This study Nutrientsconcluded that there is a negative correlation between vitamin B12 and depression, and a causal relationship between vitamin C and Alzheimer’s disease, and iron and autism.
Micronutrient deficiencies are a common public health concern, especially for iron, vitamin B12, and vitamin C. Observational studies suggest that children with iron deficiency anemia are more likely to experience developmental delays and behavioral disorders, and maintaining high serum B12 levels in older adults may prevent Alzheimer’s disease (AD), but causal evidence for the association between micronutrients and psychiatric disorders is lacking.
Genome-wide association studies (GWAS) have enabled understanding of the genetic basis of micronutrient metabolism and deficiency and have identified notable genetic variants, or SNPs (single nucleotide polymorphisms), associated with micronutrient deficiencies.
A recent report states that “the integration of genetic findings into public health and clinical practice is paving the way for personalized precision nutrition interventions.”
the study
Linkage disequilibrium scores (LDSCs) allow researchers to assess genetic correlations between multiple complex human traits using GWAS summary data, while Mendelian randomization (MR) allows for the assessment of causal relationships between exposure factors and outcomes.
Using publicly available genome-wide association study (GWAS) summary datasets, researchers from Xi’an Jiaotong University in China first conducted LDSC regression analysis to investigate the genetic correlation between psychiatric disorders and micronutrients, and then conducted MR analysis to test the causal relationship between candidate micronutrients and mental health.
Certain micronutrients, including iron, vitamin A, vitamins B6, B1, C, D, and folate, were significantly associated with the risk of mental disorders identified in previous studies. After excluding some of these due to lack of significant SNPs or lack of data, the team ultimately selected iron, vitamin C, and vitamin B12 as variables.
Psychiatric disorders were selected based on their high public health burden, availability of genetic data, and known or hypothesized associations with micronutrient levels. Six neuropsychiatric traits from the largest recent GWAS were enrolled, including Alzheimer’s disease (AD), attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), bipolar disorder (BIP), and post-traumatic stress disorder (PTSD).
LDSC detected serum iron and vitamin C as candidate micronutrients for attention-deficit hyperactivity disorder (ADHD), iron-binding capacity as a candidate micronutrient for Alzheimer’s disease (AD), and vitamin C and vitamin B12 as candidate micronutrients for major depressive disorder (MDD).
Further MR analysis suggested a potential causal relationship between vitamin B12 and MDD.
Mechanism of action
Vitamin B12 is involved in homocysteine regeneration, methionine synthesis, methylation processes, and serotonin (5-HT) synthesis, and is a necessary micronutrient for maintaining proper neuronal function. Low vitamin B12 levels impede the regeneration of homocysteine to methionine and the isomerization of methylmalonyl CoA (MMA) to succinyl CoA, leading to elevated circulating levels of homocysteine and MMA. Increased homocysteine also increases the levels of reactive oxygen species, which subsequently contribute to neuronal apoptosis and induce depressive symptoms.
Iron is deeply involved in dopamine neurotransmission and dopamine synthesis. Iron accumulation may cause neurotoxicity and synaptic toxicity via oxidative stress and ferroptosis, leading to overactivation of dopamine neurotransmission, and ultimately contributing to psychiatric disorders.
Vitamin C is a powerful antioxidant that supports neurodevelopment, regulates neurotransmitters, protects neurons from damage caused by oxidative stress, and maintains normal function of the nervous system. Vitamin C is important not only in reducing oxidative stress, but also in suppressing proinflammatory genes, neuroinflammation, and Aβ fibril formation. A correlation between plasma vitamin C levels and AD has been found in observational studies.
The authors noted that further research is needed to clarify the underlying biological mechanisms by which micronutrients affect mental health.
They also noted that genome-wide association studies (GWAS) of some micronutrients (vitamin B6, vitamin A, and serum folate) could not be used for MR analysis due to insufficient significant SNPs, and emphasized that larger GWAS are needed to comprehensively investigate the causal relationships between micronutrients and mental disorders.
sauce: Nutrients
https://doi.org/10.3390/nu16132042
“Micronutrient-related single nucleotide polymorphisms and mental health: A Mendelian randomization study”
Authors: Hui, J.; Zhang, N.; Kang, M.; Gou, Y.; Liu, C.; Zhou, R.; Liu, Y.; Wang, B.; Shi, P.; Cheng, S.; et al.
