We’re overstimulated … yet bored. We’re exhausted … but we can’t sleep. We’re anxious, moody, run-down … boy, do we need help!

According to a 2021 survey conducted by The Harris Poll on behalf of the American Psychological Association, three out of every four American adults (74%) have experienced various negative effects of stress. The survey also revealed that only 1 of every 7 Americans (16%) have a high resilience score, and the 1 out of every 4 American adults (26%) with low resilience scores were three times as likely to have experienced negative effects of stress.

Can you say COVID disruptions?

In the wake of COVID, Americans have flocked to the supplements aisles in search of immunity supplements, which are now a $5 billion concern as immune-support supplements are basically the new multi.

But COVID-adjacent conditions are now coming to the fore. Think of the ways lives have changed in the last two years. Weight gain. Sleep deprivation. Moodiness. Stress.

Chronic or occasional stress provides a lot of runway for supplements formulators. That’s because there exists a slew of ingredients that address different mechanisms of action that can hit the affliction in different ways.

“Chronic stress really opens up a Pandora’s box for a lot of bad things to happen. Where you manifest stress in your body is different from me,” said David Foreman, aka The Herbal Pharmacist. “So we need a multifaceted approach when we develop products for so many different people.”

Related:Time tested & science supported modern stress-busting health benefits from ashwagandha root – download

Calm and mood supplements are up 29% year-over-year, according to SPINS sales data, and up a whopping 115% in conventional sales channels.

At a Feb. 17 virtual event, now available on the SupplySide265 platform, Foreman laid out a list of eight top ingredients, with science and mechanisms of action, all designed to give supplement product formulators a road map for evidence-based new product developments.

Ashwagandha: The king of the Ayurvedic adaptogen botanicals, ashwagandha is dominated by two branded ingredients with a combined 34 clinical studies on their safety and efficacy. The two ingredient leaders are the KSM-66 brand, which uses the traditional roots, and the Sensoril brand, which uses the roots and leaves. “Both are great for different reasons,” said Foreman. “Both for physical and mental stress.” Sales of ashwagandha increased 50% in 2020. Ashwagandha helps decrease levels of cortisol; aka, the stress hormone. Dosage levels depends on the brand; for KSM-66 the research shows 300mg twice daily is the effective dose, while for Sensoril the dosage level is 250mg/day.

Related:Stress support with ashwagandha, tradition meets science - podcast

Caralluma (Caralluma fimbriata) supports stress reduction through multiple pathways. As 11 studies show, five of which are on humans, the botanical acts as a selective serotonin reuptake inhibitor (SSRI)—the same mechanism used by anti-depressant drugs like Prozac and Zoloft. It also reduces cortisol levels, helps with concentration and focus and supports the HPA axis—a neuroendocrine mechanism that mediates the effects of stressors by regulating physiological processes from the autonomic nervous system to metabolism. “Where would I use this?” asked Foreman. “One would be in neurotransmitter-support formulas.” Its typical dose is 500 mg twice daily.

Kanna (Sceletium tortuosum) is known by the branded ingredient name, Zembrin. Six clinical studies show it works in the stress center of the brain. It also acts as a SSRI, in as little as two hours, primarily for neurotransmitter support and to calm the stress center of the brain. “The amygdala is the stress center of the brain,” said Foreman. “If you get a bad phone call or email, the signal goes to your brain—and if you can calm that down, you can calm the cascade from there and how the body reacts. It works at the beginning of the process.” So this is yet another neurotransmitter support supplement idea because it can help calm a person down but without impeding one’s ability to focus—if anything, it could help on the cognitive focus front. Its typical dosage is 25 mg/day.

Milk protein hydrolysate goes by the brand name Lactium, an alpha-S1 casein hydrolysate. Nine clinical studies show it works directly in the brain, selective of the BZ site of the GABA receptors in the central nervous system. “The GABA BZ site is where those benzodiazepine drugs work, like a Valium or Xanax,” said Foreman. We’re not talking about the drug effects but working in a similar spot.” It also reduces cortisol and improves sleep. Because it works on both stress and sleep, the dosage varies between 150-600 mg/day.

Phospholipids PA and PS, short for soy lecithin phosphatidic acid and phosphatidylserine, which help normalize the HPA axis for adrenal support. Eight clinical studies on the branded ingredient CognoLipid show it can reduce cortisol levels, provide precursors to neurotransmitter production as well as neurotransmitter support. Dosage is at 400 mg/day.

L-theanine is the amino acid from green tea that promotes an alert state of relaxation. The leading brand is Suntheanine, and it is a very popular ingredient, thanks to 60 clinical studies at doses ranging from 50-200mg/day. It increases GABA and serotonin levels. Most studies show efficacy at 200mg/dose, though some measurements of alertness have been seen at doses as low as 50mg.

Probiotics, especially specific bacterial strains, are being studied for health states far beyond the old-school digestive health and immunity. Two such strains, HEAL9 (an L. plantarum) and HOWARU Calm (L. paracasei Lpc-27) have been shown to support the gut-brain axis. The belief is these probiotics can affect neurotransmitter production and balance as well as affect cortisol levels.

Saffron (Crocus sativas) supports the nervous system in multiple pathways. Thanks to eight human clinical studies, saffron has been shown to support neuroplasticity and help create new neurons, and provides a softer response similar to Zembrin, said Foreman. And the dosage level is a low 28 mg.

This list of ingredients should provide formulators with enough ideas for further investigation of the medical literature to see how combinations could work together to target different avenues of the body’s stress response.

“One ingredient sells a consumer short,” said Foreman. “Combine ingredients with multiple mechanisms of action. Sensoril with saffron or maybe Zembrin would be a great combination. Then look for cool delivery formats—people have pill fatigue.”