Remember the heyday of the American botanical scene? That would have been in the late 1990s. St. John’s wort. Echinacea. Garlic. Ginkgo. Ephedra. Then St. John’s wort was mugged by a landmark study showing it was no better than placebo (though the study also showed no difference with the leading pharmaceutical, but nevermind). Ephedra was pulled from the market over safety concerns. Equivocal research dampened enthusiasm for Echinacea.
And for the last decade botanical sales have been pretty much flat. Last year a report said 5 percent growth – but when you remove whole-food ingredients like cranberries, garlic and soy, the traditional herbal category remains flat.
One reason for the latter-day drag on the herb market may be the insidious issue of adulteration. This issue has gained so much concern that a collaboration among three non-profits have initiated a large-scale program to educate the industry about ingredient and product adulteration. The three players – the American Botanical Council, American Herbal Pharmacopoeia and the University of Mississippi’s National Center for natural Products Research – are focusing on the two types of adulteration: accidental due to poor quality-control procedures and economically motivated adulteration.
Vouchsafing the integrity of your supply chain goes far beyond a Certificate of Analysis. Purchasing agents have to contend with challenges from spiked botanicals to conventional drugs masquerading as supplements. Which analytical method is most appropriate for the ingredient that just arrived in your facility? Do you have the answers?
GMPs: 5 questions to ask yourself
- What specs do we need: What species and plant part of the herb to use?
- What species: Do we have a test to differentiate closely related species?
- What purity standard: What is the extraction process?
- What contaminants: We need not just a positive test for identification but we also need a negative test to see that we don’t have adulterants.
- Most important question is what scientifically valid test is appropriate for what we have. The test has to be appropriate for the specific ingredient.
“The FDA’s expectation with commodities is there are specs, and we don’t want you to have adulterants,” said Daniel Fabricant, PhD, director of FDA’s Division of Dietary Supplement Programs “We’re doing five trainings this year for GMPs, 150 inspections this year. We dive in to these issues especially when they overlap with public health concerns. If people are doing inappropriate tests, you’ll see seizures and legal actions.”
Industry quality-control misconception:
- The belief that contract manufacturers are covering your back on GMPs. That’s not acceptable – if it’s your label, you’re the ones responsible for QC tests, not the contract lab. – Roy Upton, founder, executive director, and editor of the American Herbal Pharmacopoeia (AHP)
Botanicals we like now
Sceletium: “Experiential” ingredients are trending – got caffeine in that energy drink? Sceletium tortuosum is not an energy booster, but its effects are no less profound. In two human clinicals conducted in 2012 and another (as yet unpublished) in 2013, sceletium (Zembrin) was used in randomized, double-blind, placebo-controlled studies in healthy individuals.1-2 Positive effects were noted on cognitive domains including mood, stress, coping and quality of sleep.
In a recent publication, 21 patients were given 25mg of Zembrin-brand sceletium or placebo for three weeks. Those taking the botanical experienced statistically significant improvements in executive function – the ability to take action and implement goal-directed behavior. Improvements were also seen in another stress-impacted area, called set flexibility – adapt to changing direction, multi-tasking and ability to use information to strategize and make decisions.1
Two mechanisms of action have been identified: as a selective serotonin reuptake inhibitor as well as inhibition of PDE4, elevated levels of which are associated with depression.
Its safety profile has also been validated in four studies in the last decade. Animal studies showed no untoward effects at doses of 2, 100 and 5,000 mg/kg for between 7 and 180 days. Additional cell-culture studies have shown it to be free from genotoxic potential.2-5
Stress, anxiety and mood are categories rich with potential for the right ingredient. An experiential ingredient to make happy people happier sounds like the right recipe to us.
Curcumin: The active ingredient in the Indian spice turmeric has benefited from a research tsunami of more than 1,000 studies in 2012 alone, while at the same time contending with bioavailability issues that are leading a number of companies to find a way to improve absorption and differentiate themselves from the market.
It’s now recognized that curcumin possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, growth suppression of both cancer cells and blood vessels that feed cancer cells. These effects address health conditions as diverse as cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease.6
At the same time, curcumin has an issue with bioavailability because of low intrinsic activity, poor absorption, rapid rate of metabolism, inactivity of metabolic products and/or rapid elimination and clearance from the body.
This has been the Achilles’ heel of curcumin – despite a diverse array of biological activities, bioavailability issues call into question practical health benefits of consuming Curcuma longa.
Attempts at enhancing absorption include bioavailability enhancers such as piperine, phospholipids, essential oils or gels as well as nanoparticles. These attempts have been successful in enhancing absorption, and will doubtlessly continue, in much the same manner as with other ingredients such as coQ10.7 In one case, absorption was increased about 700 percent and retained in the blood about twice as long (to 8 hours) with the BCM-95 brand, which is a reconstituted product of curcumin and an essential oil in a specific proportion.8
Spinach: Can spinach not only make Popeye mighty but also the overweight thin? According to four animal trials, one published and two as-yet unpublished human clinicals (with three more human clinicals in process), the answer could be yes.
It’s all about the thylakoids. These are found in the chloroplasts in every green leaf plant, of which a plant particularly rich in them is spinach. They work by enjoining the body to release more satiety hormones and thus curb appetite.
Specifically, thylakoids temporarily inhibit pancreatic lipase, an enzyme that in turn delays fat digestion, which allows more fat to travel further down the GI tract, which results in greater release of the satiety hormone CCK.
As this suggests, the greatest efficacy – 3.5g/dose – occurs when taking the supplement with a high-fat meal. Because the effect takes four to six hours to manifest, it’s best to take it with lunch to have effects on the higher-fat dinner meal.
In studies, the brand name Appethyl (a 50 percent thylakoid extract) has been shown to significantly reduce appetite and increase satiety (even after the first dose). Taken chronically, it can lead to significant weight loss. Secondary effects include reduced insulin levels after meals.
“This is an all-natural spinach-based appetite suppressant,” said Dan Edwall, chairman of the board and R&D coordinator for Greenleaf Medical, a Swedish firm that developed the ingredient. “I like the idea of 5-Hour Energy. I can imagine a 5-Hour Appetite Suppressant Shot.”
We’ll drink to that.
“The reason we are talking about sweetness is because big companies are talking about lo han guo and erythritol sweeteners,” said Kantha Shelke, principal at Corvus Blue consultancy. “Smaller companies can work with your product as you’re formulating it, which large companies cannot do.”
The natural, no-cal sweetener market is changing the face of product development as companies move away from synthetic sweeteners. Even cane sugar is getting its groove back as consumers prefer the once-maligned sugar to synthetics.
Stevia started the new interest when the FDA issued a “no objection” statement to GRAS submissions covering the Reb-A glycoside of stevia leaves. Despite much interest among suppliers and manufacturers, lingering off-notes led to Reb-A stevia blended with other sweetener sources, from erythritol to sugar itself.
Monk fruit, also known as luo han guo, is becoming increasingly popular as an all-natural, zero-calorie, high-intensity sweetener. In March 2013, Health Canada’s Food Directorate approved the use of monk fruit extract as a sweetener (at a maximum level of use of 0.8 percent in table-top sweeteners).
Monk fruit is a type of small subtropical melon, and has been used in Asia for its sweetness for centuries. Monk fruit's unique sweetness comes from natural antioxidants in the fruit that have a sweet taste, but are calorie-free. Its pulp is steeped in hot water to release a natural, calorie-free sweetening ingredient that’s around 200 times sweeter than sugar.
Monk fruit is also clean – in small amounts in, say, flavored water, you can label it as a natural flavor (that happens to have a bit of sweetness).
One intriguing blend is called Swerve – a zero-calorie, non-glycemic, natural sweetener based on erythritol and oligosaccharides. It acts like sugar in cold, hot and frozen beverages in a one-to-one substitution for sugar.
1. Chiu 2012. Unpublished.
2. Nell H, et al. A randomized, double-blind, plarallel-group, placebo-controlled trial of extract Sceletium torruosum (Zembrin) in healthy adults. J Alt Compl Med 2012;18:1-7.
3.Hirabayashi M., et al. Clinical application of South African tea on dementia dog. Japanese Journal of Small Animal Practice 2002;21:109-13 [Japanese].
4. Hirabayashi, M., et al. Clinical effects of South African tea for Cat. Japanese Journal of Small Animal Practice 2004;23:85–9. [Japanese].
5. Hirabayashi, M., et al. Clinical effects of South African Tea for dementia animal. Japanese Journal of Small Animal Practice 2005;24:27–31 [Japanese].
6. Anand P, et al. Bioavailability of curcumin: problems and promises. Mol Pharm 2007 Nov-Dec;4(6):807-18.
7. Mukkadan JK. Bioavailability of Curu-Gel softsules containing BCM-95 SG: a human study. http://www.bcm95.com/php/bio_availability.php