While inflammation is a culprit in affective changes related to depression, researchers have implicated a related affective state—stress—in generating inflammation. Some evidence3 shows that chronic stress in particular can trigger the immune system to flood the body with inflammatory cytokines, which themselves may go on to promote heart disease, asthma, and other disorders. Indeed, a report by the Congressional Prevention Coalition4 on stress prevention claims that 90% of disease has roots in complications associated with stress. (The coalition was founded by a bipartisan group of U.S. lawmakers to examine America’s critical social and economic problems.)
Alas, stress is as much a fixture of modern life as the SAD, and supplement marketers and users alike are eager to find ingredients to help mitigate it. “Support for stress and mood in today’s complex world is an important cognitive health trend,” says Barbara Davis, PhD, vice president, medical and scientific affairs, PLT Health Solutions (Morristown, NJ). “In the United States today, more than 75 million people experience stress, with negative consequences for their physical and mental health, quality of life, and economic activity.”
But as with mood-boosting supplements, a stress-relieving product must deliver experiential results to gain consumer buy-in. So when PLT collaborated with HG&H Pharmaceuticals (Bryanston, South Africa) to develop what would ultimately become Zembrin, their entrant into the anxiety-reduction market, they focused on a botanical with an anecdotal history of working.
That botanical is Sceletium tortuosum, which, to the San people of South Africa, is “kanna”—their traditional remedy for lowering stress. PLT and HG&H added value to the San’s remedy by standardizing their own Sceletium extract for total alkaloid content and to meet a specific profile for the main active alkaloids mesembrenone, mesembrenol, mesembranone, and mesembrine. Davis attributes the product’s safety and effectiveness to this “unique fingerprint,” which she says “is distinguished by its relatively low level of mesembrine and relatively high level of mesembrenone.”
A double-blind, placebo-controlled crossover clinical trial5 published in Neuropsychopharmacology in 2013 used functional magnetic-resonance imaging (fMRI) to show that 25 mg of the product produced a drop in the “anxiety-related activity of the amygdala and its associated anxiety circuitry” only two hours after administration—results that Davis says “provide the first evidence for the areas of brain where Zembrin’s anti-anxiety activity acts and confirmation of its potential to help in the management of stress.”
Stress Reduction without Sedation
Another question to ask is what kind of stress relief are we providing? T. P. Rao, PhD, an assistant general manager at Taiyo Kagaku Company, Ltd., (Mie, Japan) notes that while supplements like melatonin, valerian root extract, and others are popular within the stress-reduction sector, “their side effects—including dependency, sedation, and more—limit their use at any time of the day.” This has prompted marketers to seek ingredients that suppress stress without sedation.
L-theanine, an amino acid common in tea, is one. In studies, Taiyo’s purified form of the ingredient, which it markets as Suntheanine, “has been shown to offer a safe, non-sedative, and proven relaxation effect within 30 to 40 minutes after consumption,” Rao says. It crosses the blood-brain barrier “to excite the GABA”—gamma-aminobutyric acid—“and glycine vesicles to increase inhibitory neurotransmitters and promote dopamine release to induce relaxation effects, which are expressed in terms of increasing alpha brain waves that indicate an alert and relaxed state of mind in subjects.” What’s more, it appears to improve cognition, mood, focus, and quality of sleep, he adds, and its “synergistic” effects with caffeine promote “energized” relaxation by suppressing caffeine’s nerve-jangling tendency.
And it’s that desire to promote relaxation and alertness without causing overstimulation that’s driven ingredient suppliers to explore adaptogenic herbs, says Bruce Abedon, PhD, director of scientific affairs, NutraGenesis (Brattleboro, VT). “Unlike stimulants such as caffeine, which can exacerbate stress-related symptoms because they can cause rapid heartbeat, increased blood pressure, jitteriness, and make it harder to sleep, adaptogenic botanicals do the opposite, helping to bring about a balance in hormone levels and restore homeostasis disrupted by stress,” he says.
Ashwagandha (Withania somnifera) is one example, and Abedon’s company markets a standardized and patented extract of its root and leaf as Sensoril. The product contains the highest levels of ashwagandha glycowithanolide bioactives available, he says, and it’s been the subject of nine randomized, double-blind, placebo-controlled human clinical trials, as well as in vivo preclinical research. Clinical studies indicate that doses of 125 mg taken once or twice daily yield improvements in as little as 30 days, as the ingredient reduces levels of the stress hormone cortisol while increasing those of the energizing hormone DHEA (dehydroepiandrosterone). The fact that the extract is “all natural”—“an important selling point for consumers,” Abedon adds—doesn’t hurt, either.
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