A Combination of Magnesium, B Vitamins, Rhodiola, and Green Tea (L-theanine) Alleviates Chronic Stress in Healthy Volunteers: A Randomized, Placebo-Controlled Study

OBJECTIVES: The effect of a combination of magnesium, vitamin B6, B9, B12, and Teadiola(®) (rhodiola and green tea/L-theanine extracts) on stress was evaluated in chronically stressed but otherwise healthy subjects. The effects on stress-related quality-of-life (QoL) parameters, like sleep and perception of pain were also explored. METHODS: This single-blinded study (NCT04391452) included adults with stress for ≥1 month and with ≥14 points on Depression Anxiety Stress Scale (DASS)-42 stress questionnaire. Subjects were randomized (1:1) to receive either the dietary supplement combination (n = 49) or placebo (n = 51), once daily, for 28 days, with a follow-up assessment at day 56. Primary endpoint was the change in DASS-42 stress score from baseline (BL) to day 28 in dietary supplement vs placebo groups. Secondary endpoints included changes from BL in DASS-42 scores at days 14 and 56; sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at days 14, 28, and 56; pain perception (temperature threshold) in response to cold/warm thermal stimulations at day 28. RESULTS: At BL, DASS-42 score (mean [SD]) was 26.3 (6.7) with dietary supplement and 26.8 (8.0) with placebo. At day 28, the scores decreased to 17.6 (7.3) and 20.1 (9.4), respectively, with a significant between-group difference of 3 points (effect size [ES], −0.29; 95% CI [−0.57, −0.01]; p = 0.04). Similar reductions were observed earlier, at day 14 (ES, −0.40; 95% CI [−0.68, −0.11]; p = 0.006), that remained stable up to day 56 (ES, −0.34; 95% CI [−0.62, −0.06]; p = 0.02). At day 28, a significant reduction in sensitivity to cold pain was reported with dietary supplement vs placebo (p = 0.01) and a trend for lesser sensitivity to hot pain was observed (p = 0.06). No significant effect was observed on overall sleep quality, but a trend towards improvement in daytime dysfunction due to sleepiness (PSQI-7 component score) was noticed with dietary supplement vs placebo at day 28 (p = 0.06) which became significant at day 56 (p < 0.001). CONCLUSIONS: The combination is effective for management of stress in healthy individuals. Its beneficial effects on stress-related QoL aspects, notably pain perception, deserve further investigation. FUNDING SOURCES: This study was sponsored by the University Hospital of Clermont-Ferrand, France and received partial financial support from Sanofi Consumer Healthcare, the manufacturer of Stress Resist(®).