Marine omega-3 rich oils are used by more than a third of American adults for a wide range of purported benefits including prevention of cardiovascular disease. These oils are highly prone to oxidation to lipid peroxides and other secondary oxidation products. Oxidized oils may have altered biological activity making them ineffective or harmful, though there is also evidence that some beneficial effects of marine oils could be mediated through lipid peroxides. To date, human clinical trials have not reported the oxidative status of the trial oil. This makes it impossible to understand the importance of oxidation to efficacy or harm. However, animal studies show that oxidized lipid products can cause harm. Oxidation of trial oils may be responsible for the conflicting omega-3 trial literature, including the prevention of cardiovascular disease. The oxidative state of an oil can be simply determined by the peroxide value and anisidine value assays. We recommend that all clinical trials investigating omega-3 harms or benefits report the results of these assays; this will enable better understanding of the benefits and harms of omega-3 and the clinical importance of oxidized supplements.

We examined whether maternal fish oil supplementation during pregnancy could prevent development of insulin resistance in adult male offspring of rat dams fed a high-fat diet. Time-mated Sprague-Dawley rat dams were randomised into four treatment groups: Con-Con, dams fed a control diet (fat: 15% kcal) and administered water by gavage; Con-FO, control diet with unoxidised fish oil by gavage; HF-Con, high-fat diet (fat: 45% kcal) and water by gavage; and HF-FO, high-fat diet and unoxidised fish oil by gavage. Dams were fed the allocated diet ad libitum during pregnancy and lactation, but daily gavage occurred only during pregnancy. After weaning, male offspring consumed a chow diet ad libitum until adulthood. Maternal high-fat diet led to increased food consumption, adiposity, systolic blood pressure, and triglycerides and plasma leptin in adult HF-Con offspring. HF-Con offspring also exhibited lower insulin sensitivity than Con-Con rats. Male offspring from HF-FO group were similar to HF-Con regarding food consumption and most metabolic parameters. However, insulin sensitivity in the HF-FO group was improved relative to the HF-Con offspring. Supplementation with unoxidised n-3 PUFA rich oils in the setting of a maternal obesogenic diet improved insulin sensitivity, but had no impact on body composition of adult male offspring.

Faecal microbiota transplantation (FMT) has been explored as a potential treatment for obesity, but its long-term effects on metabolic health remain unclear. Here, we report 4-year follow-up findings from a double-blind, randomised, placebo-controlled trial assessing FMT in adolescents with obesity (ACTRN12615001351505, Australian New Zealand Clinical Trials Registry). This unblinded follow-up study evaluated 63% (55/87) of the original participants (27 FMT, 28 placebo). There was no difference in BMI between the two groups, after adjusting for sex, age, diet, and physical activity (−3.6 kg/m², p = 0.095). However, FMT recipients showed clinical improvements in body composition and metabolic health compared to the placebo group. Specifically, FMT recipients had smaller waist circumference (−10.0 cm, p = 0.026), total body fat (−4.8%, p = 0.024), metabolic syndrome severity score (−0.58, p = 0.003), and systemic inflammation (−68% hs-CRP, p = 0.002) and higher levels of HDL cholesterol (0.16 mmol/L, p = 0.037). No group differences were observed in glucose markers, or other lipid parameters. Shotgun metagenomic sequencing revealed sustained long-term alterations in gut microbiome richness, composition and functional capacity, with persistence of donor-derived bacterial and bacteriophage strains. These findings highlight the potential relevance of FMT as a microbiome-augmenting intervention for obesity management and metabolic health, warranting further investigation.

Introduction: Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents. Methods and analysis: A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ≥30 kg/m ² ] adolescents (males and females, aged 14–18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18–28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14 mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat. Ethics and dissemination: Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences. Trial registration number: ACTRN12615001351505; Pre-results.

Between 2005 and 2021, 49 cases of classical congenital adrenal hyperplasia were diagnosed in New Zealand, 39 were detected in newborns and 10 were not detected by screening. Currently, for every case of CAH detected by screening, 10 false-positive tests are encountered. Second-tier liquid chromatography-tandem mass spectrometry (LCMSMS) has the potential to improve screening sensitivity and specificity. A new laboratory protocol for newborn screening for CAH was evaluated. Birthweight-adjusted thresholds for first- and second-tier 17-hydroxyprogesterone, second-tier 21-deoxycortisol and a steroid ratio were applied to 4 years of newborn screening data. The study was enriched with 35 newborn screening specimens from confirmed CAH cases. Newborn screening was conducted on 232,542 babies, and 11 cases of classical CAH were detected between 2018 and 2021. There were 98 false-positive tests (specificity 99.96%, PPV = 10.1%) using the existing protocol. Applying the new protocol, the same 11 cases were detected, and there were 13 false-positive tests (sensitivity > 99.99%, PPV = 45.8%, (X² test p < 0.0001). Incorporating the retrospective specimens, screening sensitivity for classical CAH was 78% (existing protocol), compared to 87% for the new protocol (X² test p = 0.1338). Implementation of LCMSMS as a second-tier test will improve newborn screening for classical CAH in New Zealand.