Table 1 Characteristics of included human flavonoid RCTs

1. Casini et al. (2006)

78 (ITT: 78)

~44 to 54 years

Post-menopausal female

Italy

n/a

Randomised placebo-controlled trial—crossover

T: 60 mg/d total isoflavones

C: Placebo

Duration: 13 months (2 × 6 month treatments + 1 month washout)

Processing speed:

Digit symbol test (*)

Memory:

Digit span forwards (ns)

Executive function/Working memory:

Digit symbol accuracy (*)

Digit span backwards (*)

Visual search: Visual scanning test (ns)

t-tests (2-tailed)

2. Duffy et al. (2003)

33 (Excl: 3/36)

50–65 years

Post-menopausal female

UK

n/a

Double-blind randomised placebo-controlled

T: 60 mg/d total isoflavones

C: Placebo

Duration: 12 weeks

IQ:

NART—(used only to check baseline differences)

Memory:

Common Objects Recall Test (immediate) (*)

Logical Memory Test WMS-R (immediate) (ns)

Delayed Matching to Sample Test—CANTAB (delayed) (ns)

Executive function/Working memory:

Paced Auditory Serial Addition Test (*)

Stockings of Cambridge (ns)

Category generation (ns)

IDED Rule Learning and reversal—CANTAB (*—simple rule reversal condition only)

1. MANOVA

2. Univariate 2-way ANOVA (2-tailed)

3. File et al. (2001)

27

~22 to 30 years

Young adult

UK

n/a

Randomised controlled

T: 100 mg/d total isoflavones (‘high’)

C: 0.5 mg/d total isoflavones (‘low’, i.e. control)

Duration: 10 weeks

IQ:

NART—(used only to check baseline differences)

Processing speed/attention:

Digit symbol test (ns)

Memory:

Common Objects Recall Test (immediate) (*)

Logical Memory Test WMS-R (immediate) (*)

Delayed Matching to Sample Tes—CANTAB (delayed) (*)

Executive function/working memory:

Category generation task (ns)

Digit cancellation test (ns)

Paced Auditory Serial Addition Test (ns)

Stockings of Cambridge (*)

Verbal fluency: S (ns)

IDED Rule Learning and reversal—CANTAB (*)

ANOVA (2-tailed)

4. File et al. (2005)

50

51–66 years

Post-menopausal female

UK

n/a

Double-blind randomised placebo-controlled—parallel groups

T: 60 mg/d total isoflavones

C: Placebo

Duration: 6 weeks

IQ:

NART—(used only to check baseline differences)

Memory:

Common Objects Recall Test (immediate) (*)

Logical Memory Test WMS-R (immediate) (ns)

Delayed Matching to Sample Test—CANTAB (delayed) (ns)

Executive function/Working memory:

Category generation task (ns)

Paced Auditory Serial Addition Test (ns)

Stockings of Cambridge (*)

IDED Rule Learning and Reversal—CANTAB (*)

1. Two-way ANOVA

2. Three-way ANOVA

3. One-way ANOVA (2-tailed)

5. Fournier et al. (2007)

79

48–65 years

Post-menopausal female

USA

n/a

Double-blind randomised placebo-controlled

T: 70 mg/d total isoflavones (supplement + cow’s milk)

T: 71.6 mg/d total isoflavones (placebo + soy milk)

C: Cow’s milk

Duration: 16 weeks

Memory:

Digit span forwards (ns)

Corsi Block-Tapping (WAIS-R) (ns)

Pattern recognition (ns)

Benton Visual Retention Test (ns)

Executive function/Working memory:

Digit ordering (*)

Stroop (ns)

Colour matching (ns)

1. One-way ANOVA

2. Paired-difference t-tests

3. MANOVA

4. Two-way Least Square-Means (LSM) (2-tailed)

6. Francis et al. (2006)

16

18–30 years

Young adult female

UK

n/a

Double-blind randomised placebo-controlled

T: 172 mg (‘high’) cocoa flavonols

C: 13 mg (‘low’) cocoa flavanols

Duration: 2 weeks

Executive function:

Letter-digit pairs task (ns)

fMRI BOLD signal (*)

GLM—SPM99

7. Ho et al. (2007)

168 (ITT: 191)

55–76 years

Post-menopausal female

Hong Kong

MMSE > 22

Double-blind randomised placebo-controlled

T: 80 mg/d total soy isoflavones

C: Placebo

Duration: 6 months

General:

MMSE (ns)—(screening and global measure)

Memory:

Digit span forwards (ns)

Hong Kong List-Learning Test (imm/del’d) (ns)

Boston Naming Test (ns)

Executive function/working memory:

Digit span backwards (ns)

Rey-Osterrieth Complex Figure Test (ns)

Trail Making Test (ns)

Category fluency: animals/transportation (ns)

Digit Vigilance Test (ns)

Motor function:

Finger-Tapping Test (ns)

Intention-to-treat

1. t-tests

2. Chi-square

3. Estimation of treatment effect: 95% CIs

4. ANOVA

5. GLM ANCOVA (2-tailed)

8. Howes et al. (2004)

28 (ITT: 30)

60 + years

Post-menopausal female

Australia

MMSE > 26

Double-blind randomised placebo-controlled

T: 60 mg/d total isoflavones (red clover extract)

C: Placebo

Duration: 6 months

Processing speed:

Digit symbol test (ns)

Trail Making Test—Part A (ns)

Memory:

Digit recall (*)

Memory 1 (ns) & 2 tests (imm/del’d) (*)

Verbal Memory 1 & 2 tests (imm/del’d) (ns)

Visual Memory 1 & 2 tests (imm/del’d) (ns)

Boston naming test (ns)

Similarities test (ns)

Executive function/Working memory:

Block design test (*)

Arithmetic test (ns)

Trail Making Test—Part B (ns)

Verbal fluency: FAS and Animal tests (ns)

Intention-to-treat

1. Student’s t test

2. ANOVA

3. Multiple pairwise comparisons (Bonferroni correction adjusted p value (α) = 0.003) (2-tailed)

9. Kreijkamp-Kaspers et al. (2004)

153 (ITT: 202) (mITT: 175)

60–75 years

Post-menopausal female

Netherlands

n/a

Double-blind randomised placebo-controlled

T: 99 mg/d soy isoflavones

C: Placebo

Duration: 12 months

General:

MMSE (ns)—(global measure)

IQ:

DART—(used only to check baseline differences)

Memory:

Digit Span Forwards (ns)

Rey Auditory Verbal Learning Test (imm/del’d) (ns)

Doors Test (ns)

Boston Naming Test (ns)

Executive function/Working memory:

Digit span backwards (ns)

Digit Symbol Substitution Test (ns)

Trail Making Test (ns)

Verbal Fluency (ns)

Modified intention-to-treat

1. Linear regression analysis

10. Kritz-Silverstein et al. (2003)

53 (D/O: 3/56)

55–74 years

Post-menopausal female

USA

n/a

Double-blind randomised placebo-controlled

T: 110 mg/d total soy isoflavones

C: Placebo

Duration: 6 months

General:

MMSE (ns)—(baseline only)

Memory:

Logical Memory 1 & 2 (imm/del’d) (ns)

Executive function/Working memory:

Trail Making Test (ns)

Category Fluency (*)

1. ANOVA

2. Chi-Square (2-tailed)

11. Le Bars et al. (2002)

ITT: 236

45–90 years

Older adult with AD or MID

USA

MMSE > 23

MMSE < 24

MMSE < 15

Double-blind randomised placebo-controlled

T: 120 mg/d Ginkgo biloba extract Egb 761

C: Placebo

Duration: 12 months

General:

ADAS-Cog (*)

1. ANOVA (2-tailed)

12. Mix and Crews (2000)

40 (D/O: 8/48)

55–86 years

Older adult

USA

MMSE > 23

Double-blind randomised placebo-controlled

T: 180 mg/d Ginkgo biloba extract Egb 761

C: Placebo

Duration: 6 weeks

General:

MMSE (screening only)

Processing speed:

Stroop Word Naming Task (ns)

Stroop Colour Naming Task (*—one-tailed test)

Trail Making Test—Part A (ns)

Memory:

Logical Memory 1 & 2 tests (imm/del’d) (ns)

Visual memory 1 & 2 tests (imm/del’d) (ns)

Executive function/Working memory:

Stroop Colour-Word Task (ns)

Trail Making Test—Part B (ns)

1. t-tests

2. Chi-Square (1-tailed)

13. Pipingas et al. (2008)

42

50–65 years

Adult male

Australia

n/a

Double-blind randomised placebo-controlled

T: 960 mg/d Pinus radiata (contains 80% flavonoids, i.e. 768 mg/d total flavonoids) +120 mg/d vitamin C

C: 120 mg/d Vitamin C

Duration: 5 weeks

Processing speed:

Simple reaction time (ns)

Memory:

Visuospatial recognition (imm/del’d) (*—immediate RT only)

Contextual memory task (ns)

Executive function/Working memory:

Spatial working memory—RT/accuracy (*/***)

Choice reaction time (ns)

Visual vigilance (ns)

Complex visual vigilance (ns)

1. ANOVA

2. MANOVA

3. Post-hoc t-tests (2-tailed)

14. Ryan et al. (2008)

101 (D/O: 19/120)

60–85 years

Older adult

Australia

n/a

Double-blind randomised placebo-controlled

T: 150 mg/d total flavonoids (French maritime pine extract ‘Pycnogenol’)

C: Placebo

Duration: 3 months

Memory:

Delayed word recognition: CDR (ns)

Immediate number recognition: CDR (ns)

Power of attention: CDR (ns):

Digit vigilance: CDR (ns)

Simple reaction time: CDR (ns)

Choice reaction time: CDR (ns)

Quality of working memory: CDR (**):

Spatial working memory: CDR (*)

Numeric working memory: CDR (ns)

1. ANOVA

2. Post-hoc t-tests

15. Woo et al. (2003)

127

50–65 years

Post-menopausal female

Hong Kong

n/a

Double-blind randomised placebo-controlled

T: 100 mg/d total isoflavones (from Pueraria lobata)

T: HRT

C: Placebo

Duration: 3 months

General:

MMSE (*) (global measure)

Memory:

Hong Kong List-Learning Test (imm/del’d) (ns)

Executive function/Working memory:

Digit Symbol Substitution Test (*)

Boston Naming Test (ns)

Trail Making Test (e.g. Figure Trail 1 & 2) (*)

Motor function:

Finger-Tapping Test (ns)

1. Sample size calculation

2. ANCOVA (baseline value and education level adjusted)

3. Multiple-range test