The short answer
Amphetamine sulfate labeling warns that acidifying agents, including ascorbic acid (vitamin C), can lower amphetamine blood levels and effectiveness. The reviewed searches identified no human study measuring amphetamine levels or response with a vitamin C supplement. Vitamin C studies of urine acidity have mixed results and do not test its effect on gastrointestinal absorption. Tell your prescriber and pharmacist about regular vitamin C use and any change in medicine effectiveness. Review the regimen with them rather than changing the stimulant dose yourself.
What this answer covers
Vitamin C taken as ascorbic acid in tablets, capsules, powders or chewables, with oral amphetamine sulfate as EVEKEO tablets or as one of the four salts in ADDERALL and ADDERALL XR.
- Supplement or preparation
- ascorbic acid
- Medication ingredient
- amphetamine sulfate
What the labels actually say
The EVEKEO label lists ascorbic acid by name among gastrointestinal acidifying agents that lower the absorption of amphetamines, and lists urinary acidifying agents that increase how much amphetamine leaves in the urine. It concludes that both groups lower blood levels and how well amphetamines work. The ADDERALL XR label gives ascorbic acid as its example of an acidifying agent and tells the prescriber to adjust the capsule dose based on how the person responds. Neither label gives a vitamin C dose, a size of effect or a separation interval.
Why urine acidity matters for amphetamine
Amphetamine elimination depends partly on urinary pH. In seven healthy men given single doses of d-amphetamine, 35% to 44% of the dose was recovered unchanged in urine within 24 hours, with greater excretion at lower urinary pH. Another study examined amphetamine kinetics under deliberately acidified and alkalinized urine conditions. These studies support the urinary mechanism but did not test vitamin C. EVEKEO also describes a separate gastrointestinal absorption mechanism.
How much a vitamin C supplement really changes urine acidity
A review covering 150 experiments on many urinary-pH interventions included 5 vitamin C papers with 7 reported results. The vitamin C category had a reported mean change of +0.03 pH units, with none of those results marked statistically significant. Methods and populations varied. A separate controlled-diet study using 2 g of ascorbic acid three times daily reported a mean reduction of less than 0.2 units. Another study found no change in fasting urinary pH after 1 g or 2 g daily for 3 days. These findings concern urine acidity, not gastrointestinal absorption or amphetamine response.
A selected stone-patient cohort had a different result
In a retrospective review of 24 people with recurrent stones and alkaline urine, 500 mg to 2,000 mg of ascorbic acid daily was associated with a fall in urinary pH from a median 7.6 to 6.9. There was no control group. This result does not show that baseline urine acidity explains the differences across studies or predicts a larger amphetamine interaction. No amphetamine outcome was measured.
What this means in practice
Tell your prescriber and pharmacist about regular ascorbic acid use, including the dose and other ingredients in the product, and mention any change in how long or how well your medicine works. ADDERALL XR labeling advises a clinician to adjust the amphetamine dose according to clinical response when acidifying agents are used; EVEKEO gives the interaction warning without a specific adjustment instruction. Your clinician can review both products and decide whether any change is needed. Do not adjust the stimulant dose yourself. The inspected sources do not establish a vitamin C separation interval.
Evidence and practical considerations
Absorption & effectiveness
Amphetamine sulfate labeling names ascorbic acid among acidifying agents that can lower amphetamine blood levels and effectiveness. No exact-pair human study was identified in the reviewed searches. Studies of vitamin C and urinary pH give mixed results and do not assess the gastrointestinal absorption mechanism, so the practical magnitude remains uncertain.
- Exact scope
- Ascorbic acid in supplement tablets, capsules, powders and chewables, at the doses people commonly take. with Oral amphetamine sulfate, both as the single-entity tablet (EVEKEO) and as one of the four salts in mixed amphetamine salts products (ADDERALL tablets and ADDERALL XR capsules).
- Medication form and route
- oral medication; oral supplement
- Timing or duration
- Any period of regular vitamin C use, based on labeling rather than a measured onset or offset
What remains uncertain
- Label-based interaction with no exact-pair human study identified. Urinary-pH studies did not measure amphetamine or gastrointestinal absorption and cannot establish the size of a clinical effect or which starting urine pH predicts it.
Factors that may matter: Vitamin C dose; Starting urine acidity; Amphetamine product and release form; Other acidifying or alkalinizing products.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 22, 2026
Population: People prescribed amphetamine sulfate
The Drug Interactions section states that gastrointestinal acidifying agents, listing guanethidine, reserpine, glutamic acid HCl, ascorbic acid and fruit juices, lower absorption of amphetamines, and that urinary acidifying agents, listing ammonium chloride and sodium acid phosphate, increase the concentration of the ionized form and so increase urinary excretion. It concludes that both groups lower blood levels and efficacy of amphetamines.
How this applies: Exact amphetamine sulfate (RxCUI 81952) as the single active ingredient of this label; the interaction section names the supplement ingredient itself rather than a drug class only.
The label names ascorbic acid but gives no dose, no size of effect, no monitoring plan and no separation interval, and cites no study.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 22, 2026
Population: People prescribed amphetamine sulfate
Section 2.7 states that agents which alter urinary pH can affect excretion and alter blood levels of amphetamines, gives ascorbic acid as the example of an acidifying agent that decreases blood levels, and directs that the capsule dose be adjusted based on clinical response. The interaction table repeats that acidifying agents lower blood levels and efficacy and that the dose should be increased based on clinical response.
How this applies: Exact amphetamine sulfate (RxCUI 81952) as one of the four amphetamine salts in this product; the interaction statement is written for amphetamines as a group and applies to every salt in the capsule.
The instruction is to adjust the amphetamine dose. No ascorbic acid dose, threshold or timing rule is given, and no study is cited.
Source 3: original human pharmacokinetic study
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Healthy adult volunteers.
The elimination kinetics of each isomer were measured under both urine conditions. The difference in half-life between the isomers was greatest under basic urinary pH, and (+)-amphetamine was eliminated faster than the (-)-isomer.
How this applies: Human evidence about amphetamine kinetics under experimentally altered urinary pH. The abstract does not identify the acidifying or alkalinizing agents, so it does not establish the effect of any specific supplement.
Small healthy-volunteer study read as an abstract. The abstract does not give the acidifying or alkalinizing agents, their doses, or the resulting plasma concentrations, and no dietary supplement was tested.
Source 4: original human pharmacokinetic study
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Seven healthy male volunteers.
Between 35 and 44 percent of the dose was recovered in urine as unchanged amphetamine over 24 hours, and amphetamine excretion rose as urine flow increased and as urine pH fell.
How this applies: Original human evidence that a large share of an amphetamine dose leaves the body unchanged in urine and that this share tracks urine pH. It is d-amphetamine, not amphetamine sulfate, and no supplement was involved.
Healthy men, single doses, read as an abstract. The study measured urine rather than blood levels and did not give any supplement or pH-altering agent.
Source 5: systematic literature review of human trials
ebi.ac.uk · Source check Sep 22, 2026
Population: Adults and children aged 6.5 to 76.5 years across 150 experiments and 2,895 participants
Among 150 experiments from 86 studies of many urinary-pH interventions, the oral vitamin C category comprised 5 papers and 7 reported results. Its reported mean pH change was +0.03 units, with none of the 7 results marked statistically significant. The review describes substantial differences in study design, populations and measurement methods.
How this applies: Supplement-only evidence about urinary pH. It does not measure amphetamine, gastrointestinal acidity or absorption, and does not establish the effect of a vitamin C dose on stimulant response.
Literature review of urinary pH studies searched through September 2023, with heterogeneous designs, populations and pH measurements. It does not test gastric acidity or amphetamine pharmacokinetics. An intervention missing from the review is not proof that no study exists.
Source 6: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Ten healthy volunteers and ten patients with infected urine.
Mean urinary pH fell by 0.16 pH units in the volunteers and 0.18 pH units in the patients. A relationship between pH and urinary ascorbic acid appeared only above a high urinary ascorbate concentration, and the authors concluded that vitamin C cannot be recommended for lowering the pH of alkaline urine.
How this applies: Direct measurement of urinary pH after high-dose vitamin C. It does not measure gastrointestinal acidity, amphetamine absorption or blood levels.
Small controlled-diet study read as an abstract, in a language other than English, with urinary pH as the only outcome. Amphetamine was not given and blood levels were not measured.
Source 7: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Forty-seven calcium stone-forming patients and 20 healthy subjects.
Fasting urinary pH did not change after 1 g (5.8 before and 5.8 after) or after 2 g (5.8 before and 5.8 after). Urinary oxalate and a calcium oxalate crystallisation index rose significantly at both doses.
How this applies: Direct human evidence that common supplement doses of vitamin C leave urinary pH unchanged, which limits the urinary limb of the label statement. It says nothing about gastric acidity or amphetamine absorption.
Three-day exposure read as an abstract. Urinary pH was a spot fasting measurement, participants were mostly stone formers, and no amphetamine was given.
Source 8: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Twenty-four adults with recurrent urinary stones and alkaline urine, mean age 60.6 years.
Urinary pH fell significantly from a median 7.6 to 6.9. Eight of the 24 patients developed new stones during a median follow-up of about 23 months, and two had the dose reduced or stopped for new high oxalate excretion.
How this applies: A small uncontrolled retrospective cohort found lower urinary pH during ascorbic acid use in selected stone-forming patients with alkaline urine. It cannot establish baseline pH as the cause of differences between studies or predict an amphetamine interaction.
Retrospective review of a selected group who started with alkaline urine, read as an abstract. There was no control group, and amphetamine was not involved.
Research assessment: · Open full citations ↗
Timing & monitoring
No inspected source establishes an altered vitamin C requirement or a separation interval during amphetamine sulfate treatment. ADDERALL XR provides clinician-directed dose-adjustment advice for acidifying agents; EVEKEO gives the interaction warning without a specific adjustment instruction. Management should be individualized with the prescriber or pharmacist.
- Exact scope
- Ascorbic acid as a supplement at any dose, and vitamin C from food. with Oral amphetamine sulfate, both as the single-entity tablet (EVEKEO) and as one of the four salts in mixed amphetamine salts products (ADDERALL tablets and ADDERALL XR capsules).
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- Absence of identified evidence does not show that nothing changes. No study of vitamin C status or timing during amphetamine treatment was identified in the reviewed searches.
Factors that may matter: Vitamin C dose; Reason for taking vitamin C; Amphetamine dosing schedule.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 22, 2026
Population: People prescribed amphetamine sulfate
The Drug Interactions section states that gastrointestinal acidifying agents, listing guanethidine, reserpine, glutamic acid HCl, ascorbic acid and fruit juices, lower absorption of amphetamines, and that urinary acidifying agents, listing ammonium chloride and sodium acid phosphate, increase the concentration of the ionized form and so increase urinary excretion. It concludes that both groups lower blood levels and efficacy of amphetamines.
How this applies: Exact amphetamine sulfate (RxCUI 81952) as the single active ingredient of this label; the interaction section names the supplement ingredient itself rather than a drug class only.
The label names ascorbic acid but gives no dose, no size of effect, no monitoring plan and no separation interval, and cites no study.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 22, 2026
Population: People prescribed amphetamine sulfate
Section 2.7 states that agents which alter urinary pH can affect excretion and alter blood levels of amphetamines, gives ascorbic acid as the example of an acidifying agent that decreases blood levels, and directs that the capsule dose be adjusted based on clinical response. The interaction table repeats that acidifying agents lower blood levels and efficacy and that the dose should be increased based on clinical response.
How this applies: Exact amphetamine sulfate (RxCUI 81952) as one of the four amphetamine salts in this product; the interaction statement is written for amphetamines as a group and applies to every salt in the capsule.
The instruction is to adjust the amphetamine dose. No ascorbic acid dose, threshold or timing rule is given, and no study is cited.
Source 3: federal dietary supplement fact sheet
ods.od.nih.gov · Source check Sep 22, 2026
Population: General consumer population, no medication co-use data
Vitamin C is also known as ascorbic acid. The daily upper limit from all sources is 2,000 mg for adults, and the sheet states that vitamin C supplements can interact with or interfere with medicines.
How this applies: Establishes that the supplement named Vitamin C is ascorbic acid, and the intake range people take, so the label wording about ascorbic acid can be read against real supplement doses.
A general consumer overview. It does not mention amphetamines, and it gives no interaction statement for this pair.
Source 4: pharmacokinetic review
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Children, adolescents and adults taking amphetamine formulations.
Oral amphetamine is rapidly absorbed with high bioavailability, immediate-release products reach peak concentration in 2 to 3 hours, and the review states that there are few documented pharmacokinetic drug interactions of clinical significance beyond the influence of drug-induced changes in urinary pH.
How this applies: Places the urinary pH mechanism in context for the marketed amphetamine products, including those containing amphetamine sulfate. It is a review rather than an original measurement.
Narrative pharmacokinetic review read as an abstract. It does not test or quantify any dietary supplement.
Research assessment: · Open full citations ↗
Absorption & effectiveness
A 2017 pharmacokinetic review of marketed amphetamine products reported few documented pharmacokinetic drug interactions of clinical significance beyond changes in urinary pH. It did not quantify an effect from vitamin C supplements.
- Exact scope
- Any product that changes gastrointestinal or urinary acidity, including ascorbic acid. with Oral amphetamine sulfate, both as the single-entity tablet (EVEKEO) and as one of the four salts in mixed amphetamine salts products (ADDERALL tablets and ADDERALL XR capsules).
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- A narrative review read as an abstract. It does not quantify any supplement effect.
Factors that may matter: Amphetamine formulation; Urine acidity; Other medicines.
Read the supporting source summaries
Source 1: pharmacokinetic review
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Children, adolescents and adults taking amphetamine formulations.
Oral amphetamine is rapidly absorbed with high bioavailability, immediate-release products reach peak concentration in 2 to 3 hours, and the review states that there are few documented pharmacokinetic drug interactions of clinical significance beyond the influence of drug-induced changes in urinary pH.
How this applies: Places the urinary pH mechanism in context for the marketed amphetamine products, including those containing amphetamine sulfate. It is a review rather than an original measurement.
Narrative pharmacokinetic review read as an abstract. It does not test or quantify any dietary supplement.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 22, 2026
Population: People prescribed amphetamine sulfate
The Drug Interactions section states that gastrointestinal acidifying agents, listing guanethidine, reserpine, glutamic acid HCl, ascorbic acid and fruit juices, lower absorption of amphetamines, and that urinary acidifying agents, listing ammonium chloride and sodium acid phosphate, increase the concentration of the ionized form and so increase urinary excretion. It concludes that both groups lower blood levels and efficacy of amphetamines.
How this applies: Exact amphetamine sulfate (RxCUI 81952) as the single active ingredient of this label; the interaction section names the supplement ingredient itself rather than a drug class only.
The label names ascorbic acid but gives no dose, no size of effect, no monitoring plan and no separation interval, and cites no study.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Editorial update | |
| Editorial source audit clarified label scope, evidence limits and practical wording. No clinical approval was recorded. | |
| Research summary published | |
| Article prepared | |
| Prepared exact amphetamine sulfate and Ascorbic acid article from inspected current labeling and original sources, with uncertainty stated. |
Article revision: 3435df389e007aa6
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.