Photo of Balz FreiDistinguished Professor Emeritus, Linus Pauling Institute

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Research Interests

The research program in my laboratory was aimed at understanding the role of free radicals and inflammation in human chronic diseases, in particular atherosclerosis and cardiovascular disease, and the ameliorating effects of micronutrients, phytochemicals, and dietary supplements.

One of the earliest events in atherosclerosis is "activation" of the endothelium, a single-cell layer lining arterial walls. Endothelial activation may be caused by increased production of free radicals and leads to increased expression of cellular adhesion molecules (CAM) and monocyte chemoattractant protein-1 (MCP-1) by these cells. As a consequence, white blood cells called monocytes are recruited to the arterial wall, where they initiate chronic inflammation and atherosclerotic lesion development. We performed cell culture, animal, and human studies to investigate 1) the mechanisms and consequences of endothelial activation, 2) the role of transition metals like iron and copper in this process, and 3) the effectiveness of antioxidant and anti-inflammatory dietary compounds in ameliorating endothelial activation and subsequent atherosclerotic lesion development.

We found that lipoic acid and certain metal chelators (metal-binding agents) effectively inhibit CAM and MCP-1 expression by human aortic endothelial cells and suppress vascular inflammation and atherosclerosis in experimental mice. We performed randomized clinical trials to investigate the effects of lipoic acid supplementation on oxidative stress, inflammation, serum lipids and lipoproteins, blood pressure, and other coronary risk factors in healthy subjects and heart disease patients.

Additional projects in the laboratory investigated the biological mechanisms and metabolic effects of flavonoids, the interactions of lipoic acid and ascorbic acid (vitamin C) in improving vitamin C body status and antioxidant defenses in humans, and the mechanisms of pharmacological doses of vitamin C in its potential cancer therapeutic effects.


1983 B.S., Biochemistry, Swiss Federal Institute of Technology, Zürich (ETH-Z), Switzerland
1986 Ph.D., Biochemistry, Swiss Federal Institute of Technology, Zürich (ETH-Z), Switzerland

Positions and Employment

1987-1990 Post-doctoral Fellow, University of California, Berkeley, CA (Bruce N. Ames, Sponsor)
1990-1994 Assistant Professor of Nutrition and Toxicology, Harvard School of Public Health, Boston, MA (Walter C. Willett, Department Chair)
1994-1997 Associate Professor of Medicine and Biochemistry, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA
1997-2016 Director and Endowed Chair, Linus Pauling Institute, Distinguished Professor of Biochemistry and Biophysics, Oregon State University, Corvallis, OR

Professional Experience

Editorial Boards, Arch. Biochem. Biophys. (1993-96), Redox Report (1996-present), Free Radic. Biol. Med. (1997-07; 2011-present), Am. J. Clin. Nutr. (2002-04), FASEB J. (2001-06), J. Berry Res. (2010-present), Antioxidants (2012-present).

Editor, "Natural Antioxidants in Human Health and Disease," Academic Press, San Diego, CA (1994); Special Review Series "Molecular and Biological Mechanisms of Antioxidant Action," FASEB J. 13, Nos. 9 & 10 (1999); Co-Editor, "The Antioxidant Vitamins C and E," AOCS Press, Champaign, IL (2002).

NIH Study Section Service: Site Visit Team, "Oxidative Events in Cancer Therapy" (P01), University of Iowa (1994); Special Emphasis Panel (ZRG4-NTN-5R), Nutrition Study Section (1995); Temporary Member, Metabolism Study Section (1998); Special Emphasis Panel (ZRG2 NMS), Metabolism Study Section (1998); Temporary Member, Pathology A Study Section (2000-03); Program Review, "Oxidation in Inflammation and Cardiovascular Disease" (P01) (2003); Program Review, "Biobehavioral Bases of CHD Risk and Management" (P01) (2005); Temporary Member, Atherosclerosis and Inflammation of the Cardiovascular System (AICS) Study Section (2004-05); Charter Member, AICS Study Section (2005-08). Program Review, "Centers of Excellence for Research on CAM" (P01) (2008).

President, Society for Free Radical Biology and Medicine (formerly The Oxygen Society) (2002-04); President-elect (2000-02); Treasurer (1997-2000).

Chair, FASEB Conference "Molecular and Biological Mechanisms of Antioxidant Action," Copper Mt., CO (1998); 11th Gordon Research Conference on "Oxygen Radicals in Biology," Ventura, CA (2000); 10th and 11th Annual Meeting of the Society for Free Radical Biology and Medicine, Seattle, WA (2003), and St. Thomas, VI (2004); Biennial LPI Conference "Diet and Optimum Health," Portland, OR (2001-09), Corvallis, OR (2011-15).


1987 Young Scientist Career Development Award, Swiss National Foundation
1991 William F. Milton Award, Harvard Medical School
1992 Future Leader Award, International Life Sciences Institute - Nutrition Foundation
1995 Fellow of the American Heart Association (F.A.H.A.), Council on Arteriosclerosis
1997 Linus Pauling Institute Endowed Chair and Directorship
2002 Dorothy Epstein Nutrition Fellow, Hunter College of the City University of New York
2004 Distinguished Service Award, Society for Free Radical Biology and Medicine
2005 Discovery Award, Medical Research Foundation, Oregon Health & Science University
2008 Free Radical Biology & Medicine, Top Cited Papers 2005-2007 Award
2010 Distinguished Professor Award, Oregon State University
2010 Denham Harman Distinguished Lectureship in Biomedical Gerontology, University of Nebraska
2011 Free Radical Biology & Medicine, Top Cited Articles 2006-2011 Award
2013 Joan H. Facey Linus Pauling Institute Endowed Professorship
2013 Fellow of the Society of Free Radical Biology and Medicine (F-SFRBM)

Recent Publications (from a total of over 200 peer-reviewed publications; h-index: 76; sum of times cited: >23,000)

Li C, Zhang WJ, Choi J, Frei B. (2016) Quercetin affects glutathione levels and redox ratio in human aortic endothelial cells not through oxidation but formation and cellular export of quercetin-glutathione conjugates and upregulation of glutamate-cysteine ligase. Redox Biol 9:220-228.

Li C, Zhang WJ, Frei B. (2016) Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. Redox Biol 9:104-113.

Blumberg JB, Frei B, Fulgoni VL 3rd, Weaver CM, Zeisel SH. (2016) Vitamin and mineral intake is inadequate for most Americans: What should we advise patients about supplements? J Fam Pract 65:S1-S8.

Zhang WJ, Frei B (2015) Astragaloside IV inhibits NF-κB activation and inflammatory gene expression in LPS-treated mice. Mediators Inflamm, Epub ahead of print.

Kerr DC, Zava DT, Piper WT, Saturn SR, Frei B, Gombart AF. (2015) Associations between vitamin D levels and depressive symptoms in healthy young adult women. Psychiatry Res 227:46-51.

Cavender G, Liu M, Hobbs D, Frei B, Strik B, Zhao Y. (2014) Effects of different organic weed management strategies on the physicochemical, sensory, and antioxidant properties of machine-harvested blackberry fruits. J Food Sci 79:S2107-S21166.

Angelo G, Drake VJ, Frei B. (2014) Efficacy of multivitamin/mineral supplementation to reduce chronic disease risk: a critical review of the evidence from observational studies and randomized controlled trials. Crit Rev Food Sci Nutr, Epub ahead of print.

Frei B, Ames BN, Blumberg JB, Willett WC. (2014) Enough is enough.  Ann Intern Med 160:807.

McEvoy CT, Schilling D, Clay N, Jackson K, Go MD, Spitale P, Bunten C, Leiva M, Gonzales D, Hollister-Smith J, Durand M, Frei B, Buist AS, Peters D, Morris CD, Spindel ER. (2014) Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.  JAMA 311:2074-2082.

Lykkesfeldt J, Michels AJ, Frei B. (2014) Vitamin C. Adv Nutr 5:16-18.

Frei B. (2013) The case is far from closed for vitamin and mineral supplements! Comment on: Enough is enough: Stop wasting money on vitamin and mineral supplements. Ann Intern Med.

Michels AJ, Frei B. (2013) Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. Nutrients 5:5161-5192.

Wei H, Zhang WJ, Leboeuf R, Frei B. (2013) Copper induces - and copper chelation by tetrathiomolybdate inhibits - endothelial activation in vitroRedox Rep 19:40-48.

Rodriguez KJ, Wong HK, Oddos T, Southall M, Frei B, Kaur S. (2013) A purified Feverfew extract protects from oxidative damage by inducing DNA repair in skin cells via a PI3-kinase-dependent Nrf2/ARE pathway. J Dermatol Sci 72:304-310.

Michels AJ, Hagen TM, Frei B. (2013) Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annu Rev Nut 33:45-70.

Dixon BM, Barker T, McKinnon T, Cuomo J, Frei B, Borregaard N, Gombart AF. (2012) Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults. BMC Res Notes 5:575.

Wei H, Zhang WJ, McMillen TS, Leboeuf RC, Frei B. (2012) Copper chelation by tetrathiomolybdate inhibits vascular inflammation and atherosclerotic lesion development in apolipoprotein E-deficient mice. Atherosclerosis 223:306-313.

Frei B, Birlouez-Aragon I, Lykkesfeldt J. (2012) Authors' perspective: What is the optimum intake of vitamin C in humans? Crit Rev Food Sci Nutr 52:815-829.

Yilmazer-Musa M, Griffith AM, Michels AJ, Schneider E, Frei B. (2012) Grape seed and tea extracts and catechin 3-gallates are potent inhibitors of α-amylase and α-glucosidase activity. J Agric Food Chem 60:8924-8929.

Finlay LA, Michels AJ, Butler JA, Smith EJ, Monette JS, Moreau RF, Petersen SK, Frei B, Hagen TM. (2012) R-alpha-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles. Am J Physiol Regul Integr Comp Physiol 302:R587-597.