The Effect of an Infant Formula Supplemented with AA and DHA on Fatty Acid Levels of Infants with Different FADS Genotypes: The COGNIS Study

Polymorphisms in the fatty acid desaturase (FADS) genes influence the arachidonic (AA) and docosahexaenoic (DHA) acid concentrations (crucial in early life). Infants with specific genotypes may require different amounts of these fatty acids (FAs) to maintain an adequate status. The aim of this study was to determine the effect of an infant formula supplemented with AA and DHA on FAs of infants with different FADS genotypes. In total, 176 infants from the COGNIS study were randomly allocated to the Standard Formula (SF; n = 61) or the Experimental Formula (EF; n = 70) group, the latter supplemented with AA and DHA. Breastfed infants were added as a reference group (BF; n = 45). FAs and FADS polymorphisms were analyzed from cheek cells collected at 3 months of age. FADS minor allele carriership in formula fed infants, especially those supplemented, was associated with a declined desaturase activity and lower AA and DHA levels. Breastfed infants were not affected, possibly to the high content of AA and DHA in breast milk. The supplementation increased AA and DHA levels, but mostly in major allele carriers. In conclusion, infant FADS genotype could contribute to narrow the gap of AA and DHA concentrations between breastfed and formula fed infants.This research was funded by ORDESA Laboratories, S.L., Spanish Ministry of Economy, Industry and Competitiveness, NEOBEFOOD Project (2010–2013) and SMARTFOODS Project (2014–2018)—CIEN Strategy (Ministry of Innovation and Science-CDTI) through 2 different contracts established between Ordesa Laboratories and the University of Granada General Foundation (ref. nº3349 and nº4003, respectively) and between Ordesa Laboratories and the Bosch Gimpera Foundation/University of Barcelona (ref. n 306811 and 308516). The project was partially funded by EU Project DynaHEALTH (HORIZON 2020-GA No.633595)

The Effect of Maternal Obesity on Breast Milk Fatty Acids and Its Association with Infant Growth and Cognition—The PREOBE Follow-Up

This study analyzed how maternal obesity affected fatty acids (FAs) in breast milk and their association with infant growth and cognition to raise awareness about the programming effect of maternal health and to promote a healthy prenatal weight. Mother–child pairs (n = 78) were grouped per maternal pre-pregnancy body mass index (BMI): normal-weight (BMI = 18.5–24.99), overweight (BMI = 25–29.99) and obese (BMI > 30). Colostrum and mature milk FAs were determined. Infant anthropometry at 6, 18 and 36 months of age and cognition at 18 were analyzed. Mature milk exhibited lower arachidonic acid (AA) and docosahexaenoic acid (DHA), among others, than colostrum. Breast milk of non-normal weight mothers presented increased saturated FAs and n6:n3 ratio and decreased a-linolenic acid (ALA), DHA and monounsaturated FAs. Infant BMI-for-age at 6 months of age was inversely associated with colostrum n6 (e.g., AA) and n3 (e.g., DHA) FAs and positively associated with n6:n3 ratio. Depending on the maternal weight, infant cognition was positively influenced by breast milk linoleic acid, n6 PUFAs, ALA, DHA and n3 LC-PUFAs, and negatively a ected by n6:n3 ratio. In conclusion, this study shows that maternal pre-pregnancy BMI can influence breast milk FAs and infant growth and cognition, endorsing the importance of a healthy weight in future generations.This research was funded by the European Commission (DynaHEALTH-HORIZON 2020GANo: 633595) and the Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-02). Further support was obtained from, Spanish Ministry of Innovation and Science (Junta de Andalucía), Excellence Projects (P06-CTS-02341). ADLGP thanks the Mexican government and the National Council on Science and Technology (CONACYT) for her PhD grant. The funders had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript

Association of maternal weight with FADS and ELOVL genetic variants and fatty acid levels- The PREOBE follow-up.

Single nucleotide polymorphisms (SNPs) in the genes encoding the fatty acid desaturase (FADS) and elongase (ELOVL) enzymes affect long-chain polyunsaturated fatty acid (LC-PUFA) production. We aimed to determine if these SNPs are associated with body mass index (BMI) or affect fatty acids (FAs) in pregnant women. Participants (n = 180) from the PREOBE cohort were grouped according to pre-pregnancy BMI: normal-weight (BMI = 18.5-24.9, n = 88) and overweight/obese (BMI≥25, n = 92). Plasma samples were analyzed at 24 weeks of gestation to measure FA levels in the phospholipid fraction. Selected SNPs were genotyped (7 in FADS1, 5 in FADS2, 3 in ELOVL2 and 2 in ELOVL5). Minor allele carriers of rs174545, rs174546, rs174548 and rs174553 (FADS1), and rs1535 and rs174583 (FADS2) were nominally associated with an increased risk of having a BMI≥25. Only for the normal-weight group, minor allele carriers of rs174537, rs174545, rs174546, and rs174553 (FADS1) were negatively associated with AA:DGLA index. Normal-weight women who were minor allele carriers of FADS SNPs had lower levels of AA, AA:DGLA and AA:LA indexes, and higher levels of DGLA, compared to major homozygotes. Among minor allele carriers of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher DHA:EPA index than the normal-weight group; however, they did not present higher DHA concentrations than the normal-weight women. In conclusion, minor allele carriers of FADS SNPs have an increased risk of obesity. Maternal weight changes the effect of genotype on FA levels. Only in the normal-weight group, minor allele carriers of FADS SNPs displayed reduced enzymatic activity and FA levels. This suggests that women with a BMI≥25 are less affected by FADS genetic variants in this regard. In the presence of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher n-3 LC-PUFA production indexes than women with normal weight, but this was not enough to obtain a higher n-3 LC-PUFA concentration

Association of maternal weight with <i>FADS</i> and <i>ELOVL</i> genetic variants and fatty acid levels- The PREOBE follow-up

<div><p>Single nucleotide polymorphisms (SNPs) in the genes encoding the fatty acid desaturase (<i>FADS</i>) and elongase (<i>ELOVL</i>) enzymes affect long-chain polyunsaturated fatty acid (LC-PUFA) production. We aimed to determine if these SNPs are associated with body mass index (BMI) or affect fatty acids (FAs) in pregnant women. Participants (n = 180) from the PREOBE cohort were grouped according to pre-pregnancy BMI: normal-weight (BMI = 18.5–24.9, n = 88) and overweight/obese (BMI≥25, n = 92). Plasma samples were analyzed at 24 weeks of gestation to measure FA levels in the phospholipid fraction. Selected SNPs were genotyped (7 in <i>FADS1</i>, 5 in <i>FADS2</i>, 3 in <i>ELOVL2</i> and 2 in <i>ELOVL5</i>). Minor allele carriers of rs174545, rs174546, rs174548 and rs174553 (<i>FADS1</i>), and rs1535 and rs174583 (<i>FADS2</i>) were nominally associated with an increased risk of having a BMI≥25. Only for the normal-weight group, minor allele carriers of rs174537, rs174545, rs174546, and rs174553 (<i>FADS1</i>) were negatively associated with AA:DGLA index. Normal-weight women who were minor allele carriers of <i>FADS</i> SNPs had lower levels of AA, AA:DGLA and AA:LA indexes, and higher levels of DGLA, compared to major homozygotes. Among minor allele carriers of <i>FADS2</i> and <i>ELOVL2</i> SNPs, overweight/obese women showed higher DHA:EPA index than the normal-weight group; however, they did not present higher DHA concentrations than the normal-weight women. In conclusion, minor allele carriers of <i>FADS</i> SNPs have an increased risk of obesity. Maternal weight changes the effect of genotype on FA levels. Only in the normal-weight group, minor allele carriers of <i>FADS</i> SNPs displayed reduced enzymatic activity and FA levels. This suggests that women with a BMI≥25 are less affected by <i>FADS</i> genetic variants in this regard. In the presence of <i>FADS2</i> and <i>ELOVL2</i> SNPs, overweight/obese women showed higher n-3 LC-PUFA production indexes than women with normal weight, but this was not enough to obtain a higher n-3 LC-PUFA concentration.</p></div

Associations between plasma proportions of PUFAs and <i>FADS</i> and <i>ELOVL</i> polymorphisms.

<p>Associations between plasma proportions of PUFAs and <i>FADS</i> and <i>ELOVL</i> polymorphisms.</p

Characteristics of the population.

<p>Characteristics of the population.</p

Substrates and products of enzymatic indexes according to maternal SNPs and LC-PUFA levels in plasma.

<p>Substrates and products of enzymatic indexes according to maternal SNPs and LC-PUFA levels in plasma.</p

<i>FADS1</i>, <i>FADS2 and ELOVL2</i> enzymatic indexes according to maternal SNPs and LC-PUFA levels in plasma.

<p><i>FADS1</i>, <i>FADS2 and ELOVL2</i> enzymatic indexes according to maternal SNPs and LC-PUFA levels in plasma.</p