Supraphysiological ascorbic acid infusion attenuates cerebrovascular dysfunction in middle‐aged and older adults

Q: What are the key findings of this study?

Acute ascorbic acid infusion significantly increased internal carotid artery cerebrovascular reactivity in middle-aged and older adults (from 0.67% to 4.79%), whereas no effect was observed in young adults.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Healthy middle-aged and older adults (n=28). Intervention: Ascorbic acid vs. Saline. Primary outcome: Internal carotid artery cerebrovascular reactivity (ICA CVR) to transient hypercapnia (p=<0.05).

Q: What does this research mean for the field?

Acute supraphysiological ascorbic acid infusion attenuates age-related impairments in internal carotid and middle cerebral artery cerebrovascular reactivity in middle-aged and older adults. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether infusion of the antioxidant ascorbic acid restores internal carotid artery and middle cerebral artery cerebrovascular reactivity in middle-aged and older adults compared to young adults.

Theodore M. DeConne; Faria Sanjana; Elizabeth Habash; Kevin Decker; Wendy Nichols; Joshua C. Hobson; Nicholas Rizzi; Christopher R. Martens

doi:10.14814/phy2.71120

October 1, 2026Physiological ReportsOpen Access

Supraphysiological ascorbic acid infusion attenuates cerebrovascular dysfunction in middle‐aged and older adults

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Key result

Ascorbic acid infusion increases ICA cerebrovascular reactivity ~7-fold in older adults but not younger adults.

P<0.05
n=28

Figures

Graphical abstract published by Physiological Reports — Graphical abstract · Published by Physiological Reports · CC BY

Why the study?

Age-related reductions in internal carotid artery cerebrovascular reactivity may involve antioxidant-responsive mechanisms that are not well understood.

Does acute ascorbic acid infusion improve cerebrovascular reactivity in middle-aged and older adults compared to baseline?

Key Points

To determine whether infusion of the antioxidant ascorbic acid restores internal carotid artery and middle cerebral artery cerebrovascular reactivity in middle-aged and older adults compared to young adults.
Assessed an analytic sample of 9 young adults (25 ± 2 years) and 19 middle-aged and older adults (65 ± 6 years).
Measured internal carotid artery cerebrovascular reactivity to transient (30 s) hypercapnia using duplex ultrasound and middle cerebral artery reactivity to sustained (3-min) hypercapnia via transcranial Doppler ultrasound.
Administered acute intravenous infusions of supraphysiological ascorbic acid and saline control across testing visits.
In middle-aged and older adults, relative internal carotid artery reactivity increased from 0.67 ± 1.73% pre-infusion to 4.79 ± 2.67% post-ascorbic acid infusion, and absolute reactivity increased from 0.056 ± 0.11 mm to 0.32 ± 0.24 mm.
Ascorbic acid infusion increased middle cerebral artery reactivity in middle-aged and older adults when assessed by velocity or conductance, but produced no significant change in young adults.
Saline control infusion produced no significant changes in absolute or relative internal carotid artery reactivity across either age group.

Study Design

Type

RCT (n=28)

Blinding

Double-blind

Randomization

Randomization schedule

Multicenter

No

Structured PICO

Does acute ascorbic acid infusion improve cerebrovascular reactivity in middle-aged and older adults compared to baseline?

P

Population

28 healthy adults (9 young, 19 middle-aged/older) free of cardiovascular or systemic disease, evaluated in a randomized double-blind crossover trial assessing the acute effects of ascorbic acid infusion.

I

Intervention

Ascorbic acid (AA) intravenous infusion: priming bolus of 0.06 g/kg fat-free mass for 20 min followed by a drip-infusion of 0.02 g/kg fat-free mass until end of study visit.

C

Comparator

Saline intravenous infusion matching protocol.

O

Outcome

Cerebrovascular reactivity (CVR) of the internal carotid artery (ICA) in response to transient hypercapnia (30 s) and middle cerebral artery (MCA) in response to sustained hypercapnia (3-min).surrogate

Main Result

Absolute Event Rate: 4.79% vs 0.67%

p-value: p=<0.05

Acute administration of the antioxidant ascorbic acid improves blunted internal carotid and middle cerebral artery cerebrovascular reactivity in older adults, suggesting a role for redox mechanisms in age-related cerebrovascular endothelial dysfunction.

Limitations

Small sample size, varying across measurements, insufficient to assess sex or racial/ethnic differences.
Assessment of MCA CVR using TCD assumes the MCA does not dilate during hypercapnia.
Assessment of ICA vasodilation is technically challenging and difficult to implement clinically.
Lack of a comparable vasodilatory control condition limits determining specificity to NO-dependent vasodilation.
Substantial inter-individual variability and lack of consistent baseline age-related differences.
Freezer malfunction prevented measurement of serum AA and specific oxidative stress/NO biomarkers in the full cohort.
Small sample size
Lack of comparable vasodilatory control condition
Substantial inter-individual variability
Assessment of MCA CVR via TCD assumes no MCA dilation
Freezer malfunction prevented biomarker analysis in full cohort

Implication

Acute ascorbic acid may restore blunted cerebrovascular reactivity in older adults; extends redox mechanism evidence but requires larger trials.

Abstract

Cerebrovascular endothelial function can be assessed by measuring the shear-mediated dilation or cerebrovascular reactivity (CVR) of the internal carotid artery (ICA) in response to transient hypercapnia (30 s). ICA CVR is blunted with aging; however, it is not known whether age-related reductions in ICA CVR are influenced by antioxidant-responsive mechanisms. The purpose of this study was to determine whether infusion of the antioxidant, ascorbic acid (AA) restores ICA CVR in middle-aged and older (MA/O) adults. We also examined the effect of AA on middle cerebral artery (MCA) CVR to sustained (3-min) hypercapnia. We hypothesized that MA/O adults would exhibit lower cerebrovascular function compared to young (Y) adults, and that infusion of AA would improve cerebrovascular function in MA/O adults, whereas infusion of saline (SAL) would not. The primary analytic sample included nine Y adults (25 ± 2 years) and nineteen (65 ± 6 years) MA/O adults, with analyzable data varying by outcome. ICA CVR was measured using high-resolution duplex ultrasound, and MCA CVR was measured using transcranial Doppler ultrasound. AA infusion improved ICA CVR and MCA CVR in MA/O adults but had no effect in Y adults. These findings suggest that age-related impairments in cerebrovascular function may be partly attributable to mechanisms responsive to acute, supraphysiological AA administration.

Discussion

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Cite This Study

DeConne et al. (2026) conducted an RCT in Healthy middle-aged and older adults (n=28). Ascorbic acid vs. Saline was evaluated on Internal carotid artery cerebrovascular reactivity (ICA CVR) to transient hypercapnia (p=<0.05). Acute ascorbic acid infusion significantly increased internal carotid artery cerebrovascular reactivity in middle-aged and older adults (from 0.67% to 4.79%), whereas no effect was observed in young adults.

synapsesocial.com/papers/6ac6fab32f4666a3cc0f8b16 https://doi.org/10.14814/phy2.71120

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Supraphysiological ascorbic acid infusion attenuates cerebrovascular dysfunction in middle‐aged and older adults

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Supraphysiological ascorbic acid infusion attenuates cerebrovascular dysfunction in middle‐aged and older adults

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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