Impact of preconception and antenatal supplementation with myo-inositol, probiotics, and micronutrients on offspring BMI and weight gain over the first 2 years.

BACKGROUND: Nutritional intervention preconception and throughout pregnancy has been proposed as an approach to promoting healthy postnatal weight gain in the offspring but few randomised trials have examined this. METHODS: Measurements of weight and length were obtained at multiple time points from birth to 2 years among 576 offspring of women randomised to receive preconception and antenatally either a supplement containing myo-inositol, probiotics, and additional micronutrients (intervention) or a standard micronutrient supplement (control). We examined the influence on age- and sex-standardised BMI at 2 years (WHO standards, adjusting for study site, sex, maternal parity, smoking and pre-pregnancy BMI, and gestational age), together with the change in weight, length, BMI from birth, and weight gain trajectories using latent class growth analysis. RESULTS: At 2 years, there was a trend towards lower mean BMI among intervention offspring (adjusted mean difference [aMD] - 0.14 SD [95% CI 0.30, 0.02], p = 0.09), and fewer had a BMI > 95th percentile (i.e. > 1.65 SD, 9.2% vs 18.0%, adjusted risk ratio [aRR] 0.51 [95% CI 0.31, 0.82], p = 0.006). Longitudinal data revealed that intervention offspring had a 24% reduced risk of experiencing rapid weight gain > 0.67 SD in the first year of life (21.9% vs 31.1%, aRR 0.76 [95% CI 0.58, 1.00], p = 0.047). The risk was likewise decreased for sustained weight gain > 1.34 SD in the first 2 years of life (7.7% vs 17.1%, aRR 0.55 [95% CI 0.34, 0.88], p = 0.014). From five weight gain trajectories identified, there were more intervention offspring in the "normal" weight gain trajectory characterised by stable weight SDS around 0 SD from birth to 2 years (38.8% vs 30.1%, RR 1.29 [95% CI 1.03, 1.62], p = 0.029). CONCLUSIONS: Supplementation with myo-inositol, probiotics, and additional micronutrients preconception and in pregnancy reduced the incidence of rapid weight gain and obesity at 2 years among offspring. Previous reports suggest these effects will likely translate to health benefits, but longer-term follow-up is needed to evaluate this. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02509988 (Universal Trial Number U1111-1171-8056). Registered on 16 July 2015.

Maternal B-vitamin and vitamin D status before, during, and after pregnancy and the influence of supplementation preconception and during pregnancy: Prespecified secondary analysis of the NiPPeR double-blind randomized controlled trial.

BACKGROUND: Maternal vitamin status preconception and during pregnancy has important consequences for pregnancy outcome and offspring development. Changes in vitamin status from preconception through early and late pregnancy and postpartum have been inferred from cross-sectional data, but longitudinal data on vitamin status from preconception throughout pregnancy and postdelivery are sparse. As such, the influence of vitamin supplementation on vitamin status during pregnancy remains uncertain. This study presents one prespecified outcome from the randomized controlled NiPPeR trial, aiming to identify longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6 months postdelivery, and determine the influence of vitamin supplementation. METHODS AND FINDINGS: In the NiPPeR trial, 1,729 women (from the United Kingdom, Singapore, and New Zealand) aged 18 to 38 years and planning conception were randomized to receive a standard vitamin supplement (control; n = 859) or an enhanced vitamin supplement (intervention; n = 870) starting in preconception and continued throughout pregnancy, with blinding of participants and research staff. Supplement components common to both treatment groups included folic acid, ß-carotene, iron, calcium, and iodine; components additionally included in the intervention group were riboflavin, vitamins B6, B12, and D (in amounts available in over-the-counter supplements), myo-inositol, probiotics, and zinc. The primary outcome of the study was glucose tolerance at 28 weeks' gestation, measured by oral glucose tolerance test. The secondary outcome reported in this study was the reduction in maternal micronutrient insufficiency in riboflavin, vitamin B6, vitamin B12, and vitamin D, before and during pregnancy. We measured maternal plasma concentrations of B-vitamins, vitamin D, and markers of insufficiency/deficiency (homocysteine, hydroxykynurenine-ratio, methylmalonic acid) at recruitment, 1 month after commencing intervention preconception, in early pregnancy (7 to 11 weeks' gestation) and late pregnancy (around 28 weeks' gestation), and postdelivery (6 months after supplement discontinuation). We derived standard deviation scores (SDS) to characterize longitudinal changes among participants in the control group and measured differences between the 2 groups. At recruitment, the proportion of patients with marginal or low plasma status was 29.2% for folate (<13.6 nmol/L), 7.5% and 82.0% for riboflavin (<5 nmol/L and ≤26.5 nmol/L, respectively), 9.1% for vitamin B12 (<221 pmol/L), and 48.7% for vitamin D (<50 nmol/L); these proportions were balanced between the groups. Over 90% of all participants had low or marginal status for one or more of these vitamins at recruitment. Among participants in the control group, plasma concentrations of riboflavin declined through early and late pregnancy, whereas concentrations of 25-hydroxyvitamin D were unchanged in early pregnancy, and concentrations of vitamin B6 and B12 declined throughout pregnancy, becoming >1 SDS lower than baseline by 28 weeks gestation. In the control group, 54.2% of participants developed low late-pregnancy vitamin B6 concentrations (pyridoxal 5-phosphate <20 nmol/L). After 1 month of supplementation, plasma concentrations of supplement components were substantially higher among participants in the intervention group than those in the control group: riboflavin by 0.77 SDS (95% CI 0.68 to 0.87, p < 0.0001), vitamin B6 by 1.07 SDS (0.99 to 1.14, p < 0.0001), vitamin B12 by 0.55 SDS (0.46 to 0.64, p < 0.0001), and vitamin D by 0.51 SDS (0.43 to 0.60, p < 0.0001), with higher levels in the intervention group maintained during pregnancy. Markers of vitamin insufficiency/deficiency were reduced in the intervention group, and the proportion of participants with vitamin D insufficiency (<50 nmol/L) during late pregnancy was lower in the intervention group (35.1% versus 8.5%; p < 0.0001). Plasma vitamin B12 remained higher in the intervention group than in the control group 6 months postdelivery (by 0.30 SDS (0.14, 0.46), p = 0.0003). The main limitation is that generalizability to the global population is limited by the high-resource settings and the lack of African and Amerindian women in particular. CONCLUSIONS: Over 90% of the trial participants had marginal or low concentrations of one or more of folate, riboflavin, vitamin B12, or vitamin D during preconception, and many developed markers of vitamin B6 deficiency in late pregnancy. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of vitamin deficiency and depletion markers before and during pregnancy, with higher maternal plasma vitamin B12 maintained during the recommended lactational period. TRIAL REGISTRATION: ClinicalTrials.gov NCT02509988; U1111-1171-8056.

The effect of a preconception and antenatal nutritional supplement on children's BMI and weight gain over the first 2 years of life: findings from the NiPPeR randomised controlled trial.

BACKGROUND: Nutritional intervention before and throughout pregnancy might promote healthy infant weight gain; however, clinical evidence is scarce. Therefore, we examined whether preconception and antenatal supplementation would affect the body size and growth of children in the first 2 years of life. METHODS: Women were recruited from the community before conception in the UK, Singapore, and New Zealand, and randomly allocated to either the intervention (myo-inositol, probiotics, and additional micronutrients) or control group (standard micronutrient supplement) with stratification by site and ethnicity. Measurements of weight and length were obtained from 576 children at multiple timepoints in the first 2 years of life. Differences in age and sex standardised BMI at age 2 years (WHO standards) and the change in weight from birth were examined. Written informed consent was obtained from the mothers, and ethics approval was granted by local committees. The NiPPeR trial was registered with ClinicalTrials.gov (NCT02509988) on July 16, 2015 (Universal Trial Number U1111-1171-8056). FINDINGS: 1729 women were recruited between Aug 3, 2015, and May 31, 2017. Of the women randomised, 586 had births at 24 weeks or more of gestation between April, 2016, and January, 2019. At age 2 years, adjusting for study site, infant sex, parity, maternal smoking, maternal prepregnancy BMI, and gestational age, fewer children of mothers who received the intervention had a BMI of more than the 95th percentile (22 [9%] of 239 vs 44 [18%] of 245, adjusted risk ratio 0·51, 95% CI 0·31-0·82, p=0·006). Longitudinal data revealed that the children of mothers who received the intervention had a 24% reduced risk of experiencing rapid weight gain of more than 0·67 SD in the first year of life (58 [21·9%] of 265 vs 80 [31·1%] of 257, adjusted risk ratio 0·76, 95% CI 0·58-1·00, p=0·047). Risk was likewise decreased for sustained weight gain of more than 1·34 SD in the first 2 years (19 [7·7%] of 246 vs 43 [17·1%] of 251, adjusted risk ratio 0·55, 95% CI 0·34-0·88, p=0·014). INTERPRETATION: Rapid weight gain in infancy is associated with future adverse metabolic health. The intervention supplement taken before and throughout pregnancy was associated with lower risk of rapid weight gain and high BMI at age 2 years among children. Long-term follow-up is required to assess the longevity of these benefits. FUNDING: National Institute for Health Research; New Zealand Ministry of Business, Innovation and Employment; Société Des Produits Nestlé; UK Medical Research Council; Singapore National Research Foundation; National University of Singapore and the Agency of Science, Technology and Research; and Gravida.

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).

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.

Response to Bannenberg and Rice.

This manuscript is a response to concerns expressed in a letter by industry-based scientists Bannenberg and Rice in response to our recent narrative review. In the review, we largely discussed why supplementation with n-3 PUFA rich oils might have benefits to the body composition and metabolism of the offspring of overweight or obese pregnant women. Bannenberg and Rice raised concerns about a number of points that may be perceived as negative about the quality and functionality of commercial fish oils. We provide a refutation to their comments and a brief review of recent evidence regarding the n-3 PUFA content, and oxidative state of supplements available to consumers. From a clinical research perspective, there remains a need to exercise caution. An oil containing less n-3 PUFAs than expected may be ineffective, and lead to incorrect conclusions that n-3 PUFAs lack efficacy. Oxidized fish oil may be ineffective or even cause unwanted harm. Although we must not overinterpret limited evidence from animal models, we have a responsibility to minimize risk to study participants, especially those most vulnerable, such as pregnant women. Prior to selecting a fish oil to be used in a clinical trial, it is essential to independently verify the n-3 PUFA content of the oil, and that the oil is unoxidized.

Supplementation with milk enriched with complex lipids during pregnancy: A double-blind randomized controlled trial.

BACKGROUND: Gangliosides are a class of sphingolipids that are present in the cell membranes of vertebrates. Gangliosides influence a broad range of cellular processes through effects on signal transduction, being found abundantly in the brain, and having a role in neurodevelopment. OBJECTIVE: We aimed to assess the effects of maternal daily consumption of ganglioside-enriched milk vs non-enriched milk and a non-supplemented group of pregnant women on maternal ganglioside levels and pregnancy outcomes. DESIGN: Double-blind parallel randomized controlled trial. METHODS: 1,500 women aged 20-40 years were recruited in Chongqing (China) between 11 and 14 weeks of a singleton pregnancy, and randomized into three groups: Control-received standard powdered milk formulation (≥4 mg gangliosides/day); Complex milk lipid-enhanced (CML-E) group-same formulation enriched with complex milk lipids (≥8 mg gangliosides/day) from milk fat globule membrane; Reference-received no milk. Serum ganglioside levels were measured in a randomly selected subsample of 250 women per group. RESULTS: CML-E milk was associated with marginally greater total gangliosides levels in maternal serum compared to Control (13.02 vs 12.69 µg/ml; p = 0.034) but not to Reference group. CML-E milk did not affect cord blood ganglioside levels. Among the 1500 women, CML-E milk consumption was associated with a lower rate of gestational diabetes mellitus than control milk [relative risk 0.80 (95% CI 0.64, 0.99)], but which was not different to the Reference group. CML-E milk supplementation had no other effects on maternal or newborn health. CONCLUSIONS: Maternal supplementation with milk fat globule membrane, as a source of gangliosides, was not associated with any adverse health outcomes, and did not increase serum gangliosides compared with the non-supplemented reference group. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR-IOR-16007700). CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-16007700; www.chictr.org.cn/showprojen.aspx?proj=12972.

Omega-3 fats in pregnancy: could a targeted approach lead to better metabolic health for children?

The prevalence of childhood obesity is increasing worldwide, and the children of women who are obese during pregnancy are at greatest risk. This risk may be mediated by exaggeration of the normal insulin resistance of pregnancy. Omega-3 (n-3) fats are insulin sensitizing. Supplementation during pregnancy may reduce metabolic risk and adiposity in the children. Though results from animal studies are encouraging, completed clinical trials have not demonstrated this benefit. However, to our knowledge, previous studies have not targeted women who are overweight or obese while pregnant-the group at greatest risk for insulin resistance and most likely to benefit from n-3. In this narrative review, the importance of performing clinical trials restricted to women who are overweight or obese is discussed, as is the potential importance of n-3 dose, oil source and quality, and the timing of the intervention.

Double-blind RCT of fish oil supplementation in pregnancy and lactation to improve the metabolic health in children of mothers with overweight or obesity during pregnancy: study protocol.

INTRODUCTION: Maternal obesity during pregnancy is associated with adverse changes in body composition and metabolism in the offspring. We hypothesise that supplementation during pregnancy of overweight and obese women may help prevent the development of greater adiposity and metabolic dysfunction in children. Previous clinical trials investigating fish oil supplementation in pregnancy on metabolic outcomes and body composition of the children have not focused on the pregnancies of overweight or obese women. METHODS AND ANALYSIS: A double-blind randomised controlled trial of fish oil (providing 3 g/day of n-3 polyunsaturated fatty acids) versus an equal volume of olive oil (control) taken daily from recruitment until birth, and in breastfeeding mothers, further continued for 3 months post partum. Eligible women will have a singleton pregnancy at 12-20 weeks' gestation and be aged 18-40 years with body mass index ≥25 kg/m2 at baseline. We aim to recruit a minimum of 128 participants to be randomised 1:1. Clinical assessments will be performed at baseline and 30 weeks of pregnancy, including anthropometric measurements, fasting metabolic markers, measures of anxiety, physical activity, quality of life and dietary intake. Subsequent assessments will be performed when the infant is 2 weeks, 3 months and 12 months of age for anthropometry, body composition (dual-energy X-ray absorptiometry (DXA)) and blood sampling. The primary outcome of the study is a between-group difference in infant percentage body fatness, assessed by DXA, at 2 weeks of age. Secondary outcomes will include differences in anthropometric measures at each time point, percentage body fat at 3 and 12 months and homeostatic model assessment of insulin resistance at 3 months. Statistical analysis will be carried out on the principle of intention to treat. ETHICS AND DISSEMINATION: This trial was approved by the Northern A Health and Disabilities Ethics Committee, New Zealand Ministry of Health (17/NTA/154). Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12617001078347p; Pre-results.

Fish oil supplementation to rats fed high-fat diet during pregnancy prevents development of impaired insulin sensitivity in male adult offspring.

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.

Concerns with the Study on Australian and New Zealand Fish Oil Products by Nichols et al. (Nutrients 2016, 8, 703).

n/a.

Oxidized fish oil in rat pregnancy causes high newborn mortality and increases maternal insulin resistance.

Fish oil is commonly taken by pregnant women, and supplements sold at retail are often oxidized. Using a rat model, we aimed to assess the effects of supplementation with oxidized fish oil during pregnancy in mothers and offspring, focusing on newborn viability and maternal insulin sensitivity. Female rats were allocated to a control or high-fat diet and then mated. These rats were subsequently randomized to receive a daily gavage treatment of 1 ml of unoxidized fish oil, a highly oxidized fish oil, or control (water) throughout pregnancy. At birth, the gavage treatment was stopped, but the same maternal diets were fed ad libitum throughout lactation. Supplementation with oxidized fish oil during pregnancy had a marked adverse effect on newborn survival at day 2, leading to much greater odds of mortality than in the control (odds ratio 8.26) and unoxidized fish oil (odds ratio 13.70) groups. In addition, maternal intake of oxidized fish oil during pregnancy led to increased insulin resistance at the time of weaning (3 wks after exposure) compared with control dams (HOMA-IR 2.64 vs. 1.42; P = 0.044). These data show that the consumption of oxidized fish oil is harmful in rat pregnancy, with deleterious effects in both mothers and offspring.

Supplementation with a blend of krill and salmon oil is associated with increased metabolic risk in overweight men.

BACKGROUND: Krill is an increasingly popular source of marine n-3 (ω-3) PUFA that is seen as a premium product. However, to our knowledge, the effect of krill-oil supplementation on insulin sensitivity in humans has not been reported. OBJECTIVE: We assessed whether supplementation with a blend of krill and salmon (KS) oil [which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] affects insulin sensitivity in overweight men. DESIGN: The design was a randomized, double-blind, controlled crossover trial. A total of 47 men with a mean ± SD age of 46.5 ± 5.1 y, who were overweight [body mass index (in kg/m(2)) from 25 to 30] but otherwise healthy, received 5 1-g capsules of KS oil or a control (canola oil) for 8 wk and crossed over to another treatment after an 8-wk washout period. The primary outcome was insulin sensitivity assessed by using the Matsuda method from an oral-glucose-tolerance test. Secondary outcomes included lipid profiles, inflammatory markers, 24-h ambulatory blood pressure, and carotid artery intimamedia thickness. RESULTS: Unexpectedly, insulin sensitivity (per the Matsuda index) was 14% lower with the KS oil than with the control oil (P = 0.049). A mediation analysis showed that, after controlling for the likely positive effects of blood EPA and DHA (i.e., the omega-3 index), the reduction in insulin sensitivity after KS-oil supplementation was more marked [27% lower than with the control oil (P = 0.009)]. CONCLUSIONS: Supplementation with a blend of KS oil is associated with decreased insulin sensitivity. Thus, krill-oil supplementation in overweight adults could exacerbate risk of diabetes and cardiovascular disease. This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000602921.

Fish oil supplements in New Zealand are highly oxidised and do not meet label content of n-3 PUFA.

We evaluated the quality and content of fish oil supplements in New Zealand. All encapsulated fish oil supplements marketed in New Zealand were eligible for inclusion. Fatty acid content was measured by gas chromatography. Peroxide values (PV) and anisidine values (AV) were measured, and total oxidation values (Totox) calculated. Only 3 of 32 fish oil supplements contained quantities of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that were equal or higher than labelled content, with most products tested (69%) containing <67%. The vast majority of supplements exceeded recommended levels of oxidation markers. 83% products exceeded the recommended PV levels, 25% exceeded AV thresholds, and 50% exceeded recommended Totox levels. Only 8% met the international recommendations, not exceeding any of these indices. Almost all fish oil supplements available in the New Zealand market contain concentrations of EPA and DHA considerably lower than claimed by labels. Importantly, the majority of supplements tested exceeded the recommended indices of oxidative markers. Surprisingly, best-before date, cost, country of origin, and exclusivity were all poor markers of supplement quality.

Higher omega-3 index is associated with increased insulin sensitivity and more favourable metabolic profile in middle-aged overweight men.

We assessed whether omega-3 index (red blood cell concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) was associated with insulin sensitivity and other metabolic outcomes in 47 overweight men aged 46.5 ± 5.1 years. Participants were assessed twice, 16 weeks apart. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Linear associations were examined; stratified analyses were carried out with participants separated according to the omega-3 index: lower tertiles (LOI; n = 31) and highest tertile (HOI; n = 16). Increasing omega-3 index was correlated with higher insulin sensitivity (r = 0.23; p = 0.025), higher disposition index (r = 0.20; p = 0.054), and lower CRP concentrations (r = -0.39; p < 0.0001). Insulin sensitivity was 43% higher in HOI than in LOI men (Matsuda index 6.83 vs 4.78; p = 0.009). Similarly, HOI men had disposition index that was 70% higher (p = 0.013) and fasting insulin concentrations 25% lower (p = 0.038). HOI men displayed lower nocturnal systolic blood pressure (-6.0 mmHg; p = 0.025) and greater systolic blood pressure dip (14.7 vs 10.8%; p = 0.039). Men in the HOI group also had lower concentrations of CRP (41% lower; p = 0.033) and free fatty acids (21% lower, p = 0.024). In conclusion, higher omega-3 index is associated with increased insulin sensitivity and a more favourable metabolic profile in middle-aged overweight men.

Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring.

BACKGROUND: Despite newborn screening and early levothyroxine replacement, there are continued reports of mild neurocognitive impairment in children with congenital hypothyroidism (CHT). In Auckland, New Zealand, cases are identified by a neonatal screening program with rapid institution of high-dose levothyroxine replacement (10-15 µg/kg·d), producing prompt normalization of thyroid function. Subsequently, frequent monitoring and dose alterations are performed for 2 years. We aimed to assess whether the Auckland treatment strategy prevents impairment of intellectual and motor development. METHODS: This study encompassed all children with CHT born in 1993-2006 in Auckland and their siblings. Neurocognitive assessments included the following: 1) intelligence quotient via Weschler Preschool and Primary Scale of Intelligence III or Weschler Intelligence Scale for Children IV; 2) Movement Assessment Battery for Children; and 3) Beery Developmental Test of Visual-Motor Integration. Body composition was assessed by dual-energy x-ray absorptiometry. RESULTS: Forty-four CHT cases and 53 sibling controls aged 9.6 ± 3.9 years were studied. Overall intelligence quotient was similar among CHT cases and controls (95.2 vs 98.6; P = .20), and there were also no differences in motor function. Severity of CHT did not influence outcome, but greater time to normalize free T4 was associated with worse motor balance. There were no differences in anthropometry or body composition between groups. CONCLUSIONS: These findings suggest that a strategy of rapidly identifying and treating infants with CHT using high-dose levothyroxine replacement is associated with normal intellectual and motor development. The subtle negative impact on motor function associated with time to normalize free T4 levels is consistent with benefit from rapid initial correction.

Oxidation of marine omega-3 supplements and human health.

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.