Differing Relations to Early Atherosclerosis between Vitamin C from Supplements vs. Food in the Los Angeles Atherosclerosis Study: A Prospective Cohort Study

Megha Agarwal 1, Puja K Mehta 1, James H Dwyer 2, ^, Kathleen M Dwyer 2, Anne M Shircore 2, Cheryl K Nordstrom 3, Ping Sun 2, Maura Paul-Labrador 2, ^, Yuching Yang 1, C. Noel Bairey Merz 1, *
1 Women’s Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
2 Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
3 Center for Health Research, Wayne State University, Detroit, MI, USA
^ Deceased This work was supported by grants from the NHLBI (National Heart, Lung, and Blood Institute, USA; grants R01 HL49910 and R01 073108-01), TRDRP (Tobacco-Related Disease Research Program, USA; grant 7RT-0034) and a GCRC grant MO1-RR00425 from the National Center for Research Resources, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey, the Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, California, the Edythe L. Broad Women’s Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California, and the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, USA

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© Agarwal et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Health Women's Heart Center, Preventive Cardiac Center, Medicine Cedars-Sinai Heart Institute 444 S San Vicente Blvd, Suite 600, Los Angeles, CA90048, USA; Tel: 310-423-9680; Fax: 310-423-9681; E-mail:



To determine the relationship of vitamin c intake from supplements vs food on early atherosclerosis detected by carotid intima media thickness (IMT).


Oxidative stress and endothelial dysfunction play a critical role in the pathogenesis of atherosclerosis. Dietary vitamin C appears to have anti-oxidant properties and beneficial relations to endothelial function, yet vitamin C taken as a vitamin supplement does not appear to protect from cardiovascular events. The impact of vitamin c intake from supplements vs food on progression of atherosclerosis is unknown.


We examined 3-year progression of carotid IMT in a randomly sampled cohort of 573 healthy women and men aged 40-60 years. Progression of carotid IMT was determined bilaterally with B-mode ultrasound at 3 examinations (1.5-year intervals). Intake of dietary vitamin C was measured by six, 24-hour recall interviews. Intake of vitamin C from vitamin supplements was measured by questionnaire in quartiles of supplement intake and no supplement. Vitamin C wasmeasured in plasma as ascorbic acid.


Carotid IMT progressed 10.0±16.5 μm/year (mean±SD) among all those with follow-up (n=500; 87%). For those who took vitamin C supplements, carotid IMT progression increased with dose (p-trend=0.0009). Among persons in the highest quartile (857-5000 mg/day) of vitamin C supplement intake compared to those not consuming any vitamin C supplements, carotid IMT progression increased three-fold (20.3±2.6 versus 7.6±1.8 μm/year (mean±SD); p<0.001). The adverse association of vitamin C supplement intake with carotid IMT was two-fold greater in the upper tertile of serum cholesterol compared to the lower two tertiles (p=0.01). In contrast to the adverse association of vitamin C supplements, vitamin C intake from food had a weak protective relationship on carotid IMT progression (reduced progression -5.0±1.9 μm/year; p=0.008).


Vitamin C supplementation is associated with accelerated early atherosclerosis measured by carotid IMT compared to a protective association with vitamin C from food. Theadverse association of vitamin C supplementation may be greater in patients with higher serum cholesterol levels. The current results provide a potential mechanistic understanding for the observed differences between Vitamin C in supplements vs food in prior studies. Given these observations,vitamin C supplementation does not appear to be currently advisable for prevention or treatment of atherosclerosis.

Keywords: Ascorbic acid, vitamin C, atherosclerosis, cardiovascular disease..