Published Articles and Reports

Coenzyme Q10: Clinical Update and Bioavailability
Ginny Bank, MS; Daniel Kagan, PhD; and Doddabele Madhavi, PhD Journal of Evidence-Based Complementary & Alternative Medicine16(2) 129-137

A Study on the Bioavailability of a Sustained-release Coenzyme Q10-β-Cyclodextrin Complex
Doddabele Madhavi, PhD; and Daniel Kagan, PhD Integrative Medicine • Vol. 9, No. 1 • Feb/Mar 2010

The Efficacy of Perfect Smile Toothpaste Containing Coenzyme 10-β-Cyclodextrin Inclusion Complex in Reducing Mild to Moderate Gingivitis By Charles A. Babbush, DDS, MScD; Daniel Kagan, PhD; Doddabele Madhavi, PhD; and Alexander Rubido, PhD Integrative Medicine • Vol. 9, No. 1 • Feb/Mar 2010

MicroActive® Lutein Highly Bioavailable Lutein Complex: Nutritional Supplements and Food Use
D.L. Madhavi Ph.D. Daniel Kagan Ph.D. BioActives LLC Research Report October 2008

Coenzyme Q10: Clinical Update and Bioavailability

Ginny Bank, MS; Daniel Kagan, PhD; Doddabele Madhavi, PhD

Abstract
CoenzymeQ10 (CoQ10) supplementation has been reported to be beneficial in treating a variety of health conditions and diseases, with more than 200 clinical trials investigating its use as a drug or dietary supplement. Numerous reviews of the safety and clinical potential of CoQ10 have been published. Successful treatment and efficacy is dependent on the bioavailability of CoQ10, which is well known to be poor because of its lipophilic nature and large molecular weight. A number of recent clinical trials on CoQ10 have investigated new formulations of CoQ10 for improvements in absorption and bioavailability. This review provides an update of clinical efficacy trials using CoQ10 and describes recent advances in formulation technology to improve the bioavailability of CoQ10. The authors also discuss a new method to improve the standards of reporting the bioavailability results of such advanced CoQ10 formulations to help clinicians and consumers make informed decisions.

"Universal" and "Reliable" Bioavailability Claims: Criteria That May Increase Physician Confidence in Nutritional Supplements Daniel Kagan, PhD; Doddabele Madhavi, PhD; Ginny Bank, MS; Kenneth Lachlan, PhD

2009 Natural Medicine Journal 2(1), January 2010

Abstract
The benefits derived from nutritional supplements are directly related to their bioavailability, yet the dietary supplement industry lacks well-defined standards to ensure adequate bioavailability. Clinical studies of oral bioavailability report data of mean area under the curve (AUC) and standard deviations comparing groups following administration of the active ingredient by oral route over a defined time period. Comparisons primarily focus on statistical descriptions of mean AUC differences between the groups, while often failing to compare or discuss their standard deviations or inter-subject variance. This failure leaves open the question of whether or not an individual in a group is likely to experience the benefits described by the mean-difference comparisons. Further, even if this issue were discussed, it would be difficult to communicate meaning of these inter-subject variances to consumers and/or their physicians.

One way to resolve this problem might be to define "reliable" absorption results as incorporating 84% of the population and "universal" absorption as those incorporating 98% of the population. These indicators can be readily calculated using reported means and standard deviations. Examples are taken from the development of coenzyme Q10 and carotenoid products, demonstrating that some products reported to be "more bioavailable" are in fact too unreliable by these standards, thereby not providing physicians the information needed to make informed decisions.

The Efficacy of Perfect Smile Toothpaste Containing Coenzyme Q10–b-Cyclodextrin Inclusion Complex in Reducing Mild to Moderate Gingivitis

A Study on the Bioavailability of a Sustained-release Coenzyme Q10-β-Cyclodextrin Complex Daniel Kagan, PhD; Doddabele Madhavi, PhD; Ginny Bank, MS; Kenneth Lachlan, PhD

Doddabele Madhavi, PhD; and Daniel Kagan, PhD

Integrative Medicine • Vol. 9, No. 1 • Feb/Mar 2010

Objectives: The objective of this study was to compare the relative bioavailability of a coenzyme Q10 (co-Q10)-β- cyclodextrin inclusion complex (MicroActive Co-Q10 complex by BioActives in Worcester, Massachusetts) with 2 commercially available formulations: a hard gelatin capsule of crystalline co-Q10 and an oil-solubilized co-Q10 softgel containing a proprietary absorption enhancer.
Materials and Methods: The first study compared the MicroActive Co-Q10 complex to both a crystalline product and a solubilized product. Five subjects were included in a 24-hour crossover design with a single dose of 180 mg of co-Q10. The second study compared the MicroActive Co-Q10 complex with the solubilized form, using 60 mg of co-Q10 1°—/d. The study had an acute phase (0-24 h, single dose) and a 21-day accumulation phase, with 11 subjects per group.
Results: The results of the first study indicated that the MicroActive Co-Q10 complex showed a sustained release and that its bioavailability was significantly better than the crystalline form by a factor of 3.7 (P<.0001). The inter-subject variance in the bioavailability of the solubilized form was significantly greater than in the other 2 forms (P<.05).
In the second study, the 0- to 24-hour absorption confirmed the sustained-release property of the MicroActive® Co-Q10 complex as well as the significantly higher and uniform bioavailability (P<.006). All the subjects in the accumulation phase of the study showed a minimum of doubling in the plasma co-Q10 levels after 21 days of MicroActive Co-Q10 supplementation, which represents a 100% response rate. The solubilized form showed a response rate of only 44%, again confirming the greater and more uniform bioavailability of the MicroActive product.
Conclusions: Sustained release MicroActive Co-Q10 is more universally bioavailable, thereby improving its ability to deliver both maintenance and therapeutic doses of co-Q10.

The Efficacy of Perfect Smile Toothpaste Containing Coenzyme Q10–β-Cyclodextrin Inclusion Complex in Reducing Mild to Moderate Gingivitis Charles A. Babbush, DDS, MScD; Daniel Kagan, PhD; Doddabele Madhavi, PhD; and Alexander Rubido, PhD

2010 Natural Medicine Journal 2(5), May 2010

Abstract
Objective: Coenzyme Q10 (CoQ10) has been shown to be an effective ingredient in controlling periodontal disease when used in supplement form or applied directly to the site. This study explored its practical application in a toothpaste.
Methods: To overcome the hydrophobic and poor absorption characteristics of CoQ10, a more bioavailable, water-dispersible, commercially available CoQ10–b-cyclodextrin inclusion complex (MicroActive® CoQ10) was used in a toothpaste base at 1.5% concentration. A parallel-group, double-blind study tested a commercially available fluoride toothpaste with the CoQ10–b-cyclodextrin complex manufactured by Perfect Smile Corporation against the same formulation without the complex, as the control. After participants brushed twice daily, the salivary immunoglobulin (sIgA) was measured at 4 and 8 weeks using the GeneEx, Inc., Periodontitis ELISA kit. Oral tissue examinations were performed at the onset and 8-week visits. The study had 30 participants (15 in the experimental group and 15 in the control group). Positive results in the ELISA analysis were defined as a 20% or greater reduction in the sIgA level.
Results: At the end of 4 weeks, 66.6% of the experimental group showed a 20% or greater decrease in the sIgA while only 16.6% of the control group showed the same improvement (P<0.036). At the end of 8 weeks 66.6% of the experimental group showed improvement by this standard , while 33.3% of the control group showed improvement but this did not reach statistical significance. Measures of improvement in the gingiva related to changes in the degree of edema at study onset versus 8 weeks revealed significant improvement in the experimental group.
Conclusions: CoQ10–b-cyclodextrin complex toothpaste formulation significantly reduced moderate gingivitis. Further studies are warranted with increased sample size and also to test the efficacy on a younger population. The CoQ10–b-cyclodextrin complex has the potential to be incorporated into other oral care products such as gingival massage gels and chewing gum, which result in longer exposure times and improved uptake of CoQ10 by the gingiva.

MicroActive® Lutein Highly Bioavailable Lutein Complex: Nutritional Supplements and Food Use D.L. Madhavi Ph.D. Daniel Kagan Ph.D.

BioActives LLC Research Report October 2008

Conclusion
The results support the conclusion MicroActive® Lutein is not only more bioavailable, but also more reliable because it improves total uptake and dramatically improves the uptake of poor absorbers – subjects who may have greater risk for macular degeneration due to age and other factors associated also with poor absorption. From a business perspective, more of lutein in the product will be absorbed making for more efficient use if raw material costs. More importantly, more customers will absorb the lutein thereby experiencing its benefit and being retained as customers, making for more efficient use of marketing/sales costs.