase inhibitor is of greatest benefit.

Digestive conditions

In functional bowel diseases administering 1 capsule three times daily is sufficient. If the patient is sensitive to the capsule material itself, which can happen more frequently in intestinal difficulties, the free powder can be mixed with some acceptable food and swallowed.

Pediatric Use

Youngsters >10 years of age administer as in adults.
In 5-10 year olds: 1/2 cap 2-3x daily.
In 1-5 year olds: 1/4 cap x 2-3daily.
In babies: 1/8 cap 3 x daily (or a "pinch").
Start with the above recommendations and titrate upwards as needed to reach desired results.

Cancers

AKBA has been shown in recent experimental studies to be detrimental to the growth of several neoplastic cell lines. 6, 7 Nutritional use of AKBA Plus™ in clinical cases is relatively new but daily dosages of 2 capsules three times daily have been well tolerated. Depending on the severity of the case higher amounts can be beneficial.

Cardiovascular and other chronic illnesses

5-lipoxygenase over expression is now known to occur in cardiovascular, neurologic, respiratory and dermatological conditions. 8 The use of AKBA Plus™ would thus be justified in such chronic conditions in the form of a low dose daily long term therapy. Giving one single dose on a daily basis, along with for example, the appropriate antihypertensive or antilipidemic medication might constitute the standard of care in times to come.

Safety and Toxicology

Boswellic acids (BA's) are considered GRAS (generally regarded as safe) nutritional substances.
Considering that BA's have been administered for thousands of years both orally and topically, not to mention their inhalation as incense, this in itself is not surprising.

Blood tests and tissue analysis have never revealed permanent toxic effects. Boswellic acids, even in concentrated forms, have never been shown to be skin irritating.

The therapeutic range of AKBA is extremely high. Reported clinical oral amounts given on a daily basis for prolonged periods of time have never been above 1000mg pure AKBA. In animal experiments, IC50 amounts, let alone LD50's, have been 10x higher and above. 8

Purified BA's, like AKBA, have been shown to be non-selective inhibitors of the drug metabolizing CYP enzyme family (cytochrome P450). 9 Although to date the physiologic significance of this inhibition has not been established the potentially higher plasma levels of other drugs administered at the same with AKBA should be kept in mind. No negative AKBA - drug interactions have been reported to date.

For more information:

Please contact the company and request the comprehensive AKBA report, professional catalog, etc.
The Plus Line™ is exclusively distributed through licensed prescribers.

True Botanica offers phone conference calls for doctors interested in learning more about True Botanica products or wanting additional training in complementary medicine.

† AKBA Plus™ is a nutritional supplement! It is intended to strengthen the normal physiologic processes of the body. The use of the word "prescribed" is meant here in the same sense as when a diet is "prescribed" to a patient. While a good dietary program may ideally prevent an illness or lead to an improvement in the health condition, as would be expected from any good therapeutic advice, it is not meant to replace needed medical procedures.

References

1. Rubin P, Mollison KW. Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. Prostaglandins and Other Lipid Mediators. 2007;83( 3 SPEC. ISS.):188-197.
2. Whitehouse MW, Rainsford KD. Lipoxygenase inhibition: The neglected frontier for regulating chronic inflammation and pain. Inflammopharmacology. 2006;14( 3-4):99-102.
3. Scow DT, Luttermoser GK, Dickerson KS. Leukotriene inhibitors in the treatment of allergy and asthma. American Family Physician. 2007;75( 1):65-70.
4. Poeckel D, Werz O. Boswellic acids: Biological actions and molecular targets. Current Medicinal Chemistry. 2006;13( 28):3359-3369.
5. Ammon HPT. Boswellic acids (compounds of francincense) as active principles for the treatment of chronic inflammatory diseases. Wiener Medizinische Wochenschrift. 2002;152( 15-16):373-378.
6. Syrovets T, Gschwend JE, Büchele B, et al. Inhibition of IκB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo. Journal of Biological Chemistry. 2005;280( 7):6170-6180.
7. Zhao W, Entschladen F, Liu H, et al. Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells. Cancer Detection and Prevention. 2003;27( 1):67-75.
8. Poeckel D, Werz O. Boswellic acids: Biological actions and molecular targets. Current Medicinal Chemistry. 2006;13( 28):3359-3369.
9.  Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction. Journal of Chromatography A 2006;1112:255-62.