Neurocognitive effects a combined polyphenolic-rich herbal extract in healthy middle-aged adults – a randomised, double-blind, placebo-controlled study

Figures & data

Figure 1. CONSORT flow diagram of the participant progress through a randomised trial of two groups.

Table 1. Demographic and descriptive information for supplement conditions (means, SD).

Variable	Total sample (N = 52)	Active (n = 26)	Placebo (n = 26)	Test statistic
	M (SD)	M (SD)	M (SD)
Sex (n, %)				χ^2 = 3.90, p = 0.04
Female	40(76.9%)	17(32.69%)	23(44.23%)
Male	12(23.1%)	9(17.3%)	3(5.76%)
Age (Years)	50.46(9.46)	50.69(10.11)	50.23(8.98)	F = 0.030, p = .862
Education (Years)	17.31(4.65)	16.50(3.5)	18(5.49)	F = 1.58, p = .214
Dietary Quality (DST)	66.25(10.76)	65.00(14.98)	67.50(10.26)	F = .483, p = .490
Hours work (Weekly)	24.45(18.23)	21.63(18.45)	27.28(17.91)	F = 1.257, p = .268
Sick days in past 3 months	1.71(2.52)	1.65(2.51)	1.77(2.57)	F = 0.027, p = .871
Health rating (compared to others)	1.94(0.64)	2.08(0.63)	1.81(0.63)	F = 2.369, p = .130
Health rating (compared to a perfect state of health)	2.48(0.78)	2.58(0.76)	2.38(0.80)	F = 0.788, p = .379
Body Mass Index (BMI)	26.83(7.40)	27.27(5.83)	26.35(8.91)	F = 0.190, p = .665
Current medical conditions (Yes) (n, %)	23(44.2%)	13(24.98%)	10(19.21%)	χ^2 = .702., p = .402
Current medication use (Yes) (n, %)	23(45.1%)	12(23.53%)	11(21.57%)	χ^2 = 0.167, p = .683
Current supplement use (Yes) (n, %)	27 (51.9%)	13(48.1%)	14(51.82%)	χ^2= 0.07, p = .781
Exercise (days per month)	17.02(10.39)	14.65(9.58)	19.38(10.81)	F = 2.78., p = .101
Alcoholic drinks (in last Week)	2.71(3.84)	2.50(3.06)	2.92(4.55)	F = .155 p = .696
Smoker (Yes) (n, %)	3(5.77%)	1(1.92%)	2(3.85%)	χ^2= 0.354, p = .552

Table 2. Baseline and change scores for mood and behaviour measures by supplement condition, presented as mean (SD).

	Baseline scores			Post-supplement Change scores			Follow-up change scores
	Active (N = 26)	Placebo (N = 26)	F ratio, p-value	Active	Placebo	F ratio, p-value	Active	Placebo	F ratio, p-value
DASS – Dep	5.61(5.57)	5.15(7.31)	.066, p = .79	−.96(1.61)	−.38(2.41)	1.41, p = .24	.38(2.15)	.08(2.28)	.004, p = .952
DASS – Anx	3.38(3.99)	5.46(5.83)	2.24, p = .141	−.11(1.24)	−.69(2.14)	2.30, p = .135	.19(1.54)	−.57(1.50)	1.64, p = .205
DASS – Stress	10.76(6.83)	10.69(7.69)	.001, p = .970	−.53(2.73)	−.76(2.64)	.049, p = .826	−.34(2.75)	−.76(2.62)	.551, p = .462
Prosociality	61.92(10.56)	60.30(10.56)	.304, p = .584	1.07(5.36)	.03(6.27)	.948, p = .335	−2.34(5.53)	−.65(6.27)	.427, p = .516
Social Safeness	39.42(9.01)	40.73(10.50)	.232, p = .632	2.19(5.26)	1.34(5.21)	.960, p = .332	−1.0(5.65)	.538(4.35)	1.09, p = .302
FOC towards others	14.11(8.25)	16.50(8.29)	1.07, p = .304	−.46(5.42)	−1.92(5.39)	.863, p.35	−.73(4.32)	.57(5.12)	.759, p = .388
FOC – from others	9.65(8.83)	11.11(8.43)	.372, p = .544	.38(6.32)	−2.23(3.96)	4.16, p = .047	.57(5.60)	.23(6.52)	.586, p = .448
FOC – self	8.96(12.46)	9.07(8.68)	.002, p = .969	.26(4.64)	−.03(5.79)	.370, p.546	.65(4.73)	−1.07(6.74)	.025, p = .875
PANAS – positive	25.46(6.15)	28.53(5.49)	3.61, p = .063	2.46(5.13)	−.53(3.73)	8.00, p = .007	−1.26(5.93)	−.07(4.18)	.468, p = .497
PANAS – negative	20.07(4.43)	21.15(4.97)	.678, p = .414	−.42(3.83)	−34(3.68)	.001, p = .974	−.07(3.53)	−1.1(4.15)	.431, p = .515

**Gender used as covariate in all analysis, for follow-up time point analysis, days between testing was also used as covariate. FOC = Fears of compassion.

Table 4. Post supplementation reliable change score for mood measures for each condition.

Mood measures	Condition N = 26 per condition	Reliable change
		n-n ^a^: (% of n = 26)	X^2	p
DASS-Depression	Active	0	1.02	.313
	Placebo	1 improved (3.85%)
DASS-Anxiety	Active	0	1.02	.313
	Placebo	1 improved (3.85%)
DASS-Stress	Active	0	NA
	Placebo	0
Prosociality	Active	5 improved (2 decline) (19.23%: 7.69%)	.84	.35
	Placebo	4 improved (1 decline) (15.38%: 3.85%)
Social Safeness	Active	9 improved (1 decline) (34%: 3.85%)	.083	.773
	Placebo	6 improved (3 decline) (23%: 11.53%)
Fears of compassion – towards others	Active	2 improved (0 decline) (7.69%)	.754	.385
	Placebo	4 improved (0 decline) (19.23%)
Fears of compassion – from others	Active	3 improved (2 decline) (11.53%: 7.69%)	.591	.442
	Placebo	3 improved (0 decline) (11.53%)
Fears of compassion – self	Active	1 improved (2 decline) (3.85%: 3.85%)	4.35	.035
	Placebo	3 improved (4 decline) (11.53%: 15.38%)
PANAS – positive	Active	5 improved (1 decline) (19.23%:3.85)	3.01	.071
	Placebo	1 improved (2 decline) (3.85%: 7.69%)
PANAS – negative	Active	1 improved (2 decline) (3.85%)	1.08	.298
	Placebo	1 improved (0 decline) (3.85%)

^a The first n represents those that did meet reliable change index and score indicates improvement on measure, the second n represents those who did meet reliable change index and score indicates worse/decline on measure.

Table 3. Baseline and change scores (mean, SD) for cognitive performance measures by supplement condition.

	Baseline scores			Post-supplement Change scores			Follow-up Change scores
Cognitive measure	Active	Placebo	F ratio, p-value	Active	Placebo	F ratio, p-value	Active	Placebo	F ratio, p-value
Ravlt total sum (A1-A5)	53.92 (9.93)	55.76 (7.78)	.556, p = .459	5.65 (6.46)	6.15 (5.85)	.194, p = .662	3.11 (8.61)	.96 (6.69)	.407, p = .527
Ravlt B1	8.08 (2.44)	8.15 (1.93)	.016, p = .900	.583 (2.54)	.15 (2.30)	.624, p = .434	.65 (1.95)	00 (2.77)	.048, p = .828
Ravlt A6	11.50 (3.35)	12.08 (2.38)	.512, p = .477	1.30 (2.64)	.769 (1.79)	.176, p = .677	−.03 (2.00)	.30 (1.93)	.246, p = .622
Ravlt A7 (delayed recall)	11.38 (3.65)	12.58 (2.30)	1.98, p = .165	1.307 (1.95)	−.0385 (2.04)	3.70, p = .06	.19 (2.03)	.23 (1.90)	.017, p = .898
Ravlt Recog	23.62 (5.61)	25.08 (3.66)	1.23, p = .272	1.42 (2.83)	.34 (2.92)	1.40, p = .242	−.34 (3.14)	.11 (3.64)	.00, p = .998
Ravlt Distractions	18.12 (1.36)	17.23 (2.37)	2.71, p = .106	.038 (2.39)	.00 (2.36)	.035, p = .853	.23 (2.17)	.07 (2.51)	.09, p = .761
1-Back RT* (msec)	458.43 (95.33)	520.84 (107.18)**	4.92, p = .031	12.80 (81.48)	28.42 (83.56)	3.43, p = .07	18.62 (65.80)	2.64 (76.91)	.014, p = .710
1-Back Accuracy (%)	92.54 (8.48)	94.00 (9.40)	.342, p = .562	3.12 (7.95)	3.72 (7.38)	.851, p = .361	1.20 (9.01)	−1.80 (6.39)	2.43, p = .125
1-Back Error (n)	1.24 (1.74)	2.04 (3.40)	.445, p = .508	−.57 (1.39)	−1.34 (2.39)	3.89, p = .054	−.03 (1.79)	.53 (2.50)	1.43, p = .237
2-Back Response Time (msec)	466.26 (95.91)	569.16 (107.18**)	11.01, p = .002	25.78 (97.58)	19.26 (130.30)	5.12, p = .028	13.16 (121.65)	−10.96 (90.15)	.398, p = .531
2-Back Accuracy (%)	80.96 (17.22)	84.88 (13.69)	.828, p.367	4.69 (9.54)	5.91 (16.49)	1.84, p = .180	1.71 (14.21)	1.13 (9.88)	.074, p = .787
2-Back Error (n)	4.54 (3.42)	3.69 (3.57)	.760, = .387	−1.30 (2.69)	−1.00 (3.09)	.287, p = .594	−.03 (3.30)	−.30 (1.91)	.01, p = .919
3-Back RT (msec)	457.87 (164.533)	460.79 (198.19)	.065, p = .800	−5.08 (162.03)	51.38 (233)	1.57, p.309	−4.96 (138.45)	5.62 (159.37)	.002,p = .962
3-Back Accuracy (%)	63.57 (18.72)	55.99 (17.84)	2.89, p = .142	.34 (17.11)	8.74 (24.14)	3.93, p = .053	2.18 (16.61)	1.37 (21.38)	.575, p = .452
3-Back Error (n)	9.77 (4.54)	10.88 (3.89)	.990, p = .324	−.50 (4.30)	−2.50 (4.98)	3.37, p = .072	−.73 (3.48)	−.80 (4.23)	.360, p = .551
Go-NoGo RT (msec)	314.37 (36.01)	305.83 (32.61)	.802, p = .375	−2.54 (46.07)	−10.61 (53.57)	.215, p = .645	6.84 (32.20)	8.74 (31.82)	.003, p = .959
Go-NoGo Accuracy (%) (inhibited)	88.81 (7.90)	87.30 (8.44)	.441, p = .510	−1.40 (8.76)	.16 (9.37)	.329, p = .569	1.70 (5.74)	2.76 (5.42)	.448,p = .507
Go-NoGo IES^a	354.06 (26.12)	350.62 (22.04)	.263, p = .610	2.44 (30.35)	3.13 (19.67)	.009 p = .998	−1.06 (25.39)	−.40 (24.66)	.013,p = .908
Stroop Congruent RT (msec)	712.88 (121.43)	777.80 (171.71)	2.47, p = .122	−28.136 (55.89)	−36.79 (70.06)	.074, p = .786	−1.77 (49.90)	1.60 (87.53)	.287,p = .595
Stroop Congruent Accuracy (%)	98.42 (1.42)	98.62 (1.77)	.178, p = .675	−.22 (1.44)	.11 (1.58)	2.13, p = .151	.57 (1.46)	.20 (1.35)	2.58, p = .116
Stroop Test – Congruent IES^a	723.52 (117.82)	787.53 (167.66)	2.53, p = .117	−26.73 (57.36)	−37.44 (71.43)	.22, p = .640	−5.59 (51.28)	.04 (87.25)	.534, p = .46
Stroop Test – Incongruent RT (msec)	410.44 (82.83)	442.66 (95.64)	1.68, p = .200	−6.61 (60.37)	−24.73 (40.96)	1.40, p = .241	−19.90 (53.76)	−9.00 (22.72)	1.85, p = .179
Stroop Test – Incongruent Accuracy (%)	98.42 (1.51)	98.66 (1.82)	.259, p = .613	.29 (2.05)	.33 (1.23)	.837, p = .365	−.05 (1.16)	−.38 (1.77)	3.30, p = .075
Stroop Test – Incongruent IES^a	416.95 (83.87)	449.19 (100.56)	1.57, p = .215	−8.04 (59.54)	−27.23 (45.36)	1.74, p = .193	−20.02 (55.68)	−6.97 (28.09)	2.59, p = .114

**Gender used as covariate in all analysis, for follow-up time point, days between testing was also used as covariate. For N-back tasks, baseline RT (response time) was used a covariate also.

Table 5. Post supplementation reliable change score for each cognitive measure for each condition.

Cognitive measure	Condition	Reliable change index met: improved (decline)
		(n-n)^a % of N = 26	X^2	p
Ravlt total sum (A1–A5)	Active	11 improved (1 decline) (43.3%: 3.85%)	.00	1
	Placebo	11 improved (1 decline) (43.3%: 3.85%)
Ravlt B1	Active	7 improved (5 decline) (26.9%: 19.23%)	1.23	.266
	Placebo	3 improved (7 decline) (11.53%: 26.9%)
Ravlt A7 (delayed recall)	Active	12 improved (1 decline) (46.1%: 3.85%)	6.1	.046
	Placebo	5 improved (8 decline) (19.23%: 30.76%)
Ravlt Recog	Active	4 improved (1 decline) (15.38%: 3.85%)	.115	.73
	Placebo	4 improved (2 decline) (15.38%: 7.69%)
1-Back Accuracy (%)	Active	2 improved (0 decline) (7.69%)	.221	.638
	Placebo	3 improved (0 decline) (11.53%)
1-Back RT* (msec)	Active	0	1.02	.313
	Placebo	0 improved 1 decline (3.85%)
1-Back Error (n)	Active	1 improved (0 decline) (3.85%)	.354	.552
	Placebo	2 improved (0 decline) (7.69%)
2-Back Accuracy (%)	Active	0 improved (0 decline)	2.08	.09
	Placebo	2 improved (0 decline) (7.69%)
2-Back RT (msec)	Active	0 improved (3 decline) (11.53%)	2.02	.364
	Placebo	0 improved (1 decline) (3.85%)
2-Back Error (n)	Active	1 improved (0 decline) (3.85%)	.354	.552
	Placebo	2 improved (0 decline) (7.69)
3-Back Accuracy (%)	Active	1 improved (0 decline) (3.85%)	3.24	.071
	Placebo	4 improved (1 decline) (15.38%)
3-Back RT (msec)	Active	0 improved (1 decline) (3.85%)	.00	1
	Placebo	0 improved (1 decline) (3.85%)
3-Back Error (n)	Active	2 improved (0 decline) (7.69%)	2.36	.124
	Placebo	4 improved (1 decline) (15.38%:3.85%)
Go-NoGo RT (msec)	Active	4 improved (5 decline) (15.38%: 19.23%)	.087	.768
	Placebo	1 improved (7 decline) (3.85%: 26.9%)
Go-NoGo Acc** (%) (inhibited)	Active	4 improved (3 decline) (15.38%: 11.53%)	.433	.510
	Placebo	5 improved (0 decline) (19.23%)
Stroop – Congruent RT (msec)	Active	2 improved (0 decline) (7.69%)	.754	.385
	Placebo	4 improved (0 decline) (15.38%)
Stroop – Congruent Acc (%)	Active	7 improved (3 decline) (26.9%: 11.53%)	1.44	.229
	Placebo	3 improved (3 decline) (11.53%:11.53%)
Stroop – Incongruent RT (msec)	Active	2 improved (3 decline) (7.69%:11.53%)	.00	1
	Placebo	5 improved (0 decline) (19.23%)
Stroop – Incongruent Acc (%)	Active	8 improved (4 decline) (30.76%: 15.38%)	1.30	.254
	Placebo	5 improved (3 decline) (19.23%: 11.53%)

^a The first n represents those that did meet reliable change index and score indicates improved performance on measure, the second n represents those who did meet reliable change index and score indicates worse/decline in performance on measure. *RT = response time. **Acc = Accuracy.

Table 6. HbO response at baseline and change scores (mean and SD).

	Baseline scores			Post-supplement change scores			Follow-up change scores
FNIR measure for task	Active	Placebo	F ratio, p-value	Active	Placebo	F ratio, p-value	Active	Placebo	F ratio, p-value
Ravlt A	.793 (1.98)	.925 (1.15)	.087, p = .770	.505 (2.45)	.023 (1.26)	.793, p = .377	−.517 (1.99)	−.052 (1.56)	.873, p = .355
Ravlt B	.462 (2.46)	.780 (1.83)	.277, p = .601	1.01 (4.99)	.23 (3.06)	.458, p = .502	−.460 (4.94)	−.112 (3.30)	.089, p = .766
RavltA7 (delayed recall)	.497 (3.44)	1.69 (3.06)	1.76, p = .190	.691 (4.96)	−.594 (3.81)	1.09, p = .300	−.054 (4.94)	−.744 (3.42)	.341, p = .562
Ravlt Recog	1.49 (2.56)	.587 (2.63)	.786, p = .380	−.910 (4.67)	.071 (2.86)	.835, p = .365	.702 (5.02)	.622 (3.31)	.005, p = .947
1-Back	−.855 (1.12)	−.805 (1.15)	.025, p = .901	.557 (1.80)	.024 (1.57)	1.38, p = .245	−.381 (1.74)	−.023 (1.73)	.549, p = .462
2-Back	−1.40 (1.19)	−.881 (1.24)	2.44, p = .124	.835 (2.01)	−.197 (1.42)	4.53, p = .038**	−.172 (1.69)	.005 (1.68)	.143, p = .707
3-Back	−1.06 (1.44)	−1.25 (1.40)	.228, p = .635	.818 (3.07)	.707 (1.78)	.025, p = .874	−.441 (2.58)	−.183 (1.66)	.182, p = .671
Go-NoGo	−.451 (1.60)	−.589 (1.03)	.137, p = .713	.181 (1.39)	−.113 (2.5)	.275, p = .602	−.011 (1.37)	.444 (2.87)	.532, p = .469
Stroop – Congruent	−.014 (1.91)	−.198 (1.33)	.161, p = .690	−.115 (2.72)	1.29 (4.177)	2.06, p = .157	−.895 (4.96)	.131 (2.87)	.834, p = .366
Stroop – Incongruent	−.288 (1.42)	−.049 (1.49)	.349, p = .557	1.25 (5.84)	.30 (3.12)	.528, p = .471	−.792 (5.73)	−.196 (2.68)	.230, p = .634

** Change noted in left hand side 2 back F = 4.56, p = .038 only, not right hand side. No other left or right hand activation changes note.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and are available upon request to corresponding author.