Acetaminophen, Aspirin, Caffeine & Nutrient Depletion
Also searched as Excedrin Migraine, Excedrin, Excedrin Extra Strength. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Acetaminophen, Aspirin, Caffeine has been associated with depletion of FOLIC ACID, VITAMIN C, POTASSIUM and VITAMIN B12 and 1 more. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Acetaminophen, Aspirin, Caffeine long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Acetaminophen, Aspirin, Caffeine pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Acetaminophen, Aspirin, Caffeine
Each record below is shown as published in our licensed clinical database, with its evidence rating and citations. Expand a section for food sources and talking points.
FOLIC ACID
Insignificant DepletionASPIRIN
Aspirin may decrease serum folate levels by reducing binding to plasma proteins, especially when large doses are taken regularly (e.g., for treatment of rheumatoid arthritis). But there doesn't seem to be an increase in urinary folate losses and red blood cell levels remain normal. This suggests folate is being redistributed in the body and deficiency isn't likely. For information on foods that are rich in folate, see our chart.
Folic acid is a B vitamin your body needs to make new cells and keep your DNA in good shape. Aspirin, one of the ingredients in this combination, belongs to a class of drugs that may interfere with certain folate-dependent enzymes, at least in laboratory studies, though whether that translates to a real drop in folate levels in actual patients is simply not known yet. The evidence here is rated insufficient, meaning researchers have not gathered enough data to say this is a meaningful concern for most people. If you take this medication regularly and want peace of mind, a quick conversation with your pharmacist or doctor is the easiest next step.
What Folic acid (folate) does & food sources
Folate is needed for cell division, red blood cell formation, and healthy fetal development.
Common food sources:
- Leafy green vegetables
- Beans, lentils, and peas
- Fortified grains and cereals
- Citrus fruits
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Ask your provider whether folate monitoring or supplementation is appropriate for you — this matters most before and during pregnancy, and with long-term use of certain seizure or arthritis medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Folate needs are individual. With some medications (for example, methotrexate), folic acid is often prescribed deliberately on a specific schedule — follow your prescriber's instructions rather than adding your own.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: High-dose folic acid can mask vitamin B12 deficiency, so the two are often evaluated together.
Learn more about this nutrient: Folic Acid — uses, safety & interactions
References (2)
- Lawrence VA, Loewenstein JE, Eichner ER. Aspirin and folate binding: in vivo and in vitro studies of serum binding and urine excretion of endogenous folate. J Lab Clin Med 1984;103:944-8.
- Alter HJ, Zvaifler NJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid and aspirin. Blood 1971;38:405-16. DOI
VITAMIN C
Insignificant DepletionASPIRIN
Aspirin reduces tissue and leukocyte uptake of vitamin C, leaving more in the plasma to be filtered into the urine and increasing elimination. It may also reduce absorption of vitamin C from the gut. These effects are dose-related. Vitamin C supplementation has been suggested for people taking high-dose aspirin long-term. Supplements aren't needed with the low doses of aspirin used for cardiovascular indications.
Here's something worth knowing: the aspirin component in this combination can affect how your body handles vitamin C, which supports your immune system, skin, and healing. Aspirin appears to interfere with how cells take up vitamin C and may also limit how much is absorbed from the gut, causing more of it to pass out through the urine. That said, the evidence rates this as insignificant for most people, especially at the low aspirin doses found in headache combinations. If you happen to take high-dose aspirin regularly over a long period, it's worth mentioning to your pharmacist or doctor.
What Vitamin C does & food sources
Vitamin C is an antioxidant that supports the immune system, collagen formation, and iron absorption.
Common food sources:
- Citrus fruits
- Bell peppers
- Strawberries and kiwi
- Broccoli and Brussels sprouts
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Frank vitamin C deficiency is uncommon with a varied diet. If your diet is limited and you take an associated medication, ask your provider whether your intake is adequate.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Vitamin C is water-soluble and generally low-risk at food-level intakes; very high supplemental doses can cause stomach upset and may not add benefit.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Learn more about this nutrient: Vitamin C — uses, safety & interactions
References (5)
- Loh HS, Wilson CW. The interactions of aspirin and ascorbic acid in normal men. J Clin Pharmacol 1975;15:36-45. DOI
- Sahud MA, Cohen RJ. Effect of aspirin ingestion on ascorbic-acid levels in rheumatoid arthritis. Lancet 1971;1:937-8. PubMed
- Wilson CW, Greene M. The relationship of aspirin to ascorbic acid metabolism during the common cold. J Clin Pharmacol 1978;18:21-8. PubMed
- Basu TK. Vitamin C-aspirin interactions. Int J Vitam Nutr Res Suppl 1982;23:83-90.
- Johansson U, Akesson B. Interaction between ascorbic acid and acetylsalicylic acid and their effects on nutritional status in man. Int J Vitam Nutr Res 1985;55:197-204.
POTASSIUM
Moderate DepletionMETHYLXANTHINES
Methylxanthines like theophylline can reduce serum potassium levels, possibly by increasing intracellular uptake of potassium. Hypokalemia is most likely to occur after acute overdose of these drugs. However, reduced potassium levels can occur with therapeutic doses, and the incidence and degree of hypokalemia increases with increasing serum theophylline levels. Monitor potassium levels in people with other risk factors for hypokalemia. For information on foods that are rich in potassium, see our chart.
The caffeine component in this combination product belongs to a family of compounds called methylxanthines, and there is decent evidence that methylxanthines can nudge potassium levels downward by prompting your cells to pull more potassium inside them, which lowers the amount circulating in your blood. Potassium is a mineral your heart, muscles, and nerves all count on to work properly. This is rated as moderate, meaning it is worth paying attention to, especially if you have other reasons your potassium might already run low. If you take this product regularly, it is a reasonable thing to bring up with your pharmacist or doctor.
What Potassium does & food sources
Potassium keeps nerve signals, muscle contractions, and heart rhythm working normally.
Common food sources:
- Bananas and citrus fruits
- Potatoes and sweet potatoes
- Beans and lentils
- Tomatoes and leafy greens
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
Potassium is routinely checked with basic blood work. If you take a medication associated with potassium loss (like some diuretics), ask your provider how often your electrolytes should be monitored.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
Do not start potassium supplements on your own. Both low and high potassium can affect heart rhythm, and several common medications (ACE inhibitors, ARBs, potassium-sparing diuretics) raise potassium.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: Potassium supplementation can be dangerous in kidney disease or alongside potassium-raising medications — this is a decision for your prescriber, guided by lab results.
Learn more about this nutrient: Potassium — uses, safety & interactions
References (5)
- Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
- Crane J, Burgess CD, Graham AN, Maling TJB. Hypokalemic and electrocardiographic effects of aminophylline and salbutamol in obstructive airways disease. NZ Med J 1987;100:309-11. DOI
- Zantvoort FA, Derkx FHM, Boomsma F, et al. Theophylline and serum electrolytes (letter). Ann Int Med 1986;104:134-5. PubMed
- Braat MCP, Jonkers RE, Bel EH, Van Boxtel CJ. Quantification of theophylline-induced eosinopenia and hypokalamia in healthy volunteers. Clin Pharmacokinet 1992;22:231-7..
- Flack JM, Ryder KW, Strickland D, Whang R. Metabolic correlates of theophylline therapy: a concentration-related phenomenon. Ann Pharmacother 1994;28:175-9.. PubMed
VITAMIN B12
Moderate DepletionASPIRIN
Clinical research suggests that using aspirin is associated with a higher prevalence of vitamin B12 deficiency when compared with nonusers. For information on foods that are rich in vitamin B12, see our chart.
Vitamin B12 is something your nerves and red blood cells genuinely depend on, so keeping levels steady matters. The aspirin in this combination is the piece of concern here: research has found that regular aspirin users show a higher rate of low B12 compared to people who do not take it, possibly because aspirin can interfere with how well the stomach and small intestine absorb the vitamin. With a moderate rating, this is not something to dismiss, but it also does not mean everyone taking this medication ends up with a problem. If you use this combination regularly over the long term, it is worth bringing up with your pharmacist or doctor to see whether your B12 level should be checked.
What Vitamin B12 does & food sources
Vitamin B12 supports red blood cell formation, nerve function, and DNA synthesis.
Common food sources:
- Meat, poultry, and fish
- Eggs and dairy products
- Fortified cereals and nutritional yeast
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
What to discuss with your clinician
If you take an associated medication long-term, ask your healthcare provider whether checking a vitamin B12 level (sometimes with methylmalonic acid) is appropriate — especially if you notice fatigue, numbness, tingling, or memory changes.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Supplement considerations
B12 status is easy to check and low levels are usually straightforward to address, so testing before supplementing is often the sensible order. High-dose folic acid can mask a B12 deficiency, which is one reason B12 and folate questions are best sorted out together with your provider.
Do not start or stop medications or supplements without professional guidance — supplements can interact with prescription medications.
HelloPharmacist pharmacist-reviewed education — separate from the licensed record above.
Caution: B12 deficiency can look like other conditions — do not self-diagnose from symptoms alone.
Learn more about this nutrient: Vitamin B12 — uses, safety & interactions
References (1)
- van Oijen MG, Laheij RJ, Peters WH, et al. Association of aspirin use with vitamin B12 deficiency (results of the BACH study). Am J Cardiol. 2004 Oct 1;94(7):975-7. PubMed
GLUTATHIONE
Insufficient EvidenceACETAMINOPHEN
Chronic or excessive acetaminophen has been associated with low levels of glutathione. Usually a cysteine containing supplement is used to replenish glutathione. Cysteine is converted to glutathione in the body.
Glutathione is an antioxidant your body makes naturally to protect cells from damage, and the liver leans on it heavily to break down acetaminophen safely. When large or repeated doses of acetaminophen are processed, the liver can burn through its glutathione supply faster than it can rebuild it. That said, the evidence here is rated insufficient, meaning we simply do not know yet whether this matters for people taking a normal, occasional dose of this combination product. If you use acetaminophen regularly or in higher amounts, it is worth mentioning that to your pharmacist or doctor.
Learn more about this nutrient: Glutathione — uses, safety & interactions
References (1)
- Herzenberg LA, De Rosa SC, Dubs JG, et al. Glutathione deficiency is associated with impaired survival in HIV disease. Proc Natl Acad Sci USA 1997;94:1967-72. PubMed
This tool is educational and is not a substitute for professional medical advice. An association is not a diagnosis and does not mean a deficiency will occur. Always talk to your pharmacist or healthcare provider before starting, stopping, or changing any medication or supplement.
Disclaimer: This checker finds which nutrients might be depleted by prescription or over-the-counter medications. Each nutrient depletion issue is rated based on clinical significance. Use your own professional judgment prior to making clinical decisions.© 2026 Therapeutic Research Center Licensed records refresh weekly · last updated July 3, 2026.
More about Acetaminophen, Aspirin, Caffeine
What drug-induced nutrient depletion means
Some medications can, over time, lower the levels of certain vitamins, minerals, or other nutrients — through reduced absorption, increased loss, or changes in how the body uses them.
Association is not deficiency
An entry here means a depletion has been reported or studied — not that it happens to everyone, or that you are deficient. Dose, duration, diet, and your own health all matter.
Evidence varies by pair
Some drug–nutrient links (like metformin and vitamin B12) are well studied; others rest on limited or preliminary research. Each entry shows the evidence rating from our licensed clinical database.
When to ask about labs
If you take an associated medication long-term, ask your healthcare provider whether monitoring is appropriate for you. Not everyone needs testing — your provider can weigh your dose, duration, and symptoms.
Don't self-supplement blindly
Supplements are not risk-free: some can interact with medications, and some (like potassium or magnesium) can be risky with kidney disease. Talk to your pharmacist before adding anything.
Never stop a medication over this
These medications are prescribed for good reasons, and the benefit usually far outweighs a manageable nutrient consideration. Any change belongs in a conversation with your prescriber.
Food first, usually
For many nutrients, a varied diet covers the gap. Each entry lists common food sources; a supplement is a decision to make with your pharmacist or provider, not a default.
Acetaminophen, Aspirin, Caffeine & nutrients: FAQs
Does Acetaminophen, Aspirin, Caffeine deplete FOLIC ACID?
Should I take a supplement because I take Acetaminophen, Aspirin, Caffeine?
Should I stop taking Acetaminophen, Aspirin, Caffeine?
Where does this information come from?
Questions about Acetaminophen, Aspirin, Caffeine and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Acetaminophen, Aspirin, Caffeine are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for drug-induced nutrient depletions, supplements, and interactions — the basis for this page.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for medication overviews across the site.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.