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.

A nutritional supplement taken during preconception and pregnancy influences human milk macronutrients in women with overweight/obesity and gestational diabetes mellitus.

Rational: Maternal overweight/obesity and gestational diabetes mellitus (GDM) are associated with an increased risk of their offspring developing overweight/obesity or type 2 diabetes later in life. However, the impacts of maternal overweight/obesity and dysglycemia on human milk (HM) macronutrient composition are not well understood. Objective: Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on HM macronutrient concentrations, in association with maternal and infant factors including maternal pre-pregnancy body mass index (BMI) and GDM status. In addition, we aimed to characterise longitudinal changes in HM macronutrients. Methods: The control supplement contained calcium, iodine, iron, ß-carotene, and folic acid. The intervention supplement additionally contained zinc, vitamins B2, B6, B12, and D3, probiotics, and myo-inositol. HM samples were collected across seven time points from 1 week to 12 months from Singapore and/or New Zealand. HM macronutrient concentrations were measured using a MIRIS Human Milk Analyser. Potential differences in HM macronutrient concentrations were assessed using linear mixed models with a repeated measures design. Results: Overall, HM macronutrient concentrations were similar between control and intervention groups. Among the control group, overweight/obesity and GDM were associated with higher HM fat and energy concentrations over the first 3 months. Such associations were not observed among the intervention group. Of note, mothers with GDM in the intervention group had lower HM fat by 10% (p = 0.049) and energy by 6% (p = 0.029) than mothers with GDM in the control group. Longitudinal changes in HM macronutrient concentrations over 12 months of lactation in New Zealand showed that HM fat and energy decreased in the first 6 months then increased until 12 months. HM lactose gradually decreased from 1 week to 12 months while crude protein decreased from 1 week to 6 months then remained relatively constant until 12 months of lactation. Conclusion: Maternal overweight/obesity or GDM were associated with increased HM fat and energy levels. We speculate the intervention taken during preconception and pregnancy altered the impact of maternal BMI or GDM status on HM macronutrient composition. Further studies are required to identify the mechanisms underlying altered HM macronutrient concentration in the intervention group and to determine any long-term effects on offspring health. Clinical trial registration: ClinicalTrials.gov, NCT02509988, Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

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).

A nutritional supplement during preconception and pregnancy increases human milk vitamin D but not B-vitamin concentrations.

BACKGROUND & AIMS: Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D3 is involved in infant bone development, and B-vitamins are involved in various metabolic processes, including energy production. Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on human milk (HM) concentrations of vitamin D3 and B-vitamins. In addition, we aimed to characterise longitudinal changes in milk concentrations of these vitamins. METHODS: Both control and intervention supplements contained calcium, iodine, iron, ß-carotene, and folic acid, while the intervention also contained zinc, vitamins B2, B6, B12, and D3, probiotics, and myo-inositol. HM samples were collected across 4 time points from 1 week to 3 months post-delivery from 158 mothers in Singapore, and 7 time points from 1 week to 12 months from 180 mothers in New Zealand. HM vitamin D was quantified using supercritical fluid chromatography and B-vitamins with mass spectrometry. Potential intervention effects on HM vitamins D3, B2, B6, and B9, as well as other B-vitamin (B1 and B3) concentrations were assessed using linear mixed models with a repeated measures design. RESULTS: Over the first 3 months of lactation, HM 25-hydroxyvitamin D3 concentrations were 20% (95% CI 8%, 33%, P = 0.001) higher in the intervention group, with more marked effects in New Zealand. There were no observed intervention effects on HM concentrations of vitamins B1, B2, B3, B6, and B9. In New Zealand mothers, longitudinally, vitamin D3 concentrations gradually increased from early lactation up to 12 months, while vitamins B1 and B2 peaked at 6 weeks, B3 at 3 weeks, and B6 and B9 at 3 months. CONCLUSIONS: Maternal supplementation during preconception and pregnancy increased HM vitamin D, but not B-vitamin concentrations in lactation. Further studies are required to examine the discrete benefits of vitamin D supplementation starting preconception vs during pregnancy, and to further characterise the effects of supplementation on later offspring health outcomes. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov on the 16 July 2015 (identifier NCT02509988); Universal Trial Number U1111-1171-8056. This study was academic-led by the EpiGen Global Research Consortium.

A nutritional supplement containing zinc during preconception and pregnancy increases human milk zinc concentrations.

Introduction: During pregnancy and lactation minerals such as zinc are required to support maternal and infant health. Zinc is involved in various cellular processes, with requirements increasing in pregnancy and lactation. In the setting of a randomized trial, we investigated the effects on human milk (HM) zinc concentrations of a micronutrient-containing supplement including zinc in the intervention (but not control) group, started preconception and taken throughout pregnancy until birth. Additionally, we characterized longitudinal changes in HM concentrations of zinc and other minerals (calcium, copper, iodine, iron, magnesium, manganese, phosphorus, potassium, selenium, and sodium). Methods: HM samples were collected across 7 time points from 1 week to 12 months from lactating mothers from Singapore (n = 158) and New Zealand (n = 180). HM minerals were quantified using sector field inductively coupled plasma mass spectrometry. Potential intervention effects on HM mineral concentrations were assessed using linear mixed models with a repeated measures design and time-weighted area-under-the-curve analyses. Results: Over the first 3 months of lactation, HM zinc concentrations were 11% higher in the intervention group compared to the control group (p = 0.021). Higher HM zinc concentrations were most evident at 6 weeks of lactation. The intervention had no effect on HM concentrations of other minerals, which were not differently supplemented to the control and intervention groups. Temporal changes in HM minerals over 12 months of lactation were studied in the New Zealand mothers; HM zinc and copper concentrations progressively decreased throughout 12 months, while iron, potassium, sodium, and phosphorus decreased until 6 months then plateaued. HM calcium and magnesium initially increased in early lactation and iodine remained relatively constant throughout 12 months. HM manganese and selenium fell over the initial months of lactation, with a nadir at 6 months, and increased thereafter. The contrasting patterns of changes in HM mineral concentrations during lactation may reflect different absorption needs and roles at different stages of infancy. Discussion: Overall, this study indicates that HM zinc concentrations are influenced by maternal supplementation during preconception and pregnancy. Further studies are required to understand the associations between HM zinc and other minerals and both short- and long-term offspring outcomes. Trial registration: ClinicalTrials.gov, identifier: NCT02509988, Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

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.

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.

The Complexity of Food Provisioning Decisions by Maori Caregivers to Ensure the Happiness and Health of Their Children.

Obesity in children is a global health concern. In New Zealand, one in three school entrant children are overweight or obese. Maori, the indigenous people, are disproportionately represented among the lowest economic group and have a disproportionately high incidence of obesity. This study explored Maori parents' and caregivers' views of the relative importance of weight to health, and the facilitators and barriers to a healthy weight in children aged 6 months to 5 years. Using a grounded qualitative method, in-depth information was collected in focus groups with mostly urban parents and other caregivers. A general inductive thematic analysis (content driven) was used. Insufficient money was an overriding food provisioning factor, but cost interacted with the lack of time, the number of people to feed, their appetites, and allergies. Other factors included ideologies about healthy food, cultural values relating to food selection, serving, and eating, nutrition literacy, availability of food, cooking skills, and lack of help. Childhood obesity was not a priority concern for participants, though they supported interventions providing education on how to grow vegetables, how to plan and cook cheaper meals. Holistic interventions to reduce the negative effects of the economic and social determinants on child health more broadly were recommended.

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).

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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.

Many women undergoing fertility treatment make poor lifestyle choices that may affect treatment outcome.

STUDY QUESTION: What are the lifestyle choices and dietary aspects of women about to undergo fertility treatment in New Zealand? SUMMARY ANSWER: A considerable proportion of women about to undergo fertility treatment make poor lifestyle choices, including the consumption of alcohol and caffeine. WHAT IS KNOWN ALREADY: Women undergoing fertility treatment are highly motivated to achieve pregnancy, but there are relatively few published data on their lifestyle, lifestyle changes or dietary aspects. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study of 250 women aged 20-43 years, taking place between March 2010 and August 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women about to undergo IVF or ICSI treatment in two large fertility clinics in Auckland and Hamilton, New Zealand. Lifestyle and dietary intake questionnaires were individually administered once to each participant 35 days (SD = 22) prior to fertility treatment initiation. Outcome measures included incidence of smoking, consumption of alcohol and caffeinated beverages, BMI, detailed intake of dietary supplements and fertility treatment success. Consumption of certain nutrient supplements was compared with the general female New Zealand population. MAIN RESULTS AND THE ROLE OF CHANCE: There were high rates of alcohol (50.8%) and caffeine (86.8%) consumption. Most women (82.8%) reported at least one lifestyle change in preparation for fertility treatment, but less than half of women who consumed alcohol regularly reduced their intake and 60% did not change consumption of caffeinated beverages. Similarly, the majority of women did not change their exercise levels (64.4%) or BMI (83.6%) ahead of fertility treatment. Coffee intake appeared unrelated to treatment outcome, but women who consumed caffeinated herbal tea (36.4% of the study population consumed green tea) had lower odds of becoming pregnant (odds ratio, OR 0.52; P = 0.041 versus those not consuming caffeinated herbal tea). Women who abstained from drinking or reduced alcohol intake had twice the odds of becoming pregnant than those who maintained their drinking habits prior to fertility treatment (OR 2.27; P = 0.049). While 93.2% of women took a folic acid supplement, 16.8% had an inadequate intake compared with the current New Zealand prenatal recommendation of 800 mcg/day. Women who held a university degree or higher qualification had twice the odds of becoming pregnant as women with lower levels of education (OR 2.08; P = 0.017), though this finding appeared to be unrelated to lifestyle or dietary habits. LIMITATIONS, REASONS FOR CAUTION: The study involved self-reported behaviours that might have been misrepresented by respondents. In addition, our questionnaires covered the period following the first clinical assessment but ∼5 weeks prior to fertility treatment initiation, so that we cannot ascertain whether dietary intakes and lifestyle choices persisted over the course of treatment itself. WIDER IMPLICATIONS OF THE FINDINGS: Many women about to undergo fertility treatment make poor lifestyle choices that may negatively affect their chances of becoming pregnant. These findings may be more widely applicable to other women attempting to become pregnant. Specific advice for women regarding healthy lifestyle choices while undergoing fertility treatment is warranted. STUDY FUNDING/COMPETING INTERESTS: A.A.G. received financial support from Abbott Nutrition Research & Development Asia-Pacific Center; J.C.P. is a shareholder of Fertility Associates; the other authors have no financial or non-financial conflicts of interest to disclose.

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.

Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract.

Phenolic compounds derived from the olive plant (Olea europaea L.), particularly hydroxytyrosol and oleuropein, have many beneficial effects in vitro. Olive leaves are the richest source of olive phenolic compounds, and olive leaf extract (OLE) is now a popular nutraceutical taken either as liquid or capsules. To quantify the bioavailability and metabolism of oleuropein and hydroxytyrosol when taken as OLE, nine volunteers (five males) aged 42.8 ± 7.4 years were randomized to receive either capsulated or liquid OLE as a single lower (51.1 mg oleuropein, 9.7 mg hydroxytyrosol) or higher (76.6 mg oleuropein, 14.5 mg hydroxytyrosol) dose, and then the opposite strength (but same formulation) a week later. Plasma and urine samples were collected at fixed intervals for 24 h post-ingestion. Phenolic content was analyzed by LC-ESI-MS/MS. Conjugated metabolites of hydroxytyrosol were the primary metabolites recovered in plasma and urine after OLE ingestion. Peak oleuropein concentrations in plasma were greater following ingestion of liquid than capsule preparations (0.47 versus 2.74 ng/mL; p = 0.004), but no such effect was observed for peak concentrations of conjugated (sulfated and glucuronidated) hydroxytyrosol (p = 0.94). However, the latter peak was reached earlier with liquid preparation (93 versus 64 min; p = 0.031). There was a gender effect on the bioavailability of phenolic compounds, with males displaying greater plasma area under the curve for conjugated hydroxytyrosol (11,600 versus 2550 ng/mL; p = 0.048). All conjugated hydroxytyrosol metabolites were recovered in the urine within 8 h. There was wide inter-individual variation. OLE effectively delivers oleuropein and hydroxytrosol metabolites to plasma in humans.

Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial.

BACKGROUND: Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans. OBJECTIVE: To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men. DESIGN: Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4 ± 5.5 years and BMI 28.0 ± 2.0 kg/m(2)) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness. RESULTS: Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic ß-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function. CONCLUSIONS: Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic ß-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome.

Psyllium supplementation in adolescents improves fat distribution & lipid profile: a randomized, participant-blinded, placebo-controlled, crossover trial.

AIMS: We aimed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population. METHODS: This study encompassed a participant-blinded, randomized, placebo-controlled, crossover trial. Subjects were 47 healthy adolescent males aged 15-16 years, recruited from secondary schools in lower socio-economic areas with high rates of obesity. Participants received 6 g/day of psyllium or placebo for 6 weeks, with a two-week washout before crossing over. Fasting lipid profiles, ambulatory blood pressure, auxological data, body composition, activity levels, and three-day food records were collected at baseline and after each 6-week intervention. Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test. RESULTS: 45 subjects completed the study, and compliance was very high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of subjects were overweight or obese. 28% had decreased insulin sensitivity, but none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%) reduction in LDL cholesterol (p = 0.042). No associated adverse events were recorded. CONCLUSIONS: Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile (parameters of the metabolic syndrome) in an at risk population of adolescent males. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000888268.