Factors predicting outcome from enhanced recovery programmes in laparoscopic colorectal surgery: a systematic review.

OBJECTIVE: To perform a systematic review of published literature for the factors reported to predict outcomes of enhanced recovery after surgery (ERAS) programmes following laparoscopic colorectal surgery. BACKGROUND: ERAS programmes and the use of laparoscopy have been widely adopted in colorectal surgery bringing short-term patient benefit. However, there is a minority of patients that do not benefit from these strategies and their identification is not well characterised. The factors that underpin outcomes from ERAS programmes for laparoscopic patients are not understood. METHODS: A systematic search of the MEDLINE, Embase and Cochrane databases was conducted to identify suitable articles published between 2000 and 2015. The search strategy captured terms for ERAS, colorectal resection, prediction and outcome measures. RESULTS: Thirty-four studies containing 10,861 laparoscopic resections were included. Thirty-one (91 %) studies were confined to elective cases. Predictive analysis of outcome was most frequently based on length of stay (LOS), morbidity and readmission which were the main outcome measures of 29 (85 %), 26 (76 %) and 18 (53 %) of the included studies, respectively. Forty-seven percentage of included studies investigated the impact of ERAS programme compliance on these outcomes. Reduced protocol compliance was the most frequently identified modifiable predictive factor for adverse LOS, morbidity and readmission. CONCLUSION: Protocol compliance is the most frequently reported predictive factor for outcomes of ERAS programmes following laparoscopic colorectal resection. Reduced compliance increases LOS, morbidity and readmission to hospital. The impact of compliance with individual ERAS protocol elements is insufficiently studied, and the lack of a standardised framework for evaluating ERAS programmes makes it difficult to draw definite conclusions about which factors exert the greatest impact on outcome after laparoscopic colorectal resection.

Specific collagen XVIII isoforms promote adipose tissue accrual via mechanisms determining adipocyte number and affect fat deposition.

Collagen XVIII is an evolutionary conserved ubiquitously expressed basement membrane proteoglycan produced in three isoforms via two promoters (P). Here, we assess the function of the N-terminal, domain of unknown function/frizzled-like sequences unique to medium/long collagen XVIII by creating P-specific null mice. P2-null mice, which only produce short collagen XVIII, developed reduced bulk-adiposity, hepatic steatosis, and hypertriglyceridemia. These abnormalities did not develop in P1-null mice, which produce medium/long collagen XVIII. White adipose tissue samples from P2-null mice contain larger reserves of a cell population enriched in early adipocyte progenitors; however, their embryonic fibroblasts had ∼ 50% lower adipocyte differentiation potential. Differentiating 3T3-L1 fibroblasts into mature adipocytes produced striking increases in P2 gene-products and dramatic falls in P1-transcribed mRNA, whereas Wnt3a-induced dedifferentiation of mature adipocytes produced reciprocal changes in P1 and P2 transcript levels. P2-derived gene-products containing frizzled-like sequences bound the potent adipogenic inhibitor, Wnt10b, in vitro. Previously, we have shown that these same sequences bind Wnt3a, inhibiting Wnt3a-mediated signaling. P2-transcript levels in visceral fat were positively correlated with serum free fatty acid levels, suggesting that collagen α1 (XVIII) expression contributes to regulation of adipose tissue metabolism in visceral obesity. Medium/long collagen XVIII is deposited in the Space of Disse, and interaction between hepatic apolipoprotein E and this proteoglycan is lost in P2-null mice. These results describe a previously unidentified extracellular matrix-directed mechanism contributing to the control of the multistep adipogenic program that determines the number of precursors committing to adipocyte differentiation, the maintenance of the differentiated state, and the physiological consequences of its impairment on ectopic fat deposition.

How Well Is Quality Improvement Described in the Perioperative Care Literature? A Systematic Review.

BACKGROUND: Quality improvement (QI) approaches are widely used across health care, but how well they are reported in the academic literature is not clear. A systematic review was conducted to assess the completeness of reporting of QI interventions and techniques in the field of perioperative care. METHODS: Searches were conducted using Medline, Scopus, the Cochrane Central Register of Controlled Trials, the Cochrane Effective Practice and Organization of Care database, and PubMed. Two independent reviewers used the Template for Intervention Description and Replication (TIDieR) check list, which identifies 12 features of interventions that studies should describe (for example, How: the interventions were delivered [e. g., face to face, internet]), When and how much: duration, dose, intensity), to assign scores for each included article. Articles were also scored against a small number of additional criteria relevant to QI. RESULTS: The search identified 16,103 abstracts from databases and 19 from other sources. Following review, full-text was obtained for 223 articles, 100 of which met the criteria for inclusion. Completeness of reporting of QI in the perioperative care literature was variable. Only one article was judged fully complete against the 11 TIDieR items used. The mean TIDieR score across the 100 included articles was 6.31 (of a maximum 11). More than a third (35%) of the articles scored 5 or lower. Particularly problematic was reporting of fidelity (absent in 74% of articles) and whether any modifications were made to the intervention (absent in 73% of articles). CONCLUSIONS: The standard of reporting of quality interventions and QI techniques in surgery is often suboptimal, making it difficult to determine whether an intervention can be replicated and used to deliver a positive effect in another setting. This suggests a need to explore how reporting practices could be improved.

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients.

The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating five overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBPα expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3'UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis.

Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Prevalence of Alzheimer's disease in people with Down's syndrome is very high, and many such individuals who are older than 40 years have pathological changes characteristic of Alzheimer's disease. Evidence to support treatment with Alzheimer's drugs is inadequate, although memantine is beneficial in transgenic mice. We aimed to assess safety and efficacy of memantine on cognition and function in individuals with Down's syndrome. METHODS: In our prospective randomised double-blind trial, we enrolled adults (>40 years) with karyotypic or clinically diagnosed Down's syndrome, with and without dementia, at four learning disability centres in the UK and Norway. We randomly allocated participants (1:1) to receive memantine or placebo for 52 weeks by use of a computer-generated sequence and a minimisation algorithm to ensure balanced allocation for five prognostic factors (sex, dementia, age group, total Down's syndrome attention, memory, and executive function scales [DAMES] score, and centre). The primary outcome was change in cognition and function, measured with DAMES scores and the adaptive behaviour scale (ABS) parts I and II. We analysed differences in DAMES and ABS scores between groups with analyses of covariance or quantile regression in all patients who completed the 52 week assessment and had available follow-up data. This study is registered, number ISRCTN47562898. FINDINGS: We randomly allocated 88 patients to receive memantine (72 [82%] had DAMES data and 75 [85%] had ABS data at 52 weeks) and 85 to receive placebo (74 [87%] and 73 [86%]). Both groups declined in cognition and function but rates did not differ between groups for any outcomes. After adjustment for baseline score, there were non-significant differences between groups of -4·1 (95% CI -13·1 to 4·8) in DAMES scores, -8·5 (-20·1 to 3·1) in ABS I scores, and 2·0 (-7·2 to 11·3) in ABS II scores, all in favour of controls. 10 (11%) of 88 participants in the memantine group and six (7%) of 85 controls had serious adverse events (p=0·33). Five participants in the memantine group and four controls died from serious adverse events (p=0·77). INTERPRETATION: There is a striking absence of evidence about pharmacological treatment of cognitive impairment and dementia in people older than 40 years with Down's syndrome. Despite promising indications, memantine is not an effective treatment. Therapies that are effective for Alzheimer's disease are not necessarily effective in this group of patients. FUNDING: Lundbeck.

Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature.

BACKGROUND: Neoadjuvant long-course chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. OBJECTIVE: We report an evidence-based systematic review of published data supporting the optimal time to perform surgical resection after long-course neoadjuvant therapy. DATA SOURCES: A systematic literature search was undertaken of the MEDLINE and Embase electronic databases from 1995 to 2012. STUDY SELECTION: English language articles were included that compared outcomes following rectal cancer surgery performed at different times after a long course of neoadjuvant radiation-based therapy. INTERVENTIONS: : Patients received a long course of neoadjuvant therapy followed by radical surgical resection after an interval period. MAIN OUTCOME MEASURES: The rates of tumor response, R0 resection, sphincter preservation, surgical complications, and disease recurrence were the primary outcomes measured. RESULTS: Fifteen studies were identified: 1 randomized controlled trial, 1 prospective nonrandomized interventional study, and 13 observational studies. Studies compared time intervals that varied between <5 days and >12 weeks, with a large degree of variation in what the standard interval length was considered to be. Four of the 7 studies that reported rates of pathological complete response identified significantly higher rates with an extended interval between chemoradiotherapy and surgery; 3 of 8 studies demonstrated increased primary tumor downstaging with a longer interval. No significant differences have been consistently demonstrated in rates of surgical complications, sphincter preservation, or long-term recurrence and survival. LIMITATIONS: Neoadjuvant regimes, indications for neoadjuvant therapy, and time intervals after chemoradiotherapy were heterogeneous between studies; consequently, meta-analysis could not be performed. CONCLUSIONS: There is limited evidence to support decisions regarding when to resect rectal cancer following chemoradiotherapy. There may be benefits in prolonging the interval between chemoradiotherapy and surgery beyond the 6 to 8 weeks that is commonly practiced. However, outcomes need to be studied further in robust randomized studies.

Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders.

Dietary fat is an important source of nutrition. Here we identify eight mutations in SARA2 that are associated with three severe disorders of fat malabsorption. The Sar1 family of proteins initiates the intracellular transport of proteins in COPII (coat protein)-coated vesicles. Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell.

Synaptic protein expression is regulated by a pro-oxidant diet in APPxPS1 mice.

Dietary factors may play a role in Alzheimer's disease (AD) pathogenesis. In an effort to recapitulate some of the synaptic protein changes observed in the disease, AD transgenic and wild-type mice were fed either a normal or pro-oxidant diet for 3 months from three months of age. Pro-oxidant diet treatment resulted in altered expression of vesicular glutamate transporter-1 and glutamine synthetase, suggesting changes in glutamatergic synaptic function, and increased expression of urokinase plasminogen activator receptor, possibly reflecting oxidative stress.

Analysis of neuron-specific enolase and S100B as biomarkers of cognitive decline following surgery in older people.

BACKGROUND/AIMS: Post-operative cognitive decline is frequent in older individuals following major surgery; however, biomarkers of this decline are less clearly defined. METHODS: Sixty-eight participants over the age of 60 provided blood samples at baseline and 24 h post-surgery. Cognitive decline was measured at baseline and 52 weeks post-surgery using the Cambridge Assessment for Mental Disorder in the Elderly, section B (CAMCOG) score. Plasma levels of neuron-specific enolase (NSE) and S100B were measured by ELISA. RESULTS: Baseline NSE and the change in NSE levels between baseline and 24 h were correlated with the change in CAMCOG score between baseline and 52 weeks. CONCLUSION: NSE concentrations may be a useful predictor of individuals at risk of more severe long-term cognitive decline.

A pilot study examining associations between DYRK1A and α-synuclein dementias.

BACKGROUND: DYRK1A is a kinase targeting several proteins associated with the pathology of dementias, including α-synuclein and amyloid precursor protein. It is not clear if DYRK1A genetics are associated with neurodegenerative conditions. OBJECTIVE: To determine if DYRK1A also has a genetic association with α-synuclein dementias such as dementia with Lewy bodies and Parkinson's disease dementia. METHODS: DNA samples from prospectively followed cohorts of control and dementia individuals were genotyped for the DYRK1A rs8126696 polymorphism. RESULTS: The rs8126696 polymorphism altered the risk of developing an α-synuclein-associated dementia. CONCLUSION: DYRK1A could prove to be an important therapeutic target as it interacts with several proteins associated with the development of pathology in dementia.

Genetic associations of autopsy-confirmed vascular dementia subtypes.

BACKGROUND/AIMS: Genetic risk factors have not been clearly established for vascular dementias (VaD) related to stroke and cerebrovascular disease. METHODS: Samples were genotyped for APOE, MTHFR and ICAM. Aß levels and choline acetyltransferase (ChAT) activities were assayed in controls and individuals with VaD. RESULTS: Associations were found between the APOE-ε4 allele and mixed dementia, infarct/stroke dementia and subcortical ischemic vascular dementia (SIVD), and higher Aß1-42 levels and decreased ChAT activity. MTHFR was more associated with SIVD, mixed dementia, and lower ChAT activity. CONCLUSIONS: The study demonstrates important differences in the genetic associations of VaD and begins to clarify the genetic basis of key pathological substrates.

Antipsychotic medication is associated with selective alterations in ventricular cerebrospinal fluid Aß 40 and tau in patients with intractable unipolar depression.

OBJECTIVE: Alterations in plasma and in lumbar cerebrospinal fluid amyloid-B peptide (Aß) levels have been reported in Alzheimer's disease. Studies have also suggested similar changes in depressed patients. No information is available on the impact of psychotropic drugs on this in patients with depression. We therefore quantified Aß in ventricular cerebrospinal fluid (CSF) in a population of patients with treatment-resistant depression, with and without antipsychotic medication. METHOD: A cross-sectional study of 32 patients undergoing subcaudate tractotomy for major (unipolar) depressive disorder. Ventricular CSF concentrations of Aß peptide 1-40 and 1-42, also p-tau and total tau were determined by Western blotting or enzyme-linked immunosorbent assay. RESULTS: Patients taking antipsychotic medication in the 2 weeks prior to surgery demonstrated significantly higher levels of Aß 1-40 (mean ± SD: 727.3 ± 382.3 vs. 440.9 ± 337.2 pg/ml; p = 0.032, Student's t-test) but unaltered Aß 1-42 (mean 72.1 ± 67.5 vs. 60.0 ± 56.7 pg/ml; p = 0.587) compared to a matched sample not treated with antipsychotic drugs. The same group demonstrated elevated total tau (mean 945.0 ± 422.2 vs. 534.3 ± 388.3 pg/ml; p = 0.010) but not p-tau (mean 98.6 ± 71.5 vs. 88.1 ± 70.5 pg/ml; p = 0.694). No similar effect was found with lithium, antidepressants, carbamazepine or benzodiazepines. CONCLUSIONS: This preliminary study suggests antipsychotic drugs, widely used in patients with severe depression across all age ranges, may be associated with alteration of Aß 1-40 and total tau, indices strongly linked with progressive organic brain disease. Further confirmatory work is needed.

alpha-Synuclein antibodies recognize a protein present at lower levels in the CSF of patients with dementia with Lewy bodies.

BACKGROUND: Dementia with Lewy bodies (DLB) accounts for 15-20% of the millions of people worldwide with dementia. Accurate diagnosis is essential to avoid harm and optimize clinical management. There is therefore an urgent need to identify reliable biomarkers. METHODS: Mass spectrometry was used to determine the specificity of antibody alpha-synuclein (211) for alpha-synuclein. Using gel electrophoresis we measured protein levels detected by alpha-synuclein specific antibodies in the cerebrospinal fluid (CSF) of DLB patients and compared them to age matched controls. RESULTS: A 24 kDa band was detected using alpha-synuclein specific antibodies which was significantly reduced in the CSF of DLB patients compared to age matched controls (p < 0.05). Further analysis confirmed that even DLB patients with mild dementia showed significant reductions in this protein in comparison to controls. CONCLUSIONS: The current study emphasizes the necessity for further studies of CSF alpha-synuclein as a biomarker of DLB and extends our previous knowledge by establishing a potential relationship between alpha-synuclein and the severity of cognitive impairment. The identification of this 24 kDa protein is the next important step in these studies.

Amyloid beta concentrations in older people with Down syndrome and dementia.

People with Down syndrome develop Alzheimer's disease with an early age of onset. Plasma amyloid beta (Abeta) levels were measured in individuals with Down syndrome who were over the age of 40. No associations between age and Abeta1-40 and Abeta1-42 concentrations were found and nor were Abeta1-40 and Abeta1-42 levels found to vary between those with Alzheimer's-type dementia and those without dementia. The APOE genotype was not found to have an impact upon Abeta1-40 or Abeta1-42 concentrations. These data suggest that other factors play important roles in determining the onset and progression of dementia in the Down syndrome population.

The extended tau haplotype and the age of onset of dementia in Down syndrome.

BACKGROUND/AIMS: Most people with Down syndrome (DS) develop Alzheimer's disease (AD). The extended tau haplotype has been linked to AD. In this study, we examined the haplotype's effect on the age of onset of AD in DS. METHODS: People with DS were assessed for dementia. Genotyping was performed for the extended tau haplotype, APOE and a polymorphism in APP, attt(5-8). RESULTS: Haplotype frequencies vary between those developing AD before 45 and those developing dementia after this age (p = 0.03). H1/H2 individuals are more likely to develop dementia before 45 than H1/H1 individuals (OR = 3, 95% CI = 1.01-8.91). CONCLUSION: Even in a condition driven by excess amyloid pathology, factors affecting tau are also important and should be considered as potential treatment targets.

Effects of dairy products naturally enriched with cis-9,trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men.

BACKGROUND: Interest in the development of dairy products naturally enriched in conjugated linoleic acid (CLA) exists. However, feeding regimens that enhance the CLA content of milk also increase concentrations of trans-18:1 fatty acids. The implications for human health are not yet known. OBJECTIVE: This study investigated the effects of consuming dairy products naturally enriched in cis-9,trans-11 CLA (and trans-11 18:1) on the blood lipid profile, the atherogenicity of LDL, and markers of inflammation and insulin resistance in healthy middle-aged men. DESIGN: Healthy middle-aged men (n = 32) consumed ultra-heat-treated milk, butter, and cheese that provided 0.151 g/d (control) or 1.421 g/d (modified) cis-9,trans-11 CLA for 6 wk. This was followed by a 7-wk washout and a crossover to the other treatment. RESULTS: Consumption of dairy products enriched with cis-9,trans-11 CLA and trans-11 18:1 did not significantly affect body weight, inflammatory markers, insulin, glucose, triacylglycerols, or total, LDL, and HDL cholesterol but resulted in a small increase in the ratio of LDL to HDL cholesterol. The modified dairy products changed LDL fatty acid composition but had no significant effect on LDL particle size or the susceptibility of LDL to oxidation. Overall, increased consumption of full-fat dairy products and naturally derived trans fatty acids did not cause significant changes in cardiovascular disease risk variables, as may be expected on the basis of current health recommendations. CONCLUSION: Dairy products naturally enriched with cis-9,trans-11 CLA and trans-11 18:1 do not appear to have a significant effect on the blood lipid profile.

A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse.

The robotic mouse is an autosomal dominant mutant that arose from a large-scale chemical mutagenesis program. It has a jerky, ataxic gait and develops adult-onset Purkinje cell loss in the cerebellum in a striking region-specific pattern, as well as cataracts. Genetic and physical mapping of the disease locus led to the identification of a missense mutation in a highly conserved region of Af4, a putative transcription factor that has been previously implicated in leukemogenesis. We demonstrate that Af4 is specifically expressed in Purkinje cells, and we hypothesize that the expression of mutant Af4 leads to neurodegeneration. This function was not identified through knock-out studies, highlighting the power of phenotype-driven mutagenesis in the mouse to identify new pathways involved in neurological disease.

Confirmed locus on chromosome 11p and candidate loci on 6q and 8p for the triglyceride and cholesterol traits of combined hyperlipidemia.

UNLABELLED: Background- Combined hyperlipidemia is a common disorder characterized by a highly atherogenic lipoprotein profile and increased risk of coronary heart disease. The etiology of the lipid abnormalities (increased serum cholesterol and triglyceride or either lipid alone) is unknown. METHODS AND RESULTS: We assembled 2 large cohorts of families with familial combined hyperlipidemia (FCHL) and performed disease and quantitative trait linkage analyses to evaluate the inheritance of the lipid abnormalities. Chromosomal regions 6q16.1-q16.3, 8p23.3-p22, and 11p14.1-q12.1 produced evidence for linkage to FCHL. Chromosomes 6 and 8 are newly identified candidate loci that may respectively contribute to the triglyceride (logarithm of odds [LOD], 1.43; P=0.005) and cholesterol (LOD, 2.2; P=0.0007) components of this condition. The data for chromosome 11 readily fulfil the guidelines required for a confirmed linkage. The causative alleles may contribute to the inheritance of the cholesterol (LOD, 2.04 at 35.2 cM; P=0.0011) component of FCHL as well as the triglyceride trait (LOD, 2.7 at 48.7 cM; P=0.0002). CONCLUSIONS: Genetic analyses identify 2 potentially new loci for FCHL and provide important positional information for cloning the genes within the chromosome 11p14.1-q12.1 interval that contributes to the lipid abnormalities of this highly atherogenic disorder.

Linkage and association between distinct variants of the APOA1/C3/A4/A5 gene cluster and familial combined hyperlipidemia.

OBJECTIVE: Combined hyperlipidemia is a common disorder, characterized by a highly atherogenic lipoprotein profile and a substantially increased risk of coronary heart disease. The purpose of this study was to establish whether variations of apolipoprotein A5 (APOA5), a newly discovered gene of lipid metabolism located 30 kbp downstream of the APOA1/C3/A4 gene cluster, contributes to the transmission of familial combined hyperlipidemia (FCHL). METHODS AND RESULTS: We performed linkage and association tests on 128 families. Two independent alleles, APOA5c.56G and APOC3c.386G, of the APOA1/C3/A4/A5 gene cluster were overtransmitted in FCHL (P=0.004 and 0.007, respectively). This was paired with reduced transmission of the common APOA1/C3/A4/A5 haplotype (frequency 0.4461) to affected subjects (P=0.012). The APOA5c.56G genotype accounted for 7.3% to 13.8% of the variance in plasma triglyceride levels in probands (P<0.004). The APOC3c.386G genotypes accounted for 4.4% to 5.1% of the variance in triglyceride levels in FCHL spouses (P<0.007), suggesting that this allele marks a FCHL quantitative trait as well as representing a susceptibility locus for the condition. CONCLUSIONS: A combined linkage and association analysis establishes that variation at the APOA1/C3/A4/A5 gene cluster contributes to FCHL transmission in a substantial proportion of northern European families.

Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans.

BACKGROUND: Conjugated linoleic acid (CLA) is reported to have weight-reducing and antiatherogenic properties when fed to laboratory animals. However, the effects of CLA on human health and, in particular, the effects of individual CLA isomers are unclear. OBJECTIVE: This study investigated the effects of 3 doses of highly enriched cis-9,trans-11 (0.59, 1.19, and 2.38 g/d) or trans-10,cis-12 (0.63, 1.26, and 2.52 g/d) CLA preparations on body composition, blood lipid profile, and markers of insulin resistance in healthy men. DESIGN: Healthy men consumed 1, 2, and 4 capsules sequentially, containing either 80% cis-9,trans-11 CLA or 80% trans-10,cis-12 CLA for consecutive 8-wk periods. This phase was followed by a 6-wk washout and a crossover to the other isomer. RESULTS: Body composition was not significantly affected by either isomer of CLA. Mean plasma triacylglycerol concentration was higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA, although there was no influence of dose. There were significant effects of both isomer and dose on plasma total cholesterol and LDL-cholesterol concentrations but not on HDL-cholesterol concentration. The ratios of LDL to HDL cholesterol and of total to HDL cholesterol were higher during supplementation with trans-10,cis-12 CLA than during that with cis-9,trans-11 CLA. CLA supplementation had no significant effect on plasma insulin concentration, homeostasis model for insulin resistance, or revised quantitative insulin sensitivity check index. CONCLUSION: Divergent effects of cis-9,trans-11 CLA and trans-10,cis-12 CLA appear on the blood lipid profile in healthy humans: trans-10,cis-12 CLA increases LDL:HDL cholesterol and total:HDL cholesterol, whereas cis-9,trans-11 CLA decreases them.