About

Tom Brenna, Ph.D., is Professor of Pediatrics, of Chemistry, and of Human Nutrition at the Dell Medical School and College of Natural Sciences at the University of Texas at Austin. He is also Professor Emeritus of Human Nutrition, of Food Science, and of Chemistry after 28 years as an active faculty member at Cornell University in Ithaca, NY. His group’s basic research into the chemical, biochemical, metabolic, genetic, and ecological aspects of fatty acids has had a decisive influence on modern knowledge of these key nutrients. His research has transformed our understanding of endogenous synthesis of long chain polyunsaturated fatty acids (LCPUFA) and their role in human evolutionary adaptation, including the discovery of LCPUFA biochemical synthetic pathways. In the 1990s, his studies on omega-3 and omega-6 fatty acids contributed to the US FDA’s approval of DHA and arachidonic acid in US infant formulas. He has contributed to numerous policy efforts, including serving as a member of the US Dietary Guidelines Advisory Committee and the FAO/WHO Expert Panel on Fats and Fatty Acids. Brenna has been honored with the ASN’s Osborne and Mendel Award for outstanding contributions to basic research in nutrition in 2017 and the ASN’s Robert Herman Award for advancement of clinical nutrition in 2013.

Research topics

• Medicine
• Food science
• Internal medicine
• Environmental health
• Chemistry
• Biochemistry

Selected publications

• Dietary nutritional strategies for circadian rhythm regulation: advances, challenges and future directions

  Critical Reviews in Food Science and Nutrition · 2026-04-14

  article

  The escalation of urban light pollution and the trend toward a globalized lifestyle have led to a notable increase in circadian rhythm disruption (CRD), which is emerging as a concealed epidemic in contemporary society. Dietary nutritional strategies (DNS) that optimize meal timing, dietary structure, and nutrient composition show promising potential for regulating CR and improving metabolic health. This review systematically analyzes the characteristics, mechanisms of action, and clinical applicability of current lipid-based nutritional strategies. This review critically assesses the challenges in CR regulation, analyzes characteristics and mechanisms of action, and discusses integrating precision nutrition concepts and emerging technologies to advance DNS for CR regulation and health management in special populations. We propose a four-dimensional classification for DNS: time window-based, energy intake-based, macronutrient-based, and natural bioactive compound-based dietary regulation. Challenges include the absence of standardized assessment frameworks for CRD, the limited predictive value of preclinical models in translating findings to human responses, insufficient development of phenotype-driven precision nutrition protocols, and an incomplete understanding of structure-activity relationships among chrono-nutrition compounds. Integration of multimodal dietary strategies, establishment of CRD-based population stratification systems, and utilization of artificial intelligence to create intelligent monitoring networks are essential steps in advancing adaptive and personalized precision nutrition interventions.

  PublisherDOI

• Oral Deuterated Docosahexaenoic Acid Protects Against Onset and Progression of RPE Degeneration in a Mouse Model of Chronic Oxidative Stress

  Investigative Ophthalmology & Visual Science · 2026-04-14

  articleOpen access

  Purpose: Oxidative stress is associated with many retinal diseases, including age-related macular degeneration (AMD). The purpose of this study is to investigate the efficacy of oral deuterated docosahexaenoic acid (D-DHA), an oxidation-resistant lipid, in a mouse model with features of dry AMD. We also evaluated whether long-term D-DHA dosing affects normal retinal structure or function. Methods: Liver-specific hepcidin (Hepc) and ceruloplasmin/hepcidin (Cp/Hepc) knock-out (KO) mice were fed experimental diet containing 0.25% D-DHA or control containing normal H-DHA during various stages of disease progression. Retinal pigment epithelium (RPE) damage was assessed with in vivo scanning laser ophthalmoscopy (SLO) imaging and histology. For the safety study, wild-type mice were fed the diets beginning in utero or at 3 months of age, continuing for 12 months. These mice were analyzed to assess retinal structure (SLO, optical coherence tomography [OCT], and transmission electron microscopy [TEM]), function (ERG), and gene expression (qPCR). Results: KO mice fed control diet developed expanding autofluorescent patches of hypertrophic RPE cells. This damage was markedly prevented or halted by diet with D-DHA, depending on age at diet onset. Wild-type mice administered diet with D-DHA from age 3 to 15 months had no retinal abnormalities. Mice administered D-DHA beginning in utero had normal retinal development and structure but minor deficits in ERG amplitudes and Rpe65 expression by age 12 months. Conclusions: Oral D-DHA was strongly protective against RPE ferroptosis, with minimal side effects. This study suggests that DHA oxidation is a key mechanism of retinal iron toxicity and supports the potential clinical application of D-DHA for diseases involving retinal oxidative stress.

  PublisherDOI

• Widespread but moderate genetic overlap between circulating polyunsaturated fatty acids and brain disorders

  Journal of Lipid Research · 2025-08-25

  articleOpen access

  Polyunsaturated fatty acids (PUFAs) are indispensable for proper neuronal function. PUFA deficiency and imbalance have been linked to various brain disorders, including major depressive disorder (MDD) and anxiety. However, the effects of PUFAs on brain disorders remain inconclusive, and the extent of their shared genetic determinants is largely unknown. We utilized genome-wide association summary statistics from six phenotypes of circulating PUFAs (N = 114,999) and 20 brain disorders (N = 9,725-762,917). We performed genome-wide analysis for each of the 120 trait pairs. We evaluated the correlation of genetic effects with genetic correlation, estimated the number of shared genetic variants with polygenic overlap, and prioritized potential causal relationships with two-sample Mendelian randomization (MR). We pinpointed specific shared variants with colocalization and statistical fine-mapping. Genetic correlation and polygenic overlap analyses revealed a widespread but moderate shared genetic basis for 77 PUFA-brain disorder trait pairs. MR suggested potential causal relationships for 16 pairs. Colocalization identified 40 shared loci (13 unique) and 22 candidate shared causal variants, including rs1260326 (GCKR), rs174564 (FADS2), and rs4818766 (ADARB1). These genes were mapped to lipid metabolism pathways. Integrating evidence from multiple approaches, we prioritized four PUFA-brain disorder pairs with potential causal links, including PUFA% with MDD, and omega-6% with alcohol consumption. These findings reveal a widespread but moderate shared genetic basis between PUFAs and brain disorders, pinpoint specific shared variants, and provide support for potential effects of PUFAs on certain brain disorders, especially MDD and alcohol consumption. Future studies are needed to elucidate potential causal effects.

  PublisherOA PDFDOI

• Fish consumption advice is depriving children of neurolipids and other nutrients essential to brain and eye development

  NeuroToxicology · 2025-05-20 · 6 citations

  reviewOpen access
  PublisherOA PDFDOI

• The Impact of Fatty Acid Reporting Methods on Associations with Cardiometabolic Biomarkers

  medRxiv · 2025-11-20

  preprint

  Background: Global dietary guidelines for polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and its metabolite arachidonic acid (ARA), remain debated. Almost all research to date has used fatty acid (FA) data expressed as percent of total FA (% total). Objective: The objective of this study was to determine whether expressing fatty acid (FA) data as % of total or as absolute concentrations alters associations with clinical biomarkers. Methods: Serum FA data obtained via electron capture negative-ion mass spectrometry was obtained from NHANES. Each FA was expressed both as % total and absolute concentration (µmol/L). Associations were examined between individual and total FAs and a panel of lipid and non-lipid biomarkers, including total cholesterol, LDL-C, HDL-C, triglycerides, blood pressure, body mass index, waist circumference, glucose, and insulin. Results: Associations between LA and clinical biomarkers including triglycerides, cholesterol, HDL-C, BMI, glucose, and insulin, reversed direction depending on whether LA was expressed as % total or as a concentration. Similar reversals were observed for ARA, DHA, DPA, and stearic acid. Increases in total FA levels were accompanied by decreases in % total of several PUFAs and HUFAs, despite rising absolute concentrations. Total FA was positively associated, often strongly, with nine clinical markers and negatively associated with HDL-C. Conclusions: Expression format significantly impacts observed FA associations. Reliance on % total FA values alone may misrepresent true associations between individual FAs and clinical endpoints, especially when the total fatty acid pool also changes size. To develop effective dietary guidance or clinical recommendations, it is essential to consider the underlying FA biology and total FA pool size when determining whether % total or absolute FA concentrations are more appropriate.

  PublisherDOI

• Leucine as a feed additive enhances the concentration of branched-chain fatty acids in cow's milk

  Journal of Agriculture and Food Research · 2025-03-19 · 1 citations

  articleOpen access

  The feasibility of exogenously adding leucine (Leu) to produce branched-chain fatty acids (BCFA) enriched milk by simulating rumen fermentation in vitro and feeding study in vivo was investigated. Treatments for in vitro fermentation trial were control, 0 mM of Leu (CON1); 1 mM of Leu (LEU1); 2 mM of Leu (LEU2); and 4 mM of Leu (LEU4). For the in vivo feeding study, 20 Holstein dairy cows were allocated to 2 treatments: control, 0 g/cow/d Leu (CON2; n = 10); and 80 g/cow/d Leu supplementation (LEU80; n = 10). The concentration of BCFA including iso -13:0 ( P < 0.01), iso -15:0 ( P < 0.01), anteiso -15:0 ( P < 0.01), iso -16:0 ( P = 0.02) and total BCFA ( P = 0.01) in fermentation liquid increased linearly with increasing Leu inclusion rates. According to 16S rRNA sequencing, the abundances of Firmicutes ( P = 0.04), Clostridia ( P = 0.03) and Saccharofermentans ( P = 0.04) in the LEU4 group were higher compared to CON1 group. Pathway analysis revealed that the differential metabolites are primarily associated with lysine degradation, glycerophospholipid metabolism, purine metabolism, trothane, piperidine and pyridine alkaloid biosynthesis. In the in vivo trial, the result showed that Leu supplementation increased the concentration of BCFA in milk, including iso -13:0 ( P = 0.01), iso -15:0 ( P = 0.02), anteiso -15:0 ( P = 0.01), iso -16:0 ( P = 0.01), iso -17:0 ( P = 0.02), and anteiso -17:0 ( P < 0.02). Compared to the CON2 group, the concentration of total BCFA was increased by 26.2 % (891 μg/mL vs 706 μg/mL). In conclusion, supplementation of dairy cow's diets with Leu can enrich BCFA in milk. This can be useful for the design and development of functional dairy products that are beneficial for human health. • Leucine increased branched-chain fatty acids (BCFAs) concentration in rumen. • Firmicutes may be dominant phylum that utilizes leucine to synthesize BCFAs. • Leucine increased BCFAs concentration in milk. • The study will be useful to produce enriched BCFA milk products.

  PublisherDOI

• <i>Bis</i>-Allylic Deuterated Docosahexaenoic Acid-Esterified Phospholipids Resist In Vivo Peroxidation in Rat Brain

  Journal of the American Chemical Society · 2025-05-23

  articleOpen accessSenior authorCorresponding

  The human central nervous system simultaneously has the most highly unsaturated fatty acids (HUFAs) and the highest metabolic rate among body tissue. Up to 1% of consumed O2 is converted to reactive oxygen species (ROS) that cause unregulated damage to HUFA-rich membrane phospholipids (PLs). Docosahexaenoic acid (DHA) is the brain’s most unsaturated and abundant HUFA. Reinforcing the ROS-labile bis-allylic positions with deuterium (D-DHA) protects against oxidative damage in vitro and in vivo. We developed an LC–MS/MS method to detect ambient levels of nascent oxidation products of DHA and D-DHA containing PLs in vivo in rat brain lipid extracts. Multiple reaction monitoring (MRM)-triggered mass spectra confirmed D-DHA incorporation in D-DHA-fed rat brain PLs. DHA-PL nascent oxidation products add 2 O, consistent with known peroxidation reactions. In contrast, D-DHA oxidation is primarily detected as a single O addition, consistent with epoxidation. D-DHA-PL showed 20%–30% lower overall oxidation compared to DHA-PL. Our data are consistent with a mechanism of action whereby D-DHA blocks excess lipid peroxidation, leading to lower overall membrane damage. D-DHA is a unique therapeutic approach against neurodegenerative diseases where ROS-driven oxidation is implicated.

  PublisherDOI

• An Examination of the Effects of FADS Indel Genotype on Stress Reactivity in Black Pregnant Women

  Current Developments in Nutrition · 2025-05-01

  articleOpen access

  Objectives: Black American women living in urban low-resourced areas are exposed to high levels of stress that impact their health throughout the lifespan, including during pregnancy. Fatty acid status is associated with improved stress regulation during pregnancy for Black women (Keenan et al., 2016). Genes associated with fatty acid metabolism may be important for understanding individual differences in stress physiology and stress related health problems in this population of women. The FADS Indel is a 22-base pair I(nsertion)-D(eletion) (Indel) polymorphism that controls FADS1 expression (Brenna & Kothapalli, 2022).

  PublisherOA PDFDOI

• The Quantum Brain: The Untold Story of Docosahexaenoic Acid’s Role in Brain Evolution, Biophysics, and Cognition

  International Journal of Molecular Sciences · 2025-11-28

  reviewOpen access

  Docosahexaenoic acid (DHA), the dominant polyunsaturated fatty acid in photoreceptors, neurons, and synapses, is usually described as a passive structural membrane constituent. We propose a different view: DHA is a quantum-electronically active molecule whose methylene interrupted double-bond system creates an electron-rich matrix that couples with proteins to form quantum "clouds" and high-speed signaling central to recognition, recall, and cognition. Integrating evidence from molecular evolution, biophysics, and neuroscience, we argue that, as the original chromophore, DHA's unique properties enabled the emergence of the nervous system and continue to provide the electronic substrate for cognition. By suggesting that cognition depends not only on protein-based mechanisms but on DHA-mediated electron dynamics at the membrane-protein interface, this perspective reframes DHA as an active, conserved determinant of brain evolution and function.

  PublisherDOI

• FDA Expert Panel on Infant Formula “Operation Stork Speed” June 2025: Part 1, Nutrient Considerations

  Preprints.org · 2025-08-04

  preprintOpen access

  Operation Stork Speed, launched by the Food and Drug Administration(FDA) in March 2025, represents a comprehensive initiative to update infant formula regulations that have remained largely unchanged since the 1980’s. This expert panel review addresses recommendations for nutrients considering four decades of accumulated scientific evidence since then. Current FDA fatty acid regulations specify only total fat content and minimum linoleic acid requirements despite substantial international consensus on polyunsaturated fatty acid specifications. Evidence strongly supports establishing maximum linoleic acid levels and docosahexaenoic acid (DHA) and arachidonic acid (ARA) requirements, reflecting the critical role of omega-3 fatty acids in neurocognitive development and visual acuity. The panel emphasizes that saturated and monounsaturated fatty acids comprise over 80% of human milk fatty acids, while acknowledging recent concerns about seed oils and supporting balanced PUFA formulations. Carbohydrate composition presents significant concerns, as over half of US formulas contain glucose polymers (e.g. corn syrup solids) despite lactose being the primary carbohydrate energy source in human milk. Observational studies link corn syrup-based formulas to multiple possible health risks, including excess weight gain, warranting reconsideration of the value of non-lactose carbohydrate substitutions in formulas for healthy children. Protein content recommendations support decreasing the upper range of allowable intake, aligning with European standards and addressing concerns about excessive protein intake contributing to later obesity risk. Micronutrient evaluation reveals the need to reduce the iron content in routine formulas to lower levels, consistent with European Food Safety Authority recommendations and emerging safety data and a need to set upper limits for the concentration of calcium and phosphorus. Overall, infant formula is a healthy product and has many decades of successfully feeding infants. These comprehensive updates aim to more closely align US infant formula regulations with current scientific understanding and international standards while supporting optimal infant growth, development, and long-term health outcomes.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AT007003

  NIH · $1.9M · 2018

• NIH Grant R01GM049209

  NIH · $2.6M · 2006

• NIH Grant R01GM103437

  NIH · $913k · 2016

• NIH Grant R03HD052138

  NIH · $156k · 2010

• NIH Grant R21HD064604

  NIH · $427k · 2013

Frequent coauthors

• Kumar S.D. Kothapalli

  143 shared

• Peter Lawrence

  Cornell University

  97 shared

• Hui Gyu Park

  The University of Texas at Austin

  88 shared

• Dong Hao Wang

  Sun Yat-sen University

  53 shared

• Zhen Wang

  Dalian Minzu University

  49 shared

• Herbert J. Tobias

  48 shared

• Peter W. Nathanielsz

  Texas Biomedical Research Institute

  43 shared

• Anthony Michaud

  Centre Hospitalier Universitaire de Poitiers

  26 shared

Education

• PhD, Chemistry

  Cornell University

  1985

• BS, Nutritional Sciences

  University of Connecticut

  1980

Awards & honors

• ASN’s Osborne and Mendel Award for outstanding contributions…
• ASN’s Robert Herman Award for advancement of clinical nutrit…