Close

Strategic product development for a personalized, practitioner-driven approach to cardiovascular, metabolic, and cognitive health

Developing innovative dietary supplement products for nutrition-trained or functional medicine practitioners who engage in a personalized approach to patient management presents interesting challenges and opportunities.

How do you develop, manufacture (under strict GMP compliant conditions), and properly study dietary supplements aimed at a population of n=1?
 
A central part of our approach at Atrium Innovations is to view these not just as products, but as the clinical tools used by health care practitioners to improve the health of their patients.  In other words, it is the application of these well-designed clinical tools that allows the practitioner to manage the patient as an individual, as opposed to a diagnosis.

The functional or P4 practitioner utilizes comprehensive laboratory testing and other intake data to design a treatment protocol around the patient’s individual needs, influenced by genetic, biochemical, environmental, lifestyle, social, or other factors.  A personalized approach to patient management, then, demands a full tool box. 
Three key strategies are required to provide effective tools. 

The first strategy is careful attention to nutrient forms, doses, and finished product formats.  For example, we focus on bioactive ingredient forms, such as methylated vitamins, a quality feature that separates many health care professional products from the mass market offerings.  Such ingredients tend to be more expensive, but are preferred by the practitioner. 

Metafolin, a 5-methyl folate as an alternative to folic acid, is one example of a vitamin form preferred by many practitioners who embrace a personalized approach to patient management.  This form of folate circumvents well-established genetic polymophisms that may interfere with the utility of standard folic acid.  Identifying such polymorphisms and providing targeted supplementation is a very clear example of personalized nutrition. 

Innovations in alternative product formats, including liquids, sprays, powders, or matrices that improve ingredient stability or bioavailability, are also important differentiators in meeting the needs of the health care practitioner and his or her individual patients.

Practitioner-driven formulations
A second strategy we employ to ensure the development of clinically relevant and effective products is the use of practitioner-driven formulations.  We work with a large body of medical advisors with backgrounds in family medicine, naturopathy, bariatrics, functional medicine, optometry, psychiatry, anti-aging medicine, dietetics, neurology, and pharmacology.  These practitioners bring a wide spectrum of expertise in product areas such as probiotics, botanicals, vitamins and minerals, and proteins, as well as condition-specific approaches to hormonal support, cardiometabolic health, sports nutrition, and more. 

Contributions by qualified medical advisors make a significant impact on the development of a strategic product development pipeline.  In essence, working closely with practitioners allows us to bring clinical experience from the bed side to the white board to the bench and, ultimately, to the bottle.

Finally, innovative product development must be grounded in rigorous science.  Clinical studies, while somewhat reductionist on their surface (ie, capturing statistical significance across a population and then applying the result to an individual), provide incremental insights that eventually generate an idea swell that drives innovation.  The tools we develop from such advancements can then be applied to a personalized approach to patient management.

Research
One example of this approach to nutritional research is our Applied Clinical Research Program on Cardiometabolic Health.  The metabolic syndrome, characterized as obesity and associated chronic risk factors, such as dyslipidemia, hypertension, and impaired fasting glucose, confers an increased risk for cardiovascular disease, cardiac events, type 2 diabetes, and cognitive decline, as well as related mortality.  These risk factors are well established to be modifiable by nutrition and lifestyle interventions, making the metabolic syndrome an attractive target for researching the potential health benefits of natural bioactives.

In order to develop nutritional strategies to prevent or manage the symptoms of metabolic syndrome, we launched a comprehensive research program in collaboration with one of our academic partners, the Institute of Nutrition and Functional Foods at Laval University in Quebec, Canada.  The overarching objective of our program is to better understand and manage common factors linking cardiovascular, metabolic, and cognitive health, including low-level, or silent,  inflammation, oxidative stress, endothelial dysfunction, and insulin resistance.

Polyphenols
Central to our efforts is a robust ongoing investigation into the cardiometabolic health benefits of polyphenols.  Polyphenols are present in most foods of plant origin, including fruits (especially berries), vegetables, cocoa, coffee, tea, wine, and spices.  The health benefits of these foods are attributed, in large part, to their providing a diverse spectrum of polyphenol compounds, including flavonoids (anthocyanins, catechins, flavonols, flavanones, and isoflavones), curcuminoids, stilbenes, and tannins such as proanthocyanidins.  Understanding the health benefits of specific polyphenol compounds is an emerging area of intense research, including our own. 

In 2013, we published study examining the effects of type A proanthocyanidins from cranberries on promoting endothelial function in healthy athletes.  Consumption of a cranberry-rich polyphenol blend increased flow-mediated dilation (FMD) of the  brachial artery, a measure of endothelial response, by 2.8% [1].  In a systematic review and meta-analysis by Ras and colleagues of 23 studies and over 14,000 subjects, the pooled overall risk of a cardiovascular event was reduced by 8% for every 1% increase in FMD [2].  

A recently concluded clinical trial in overweight subjects with insulin resistance (pre-diabetic) has demonstrated a remarkable protective effect of strawberry and cranberry extracts in promoting insulin sensitivity compared to placebo control and preventing a hyperinsulinemic response immediately following a glucose load.  Such results are very promising indications of a role for dietary or supplemental polyphenols in attenuating the progression from early stage insulin resistance to type 2 diabetes.  

Furthermore, among foods rich in polyphenols, blueberries have been identified for their particular benefits in slowing age-associated memory and motor decline through potential mechanisms of reducing oxidative stress, inflammation, and/or altering neuronal signaling.  Our preclinical results support such a role for blueberry and grape extracts in improving memory and learning functions in aged animals, and a 200-subject, 6-month clinical investigation is underway.

Taken together, these results support both the general and specific health benefits of polyphenols in mitigating the pathophysiology of the metabolic syndrome and associated conditions.  These findings suggest an role for targeted polyphenol-based nutritional interventions in meeting condition-specific, personalized health objectives.

So, essentially our role is to develop science-based, safe and effective dietary supplements that health care practitioners can use as tools in personalized patient management.  We achieve this, in part, through careful formulation with the best ingredients at effective doses, the use of multiple product formats, consultation with experts in clinical practice, and rigorous science.  This is our small—but important—contribution to this exciting movement that is rapidly bringing back a patient-centered approach to evidence-based medicine.

By Barry W. Ritz, PhD, VP Scientific and Regulatory Affairs, Atrium Innovations Inc
PLMI 2014 Conference 2014 

 

References

[1] Labonte K, et al. Acute effects of polyphenols from cranberries and grape seeds on endothelial function and performance in elite athletes. Sports. 2013;1:55-68.

[2] Ras RT, et al. Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis. Intl J Cardiol.