Effect of n-3 (Omega-3) Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers and Body Weight in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of RCTs.

Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM), using a meta-analysis of randomized, controlled trials (RCTs). Online databases PubMed, Embase, Web of Science, and Science Direct were searched until 2021 to identify eligible articles. Thirty trials were included. The results showed that n-3 consumption can significantly reduce glycemic factors including fasting blood sugar (FBS) (-0.36 (-0.71 to -0.01)), glycated hemoglobulin (HbA1c) (-0.74 (-1.13 to -0.35)), and homeostatic model assessment of insulin resistance (HOMA.IR) (-0.58 (-1.13 to -0.03)). Furthermore, significant improvement in lipid profile including triglycerides (TG) (-0.27 (-0.37 to -0.18)), total cholesterol (-0.60 (-0.88 to -0.32)), low density lipoprotein (LDL) (-0.54 (-0.85 to -0.23)), and high-density lipoprotein (HDL) (0.60 (0.23 to 0.96)) levels were found in the present meta-analysis. The reduction in the inflammatory marker's tumor necrosis factor-alpha (TNF-α) (-0.13 (-0.75 to 0.48)) and c-reactive protein (CRP) (-0.72 (-1.70 to 0.27)), as well as weight (-0.09 (-0.24 to 0.07)) and BMI (-0.13 (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of n-3 consumption for patients with T2DM is 1000-2000 mg/d for more than 8 weeks. The present meta-analysis and review reveals that n-3 supplementation can improve glycemic factors and lipid profile in patients with T2DM. Furthermore, n-3 supplementation may provide beneficial effects on inflammatory markers and body weight if used at the appropriate dose and duration.

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. METHODS: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. RESULTS: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). CONCLUSIONS: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.

Relationship between Fatty Acid Habitual Intake and Early Inflammation Biomarkers in Individuals with and without Type 2 Diabetes in Mexico.

BACKGROUND: Lifestyle changes have led to a high global incidence of type 2 Diabetes mellitus (T2DM). Evidence suggests beneficial effects of the intake of n-3 and n-6 polyunsaturated fatty acids (PUFA) in patients with T2DM. OBJECTIVE: To investigate the relationship between habitual fatty acid intake and inflammatory biomarkers in Mexican individuals with and without T2DM. METHODS: A cross-sectional study of 120 adults with and 120 without T2DM; anthropometric assessments (BMI, waist circumference and body fat), blood pressure, PUFA intake, biochemical analyses (glucose and lipid profile) and inflammation biomarkers (IFN-γ, TNF-α, IL-1 ß, IL-2, IL-6, IL-8 and IL-13) was undertaken. RESULTS: Low n-3 intake was found in both groups (0.68 ± 0.55g/day in T2DM vs 0.81 ± 0.53 g/day in non-T2DM). Comparison between groups showed significantly higher concentrations of triacylglcerols (p=.001) and IL-6 (p=.018) in the T2DM group, as well as significant correlations between serum TNF-α and total n-3 fatty acid intake (r=.507, p= .001), EPA (r=.284, p=.002), DHA (r=.404, p=.001), and a weak but significant correlation between serum IL-1ß and total PUFA (r=.245, p=.005), total n-3 (r=.214, p=.019) and total n-6 (r=.241, p=.008) intake. CONCLUSIONS: Patients with T2DM had a tendency for higher pro-inflammatory cytokines than subjects without T2DM. There was an association between PUFA intake and pro-inflammatory biomarkers in patients with T2DM. Further studies of anti-inflammatory nutrients and plasma and cell fatty acid profiles are needed to corroborate the present findings in patients with and without T2DM.

Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis.

Epidemiological, biochemical, animal model and clinical trial data described in this overview strongly suggest that polyunsaturated fatty acids, particularly n-6 fatty acids, have a role in the pathogenesis and treatment of multiple sclerosis (MS). Data presented provides further evidence for a disturbance in n-6 fatty acid metabolism in MS. Disturbance of n-6 fatty acid metabolism and dysregulation of cytokines are shown to be linked and a "proof of concept clinical trial" further supports such a hypothesis. In a randomised double-blind, placebo controlled trial of a high dose and low dose selected GLA (18:3n-6)-rich oil and placebo control, the high dose had a marked clinical effect in relapsing-remitting MS, significantly decreasing the relapse rate and the progression of disease. Laboratory findings paralleled clinical changes in the placebo group in that production of mononuclear cell pro-inflammatory cytokines (TNF-alpha, IL-1beta) was increased and anti-inflammatory TGF-beta markedly decreased with loss of membrane n-6 fatty acids linoleic (18:2n-6) and arachidonic acids (20:4n-6). In contrast there were no such changes in the high dose group. The improvement in disability (Expanded Disability Status Scale) in the high dose suggests there maybe a beneficial effect on neuronal lipids and neural function in MS. Thus disturbed n-6 fatty acid metabolism in MS gives rise to loss of membrane long chain n-6 fatty acids and loss of the anti-inflammatory regulatory cytokine TGF-beta, particularly during the relapse phase, as well as loss of these important neural fatty acids for CNS structure and function and consequent long term neurological deficit in MS.

Long-chain polyunsaturated fatty acids in Chinese and Swedish mothers: diet, breast milk and infant growth.

UNLABELLED: Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential dietary nutrients required for the optimal growth and development of infants, particularly of the brain and retina. It is important for exclusively breastfed infants to receive milk of a correct balance between omega-6 and omega-3 fatty acids. In this study, we compared the composition of LC-PUFAs in the diet and milk of mothers and their infants' growth between Chinese and Swedish. Twenty-three and 19 mother-term infant pairs from a rural area of northern Beijing, China, and Stockholm, Sweden, who were 3 mo old and exclusively breastfed, were studied. The Chinese diet was higher in carbohydrate (17% of energy) but lower in protein (4% of energy) and fat (12% of energy) than the Swedish diet. The intake of Chinese mothers contained more linoleic acid (LA, C(18 ratio 2 omega-6)) and less arachidonic acid (AA, C(20 ratio 4 omega-6)), eicosapentaenoic acid (EPA, C(20 ratio 5 omega-3)) and docosahexaenoic acid (DHA, C(22 ratio 6 omega-3)) than that of Swedish mothers. The breast milk of the Chinese mothers had significantly higher LA and lower EPA and DHA levels than that of the Swedish mothers. However, in Chinese breast milk the AA level was significantly higher than that in Swedish breast milk. The recommended ranges of the ratios of LA to alpha-linolenic acid (LNA, C(18 ratio 3 omega-3)) and of AA to DHA in human milk are 5-10 and 0.5-1 compared with 23.0 and 3.1 in the Chinese breast milk, and 7.5 and 1.6 in the Swedish breast milk, respectively. CONCLUSION: The diet of the studied Chinese mothers is less balanced with regard to the levels of omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) than that of the Swedish mothers, which is also mirrored in the breast milk of these mothers. The clinical relevance of the difference between the levels of LC-PUFAs in the breast milk of Chinese and Swedish mothers may be elucidated by a follow-up study of the cognitive and visual functions of the infants involved.

Evidence for cytokine dysregulation in multiple sclerosis: peripheral blood mononuclear cell production of pro-inflammatory and anti-inflammatory cytokines during relapse and remission.

We investigated circulating anti-inflammatory and pro-inflammatory cytokines, and their ex vivo PBMC production in the absence or presence of the neuroantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) and T cell mitogen (PHA) in MS patients in relapse and remission, patients with other neurological disorders (OND) and normal healthy controls. MS patients in relapse exhibited significantly increased PBMC production of TNF-alpha spontaneously compared with MS remission and healthy controls and with MBP compared with MS remission. Patients in relapse had significantly increased spontaneous, PHA- and MBP-induced PBMC IL-1beta production compared with remission MS, and was increased compared (PHA only) with OND and healthy controls. In relapse there was also significantly increased PBMC IFN-gamma production (PHA only) compared with remission and a significantly lower production of biologically active TGF-beta1 (PHA only) compared with remission MS and OND. In contrast, MS patients in remission produced significantly less spontaneous and MBP-induced TNF-alpha, spontaneous, PHA- and MBP-induced IL-1beta and PHA-induced IFN-gamma together with increased production of biologically active TGF-beta1. MOG non-specifically increased PBMC TNF-alpha and IL-1beta production in all groups. Pro-inflammatory cytokines in corresponding plasma samples were undetectable whilst the concentration of biologically active TGF-beta1 was the reverse of ex vivo PBMC findings. The increase in biologically active TGF-beta1 production ex vivo in OND patients, despite active disease, compared with the low level in the MS relapse may indicate a regulatory defect in MS. We conclude that the balance between biologically active TGF-beta1 and the pro-inflammatory TNF-alpha, IL-1beta and IFN-gamma is dysregulated during MS relapse-remission and that normal counter-regulatory mechanisms during the relapse phase are defective.

Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3.

The essentiality of n-6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20:4n-6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (1 8:2n-6, LA) for membrane phospholipids. Low n-6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2-like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer-chain n-6 PUFA produced by gamma-linolenic acid (18:3n-6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n-6 PUFA, GLA, dihomo-gamma-linolenic acid (20:3n-6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (TGF)-beta-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha production. Low intakes of long-chain n-3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and Th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long-chain n-3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n-3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n-3 PUFA augment disease, whereas n-6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n-6 and n-3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n-6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.