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Dietary Supplement Formula Development


Creating a successful product is a lot more than creating a list of ingredients that mix well together.

NaturPro has a broad base of knowledge in product development and production of dietary supplements, healthy foods and natural products, spanning from raw material to finished consumer product.

We guide our clients in the right direction, by helping to manage all or parts of the process for natural product formulation and development — from seed to shelf — for dietary supplement and health food products.

 

 

Supplement Product Development

The sky is the limit for healthy food and supplement product development

Dietary Supplement Formula Development

Our client list includes folks of all shapes and sizes, from startup to large corporation.

No two clients or projects are the same, but there are some common approaches found in our Product Development Toolbox:

Product Development Toolbox: Top 10 Product Development Tools:

Product development requires a ‘toolbox’ of analysis including the following

  1. Market Analysis, Competitive Analysis and Positioning
  2. Regulatory Status / Safety Assessment
  3. Claims Development and Substantiation
  4. Product Costing and Financials
  5. Ingredient Readiness, Supplier Qualification
  6. GMP’s, Specifications, and Analytical Testing
  7. Intellectual Property Development
  8. Manufacturing Feasibility
  9. Contract Manufacturer Qualification and Negotiation 

 

 

 

food supplement product development

In food and supplement product development, it’s sink or swim.

 

 

Contact Us

 

 

 

Food and Supplement Claims with Confidence


Labeling laws and truthful claims are not just critical for protecting the consumer, and they also ensure a level playing field for participants. Even during times of stalled regulatory clarity and enforcement, there is still the ‘golden rule’: do unto others by ensuring product labels are truthful and not misleading.

As we know in this era of alternative facts, it’s easy to make a claim, but harder to verify it with facts and science. (Go science.) But science has a problem. Even when fully developed, it rarely provides the full 100% confidence that may be required to change beliefs and opinions. (Boo, science.)

First example: identity claims. Many are aware that the identity of dietary ingredients need to be stated on the product label, and the specification. What is often missed is that verification through analytical tests to confirm identity are required on every batch of dietary ingredients – a minimum requirement under GMP.

Unfortunately, many identity methods miss the mark for validity and fitness for purpose – also a minimum requirement under GMP which tends to be overlooked. But if an ID method does not detect the presence or absence of common adulterants for a particular material, then how is it meeting the minimum requirement? How is it considered suitable for its purpose? In most cases, more work is needed: an adulterants review, developing and adopting multiple methods that determine a material’s identity, and adequate supplier qualification are all keys to providing a more reliable assurance of identity. The ‘totality’ approach to assuring identity is especially helpful when non-specific or indirect measures are used, like those based on infrared spectroscopy or thin layer chromatography.

Health claims also require scientific evidence. (Go science.) Here the standards are more clear, but not without some confusion. It is pretty clear that the U.S. scientific establishment plus judge and jury has decided that animal data, anecdotes and traditional use are not scientific, and therefore are not sufficient evidence to support a health claim. Past that, there’s some gaps in minimum requirements, and ask ten experts to get ten opinions (One or two studies? Published or not?). But most agree that well-designed human studies, with differences in treatment versus control groups different to more than a 95% confidence limit (known as p<0.05) are the path to health claims substantiation. This arbitrary statistical cutoff can be criticized, too, because when p=0.051 (a confidence of 94.9%), a product is deemed no more effective than placebo. The difference is the line between effective supplement and worthless snake oil. This confuses even most scientists, but it does set a pass/fail that can be evenly applied.

Science is becoming increasingly useful in the verification of content claims. Now that analytical tools can quantify at picomolar concentrations, almost down to the molecule, content claims can be powerful and truthful if investments are made in developing and verifying them. On the other hand, content claims are increasingly policed by consumer groups and class action attorneys, so a failure to verify content claims can be painful. In one recent example, the kombucha tea industry has been hit hard by a series of settlements involving mislabeling of alcohol, sugar and antioxidant content, and exploding bottles. Debate over which test methods were suitable for ethanol (one of the most frequently analyzed substances) led to an industry-wide effort to validate a method specific for kombucha. The validation in kombucha compositions was the last step required in order to rule out the slim possibility that kombucha contained unique matrix interferences that could make it difficult to measure with reliability. As a participant in the project, validation results from our partner laboratories showed a GC-FID method commonly used for ethanol in foods and beverages was indeed fit for purpose. After approval by the AOAC scientific expert review panel, the method is now becoming adopted by the kombucha industry as a standard method.

While not all methods require this kind of validation, the process is the key part to pay attention to. First you need to verify the test method. Then you verify the product against the claim you want to use, with the verified test method. Then you can put the claim on your label. In that order.

Here’s another catch about claims: your evidence is only so good as it verifies the claim. Picture an ingredient made on the same manufacturing line as a common allergen. Is a test report and supplier checklist from last year sufficient on its own to prove that a new shipment you just received is allergen-free? Maybe, maybe not. The best test method in the world will not make up for a lack in understanding whether you should reasonably expect the same results with the new lot as you did before. Verification is not just about testing.

Regardless, for those who are interested in verifying label claims, hopefully we can all agree that there should be rules, and the same rules should apply to everyone. What should also be agreed is that whether claims are truthful and misleading should be based on science and facts, not beliefs and opinions. Go, science!

 

By: Blake Ebersole

Published in Natural Products Insider, 2017

 

New Omega-3 Technologies Evolving


Emerging sources and technologies for omega-3, omega-6 and healthy fats:

We didn’t need to add butter to coffee to demonstrate the importance of fats as energy in the diet, but maybe it helped. The concept that there are healthy fats other than omega-3’s and 6’s may present a challenge to market growth. Fortunately, the quality problems that plagued the sector for years have moved on. We no longer need to worry how to clean up fish oil, and make it taste like key lime pie.  But where to go from here?

Hopefully the benefits of omega-3’s will continue to be found from the hundreds of clinical studies in progress.  But no dietary ingredient exists in a vacuum, and there are ways to further optimize omega-3’s beyond the old standbys.  For example, phospholipids naturally present in krill oil have been shown to increase the absorption of DHA, allowing for a lower dose substantiated for phospholipid-rich krill oil. This is nature’s way of optimizing absorption. Both phospholipids and omega-3 are stored in cell membranes, where they serve similar roles.  It is reasonable to think there might be a benefit to consuming both together, beyond the increased bioavailability. Are there better optimized combinations of phospholipids and cofactors which closer represent the nutrient profile of salmon, and may be even more beneficial?  Perhaps.

Meanwhile, man continues to create products based on nature, inspired by milk emulsions and small intestine micelles, developing ways that (at least theoretically) increase the body’s ability to assimilate nutrients.  But some caution is to be given with the re-emergence of New Dietary Ingredient guidance. If NDI’s are to be taken literally, any dietary ingredient having a different composition than one marketed before 1994 requires a notification to FDA. So, it’s probably a good idea to start putting together the safety assessments that will be required for omega-3 ingredients and technologies that were not around before 1994.

Back to the clinicals. In addition to the hundreds already published, there are more than 250 clinical trials listed on clinicaltrials.gov for omega-3, which are just getting started.  You name the health condition and it’s probably represented.  Add on the current study conducted by the U.S. Army, to determine if krill oil improves cognitive performance of soldiers. Out of all the supplements (and likely drugs) possible for a study like this, omega-3’s were selected.  With all this interest, there must be some evidence that the stuff works.

For product development, in case a high-quality omega-3 source is not sexy enough on it’s own, the literature is abound with examples of combinations of omegas with other nutrients.  DHA with EPA and GLA have led to improvements in multiple studies on people with cognitive impairment.  Look for the combinations of omega-6 to be balanced with omega-3 sources like flax and krill. And stearidonic acid (18:4 n-3) from echium and Buglossoides arvensis may be a cofactor to help improve absorption of DHA and other omega-3’s.

Combinations of omega-3 with ingredients that are not necessarily fat soluble may be trending. In a 2014 placebo-controlled study, a probiotic blend and omega-3 combination increased HDL and lowered insulin resistance better than either alone.  The addition of Vitamin E and C to DHA has been researched in clinical trials, and several studies have observed the benefits of statins with omega-3.  Omega-3 blood levels may also affect whether B-vitamins can slow the brain’s decline during aging.  And their addition with Vitamin D has been shown to improve symptoms in people with mental illness. So there is some basis to believe omega-3’s are able to potentiate the effects of both water-soluble and fat-soluble nutrients, likely in different ways.

Our understanding of the relationships between PUFA, fat metabolism and inflammation has created many connections with pathways regulated by other nutrients. Thinking in terms of focused nutrition, a combination of omega-3’s with other sources of healthy fats such as MCT, at a certain dose and balance could provide optimal brain nutrition for certain people.   The addition of other cofactors along the arachidonic acid and inflammatory pathways, in addition to mediators along the endocannabinoid pathways may provide systemic support for the pathways which rely on a steady stream of fatty acids as signaling molecules.

New sources of omega-3 are likely to pop up as they always have. Perilla, new types of microalgae, and plants like canola bred to produce greater amounts of omega fatty acids are in the pipeline.  And a few consumer product categories are starting to emerge as opportunities for fortification with omega-3. Meal replacement powders and liquids are beginning to see omegas being added successfully, benefitting from new powdering and emulsion technologies.  The infusion of omega-3 into food products like eggs, chickens and even prepared foods has been achieved through integration of DHA-rich algae or flaxseed into animal feed.  Thanks to long-term and growing interest, the omega-3 rich products of today don’t look or taste anything like grandmother’s cod liver oil, but are just as healthy.

By: Blake Ebersole

First published in Natural Products Insider, October 2016

References

  1. http://www.hindawi.com/journals/mi/2014/348959/tab1/
  2. http://www.eurekalert.org/pub_releases/2014-05/bawh-nss050114.php
  3. http://www.ncbi.nlm.nih.gov/pubmed/12837515
  4. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1676-26492011000400007
  5. http://content.iospress.com/articles/journal-of-alzheimers-disease/jad150777
  6. http://www.hindawi.com/journals/ije/2013/361895/
  7. https://www.army.mil/article/172714/omega_3_study_aims_to_give_soldiers_a_cognitive_advantage
  8. http://www.foodingredientsfirst.com/news/Waitrose-Launch-Omega-3-Rich-Chicken-As-Alternative-To-Unpopular-Oily-Fish.html
  9. http://www.fasebj.org/content/26/1_Supplement/125.6
  10. http://www.ncbi.nlm.nih.gov/pubmed/26793308

Testing Lab and Method Qualification


There are thousands of variations of analytical methods used for natural products.  Not all of them are fit for purpose, failing to meet a central requirement for dietary supplement cGMP’s.

Identity methods for botanical products are especially problematic, as demonstrated by the mass confusion set off by the NY A.G.

And manufacturers and contract labs are stuck in the middle of a supply chain that can lack an understanding of the source or processing method, which are important factors for labs to determine appropriate methods.

The slide deck at the link below is from a 2016 talk at SupplySide West that presented challenges and best practices for method selection and validation against established guidance. A process for laboratory qualification, method development and ‘red flags’ are included in these slides.

Access the slides here

NaturPro Supports AOAC Official Method for Ethanol in Kombucha


NaturPro Scientific presented method validation data leading to a unanimous vote for adoption of first action Official Method status at the 130th Annual Meeting of AOAC International, September 18-21, 2016.

The Official Method status is thought to be the first method to demonstrate scientific validity for ethanol in kombucha under peer review, and is the result of a truth-in-labeling initiative supported by industry.

Kombucha is a fermented tea marketed for probiotic properties, which is expected to continue 25% yearly growth, to nearly $2 billion by the year 2020.

The validation data has been submitted to the Journal of AOAC for publication.

A preliminary validation study, including data from multiple laboratories, is available here. 

NDI, GRAS and Supplement Safety Assessment


The objective of NDI and GRAS  for supplements and foods is to provide a baseline evaluation of the safety aspects of an ingredient.

FDA issued draft guidance on the NDI and final guidance on the updated GRAS requirement in August 2016. The guidances are likely to require a significant amount of information related to safety and quality of dietary ingredients to be compiled and evaluated by scientific experts.

Four Steps to Compliance:

1. Determine the most likely regulatory status of your ingredient:  ODI, NDI, GRAS or other based on a preliminary review of regulatory status and toxicology data.
2. Compile a master file of all your safety and quality documents supporting the new CFR 117 and the new FDA guidances. Most master files are more than a hundred pages long, including references.
3. Have the master file reviewed for gaps according to the regulatory status. Perform a risk assessment to safety, quality or brand presented from the analysis.
4. Chart a plan of action to meet the requirements.
Toxicology and safety studies are expensive to conduct, so you need to know if your ingredients need to go through the new GRAS Notification process, require a NDI Notification, and also carry any specific risk for adulteration or contamination. Take care of these elements, and you can be fairly sure that you will not be blind sided by regulators, consumers, or class action attorneys.

A pre-assessment is typically conducted quickly to determine the appropriate strategy and level of risk.  Contact us to determine the best strategy for you.

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For more detail, here is a framework of basic requirements for a safety assessment

  1. Clinical, Medicinal and Food Use 
    1. In country to market
    2. Global
  2. Regulatory Status
    1. ODI or NDI (if ingredient used for supplement)
    2. GRAS
    3. Other
  3. Toxicity Summary
    1. History of human consumption in foods/supplements including dosage amount and composition
    2. LD50/acute toxicity/chronic/subchronic toxicity studies
    3. Bioavailability and ADME
    4. Clinical trials
    5. Other (genotoxicity, carcinogenicity, reproductive toxicity etc)
    6. Case reports, AER and Drug Interaction Review
  4. Dietary Supplement Manufacturing Risk Review (or CMC, Chemistry/Manufacturing/Control)

    1. Chemical and Nutritional Characterization
      1. Literature review
      2. Specification, Certificate of Analysis, ID and contaminants
    2. Manufacturing Facility GMP evaluation (self-assessment and audits)
    3. Potential adulterants and their controls

Contact us for more information.

Dose Delivery: Oil Into Water


The gut is by nature one of the best machines imaginable for chemical conversion of food into energy. As a result, the majority of what we consume is changed into something different with incredible efficiency. The stomach begins this process with the pH of battery acid, plus enzymes. Then, the intestines—25 feet long and filled with hungry bacteria and more enzymes— do the rest. Considering the environment, it is surprising that anything we consume actually absorbs into our bloodstream intact.

Bioavailability, often defined as the amount of a compound put into the body compared to the amount reaching blood circulation, is an unexpectedly complex subject. Luckily, the pharmaceutical scientific literature has given us some good tools to understand it adequately.

In order to be bioavailable, a compound must first remain stable and retain its identity in the gut, which is no small order. Assuming it stays intact, its bioavailability can be divided into four main classes, categorized by the Biopharmaceutics Classification System (BCS). According to the BCS system, there are only two chemical factors driving bioavailability: its solubility and its permeability. Water-soluble compounds like ascorbic acid are considered class I (high solubility and permeability), the ideal scenario for bioavailability. However, many fat-soluble compounds such as curcumin are considered BCS Class IV, possessing low solubility and permeability. With the potential of curcumin and its more than 6,700 published studies, this means a lot of opportunity in the face of a lot of challenge.

For Class I to III compounds, dose delivery is often fairly easy to solve. Optimizing these based on pH, particle size, solid dispersions, crystallization or salt forms can be enough to ensure adequate absorption. But what to do about the difficult Class IV compounds?

The water solubility of a compound is based on its chemical polarity, which depends on the electric charge of a compound (given by the presence of charged atoms like oxygen) and its asymmetry. Water (H2O) is polar, because it’s an asymmetric molecule containing mostly oxygen by weight. On the other hand, fats and oils, generally symmetric compounds with a lot of uncharged carbons, are nonpolar and not very water soluble.

The spectrum of polarity includes some compounds called amphiphilic (meaning both-loving) which are able to interact with both polar and nonpolar compounds. As a result, they are ideal to include in many dose-delivery systems. Because ‘like dissolves like’, amphiphiles can dissolve both fat- and water-soluble compounds; detergents like soap, which dissolves grease into water, are one everyday example of this type of compound.

The use of amphiphiles to improve bioavailability has already been perfected in our gut. High-purity phospholipids are the key components used by the small intestine to absorb dietary fat. Phospholipids are also a main part of cell membranes, whose critical function is to separate the cell from its environment while at the same time allowing both polar and nonpolar nutrients to pass through. In the past few years, science has harnessed these unique and interesting properties of phospholipids to better deliver active compounds to target tissues.

To date, thousands of studies have been published on improved bioavailability technologies such as solid-lipid particles, nanoparticles, micelles, liposomes, emulsions, microparticles and others. Phospholipids are one common factor among these technologies, which ultimately stabilize and solubilize compounds of a class IV nature. Curcumin, resveratrol and other fat-soluble compounds all clearly benefit from some of these advanced dose delivery systems.

Yet challenges remain. In the view of the literature and medical use, reliable human efficacy is achieved infrequently; the number of successful human studies using these advanced technologies pales in comparison to the number of successful test tube or animal studies. Why? From a dose delivery view, it is also well understood that there is an ideal concentration of active in the body: too little is ineffective, while too much may be counterproductive. Striking that balance is a difficult task.

The human body and how exactly it works remains much of a mystery, still with vast areas of uncharted territory. And some big differences exist in how we absorb, metabolize and excrete what we consume, due to genetics, diet, what we consume it with and other variables. Plus, each active compound is an individual chemical entity with unique physicochemical characteristics and bioavailability. Hence, the need for good and rigorous science.

Also, our current capabilities and standards for measuring bioavailability are sometimes not relevant to efficacy. For example, bioavailability of fat-soluble compounds is generally measured in blood plasma, because plasma is mostly water-based and the best medium to measure water-soluble compounds. However, plasma data often does not reflect actual bioavailability of fat-soluble compounds, because plasma does not generally attract these compounds like blood cell membranes and organ tissues do. Many dose-delivery technologies work magnificently in the test tube, but may not survive stomach acid or the small intestine intact. And some delivery systems may appear to improve bioavailability but only for an inactive metabolite like a glucuronide.

In these cases, the chemical identity of what we measure in the blood, in addition to what part of the blood we are measuring, proves to be more important than the amount we are measuring. When the science of a bioavailability study is off-kilter, it can ultimately lead to the selection of poor clinical study material and a failure to show efficacy. Good science in the early stages of development is critical, and while oil and water can mix, dose delivery is ultimately just a means to promoting health.

By: Blake Ebersole

This article was originally published in Natural Products Insider in August 2014

 

How To Design a Clinical Trial


Designing and executing a clinical trial that meets scientific and marketing requirements can be a tall order. Lots of variable exist, and often a meaningful clinical study result is a moving target. So study design requires significant expertise in the therapeutic area, and an understanding of market dynamics.

Here are four main questions to ask.

1.) What are the rationale and central questions to the study? There are a number of questions that need answers, but in general, clinical studies should start with one or two central questions, and a reason for why the material should be studied. This results in the development of primary and secondary endpoints. Are you trying to see whether a nutritional product can improve joint pain in baby boomers, or muscle pain in athletes? Because the study design may be completely different for what may appear to be very similar studies.

How the product will be perceived by the market post-study is also important. What study endpoints will allow for solid marketing claims? If your product has a significant effect in the study, will it help to differentiate your product against the leaders in the category? In the drug industry, studies on new products are compared against the “standard of care,” and the approach for supplement clinicals can take the same approach, particularly if the product is not very well differentiated in other ways.  Are there new mechanisms of action or emerging markers that can be added as secondary endpoints, which would help to differentiate your product?

Accumulation of data to support safety and global regulatory acceptance such as GRAS determinations should always be an objective, so any efficacy study is also a great opportunity to inexpensively accumulate safety data.

2.) What is the dose? Often, this is the most challenging and critical question across all drug and nutrition clinical studies. For many products that are complex mixtures of active compounds, pharmacokinetics or bioavailability is unknown or untenable, making dosing a wild guess. In cases where there are only a couple active compounds, bioavailability should be assessed before moving on to clinical efficacy trials.

In cases where bioavailability cannot be easily determined, a dose-response study (using multiple doses) should be performed. Ideally, a dose-response study observes a small effect at a lower dose, and a greater effect at a higher dose. In other cases, a linear dose-response relationship should not be assumed; a higher dose may not work as well (or reveal safety issues) compared to a lower dose.

Market considerations, such as cost per day and number of capsules should also be included in this evaluation. While a randomized, placebo-controlled clinical trial is wonderful to have, if the product never reaches the shelf (or the dose is too high for the consumer to stomach) then the best-designed study is like a tree falling in the woods.

3.) How many subjects are needed for the study to be adequately powered? A minimum requirement today for nutritional products is that the changes in the group taking the active dose must be significantly different than the changes in the placebo or control group. It makes no sense to design and invest in a study that will show no difference between your product and a sugar pill. For some subjective measures such as pain, the placebo effect and inter-individual variation can be very high, due to the subjective and ever-changing nature of pain perception. In this case, the number of subjects required to get reliable statistical separation between the active versus control groups is relatively high. For other endpoints, such as blood concentrations of actives in pharmacokinetic studies, placebo effects are almost nil, and therefore a lower ‘n’ is likely to result in significant changes versus controls.

4.) What is the budget and timeline? Research is an investment, one that can be expensive and time-consuming. For example, if the therapeutic area and endpoints include testing of blood markers, then the drawing, processing and testing of blood samples is a major cost center in the research budget.  Common blood markers such as blood lipids are relatively easy using standard kits, while other less standard markers can require method development and increase costs, and may provide unreliable data that needs to be repeated.

A university-based study offers the independence and clout of world-class clinical studies, but the prestige can be balanced with increased costs and more uncertainty in the timeline, particularly when your study is relatively small and relies on shared resources. While a contract research organization is often faster than a university, this option can also come with greater costs. A research services contract with a detailed protocol and time-based milestones is critical to have in place.

Ethical approval (typically through an Institutional Review Board, or IRB) is also required for all human studies. Some research centers can get IRB approval within a month, while others are mired in bureaucracy and generally take six months or more.

Recruiting also contributes to the study timeline. If you are excluding a lot of lifestyle factors, then your available population is low, and getting the required number of subjects can be costly if not impossible.  Many clinical studies never get off the ground when recruiting is not taken into account.

Lastly, it is critical to do the homework up front and ask a lot of questions. Make sure you have someone in your corner, who speaks the language and is looking out for your best interests. Only then can you ensure the returns on your research investment are maximized.

By: Blake Ebersole

This article was previously published in Natural Products Insider, June 2015.

The Way to My Heart? Through My Stomach…


Heart health, gut microbiota and diet are closely linked in ways we are just beginning to understand. It is well-known that diet can alter microflora balance and tip the scales toward a pro-inflammatory status affecting heart health, but new research has uncovered other interesting links between gut and heart health. A 2015 study published in Metabolism found women with and without metabolic syndrome who produced equol, a gut bacteria metabolite resulting from soy consumption, enjoyed cardiovascular benefits from consuming soy nuts.1 However, non-equol producers experienced no improvement. This suggests the possibility that in order to enjoy the cardiovascular benefits from soy, a certain balance or type of gut bacteria is required.

Many nutritional interventions appear to work regardless of gut microbiota. A 2015 randomized, controlled clinical trial published in the journal Hypertension by a university group in London, found the primary active constituents of beet root are the nitrates like betain.2 In this study, 250 ml of beet root juice (compared to a placebo of nitrate-free beet juice) reliably lowered blood pressure in hypertensive patients, as well as improved endothelial function by 20 percent (p<0.001). Remarked the authors, “This is the first evidence of durable BP reduction with dietary nitrate supplementation in a relevant patient group.”

But juicers might want to keep the fiber. A study in the American Journal of Clinical Nutrition following 7,216 men and women for eight years found baseline consumption of fruits and fiber was associated with a significantly lower death rate, and those consuming the highest level of fruits (>210 g/d) had a 41-percent lower risk of mortality, which was mainly associated with cardiovascular disease.3

The questions around cardioprotective effects of whole grains continues. The Dietary Guidelines for Americans recommends at least half of our grain consumption come from whole grains, but study findings tend to be inconsistent. In a well-designed controlled crossover study in the Journal of Nutrition, which was co-authored by researchers from Nestlé and General Mills, an increase of 140 g/d in whole grain consumption did not result in significant effects in blood pressure, fecal measurements or gut microbiology.4

Studies like this one lead to more questions than answers, such as whether the “gold standard” randomized controlled trial is adequate to measure effects of interventions such as whole grains, especially when it is difficult to control every possible mitigating factor (such as the elimination of whole grains from subjects’ diet during the washout period). Perhaps the type of whole grain was a factor as well, but some also suggest that a lack of effect also illustrates why simply eating a balanced diet according to prevailing nutrition recommendations may not be sufficient to impact health, especially as we age.

Lest we forget that diet does not exist in a vacuum, there are a number of psychological and social factors that impact nutrition and cardiovascular outcomes. In the Cardiovascular Risk in Young Finns Study published in Circulation, 1,089 children were followed for 27 years, which resulted in a fantastic dataset.5 Higher ratings of emotional, parental health and self-control behavior patterns in children resulted in a significantly better cardiovascular risk rating as adults. Although the study did not focus on specific nutritional aspects, it may be worth our time as an industry to consider ways to integrate dietary interventions with lifelong behaviors that optimize health outcomes.

Reams of evidence suggest polyphenols support cardiovascular health. A recent six-week controlled clinical trial in Portugal was published in the American Journal of Clinical Nutrition, which compared the effects of two olive oils containing different levels of polyphenols on proteomic biomarker scores related to coronary artery disease.6 The findings were surprising: the olive oil lower in polyphenols was slightly more effective than the enriched olive oil. Could there be other compounds in olive oil other than polyphenols responsible for its well-known health benefits?

Regardless, the research on polyphenols continues, with berries as the main focus. Ongoing trials on polyphenols from colored berries and flowers, based on a search of ClinicalTrials.gov, include the following: a study on a hibiscus extract beverage on cardiovascular and endothelial health, which completed in February 2015; another study on a chokeberry extract in former smokers, to complete in May; and another study on cranberry extract in obese, insulin-resistant humans at Pennington Biomedical Research Center, anticipated to complete in July.

On berries, a study published in Italy in April 2015 found that a formulation of white mulberry leaf extract, berberine and red yeast rice both lowered low-density lipoprotein (LDL) and raised high-density lipoprotein (HDL) cholesterol in humans with high cholesterol not already on statins.7 This formulation was compared to a similar one without mulberry, but with astaxanthin, folic acid, policosanol and CoQ10. Based on the complexity of the formulations, it is difficult to conclude much about the contributions of each ingredient; however, the authors suggested that the mulberry extract might have made the difference for the high-performing formulation.

Future research is expected to add to our increasing knowledge of how to reach the heart through the gut.

References:

1.       Acharjee S et al. “Effect of soy nuts and equol status on blood pressure, lipids and inflammation in postmenopausal women stratified by metabolic syndrome status.” Metabolism. 2015 Feb;64(2):236-43. DOI: 10.1016/j.metabol.2014.09.005.

2.       Kapil V et al. “Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study.” Hypertension. 2015 Feb;65(2):320-7. DOI: 10.1161/HYPERTENSIONAHA.114.04675.

3.       Buil-Cosiales P et al. “Fiber intake and all-cause mortality in the Prevención con Dieta Mediterránea (PREDIMED) study.” Am J Clin Nutr. 2014 Dec;100(6):1498-507. DOI: 10.3945/ajcn.114.093757.

4.       Ampatzoglou A et al. “Increased whole grain consumption does not affect blood biochemistry, body composition, or gut microbiology in healthy, low-habitual whole grain consumers.” J Nutr. 2015 Feb;145(2):215-21. DOI: 10.3945/jn.114.202176.

5.       Pulkki-Råback L et al. “Cumulative effect of psychosocial factors in youth on ideal cardiovascular health in adulthood: the Cardiovascular Risk in Young Finns Study.” Circulation. 2015 Jan 20;131(3):245-53. DOI: 10.1161/CIRCULATIONAHA.113.007104.

6.       Silva S et al. “Impact of a 6-wk olive oil supplementation in healthy adults on urinary proteomic biomarkers of coronary artery disease, chronic kidney disease, and diabetes (types 1 and 2): a randomized, parallel, controlled, double-blind study.” Am J Clin Nutr. 2015 Jan;101(1):44-54. DOI: 10.3945/ajcn.114.094219.

7.       Trimarco V et al. “Effects of a New Combination of Nutraceuticals with Morus alba on Lipid Profile, Insulin Sensitivity and Endotelial Function in Dyslipidemic Subjects. A Cross-Over, Randomized, Double-Blind Trial.” High Blood Press Cardiovasc Prev. 2015 Apr 14.

By: Blake Ebersole

This article was first published in Natural Products Insider in June 2015

Extracts: More Than a Cup of Tea


Why extract when you can just consume the whole plant? Extracts concentrate the bioactive part of plants into a manageable dose, while removing the inert parts such as cellulose. And since a lot of botanicals that support health don’t taste very good, we would prefer to be able to consume them as one or two capsules—not 10 or 20.

On a basic level, making a botanical extract is like making a cup of tea: Just soak some plant material in some hot water and enjoy.

Yet, as many tea connoisseurs know, making tea is both an art and a science. The quality of the cup of tea is predicated on a number of variables that include raw material composition, the solvent (such as water or alcohol), the amount of tea to water, the water’s temperature and steeping time. Changes in these variables necessarily results in differences in the end product that are detectable by the human palate.

Let’s say you want to make a powdered extract from this cup of tea. The temperature, time and method of removing the water all impact the quality of the end product. To standardize the extract to a certain specification, including potency, color, powder size and impurities, requires another additional set of controls and experience.

Lastly, maintaining consistency from batch to batch is an additional challenge with natural products prone to variations in climate, geography and harvest methods.

The choice of solvent is a key variable that, along with raw material selection, has the most impact on the final extract. Different solvents will extract different classes of bioactive compounds, so it is important to know what you are trying to extract.

Historically, extraction facilities often selected solvents that provided the best yield, with little regard for safety or regulatory acceptance. As regulators and consumers have become more discerning, so have the processing methods. Today, “green” extraction methods offer a lot of the positives consumers demand—but not without some key tradeoffs.

Like dissolves like, so water will dissolve similarly polar compounds such as flavonoids. Water as a solvent is often preferred by consumers because of its “clean” image; however, it is also a challenge to work with as a master oxidizing agent and a great medium for microbial growth.

Due to its low vapor pressure, water is also among the most difficult solvents to remove during drying, resulting in extra heat and time that can further degrade the native composition of the original plant. Powdered extracts made with water are often hygroscopic, meaning they attract moisture from the air readily, which can lead to clumping and microbial growth in what was once a perfectly clean and flowable extract.

Ethanol is often preferred as a solvent, because it does not present many of the challenges of water. Many generations of physicians have produced liquid extracts known as tinctures—herbs steeped typically in ethanol at established concentrations.

Ethanol is good to dissolve diverse types of compounds, but for many fat-soluble molecules, saturation is reached at a low concentration, resulting in poor extraction efficiency. Thus, extracts using ethanol only often demand a premium price, and may not reach the level of potency offered by other non-polar solvents.

Supercritical extracts using solvents such as carbon dioxide (CO2) have become popular, and for good reason. This method of extraction can be performed at moderate temperatures, and CO2 is one of the cleanest and lowest cost solvents around. Supercritical COis often used to remove caffeine from tea, and extract essential oils from spices and herbs.

The main disadvantages of supercritical extraction include high capital and operating costs, poor selectivity of compounds without optimization, and the time and expertise required to perfect or optimize a process. Often, to achieve a standardized product, a supercritical extraction may have to be paired with other processing methods, which can add to cost.

Standard methods of extraction can be complemented with emerging technologies to achieve a superior product.

Ion-exchange chromatography is one of the best ways to purify natural products, although the higher concentrations of actives achieved are offset by lower yields and higher processing costs. Ultrasound and microwave-assisted extraction are newer ways to achieve better yields during standard solvent extraction, as they act to break the plant cells and release active components better than simple heat or static mixing.

Today’s botanical extraction toolbox offers endless possibilities to achieve desired purity while retaining the natural composition of the botanical.

 

By: Blake Ebersole

This article was first published in Natural Products Insider in February 2015