Mirtogenol™….is It The Real Deal?
Written by Larry J Alexander OD FAAO Friday, 08 February 2013
Glaucoma is a multifaceted disorder as described in the up-coming series…Challenging the Glaucoma Archetype in eyelessons.com. The standard methods of treatment revolve around lowering the IOP to an acceptable range….whatever that may be. That pressure-lowering approach is a paradigm that really does not recognize all of the components of the glaucoma issues yet it remains the standard of care. The glaucoma concept as a systemic disorder is addressed in the companion piece in eyelessons.com but the topic of Mirtogenol™ deserves a separate highlight. Mirtogenol™ is a supplement that has been suggested as being potentially beneficial in the management of glaucoma. This is a report of this product and should neither be considered an endorsement nor an encouragement to prescribe.
From a blog at http://www.online-eye-info.com/Mirtogenol.html responding to the potential benefit of Mirtogenol™ for the potential management of glaucoma.
“clinical ophthalmology is not considered a top journal-i never heard of it. so i cant comment on the quality of the research printed there.”
“no respectable ophthalmologist would rely on a natural supplement instead of standard medications; at the most, we would add it.”
These quotes set the stage for a discussion on the compound. Certainly there will be controversy. “As we all remember….at least those of us old enough to remember….that recommending nutritional supplementation to minimize the risk of macular degeneration is without substance! Well maybe things are a bit different now as the paradigm has shifted.”
Mirtogenol™ is a combination of two phenolic extracts extracted from bilberry, (Mirtoselect®) (standardized to 36% anthocyanins; USP 31) and French maritime pine bark (Pycnogenol® ) (standardized to 70% procyanidins; USP 31). A phenolic extract is any of a class of organic compounds with a hydroxyl group attached to a carbon atom in a ring of an aromatic compound. Mirtoselect® is reported to be a powerful antioxidant and to promote benefits for retinal capillaries. Pycnogenol® is likewise an antioxidant but is reported to have the effect of improving blood viscosity by reducing plasma endothelin-1 and enhancing the activity of nitric oxide. http://www.online-eye-info.com/mirtogenol.html
Previous work in the area of mechanism of action of Pycnogenol® was in the control of capillary leakage in diabetic retinopathy. Pycnogenol® has been tested for treatment and prevention of retinopathy in five clinical trials with a total number of 1289 patients since the late 1960's. In a review it was reported that all of these studies unequivocally showed that Pycnogenol® retains progression of retinopathy and partly recovers visual acuity. It was also concluded that Pycnogenol® was shown to improve capillary resistance and reduce leakages into the retina. 1 Other studies illustrated control of capillary leakage and decreased retinal bleeding associated with Pycnogenol® . 2-3
Pycnogenol® has also been reported to improve endothelial function which is altered in POAG. 4-5 Mirtoselect® is reported to counteract the hyperpermeability of ciliary capillaries…acting on aqueous secretion. 6
Mirtogenol™ and Glaucoma
While not universally accepted as standard of care in the management of glaucoma, research has been conducted on the effects and benefits of the utilization of Mirtogenol™. In a 2008 controlled study, Steigerwalt et al analyzed 38 asymptomatic subjects with intraocular hypertension of 22 mm Hg to 26 mm Hg. After 2 months of supplementation of 20 patients with Mirtogenol™(80 mg Pycnogenol® and 160 mg Mirtoselect) , they reported that IOP was significantly lowered compared to that of untreated controls. In the treated group the IOP baseline was 25.2+/-3.1 mm Hg and the control was 24.6+/-2.8 mm Hg.
At two months the treated group IOP dropped to 22.2+/-2.1 mm Hg or an 11.9% decline compared to the untreated group with an IOP drop to 24.0+/-2.6 mm Hg or a 2.4% drop. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447819/
Affect of Mirtogenol™on IOP in Ocular Hypertensives
The group also reported no side effects and also reported improvement in systolic and diastolic blood flow in the central retinal, ophthalmic and posterior ciliary arteries. The table below reflects the percentage increase in blood flow velocity from baseline in the CENTRAL RETINAL ARTERY (CRA), the OPHTHALMIC ARTERY (OPH) and the POSTERIOR CILIARY ARTERY (PCA). All vessels measured demonstrated an increase in velocity from 13% for systolic CRA to 39% for diastolic CRA. It is noteworthy that the maximum effect occurred between months two and three.
Affect of Mirtogenol™on Color Doppler Velocity Measurements of Ocular Arteries in Ocular Hypertensives
The rationale for use of Mirtogenol™ for intraocular pressure issues summarized in this study is:
- Normalization of high intraocular pressure occurs by
lowering aqueous humour release from ciliary body
- Improved ocular blood flow occurs with the aim of reducing
imbalance of aqueous humor inflow and outflow
- Both Pycnogenol® and Mirtoselect® function to decrease the filtration of
liquid across capillary membranes
- Pycnogeno®l enhances capillary endothelial function
Bilberry extract Mirtoselect® was demonstrated to improve
ciliary body function in animal testing. 7
The associated effect of Mirtogenol™ has been proposed to be secondary to the vaso-constrictory peptide, endothelin-1. This has been found elevated in the aqueous of patients with POAG. Likewise there has been evidence of endothelial nitric oxide being involved in the regulation of ocular vascular tone. 8-9
In other studies Pycnogenol® has previously been shown to enhance the generation of endothelial nitric oxide in healthy humans as well as lowering plasma endothelin-1 in patients with type II diabetes. 5, 10 Mirtoselect® bilberry extract also was found to stimulate arteriolar vasomotion in preclinical tests. 11
The second clinical study conducted by Steigerwalt et al in 2010 assessed the effect of a reduced dosage of Mirtogenol™ on seventy-nine asymptomatic ocular hypertensive patients in three groups receiving the supplement, latanoprost, or both. The baseline IOP values were 37.7+/-2.0 mm Hg in the latanoprost group, 38.1+/-2.0 mm Hg in the Mirtogenol™ group and 38.0+/-3.1 mm Hg in the combined group. Most patients had previously used latanoprost but had discontinued use in the past. Mirtogenol™(40 mg Pycnogenol® and 80 mg Mirtoselect) was dosed to the patients in the selected groups. The results on the effect on IOP are shown below. Latanoprost quickly lowered the IOP 29% within 4 weeks to stability with Mirtogenol™ alone taking up to 20 weeks plus to achieve a similar effect of 20%. The combination of both, however was even more effective at lowering IOP by 42% at 20 weeks.
IOP LOWERING EFFECT OF MIRTOGENOL™, LATANOPROST, AND A COMBINATION OF THE TWO IN A COHORT OF ASYMPTOMATIC OCULAR HYPERTENSIVE PATIENTS
The diastolic and systolic blood flow velocity was also measured in the cohort. The diastolic flow is reported below. At the end of 24 weeks the report demonstrates an increase from baseline of 140% on Mirtogenol alone, an increase of 38% on Latanoprost alone and an increase of 192% with a Combination for diastolic blood flow.
DIASTOLIC BLOOD FLOW OF THE CENTRAL RETINAL ARTERY IN CM/S WITH MIRTOGENOL™, LATANOPROST, AND A COMBINATION OF THE TWO IN A COHORT OF ASYMPTOMATIC OCULAR HYPERTENSIVE PATIENTS
The systolic flow is reported below. At the end of 24 weeks the report demonstrates an increase from baseline of 17% on Mirtogenol alone, an increase of 24% on Latanoprost alone and an increase of 39% with a Combination for diastolic blood flow.
SYSTOLIC BLOOD FLOW OF THE CENTRAL RETINAL ARTERY IN CM/S WITH MIRTOGENOL™, LATANOPROST, AND A COMBINATION OF THE TWO IN A COHORT OF ASYMPTOMATIC OCULAR HYPERTENSIVE PATIENTS
A summary of the study would include that the additive effects of Latanoprost and Mirtogenol™ for lowering IOP and increasing blood flow velocity appear to really start to occur at about weeks 4 to 6. The combination of the effects is more dynamic than the individual effects alone. In the discussion the authors conclude “The improved ocular blood flow shown in this study supports the assumption that the dietary supplement may exert an action on lowering IOP by decreasing humor inflow. Yet, it will remain difficult to identify whether the supplement affects outflow pathways, or aqueous humor inflow, or both.” They also report “We speculate that the effect of the combination of Mirtoselect and Pycnogenol predominantly affects vascular responses involved in ocular hypertension by normalizing capillary filtration of the ciliary body.” 12
The scientific evidence for the utilization of the supplement Mirtogenol™ , a combination of two phenolic extracts extracted from bilberry, (Mirtoselect®) (standardized to 36% anthocyanins; USP 31) and French maritime pine bark (Pycnogenol® ) (standardized to 70% procyanidins; USP 31), for the management of IOP and blood flow in glaucoma has been reviewed. It would be difficult to extrapolate a wide scale recommendation for the utilization of this product from the data presented. While the data presented is certainly compelling, it should be noted that it has been presented by one series of investigators and has not totally stood up to the scientific challenge. None-the-less with the cost of the supplement at about $1/day and the results of the two provocative studies, we will leave the decision to investigate the utilization of this supplement for the management of glaucoma up to the practitioner. There is no question that POAG suffers from low compliance from patients and anything that has the potential to help in that compliance may be of benefit.
Clearly, further work must be done to take this to the level of recommending this as standard of care. Likewise, the practitioner must be aware of this opportunity for their patients as the patients will search options on their own. If they look at the blogs regarding this issue there is more positive response than negative.
Sources for obtaining Mirtogenol™ include but are not limited to:
The author has no association with any of these sources nor validates the quality of any of these products
- Meso-Zeaxanthin: A summary of the research
- Ocular Side Effects of Systemic Drugs and Nutraceuticals
- Pycnogenol® For Diabetes Mellitus
About the Author(s)
Dr. Alexander (1948-2016) was a 1971 graduate of Indiana University School of Optometry. He served in the US Navy then served as a Professor at the University of Alabama Birmingham School of Optometry. Larry contributed to a number of chapters in textbooks and has published three editions of Primary Care of the Posterior Segment, as well as contributed to the professional literature. He also lectured extensively in the area of ocular and systemic disease. His areas of special interest included dysfunctional tear syndrome, glaucoma and macular degeneration. His lessons are the basis for this site and he will be dearly missed.