Tags

Type your tag names separated by a space and hit enter

Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils.
Am J Clin Nutr. 2020 05 01; 111(5):1068-1078.AJ

Abstract

BACKGROUND

Unexplained heterogeneity in clinical trials has resulted in questions regarding the effectiveness of ɣ-linolenic acid (GLA)-containing botanical oil supplements. This heterogeneity may be explained by genetic variation within the fatty acid desaturase (FADS) gene cluster that is associated with circulating and tissue concentrations of arachidonic acid (ARA) and dihomo-ɣ-linolenic acid (DGLA), both of which may be synthesized from GLA and result in proinflammatory and anti-inflammatory metabolites, respectively.

OBJECTIVES

The objective of this study was to prospectively compare the capacity of a non-Hispanic white cohort, stratified by FADS genotype at the key single-nucleotide polymorphism (SNP) rs174537, to metabolize 18-carbon omega-6 (n-6) PUFAs in borage oil (BO) and soybean oil (SO) to GLA, DGLA, and ARA.

METHODS

Healthy adults (n = 64) participated in a randomized, double-blind, crossover intervention. Individuals received encapsulated BO (Borago officinalis L.; 37% LA and 23% GLA) or SO [Glycine max (L.) Merr.; 50% LA and 0% GLA] for 4 wk, followed by an 8-wk washout period, before consuming the opposite oil for 4 wk. Serum lipids and markers of inflammation (C-reactive protein) were assessed for both oil types at baseline and during weeks 2 and 4 of the intervention.

RESULTS

SO supplementation failed to alter circulating concentrations of any n-6 long-chain PUFAs. In contrast, a modest daily dose of BO elevated serum concentrations of GLA and DGLA in an rs174537 genotype-dependent manner. In particular, DGLA increased by 57% (95% CI: 0.38, 0.79) in GG genotype individuals, but by 141% (95% CI: 1.03, 2.85) in TT individuals. For ARA, baseline concentrations varied substantially by genotype and increased modestly with BO supplementation, suggesting a key role for FADS variation in the balance of DGLA and ARA.

CONCLUSIONS

The results of this study clearly suggest that personalized and population-based approaches considering FADS genetic variation may be necessary to optimize the design of future clinical studies with GLA-containing oils. This trial was registered at clinicaltrials.gov as NCT02337231.

Authors+Show Affiliations

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA. Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA.BIO5 Institute, University of Arizona, Tucson, AZ, USA.Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA. Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA. Department of Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA. Department of Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA. Department of Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA. Johns Hopkins Bloomberg School of Public Health, Department of Biostatistics, Baltimore, MD, USA.BIO5 Institute, University of Arizona, Tucson, AZ, USA.Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA. Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine,Winston-Salem, NC, USA. BIO5 Institute, University of Arizona, Tucson, AZ, USA.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32167131

Citation

Sergeant, Susan, et al. "Prospective Clinical Trial Examining the Impact of Genetic Variation in FADS1 On the Metabolism of Linoleic Acid- and Ɣ-linolenic Acid-containing Botanical Oils." The American Journal of Clinical Nutrition, vol. 111, no. 5, 2020, pp. 1068-1078.
Sergeant S, Hallmark B, Mathias RA, et al. Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils. Am J Clin Nutr. 2020;111(5):1068-1078.
Sergeant, S., Hallmark, B., Mathias, R. A., Mustin, T. L., Ivester, P., Bohannon, M. L., Ruczinski, I., Johnstone, L., Seeds, M. C., & Chilton, F. H. (2020). Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils. The American Journal of Clinical Nutrition, 111(5), 1068-1078. https://doi.org/10.1093/ajcn/nqaa023
Sergeant S, et al. Prospective Clinical Trial Examining the Impact of Genetic Variation in FADS1 On the Metabolism of Linoleic Acid- and Ɣ-linolenic Acid-containing Botanical Oils. Am J Clin Nutr. 2020 05 1;111(5):1068-1078. PubMed PMID: 32167131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils. AU - Sergeant,Susan, AU - Hallmark,Brian, AU - Mathias,Rasika A, AU - Mustin,Tammy L, AU - Ivester,Priscilla, AU - Bohannon,Maggie L, AU - Ruczinski,Ingo, AU - Johnstone,Laurel, AU - Seeds,Michael C, AU - Chilton,Floyd H, PY - 2019/08/08/received PY - 2020/01/30/accepted PY - 2020/3/14/pubmed PY - 2020/7/1/medline PY - 2020/3/14/entrez KW - PUFAs KW - arachidonic acid KW - borage oil KW - gamma-linolenic acid KW - gene–diet interaction KW - n-3 fatty acids KW - n-6 fatty acids KW - precision nutrition KW - randomized cross-over design KW - soybean oil SP - 1068 EP - 1078 JF - The American journal of clinical nutrition JO - Am J Clin Nutr VL - 111 IS - 5 N2 - BACKGROUND: Unexplained heterogeneity in clinical trials has resulted in questions regarding the effectiveness of ɣ-linolenic acid (GLA)-containing botanical oil supplements. This heterogeneity may be explained by genetic variation within the fatty acid desaturase (FADS) gene cluster that is associated with circulating and tissue concentrations of arachidonic acid (ARA) and dihomo-ɣ-linolenic acid (DGLA), both of which may be synthesized from GLA and result in proinflammatory and anti-inflammatory metabolites, respectively. OBJECTIVES: The objective of this study was to prospectively compare the capacity of a non-Hispanic white cohort, stratified by FADS genotype at the key single-nucleotide polymorphism (SNP) rs174537, to metabolize 18-carbon omega-6 (n-6) PUFAs in borage oil (BO) and soybean oil (SO) to GLA, DGLA, and ARA. METHODS: Healthy adults (n = 64) participated in a randomized, double-blind, crossover intervention. Individuals received encapsulated BO (Borago officinalis L.; 37% LA and 23% GLA) or SO [Glycine max (L.) Merr.; 50% LA and 0% GLA] for 4 wk, followed by an 8-wk washout period, before consuming the opposite oil for 4 wk. Serum lipids and markers of inflammation (C-reactive protein) were assessed for both oil types at baseline and during weeks 2 and 4 of the intervention. RESULTS: SO supplementation failed to alter circulating concentrations of any n-6 long-chain PUFAs. In contrast, a modest daily dose of BO elevated serum concentrations of GLA and DGLA in an rs174537 genotype-dependent manner. In particular, DGLA increased by 57% (95% CI: 0.38, 0.79) in GG genotype individuals, but by 141% (95% CI: 1.03, 2.85) in TT individuals. For ARA, baseline concentrations varied substantially by genotype and increased modestly with BO supplementation, suggesting a key role for FADS variation in the balance of DGLA and ARA. CONCLUSIONS: The results of this study clearly suggest that personalized and population-based approaches considering FADS genetic variation may be necessary to optimize the design of future clinical studies with GLA-containing oils. This trial was registered at clinicaltrials.gov as NCT02337231. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/32167131/Prospective_clinical_trial_examining_the_impact_of_genetic_variation_in_FADS1_on_the_metabolism_of_linoleic_acid__and_ɣ_linolenic_acid_containing_botanical_oils_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.1093/ajcn/nqaa023 DB - PRIME DP - Unbound Medicine ER -