Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I² statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (−2.14 [95% CI −3.22 to −1.07]; p < 0.0001; I² = 97%), EPA (−0.72 [95% CI −1.25 to −0.18]; p = 0.008; I² = 88%), and ARA (−0.83 [95% CI, −1.48 to −0.17]; p = 0.01; I² = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I² = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (−1.96 [95% CI −3.5 to −0.34]; p = 0.02; I² = 0) and repetitive and restricted interests and behaviours (−1.08 [95% CI −2.17 to −0.01]; p = 0.05; I² = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA.

Long-chain polyunsaturated fatty acids (LCPUFAs) and their metabolites are considered essential factors to support bone and joint health. The n-6 PUFAs suppress the osteoblasts differentiation via increasing peroxisome proliferator-activated receptor gamma (PPARγ) expression and promoting adipogenesis while n-3 PUFAs promote osteoblastogenesis by down-regulating PPARγ and enhancing osteoblastic activity. Arachidonic acid (AA) and its metabolite prostaglandin E2 (PGE2) are key regulators of osteoclast differentiation via induction of the receptor activator of nuclear factor kappa-Β ligand (RANKL) pathway. Marine-derived n-3 LCPUFAs have been shown to inhibit osteoclastogenesis by decreasing the osteoprotegerin (OPG)/RANKL signalling pathway mediated by a reduction of pro-inflammatory PGE2 derived from AA. Omega-3 PUFAs reduce the expression of cartilage degrading enzyme matrix metalloproteinase-13 (MMP-13) and a disintegrin and metalloprotease with thrombospondin motifs-5 (ADAMTS-5) protein, oxidative stress and thereby apoptosis via nuclear factor kappa-betta (NF-kβ) and inducible nitric oxide synthase (iNOS) pathways. In this review, a diverse range of important effects of LCPUFAs on bone cells and chondrocyte was highlighted through different mechanisms of action established by cell cultures and animal studies. This review allows a better understanding of the possible role of LCPUFAs in bone and chondrocyte metabolism as potential therapeutics in combating the pathological complications such as osteoporosis and osteoarthritis.

Low vitamin D status in early development has been hypothesised as an environmental risk factor for Autism Spectrum Disorder (ASD), given the concurrent increase in the prevalence of these two conditions, and the association of vitamin D with many ASD-associated medical conditions. Identification of vitamin D-ASD factors may provide indications for primary and secondary prevention interventions. We systematically reviewed the literature for studies on vitamin D-ASD relationship, including potential mechanistic pathways. We identified seven specific areas, including: latitude, season of conception/birth, maternal migration/ethnicity, vitamin D status of mothers and ASD patients, and vitamin D intervention to prevent and treat ASD. Due to differences in the methodological procedures and inconsistent results, drawing conclusions from the first three areas is difficult. Using a more direct measure of vitamin D status—that is, serum 25(OH)D level during pregnancy or childhood—we found growing evidence for a relationship between vitamin D and ASD. These findings are supported by convincing evidence from experimental studies investigating the mechanistic pathways. However, with few primary and secondary prevention intervention trials, this relationship cannot be determined, unless randomised placebo-controlled trials of vitamin D as a preventive or disease-modifying measure in ASD patients are available.

Maximizing peak bone mass during adolescence may be the key to postponing and perhaps preventing bone fractures due to osteoporosis in later life. One mechanism to maximize peak bone mass is to maximize calcium absorption, and it has been suggested that inulin and oligofructose might be one of the ways of doing so. In this study, fructooligosaccharides with various degrees of polymerization have been compared in terms of impact on calcium absorption, bone density, and excretion of collagen cross-links in the young adult male rat. The various oligosaccharides were oligofructose (DP2-8), inulin (DP>23), and a mixture of 92% inulin and 8% short-chain oligofructose (DP2-8). Measuring ex vivo bone mineral density (BMD) and bone mineral content (BMC) showed that BMD was significantly higher in the group fed inulin (DP>23) in both femurs, whereas BMC was significantly higher in the spine. The excretion of fragments of Type 1 collagen decreased in all groups over the 4 weeks of feeding, but the decrease was most significant in the group fed inulin (DP>23). Several hypotheses have been offered to explain the effect of the fructooligosaccharides on calcium absorption and retention. These include the production of organic acids that would acidify the luminal contents and enhance solubility and hence absorption, or possibly a mechanism via calbindinD9k. This study is unique in that it compares the different fructooligosaccharides in the same model, and it clearly shows that the various fructans do not have the same effect. In our model, inulin (DP>23) had the most significant effect on calcium bioavailability.