Benjamin B. Albert

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.

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.

Etiology of Increasing Incidence of Congenital Hypothyroidism in New Zealand from 1993–2010

BACKGROUND Recent reports suggest that the incidence of congenital hypothyroidism (CHT) is increasing in some countries. The etiology of this change is unclear, and it may relate to changes in screening thresholds. We aimed to determine whether the incidence of CHT in New Zealand has changed and whether ethnic-specific rates and the rates of CHT subtypes have also changed. METHODS The New Zealand neonatal TSH-based screening program has prospectively identified cases of CHT using the same assay and screening thresholds since 1993. Thyroid scintiscans are routinely recommended. We retrospectively identified all cases of CHT requiring levothyroxine treatment from 1993-2010 recorded by the national newborn screening program (>99.5% coverage). Among other parameters, ethnic and CHT subtype-specific incidence rates were calculated. RESULTS There were 330 new cases of CHT and 1,053,457 live births registered in New Zealand in the 18-yr period, and 86% of cases had a scintiscan, 67% of which had thyroid dysgenesis (female to male ratio 5.0:1.0) and 33% dyshormonogenesis (0.9:1.0). The overall incidence of CHT rose from 2.6 to 3.6 per 10,000 live births (P < 0.01). The incidence of dyshormonogenesis (P = 0.01) increased but not of dysgenesis (P = 0.13). This was mediated by a 2-fold increase in Asian births and 40% increase in Pacific Island births. Both ethnic groups displayed higher rates of dyshormonogenesis compared with New Zealand Europeans (odds ratio 3.3 and 2.6, respectively). There was no change in the ethnic-specific incidences of CHT. CONCLUSION Although the incidence of congenital hypothyroidism in New Zealand has increased, this is due to changes in the countrys ethnic composition.

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.

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.

15-year incidence of diabetic ketoacidosis at onset of type 1 diabetes in children from a regional setting (Auckland, New Zealand)

We assessed the incidence of diabetic ketoacidosis (DKA) in children aged <15 years with newly diagnosed type 1 diabetes mellitus (T1DM) in the Auckland Region (New Zealand) in 1999–2013, in a retrospective review of a complete regional cohort. DKA and its severity were classified according to ISPAD 2014 guidelines. Of 730 children presenting with new-onset T1DM over the 15-year time period, 195 cases had DKA of any severity (27%). There was no change in the incidence of DKA or the proportion of children with severe DKA at presentation. The incidence of DKA among children aged <2.0 years (n = 40) was 53% compared to 25% for those aged 2–14 years (n = 690; p = 0.005). In children aged 2–14 years, increasing age at diagnosis was associated with greater likelihood of DKA at presentation (p = 0.025), with the odds of DKA increasing 1.06 times with each year increase in age. Non-Europeans were more likely to present in DKA than New Zealand Europeans (OR 1.52; p = 0.048). Despite a consistent secular trend of increasing incidence of T1DM, there was no reduction in the incidence of DKA in new-onset T1DM in the Auckland Region over time. Thus, it is important to explore ways to reduce DKA risk.

Among overweight middle-aged men, first-borns have lower insulin sensitivity than second-borns

We aimed to assess whether birth order affects metabolism and body composition in overweight middle-aged men. We studied 50 men aged 45.6 ± 5.5 years, who were overweight (BMI 27.5 ± 1.7 kg/m2) but otherwise healthy in Auckland, New Zealand. These included 26 first-borns and 24 second-borns. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Other assessments included DXA-derived body composition, lipid profiles, 24-hour ambulatory blood pressure, and carotid intima-media thickness. First-born men were 6.9 kg heavier (p = 0.013) and had greater BMI (29.1 vs 27.5 kg/m2; p = 0.004) than second-borns. Insulin sensitivity in first-born men was 33% lower than in second-borns (4.38 vs 6.51; p = 0.014), despite adjustment for fat mass. There were no significant differences in ambulatory blood pressure, lipid profile or carotid intima-media thickness between first- and second-borns. Thus, first-born adults may be at a greater risk of metabolic and cardiovascular diseases.

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.

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.