Vitamin C Status and Cognitive Function: A Systematic Review
Abstract
:1. Introduction
2. Methods
2.1. Search Strategy
2.2. Selection of Trials
2.3. Quality Assessment
2.4. Analysis of Trials Using Comparable Methods
2.5. Blood Plasma Vitamin C
2.6. Measure of Cognition
2.7. Z Statistical Analysis-Correlation Between Blood Vitamin C and MMSE Score
3. Results
4. Discussion
4.1. Limitations
4.2. Future Directions
5. Conclusions
Author Contributions
Conflicts of Interest
References
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Paper | Study Design | N | Age (years) | Condition | Quality Rating | Cognitive Measure | Vitamin C Measure | Outcome |
---|---|---|---|---|---|---|---|---|
Arlt, 2012 [37] | RCT | 23 | 60–80 | AD | 6 | MMSE, Word fluency, Immediate/delayed verbal recall, Trail-making task | CSF | 1000 mg/day of vit C and E (400 mg/day) increased CSF concentrations after 1 year, but decreased MMSE score and no effect on other measures |
Galasko, 2012 [47] | RCT | 78 | 50–85 | AD | 4.5 | MMSE | CSF | Decline in MMSE score occurred in E/C/ALA group. (500 mg/day vit C, vit E, alpha lipoic acid) did not influence CSF biomarkers related to amyloid |
Burns, 1989 [39] | RCT | 81 | ≥65 | Senile Dementia, Community dementia | 4.5 | MMSE | Blood tests | 200 mg Vit C, vits B1, B2, B3 No correlation between vit C intake and cognitive impairment |
Bowman, 2009 [26] | Pros | 32 | 71 | AD | 5 | MMSE | CSF, plasma ascorbate | Neither Plasma nor CSF AA predictive of AD across 1 year |
Zandi, 2004 [40] | Pros | 4740 (4540 healthy) | ≥65 | AD | 3.5 | 3MS, Dementia Questionnaire (DQ) | Supplement, Interview | vit E (>400 IU) and C (500 mg) supplements reduced the AD prevalence and incidence. Supplements alone had no protective affect across 2 years |
Deijen, 2003 [41] | Pros | 90 | >65 | Psychiatry nursing home | 4.5 | Dutch geriatric nursing scale, Zorg Index geriatrie (ZIG) | Food record | Higher vitamin intakes were associated with a worse daily functioning across 6 months |
Rinaldi, 2003 [42] | Cross | 141 | >70 | MCI, AD | 3 | Clinical dementia rating scale, MMSE, clock drawing test, Babcock story recall, auditory verbal learning test, Corsi block tapping test, Token test, category naming test, Oral word association test, visual search test, digit forward and backward test, Raven’s progressive colored matrices | Plasma ascorbate | Lower vit C concentrations in patients with AD and MCI. MCI sig lower then controls |
Polidori, 2004 [43] | Cross | 141 | ≥65 | AD, VaD | 2 | MMSE | Plasma ascorbate | Plasma AA lower in AD and VD |
Richardson, 2002 [44] | Cross | 37 | 65–97 | In-patient ward | 2 | MMSE | Plasma ascorbate | 75% with dementia had low concentrations of vitamin C |
Lu, 2016 [45] | Cross | 2892 (768 MCI) | 58 | MCI | 2.5 | Montreal cognitive assessment | FFQ | Carotenoids, vit C, and vitamin B6 exhibited the highest protective factor loadings |
Charlton, 2004 [46] | CC | 93 | ≥65 | Dementia | 4 | MMSE | Plasma Ascorbate/FFQ | Plasma AA lower in dementia, not explained by diet |
Glaso, 2004 [47] | CC | 38 | 75–85 | AD | 4 | MMSE | Serum ascorbate/CSF | Both plasma vitamin C and CSF lower in AD. CSF: plasma AA ratio higher in AD |
Riviere,1999 [48] | CC | 69 | >75 | Severe AD, Moderate AD, Hospitalised AD | 3.5 | MMSE | Plasma ascorbate, FFQ | Nutritional intake lower in Severe AD, plasma vit C lower in more severe AD, not explained by vit C intake |
Masaki, 2000 [49] | CC | 3735 men | 71–93 | Dementia | 3 | Hasegawa scale, MMSE | Self-report supplementation | After controlling for factors such as age, education, stroke, there was an association with cognitive performance |
Paper | Study Design | N | Age (years) | Quality Assessment | Cognitive Measure | Vitamin C Measure | Outcome |
---|---|---|---|---|---|---|---|
Chandra, 2001 [50] | RCT | 86 | ≥65 | 5.5 | Wechsler memory test, Halstead-Reitan categories test, Buschke consistent long-term retrieval, digit span forward, salthouse listening span test, long-term memory recall, MMSE | Plasma spectrophotometry | 80 mg of vitamin C in a multivitamin improved cognitive performance, not Long-term memory across 1 year |
Dror, 1996 [51] | RCT | 21 | >80 | 3.5 | MMSE | Plasma Assay | No changes in MMSE scores following 42-day supplementation with 45mg/day of vitamin C with other vitamins (Vit D, E B12, B6) |
Gale, 1996 [52] | Pros | 921 | ≥65 | 2.5 | Hodkinson mental test (Dementia assessment) | Dietary intake/Ascorbate plasma | Cognitive function was poorest in those with the lowest vitamin C over 1 year |
La Rue, 1997 [53] | Pros | 137 | 66–90 | 5 | Abstract performance, visuospatial performance, memory assessment | Plasma Ascorbate, Nutritional status | Visuospatial performance was higher with higher ascorbate concentrations after 6 years |
Paleologos, 1998 [54] | Pros | 117 | 69–91 | 4 | MMSE, Reid brief neuropsychological Screen, the animals test of category fluency, the F, A, S test of verbal fluency | Semi-quantitative food frequency | After adjusting for age, sex, smoking, education, energy, vit C supplement linked to less severe cognitive decline, not verbal/category fluency across 4 years |
Devore, 2002 [55] | Pros | 16,010 | >70 Women | 5 | MMSE, Telephone interview for cognitive status (TICS). East Boston memory test (immediate/delayed) category fluency, Delayed TICS, Digit span backwards | Semi-quantitative food frequency | Dietary vitamin C intake not associated with cognitive decline. Supplemental vit C associated with worse decline over 6 years |
Engelhart, 2002 [56] | Pros | 5395 | >55 | 3.5 | DSM-III-R criteria, MMSE | Semi-quantitative food frequency (SFFQ) | Higher dietary vit C intake associated with less AD after a mean of 6.5 years, controlling for supplements |
Kalmijn, 1997 [57] | Pros | 342 Men | 69–89 | 3 | MMSE | Dietary history FFQ | Higher vit C intake not correlated with cognitive decline or impairment after 3 years |
Laurin, 2003 [58] | Pros | 2549 Men | 45–68 | 4 | Hasegawa dementia screening instrument, MMSE, 3MS | 24-h dietary recall | Vit C was not associated with the risk of dementia or its subtypes across an 8-year period |
Basambombo, 2016 [59] | Pros | 5269 | ≥65 | 2.5 | Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) | Self-reported supplementation | The use of vitamin C supplements associated with a reduced risk of cognitive decline during 3, 5 year intervals |
Nooyens, 2015 [60] | Pros | 2613 | 43–70 | 5 | 15 Words Learning Test, the Stroop Test, Word Fluency test, Letter Digit Substitution Test | 178-item semi-quantitative FFQ | No associations between intakes of vit C and cognitive decline across 5 years |
Peneau, 2011 [61] | Pros | 2533 | 45–60 | 4.5 | RI-48 cued recall, semantic, and phonemic fluency tests, trail-making and forward and backward digit span tests | 24-h dietary record | vit C–rich FVs (P-trend = 0.03), vitamin C (P-trend = 0.005) positively associated with verbal memory across 13 years |
Fotuhi, 2008 [62] | Pros | 3376 | ≥65 | 2.5 | 3MS | Self-report | Combined vit C, E, and anti-inflammatory resulted in a lower decline on the 3MS across 8 years. Vit C alone had no affect |
Gray, 2008 [63] | Pros | 2969 | ≥65 | 3.5 | Cognitive abilities screening instrument | Self-report | No association between vitamin C and AD incidence, or vit C and E together after 2.8–8.7 years |
Wengreen, 2007 [64] | Pros | 3831 | ≥65 | 3.5 | 3MS | Food frequency | Higher quartiles of vit C intake had a greater 3MS score and lower vit C intake had a greater rate of decline during 7 years |
Fillenbaum, 2005 [65] | Pros | 616 | 65–105 | 3.5 | Short portable mental status questionnaire | In home interview | Vitamin C did not reduce AD or dementia incidence over either 3 or 14-year interval |
Maxwell, 2005 [66] | Pros | 894 | ≥65 | 3.5 | 3MS | Self-report | Subjects reporting supplementation of vit C were less likely to have cognitive decline or to be diagnosed with VCI after 5 years |
Grodstein, 2003 [67] | Pros | 14,968 | 70–79 women | 4.5 | Telephone Interview of Cognitive Status, Delayed recall of 10 word lists, Immediate and delayed recall of paragraph, Verbal fluency, Digit span backwards | Supplementation questionnaire | Vit C and E had higher mean global scores than non-supplemented. Vit C alone did not affect global score after 5 years |
Luchsinger, 2003 [68] | Pros | 980 | ≥65 | 4.5 | Neuropsychological test battery | Semi quantitative food frequency | Neither dietary, supplemental nor total intake of vit C across 4 years was linked to AD Incidence |
Morris, 2002 [69] | Pros | 815 | >65 | 3 | Consortium Established for Research on AD | FFQ | Intake of vitamin C was not significantly associated with risk of AD across 3.9 years |
Peacock, 2000 [70] | Pros | 12,187 | 48–67 | 4.5 | Delayed word recall test, Wechsler adult intelligence scale, Revised digit symbol subtest, word fluency test | Food frequency questionnaire | No consistent association between dietary and supplemental vit C and cognition across 8 years |
Morris, 1998 [71] | Pros | 633 | ≥65 | 3.5 | Criteria for clinical diagnosis | Supplementation questionnaire | None of the vitamin C users were diagnosed after a mean of 4.3 years |
Mendelsohm, 1996 [72] | Pros | 1059 | ≥65 | 2.5 | Neuropsychological battery (15 items) | 297 vitamin C self-report supplementation | After adjustment for age, race, income, education, vit C supplementation did not relate to cognitive scores during 2 years |
Berti, 2015 [73] | Cross | 52 Women | 54–66 | 1.5 | Clinical dementia rating, Global deterioration score, MMSE | Harvard/Willet FFQ | Antioxidant consumption positively associated with METglc (p < 0.001) |
Beydoun, 2015 [74] | Cross | 1274 | 30–60 | 2 | MMSE, CLVT-list A, CVLT-DFR, digit span forward/backwards, Benten visual retention test, Animal fluency test, Brief test of attention, trail making test, Clock drawing test, card rotations, identical pictures | Two 24-h recalls | Vitamin C not associated with cognition on either cognitive task, MMSE error count (p = 0.17) |
Chaudhari, 2015 [75] | Cross | 582 | 40–96 | 2 | Repeatable battery for the assessment of neurological status, The executive interview | Ascorbate supplementation (self-report) | Vit C led to better immediate memory (p = 0.04), visuospatial skills (p = 0.002), language (p = 0.01), global cognition (p = 0.006) |
Goodwin, 1983 [76] | Cross | 260 | >60 | 2 | Halstead-Reitan Categories, (Non-verbal abstract thinking), Wechsler Memory Test | Dietary intake/Ascorbate plasma | Performance worse on both tasks in those with low vit C (5–10% lowest levels) |
Jama, 1996 [77] | Cross | 5182 | 55–95 | 2.5 | MMSE | Semi-quantitative food frequency questionnaire | No association between cognitive function and intake of vitamin C intake (<70mg/day (odd ratio) = 1.14, 130–160 mg/day (od) = 1.21 |
Lindemann, 2000 [78] | Cross | 195 | ≥65 | 3 | MMSE, WAIS-R Digits Forward, Fuld Object Memory Evaluation, Clock drawing, Two Color Trail Making Tests | Serum ascorbate | Lower vit C not associated with cognition. There was a trend. Low vit C linked with a history of depression |
Perrig, 1997 [79] | Cross | 442 | ≥65 | 3 | Computerised cognitive test (assessed working, implicit and explicit memory), WAIS-R vocabulary test | Plasma Ascorbate | Free recall, recognition, and vocabulary (not priming or working memory) correlated with ascorbic acid concentrations (semantic memory p = 0.034, vocabulary test p ≤ 0.021) |
Schmidt, 1998 [80] | Cross | 1769 | 50–75 | 2 | Mattis Dementia Rating Scale | Plasma (chromatograph) | No association between cognitive scores and plasma concentrations (odds ratio = 1, p = 0.87) |
Sato, 2006 [81] | Cross | 544 | ≥65 | 2.5 | Digit symbol substitution task (DSST), MMSE | Ascorbate plasma, Block’s FFQ | Highest fifth of plasma ascorbate associated with better DSST, marginally with MMSE |
Whalley, 2003 [82] | Cross | 176 | 77 | 2.5 | MMSE, Raven’s Progressive Matrices | Ascorbate plasma, FFQ (MONICA) | No difference between those taking vitamin C supplements and controls, after controlling for childhood IQ, education, socioeconomic status and cardiovascular health |
Perkins, 1998 [83] | Cross | 4809 | >60 | 2 | Delayed word recall, Delayed story recall | Serum ascorbate | After adjusting for socioeconomic factors and other trace elements, vitamin C concentrations were not associated with poor memory performance |
Ortega, 1997 [84] | Cross | 260 | 65–90 | 1.5 | MMSE, Pfeiffer’s mental status questionnaire | Food frequency for 7 days | Higher cognition correlated with great vitamin C intake across 7 days |
Requejo, 2003 [85] | Cross | 168 | 65–90 | 0.5 | MMSE | Food record | Those with a greater intake of vitamin C were more likely to display adequate cognitive ability |
Study | Study Design | Reason for Exclusion |
---|---|---|
Kennedy (2011) [86] | RCT | Mood/fatigue primary measures, vitamin C status not assessed |
Smith (1999) [87] | RCT | Self-reported cognitive failures (subjective cognitive assessment) |
Kumar (2008) [88] | RCT | Vitamin C status not assessed |
Yaffe (2004) [89] | RCT | Cognition not assessed at baseline, vitamin C status not assessed |
Kang (2009) [90] | RCT | Cognition not assessed at baseline, only 3.5 years after intervention |
Chui (2008) [91] | RCT | Vitamin C status not assessed, no placebo/blinding |
Day (1988) [92] | RCT | Vitamin C status not assessed, assessed only confusion |
Paraskevas (1997) [93]/Quinn (2004) [27]/Woo (1989) [94]/Polidori (2002) [95]/Foy (1998) [96] | CS | No cognitive tests administered |
Talley [97] | Pre-test post-test | Simple orientation/consciousness assessment |
Paper | Study Design | N | Mean Vitamin C Level in μmol/L (SD) | Mean MMSE Score (SD) |
---|---|---|---|---|
Burns (1989) [39] | RCT | 81 | Intervention baseline-33.5 (28) Placebo baseline-31.8 (31) Placebo final-25 (28) # | 1.9 (3.3) 5.7 (9.1) 5.7 (10.6) # |
Bowman (2009) [26] | Pros | 32 | 41 (30) | 19 (5) |
Rinaldi (2003) [42] | CS | 25 63 | MCI-24.9 (2.4) AD-25.9 (8.9) | 26.9 (2) 13.5 (6.5) |
Polidori (2004) [43] | CS | 63 23 | AD-25.9 (8.9) Vascular AD-26.6 (11.3) | 20.4 (3) 19.8 (3) |
Glaso (2004) [47] | CC | 20 | AD-44 (25) | 16.9 |
Rivierie (1999) [48] | CC | 24 9 20 | Moderate AD-35.7 Hospitalized AD-19.3 Severe AD-20.4 | 17.2 (4.9) 16.3 (6.1) 3.3 (3.1) |
Paper | Study Design | N | Vitamin C Level in μmol/L (SD) | MMSE Score (SD) |
---|---|---|---|---|
Engelhart (2002) [56] * | Pros | 5395 | 61.7 (27) | 28 |
Jama (1996) [77] * | CS | 5182 | 57.5 | 28 |
Ortega (1997) [84] | CS | 260 | 62.7 (33.5) | 27.4 (4.8) |
Whalley (2003) [82] | CS | 79 31 | Non-supplement user-33.7 (26.2) Supplement user-48.2 (25.7) | 28.5 (1.4) 28.9 (1.4) |
Glaso (2004) [47] | CC | 18 | Control group-80 (28) | 27.2 |
Polidori (2004) [43] | CS | 55 | Control group-52.4 (16.4) | 28.7 (1) |
Rinaldi (2003) [42] | CS | 53 | Control group-52.4 (16.5) | 28.1 (1.4) |
Chandra (2001) [50] # | RCT | 86 | Adequate Deficient | 28 (6.3) 17 (4) |
Lindemann (2003) [78] # | CC | 195 | >57 <57 | 27.2 (2.4) 26.4 (2.9) |
Sato (2006) [81] # | CC | 544 | Median = 74.9 (interquartile range = 57.8–90.7) Median = 78.9 (interquartile range = 64.1–99.2) | <27 >27 |
Richardson (2002) [44] # | CC | 37 | <11 11–40 40–100 | 23 (12.3) 25 (6.0) 27 (5.1) |
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Travica, N.; Ried, K.; Sali, A.; Scholey, A.; Hudson, I.; Pipingas, A. Vitamin C Status and Cognitive Function: A Systematic Review. Nutrients 2017, 9, 960. https://doi.org/10.3390/nu9090960
Travica N, Ried K, Sali A, Scholey A, Hudson I, Pipingas A. Vitamin C Status and Cognitive Function: A Systematic Review. Nutrients. 2017; 9(9):960. https://doi.org/10.3390/nu9090960
Chicago/Turabian StyleTravica, Nikolaj, Karin Ried, Avni Sali, Andrew Scholey, Irene Hudson, and Andrew Pipingas. 2017. "Vitamin C Status and Cognitive Function: A Systematic Review" Nutrients 9, no. 9: 960. https://doi.org/10.3390/nu9090960