Comparative Effectiveness of Ascorbic Acid vs. Calcium Ascorbate Ingestion on Pharmacokinetic Profiles and Immune Biomarkers in Healthy Adults: A Preliminary Study
Open accessAbstract
Background: Previous trials have displayed augmented intracellular vitamin C concentrations in the leukocytes at 24 h after acute supplementation with 1000 mg calcium ascorbate (CA), compared to ascorbic acid (AA). Objective: The primary objective was to evaluate comparative leukocyte vitamin C accumulation kinetics over 32 h following acute 250 mg or 500 mg doses from the two sources. Secondary objectives were to evaluate neutrophil phagocytic function and lymphocyte differentiation between the two sources of vitamin C. Methods: Ninety-three healthy females (250 mg, n = 27; 500 mg, n = 24) and males (250 mg, n = 19; 500 mg, n = 23) were assigned to ingest a single dose of CA or AA providing 250 mg or 500 mg of vitamin C in two separate double-blind, randomized crossover trials. Results: There were no significant differences in the primary or secondary outcomes between the two treatments in the 250 mg low-dose study. Conversely, there was evidence that ingestion of 500 mg of CA increased DHA in plasma, increased neutrophil functionality during the first 8 h of the PK study, promoted increased natural killer cells, and altered weight-adjusted PK profiles, suggesting greater volume distribution and clearance from the blood. Conclusions: These findings indicate that 500 mg of CA may promote some immune benefits compared to 500 mg of AA ingestion.
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Pharmacokinetic analysis showed Calcium ascorbate EC had a greater volume of distribution and clearance from the blood compared to ascorbic acid, especially at 500 mg.
“Pharmacokinetic analysis showed Calcium ascorbate EC had a greater volume of distribution and clearance from the blood compared to ascorbic acid, especially at a dosage of 500 mg, indicating its more effective utilization by the body.”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
The Results (§4.6, page unavailable) report that at 500 mg, total vitamin C volume of distribution significantly decreased with calcium ascorbate, contrary to the claimed increase. Clearance measures only tended to be higher (p = 0.073 and 0.058), so the results also do not establish greater clearance or more effective utilization. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAt 500 mg, Calcium ascorbate EC significantly increased dehydroascorbic acid levels in plasma compared to ascorbic acid.
“However, at 500 mg, Calcium ascorbate EC significantly increased dehydroascorbic acid levels in plasma, indicating better absorption compared to ascorbic acid, suggesting that calcium ascorbate EC can enhance vitamin C bioavailability at higher doses.”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
The Results (section 4.3) report significantly higher plasma dehydroascorbic acid AUC after 500 mg calcium ascorbate than after ascorbic acid, and the Discussion (section 5.1) reports higher levels at most post-dose time points. However, the Methods (section 2.4) identify the tested material as calcium ascorbate, not a formulation designated “EC,” so that added specificity is not established by our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe study found no significant differences between Calcium ascorbate EC and ascorbic acid at the 250 mg dose.
“The study found no significant differences between Calcium ascorbate EC and ascorbic acid at the 250 mg dose.”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
The Abstract and Conclusions (no page numbers supplied) report no significant differences in the main outcomes between calcium ascorbate and ascorbic acid at 250 mg. However, Results §4.6 reports a significantly faster total vitamin C half-life with calcium ascorbate in the low-dose study (p = 0.039), so the unqualified claim of no significant differences is too broad. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe lower infection risk reported with Calcium ascorbate EC is consistent with reported improvements in immune cell function and in leucocyte vitamin C reported in other studies.
“The lower infection risk reported with Calcium ascorbate EC in [28] is consistent with the reported improvements in immune cell function [30] and in leucocyte vitamin C reported in other studies [16,27].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
The Introduction (page unavailable) reports that another study found fewer and less severe cold-like symptoms after 60 days of calcium ascorbate supplementation. This paper’s own crossover studies measured pharmacokinetics and immune biomarkers, not infection risk, so it does not establish a lower infection risk for Calcium ascorbate EC in its participants. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAt 500 mg, Calcium ascorbate EC improved neutrophil phagocytosis and increased natural killer cell counts.
“Also, at 500 mg, Calcium ascorbate EC improved neutrophil phagocytosis and increased natural killer cell counts, suggesting superior immune support over ascorbic acid.”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
The Discussion (§5.2) reports that 500 mg calcium ascorbate increased neutrophil phagocytosis from baseline and increased CD16+ and CD56+ natural killer cells; the Conclusions (§6) suggest possible immune benefits compared with ascorbic acid. However, the Supplementation Procedure (§2.4) identifies the tested material as calcium ascorbate, not as an “EC” formulation, so that added designation is not established by our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measured
The increase in dehydroascorbic acid levels at 500 mg indicates better absorption of Calcium ascorbate EC compared to ascorbic acid.
“However, at 500 mg, Calcium ascorbate EC significantly increased dehydroascorbic acid levels in plasma, indicating better absorption compared to ascorbic acid, suggesting that calcium ascorbate EC can enhance vitamin C bioavailability at higher doses.”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
The Results (§4.3; page unavailable) report higher plasma dehydroascorbic acid (DHA) exposure after 500 mg calcium ascorbate than after ascorbic acid, and the Discussion (§5.1) interprets the higher dose as enhancing vitamin C absorption kinetics. However, total plasma vitamin C did not differ between treatments, so greater overall bioavailability is not established. The Methods (§2.4) identify the tested material as calcium ascorbate but do not identify it as an “EC” formulation. (LLM, conf=0.82)
Experimental — accuracy not yet measuredStudies using Calcium ascorbate EC reported favorable effects on leukocyte vitamin C concentration, showed improved immunity based on cell functions and numbers, and reported fewer colds and a shorter duration of severe cold symptoms compared to placebo.
“Studies using Calcium ascorbate EC reported favorable effects on leukocyte vitamin C concentration [16,27], showed improved immunity (based on cell functions and numbers) [30], and reported fewer colds and a shorter duration of severe cold symptoms compared to placebo [28].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe improvements in neutrophil phagocytosis and natural killer cell counts at 500 mg suggest superior immune support of Calcium ascorbate EC over ascorbic acid.
“Also, at 500 mg, Calcium ascorbate EC improved neutrophil phagocytosis and increased natural killer cell counts, suggesting superior immune support over ascorbic acid.”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
One study investigated the effect of Calcium ascorbate EC on immune function by assessing neutrophil functionality (phagocytosis) and lymphocyte subsets and natural killer cells after ex vivo stimulation.
“One study investigated the effect of Calcium ascorbate EC on immune function by assessing neutrophil functionality (phagocytosis) and the number of different lymphocyte subsets and natural killer cells after ex vivo stimulation [30], while another captured the incidence and symptoms of the common cold [28].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
Dickerson et al. found no significant differences in plasma and leukocyte vitamin C levels between ascorbic acid and Calcium ascorbate EC at 250 mg.
“The study found no significant differences in plasma and leukocyte vitamin C levels between ascorbic acid and Calcium ascorbate EC at 250 mg.”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
Only four studies (31%) reported leukocyte vitamin C concentration, three (in four articles) for Calcium ascorbate EC and one for liposomal-encapsulated vitamin C.
“Only four studies (31%) reported leukocyte vitamin C concentration, three (in four articles) for Calcium ascorbate EC [16,27,30,38] and one for liposomal-encapsulated vitamin C [37].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
Out of thirteen analyzed studies, eight (62%) did not report any adverse events for the intervention or comparators.
“Out of the thirteen analyzed studies, eight (62%) did not report any adverse events, either for the intervention or the comparators [12,27,30,31,33,35,36,37].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
From the NICE checklist quality assessment of thirteen RCTs, ten (77%) showed low risk of bias, two (15%) high risk, and one (8%) unclear risk.
“From the assessment of the methodological quality of thirteen RCTs, ten (77%) showed a low risk of bias [12,16,27,28,29,30,31,32,35,37,38], two (15%) showed a high risk of bias [33,36] and one (8%) showed an unclear risk of bias [34].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
Ingestion of 500 mg Calcium ascorbate EC significantly increased dehydroascorbic acid in plasma, enhanced neutrophil functionality, and promoted an increase in natural killer cells compared to ascorbic acid.
“The study by Dickerson et al. further supports these findings, showing that the ingestion of 500 mg Calcium ascorbate EC significantly increased dehydroascorbic acid in plasma, enhanced neutrophil functionality, and promoted an increase in natural killer cells compared to ascorbic acid [30].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
Four included studies reported vitamin C concentration in both plasma and leukocytes for different formulations; two examined 1000 mg doses and two examined lower doses (250 and 500 mg).
“Four included studies reported vitamin C concentration in both plasma and leukocytes for different formulations. Two studies examined 1000 mg doses [16,27], and two examined lower doses (250 and 500 mg) [30,37].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
At the 500 mg dose, Calcium ascorbate EC showed greater volume distribution and clearance from blood, suggesting enhanced bioavailability that might relate to observed immune benefits.
“However, at the 500 mg dose, Calcium ascorbate EC showed greater volume distribution and clearance from blood, suggesting enhanced bioavailability that might relate to the observed immune benefits [30].”
From Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults (2025) · cites this paper as [30]
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Calder, P. C., Kreider, R. B., & McKay, D. L. (2025) · Nutrients · doi:10.3390/nu17020279 · Cited by 12 · see citing works
Self-citation
- Authors
- Dickerson, B., Gonzalez, D. E., Sowinski, R., Xing, D., Leonard, M., Kendra, J., Jenkins, V., Gopalakrishnan, S., Yoo, C., Ko, J., Pillai, S. S., Bhamore, J. R., Patil, B. S., Wright, G. A., Rasmussen, C. J., & Kreider, R. B.
- Affiliations
- Texas A&M University (US)
- Corresponding author
- Kreider, Richard B.
- ORCID
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2024-10-02
- Volume
- 16
- Issue
- 19
- Pages
- 3358
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC11479081
- OpenAlex
- W4403064126
- Cited by
- 1
- References
- 58
- Citations by year
- 2025: 1
- FWCI
- 0.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- The Bountiful Co. (Ronkonkoma, NY, USA) (NBTY001)
- Exercise & Sport Nutrition Lab (NBTY001)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- vitamin C, calcium ascorbate, pharmacokinetics, immunological markers, lymphocyte differentiation, natural killer cells, docosahexaenoic acid, healthy adults
- MeSH terms
- Adult, Ascorbic Acid, Double-Blind Method, Female, Humans, Male, Neutrophils, Phagocytosis, Biomarkers, Cross-Over Studies, Dietary Supplements, Young Adult, Healthy Volunteers
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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