Published Articles and Reports

Doddabele Madhavi, PhD; Daniel Kagan, PhD: Integrative Medicine, Vol. 13, No. 3, June 2014

Doddabele Madhavi, PhD; Daniel Kagan, PhD; Venkatesh Rao, MD; and Michael T. Murray, ND: Natural Medicine Journal, April 4, 2013

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

Daniel Kagan, PhD; Doddabele Madhavi, PhD; Ginny Bank, MS; Kenneth Lachlan, PhD: 2009 Natural Medicine Journal 2(1), January 2010

Doddabele Madhavi, PhD; and Daniel Kagan, PhD: Integrative Medicine, Vol. 9, No. 1, Feb/Mar 2010

Charles A. Babbush, DDS, MScD; Daniel Kagan, PhD; Doddabele Madhavi, PhD; and Alexander Rubido, PhD: Integrative Medicine, Vol. 9, No. 1, Feb/Mar 2010

D.L. Madhavi Ph.D. Daniel Kagan Ph.D.: BioActives LLC Research Report October 2008

 

Bioavailability of a Sustained Release Formulation of Curcumin

Doddabele Madhavi, PhD; Daniel Kagan, PhD
Integrative Medicine, Vol. 13, No. 3, June 2014
Objective:

The objective of this study was to compare the relative bioavailability of MicroActive Curcumin, an advanced, micronized formulation of curcumin that is 25% curcuminoids in a sustained release matrix, with that of an unformulated, 95% pure curcumin powder.

 

Study Design:

A dissolution study compared the solubility of the formulated and the unformulated curcumin. The research team also performed a single-dose, 12-h, crossover uptake study with 10 participants and a highdose tolerability and accumulation study with 3 participants, comparing the 2 forms of curcumin.

 

Results:

The dissolution study indicated that the sustained-release curcumin had greater dissolution for 12 h at all points tested, compared with the unformulated curcumin. Very little of the unformulated curcumin powder had been released at the end of the 12 h. The results of the single-dose uptake study indicated that the sustained-release formula was 9.7 × more bioavailable than the unformulated powder (P < .001, paired t test). Additionally, all participants showed uptake from the sustained-release formulation. That formulation also resulted in significant increases in the plasma demethoxylated curcuminoids, but the research team did not observe the same increases for the unformulated curcumin powder. The sustained-release formulation was well tolerated, without adverse effects in the highdose tolerability study.

 

Conclusions:

Formulation of micronized curcumin in a combination of surfactants, oils, and polymers improves the absorption of curcumin. In addition, the unique plasma demethylated curcuminoid profile may enhance the therapeutic effects of MicroActive Curcumin not observed with unformulated curcumin at moderate and well-tolerated doses. MicroActive Curcumin was well tolerated, without any adverse effects in a high-dose tolerability study. These properties have the potential to make high-dose curcumin supplementation more accessible through simplified incorporation into food and beverage preparations.

Email Daniel Kagan to request reprint in pdf format.

 

A Pilot Study to Evaluate the Antihypertensive Effect of a Celery Extract in Mild to Moderate Hypertensive Patients. Original research suggest celery extract may decrease blood pressure.

Doddabele Madhavi, PhD; Daniel Kagan, PhD; Venkatesh Rao, MD; Michael T. Murray, ND
Natural Medicine Journal, April 4, 2013
Objective:

To evaluate the efficacy of a standardized extract of celery seed, 150 mg/d, supplying 85% 3-n-butylphthalide (3nB) in mild to moderate hypertensive patients.

 

Study Design:

A single-arm study of 30 mild to moderate hypertensive patients given the test medication following a 7-day wash out period. The primary clinical assessment was the effect on blood pressure at week 3 and week 6. Secondary measures were fasting blood levels of total cholesterol, LDL cholesterol, HDL cholesterol, VLDL cholesterol, free fatty acids, and serum electrolytes (i.e., sodium, potassium, calcium).

 

Results:

There was statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 3 and week 6 compared to baseline. The change at week 6 for the SBP was 8.2 mmHg (SD=3.6, P<0.005) and for the DBP was 8.5 mmHG (SD=2.9, P<0.005).

 

Conclusions:

The results from this pilot study suggest that celery seed extract may have clinically relevant blood pressure, lowering effects, indicating that additional clinical research is warranted.Email Daniel Kagan to request reprint in pdf format.

 

Coenzyme Q10: Clinical Update and Bioavailability

Ginny Bank, MS; Daniel Kagan, PhD; Doddabele Madhavi, PhD
Journal of Evidence-Based Complementary & Alternative Medicine 16(2) 129-137
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.

 

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
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-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.

BioActives Publications, Updated July 6, 2015