Relationship Between Vitamin D During Perinatal Development and Health

The Effects of Early Vitamin D Exposure on Type 1 Diabetes

Type 1 diabetes is an autoimmune disease that begins in infancy and results in the destruction of insulin-producing β cells in the pancreas. The initiation of this process is not well understood, but it is estimated that by the time type 1 diabetes is diagnosed, 80% to 90% of β cells have been destroyed.^[51] Prevention (rather than treatment strategies) may be most effective in the fight against type 1 diabetes.

There is evidence from epidemiology (Table 1) that vitamin D is a contributing factor in the development of type 1 diabetes. Experimental studies suggest that vitamin D deficiency may be involved in the pathogenesis of type 1 diabetes,^[52,53] possibly because vitamin D is a potent modulator of the immune system and is involved in regulating cell proliferation and differentiation.^[54] According to a Finnish study, children who receive a daily dose of 2000 IU of vitamin D starting in the first year of life have a reduced risk of developing type 1 diabetes.^[55] Likewise, Norwegian children with rickets who take cod liver oil (rich in vitamin D) in the first year of life have a lower risk of developing type 1 diabetes.^[56] The exact mechanism by which vitamin D protects against type 1 diabetes remains unknown, but the identification of VDR in both β cells and immune cells has led to a number of studies of the delineation of these pathways.^[57] The scientific evidence thus far suggests that vitamin D supplementation early in life may be important in the protection of β cells' function and prevention of type 1 diabetes.^[58,59]

Table 1. Epidemiologic Evidence Linking Vitamin D and Disease
Disease Relationship	Variables Used in Epidemiology to Infer a Relationship to Vitamin D
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

Table 1. Epidemiologic Evidence Linking Vitamin D and Disease

Disease Relationship

Variables Used in Epidemiology to Infer a Relationship to Vitamin D

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