Genetics of caffeine and brain-related outcomes - a systematic review of observational studies and randomized trials.

CONTEXT: Although the stimulant and anxiogenic properties of caffeine are widely accepted, research on its specific effects on the brain remains controversial. Growing evidence shows that interindividual differences in caffeine response may be partly due to variations in genes such as CYP1A2 and ADORA2A, which have been used to identify individuals as "fast" or "slow" caffeine metabolizers and as having a "high" or "low" caffeine sensitivity, respectively. OBJECTIVE: The objective of this review was to identify, evaluate, and discuss current evidence on the associations between common genetic variants, caffeine consumption, and brain-related outcomes in humans. DATA SOURCES: PubMed and Embase databases were searched for relevant reports based on a predetermined search strategy. DATA EXTRACTION: Reports of observational and experimental studies on healthy adults who underwent (a) genetic analysis for polymorphisms in genes associated with caffeine metabolism and effects and (b) measurements of brain-related effects such as anxiety, insomnia, and cognitive performance associated with the consumption of caffeine (habitual intake or supplementation) were included. DATA ANALYSIS: Of the 22 records included, 15 were randomized controlled trials, 6 were cross-sectional studies, and 1 was a genome-wide association study. The main outcomes identified were cognitive performance (n = 9), anxiety (n = 7), and sleep disturbance/insomnia (n = 6). Polymorphisms in the CYP1A2 gene were associated with cognitive function, while variations in the ADORA2A gene were associated with anxiety and sleep disturbance. CONCLUSION: The present review has provided evidence that variability in the CYP1A2 and the ADORA2A genes may modulate the association between caffeine and brain-related outcomes. Future studies are warranted to investigate the specific polymorphisms implicated in each brain outcome, which cognitive functions are particularly related to caffeine (simple vs complex), whether there are gender differences in anxiety effects, and how habitual caffeine intake may influence the acute effects of caffeine. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021257556.

The efficacy of genotype-based dietary or physical activity advice in changing behavior to reduce the risk of cardiovascular disease, type II diabetes mellitus or obesity: a systematic review and meta-analysis.

CONTEXT: Despite clear evidence that adherence to dietary and physical activity advice can reduce the risk of cardiometabolic disease, a significant proportion of the population do not follow recommendations. Personalized advice based on genetic variation has been proposed for motivating behavior change, although research on its benefits to date has been contradictory. OBJECTIVE: To evaluate the efficacy of genotype-based dietary or physical activity advice in changing behavior in the general population and in individuals who are at risk of cardiovascular disease (CVD) or type II diabetes mellitus (T2DM). DATA SOURCES: MEDLINE, EMBASE, PsycInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to January 7, 2022. Randomized controlled trials of a genotype-based dietary and/or physical activity advice intervention that aimed to change dietary and/or physical activity behavior were included. DATA EXTRACTION: Abstracts of 7899 records were screened, and 14 reports from 11 studies met the inclusion criteria. DATA ANALYSIS: Genotype-based dietary or physical activity advice was found to have no effect on dietary behavior in any of the studies (standardized mean difference [SMD] .00 [-.11 to .11], P = .98), even when analyzed by subgroup: "at risk" (SMD .00 [-.16 to .16, P = .99]; general population (SMD .01 [-.14 to .16], P = .87). The physical activity behavior findings were similar for all studies (SMD -.01 [-.10 to .08], P = .88), even when analyzed by subgroup: "at risk" (SMD .07 [-.18 to .31], P = .59); general population (SMD -.02 [-.13 to .10], P = .77). The quality of the evidence for the dietary behavior outcome was low; for the physical activity behavior outcome it was moderate. CONCLUSIONS: Genotype-based advice does not affect dietary or physical activity behavior more than general advice or advice based on lifestyle or phenotypic measures. This was consistent in studies that recruited participants from the general population as well as in studies that had recruited participants from populations at risk of CVD or T2DM. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021231147.

Does personalised nutrition advice based on apolipoprotein E and methylenetetrahydrofolate reductase genotype affect dietary behaviour?

Background: Dietary intake is linked to numerous modifiable risk factors of cardiovascular disease. Current dietary recommendations in the UK to reduce the risk of cardiovascular disease are not being met. A genotype-based personalised approach to dietary recommendations may motivate individuals to make positive changes in their dietary behaviour. Aim: To determine the effect of a personalised nutrition intervention, based on apolipoprotein E (ApoE, rs7412; rs429358) and methylenetetrahydrofolate reductase (MTHFR, rs1801133) genotype, on reported dietary intake of saturated fat and folate in participants informed of a risk genotype compared to those informed of non-risk genotype. Methods: Baseline data (n = 99) were collected to determine genotype (non-risk vs risk), dietary intake and cardiovascular risk (Q-Risk®2 cardiovascular risk calculator). Participants were provided with personalised nutrition advice via email based on their ApoE and MTHFR genotype and reported intake of folate and saturated fat. After 10 days, dietary intake data were reported for a second time. Results: Personalised nutrition advice led to favourable dietary changes, irrespective of genotype, in participants who were not meeting dietary recommendations at baseline for saturated fat (p < 0.001) and folate (p = 0.002). Only participants who were informed of a risk ApoE genotype met saturated fat recommendations following personalised nutrition advice. Conclusion: Incorporation of genotype-based personalised nutrition advice in a diet behaviour intervention may elicit favourable changes in dietary behaviour in participants informed of a risk genotype. Participants informed of a non-risk genotype also respond to personalised nutrition advice favourably but to a lesser extent.

The Association of Parental Genetic, Lifestyle, and Social Determinants of Health with Offspring Overweight.

INTRODUCTION: In the UK, the number of comorbidities seen in children has increased along with the worsening obesity rate. These comorbidities worsen into adulthood. Genome-wide association studies have highlighted single nucleotide polymorphisms associated with the weight status of adults and offspring individually. To date, in the UK, parental genetic, lifestyle, and social determinants of health have not been investigated alongside one another as influencers of offspring weight status. A comprehensive obesity prevention scheme would commence prior to conception and involve parental intervention including all known risk factors. This current study aims to identify the proportion of overweight that can be explained by known parental risk factors, including genetic, lifestyle, and social determinants of health with offspring weight status in the UK. METHODS: A cross-sectional study was carried out on 123 parents. Parental and offspring anthropometric data and parental lifestyle and social determinants of health data were self-reported. Parental genetic data were collected by use of GeneFiX saliva collection vials and genotype were assessed for brain-derived neurotrophic factor (BDNF) gene rs6265, melanocortin 4 receptor (MC4R) gene rs17782313, transmembrane protein 18 (TMEM18) gene rs2867125, and serine/threonine-protein kinase (TNN13K) gene rs1514175. Associations were assessed between parental data and the weight status of offspring. RESULTS: Maternal body mass index modestly predicted child weight status (p < 0.015; R2 = 0.15). More mothers of overweight children carried the MC4R rs17782313 risk allele (77.8%; p = 0.007) compared to mothers of normal-weight children. Additionally, fathers who were not Caucasian and parents who slept for <7 h/night had a larger percentage of overweight children when compared to their counterparts (p = 0.039; p = 0.014, respectively). CONCLUSION: Associations exist between the weight status of offspring based solely on parental genetic, lifestyle, and social determinants of health data. Further research is required to appropriately address future interventions based on genetic and lifestyle risk groups on a pre-parent cohort.