5 Top mood-support ingredients: A pharmacist’s perspective

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The pursuit of happiness is having a renaissance moment, especially in a year of great challenges, not the least of which is the COVID-19 pandemic. Consumers are actively searching out more ways to find joy, meaning, and purpose as they deal with life’s difficulties. This search is driving growth in several wellness categories. Mood-support supplements, in particular, are becoming more popular.

As mood ingredients see growing demand, consumers will seek out the most effective and best-validated supplements for mood support. Nutritional Outlook spoke with David Foreman, RPh, a renowned former pharmacist and founder of Herbal Pharmacist (Oceanside, CA), about which mood-support ingredients have the most scientific backing behind them.

Ashwagandha Acts on Mood and Sleep

Adaptogenic herbs like ashwagandha (Withania somnifera) are particularly well suited to act as mood-support ingredients. Foreman notes that ashwagandha’s effects on sleep enable it to enhance mood on two fronts.

“Ashwagandha is a great option thanks to its effects on both stress and sleep,” Foreman says. “Poor sleep leads to higher stress and vice versa, which is why this ingredient provides benefits that can help regardless of which condition is the root culprit of the mood problems.”

One study, a randomized, double-blind, placebo-controlled clinical trial sponsored by ashwagandha supplier Natreon Inc. (New Brunswick, NJ), assessed the effects of the company’s Sensoril- and Essentra-brand ashwagandha on 130 men and women aged 18 to 60 who scored in the moderate to severe range on the Hamilton Anxiety Rating Scale (HAM-A). Participants were randomly assigned to receive either 1) two 125-mg capsules of ashwagandha once per day (n=35), 2) one 125-mg capsule of ashwagandha and one 125-mg capsule of a matching placebo per day (n=30), 3) two 125-mg placebo capsules per day (n=30), or 4) two 250-mg capsules of ashwagandha per day (n=35), for 60 days. All subjects were assessed on the modified Hamilton Anxiety (mHAM-A) scale at baseline and on days 30 and 60, and were assessed for biochemical stress markers at baseline and on day 60.

Of the original 130 subjects, 98 completed the study. After 60 days, the study participants in all ashwagandha groups saw statistically significant decreases in cortisol levels, blood pressure, heart rate, and mHAM-A symptom scores, and the effect was dose-dependent. The placebo-only group did not exhibit any statistically significant changes in any biochemical stress markers or in mHAM-A scores. The study authors concluded that ashwagandha reduces subjective feelings of anxiety and stress, and this finding supports claims that ashwagandha has an anti-stress effect.¹

Sceletium Improves Resilience to Stress

Sceletium (Sceletium tortuosum) has a long history of use in South African folk medicine. The first written account of sceletium use occurred in 1662 when Dutch explorer Jan van Riebeeck was overseeing construction of a European settlement at what would become Cape Town, South Africa.² Now, modern research is validating sceletium’s stress-reducing properties. Foreman says that Zembrin, a branded sceletium extract from HG&H Pharmaceuticals (Johannesburg, South Africa) and distributed by PLT Health Solutions (Morristown, NJ), acts on the brain’s stress center to reduce anxiety and boost stress resilience.

“Zembrin has been proven to act on the amygdala and decrease the cascade of biochemical reactions that are initiated when the amygdala is activated,” Foreman explains. “Slowing or stopping this cascade can reduce the many symptoms triggered by stress.”

One study on Zembrin, a 2013 double-blind, placebo-controlled crossover trial, measured the effect of a single dose of Zembrin on amygdala reactivity in response to fearful stimuli. This study, funded by H.L. Hall & Sons (the original owners of the Sceletium tortuosum extract patent and Zembrin investors), followed 16 healthy University of Cape Town undergraduate students between the ages of 18 and 21. Participants were given one 25-mg Zembrin capsule (n=8), or a matching placebo (n=8), and received an fMRI scan two hours post-administration. After five to nine days, participants crossed over to the other condition and repeated the fMRI scan. During the fMRI scan, participants were given two cognitive tests: a perceptual-load task test and the Emotion-Matching Task test.

The fMRI results showed that Zembrin administration reduced amygdala reactivity to fearful stimuli and attenuated amygdala-hypothalamus coupling, indicating a reduced sensitivity to threatening images. The study authors attribute Zembrin’s anxiolytic properties to its ability to act as a dual serotonin reuptake/phosphodiesterase-4 inhibitor.³

Rhodiola Provides Nervous System Support

Foreman says that rhodiola (Rhodiola rosea) is unique in its role as a mood-support ingredient. This adaptogen, he says, may improve mood by acting on the physiological mechanisms that underlie stress. One 2018 literature review found that rhodiola normalizes the expression of stress hormones, boosts ATP synthesis, inhibits the SAPK pathway, and may offer protection against stress-induced damage to proteins and membranes through its anti-inflammatory and anti-oxidative properties.⁴

“Rhodiola provides unique support to the nervous system by helping to balance the body’s response to stress,” Foreman says. “Keeping the body balanced over time improves mood by alleviating long-term stress and contributing to reduced reactivity to stress.”

Holy Basil Decreases Cortisol

Holy basil (Ocimum tenuiflorum) is a traditional Ayurvedic ingredient known for its adaptogenic properties. In Ayurvedic medicine, holy basil is a sacred herb that is thought to serve as a vivifying tonic.

“Holy basil is adaptogenic and will keep the body balanced under prolonged periods of stress,” Foreman notes. “Research shows that it helps improve the body’s stress response by decreasing cortisol levels and improving neurotransmitter levels in the brain.”

A 2017 literature review of 24 clinical trials involving 1,111 participants aged 10 to 80 examined the efficacy of holy basil as an adaptogen, assessing its effects on various dimensions of health. The study authors examined holy basil’s effects on mood, stress, and cognitive function in four clinical trials, two of which were randomized, double-blind, placebo-controlled trials. The four trials involved a total of 249 participants between the ages of 18 and 80. Three of the four trials found that holy basil caused a statistically significant reduction in stress-related symptoms and self-reported anxiety. The fourth trial found that holy basil caused a statistically significant reduction in salivary cortisol levels relative to a placebo.⁵

Saffron Modulates Mood, Anxiety, and Memory

Saffron (Crocus sativus) is well known for its use in traditional folk medicine. Practitioners of Traditional Chinese Medicine have claimed that long-term saffron ingestion “causes a person’s heart to be happy."⁶ Now, modern research is showing that saffron may indeed do exactly that.

A 2018 literature review identified multiple studies that found saffron has mood-boosting and antidepressant effects.⁷ In one of the randomized, double-blind clinical trials included in the literature review, 30 adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for major depressive disorder and who scored at least 18 on the Hamilton Depression Rating Scale were randomly assigned to receive either 30 mg of saffron extract per day (n=15) or 100 mg of the tricyclic antidepressant imipramine per day (n=15) for six weeks. After six weeks, both groups showed statistically significant improvements (p < 0.0001) in Hamilton scores. There were no statistically significant differences between the two groups’ improvements; the imipramine condition and the saffron extract condition saw nearly identical score improvements. The study authors concluded that 30 mg/day of saffron extract was comparably effective to 100 mg/day of pharmaceutical imipramine in relieving the symptoms of mild to moderate depression. While this trial lacked a placebo control group (an important limitation), its findings warrant further investigation into saffron extract’s mood-boosting properties.⁸

“Research on saffron shows that it improves symptoms associated with mild to moderate anxiety,” Foreman says. “It also appears to benefit other areas of mental wellness, such as depression and memory.”

Happy Hour for Mood Ingredients

Mood-support ingredients are rapidly gaining popularity among consumers, making mood ingredients an important subset of the brain health market. However, consumers are also becoming more sophisticated by the day and are looking for supplements and ingredients that have been validated for their safety and efficacy. As more supplement users look for natural ways of supporting their emotional health, expect demand for proven, research-backed mood-boosting ingredients to grow.

References

1. Auddy B et al. “A standardized Withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study.” Journal of the American Nutraceutical Association, vol. 11, no. 1 (January 2008): 50-56
2. Johnson D. Ethnobotany, the Leaves of Life. Published February 2018.
3. 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
4. Anghelescu I et al. “Stress management and the role of Rhodiola rosea: a review.” International Journal of Psychiatry in Clinical Practice, vol. 22, no. 4 (October 2018): 242-252
5. Jamshidi N et al. “The clinical efficacy and safety of tulsi in humans: a systematic review of the literature.” Evidence-Based Complementary and Alternative Medicine. Published online March 16, 2017.
6. Bensky D. Chinese Herbal Medicine, Materia Medica, 3rd. Publisher: Eastland Press, 3rd Edition. Published December 2015.
7. Siddiqui MJ et al. “Saffron (Crocus sativus L.): As an antidepressant.” Journal of Pharmacy and BioAllied Sciences, vol. 10, no. 4 (October-December 2018): 173-180
8. Akhondzadeh S et al.“Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial.” BMC Complementary and Alternative Medicine. Published online September 2, 2004.