Effect of oral vitamin D on cognitive function: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

ZHANG Xiaoli ¹ , ZHANG Yiyin ¹ , YIN Yuhuan ¹ , YE Jianying ¹ ,  ZHANG Juxia ²

1. School of Nursing, Gansu University of Chinese Medicine, Lanzhou 730000, P. R. China;
2. Clinical Education Department, Gansu Provincial Hospital, Lanzhou 730000, P. R. China;

Corresponding?author：

ZHANG Juxia, Email: 364954672@qq.com

Keywords：

Alzheimer’s disease; Cognitive impairment; Dementia; Vitamin D; Meta-analysis

DOI：

10.7507/1672-2531.202209117

Video：

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Objective To systematically review the effect of vitamin D (VitD) supplementation on cognitive function in people with cognitive impairment and non-cognitive disorders. Methods The PubMed, Web of Science, Cochrane Library, EMbase, CBM, CNKI, WanFang Data and VIP databases were searched to collect randomized controlled trials (RCTs) about the effect of VitD supplementation on cognitive function of patients with cognitive impairment or non-cognitive disorders from inception to March, 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.4 software. Results A total of 19 articles including 8 684 cases were included. The results of meta-analysis showed that mini-mental state examination (MMSE) score (MD=1.70, 95%CI 1.20 to 2.21, P<0.01), Montreal cognitive assessment (MoCA) score (MD=1.51, 95%CI 1.00 to 2.02, P<0.01), Wechsler Adult Intelligence Scale-Revised (WAIS-RC) score (MD=9.12, 95%CI 7.77 to 10.47, P<0.01) and working memory (SMD=1.87, 95%CI 1.07 to 2.67, P<0.01) in the VitD group of patients with cognitive impairment were all better than those in the control group. However, the overall cognitive function and working memory of the non-cognitive impairment population were not significantly different compared with the control group. In terms of language fluency and language memory, there was no significant difference between the VitD group and the control group. In terms of the executive functions, at the intervention time of> 6 months, the VitD and control groups were statistically significant (SMD=0.15, 95%CI 0.01 to 0.28, P=0.03). Conclusion Current evidence suggests that VitD supplementation can effectively improve the overall cognitive function and working memory of patients with cognitive impairment, and has a positive effect on executive function at an intervention time of >6 months. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.

Citation： ZHANG Xiaoli, ZHANG Yiyin, YIN Yuhuan, YE Jianying, ZHANG Juxia. Effect of oral vitamin D on cognitive function: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2023, 23(4): 416-421. doi: 10.7507/1672-2531.202209117 Copy

1.	Goh AMY, Gaffy E, Hallam B, et al. An update on dementia training programmes in home and community care. Curr Opin Psychiatry, 2018, 31(5): 417-423.
2.	Alzheimer's disease international world Alzheimer report 2019.
3.	Wang LP, Li YJ, Yan WZ, et al. Development and psychometric testing chinese version of the frommelt attitude toward care of the dying scale, form b in nurses and nursing students. J Cancer Educ, 2016, 31(1): 123-130.
4.	Xu J, Wang J, Wimo A, et al. The economic burden of dementia in China, 1990-2030: implications for health policy. Bull World Health Organ, 2017, 95(1): 18-26.
5.	Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis, 2013, 33(3): 659-674.
6.	Shih EJ, Lee WJ, Hsu JL, et al. Effect of vitamin D on cognitive function and white matter hyperintensity in patients with mild Alzheimer's disease. Geriatr Gerontol Int, 2020, 20(1): 52-58.
7.	Miller JW, Harvey DJ, Beckett LA, et al. Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adults. JAMA Neurol, 2015, 72(11): 1295-1303.
8.	Chai B, Gao F, Wu R, et al. Vitamin D deficiency as a risk factor for dementia and Alzheimer's disease: an updated meta-analysis. BMC Neurol, 2019, 19(1): 284.
9.	Jayedi A, Rashidy-Pour A, Shab-Bidar S. Vitamin D status and risk of dementia and Alzheimer's disease: a meta-analysis of dose-response. Nutr Neurosci, 2019, 22(11): 750-759.
10.	Mehri N, Haddadi R, Ganji M, et al. Effects of vitamin D in an animal model of Alzheimer's disease: behavioral assessment with biochemical investigation of Hippocampus and serum. Metab Brain Dis, 2020, 35(2): 263-274.
11.	Mokhtari-Zaer A, Hosseini M, Salmani H, et al. Vitamin D₃ attenuates lipopolysaccharide-induced cognitive impairment in rats by inhibiting inflammation and oxidative stress. Life Sci, 2020, 253: 117703.
12.	Annweiler C, Herrmann FR, Fantino B, et al. Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: a pre-post pilot study. Cogn Behav Neurol, 2012, 25(3): 121-127.
13.	Jia J, Hu J, Huo X, et al. Effects of vitamin D supplementation on cognitive function and blood Aβ-related biomarkers in older adults with Alzheimer's disease: a randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry, 2019, 90(12): 1347-1352.
14.	Owusu JE, Islam S, Katumuluwa SS, et al. Cognition and Vitamin D in older African-American women- physical performance and osteoporosis prevention with vitamin D in older African Americans trial and dementia. J Am Geriatr Soc, 2019, 67(1): 81-86.
15.	Hasegawa, N, Mochizuki, M, Kato, M, et al. Vitamin D₃ supplementation improved physical performance in healthy older adults in Japan: a pilot study. Health, 2018, 10: 1200-1209.
16.	Chai X, Jin Y, Wei Y, et al. The effect of vitamin D supplementation on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: a protocol for systematic review and meta-analysis. Medicine (Baltimore), 2022, 101(49): e32254.
17.	Yang T, Wang H, Xiong Y, et al. Vitamin D supplementation improves cognitive function through reducing oxidative stress regulated by telomere length in older adults with mild cognitive impairment: a 12-month randomized controlled trial. J Alzheimers Dis, 2020, 78(4): 1509-1518.
18.	Bischoff-Ferrari HA, Vellas B, Rizzoli R, et al. Effect of Vitamin D supplementation, omega-3 fatty acid supplementation, or a strength-training exercise program on clinical outcomes in older adults: the DO-HEALTH randomized clinical trial. JAMA, 2020, 324(18): 1855-1868.
19.	沈佳英, 潘云菲, 任菁菁. 口服維生素D對高血壓伴輕度認知功能障礙患者認知功能的影響. 中國老年學雜志, 2022, 42(3): 631-634.
20.	Gangwar AK, Rawat A, Tiwari S, et al. Role of Vitamin-D in the prevention and treatment of Alzheimer's disease. Indian J Physiol Pharmacol, 2015, 59(1): 94-99.
21.	鄧增山, 彭志鋒. 鹽酸美金剛聯合維生素D對阿爾茨海默病患者認知功能的影響. 中國藥物與臨床, 2016, 16(6): 881-883.
22.	Hu J, Jia J, Zhang Y, et al. Effects of vitamin D₃ supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry, 2018, 89(12): 1341-1347.
23.	Schietzel S, Fischer K, Brugger P, et al. Effect of 2000 IU compared with 800 IU Vitamin D on cognitive performance among adults age 60 years and older: a randomized controlled trial. Am J Clin Nutr, 2019, 110(1): 246-253.
24.	趙曉暉, 朱玉萍, 劉慧琴, 等. 骨化三醇對腦白質疏松所致輕度認知功能障礙的療效分析. 中國動脈硬化雜志, 2015, 23(10): 1012-1016.
25.	Zajac IT, Barnes M, Cavuoto P, et al. The effects of Vitamin D-enriched mushrooms and vitamin d3 on cognitive performance and mood in healthy elderly adults: a randomised, double-blinded, placebo-controlled trial. Nutrients, 2020, 12(12): 3847.
26.	汪婷, 章秋, 劉安諾, 等. 維生素D口服輔助治療2型糖尿病伴輕度認知功能障礙臨床觀察. 山東醫藥, 2017, 57(27): 73-75.
27.	高暢, 唐志雄, 傅小玲, 等. 骨化三醇對阿爾茨海默病治療效果的影響. 中日友好醫院學報, 2018, 32(3): 152-154,164.
28.	Rossom RC, Espeland MA, Manson JE, et al. Calcium and vitamin D supplementation and cognitive impairment in the women's health initiative. J Am Geriatr Soc, 2012, 60(12): 2197-2205.
29.	Jorde R, Kubiak J, Svartberg J, et al. Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects. J Neurol Sci, 2019, 396: 165-171.
30.	Byrn MA, Adams W, Penckofer S, et al. Vitamin D supplementation and cognition in people with type 2 diabetes: a randomized control trial. J Diabetes Res, 2019, 2019: 5696391.
31.	安玉蘭. 對接受家庭護理的阿爾茨海默病患者使用維生素D滴劑進行治療的效果探討. 當代醫藥論叢, 2018, 16(14): 196-198.
32.	Latimer CS, Brewer LD, Searcy JL, et al. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proc Natl Acad Sci U S A, 2014, 111(41): E4359-E4366.
33.	Briones TL, Darwish H. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J Neuroinflammation, 2012, 9: 244.
34.	Lin CI, Chang YC, Kao NJ, et al. 1, 25(OH)₂D₃ alleviates aβ(25-35)-induced tau hyperphosphorylation, excessive reactive oxygen species, and apoptosis through interplay with glial cell line-derived neurotrophic factor signaling in SH-SY5Y cells. Int J Mol Sci, 2020, 21(12): 4215.
35.	SanMartin CD, Henriquez M, Chacon C, et al. Vitamin D increases aβ140 plasma levels and protects lymphocytes from oxidative death in mild cognitive impairment patients. Curr Alzheimer Res, 2018, 15(6): 561-569.
36.	Koshkina A, Dudnichenko T, Baranenko D, et al. Effects of vitamin D3 in long-term ovariectomized rats subjected to chronic unpredictable mild stress: BDNF, NT-3, and NT-4 implications. Nutrients, 2019, 11(8): 1726.
37.	?ahin S, Gürgen SG, Yazar U, et al. Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats. Epilepsy Res, 2019, 149: 107-116.
38.	Al-Amin MM, Sullivan RKP, Kurniawan ND, et al. Adult vitamin D deficiency disrupts hippocampal-dependent learning and structural brain connectivity in BALB/c mice. Brain Struct Funct, 2019, 224(3): 1315-1329.
39.	Al-Amin M, Bradford D, Sullivan RKP, et al. Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment. Hum Brain Mapp, 2019, 40(2): 394-406.
40.	Du Y, Liang F, Zhang L, et al. Vitamin D supplement for prevention of Alzheimer's disease: a systematic review and meta-analysis. Am J Ther, 2020, 28(6): e638-e648.
41.	Cheng L, Dong R, Song C, et al. Mediation effects of IL-1β and IL-18 on the association between vitamin d levels and mild cognitive impairment among chinese older adults: a case-control study in taiyuan, china. Front Aging Neurosci, 2022, 14: 836311.
42.	Pettersen JA. Does high dose vitamin D supplementation enhance cognition. A randomized trial in healthy adults. Exp Gerontol, 2017, 90: 90-97.
43.	Buell JS, Scott TM, Dawson-Hughes B, et al. Vitamin D is associated with cognitive function in elders receiving home health services. J Gerontol A Biol Sci Med Sci, 2009, 64(8): 888-895.
44.	Glerup H, Mikkelsen K, Poulsen L, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int, 2000, 66(6): 419-424.

1. Goh AMY, Gaffy E, Hallam B, et al. An update on dementia training programmes in home and community care. Curr Opin Psychiatry, 2018, 31(5): 417-423.
2. Alzheimer's disease international world Alzheimer report 2019.
3. Wang LP, Li YJ, Yan WZ, et al. Development and psychometric testing chinese version of the frommelt attitude toward care of the dying scale, form b in nurses and nursing students. J Cancer Educ, 2016, 31(1): 123-130.
4. Xu J, Wang J, Wimo A, et al. The economic burden of dementia in China, 1990-2030: implications for health policy. Bull World Health Organ, 2017, 95(1): 18-26.
5. Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis, 2013, 33(3): 659-674.
6. Shih EJ, Lee WJ, Hsu JL, et al. Effect of vitamin D on cognitive function and white matter hyperintensity in patients with mild Alzheimer's disease. Geriatr Gerontol Int, 2020, 20(1): 52-58.
7. Miller JW, Harvey DJ, Beckett LA, et al. Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adults. JAMA Neurol, 2015, 72(11): 1295-1303.
8. Chai B, Gao F, Wu R, et al. Vitamin D deficiency as a risk factor for dementia and Alzheimer's disease: an updated meta-analysis. BMC Neurol, 2019, 19(1): 284.
9. Jayedi A, Rashidy-Pour A, Shab-Bidar S. Vitamin D status and risk of dementia and Alzheimer's disease: a meta-analysis of dose-response. Nutr Neurosci, 2019, 22(11): 750-759.
10. Mehri N, Haddadi R, Ganji M, et al. Effects of vitamin D in an animal model of Alzheimer's disease: behavioral assessment with biochemical investigation of Hippocampus and serum. Metab Brain Dis, 2020, 35(2): 263-274.
11. Mokhtari-Zaer A, Hosseini M, Salmani H, et al. Vitamin D₃ attenuates lipopolysaccharide-induced cognitive impairment in rats by inhibiting inflammation and oxidative stress. Life Sci, 2020, 253: 117703.
12. Annweiler C, Herrmann FR, Fantino B, et al. Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: a pre-post pilot study. Cogn Behav Neurol, 2012, 25(3): 121-127.
13. Jia J, Hu J, Huo X, et al. Effects of vitamin D supplementation on cognitive function and blood Aβ-related biomarkers in older adults with Alzheimer's disease: a randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry, 2019, 90(12): 1347-1352.
14. Owusu JE, Islam S, Katumuluwa SS, et al. Cognition and Vitamin D in older African-American women- physical performance and osteoporosis prevention with vitamin D in older African Americans trial and dementia. J Am Geriatr Soc, 2019, 67(1): 81-86.
15. Hasegawa, N, Mochizuki, M, Kato, M, et al. Vitamin D₃ supplementation improved physical performance in healthy older adults in Japan: a pilot study. Health, 2018, 10: 1200-1209.
16. Chai X, Jin Y, Wei Y, et al. The effect of vitamin D supplementation on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: a protocol for systematic review and meta-analysis. Medicine (Baltimore), 2022, 101(49): e32254.
17. Yang T, Wang H, Xiong Y, et al. Vitamin D supplementation improves cognitive function through reducing oxidative stress regulated by telomere length in older adults with mild cognitive impairment: a 12-month randomized controlled trial. J Alzheimers Dis, 2020, 78(4): 1509-1518.
18. Bischoff-Ferrari HA, Vellas B, Rizzoli R, et al. Effect of Vitamin D supplementation, omega-3 fatty acid supplementation, or a strength-training exercise program on clinical outcomes in older adults: the DO-HEALTH randomized clinical trial. JAMA, 2020, 324(18): 1855-1868.
19. 沈佳英, 潘云菲, 任菁菁. 口服維生素D對高血壓伴輕度認知功能障礙患者認知功能的影響. 中國老年學雜志, 2022, 42(3): 631-634.
20. Gangwar AK, Rawat A, Tiwari S, et al. Role of Vitamin-D in the prevention and treatment of Alzheimer's disease. Indian J Physiol Pharmacol, 2015, 59(1): 94-99.
21. 鄧增山, 彭志鋒. 鹽酸美金剛聯合維生素D對阿爾茨海默病患者認知功能的影響. 中國藥物與臨床, 2016, 16(6): 881-883.
22. Hu J, Jia J, Zhang Y, et al. Effects of vitamin D₃ supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry, 2018, 89(12): 1341-1347.
23. Schietzel S, Fischer K, Brugger P, et al. Effect of 2000 IU compared with 800 IU Vitamin D on cognitive performance among adults age 60 years and older: a randomized controlled trial. Am J Clin Nutr, 2019, 110(1): 246-253.
24. 趙曉暉, 朱玉萍, 劉慧琴, 等. 骨化三醇對腦白質疏松所致輕度認知功能障礙的療效分析. 中國動脈硬化雜志, 2015, 23(10): 1012-1016.
25. Zajac IT, Barnes M, Cavuoto P, et al. The effects of Vitamin D-enriched mushrooms and vitamin d3 on cognitive performance and mood in healthy elderly adults: a randomised, double-blinded, placebo-controlled trial. Nutrients, 2020, 12(12): 3847.
26. 汪婷, 章秋, 劉安諾, 等. 維生素D口服輔助治療2型糖尿病伴輕度認知功能障礙臨床觀察. 山東醫藥, 2017, 57(27): 73-75.
27. 高暢, 唐志雄, 傅小玲, 等. 骨化三醇對阿爾茨海默病治療效果的影響. 中日友好醫院學報, 2018, 32(3): 152-154,164.
28. Rossom RC, Espeland MA, Manson JE, et al. Calcium and vitamin D supplementation and cognitive impairment in the women's health initiative. J Am Geriatr Soc, 2012, 60(12): 2197-2205.
29. Jorde R, Kubiak J, Svartberg J, et al. Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects. J Neurol Sci, 2019, 396: 165-171.
30. Byrn MA, Adams W, Penckofer S, et al. Vitamin D supplementation and cognition in people with type 2 diabetes: a randomized control trial. J Diabetes Res, 2019, 2019: 5696391.
31. 安玉蘭. 對接受家庭護理的阿爾茨海默病患者使用維生素D滴劑進行治療的效果探討. 當代醫藥論叢, 2018, 16(14): 196-198.
32. Latimer CS, Brewer LD, Searcy JL, et al. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proc Natl Acad Sci U S A, 2014, 111(41): E4359-E4366.
33. Briones TL, Darwish H. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J Neuroinflammation, 2012, 9: 244.
34. Lin CI, Chang YC, Kao NJ, et al. 1, 25(OH)₂D₃ alleviates aβ(25-35)-induced tau hyperphosphorylation, excessive reactive oxygen species, and apoptosis through interplay with glial cell line-derived neurotrophic factor signaling in SH-SY5Y cells. Int J Mol Sci, 2020, 21(12): 4215.
35. SanMartin CD, Henriquez M, Chacon C, et al. Vitamin D increases aβ140 plasma levels and protects lymphocytes from oxidative death in mild cognitive impairment patients. Curr Alzheimer Res, 2018, 15(6): 561-569.
36. Koshkina A, Dudnichenko T, Baranenko D, et al. Effects of vitamin D3 in long-term ovariectomized rats subjected to chronic unpredictable mild stress: BDNF, NT-3, and NT-4 implications. Nutrients, 2019, 11(8): 1726.
37. ?ahin S, Gürgen SG, Yazar U, et al. Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats. Epilepsy Res, 2019, 149: 107-116.
38. Al-Amin MM, Sullivan RKP, Kurniawan ND, et al. Adult vitamin D deficiency disrupts hippocampal-dependent learning and structural brain connectivity in BALB/c mice. Brain Struct Funct, 2019, 224(3): 1315-1329.
39. Al-Amin M, Bradford D, Sullivan RKP, et al. Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment. Hum Brain Mapp, 2019, 40(2): 394-406.
40. Du Y, Liang F, Zhang L, et al. Vitamin D supplement for prevention of Alzheimer's disease: a systematic review and meta-analysis. Am J Ther, 2020, 28(6): e638-e648.
41. Cheng L, Dong R, Song C, et al. Mediation effects of IL-1β and IL-18 on the association between vitamin d levels and mild cognitive impairment among chinese older adults: a case-control study in taiyuan, china. Front Aging Neurosci, 2022, 14: 836311.
42. Pettersen JA. Does high dose vitamin D supplementation enhance cognition. A randomized trial in healthy adults. Exp Gerontol, 2017, 90: 90-97.
43. Buell JS, Scott TM, Dawson-Hughes B, et al. Vitamin D is associated with cognitive function in elders receiving home health services. J Gerontol A Biol Sci Med Sci, 2009, 64(8): 888-895.
44. Glerup H, Mikkelsen K, Poulsen L, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int, 2000, 66(6): 419-424.

Chinese Journal of Evidence-Based Medicine

Effect of oral vitamin D on cognitive function: a meta-analysis

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