Acetaminophen, Ibuprofen & Nutrient Depletion
Also searched as Combogesic. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Acetaminophen, Ibuprofen has been associated with depletion of FOLIC ACID and GLUTATHIONE. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Acetaminophen, Ibuprofen long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Acetaminophen, Ibuprofen pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Acetaminophen, Ibuprofen
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
Insufficient EvidenceNONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
Folate-dependent enzymes are inhibited in vitro by NSAIDs with carboxylic acid-containing side chains. The clinical significance of this inhibition is unknown. For information on foods that are rich in folate, see our chart.
Folic acid is a B vitamin your body needs to build healthy cells and support DNA repair. Ibuprofen and similar anti-inflammatory drugs have been shown in lab studies to interfere with enzymes that depend on folate, but whether this actually lowers folate levels in real people is still unclear. The evidence here is genuinely insufficient, so there is no reason to worry right now. If you take ibuprofen regularly over the long term, it is worth mentioning to your pharmacist or doctor just to keep it on their radar.
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)
- Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
- Baggott JE, Morgan SL, Ha T, et al. Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs. Biochem J 1992;282:197-202. 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 help clear out harmful substances. Acetaminophen is the one to know about here: when it breaks down in the liver, that process can use up glutathione, and heavy or long-term use has been linked to lower levels. For ibuprofen, this connection is not well studied. Overall, the evidence is still too thin to know whether this matters clinically for most people, so there is no action needed right now. If you take acetaminophen regularly at higher doses, it is worth a quick conversation with 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, Ibuprofen
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, Ibuprofen & nutrients: FAQs
Does Acetaminophen, Ibuprofen deplete FOLIC ACID?
Should I take a supplement because I take Acetaminophen, Ibuprofen?
Should I stop taking Acetaminophen, Ibuprofen?
Where does this information come from?
Questions about Acetaminophen, Ibuprofen and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Acetaminophen, Ibuprofen 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.