Clinical research

Therapeutic effect of combined vitamin D and DHA supplementation on preschool children with attention deficit hyperactivity disorder

  • ZHANG Yue ,
  • ZHANG Lishan ,
  • DING Xiaoyuan ,
  • SHEN Zhimin ,
  • BIAN Zouji ,
  • YU Xiaodan
Expand
  • 1.Department of Developmental Behavioral Pediatrics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    2.Business Management Office, Shanghai Pudong Center for Women and Children's Health, Shanghai 201399, China
    3.Department of Pediatrics, Shanghai Pudong New Area People's Hospital, Shanghai 201299, China
YU Xiaodan, E-mail: xdyu1108@163.com.

Received date: 2024-05-01

  Accepted date: 2025-02-28

  Online published: 2025-05-28

Supported by

National Key Research and Development Program of China(2022YFC2705203);Clinical Research Center of Attention-Deficit Hyperactivity Disorder Affiliated with Pediatric College, Shanghai Jiao Tong University School of Medicine(ELYZX202207)

Abstract

Objective ·To investigate the therapeutic effect of combined vitamin D and docosahexaenoic acid (DHA) supplementation on preschool children with attention deficit hyperactivity disorder (ADHD). Methods ·From April 2021 to May 2021, a total of 1 412 children aged 4 to 6 years from eight kindergartens in Pudong New Area of Shanghai, including Tangqiao Street, Chuansha Town, and Heqing Town, were randomly selected by stratified cluster random sampling method. Attention and hyperactivity symptom assessment was performed using the Conner′s Scale, Diagnosis and Statistical Manual of Mental Disorders(fifth edition, DSM-Ⅴ), and Swanson, Nolan, and Pelham (version Ⅳ, SNAP-Ⅳ) Scale, and other neurodevelopmental disorders were excluded using the Wechsler Intelligence Scale. A total of 82 preschool children with ADHD were enrolled, and after fully informing them of the intervention measures, they were divided into an intervention group (n=64) and a control group (n=18) based on their parents′ choice. The control group received routine health education. In addition to routine health education, the intervention group received daily supplementation of Vitamin D (800 IU) and DHA (400 mg). Venous blood samples were collected from both groups at baseline, 3 months, and 12 months for the measurement of serum 25 hydroxy vitamin D [25 (OH) D] and DHA levels. ADHD symptoms were evaluated using Conner′s Scale, SNAP-Ⅳ Scale, and DSM-Ⅴ. Results ·After 3 and 12 months of intervention in the intervention group, serum 25 (OH) D levels and DHA levels were significantly higher (P<0.05), the ADHD symptom scores, including impulsivity-hyperactivity and hyperactivity index scores in Conner′s Scale, the attention and hyperactivity/impulsivity scores in SNAP-Ⅳ Scale, and the attention and hyperactivity/impulsivity scores in DSM-Ⅴ, were significantly reduced compared with the scores before the intervention (P<0.05). There was no significant difference in serum 25 (OH) D and DHA levels, or ADHD symptom scores, at the 3- and 12-month follow-ups compared to baseline. After 3 months of nutritional intervention in the intervention group, the hyperactivity/impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ were significantly improved compared to the control group (P<0.05). After 12 months of intervention, conduct problems, impulsive-hyperactivity and hyperactivity index scores in Conner′s Scale, and hyperactivity/ impulsivity scores in SNAP-Ⅳ Scale and DSM-Ⅴ showed significant improvement compared to the control group (P<0.05). Conclusion ·Combined supplementation with vitamin D and DHA significantly improves serum 25 (OH) D and DHA levels and alleviates ADHD symptoms in preschool children.

Cite this article

ZHANG Yue , ZHANG Lishan , DING Xiaoyuan , SHEN Zhimin , BIAN Zouji , YU Xiaodan . Therapeutic effect of combined vitamin D and DHA supplementation on preschool children with attention deficit hyperactivity disorder[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(5) : 570 -577 . DOI: 10.3969/j.issn.1674-8115.2025.05.005

References

1 SCHIWECK C, ARTEAGA-HENRIQUEZ G, AICHHOLZER M, et al. Comorbidity of ADHD and adult bipolar disorder: a systematic review and meta-analysis[J]. Neurosci Biobehav Rev, 2021, 124: 100-123.
2 童连, 史慧静, 臧嘉捷. 中国儿童ADHD流行状况Meta分析[J]. 中国公共卫生, 2013, 29(9): 1279-1283.
  TONG L, SHI H J, ZANG J J. Prevalence of ADHD in children of China: a systematic review and meta analysis[J]. Chinese Journal of Public Health, 2013, 29(9): 1279-1283.
3 LAW E C, SIDERIDIS G D, PROCK L A, et al. Attention-deficit/hyperactivity disorder in young children: predictors of diagnostic stability[J]. Pediatrics, 2014, 133(4): 659-667.
4 中华医学会儿科学分会发育行为学组. 注意缺陷多动障碍早期识别、规范诊断和治疗的儿科专家共识[J]. 中华儿科杂志, 2020, 58(3): 188-193.
  The Subspecialty Group of Developmental and Behavioral Pediatrics, the Society of Pediatrics, Chinese Medical Association. Consensus on pediatric clinical practice of early identification, standardized diagnosis and treatment of attention deficit hyperactivity disorder[J]. Chinese Journal of Pediatrics, 2020, 58(3): 188-193.
5 HUSMANN C, FRANK M, SCHMIDT B, et al. Low 25(OH)-vitamin D concentrations are associated with emotional and behavioral problems in German children and adolescents[J]. PLoS One, 2017, 12(8): e0183091.
6 FUENTES-ALBERO M, MARTíNEZ-MARTíNEZ M I, CAULI O. Omega-3 long-chain polyunsaturated fatty acids intake in children with attention deficit and hyperactivity disorder[J]. Brain Sci, 2019, 9(5): 120.
7 SALDANHA I J, ADAM G P, BA?EZ L L, et al. Inclusion of nonrandomized studies of interventions in systematic reviews of interventions: updated guidance from the Agency for Health Care Research and Quality Effective Health Care program[J]. J Clin Epidemiol, 2022, 152: 300-306.
8 CHANG J P, SU K P, MONDELLI V, et al. Omega-3 polyunsaturated fatty acids in youths with attention deficit hyperactivity disorder: a systematic review and meta-analysis of clinical trials and biological studies[J]. Neuropsychopharmacology, 2018, 43(3): 534-545.
9 GAN J, GALER P, MA D, et al. The effect of vitamin D supplementation on attention-deficit/hyperactivity disorder: a systematic review and meta-analysis of randomized controlled trials[J]. J Child Adolesc Psychopharmacol, 2019, 29(9): 670-687.
10 王鹭, 黄彦科, 江文庆, 等. 学龄前儿童注意缺陷多动障碍筛查量表的研究进展[J]. 中国儿童保健杂志, 2018, 26(10): 1100-1103.
  WANG L, HUANG Y K, JIANG W Q, et al. Research advances on screening scale for preschool children with attention deficit hyperactivity disorder[J]. Chinese Journal of Child Health Care, 2018, 26(10): 1100-1103.
11 周晋波, 郭兰婷, 陈颖. 中文版注意缺陷多动障碍SNAP-Ⅳ评定量表-父母版的信效度[J]. 中国心理卫生杂志, 2013, 27(6): 424-428.
  ZHOU J B, GUO L T, CHEN Y. Reliability and validity of the Chinese version of Swanson, Nolan, and Pelham Version Ⅳ Rating Scale-Parent Dorm for attention-deficit/hyperactivity disorder[J]. Chinese Mental Health Journal, 2013, 27(6): 424-428.
12 JIAO X, YUAN Y, WANG X, et al. Development of a sensitive HPLC-MS/MS method for 25-hydroxyvitamin D2 and D3 measurement in capillary blood[J]. J Clin Lab Anal, 2020, 34(10): e23451.
13 LANGE K W, LANGE K M, NAKAMURA Y, et al. Nutrition in the management of ADHD: a review of recent research[J]. Curr Nutr Rep, 2023, 12(3): 383-394.
14 HOLICK M F, BINKLEY N C, BISCHOFF-FERRARI H A, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline[J]. J Clin Endocrinol Metab, 2011, 96(7): 1911-1930.
15 PINTO S, CORREIA-DE-Sá T, SAMPAIO-MAIA B, et al. Eating patterns and dietary interventions in ADHD: a narrative review[J]. Nutrients, 2022, 14(20): 4332.
16 DECSI T, LOHNER S. Gaps in meeting nutrient needs in healthy toddlers[J]. Ann Nutr Metab, 2014, 65(1): 22-28.
17 KHOSHBAKHT Y, BIDAKI R, SALEHI-ABARGOUEI A. Vitamin D status and attention deficit hyperactivity disorder: a systematic review and meta-analysis of observational studies[J]. Adv Nutr, 2018, 9(1): 9-20.
18 CARDOSO C, AFONSO C, BANDARRA N M. Dietary DHA, bioaccessibility, and neurobehavioral development in children[J]. Crit Rev Food Sci Nutr, 2018, 58(15): 2617-2631.
19 BENEDIK E. Sources of vitamin D for humans[J]. Int J Vitam Nutr Res, 2022, 92(2): 118-125.
20 LAURITZEN L, BRAMBILLA P, MAZZOCCHI A, et al. DHA effects in brain development and function[J]. Nutrients, 2016, 8(1): 6.
21 MARTíNEZ-MARTíNEZ M I, ALEGRE-MARTíNEZ A, CAULI O. Omega-3 long-chain polyunsaturated fatty acids intake in children: the role of family-related social determinants[J]. Nutrients, 2020, 12(11): 3455.
22 HAWKEY E, NIGG J T. Omega-3 fatty acid and ADHD: blood level analysis and meta-analytic extension of supplementation trials[J]. Clin Psychol Rev, 2014, 34(6): 496-505.
23 乔娟, 熊子珺, 苏邹, 等. 二十二碳六烯酸对注意缺陷多动障碍儿童临床疗效、血清胶质源性神经营养因子及炎症因子水平的影响[J]. 临床精神医学杂志, 2022, 32(1): 21-25.
  QIAO J, QIONG Z J, SU Z, et al. Effects of docosahexaenoic acid on clinical efficacy and glial-derived neurotrophic factor and inflammatory cytokines in children with attention-deficient hyperactivity disorder[J]. Journal of Clinical Psychiatry, 2022, 32(1): 21-25.
24 中国儿童维生素D营养相关临床问题实践指南[J]. 中华儿科杂志, 2022, 60(5): 387-394.
  The Subspecialty Group of Children Health, the Society of Pediatrics, Chinese Medical Association the Editorial Board, Chinese Journal of Pediatrics. Practical guidelines for clinical issues related to vitamin D nutrition in Chinese children[J]. Chinese Journal of Pediatrics, 2022, 60(5): 387-394.
25 D?PFNER M, DOSE C, BREUER D, et al. Efficacy of omega-3/omega-6 fatty acids in preschool children at risk of ADHD: a randomized placebo-controlled trial[J]. J Atten Disord, 2021, 25(8): 1096-1106.
26 ANDO E, MORISAKI N, ASAKURA K, et al. Association between dietary intake and serum biomarkers of long-chain PUFA in Japanese preschool children[J]. Public Health Nutr, 2020, 24(4): 1-11.
27 王汐蕊, 余晓丹, 张丽珊, 等. 健康学龄前351名儿童25-羟维生素D水平及影响因素[J]. 中国儿童保健杂志, 2020, 28(10): 1101-1105.
  WANG X R, YU X D, ZHANG L S, et al. Serum 25-hydroxy vitamin D status and the influencing factors in 351 healthy preschool children[J]. Chinese Journal of Child Health Care, 2020, 28(10): 1101-1105.
28 EYLES D W, SMITH S, KINOBE R, et al. Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain[J]. J Chem Neuroanat, 2005, 29(1): 21-30.
29 PATRICK R P, AMES B N. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior[J]. FASEB J, 2015, 29(6): 2207-2222.
30 CUSTERS, EMMA E M, KILIAAN, et al. Dietary lipids from body to brain[J]. Prog Lipid Res, 2022, 85: 101144.
Outlines

/