Vitamin D Status in Children with Autism Spectrum Disorders: Determinants and Effects of the Response to Probiotic Supplementation

Abstract

A relationship between the presence of clinical symptoms and gastrointestinal (GI) disturbances associated with nutritional deficiencies, including vitamin D (25(OH)D) deficiency, has been observed in autism spectrum disorder (ASD). The aim was to evaluate 25(OH)D levels according to the annual rhythm cycle, gender, the severity of autism, nutritional or clinical status, inflammatory and metabolic biomarkers, GI symptoms, and the clinical response to probiotic/placebo supplementation in preschooler children with ASD. Eighty-one ASD preschoolers (67 males) were assessed with standardized tools for ASD severity (ADOS score) and GI symptoms (by GI-Index at six-items and at nine-items, the latter defined as the Total GI-Index). The 25(OH)D levels were compared among different ASD subgroups according to metabolic and inflammatory biomarkers (leptin, insulin, resistin, PAI-1, MCP-1, TNF-alfa, and IL-6), gender, and the presence or absence of: (i) GI symptoms, (ii) the response to probiotic supplementation (the improvement of GI symptomatology), (iii) the response to probiotic supplementation (improvement of ASD severity). Only 25% of the ASD children presented an adequate 25(OH)D status (≥30 ng/mL according to the Endocrine Society guidelines). All the 25(OH)D levels falling in the severe deficiency range (<10 ng/mL) were observed in the male subgroup. A significant inverse correlation between 25(OH)D and leptin was observed (R = −0.24, p = 0.037). An inverse correlation was found between 25(OH)D levels and the GI Index 6-Items and Total GI-Index (R = −0.25, p = 0.026; −0.27, = 0.009) and a direct relationship with the probiotic response (R = 0.4, p = 0.05). The monitoring of 25(OH)D levels and the co-administration of 25(OH)D and probiotic supplementation could be considered in ASD from early ages.

Vitamin D deficiency as a risk factor for developing autism in childhood – literature review

“…First reports on the possibility of using vitamin D to treat autism originate from 2014 when vitamin D was administered intramuscularly and orally to a three-yearold boy with ASD. A significant improvement in his health was noticed after increasing the vitamin level [5,22]. Further research has shown that vitamin D supplementation may relieve ASD symptoms [15] in about 75% of autistic children.…”

“…A relationship between the neurological symptoms and gastrointestinal problems associated with nutritional deficiencies, including (25(OH)D) deficiency, has been frequently frequently observed in ASD in the scientific literature. [22].…”

“…Other peripheral markers of inflammation, e.g. IL-1β, IL-6 or TNF-α, have also been found to be elevated in children with ASD [20,22]. Vitamin D has pro-apoptotic and anti-proliferative properties and participates in neuronal differentiation [8,21], it also indirectly affects the expression of protein Nrf2 and the anti-aging protein Klotho, both of which are also important regulators of many cell signalling systems.…”

The metabolic role of vitamin D in children’s neurodevelopment: a network study

“…Prior studies have linked ASD to Vitamin D deficiency during pregnancy and early childhood 12,13,39 . The underlying molecular mechanisms remain poorly understood, but a key role for neurotransmitter metabolism has been recently suggested 13,39 .…”

“…Metaanalyses have also identified a series of environmental risk factors, including pre-natal, perinatal, and post-natal elements 5,6,10 . Among these factors, vitamin D has been increasingly implicated in ASD pathogenesis [11][12][13] .…”