Objectives: We conducted a secondary analysis of a randomized controlled trial where 250 infants were randomly assigned to receive either a protein-

Overview

This source page is a mechanical bulk-ingest record for a PDF in the methylmercury infant-formula research pull. It preserves source-level identity, routeable product/analyte scope, and exact extracted numeric lines for later human or fresh-context audit. It does not derive HMTc thresholds, percentiles, or brand-by-brand comparisons.

Key numbers

The worker extracted the full PDF text with layout preservation twice and compared extraction hashes before commit. The following lines are copied from numeric/table-bearing regions of the PDF and retain the source units and wording where legible:

• The American Journal of Clinical Nutrition 123 (2026) 101238
• Xuan He 1, 2, Zhichao Zhang 1, Ulrica Johansson 3, Daniel J Tancredi 4, Olle Hernell 3, Bo L€onnerdal 1,
• Department of Nutrition, University of California-Davis, Davis, CA, United States; 2 Department of Food Science and Technology, University of
• California-Davis, Davis, CA, United States; 3 Department of Clinical Sciences, Pediatrics, Umeå University, Sweden; 4 Department of Pediatrics,
• Objectives: We conducted a secondary analysis of a randomized controlled trial where 250 infants were randomly assigned to receive either a protein-
• amino acids (BCAAs), insulin-like growth factor-1 (IGF-1), and growth outcomes using structural equation modeling (SEM).
• Methods: Targeted proton nuclear magnetic resonance (1H-NMR) metabolomics was performed on plasma samples collected at 12 and 18 mo. Two
• SEM models were constructed: one modeled body weight and the other modeled BMI as growth outcomes using data collected up to age 18 mo. Model
• IGF-1 concentrations {weight-based SEM: β = 0.40 (95% confidence interval (CI): 0.03, 0.48); BMI-based SEM: β = 0.43 (95% CI: 0.05, 0.50)}.
• Plasma total BCAAs were positively associated with plasma IGF-1 levels (weight-based SEM: β = 0.16 (95% CI: 0.00, 0.76); BMI-based SEM: β =
• 0.17 (95% CI: 0.02, 0.78)). After accounting for metabolite-mediated effects on IGF-1 and insulin, cumulative protein intake remained significantly
• associated with infant body weight (β=0.36 (95% CI: 0.02, 0.99)), but not BMI.
• Early-life nutrition is crucial for supporting optimal growth and the age of 4 to 6 mo and continues until 2 y (3). Exactly which foods
• development and establishing a foundation for long-term health (1,2). are best for optimal growth and development during this period is not
• covariance-based structural equation modeling; CFI, comparative fit index; D2O, deuterium oxide; DOHaD, developmental origins of health and disease; DONALD, Dortmund
• nutritional and longitudinally designed; DSS-d6, 3-(trimethylsilyl)-1-propanesulfonic acid-d6; EDTA, ethylenediaminetetraacetic acid; EU CHOP, European childhood obesity
• project; FDR, false discovery rate; FMI, fat mass index; GFI, goodness-of-fit index; HAZ, height-for-age z-score; IFI, incremental fit index; IGF-1, insulin-like growth factor 1;
• MCD, milk cereal drink; MLR, maximum likelihood estimation; mTORC1, mechanistic target of rapamycin complex 1; NFI, normed fit index; NF-κB, nuclear factor-κB; NMR,
• This study was registered at clinicaltrials.gov as NCT02634749.
• 0002-9165/© 2026 The Authors. Published by Elsevier Inc. on behalf of American Society for Nutrition. This is an open access article under the CC BY license (http://
• creativecommons.org/licenses/by/4.0/).
• X. He et al. The American Journal of Clinical Nutrition 123 (2026) 101238
• (4–6). For example, in the Nordic and Baltic countries, the Nordic design, conducted in Umeå, Sweden, from April 2015 to January 2018.
• Nutrition Recommendations (NNR) (7) emphasize higher intakes of A total of 250 healthy Swedish infants were recruited and randomly
• regionally produced and seasonal foods that are low in saturated fats as assigned to 1 of 2 groups: the Nordic diet group (intervention, n =
• well as added sugar and salt and include fruits, vegetables, legumes, 125) or the conventional diet group (control, n = 125). At the time of
• processed meats, sweetened beverages and sweets (8,9). Although this These infants were then introduced to different complementary
• dietary pattern has been linked to reduced risk of noncommunicable feeding regimens from baseline (4 to 6 mo), and these diets were
• diseases (10,11), the integration of the Nordic diet into complementary continued until age 18 mo. Participating families were contacted
• risk of obesity later in life (12,13). Specifically, high protein infant Research Unit at the Department of Clinical Sciences, Pediatrics,
• formula given before age 6 mo and high animal and dairy protein Umeå University Hospital, scheduled at enrollment, 9, 12, and 18 mo
• intake at 12 mo have been associated with elevated circulating of age. All participating families, regardless of group assignment,
• insulin-like growth factor-1 (IGF-1) and higher body weight during received comprehensive services from the local community child
• infancy, and higher BMI in later childhood. (14–17). This proposed health care centers, which included vaccination, growth monitoring, as
• growing recognition of the importance of protein quality (18). In ondary outcomes have also been published (22–24). The present
• developed countries, protein intake among children and adolescents analysis focused on plasma metabolomics outcomes at 12 and 18 mo
• has been reported to be 2 to 3 times higher than currently recom- of age, which were not reported earlier.
• (19,20). A recent survey in Sweden revealed that >80% of infants at estimation of sample size, randomization, and blinding techniques,
• mended (21). and randomly assigned to one of the complementary feeding regimens
• To understand the impact of complementary feeding on infant using a computerized tool in blocks of 10. Blinding in the study was
• randomized controlled trial where 250 infants were assigned to either aware of the group allocations because food items and the menu were
• practices (conventional diet) group from baseline (4 to 6 mo) to age Eligible participants were healthy, singleton infants aged 4 to 6 mo

Methods (brief)

• amino acids (BCAAs), insulin-like growth factor-1 (IGF-1), and growth outcomes using structural equation modeling (SEM).
• Methods: Targeted proton nuclear magnetic resonance (1H-NMR) metabolomics was performed on plasma samples collected at 12 and 18 mo. Two
• SEM models were constructed: one modeled body weight and the other modeled BMI as growth outcomes using data collected up to age 18 mo. Model
• Results: The Nordic diet led to reduced-protein intake and a distinct infant plasma metabolomic profile. Circulating BCAAs and their catabolites were
• Plasma total BCAAs were positively associated with plasma IGF-1 levels (weight-based SEM: β = 0.16 (95% CI: 0.00, 0.76); BMI-based SEM: β =
• (19,20). A recent survey in Sweden revealed that >80% of infants at estimation of sample size, randomization, and blinding techniques,
• relationship between protein intake and circulating BCAAs, IGF-1, group. With a 20% dropout rate, 125 infants per group were needed to
• NCT02634749. Written informed consent was obtained from both collected within 2 wk of the 6, 9, 12, and 18 mo study visits. Parents
• and progressing through green pea, raspberry, cauliflower, lingonber- Blood sample collection for metabolomics analysis
• ry/buckthorn, turnip, cranberry, and finally white radish. All ingredients, EDTA plasma samples were collected by experienced pediatric
• except for buckthorn berry, are available year-round. When buckthorn research nurses via venipuncture blood samples at age 12 and 18 mo
• were advised to offer 3 daily exposures (5–15 mL per exposure) for 3 cream was applied prior to blood collection. Once collected, EDTA
• vegetable puree was introduced until all 9 had been sampled, allowing for 10 min at room temperature. The plasma layer was carefully
• ingredients. Protein-reduced, Nordic ingredient-based baby food Each EDTA plasma sample was prepared for NMR analysis by
• specially formulated, protein-reduced Milk Cereal Drinks (MCDs), (Amicon Ultra-0.5 mL, Millipore). Prior to sample filtration, filters were
• vegetable puree recipes were provided beyond the 8 initial taste- and NaOH. Finally, 180 μL of each sample was transferred to 3 mm
• plasma total BCAAs were natural-log-transformed, and cumulative
• intake over time), plasma total BCAAs, plasma IGF-1, plasma insulin- nificant differences in infant enrollment age or anthropometric mea-

Implications

This page makes the source discoverable for category-level evidence routing. Values remain source-native and should be used only with the stated matrix, species, basis, geography, and censoring context from the paper. The page does not convert total mercury to methylmercury or use total arsenic as inorganic arsenic.

Wiki pages this source may touch

• Infant Formula Powder
• Fish — marine, non-predatory (sardines, anchovies, salmon, cod)
• Shellfish (shrimp, crab, lobster, clams, oysters, mussels)
• Seaweed/kelp foods (nori, wakame, kombu, dulse — as food products)
• Aluminum

Verification notes

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Update history

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