Polymorphisms in SLC44A1 are associated with cognitive improvement in children diagnosed with fetal alcohol spectrum disorder: an exploratory study of oral choline supplementation

Smith, Susan; Virdee, Manjot S; Eckerle, Judith K.; Sandness, Kristin E.; Georgieff, Michael; Boys, Christopher J.; Zeisel, Steven H.; Wozniak, Jeffrey R.

doi:10.1093/ajcn/nqab081

Cited by 13 publications

(15 citation statements)

References 41 publications

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“…This may suggest that the beneficial effects of choline supplementation are additive and may compound with age, and there may be a relatively narrow developmental window for postnatal supplementation [ 168 ]. Emerging evidence also suggests genetic factors (e.g., choline-related single-nucleotide polymorphisms) may partially mediate neuroprotective effects in this population [ 166 ], pointing to the need for further study.…”

Section: Discussionmentioning

confidence: 99%

“…In a retrospective analysis of data from this trial [ 163 ], Smith et al [ 166 ] examined the role of multiple choline-related single-nucleotide polymorphisms (SNPs) in explaining the cognitive improvement associated with choline supplementation. Results indicated SNPs within the cellular choline transporter gene solute carrier family 44 member 1 (SLC44A1), implicated in transporting choline across plasma and mitochondrial membranes, were significantly associated with EI performance.…”

Section: Human Studies Also Demonstrate Choline Benefits Following Paementioning

confidence: 99%

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Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder

Ernst

Gimbel²,

Water³

et al. 2022

Nutrients

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Fetal alcohol spectrum disorder (FASD) is common and represents a significant public health burden, yet very few interventions have been tested in FASD. Cognitive deficits are core features of FASD, ranging from broad intellectual impairment to selective problems in attention, executive functioning, memory, visual–perceptual/motor skills, social cognition, and academics. One potential intervention for the cognitive impairments associated with FASD is the essential nutrient choline, which is known to have numerous direct effects on brain and cognition in both typical and atypical development. We provide a summary of the literature supporting the use of choline as a neurodevelopmental intervention in those affected by prenatal alcohol. We first discuss how alcohol interferes with normal brain development. We then provide a comprehensive overview of the nutrient choline and discuss its role in typical brain development and its application in the optimization of brain development following early insult. Next, we review the preclinical literature that provides evidence of choline’s potential as an intervention following alcohol exposure. Then, we review a handful of existing human studies of choline supplementation in FASD. Lastly, we conclude with a review of practical considerations in choline supplementation, including dose, formulation, and feasibility in children.

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Section: Discussionmentioning

confidence: 99%

Section: Human Studies Also Demonstrate Choline Benefits Following Paementioning

confidence: 99%

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder

Ernst

Gimbel²,

Water³

et al. 2022

Nutrients

View full text Add to dashboard Cite

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“…This foundational centrality of epigenotoxicity to the understanding of cannabinoid toxicity is highly reminiscent of the central understanding which the fundamentally epigenomic nature of fetal alcohol syndrome has been shown to display [ 309 , 310 , 311 , 312 , 313 , 314 , 315 , 316 , 317 , 318 , 319 , 320 ]. Indeed, fetal alcohol syndrome has been shown to be primarily mediated epigenomically via cannabinoid type 1 receptors (CB1Rs) [ 321 , 322 , 323 , 324 , 325 , 326 , 327 , 328 , 329 , 330 , 331 ].…”

Section: Resultsmentioning

confidence: 99%

Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis

Reece

Hulse

2022

IJERPH

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Background: Twelve separate streams of empirical data make a strong case for cannabis-induced accelerated aging including hormonal, mitochondriopathic, cardiovascular, hepatotoxic, immunological, genotoxic, epigenotoxic, disruption of chromosomal physiology, congenital anomalies, cancers including inheritable tumorigenesis, telomerase inhibition and elevated mortality. Methods: Results from a recently published longitudinal epigenomic screen were analyzed with regard to the results of recent large epidemiological studies of the causal impacts of cannabis. We also integrate theoretical syntheses with prior studies into these combined epigenomic and epidemiological results. Results: Cannabis dependence not only recapitulates many of the key features of aging, but is characterized by both age-defining and age-generating illnesses including immunomodulation, hepatic inflammation, many psychiatric syndromes with a neuroinflammatory basis, genotoxicity and epigenotoxicity. DNA breaks, chromosomal breakage-fusion-bridge morphologies and likely cycles, and altered intergenerational DNA methylation and disruption of both the histone and tubulin codes in the context of increased clinical congenital anomalies, cancers and heritable tumors imply widespread disruption of the genome and epigenome. Modern epigenomic clocks indicate that, in cannabis-dependent patients, cannabis advances cellular DNA methylation age by 25–30% at age 30 years. Data have implications not only for somatic but also stem cell and germ line tissues including post-fertilization zygotes. This effect is likely increases with the square of chronological age. Conclusion: Recent epigenomic studies of cannabis exposure provide many explanations for the broad spectrum of cannabis-related teratogenicity and carcinogenicity and appear to account for many epidemiologically observed findings. Further research is indicated on the role of cannabinoids in the aging process both developmentally and longitudinally, from stem cell to germ cell to blastocystoids to embryoid bodies and beyond.

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“…Some syndromes were chosen because they are known to have pathophysiological overlap with cannabinoid effects, such as foetal alcohol syndrome, which has been shown to signal to the epigenome through the cannabinoid type 1 receptor (CB1R) [ 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ]. Moreover, cannabis is often co-abused with alcohol and each has been described as being a gateway drug for the other [ 38 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study

Reece

Hulse

2023

Pediatric Reports

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Introduction: Recent series of congenital anomaly (CA) rates (CARs) have showed the close and epidemiologically causal relationship of cannabis exposure to many CARs. We investigated these trends in Europe where similar trends have occurred. Methods: CARs from EUROCAT. Drug use from European Monitoring Centre for Drugs and Drug Addiction. Income data from World Bank. Results: CARs were higher in countries with increasing daily use overall (p = 9.99 × 10−14, minimum E-value (mEV) = 2.09) and especially for maternal infections, situs inversus, teratogenic syndromes and VACTERL syndrome (p = 1.49 × 10−15, mEV = 3.04). In inverse probability weighted panel regression models the series of anomalies: all anomalies, VACTERL, foetal alcohol syndrome, situs inversus (SI), lateralization (L), and teratogenic syndromes (TS; AAVFASSILTS) had cannabis metric p-values from: p < 2.2 × 10−16, 1.52 × 10−12, 1.44 × 10−13, 1.88 × 10−7, 7.39 × 10−6 and <2.2 × 10−16. In a series of spatiotemporal models this anomaly series had cannabis metric p-values from: 8.96 × 10−6, 6.56 × 10−6, 0.0004, 0.0019, 0.0006, 5.65 × 10−5. Considering E-values, the cannabis effect size order was VACTERL > situs inversus > teratogenic syndromes > FAS > lateralization syndromes > all anomalies. 50/64 (78.1%) E-value estimates and 42/64 (65.6%) mEVs > 9. Daily cannabis use was the strongest predictor for all anomalies. Conclusion: Data confirmed laboratory, preclinical and recent epidemiological studies from Canada, Australia, Hawaii, Colorado and USA for teratological links between cannabis exposure and AAVFASSILTS anomalies, fulfilled epidemiological criteria for causality and underscored importance of cannabis teratogenicity. VACTERL data are consistent with causation via cannabis-induced Sonic Hedgehog inhibition. TS data suggest cannabinoid contribution. SI&L data are consistent with results for cardiovascular CAs. Overall, these data show that cannabis is linked across space and time and in a manner which fulfills epidemiological criteria for causality not only with many CAs, but with several multiorgan teratologic syndromes. The major clinical implication of these results is that access to cannabinoids should be tightly restricted in the interests of safeguarding the community’s genetic heritage to protect and preserve coming generations, as is done for all other major genotoxins.

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Polymorphisms in SLC44A1 are associated with cognitive improvement in children diagnosed with fetal alcohol spectrum disorder: an exploratory study of oral choline supplementation

Cited by 13 publications

References 41 publications

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder

Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis

Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study

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