Relationship Between Vitamin D During Perinatal Development and Health

Jovana Kaludjerovic, MSc; Reinhold Vieth, PhD

J Midwifery Womens Health. 2010;55(6):550-560.

How Does Vitamin D Modulate Human Health?

The mechanism by which vitamin D modulates human health has not yet been identified. However, it has been proposed that metabolic imprinting may be responsible for the long-term program effects of 25(OH)D. Metabolic imprinting is an adaptive process that fine tunes the expression of specific genes, without directly altering the DNA sequence, to produce a phenotype that is best suited to survive in its predicted environment.^[16]

To better understand the concept of metabolic imprinting, the human body can be thought of as a factory and metabolic imprinting as quality control. In a factory, quality control ensures that the product is designed and produced to meet or exceed consumer requirements. If the product is defective or if there is a possibility that it may malfunction in its given environment, minor modifications are used through various processes to optimize product success and longevity. However, these modifications can only be made if appropriate tools and resources (i.e., raw material) are available. Similarly, in the human body, metabolic imprinting, which takes place during critical windows of development such as the prenatal and neonatal stages of life, ensures that an array of differentiated tissues produces a phenotype that can survive in its given environment.^[17] If the phenotype is well matched to its environment, the organism will remain healthy; however, if there is any sort of mismatch, the organism's ability to respond to environmental challenges may be inadequate and risk of disease may be high.^[16] An overview of how vitamin D modulates system development and chronic disease susceptibility is summarized in Figure 2 and Table 1 and expanded upon below.

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Figure 2.

Summary of mechanisms by which a lack of vitamin D leads to disease. The arrows indicated by solid lines represent endocrine signals (i.e., molecules moving via the circulation to produce their effects). The large block arrows represent paracrine action of 25(OH)D (i.e., the effects of vitamin D produced by the local production of 1,25(OH)₂D to permit communication between cells within each tissue). The arrows with light dashed lines represent mechanistic pathways. The asterisk (*) signifies that through a similar pathway, low plasma 25(OH)D can promote breast, prostate, or brain cancer.

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Table 1. Epidemiologic Evidence Linking Vitamin D and Disease
Disease Relationship	Variables Used in Epidemiology to Infer a Relationship to Vitamin D
Disease Relationship	Sun Exposure	Migration Away From High Sun Exposure	Season of Birth	Skin Pigmentation	Dietary Vitamin D
Osteomalacia and rickets	Decreased sun exposure in third trimester is associated with decreased bone mass²⁹	Afro-Caribbean immigrants in the UK are associated with an increased incidence of rickets⁶⁸	To our knowledge, no epidemiologic studies have shown this relationship	Children with darker skin have a higher prevalence of having poor bone health and rickets^17,69,70	Low maternal 25(OH)D concentrations during pregnancy are associated with decreased bone mineral content in children at 9 years of age²⁹ Vitamin D deficiency in early life is associated with rickets, mild respiratory distress, weak muscle tone, decreased calcium and increased parathyroid hormone levels⁷¹
Multiple sclerosis (MS)	Increased sun exposure during early life is associated with a decreased risk of MS⁷² MS relapse is inversely associated with UV exposure and 25(OH)D levels⁷³	Indian and Pakistani immigrants who enter the UK between 0–4 years of age are at increased risk of having MS⁷⁴ Second-generation Afro-Caribbean immigrants in the UK are associated with an increased MS risk⁷⁵	Data pooled from 4 countries shows that spring births are associated with an increased MS risk and fall births are associated with a decreased MS risk⁷⁶	Having white skin lowers the prevalence of MS disability⁷⁷	Consumption of fish 3–4 times a week is associated with a decreased MS risk⁷² Diets low in fish but high in meat and dairy products are associated with an increased prevalence of MS⁷⁸ Intake of vitamin D from supplements is inversely associated with MS risk⁷⁹
Schizophrenia	Increased sun exposure is associated with decreased risks of having schizophrenia, and schizophrenia-induced symptoms are weaker and less regular⁸⁰	Second-generation immigrants from Morocco and Surinam to the Netherlands are associated with an increased risk of schizophrenia⁸¹ Afro-Caribbean immigrants to the UK are associated with an increased risk of schizophrenia⁸²	Data pooled from 6 countries shows that winter births are associated with an increased incidence of schizophrenia^{83, 84}	Having black skin may be associated with an increased incidence of schizophrenia⁸⁵	Vitamin D supplementation during the first year of life lowered the risk of developing schizophrenia in males, but not females⁸⁶ Maternal 25(OH)D was not a risk factor for schizophrenia. But the results in the black subgroup raise the possibility that below a certain threshold low levels of 25(OH)D may be associated with an increased risk of schizophrenia⁸⁵
Type 1 diabetes	Monthly sunshine availability is inversely associated with having type 1 diabetes⁸⁷	Children who migrated to an area prevalent in diabetes (northern region) had a greater risk of developing type 1 diabetes⁸⁸	Winter and spring births are associated with higher frequency of type 1 diabetes^89–91 than summer births⁹¹	Children with black skin are at a higher risk of having type 1 diabetes than children with white skin⁹²	In a meta-analysis, vitamin D supplementation was associated with a decreased risk of type 1 diabetes⁹³ Children who consumed vitamin D supplements had an 80% lower risk of having type 1 diabetes⁵⁵ Use of cod liver oil by mothers during pregnancy and infants in the first year of life lowered the infants' risk of developing type 1 diabetes⁵⁶

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