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Journal of Dairy Science Jan 2023Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species... (Review)
Review
Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models.
Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species associated with dairy consumption mediate this relationship. This scoping review aimed to identify the existing literature in animal and human trials investigating the impact of dairy products, including milk, yogurt, and cheese as well as dairy-derived PL supplementation on PL and its species in the circulation, summarizing the characteristics of these studies and identifying research gaps. A systematic search was conducted across 3 databases (PubMed, Scopus, and Web of Science) in March 2021. Of 2,427 identified references, 15 studies (7 humans and 8 animal studies) met the eligibility criteria and were included in the final narrative synthesis. The evidence base was heterogeneous, involving a variety of clinical and preclinical studies, metabolically healthy or obese/diabetic participants or animal models, and displayed mixed findings. Circulating postprandial concentrations of total PL were elevated acutely but unchanged after longer intervention with dairy products. The PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL, which may be related to increased fecal excretion; however, certain phosphatidylcholine (PC) or lysophosphatidylcholine species were increased in circulation by interventions. These include several PC species with 32 to 38 total carbons in addition to the dairy biomarkers C15:0 and C17:0. The results of this scoping review demonstrate a small body of literature indicating that dairy products can influence blood concentrations of PC and lysophosphatidylcholine species in both rodents and humans without alteration of total PL and PC. There is a lack of well-designed trials in humans and animals that explore the potential differences between individual dairy foods on PL species. In addition, trials to understand the bioactive properties of PC and lysophosphatidylcholine species on cardiometabolic risk are needed.
Topics: Animals; Humans; Dairy Products; Diabetes Mellitus, Type 2; Diet; Liver; Lysophosphatidylcholines; Milk; Models, Animal; Phosphatidylcholines; Students; Yogurt
PubMed: 36400621
DOI: 10.3168/jds.2022-21938 -
Advances in Nutrition (Bethesda, Md.) Feb 2024Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating... (Review)
Review
The Relationship of Circulating Choline and Choline-Related Metabolite Levels with Health Outcomes: A Scoping Review of Genome-Wide Association Studies and Mendelian Randomization Studies.
Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating choline metabolites can help identify new determinants of choline metabolism, requirements, and their link to disease endpoints. We conducted a scoping review to identify studies assessing the association of genetic polymorphisms on circulating choline and choline-related metabolite concentrations and subsequent associations with health outcomes. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Literature was searched to September 28, 2022, in 4 databases: Embase, MEDLINE, Web of Science, and the Biological Science Index. Studies of any duration in humans were considered. Any genome-wide association study (GWAS) investigating genetic variant associations with circulating choline and/or choline-related metabolites and any Mendelian randomization (MR) study investigating the association of genetically predicted circulating choline and/or choline-related metabolites with any health outcome were considered. Qualitative evidence is presented in summary tables. From 1248 total reviewed articles, 53 were included (GWAS = 27; MR = 26). Forty-two circulating choline-related metabolites were tested in association with genetic variants in GWAS studies, primarily trimethylamine N-oxide, betaine, sphingomyelins, lysophosphatidylcholines, and phosphatidylcholines. MR studies investigated associations between 52 total unique choline metabolites and 66 unique health outcomes. Of these, 47 significant associations were reported between 16 metabolites (primarily choline, lysophosphatidylcholines, phosphatidylcholines, betaine, and sphingomyelins) and 27 health outcomes including cancer, cardiovascular, metabolic, bone, and brain-related outcomes. Some articles reported significant associations between multiple choline types and the same health outcome. Genetically predicted circulating choline and choline-related metabolite concentrations are associated with a wide variety of health outcomes. Further research is needed to assess how genetic variability influences choline metabolism and whether individuals with lower genetically predicted circulating choline and choline-related metabolite concentrations would benefit from a dietary intervention or supplementation.
Topics: Humans; Choline; Betaine; Genome-Wide Association Study; Sphingomyelins; Mendelian Randomization Analysis; Lysophosphatidylcholines; Phosphatidylcholines; Polymorphism, Single Nucleotide
PubMed: 38128611
DOI: 10.1016/j.advnut.2023.100164 -
The British Journal of Nutrition Dec 2019Little is known about the association between dietary choline intake and mortality. We evaluated the link between choline consumption and overall as well as... (Meta-Analysis)
Meta-Analysis
Dietary choline is positively related to overall and cause-specific mortality: results from individuals of the National Health and Nutrition Examination Survey and pooling prospective data.
Little is known about the association between dietary choline intake and mortality. We evaluated the link between choline consumption and overall as well as cause-specific mortality by using both individual data and pooling prospective studies by meta-analysis and systematic review. Furthermore, adjusted means of cardiometabolic risk factors across choline intake quartiles were calculated. Data from the National Health and Nutrition Examination Survey (1999-2010) were collected. Adjusted Cox regression was performed to determine the risk ratio (RR) and 95 % CI, as well as random-effects models and generic inverse variance methods to synthesise quantitative and pooling data, followed by a leave-one-out method for sensitivity analysis. After adjustments, we found that individuals consuming more choline had worse lipid profile and glucose homeostasis, but lower C-reactive protein levels (P < 0·001 for all comparisons) with no significant differences in anthropometric parameters and blood pressure. Multivariable Cox regression models revealed that individuals in the highest quartile (Q4) of choline consumption had a greater risk of total (23 %), CVD (33 %) and stroke (30 %) mortality compared with the first quartile (Q1) (P < 0·001 for all comparison). These results were confirmed in a meta-analysis, showing that choline intake was positively and significantly associated with overall (RR 1·12, 95 % CI 1·08, 1·17, I2 = 2·9) and CVD (RR 1·28, 95 % CI 1·17, 1·39, I2 = 9·6) mortality risk. In contrast, the positive association between choline consumption and stroke mortality became non-significant (RR 1·18, 95 % CI 0·97, 1·43, P = 0·092, I2 = 1·1). Our findings shed light on the potential adverse effects of choline intake on selected cardiometabolic risk factors and mortality risk.
Topics: Adult; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Choline; Diet; Ethnicity; Female; Glycerophospholipids; Humans; Lipids; Male; Middle Aged; Mortality; Nutrition Surveys; Odds Ratio; Socioeconomic Factors; Stroke
PubMed: 31288869
DOI: 10.1017/S0007114519001065 -
Frontiers in Nutrition 2024Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome...
BACKGROUND
Studies have shown that sphingomyelin (SM) and its metabolites play signaling roles in the regulation of human health. Endogenous SM is involved in metabolic syndrome (MetS), while dietary SM supplementation may maintain lipid metabolism and prevent or alleviate MetS. Therefore, we hypothesized that dietary SM supplementation is beneficial for human health.
AIMS
In order to examine the impacts of dietary SM on metabolic indexes in adults without MetS, we performed a meta-analysis to test our hypothesis.
METHODS
A comprehensive search was performed to retrieve randomized controlled trials that were conducted between 2003 and 2023 to examine the effects of dietary SM supplementation on metabolic parameters in the Cochrane Library, PubMed, Web of Science, Embase, and ClinicalTrials.gov databases. RevMan 5.4 and Stata 14.0 software were used for meta-analysis, a sensitivity analysis, the risk of bias, and the overall quality of the resulted evidence.
RESULTS
Eventually, 10 articles were included in this meta-analysis. Dietary SM supplementation did not affect the endline blood SM level. When compared to the control, SM supplementation reduced the blood total cholesterol level [MD: -12.97, 95% CI: (-14.57, -11.38), < 0.00001], low-density lipoprotein cholesterol level [MD: -6.62, 95% CI: (-10.74, -2.49), = 0.002], and diastolic blood pressure [MD: -3.31; 95% CI (-4.03, -2.58), < 0.00001] in adults without MetS. The supplementation also increased high-density lipoprotein level [MD:1.41, 95% CI: (0.94, 1.88), < 0.00001] and muscle fiber conduction velocity [MD: 95% 1.21 CI (0.53, 1.88), = 0.0005]. The intake of SM had no effect on the blood phospholipids and lyso-phosphatidylcholine, but slightly decreased phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol concentrations. Dietary SM supplementation reduced insulin level [MD: -0.63; 95% CI (-0.96, -0.31), = 0.0001] and HOMA-IR [MD: -0.23; 95% CI (-0.31, -0.16), < 0.00001] without affecting blood levels of glucose and inflammatory cytokines.
CONCLUSION
Overall, dietary SM supplementation had a protective effect on blood lipid profiles and insulin level, but had limited impacts on other metabolic parameters in adults without MetS. More clinical trials and basic research are required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023438460.
PubMed: 38463938
DOI: 10.3389/fnut.2024.1363077 -
Orphanet Journal of Rare Diseases Jun 2018Despite early and ongoing dietary management with a phe-restricted diet, suboptimal neuropsychological function has been observed in PKU. The restrictive nature of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite early and ongoing dietary management with a phe-restricted diet, suboptimal neuropsychological function has been observed in PKU. The restrictive nature of the PKU diet may expose patients to sub-optimal nutritional intake and deficiencies which may impact normal brain function. A systematic review of the published literature was carried out, where possible with meta-analysis, to compare the status of nutrients (Nutrients: DHA, EPA phospholipids, selenium, vitamins B, B, E, C, A, D, folic acid, choline, uridine, calcium, magnesium, zinc, iron, iodine and cholesterol) known to be important for brain development and functioning between individuals with PKU and healthy controls.
RESULTS
Of 1534 publications identified, 65 studies met the entry criteria. Significantly lower levels of DHA, EPA and cholesterol were found for PKU patients compared to healthy controls. No significant differences in zinc, vitamins B, E and D, calcium, iron and magnesium were found between PKU patients and controls. Because of considerable heterogeneity, the meta-analyses findings for folate and selenium were not reported. Due to an insufficient number of publications (< 4) no meta-analysis was undertaken for vitamins A, C and B, choline, uridine, iodine and phospholipids.
CONCLUSIONS
The current data show that PKU patients have lower availability of DHA, EPA and cholesterol. Compliance with the phe-restricted diet including the micronutrient fortified protein substitute (PS) is essential to ensure adequate micronutrient status. Given the complexity of the diet, patients' micronutrient and fatty acid status should be continuously monitored, with a particular focus on patients who are non-compliant or poorly compliant with their PS. Given their key role in brain function, assessment of the status of nutrients where limited data was found (e.g. choline, iodine) should be undertaken. Standardised reporting of studies in PKU would strengthen the output of meta-analysis and so better inform best practice for this rare condition.
Topics: Brain; Docosahexaenoic Acids; Fatty Acids; Humans; Micronutrients; Phenylketonurias; Phospholipids
PubMed: 29941009
DOI: 10.1186/s13023-018-0839-x -
The American Journal of Psychiatry Jul 2018Genes, infection, malnutrition, and other factors affecting fetal brain development are a major component of risk for a child's emotional development and later mental...
Genes, infection, malnutrition, and other factors affecting fetal brain development are a major component of risk for a child's emotional development and later mental illnesses, including schizophrenia, bipolar disorder, and autism. Prenatal interventions to ameliorate that risk have yet to be established for clinical use. A systematic review of prenatal nutrients and childhood emotional development and later mental illness was performed. Randomized trials of folic acid, phosphatidylcholine, and omega-3 fatty acid supplements assess effects of doses beyond those adequate to remedy deficiencies to promote normal fetal development despite genetic and environmental risks. Folic acid to prevent neural tube defects is an example. Vitamins A and D are currently recommended at maximum levels, but women's incomplete compliance permits observational studies of their effects. Folic acid and phosphatidylcholine supplements have shown evidence for improving childhood emotional development associated with later mental illnesses. Vitamins A and D decreased the risk for schizophrenia and autism in retrospective observations. Omega-3 fatty acid supplementation during early pregnancy increased the risk for schizophrenia and increased symptoms of attention deficit hyperactivity disorder, but in later pregnancy it decreased childhood wheezing and premature birth. Studies are complicated by the length of time between birth and the emergence of mental illnesses like schizophrenia, compared with anomalies like facial clefts identified at birth. As part of comprehensive maternal and fetal care, prenatal nutrient interventions should be further considered as uniquely effective first steps in decreasing risk for future psychiatric and other illnesses in newborn children. [AJP at 175: Remembering Our Past As We Envision Our Future July 1959: Longitudinal Observations of Biological Deviations in a Schizophrenic Infant Barbara Fish described the course of an infant born with fluctuating motor problems who developed schizophrenia. (Am J Psychiatry 1959; 116:25-31 )].
Topics: Dietary Supplements; Fatty Acids, Omega-3; Female; Folic Acid; Humans; Mental Disorders; Micronutrients; Phosphatidylcholines; Pregnancy; Prenatal Care; Primary Prevention
PubMed: 29558816
DOI: 10.1176/appi.ajp.2018.17070836 -
The Cochrane Database of Systematic... Apr 2020Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review.
OBJECTIVES
To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of last search: 01 April 2020. We also searched online study registries and contacted authors. Date of last search: 12 February 2020.
SELECTION CRITERIA
Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
The searches identified 23 studies; five studies with 106 participants (children and adults) were included; duration of studies and interventions differed. Two studies compared omega-3 fatty acids to olive oil for six weeks; one study compared omega-3 fatty acids and omega-6 fatty acids to control capsules (customised fatty acid blends) for three months; one study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months; and one study compared omega-3 fatty acids to a placebo for 12 months. Three studies had a low risk of bias for randomisation, but the risk was unclear in the remaining two studies; all studies had an unclear risk of bias for allocation concealment. Three of the studies adequately blinded participants; the risk of bias for selective reporting was high in one study and unclear for four studies. Two studies reported the number of respiratory exacerbations. At three months, one study (43 participants) reported no change in antibiotic usage. At 12 months the second study (15 participants) reported a reduction in the number of pulmonary exacerbations and cumulative antibiotic days in the supplement group compared to the previous year (no data for the control group); very low-quality evidence means we are unsure whether supplementation has any effect on this outcome. With regards to adverse events, one six-week study (12 participants) reported no difference in diarrhoea between omega-3 or placebo capsules; the very low-quality evidence means we are unsure if supplementation has any effect on this outcome. Additionally, one study reported an increase in steatorrhoea requiring participants to increase their daily dose of pancreatic enzymes, but three studies had already increased pancreatic enzyme dose at study begin so as to reduce the incidence of steatorrhoea. One study (43 participants) reported stomach pains at three months (treatment or control group not specified). One six-week study (19 participants) reported three asthma exacerbations leading to exclusion of participants since corticosteroid treatment could affect affect essential fatty acid metabolism. Four studies reported lung function. One six-week study (19 participants) reported an increase in forced expiratory volume in one second (FEV) (L) and forced vital capacity (FVC) (L), but the very low-quality evidence means we are unsure if supplementation has any effect on lung function. The remaining studies did not report any difference in lung function at three months (unit of measurement not specified) or at six months and one year (FEV % predicted and FVC % predicted). No deaths were reported in any of the five studies. Four studies reported clinical variables. One study reported an increase in Schwachman score and weight alongside a reduction in sputum volume with supplementation compared to placebo at three months (data not analysable). However, three studies reported no differences in either weight at six weeks, in body mass index (BMI) standard deviation (SD) score at six months (very low-quality evidence) or BMI Z score at 12 months. Three studies reported biochemical markers of fatty acid status. One study showed an increase from baseline in both EPA and DHA content of serum phospholipids in the omega-3 group compared to placebo at three months and also a significant decrease in n-6/n-3 ratio in the supplement group compared to placebo; since the quality of the evidence is very low we are not certain that these changes are due to supplementation. One six-month cross-over study showed a higher EPA content of the neutrophil membrane in the supplement group compared to the placebo group, but, no difference in DHA membrane concentration. Furthermore, the leukotriene B to leukotriene B ratio was lower at six months in the omega-3 group compared to placebo. A one-year study reported a greater increase in the essential fatty acid profile and a decrease in AA levels in the treatment arm compared to placebo.
AUTHORS' CONCLUSIONS
This review found that regular omega-3 supplements may provide some limited benefits for people with cystic fibrosis with relatively few adverse effects: however, the quality of the evidence across all outcomes was very low. The current evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes when providing omega-3 supplementation or olive oil placebo capsules. More research is required to determine the exact dose of pancreatic enzyme required.
Topics: Adult; Bias; Child; Cystic Fibrosis; Dietary Supplements; Disease Progression; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Forced Expiratory Volume; Humans; Olive Oil; Randomized Controlled Trials as Topic; Vital Capacity
PubMed: 32275788
DOI: 10.1002/14651858.CD002201.pub6 -
International Journal of Molecular... Aug 2020The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying...
The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying their benefic properties are still partially unknown. These agents seem to express their action on the membrane phospholipid composition and permeability and modulation of second messenger cascades. In psychiatry, the efficacy and tolerability of omega-3 fatty acids were investigated in several psychiatric disorders, including major depression, bipolar disorder, personality disorders, high-risk conditions to develop psychosis, attention-deficit hyperactivity disorder, and autism spectrum disorders. Initial findings in this field are promising, and some relevant questions need to be addressed. In particular, the effects of these agents on the main symptom dimensions have to be investigated in a trans-diagnostic perspective. The present systematic review is aimed to examine the available data on the efficacy of omega-3 fatty acids on domains of psychotic symptoms, affective symptoms, impulsivity, and aggressiveness, and harmful behaviors, and suicide risk.
Topics: Affective Symptoms; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bipolar Disorder; Depressive Disorder, Major; Dietary Supplements; Fatty Acids, Omega-3; Humans; Personality Disorders; Psychopathology; Psychotic Disorders; Randomized Controlled Trials as Topic; Suicidal Ideation
PubMed: 32839416
DOI: 10.3390/ijms21176042 -
The British Journal of Nutrition Dec 2018Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed,...
Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed, particularly in a mild cognitive impairment (MCI) population. This review examined the effect of diet on cognitive outcomes in MCI patients. A total of five databases were searched to find randomised controlled trial (RCT) studies, with diet as the main focus, in MCI participants. The primary outcome was incident dementia and/or Alzheimer's disease (AD) and secondary outcomes included cognitive function across different domains using validated neuropsychological tests. Sixteen studies met the inclusion criteria. There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making study comparisons difficult. Supplementation with vitamin E (one study, n 516), ginkgo biloba (one study, n 482) or Fortasyn Connect (one study, n 311) had no significant effect on progression from MCI to dementia and/or AD. For cognitive function, the findings showed some improvements in performance, particularly in memory, with the most consistent results shown by B vitamins, including folic acid (one study, n 266), folic acid alone (one study, n 180), DHA and EPA (two studies, n 36 and n 86), DHA (one study, n 240) and flavonol supplementation (one study, n 90). The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients. Further well-designed trials are needed, with standardised and robust measures of cognition to investigate the influence of diet on cognitive status.
Topics: Alzheimer Disease; Attention; Biomarkers; Cognition; Cognitive Dysfunction; Dementia; Diet; Dietary Supplements; Disease Progression; Docosahexaenoic Acids; Eicosapentaenoic Acid; Executive Function; Folic Acid; Ginkgo biloba; Humans; Language; Neuropsychological Tests; Phospholipids; Randomized Controlled Trials as Topic; Vitamin E
PubMed: 30409231
DOI: 10.1017/S0007114518002945 -
The Cochrane Database of Systematic... Jul 2021The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD.
OBJECTIVES
• To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD.
SELECTION CRITERIA
We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation.
DATA COLLECTION AND ANALYSIS
We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.
MAIN RESULTS
We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up.
AUTHORS' CONCLUSIONS
The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes).
Topics: Bayes Theorem; Bias; Dietary Supplements; Humans; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Odds Ratio; Proportional Hazards Models; Randomized Controlled Trials as Topic
PubMed: 34280304
DOI: 10.1002/14651858.CD013157.pub2