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Joel A. Simon, MD, MPH; Esther S. Hudes, PhD, MPH

Arch Intern Med. 1999;159:619-624.

Background  Concern has been raised that high levels of ascorbic acid consumption may lead to potential adverse effects, such as vitamin B₁₂ deficiency, iron overload, and kidney stones.

Objective  To examine the relation of serum ascorbic acid level, which reflects intake, to serum vitamin B₁₂ level, serum ferritin level, and kidney stones.

Methods  We analyzed data collected on a random sample of the US population enrolled in the Second National Health and Nutrition Examination Survey, 1976-1980. We analyzed data using linear and logistic regression models. Serum ascorbic acid, serum vitamin B₁₂, hemoglobin, red blood cell mean corpuscular volume (MCV), and serum ferritin levels were measured using standardized protocols. History of kidney stones was determined by self-report.

Results  After multivariate adjustment, serum ascorbic acid level was associated with higher serum vitamin B₁₂ levels among women in regression models that assumed a linear relationship; each 57-µmol/L (1.0-mg/dL) increase in serum ascorbic acid level (range, 6-153 µmol/L [0.1 to 2.7 mg/dL]) was independently associated with a serum vitamin B₁₂ level increase of 60 pmol/L (81 pg/mL) (P<.001). Among men, serum ascorbic acid level was marginally associated with higher serum vitamin B₁₂ levels: each 57-µmol/L (1.0-mg/dL) increase in serum ascorbic acid level was associated with a serum vitamin B₁₂ level increase of 27 pmol/L (36 pg/mL) (P = .10). In addition, serum ascorbic acid level was not associated with correlates of vitamin B₁₂ deficiency, such as higher MCV levels, macrocytosis (MCV >100), or lower hemoglobin concentrations. Serum ascorbic acid level was not independently associated with serum ferritin levels. However, among women only, serum ascorbic acid levels were associated in a nonlinear fashion with prevalence of elevated serum ferritin levels (P = .02). We found no association between serum ascorbic acid level and prevalence of kidney stones in women or men (both P>.05).

Conclusions  Serum ascorbic acid levels were not associated with decreased serum vitamin B₁₂ levels (or indicators of vitamin B₁₂ deficiency), prevalence of kidney stones, serum ferritin levels, or—among men—prevalence of elevated serum ferritin levels. Serum ascorbic acid levels were associated with prevalence of elevated serum ferritin levels among women. Although the clinical relevance of these findings is uncertain, it seems prudent to suggest that women with a genetic susceptibility to iron overload should consider moderating their intake of ascorbic acid.

From the General Internal Medicine Section, Medical Service, Veterans Affairs Medical Center, San Francisco, Calif (Dr Simon), and Department of Epidemiology and Biostatistics, University of California, San Francisco (Drs Simon and Hudes).

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