Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study

Abstract

Introduction: This randomized, controlled, single-blinded trial assessed the effect of magnesium (Mg)-Teadiola (Mg, vitamins B6, B9, B12, Rhodiola, and green tea/L-theanine) versus placebo on the brain response to stressful thermal stimulus in chronically stressed, but otherwise healthy subjects. Impacts on stress-related quality-of-life parameters (depression, anxiety, sleep, and perception of pain) were also explored.

Methods: The study recruited a total of 40 adults (20 per group), suffering from stress for more than 1 month and scaling ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire at the time of inclusion. Individuals received oral Mg-Teadiola or placebo for 28 days (D). fMRI analysis was used to visualize the interplay between stress and pain cerebral matrices, using thermal stress model, at baseline (D0) and after D28.

Results: Based on blood-oxygen-level-dependent (BOLD) signal variations during the stress stimulation (before pain perception), a significantly increased activation between D0 and D28 was observed for left and right frontal area (p = 0.001 and p = 0.002, respectively), left and right anterior cingulate cortex (ACC) (p = 0.035 and p = 0.04, respectively), and left and right insula (p = 0.034 and p = 0.0402, respectively) in Mg-Teadiola versus placebo group. During thermal pain stimulation, a significantly diminished activation of the pain matrix was observed between D0 and D28, for left and right prefrontal area (both p = 0.001), left and right insula (p = 0.008 and p = 0.019, respectively), and left and right ventral striatum (both p = 0.001) was observed in Mg-Teadiola versus placebo group. These results reinforce the clinical observations, showing a perceived benefit of Mg-Teadiola on several parameters. After 1 month of treatment, DASS-42 stress score significantly decreased in Mg-Teadiola group [effect size (ES) -0.46 (-0.91; -0.01), p = 0.048]. Similar reductions were observed on D14 (p = 0.011) and D56 (p = 0.008). Sensitivity to cold also improved from D0 to D28 for Mg-Teadiola versus placebo [ES 0.47 (0.02; 0.92) p = 0.042].

Conclusion: Supplementation with Mg-Teadiola reduced stress on D28 in chronically stressed but otherwise healthy individuals and modulated the stress and pain cerebral matrices during stressful thermal stimulus.

Keywords: L-theanine; Rhodiola; chronic stress; fMRI; green tea; magnesium; pain; vitamins.

Figure 1

Study design and thermal pain stimulus cycles (A) Study design (B) Thermal pain stimulus cycles Mg-Teadiola, a combination of 150 mg magnesium (Mg), 0.7 mg vitamin B6, 0.1 mg vitamin B9, 1.25 μg vitamin B12, 222 mg of Rhodiola extract, and 125 mg of green tea extract including 50 mg of L-theanine. D, day; DASS-42, Depression Anxiety Stress Scale; Mg, magnesium; NPS, Neuropathic Pain Scale; NS, numerical scale.

Figure 2

Patient disposition Mg-Teadiola, combination of 150 mg Mg, 0.7 mg vitamin B6, 0.1 mg vitamin B9, 1.25 μg vitamin B12, 222 mg of Rhodiola extract, and 125 mg of green tea extract including 50 mg of L-theanine. Mg, magnesium.

Figure 3

Stress matrix at D0 showing activation of the left (L) and right (R) of anterior cingulate cortex (ACC), the L and R of anterior insula (AI), the L and R of ventral striatum, the L and R of precuneus, and supplementary motor cortices One-sample t-test statistical results of the whole-brain analysis of the BOLD responses of stress stimulation > rest contrast at D0 for all individuals was performed. Statistical t maps were overlaid on MNI slices using a voxel-wise threshold of p < 0.001 and an extent threshold of 20 voxels. Regions were automatically labeled using the Anatomy Toolbox atlas of SPM and were presented in the table below. x, y, and z were MNI coordinates in the L-R, anterior–posterior, and inferior–superior dimensions, respectively. All peaks were significant at a voxel-wise threshold of p < 0.001 (extend threshold = 20 voxels). ACC, anterior cingulate cortex; AI, anterior insula; BOLD, blood oxygen level dependent; L, left; R, right; MNI, Montreal Neurological Institute; SPM, Statistical Parametric Mapping.

Figure 4

Pain matrix at D0 showing activation of the L and R of prefrontal cortices, ACC, anterior and posterior, the L and R of insula, and supplementary motor cortices One-sample t-test statistical results of the whole-brain analysis of the BOLD responses of pain stimulation > rest contrast at D0 for all individuals was performed. Statistical t maps are overlaid on MNI slices using a voxel-wise threshold of p < 0.001 and an extent threshold of 20 voxels. Regions were automatically labeled using the Anatomy Toolbox atlas of SPM and were presented in the table below. x, y, and z were MNI coordinates in the L-R, anterior–posterior, and inferior–superior dimensions, respectively. All peaks were significant at a voxel-wise threshold of p < 0.001 (extend threshold = 20 voxels). ACC, anterior cingulate cortex; BOLD, blood oxygen level dependent; L, left; R, right; MNI, Montreal Neurological Institute; SPM, Statistical Parametric Mapping.

Figure 5

Whole-brain analysis of the blood-oxygen-level-dependent (BOLD) responses of the Mg-Teadiola (D0 > D28) > Placebo (D0 > D28) contrast during stress stimulation Statistical t maps were overlaid on MNI slices using a voxel-wise threshold of p < 0.05 and an extent threshold of five voxels. They were covering frontal area (A), ACC (B), and insula (C). Black arrow points each region of interest at L and R. Regions were automatically labeled using the Anatomy Toolbox atlas of SPM and were presented in the table below. x, y, and z were MNI coordinates in the L-R, anterior–posterior, and inferior–superior dimensions, respectively. All peaks were significant at a voxel-wise threshold of p < 0.05 (extend threshold = 5 voxels). ACC, anterior cingulate cortex; L, left; R, right; MNI, Montreal Neurological Institute; SPM, Statistical Parametric Mapping.

Figure 6

Whole-brain analysis of the BOLD responses of the Mg-Teadiola (D0 > D28) < Placebo (D0 > D28) contrast during pain stimulation Statistical t maps are overlaid on MNI slices using a voxel-wise threshold of p < 0.05 and an extent threshold of five voxels. They are covering frontal and prefrontal area (A), insula (B), and ventral striatum (C). Black arrow points each region of interest at L and R. Regions are automatically labeled using the Anatomy Toolbox atlas of SPM and are presented in the table below. x, y, and z are MNI coordinates in the L-R, anterior–posterior, and inferior–superior dimensions, respectively. All peaks are significant at a voxel-wise threshold of p < 0.05 (extend threshold = 5 voxels). L, left; R, right; MNI, Montreal Neurological Institute; SPM, Statistical Parametric Mapping.