Evidence-Based Opinions from Multidisciplinary Experts on Use of Naturopathic Herbal Remedies in Pain Management.

Background: Pharmacological approaches to acute and chronic pain management, including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, are respectively associated with adverse reactions (such as gastrointestinal, cardiovascular, and renal effects) that might limit their use in patients with comorbidities and controversy related to inappropriate use. Naturopathic remedies might offer patients alternative and integrative treatments with minimal side effects. Objective: To explore the regional variation in the acceptance and use of naturopathic remedies in pain management. Methods: Two expert panel discussions were held by GlaxoSmithKline Consumer Healthcare (now Haleon Pte. Ltd.) over 9 and 12 hours in 2020 and 2021, respectively, and attended by multidisciplinary experts in naturopathy, Ayurvedic medicine, community pharmacy, physiotherapy, clinical pharmacy, Western medicine, academics, and naturopathic pain relief. Experts shared and discussed their experiences of naturopathic treatments and relevant clinical evidence related to different types of pain (including joint and muscle pain, migraine, sleeplessness due to pain, and general pain) and examined barriers to providing support to patients. Results: Experts agreed on the potential for curcumin (2020, 71.4% [5/7]; 2021, 91.7% [11/12]) and fish oil (2020, 100% [7/7]) for management of osteoarthritic joint pain although these are not uniformly recommended in osteoarthritis treatment guidelines. In treatment of migraines, coenzyme Q10 and magnesium were favored by experts (2021, 90.9% [10/11] and 63.6% [7/11], respectively). Conclusion: The need was emphasized for more and higher quality clinical studies to support naturopathic remedies, which might not be reflected in the latest treatment guidelines. The expert panel also highlighted missed opportunities for physicians and pharmacists to recommend effective naturopathic treatments.

Fish oil supplementation during pregnancy and postpartum in mothers with overweight and obesity to improve body composition and metabolic health during infancy: A double-blind randomized controlled trial.

BACKGROUND: Maternal obesity during pregnancy is associated with an increased risk of obesity and metabolic disease in the offspring. Supplementation with fish oil (FO), which is insulin sensitizing, during pregnancy in mothers with overweight or obesity may prevent the development of greater adiposity and metabolic dysfunction in their children. OBJECTIVES: To determine the effects of FO supplementation throughout the second half of pregnancy and lactation in mothers with overweight or obesity on infant body composition and metabolism. METHODS: A double-blind randomized controlled trial of 6 g FO (3.55 g/d of n-3 PUFAs) compared with olive oil (control) from mid-pregnancy until 3 mo postpartum. Eligible women had singleton pregnancies at 12-20 wk of gestation, and BMI ≥ 25 kg/m2. The primary outcome was the infant body fat percentage (DXA scans) at 2 wk of age. Secondary outcomes included maternal metabolic markers during pregnancy, infant anthropometry at 2 wk and 3 mo of age, and metabolic markers at 3 mo. RESULTS: A total of 129 mothers were randomized, and 98 infants had a DXA scan at 2 wk. PRIMARY OUTCOME: Imputed and nonimputed analyses showed no effects of FO supplementation on infant body fat percentage at age 2 wk. SECONDARY OUTCOMES: There were no treatment effects on infant outcomes at 2 wk, but FO infants had a higher BMI z-score (P = 0.025) and ponderal index (P = 0.017) at age 3 mo. FO supplementation lowered maternal triglycerides by 17% at 30 wk of pregnancy (P = 0.0002) and infant triglycerides by 21% at 3 mo of age (P = 0.016) but did not affect maternal or infant insulin resistance. The rate of emergency cesarean section was lower with FO supplementation [aRR = 0.38 (95%CI 0.16, 0.90); P = 0.027]. CONCLUSIONS: FO supplementation of mothers with overweight or obesity during pregnancy did not impact infant body composition. There is a need to follow up the offspring to determine whether the observed metabolic effects persist. CLINICAL TRIAL REGISTRY NUMBER: This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001078347p). In addition, the Universal Trial Number, WHO, was obtained (U1111-1199-5860).

Medium-chain fatty acids for the prevention or treatment of Alzheimer's disease: a systematic review and meta-analysis.

CONTEXT: In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. OBJECTIVE: This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD. DATA SOURCES: A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. DATA EXTRACTION: Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (n = 17 studies) met the inclusion criteria. DATA ANALYSIS: All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. CONCLUSION: MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019146967.

Effect of a polyphenol-rich dietary supplement containing Pinus massoniana bark extract on blood pressure in healthy adults: A parallel, randomized placebo-controlled trial.

OBJECTIVES: High blood pressure (BP) is a major risk factor for cardiovascular disease and prevalence rates continue to rise with ageing populations. Polypharmacy remains a burden among the ageing, thus alternative effective strategies are warranted. This study investigated the effects of a polyphenols rich dietary supplement containing Pinus massoniana bark extract (PMBE) for modulating BP in healthy Australian adults. DESIGN: This study is a secondary analysis of data from a double-blinded, placebo-controlled clinical trial. METHODS: Sixty-two healthy adults aged 55-75 years were randomized to receive 50 mL dietary supplement containing placebo (0 mg PMBE) or PMBE (1322 mg PMBE) daily for 12 weeks. Seated systolic BP (SBP) and diastolic (DBP) were measured at baseline, 6 weeks and 12 weeks. Effects of PMBE on modulating BP was also explored in this study stratified for SBP status (optimal v high) as well as by SBP medication status. Mixed effect regression modelling was employed involving fixed categorical effects for elapsed time, treatment assignment and their interaction as well as random subject-level intercept to account for within-subject correlations resulting from repeated measurements. Significant models were further examined by addition of covariates and power calculations were performed since this study was a secondary analysis. RESULTS: SBP significantly reduced (-3.29 mmHg, p = 0.028) after PMBE at 12 weeks compared to baseline. SBP in individuals with normal-high SBP (>120 mmHg) in the PMBE group reduced by - 6.46 mmHg (p = 0.001) at 12 weeks compared to baseline. No significant changes were reported for individuals with optimal (≤120 mmHg) SBP nor did DBP significantly change in either study groups. In individuals with non-medicated normal-high SBP, SBP significantly reduced by - 7.49 mmHg (p = 0.001) and DBP by - 3.06 mmHg (p = 0.011) at 12 weeks compared to baseline after PMBE. Cross-group comparisons were not statistically different. CONCLUSIONS: A polyphenol-rich dietary supplement derived from PMBE led to a clinically and statistically significant reduction in SBP in adults. Future studies to investigate the effects of PMBE-polyphenol supplementation on BP are warranted to confirm and explore optimal dose and impact on hypertension.

Potential complementary and/or synergistic effects of curcumin and boswellic acids for management of osteoarthritis.

For several thousand years (~4000) Boswellia serrata and Curcuma longa have been used in Aryuvedic medicine for treatment of various illnesses, including asthma, peptic ulcers, and rheumatoid arthritis, all of which are mediated through pathways associated with inflammation and pain. Although the in vivo pharmacology of both these natural ingredients is difficult to study because of poor bioavailability, in vitro data suggest that both influence gene expression mediated through nuclear factor kappa B (NF-κB). Therefore, the activity of pathways associated with inflammation (including NF-κB and lipoxygenase- and cyclooxygenase-mediated reduction in leukotrienes/prostaglandins) and those involved in matrix degradation and apoptosis are reduced, resulting in a reduction in pain. Additive activity of boswellic acids and curcumin was observed in preclinical models and synergism was suggested in clinical trials for the management of osteoarthritis (OA) pain. Overall, studies of these natural ingredients, alone or in combination, revealed that these extracts relieved pain from OA and other inflammatory conditions. This may present an opportunity to improve patient care by offering alternatives for patients and physicians, and potentially reducing nonsteroidal anti-inflammatory or other pharmacologic agent use. Additional research is needed on the effects of curcumin on the microbiome and the influence of intestinal metabolism on the activity of curcuminoids to further enhance formulations to ensure sufficient anti-inflammatory and antinociceptive activity. This narrative review includes evidence from in vitro and preclinical studies, and clinical trials that have evaluated the mechanism of action, pharmacokinetics, efficacy, and safety of curcumin and boswellic acids individually and in combination for the management of OA pain.

Toxicity of oxidized fish oil in pregnancy: a dose-response study in rats.

Fish oil (FO) supplements are consumed during pregnancy to increase dietary omega-3. However, FO is often oxidized past recommended limits. In rats, a large dose of highly oxidized FO substantially increased newborn mortality, but the effects of human-relevant doses of less oxidized oil are unknown. A dose-response study in rats was conducted to estimate the safe level of oxidation during pregnancy. Sprague-Dawley rat dams were mated, then individually housed and provided with a gel treatment on each day of pregnancy. Treatment groups differed only in the FO content of the gel; control (no oil), PV5, PV10, and PV40 [0.05 mL of FO oxidized to a peroxide value (PV) of 5, 10, or 40 meq/kg], or PV40(1 mL) (1 mL of PV40). A subset of dams was culled on gestational day 20 to enable sampling, and the remainder were allowed to give birth. Newborn mortality was recorded. Offspring were sampled on postnatal days 2 and 21, and dams on day 21. There were no signs of unwellness during pregnancy. However, there was markedly increased neonatal mortality affecting the PV40(1 mL) (12.8%) and PV40 (6.3%) groups, but not the control, PV5, or PV10 groups (1%-1.4%). Dietary-oxidized FO altered the expression of placental genes involved in antioxidant pathways and the production of free radicals. Highly oxidized FO was toxic in rat pregnancy leading to a marked increase in mortality even at a human-relevant dose. We observed no toxic effects of FOs with PV ≤10 meq/kg, suggesting that this is an appropriate maximum limit.

Extra virgin olive oil high in polyphenols improves antioxidant status in adults: a double-blind, randomized, controlled, cross-over study (OLIVAUS).

PURPOSE: Olive oil polyphenols have been associated with cardiovascular health benefits. This study examined the antioxidant and anti-inflammatory effect of extra-virgin high polyphenol olive oil (HPOO) vs. low polyphenol olive oil (LPOO) in healthy Australian adults. METHODS: In a double-blind cross-over trial, 50 participants (aged 38.5 ± 13.9 years, 66% females) were randomized to consume 60 mL/day of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for three weeks. Following a 2-week wash-out period, participants crossed-over to the alternate treatment. Plasma oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP) and anthropometrics were measured at baseline and follow-up. RESULTS: Fourty-three participants completed the study. Although there were no significant differences between treatments in the total sample, plasma ox-LDL decreased by 6.5 mU/mL (95%CI - 12.4 to - 0.5) and TAC increased by 0.03 mM (95% CI 0.006-0.05) only in the HPOO arm. Stratified analyses were also performed by cardiovascular disease risk status defined by abdominal obesity (WC > 94 cm in males, > 80 cm in females) or inflammation (hs-CRP > 1 mg/L). In the subgroup with abdominal obesity, ox-LDL decreased by 13.5 mU/mL (95% CI - 23.5 to - 3.6) and TAC increased by 0.04 mM (95% CI 0.006-0.07) only after HPOO consumption. In the subgroup with inflammation, hs-CRP decreased by 1.9 mg/L (95% CI - 3.7 to -0.1) only in the HPOO arm. CONCLUSIONS: Although there were no significant differences between treatments, the changes observed after HPOO consumption demonstrate the antioxidant and anti-inflammatory effect of this oil, which is more pronounced in adults with high cardiometabolic risk (Clinical Trial Registration: ACTRN12618000706279).

Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer's Disease.

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neurodegenerative disorders including Alzheimer's disease (AD). Apart from traditionally targeting amyloid beta (Aß), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bioactive food components, known as nutraceuticals, may serve as such agents to combat AD. Urolithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, anti-inflammatory, anti-atherogenic, anti-Aß, and pro-mitophagy properties are increasingly recognized. However, the underlying mechanisms of urolithin A in inducing mitophagy is poorly understood. This review discusses the mitophagy deficits in AD and examines potential molecular mechanisms of its activation. Moreover, the current knowledge of urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy. Specifically, this review proposes potential mechanisms by which urolithin A may activate and promote mitophagy.

Anti-inflammatory effects of oral supplementation with curcumin: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Chronic inflammation is a major contributor to the development of noncommunicable diseases. Curcumin, a bioactive polyphenol from turmeric, is a well-known anti-inflammatory agent in preclinical research. Clinical evidence remains inconclusive because of discrepancies regarding optimal dosage, duration, and formulation of curcumin. OBJECTIVE: The aim of this systematic review, conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and checklist, was to evaluate the efficacy of curcumin supplementation on systemic inflammatory mediators, comparing dose, duration, and bioavailability status of interventions. DATA SOURCES: The Medline, CINAHL, EMBASE, Scopus, and Cochrane literature databases were searched from 1980 to May-end 2019. Randomized controlled trials investigating effects of dietary curcumin on inflammatory mediators in humans not receiving anti-inflammatory treatment were eligible for inclusion. Two authors independently assessed titles and abstracts of identified articles for potential eligibility and respective, retrieved, full-text articles; disagreements were resolved by a third author. Evidence quality was critically appraised using the Quality Criteria Checklist for Primary Research. DATA EXTRACTION: Thirty-two trials (N = 2,038 participants) were included and 28 were meta-analyzed using a random-effects model; effect sizes were expressed as Hedges' g (95%CI). DATA ANALYSIS: Pooled data (reported here as weighted mean difference [WMD]; 95%CI) showed a reduction in C-reactive protein (-1.55 mg/L; -1.81 to -1.30), interleukin-6 (-1.69 pg/mL, -2.56 to -0.82), tumor necrosis factor α (-3.13 pg/mL; -4.62 to -1.64), IL-8 (-0.54 pg/mL; -0.82 to -0.28), monocyte chemoattractant protein-1 (-2.48 pg/mL; -3.96 to -1.00), and an increase in IL-10 (0.49 pg/mL; 0.10 to 0.88), with no effect on intracellular adhesion molecule-1. CONCLUSION: These findings provide evidence for the anti-inflammatory effects of curcumin and support further investigation to confirm dose, duration, and formulation to optimize anti-inflammatory effects in humans with chronic inflammation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019148682.

Postprandial lipaemia following consumption of a meal enriched with medium chain saturated and/or long chain omega-3 polyunsaturated fatty acids. A randomised cross-over study.

BACKGROUND & AIMS: Postprandial lipaemic response has emerged as a risk factor for cardiovascular disease. Dietary fats such as medium-chain saturated fatty acids (MCSFA) and long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) are known to reduce postprandial lipaemic responses. The combination of the two could potentially have complementary and/or synergistic effects for optimising cardiovascular health. This study aims to investigate the effects of MCSFA (coconut oil) with or without LCn-3PUFA (fish oil) inclusion in the test meal on postprandial blood lipids in healthy adults. METHODS: In a randomised, double-blinded, placebo-controlled, 2 × 2 factorial cross-over study, participants (n = 15) were randomised to receive four standardised isocaloric test meals. Test meals include: placebo [PL, containing no fish oil (0 g EPA & DHA) or coconut oil (0 g MCSFA)], fish oil [FO, 6 g fish oil (3.85 g EPA & DHA), containing no coconut oil (0 g MCSFA)], coconut oil [CO, 18.65 g coconut oil (15 g MCSFA), containing no fish oil (0 g EPA & DHA)] and coconut oil + fish oil [COFO, 18.65 g coconut oil (15 g MCSFA) + 6 g fish oil (3.85 g EPA & DHA)]; all providing a total fat content of 33.5 g. Participants received all four treatments on four separate test days with at least 3 days washout in between. Blood parameters were measured by finger pricks at 7 timepoints between 0 and 300min. The primary outcome of this study was the change in postprandial triglycerides (TG) concentrations with secondary outcomes as total cholesterol, high-density lipoprotein cholesterol and blood glucose concentrations. RESULTS: TG area under the curve (AUC) (mmol/L/min) was significantly lower for FO (383.67, p = 0.0125) and COFO (299.12, p = 0.0186) in comparison to PL (409.17) only. TG incremental area under the curve (iAUC) (mmol/L/min) was significantly lower with COFO (59.67) in comparison to CO (99.86), (p = 0.0480). Compared to PL, the change in absolute TG concentrations (mmol/L) from baseline to post TG peak time (180min) after FO were significantly less at 240min (0.39 vs 0.15), 270min (0.2 vs 0.1), and 300min (0.28 vs 0.06), and after COFO was significantly less at 300min (0.28 vs 0.16) (p < 0.05). No significant differences in postprandial AUC and iAUC for any other blood parameters were reported. CONCLUSIONS: Our study demonstrated that LCn-3PUFA with or without MCSFA but not MCSFA alone are effective in reducing postprandial TG in healthy individuals.

Dietary supplementation with docosahexaenoic acid rich fish oil increases circulating levels of testosterone in overweight and obese men.

Pre-clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs), in particular, docosahexaenoic acid (DHA) have been shown to affect testosterone synthesis in males. This study is a secondary analysis of a randomized controlled trial which determined the effect of a DHA-enriched fish oil supplement on insulin resistance. The aim of the current study was to determine whether testosterone levels change in response to a DHA-enriched fish oil intervention. Overweight and obese men and women without diabetes were recruited to the study. Participants were stratified by sex and randomly allocated to intervention (860 mg DHA + 120 g EPA/day; FO) or an isocaloric control (corn oil; CO) for 12 weeks. A fasted blood sample was collected pre- and post-intervention. Fatty acid composition of erythrocyte membranes was measured using gas chromatography. Total testosterone and metabolic parameters were measured by an accredited commercial pathology laboratory. Sixty-one participants (CO/FO: n = 29/32) were included in the current analysis (male: n = 22, 36.07%).  DHA-enriched fish oil supplementation increased total testosterone levels in males after adjusting for baseline levels, age and BMI. There was no treatment effect in females. Changes in testosterone levels in males were positively associated with changes to omega-3 PUFAs EPA and DHA and inversely correlated with omega-6 PUFA, arachidonic acid and dihomo-gamma-linolenic acid content in erythrocyte membranes, and was associated with beneficial changes to fasting insulin and HOMA-IR across the course of the study. DHA-enriched fish oil supplementation increases testosterone levels in overweight and obese men. Further research is warranted to substantiate these findings with a larger sample size and a longer follow-up period.

Docosahexaenoic Acid-Rich Fish Oil Supplementation Reduces Kinase Associated with Insulin Resistance in Overweight and Obese Midlife Adults.

Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer's disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7 ± 1.7 years, BMI: 31.9 ± 0.8 kg/m2) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules (n = 27) per day for 12 weeks. Compared to placebo, DHA-rich fish oil significantly reduced GSK-3ß by -2.3 ± 0.3 ng/mL. An inverse correlation (p < 0.05) was found between baseline insulin and IR and their changes following intervention only in participants with C-reactive protein levels higher than 2.4 mg/L. DHA-rich fish oil reduces GSK-3 and IR, suggesting a potential role of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) in ameliorating AD risk.

Association between Obesity and Omega-3 Status in Healthy Young Women.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for healthy development and protect against metabolic disease. However, individuals with obesity may be pre-disposed to experiencing lower n-3 PUFA status than normal-weight individuals. This cross-sectional study examined the relationship between the omega-3 index (O3I), body mass index (BMI) and dietary intake in healthy young women (n = 300; age = 18-35 y), a group not previously focused on. Intake was adjusted for energy using the residuals method, and associations were explored using independent t-tests and Pearson's correlations. Participants with obesity were found to have significantly lower O3I than normal-weight participants (p < 0.0001); however, no significant differences were observed in mean n-3 PUFA intakes. Even so, energy-adjusted intakes of n-3 PUFAs, with the exception of alpha-linolenic acid, were significantly correlated with O3I. This study demonstrates that O3I is influenced by both BMI and diet in young women; however the relationship between these two variables may be complex. Current intakes of n-3 PUFA observed in young women may not be effective in achieving target O3I levels in those with obesity, and further research is needed to find effective ways of improving n-3 PUFA status in a group already at increased risk of metabolic disease.

Dietary Supplementation with Curcumin Reduce Circulating Levels of Glycogen Synthase Kinase-3ß and Islet Amyloid Polypeptide in Adults with High Risk of Type 2 Diabetes and Alzheimer's Disease.

Dietary supplementation with curcumin has been previously reported to have beneficial effects in people with insulin resistance, type 2 diabetes (T2D) and Alzheimer's disease (AD). This study investigated the effects of dietary supplementation with curcumin on key peptides implicated in insulin resistance in individuals with high risk of developing T2D. Plasma samples from participants recruited for a randomised controlled trial with curcumin (180 mg/day) for 12 weeks were analysed for circulating glycogen synthase kinase-3 ß (GSK-3ß) and islet amyloid polypeptide (IAPP). Outcome measures were determined using ELISA kits. The homeostasis model for assessment of insulin resistance (HOMA-IR) was measured as parameters of glycaemic control. Curcumin supplementation significantly reduced circulating GSK-3ß (-2.4 ± 0.4 ng/mL vs. -0.3 ± 0.6, p = 0.0068) and IAPP (-2.0 ± 0.7 ng/mL vs. 0.4 ± 0.6, p = 0.0163) levels compared with the placebo group. Curcumin supplementation significantly reduced insulin resistance (-0.3 ± 0.1 vs. 0.01 ± 0.05, p = 0.0142) compared with placebo group. Dietary supplementation with curcumin reduced circulating levels of IAPP and GSK-3ß, thus suggesting a novel mechanism through which curcumin could potentially be used for alleviating insulin resistance related markers for reducing the risk of T2D and AD.

High molecular weight oat ß-glucan enhances lipid-lowering effects of phytosterols. A randomised controlled trial.

BACKGROUND & AIMS: Oat ß-glucan (OBG) and phytosterols (PS) are known to lower blood cholesterol levels via different mechanisms. Combination of high molecular weight (MW) OBG and PS in a single functional food could have complementary and/or synergistic effects for optimising heart health. The aim of this study was to investigate the effects of dietary supplementation with high-MW OBG with or without PS on plasma lipids in hypercholesterolaemic individuals. METHODS: In a double-blinded, placebo-controlled, 2 × 2 factorial trial, participants were randomised to receive biscuits fortified with either no PS or OBG (PL, n = 18) or 2 g PS (PS, n = 18), 3 g OBG (OBG, n = 18), or combination of 2 g PS and 3 g OBG (PS-OBG, n = 18) per day for 6 weeks. Primary outcome was fasting plasma total cholesterol (TC) and secondary outcomes were LDL-cholesterol, LDL-C; HDL-cholesterol, HDL-C; triglycerides, TG and TC to HDL-cholesterol (TC:HDL) ratio. RESULTS: TC and LDL-C were significantly lowered following PS (-4.6% and -7.6% respectively; p < 0.05), OBG (-5.7% and -8.6%; p < 0.01) and PS-OBG (-11.5% and -13.9%; p < 0.0001) administration. The reduction in TC in the PS-OBG group was significantly greater compared to PL (p < 0.001) and PS (p < 0.05). PS-OBG group had a significantly greater reduction in LDL-C compared to PL (p < 0.01) but not in comparison to PS or OBG groups. TC:HDL ratio was significantly reduced following PS-OBG (-8.9%; p < 0.01) only, and there was no significant difference found between groups. Plasma TG reduced by 8.4% following PS-OBG, however, this was statistically non-significant. Plasma HDL-C remained unchanged across all groups. CONCLUSIONS: Dietary supplementation with high-MW OBG and PS in a single functional food enhances their lipid-lowering potential. Blood cholesterol lowering by PS and OBG is additive. Delivery of these two bioactive nutrients in a single food allows optimisation of their lipid-lowering effects and may provide added heart health benefits with enhanced compliance. The trial was registered with the Australian New Zealand Clinical Trials Registry at http://www.anzctr.org.au/(ACTRN12618001455257).

Association between plasma phospholipid omega-3 polyunsaturated fatty acids and type 2 diabetes is sex dependent: The Hunter Community Study.

BACKGROUND & AIMS: Chronic inflammation drives the development of insulin resistance and type 2 diabetes. Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) eicosapentaenoic acid (EPA, c20:5n-3) and docosahexaenoic acid (DHA, c22:6n-3) may protect against type 2 diabetes development. The aim of this current study is to determine whether LCn-3PUFA status is associated with type 2 diabetes in the Hunter Community Study. METHODS: Men and women aged 55-85 years were randomly selected from the electoral roll and invited to participate. Participants were included in the current study if they had plasma phospholipid fatty acid composition data available and diabetes status could be determined. LCn-3PUFA status was determined by fatty acid composition of plasma phospholipids (EPA + DHA, %,w/w). Diabetes was determined according to World Health Organisation criteria. Insulin was measured in n = 251 participants and HOMA-IR calculated. RESULTS: In total, n = 2092 (diabetes: n = 249) participants were included. After adjusting for confounders of diabetes, LCn-3PUFA status was inversely associated with diabetes in overweight/obese females (OR [95%CI]: 0.90 [0.80, 1.00], p = 0.045) but not males (p-interactionsex = 0.041). Overweight/obese females with diabetes had significantly lower levels of DHA than those without diabetes (mean difference [95%CI]: -0.53 [-0.87, -0.20], p = 0.002), with no difference in EPA. LCn-3PUFA was inversely associated with HOMA-IR (r = -0.175, p = 0.005). CONCLUSIONS: This study provides further evidence of a sex-dependent association between LCn-3PUFA and type 2 diabetes. Causal pathways between LCn-3PUFA and type 2 diabetes merits delineation.

Long-chain omega-3 polyunsaturated fatty acids and cognitive decline in non-demented adults: a systematic review and meta-analysis.

CONTEXT: Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) are widely considered as nootropic agents that may be beneficial in reversing cognitive impairment. OBJECTIVE: The present systematic review of randomized controlled trials was conducted to determine the changes in cognitive function after intervention with LCn-3PUFA supplementation in non-demented adults, including those with mild cognitive impairment. DATA SOURCES: Five databases (MEDLINE, CINAHL, Scopus, EMBASE, and the Cochrane Library) were searched systematically along with reference lists of selected articles. STUDY SELECTION: Studies were eligible for inclusion if they measured the effect of LCn-3PUFA supplementation on cognition in non-demented adults. DATA EXTRACTION: A total of 787 records were screened, of which 25 studies were eligible for inclusion. Treatment effects were summarized as global cognitive function for primary outcome and measured using the Mini-Mental State Examination and individual cognitive domains for secondary outcome. The pooled effect sizes were estimated using Hedge's g and random-effects modeling. DATA ANALYSIS: Results from randomized controlled trials indicate that LCn-3PUFAs have no effect on global cognitive function (Hedge's g = 0.02; 95% confidence interval, -0.12 to 0.154), and among the specific cognitive domains, only memory function showed a mild benefit (Hedge's g = 0.31; P = 0.003; z = 2.945). CONCLUSION: The existing literature suggests that LCn-3PUFA supplementation could provide a mild benefit in improving memory function in non-demented older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017078664.

Omega-3 polyunsaturated fatty acids status and cognitive function in young women.

BACKGROUND: Research indicates that low omega-3 polyunsaturated fatty acid (n-3 PUFA) may be associated with decreased cognitive function. This study examined the association between n-3 PUFA status and cognitive function in young Australian women. METHODS: This was a secondary outcome analysis of a cross-sectional study that recruited 300 healthy women (18-35 y) of normal weight (NW: BMI 18.5-24.9 kg/m2) or obese weight (OB: BMI ≥30.0 kg/m2). Participants completed a computer-based cognition testing battery (IntegNeuro™) evaluating the domains of impulsivity, attention, information processing, memory and executive function. The Omega-3 Index (O3I) was used to determine n-3 PUFA status (percentage of EPA (20:5n-3) plus DHA (22:6n3) in the red cell membrane) and the participants were divided into O3I tertile groups: T1 < 5.47%, T2 = 5.47-6.75%, T3 > 6.75%. Potential confounding factors of BMI, inflammatory status (C-reactive Protein), physical activity (total MET-min/wk), alpha1-acid glycoprotein, serum ferritin and hemoglobin, were assessed. Data reported as z-scores (mean ± SD), analyses via ANOVA and ANCOVA. RESULTS: Two hundred ninety-nine women (26.9 ± 5.4 y) completed the study (O3I data, n = 288). The ANOVA showed no overall group differences but a significant group × cognition domain interaction (p < 0.01). Post hoc tests showed that participants in the low O3I tertile group scored significantly lower on attention than the middle group (p = 0.01; ES = 0.45 [0.15-0.74]), while the difference with the high group was borderline significant (p = 0.052; ES = 0.38 [0.09-0.68]). After confounder adjustments, the low group had lower attention scores than both the middle (p = 0.01) and high (p = 0.048) groups. These findings were supported by univariate analyses which found significant group differences for the attention domain only (p = 0.004). CONCLUSIONS: Cognitive function in the attention domain was lower in women with lower O3I, but still within normal range. This reduced but normal level of cognition potentially provides a lower baseline from which cognition would decline with age. Further investigation of individuals with low n-3 PUFA status is warranted.

Food matrix and co-presence of turmeric compounds influence bioavailability of curcumin in healthy humans.

The natural food-derived compound curcumin (from turmeric root) is known for its anti-inflammatory and anti-oxidant effects. However, due to its poor solubility when consumed in isolation, it is poorly bioavailable. In this crossover study we compared the bioavailability of curcumin from a meal containing either curcumin powder, turmeric powder or grated fresh turmeric root, all containing 400 mg of curcumin, along with mashed potatoes and cream. Healthy male participants consumed the meals following overnight fasting, and postprandial blood samples were taken to measure plasma curcuminoids (curcumin, dimethylcurcumin (DMC) and bisdimethylcurcumin (BDMC)). All plasma curcumin values refer to total curcumin (sum of free and conjugated curcumin). The meals were also analysed using confocal laser scanning microscopy to determine the location of curcuminoids. Both of the turmeric meals produced significantly higher amounts (p < 0.05) of plasma curcuminoids at 1-3 hours after the meal was consumed, as compared to the curcumin powder. Plasma curcumin Cmax was 4.9 ng ml-1 95% CI (confidence interval) [2.2, 7.5] for the fresh turmeric meal, 8.4 ng ml-1 95% CI [4.4, 12.48] for the turmeric powder meal and 0.19 ng ml-1 95% [-0.08, 0.47] for the curcumin powder meal. Plasma DMC and BDMC were significantly higher (p < 0.05) following the turmeric powder meal, compared with the fresh turmeric meal and the curcumin powder meal. Microscopy images showed that the curcuminoid particles were mostly confined within curcuminoid cells in the fresh turmeric meal. They were unconfined but in clusters in the turmeric powder meal, while the curcuminoid particles appeared smaller in the curcumin powder meal. Conclusion: curcumin bioavailability is enhanced when consumed as fresh or powdered turmeric, which could be due to the co-presence of other turmeric compounds and/or a turmeric matrix effect.

Modulation of Circulating Trimethylamine N-Oxide Concentrations by Dietary Supplements and Pharmacological Agents: A Systematic Review.

Discovery of the association of plasma/serum trimethylamine N-oxide (TMAO) concentrations with atherosclerosis has sparked immense interest in exploring TMAO as a predictor of cardiovascular disease risk. A spectrum of antibiotics and other therapeutic strategies have been employed to test their potential to modulate TMAO concentrations, assuming the gut microbiome to be the key source of TMAO. The aim of this systematic review was to determine whether dietary supplements or pharmacological agents affect TMAO concentrations in adults. Six databases were searched (Medline, EMBASE, CINAHL, Scopus, ProQuest, and PubMed) for randomized and nonrandomized controlled trials. Searches were limited to the English language and to studies in adults. Thirteen eligible trials were identified, including 6 studies on dietary supplements and 7 on pharmacological agents. Whereas intervention studies involving dietary supplements were mostly randomized controlled trials, those involving pharmacological agents appeared opportunistic and varied greatly in study design and duration. Different interventional products were tested, and the studies lacked the consistency to reliably synthesize any evidence for the modifiability of TMAO concentrations by dietary supplements or pharmacological agents. Choline and l-carnitine are conditionally essential nutrients, and carefully designed placebo-controlled randomized trials specifically aimed at reducing the synthesis of microflora-dependent TMAO production from choline-containing precursors by pro- and/or prebiotics, antibiotics, or other pharmaceutical agents may be the way forward for future research.