Mood and Relaxation Dietary Supplements: Hope in a Bottle

Some still consider the market for mood and stress-relief supplements niche. But could things start looking up?

The U.S. market for mood-supporting dietary supplements clocks in at roughly $500 million–$550 million, according to Julian Mellentin, director of global nutrition insights firm New Nutrition Business (London). But if you’re thinking, “Not bad,” Mellentin is quick to point out that the value “looks impressive until you remember that sales of pharma products are over $28 billion.” And though mood-supplement sales are growing, the wide berth between supplement and pharma numbers “really puts the two different approaches in perspective,” he says.

So Mellentin classifies mood supplements as a niche category, accounting for less than 2% of U.S. supplement sales and “likely to stay that way for some time.” Standing in the way of breakout velocity are issues like safety, efficacy, and, most importantly, tangible consumer benefits, he adds-all of which are “just too big” for the category to reach full speed, at least for now.

Just consider that last point. How many times have we been told that in order for a health product to be successful, consumers need to be able to “feel the benefit”? When consumers take a supplement for the express purpose of feeling less stressed or melancholy, Mellentin says, “they want to feel the benefit-and fast.” By contrast, consumers taking supplements as a hedge against, say, poor heart or bone health may be more inclined to accept that they may see results down the road.

But in the mood aisle, consumers expect to feel the change. Perhaps that’s why antidepressant and antianxiety medications so dominate the landscape-they work for many, and expediently so. Supplements that address the same needs, Mellentin says, just don’t yield the same rapid results.

But Is There Hope?

But results delayed aren’t necessarily results denied-at least not for consumers growing weary, and wary, of medicating away their blue or anxious moods. For them, addressing depression and stress via “natural” interventions may well be worth the wait.

As Deanne Dolnick, vice president, Next Pharmaceuticals (Salinas, CA), says, “The trend to take supplements is getting a stronger foothold across all demographics, as well as in the medical community. The consumer is getting smarter when it comes to taking prescription medications, and they’re asking doctors the tough questions and getting frustrated with the side effects of drugs.”

Even setting side effects aside, it’s worth noting that not all patients improve with pharmaceutical therapy in the first place, prompting some to “go looking for a natural solution when they’re not getting the results for which they’d hoped via mainstream medicine,” says Cheryl Myers, head of education and scientific affairs, EuroPharma Inc. (Green Bay, WI). “This may be the impetus for many to explore natural or integrative options.”

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Mood Food

Fundamental to integrative options-and to nutritional supplementation generally-is the notion that our bodies (minds included) are products of what we bring into and do with them. Or, as Dolnick says, “We feel better when we eat better and exercise. When we have control over our diets and activity, we’re controlling our lives, and that’s powerful in giving people a sense of satisfaction and calm.”

Unfortunately, today’s standard American diet-a.k.a. SAD-predisposes us to anxiety, stress, and depression, says Myers. By triggering systemic inflammation, SAD presents a real threat to mental wellbeing because inflammation doesn’t just cause muscle pain or hamper exercise recovery; it affects the brain. “When highly refined, over-sweetened foods and beverages are your only sources of ‘nourishment’”-and Myers uses the term loosely-“you’re going to see issues.” And people with major depressive disorder often do exhibit higher states of inflammation than those without.

Add it all up and you have “a population crying out for the benefits of real nutrition,” Myers concludes. Mellentin would agree, and he predicts that “we’ll see people turn more to ‘regular food’ than to supplements to improve their mood and sense of wellbeing.” As they do, they’ll likely bolster the current “free-from” movement that’s made everything from gluten to high-fructose corn syrup ingredients that today’s consumers avoid. “The idea that certain carbs are bad for your brain has taken hold among a small but growing percentage of consumers,” Mellentin notes, citing the traction that books like neurologist David Perlmutter’s Grain Brain enjoy.

Rooting Out Inflammation

But free-from diets are only one tool among many for improving mood and affect-and one for which supporting evidence is far from conclusive. More encouraging are findings about how nutritional ingredients act within the brain and body to make us, literally, feel better. “Natural supplements can help mitigate the effects of stressors or triggers for depressive states of mind to help restore healthy brain function,” Myers says. “And many botanicals, including rhodiola, ashwagandha, lemon balm, holy basil, and-my favorite-curcumin, support overall health in many other ways.” She calls these “side benefits instead of side effects.”

Curcumin, for example, is attracting attention for its anti-inflammatory properties. Its parent plant turmeric (Curcuma longa) has a long track record in ayurvedic medicine, and researchers are now sketching a clearer picture of how it’s earned its keep. Namely, the compound lowers levels of inflammatory biomarkers that travel to the brain where they do their damage. Myers adds that curcumin also “prevents the low levels of serotonin, noradrenaline, and dopamine” associated with depression and stress, and that recent research suggests that it participates in neurogenesis-the formation of brain cells-which she says is inversely related to depression.

A randomized, double-blind, placebo-controlled trial published last year in European Neuropsychopharmacology¹ investigated curcumin’s potential mechanisms. For eight weeks, 50 subjects with major depressive disorder (MDD) received either supplementation twice daily with 500 mg of EuroPharma’s patented high-absorption curcumin with turmeric essential oil-marketed as BCM-95-or a placebo. Analysis of pre- and post-intervention salivary, urinary and blood samples showed not only higher baseline plasma endothelin-1 and leptin levels in the curcumin group, but an association between those higher biomarker levels and the group’s greater score reductions on the Inventory of Depressive Symptomatology self-rated version (IDS-SR30), the study’s primary depression outcome measure.

Another study², published this year in Phytotherapy Research, looked at the antidepressant effects of a combination of curcuminoids and piperine-an alkaloid in black pepper that increases curcumin’s bioavailability. The study, which used ingredient supplier Sabinsa’s (East Windsor, NJ) Curcumin C3 Complex plus BioPerine delivered in two daily doses of 500 mg for six weeks, concluded that the supplement was effective in reducing scores on the Hospital Anxiety and Depression Scale (HADS) and thus had potential to alleviate symptoms of depression. “The authors suggested that the mechanism of action involved multiple pathways,” says Anurag Pande, PhD, vice president, scientific affairs, Sabinsa, “including the anti-inflammatory activity of curcuminoids, inhibition of monoamine oxidase, restoration of depleted levels of the neurotransmitters serotonin and dopamine, and reduction of corticosterone-induced neurotoxicity.”

Studies like these demonstrate that curcumin “can be an effective and safe treatment for patients with major depressive disorder without serious adverse effects,” Myers says. Even so, she’d “like to see a greater emphasis on the fact that brain and mood health concerns are largely due to inflammation and aren’t just chemical imbalances. That’s one of the main reasons that curcumin performs so well in the realm of cognitive health.”

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Keep Calm

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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A Brighter Future

Such supplements represent the mood and cognitive-health sector’s promise. All the same, headwinds remain. Regulations, Myers says, “make it a challenge to go head-to-head with pharmaceuticals.” And skepticism that the products are “too good to be true,” she adds, “hovers like a ghost in any conversation you have with the public at large.” To contend with that skepticism, she suggests “building trust and talking about research to keep the message strong and reach people who need high-quality natural products that work.”

Supplement users themselves should keep their expectations in check-and be patient. “Consumers need to understand that supplements don’t always work as quickly as prescription medications,” Dolnick points out. “And I think that’s the biggest issue for the consumer.”

That and reluctance to admit the need for help. “I think there is still a lot of stigma about depression and anxiety out there, and it can prevent people from seeking the professional help they need,” Myers says. “I urge anyone to talk to a professional about the concerns they are facing. If you’re dealing with depression or anxiety, it doesn’t just affect you-it affects everyone you love, work with, or meet during the day.”

One thing is clear: there is a need for help. As Sabinsa’s Pande points out, “Major depressive disorder is one of the most common mental disorders in the United States, with 6.7% of people suffering from it every year due to different reasons, according to NIH data. Stress takes its toll, too-on the body, cognitive health, and EQ, or ‘emotional quotient.’” That means we’ll need all the arrows in the mental-health quiver-counseling and pharmaceuticals, yes, but mood-boosting nutritional supplements and the occasional weekend getaway, as well-to help people cope.

References

1. Lopresti AL et al., “Curcumin and major depression: A randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change,” European Neuropsychopharmacology,vol. 25, no. 1 (January 2015): 38-50
2. Panahi Y et al., “Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder,” Phytotherapy Research,vol. 29, no. 1 (January 2015): 17–21
3. The New York TimesHealth Guide: Stress and Anxiety, www.nytimes.com/health/guides/symptoms/stress-and-anxiety/possible-complications.html
4. The Congressional Prevention Coalition; Institute of Science, Technology and Public Policy, http://istpp.org/coalition/
5. Terburg D et al., “Acute effects of Sceletium tortuosum(Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus,” Neuropsychopharmacology, vol. 38, no. 13 (December 2013): 2708-2716

Photo © iStockphoto.com/LivingImagesPhoto © iStockphoto.com/AGrigorjeva
Edited by Quinn Williams.