LMBB - Section of Nutritional Neuroscience (NN)

Norman Salem, Jr. PhD, Section Chief

National Institute on Alcohol Abuse and Alcoholism

National Institutes of Health

5625 Fishers Lane, Room 3N07:MSC 9410

Bethesda MD 20892-9410

telephone: +1 301 443 2393

fax: +1 301 594 0035

e-mail: nsalem@nisaaa.nih.gov

Mission Statement

Plans and conducts nutritional studies involving supplementation with omega-3 or omega-6 fatty acids in combination with alcohol;

conducts clinical investigations to evaluate the alterations in lipid composition and metabolism caused by alcohol abuse;

establishes a model of omega-3 fatty acid deficiency in the mammalian nervous system in order to evaluate the functional ramifications of the alcohol-induced loss of neuronal docosahexaenoate;

develops mass spectrometric assays for the in vivo assay of fatty acid desaturation and elongation in order to evaluate the contribution of biosynthesis to the maintenance of tissue long chain polyunsaturate levels and the importance of alcohol effects on these enzymes; and

serves an integrating function in the planning of research investigations between investigators in the Office with those in other units.

Current staff

		Joseph Hibbeln, MD Senior Clinical Investigator 301.435.4028 jhibbeln@mail.nih.gov Current projects: This project examines whether inadequate dietary intake of omega-3 essential fatty acids increases the risk for pathological traits and behaviors associated with alcoholism, specifically depression, aggression and suicide. Randomized placebo-controlled clinical intervention trials are being conducted in adult populations of aggressive alcoholics, women with depression during pregnancy and suicide attempters.
		Yuhong Lin, PhD Staff Scientist 301.443.9031 yulin@mail.nih.gov Current projects: Studies dietary effects on in vivo essential fatty acid metabolism in normal or pathological states, including underling mechanisms and mechanisms of polyunsaturated fatty acid accretion in brain and other organs. Applies stable isotope tracer techniques coupled with gas chromatography / mass spectrometry for fatty acid metabolic and enzymological analyses
		*Sharon Majchrzak, MS* Chemist 301.443.3114 sfm@mail.nih.gov Current projects: An expert analytical biochemist who concentrates on analyses such as polyunsaturated fatty acid content by GC and GC-MS and, more recently, using a fast GC method developed in the lab. Analyzes human samples for fatty acid content in a variety of human trials and experimental conditions. Supports a variety of human dietary studies including a novel method for the artificial rearing model of rodents.
		*James Loewke, BS* Chemist 301.443.3114 jloewke@mail.nih.gov Current projects: An expert analytical biochemist that performs lipid extractions, separation of complex lipid classes and fatty acid analyses using GC. Analyzes human samples for fatty acid content in a variety of human trials and experimental conditions. Supports a variety of human dietary studies including a novel method for the artificial rearing model of rodents.
		*Irina Fedorova, PhD* Research Fellow 301.443.4871 fedorovai@mail.nih.gov Current projects: Studies the influence of diet manipulation, primarily the level of n-3 fatty acids, on animal behavior. The open field test is used to explore locomotion and exploratory activity, elevated plus maze – to evaluate anxiety and the startle apparatus – to test prepulse inhibition of the acoustic startle response. Cognitive functions including spatial working and reference memory are tested in the Barnes circular maze.
		*Nahed Abdalla, PhD* Visiting Fellow 301.443.5881 husseinn@mail.nih.gov Current projects: Development of artificial feeding method for rodents for the precise control of essential fatty acid intakes over the life span. Use of artificial feeding for the introduction of alcohol to rats to model fetal alcohol syndrome. Studies early requirements of essential fatty acid for the mammalian nervous system, particularly for DHA.
		Athar Masood, PhD IRTA Fellow 301.443.2717 masoodaa@mail.nih.gov Current projects: Development and management of robotic applications for high through-put sample preparation involving transesterification reactions of complex lipids present in biological samples. Development and validation of fast GC methods for polyunsaturated fatty acid analysis. Development of methods for fatty acid analysis for large clinical, population, and epidemiological studies.
		James Demar, PhD Contractor/MedData 301.443.2393 demarj@mail.nih.gov Current projects: Studies focus on how dietary levels of n-3 polyunsaturated fatty acids influence both their potential in vivo synthesis and whole body tissue distributions. This is being done using rats given tracer labeled alpha-linolenic acid to follow changes in their metabolism with variation in the level of dietary DHA intake. Also under investigation is the association between decreased plasma levels of n-3 polyunsaturated fatty acids in human alcoholics and the severity of their symptoms as well as a poor response to treatment interventions.
		*Tanya Blasbalg, MS* Technical IRTA 301.435.4029 blasbalgt@mail.nih.gov Current projects: Authoring and editorial work on several manuscripts, including Healthy intakes of n-3 and n-6 fatty acids: Estimations considering worldwide diversity, Roles of Omega-3 Fatty Acids in Aggression; Hostility, and Depression: Neurodevelopmental Predispositions in Childhood and Opportunities for Treatment, and a look at changes in the consumption of linoleic acid in the United States over the last 100 years.
		Carmine Di Martino, BS Postbac IRTA 301.443.2716 martinoc@mail.nih.gov Current projects: Investigates the dietary influence of omega-3 fatty acid deficiency during early postnatal development on the emotional status and cognitive ability of ICR mice as assessed by behavioral tasks. Assess the impact of dietary docosahexaenoic acid (DHA) on the metabolic pathways regulating biosynthesis of omega-3 fatty acids.
		*Levi Nieminen, BS* Postbac IRTA 301.435.4029 levi.nieminen@mail.nih.gov Current projects: Projects focus on examining the role of omega-3 fatty acids in the etiology and treatment of alcoholism, aggression, and other psychiatric disorders. Process brain images of aggressive alcoholics to quantify the cortical gray matter, white matter, cerebrospinal fluid, and ventricular volume in order to determine if omega-3 fatty acids can reverse cortical atrophy. Supports data collection and management of a clinical protocol involving omega-3 fatty acid treatment of alcoholics.
		*Weiyin Zhou, BS* Technical IRTA 301.402.8564; 301.443.2716 weiyin.zhou@mail.nih.gov Current projects: Conduct statistics and data analysis of PET functional images and MR images for a clinical trial to investigate difference of brain consumption of DHA in control and alcoholic groups. Design, write and develop macro programs to automate GC data processing and analysis. Lab web design and management.

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Collaborators

Dr. Paul Sieving, Director, NEI, NIH; and his associates Drs. Ron Bush and Dorit Raz. Clinical study of Stargardt Muscular Dystrophy and animal models of ELOVL4 knock out and knock ins.

Drs. Emily Chew and John Paul San Giovanni, NEI, NIH - Mouse models of retinopathy of prematurity.

Dr. Chi-Chan Chao, NEI, NIH - Fat-1 mouse, omega-3 fatty acid status and experimentally induced uveitis.

Dr. Stanley Rapoport, NIA, NIH; Dr. John Umhau, LCTS, NIH; Drs. Richard Carson, Peter Herscovitz, PET Center, CC, NIH - PET imaging of human brain and heart using 11C-DHA.

Drs. Robert Sokol, John Hannigan, Janice Whitty, Fetal Alcohol Research Center, Wayne State University - This collaboration centers on the study of the involvement of essential fatty acids in mediating aspects of the Fetal Alcohol Syndrome. Maternal and newborn cord blood is obtained as well as alcohol history and nutrient intake; fatty acid compositional analysis is performed.

Dr. Manubu Nakamura, University of Illinois - Characterization of a delta-6 desaturase knock out mouse.

Dr. Greg Cole, UCLA - Effect of DHA on a mouse model of dementia.

Dr. Radha Ayyagari, University of Michigan - Fatty acid compositional changes and effects of diet on retinal pathology associated with ELOVL4 knock out mice.

Dr. Lois Smith, Harvard University - Effects of EPA and DHA on mouse models of retinopathy of prematurity.

Dr. Jan Palmblad, Karolinska Institute - Fatty acid composition of cerebrospinal fluid in patients with Alzheimer’s disease treated with DHA.

Drs. Kavita Shankar, Christopher DeGiorgio, UCLA - Analysis of essential fatty acids in plasma of intractable partial seizures.

Dr. Junji Hoshiba, Okuyama University, Japan - Collaborate on the development of artificial rearing methodology and application to the n-3 deficient rat model.

Dr. Lynn Goldman, Johns Hopkins University. Correlations of n-3 essential fatty acid status and mercury exposure with infant outcomes.

Drs. Ricardo Uauy, and Adolfo Llanos, INTA University of Chile, Santiago, Chile - Collaboration on the study of essential fatty acid metabolism in vivo in human infants in the first weeks of life.

Dr. Bruce Watkins, Purdue University - Collaborate on bone fatty acid compositional changes and mechanical properties during n-3 fatty acid depletion and repletion.

Drs. Jean Golding, Dieter Wolke, John M. Davis, ALSPAC Study Group, University of Bristol, UK - Adverse neurodevelopmental outcomes associated with the restriction of seafood consumption during pregnancy in compliance with the 2004 EPA/FDA advisory.

Dr. Marlene Freeman, University of Arizona - (K-23 mentor) - Omega-3 fatty acids in the treatment of depression in perinatal and postnatal periods.

Drs. Marc Schuckit, University of San Diego, Jean Golding, University of Bristol, UK, John M. Davis, University of Illinois - Prospective characterization of drinking behavior among 8,000 early adolescents.

Drs. Budens-Branchey and Branchey, VAMC, Brooklyn, NY - Treatment of mixed substance misuse subjects with omega-3 fats, a double blind placebo controlled trial.

Drs. Garland and Hallahan, University of Dublin, Ireland - John M. Davis, University of Illinois - Omega-3 essential fatty acid supplementation in patients with recurrent deliberate self harm: a double blind randomized controlled trial.

Drs. Mann, Sublette, Columbia University, NY- Low DHA status as a predictor of future suicide attempts.

Selected Recent Publications

Hibbeln JR, Ferguson TA, Blasbalg TL. Omega-3 fatty acid deficiencies in neurodevelopment, aggression and autonomic dysregulation: opportunities for Intervention. Intl Review Psychiatry. 18(2):107-118, 2006. PubMed [PDF]

Masood A, Stark KD, Salem N Jr. A simplified and efficient method for the analysis of fatty acid methyl esters suitable for large clinical studies. J Lipid Res. 46(10):2299-2305, 2005. PubMed [PDF]

Lin YH, Salem N Jr. In vivo conversion of 18- and 20-C essential fatty acids in rats using the multiple simultaneous stable isotopes method. J Lipid Res. 46(9):1962-1973, 2005. PubMed [PDF]

Lim S-Y, Hoshiba J, Salem Jr N. An extraordinary degree of structural specificity is required in neural phospholipids for optimal brain function: n-6 docosapentaenoic acid substitution for docosahexaenoic acid leads to a loss in spatial task performance. J Neurochem. 95(3):848-857, 2005. PubMed [PDF]

Salem N Jr, Loewke J, Catalan JN, Majchrzak S, Moriguchi T. Incomplete replacement of docosahexaenoic acid by n-6 docosapentaenoic acid in the rat retina after an n-3 fatty acid deficient diet. Exp Eye Res. 81(6):655-863, 2005. PubMed [PDF]

Stark KD, Beblo S, Murthy M, Buda-Abela M, Janisse J, Rockett H, Whitty JE, Martier SS, Sokol RJ, Hannigan JH, Salem N Jr. Comparison of bloodstream fatty acid composition from African-American women at gestation, delivery and postpartum. J Lipid Res. 46(3):516-525, 2005. PubMed [PDF]

Lim SY, Hoshiba J, Moriguchi T, Salem N Jr. N-3 fatty acid deficiency induced by a modified artificial rearing method leads to poorer performance in spatial learning tasks. Ped Res. 58(4):741-748, 2005. PubMed [PDF]

Stark KD, Beblo S, Murthy M, Whitty JE, Buda-Abela M, Janisse J, Rockett H, Martier SS, Sokol RJ, Hannigan JH, Salem N Jr. Alcohol consumption in pregnant, black women is associated with decreased plasma and erythrocyte docosahexaenoic acid. Alcohol Clin Exp Res. 29(1):130-140, 2005. PubMed [PDF]

Lefkowitz W, Lim SY, Lin Y, Salem N Jr. Where does the developing brain obtain its docosahexaenoic acid? Relative contributions of dietary alpha-linolenic acid, docosahexaenoic acid, and body stores in the developing rat. Pediatr Res. 57(1):157-165, 2004. PubMed [PDF]

Pawlosky RJ, Salem N Jr. Development of alcoholic fatty liver and fibrosis in rhesus monkeys fed a low n-3 fatty acid diet. Alcohol Clin Exp Res. 28(10): 1569-1576, 2004. PubMed [PDF]

Moriguchi T, Lim S-Y, Greiner R, Lefkowitz W, Loewke J, Hoshiba J, Salem N Jr. Effects of an n-3 deficient diet on brain, retina and liver fatty acyl composition in artificially reared rats. J Lipid Res. 45:1437-1445, 2004. PubMed [PDF]

Hibbeln JR, Bissette G, Umhau JC, Georgo DT. Omega-3 status and cerebrospinal fluid corticotrophin releasing hormone in perpetrators of domestic violence. Biol Psychiatry. 56(11):895-897, 2004. PubMed [PDF]

Hibbeln JR, Nieminen LR, Lands WE. Increasing homicide rates and linoleic acid consumption among five Western countries, 1961-2000. Lipids. 39(12):1207-1213, 2004. PubMed [PDF]

Greiner RS, Catalan J and Salem Jr N. Docosapentaenoic acid does not completely replace docosahexaenoic acid in n-3 FA-deficient rats during early development. Lipids. 38(4):431-435, 2003. PubMed [PDF]

Pawlosky RJ, Hibbeln JR, Lin Y, Goodson S, Riggs P, Brown GL and Salem N Jr. Effects of beef- and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects. Am J Clin Nutr. 77: 565-572, 2003. PubMed [PDF]

Moriguchi T, N Salem Jr. Recovery of brain docosahexaenoate leads to recovery of spatial task performance. J Neurochem. 87(2):297-309, 2003. PubMed [PDF]

Hibbeln JR, Makino KK, Martin CE, Dickerson F, Boronow J, Fenton WS. Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder. Biol Psychiatry. 53(5):431-441, 2003. PubMed [PDF]

Buydens-Branchey J, Branchey M, McMakin D, Hibbeln JR. Polyunsaturated fatty acids and relapse vulnerability in cocaine addicts. Psychiatry Research. 120(1):29-35, 2003. PubMed [PDF]

Budens-Branchey J, Branchey M, McMakin D, Hibbeln JR. Polyunsaturated fatty acid status and aggression in cocaine addicts. Drug Alcohol Dependence. 71(3):319-323, 2003. PubMed [PDF]

Lin Y, Salem N Jr. A technique for the in vivo study of multiple stable isotope-labeled essential fatty acids. Prostaglandins Leukotrienes Essential Fatty Acids. 67(2-3):141-146, 2002. PubMed

Catalan J, Moriguchi T, Slotnick B, Murthy M, Greiner RS, Salem N Jr. Cognitive deficits in docosahexaenoic acid-deficient rats. Behavioral Neurosci. 116(6):1022-1031, 2002. PubMed [PDF]

Ahmad A, Moriguchi T, Salem N. Decrease in neuron size in docosahexaenoic acid-deficient brain. Ped Neurology. 26(3):210-218, 2002. PubMed [PDF]

Hibbeln JR. Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord. 69(1-3):15-29, 2002. PubMed [PDF]

Champoux M, Hibbeln JR, Shannon C, Majchrzak S, Suomi SJ, Salem N Jr, Higley JD. Fatty acid formula supplementation and neuromotor development in rhesus monkey neonates. Pediatr Res. 51(3):273-281, 2002. PubMed [PDF]

Pawlosky RJ, Bacher J, Salem N Jr. Ethanol consumption alters electroretinograms and depletes neural tissues of docosahexaenoic acid in rhesus monkeys: nutritional consequences of a low n-3 fatty acid diet. Alcohol Clin Exp Res. 25(12):1758-1765, 2001. PubMed [PDF]

Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr. Physiological compartmental analysis of alpha–linolenic acid metabolism in adult humans. J Lipid Res. 42(8):1257-1265, 2001. PubMed [PDF]

Salem N Jr, Litman B, Kim HY, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 36(9):945-59, 2001. PubMed [PDF]

Moriguchi T, Loewke J, Garrison M, Catalan JN, Salem N Jr. Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver and serum. J Lipid Res. 42(3):419-427, 2001. PubMed [PDF]

Salem N Jr, Moriguchi T, Greiner RS, McBride K, Ahmad A, Catalan JN, Slotnick B. Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids. J Molecular Neurosci. 16:299-307, 2001. PubMed [PDF]

Greiner RS, Moriguchi T, Slotnick BM, Hutton A, and Salem N. Olfactory discrimination deficits in n-3 fatty acid deficient rats. Physiology & Behavior. 72:379-385, 2001. PubMed

Hibbeln JR. Seafood consumption and homicide mortality. A cross-national analysis. World Rev Nutr Diet. 88:41-46, 2001. PubMed [PDF]

Tanskanen A, Hibbeln JR, Tuoileheto J, Uutela A, Haukkala A, Viinamaki H, Lehtonen J, Vartainen E. Fish consumption and depressive symptoms in the general population in Finland. Psychiatr Serv. 52(4):529-531, 2001. PubMed

Tanskanen A, Hibbeln JR, Hintikka J, Haatainen K, Honkalampi K, Viinamäki H. Fish consumption, depression, and suicidality in a general population. Arch Gen Psychiatry. 58(5):512-513, 2001. PubMed [PDF]

Fenton WS, Dickerson F, Boronow J, Hibbeln JR, Knable M. A placebo-controlled trial of omega-3 fatty acid (ethyl-EPA) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 158(12):2071-2074, 2001. PubMed

Moriguchi T, Greiner RS, Salem N Jr. Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J Neurochem. 75(6):2563-2573, 2000. PubMed [PDF]

Uauy R, Mena P, Wegher B, Nieto S, Salem N Jr. Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Pediatr Res. 47(1):127-135, 2000. PubMed

Hibbeln JR, Umhau JC, George DT, Shoaf SE, Regan P, Linnoila M, Salem N Jr. Plasma total cholesterol concentrations do not predict cerebrospinal fluid neurotransmitter metabolites: implications for the biophysical role of highly unsaturated fatty acids. Am J Clin Nutr. 71(1 Suppl):331S-338S, 2000. PubMed

Pawlosky RJ, Salem N Jr. Alcohol consumption in rhesus monkeys depletes tissues of polyunsaturated fatty acids and alters essential fatty acid metabolism. Alcohol Clin Exper Res. 23(2):311-317, 1999. PubMed

Hibbeln JR, Umhau JC, Linnoila M, George DT, Ragan PW, Shoaf SE, Vaughan MR, Rawlings R, Salem Jr N. A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids. Biol Psych. 44(4):243-249, 1998. PubMed

Olsson NU, Shoaf SE and Salem N Jr. The effect of dietary polyunsaturated fatty acids and alcohol on neurotransmitter levels in rat brain. Nutritional Neurosci. 1:133-140, 1998.

Hibbeln JR. Fish consumption and major depression. Lancet. 351(9110):1213, 1998. PubMed

Salem N Jr, Wegher B, Mena P, Uauy R. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci USA. 93(1):49-54, 1996. PubMed [PDF]

Hibbeln JR and Salem N Jr. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clinical Nutr. 62(1):1-9, 1995. PubMed [PDF]

FIND PUBLICATIONS USING PubMed

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NN Clinical Protocols:

01-AA-0141: Polyunsaturated Fatty Acids and the Neurochemistry of Cardiovascular and Motor Reactivity

04-AA-0058: Positron Emission Tomography Imaging of Incorporation of Docosahexaenoic Acid (DHA) from Plasma into Human Brain

NIAAA Clinicals Protocols & link to all NIH Clinical Protocols

FIND ANNUAL REPORT PROJECTS USING NIDB Resources

1 Z01 AA000262-23: (2005) Desaturation Of Essential Fatty Acids Using Stable Isotope GC/MS

1 Z01 AA000235-23: (2005) Nutritional Effects On Essential Fatty Acid Composition

1 Z01 AA000115-06: (2005) Essential Fatty Acids In Psychiatric Disorders

NIH Research and Training Opportunities

Last updated: June 2006