Drug-induced nutrient depletion

Aspirin, Caffeine & Nutrient Depletion

Also searched as Anacin. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.

4Nutrient associations
Insignificant DepletionHighest rating
The bottom line

Aspirin, Caffeine has been associated with depletion of FOLIC ACID, VITAMIN C, POTASSIUM and VITAMIN B12. This does not mean a deficiency will occur — it means these are worth knowing about and, if you take Aspirin, Caffeine long-term, worth raising with your pharmacist or healthcare provider.

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The evidence

Reported nutrient depletions with 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 Depletion

ASPIRIN

Aspirin might affect folate protein binding and affect folate excretion; however, this is not likely to be clinically significant.

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.
Taking Aspirin, Caffeine? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Folic acid is a B vitamin your body uses to build healthy red blood cells and support cell growth. Aspirin appears to nudge folate out of its normal spot on certain blood proteins, which can nudge measured levels in the bloodstream a bit lower, particularly at higher doses taken long-term. Even so, the folate seems to simply redistribute within the body rather than truly disappear, and red blood cell levels stay normal. This is rated insignificant, meaning most people taking this combination do not need a supplement, but if you have concerns your pharmacist or doctor can take a look.

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)
  1. 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.
  2. Alter HJ, Zvaifler NJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid and aspirin. Blood 1971;38:405-16. DOI

VITAMIN C

Insignificant Depletion

ASPIRIN

Aspirin might reduce levels of vitamin C.

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.
Taking Aspirin, Caffeine? A supplement is not needed for most patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Vitamin C is something your immune cells and tissues depend on for repair and fighting off illness. Aspirin appears to interfere with how well those cells hold onto vitamin C, which can push more of it out through the urine rather than keeping it where the body needs it. That said, this interaction is rated insignificant at the low doses most people take for heart health, so the average person following a typical aspirin regimen does not need to worry about it. If you are on high-dose aspirin long-term for any reason, it is worth bringing up with 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)
  1. Loh HS, Wilson CW. The interactions of aspirin and ascorbic acid in normal men. J Clin Pharmacol 1975;15:36-45. DOI
  2. Sahud MA, Cohen RJ. Effect of aspirin ingestion on ascorbic-acid levels in rheumatoid arthritis. Lancet 1971;1:937-8. PubMed
  3. Wilson CW, Greene M. The relationship of aspirin to ascorbic acid metabolism during the common cold. J Clin Pharmacol 1978;18:21-8. PubMed
  4. Basu TK. Vitamin C-aspirin interactions. Int J Vitam Nutr Res Suppl 1982;23:83-90.
  5. 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 Depletion

METHYLXANTHINES

Methylxanthines can decrease serum levels of potassium.
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.
Taking Aspirin, Caffeine? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Caffeine belongs to a chemical family called methylxanthines, and one well-recognized effect of these compounds is that they can push potassium out of the bloodstream and into cells, which lowers the level circulating in your blood. Potassium is a mineral your heart, muscles, and nerves depend on to work properly. This is rated as a moderate concern, meaning it is worth paying attention to, especially if you use caffeine regularly or already have other reasons your potassium might run low. Worth a quick conversation with your pharmacist or doctor if you are a long-term user.

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)
  1. Ellenhorn MJ, et al. Ellenhorn's Medical Toxicology: Diagnoses and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams & Wilkins, 1997.
  2. 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
  3. Zantvoort FA, Derkx FHM, Boomsma F, et al. Theophylline and serum electrolytes (letter). Ann Int Med 1986;104:134-5. PubMed
  4. 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..
  5. 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 Depletion

ASPIRIN

Aspirin might reduce levels of vitamin B12 and increase the risk of deficiency.

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.
Taking Aspirin, Caffeine? Monitor for depletion; a supplement is needed for some patients. ⓘ
Dr. Brian Staiger, Pharm.D explains

Vitamin B12 is something your body needs to keep your nerves working properly and to build healthy red blood cells. Research has found that people who use aspirin regularly tend to have lower B12 levels than those who don't, though exactly why isn't fully pinned down. It may have to do with how aspirin affects the stomach lining and your body's ability to absorb B12 from food over time. Because this is rated as a moderate concern, long-term aspirin users are worth watching, so it's a good idea to bring this up with your pharmacist or doctor and ask whether your levels 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)
  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
Important

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.
Understand the basics

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.

Common questions

Aspirin, Caffeine & nutrients: FAQs

Does Aspirin, Caffeine deplete FOLIC ACID?
Aspirin, Caffeine has been associated with lower FOLIC ACID levels in the clinical literature — see the evidence rating and details above. An association is not a guarantee: dose, duration, diet, and your own health all matter. If you take Aspirin, Caffeine long-term, ask your healthcare provider whether checking your FOLIC ACID status is appropriate.
Should I take a supplement because I take Aspirin, Caffeine?
Not automatically. The right first step is usually a conversation with your pharmacist or provider — they can weigh your dose and duration, decide whether testing makes sense, and recommend food-first strategies or a supplement if genuinely needed. Some supplements can interact with medications, so do not add one without checking.
Should I stop taking Aspirin, Caffeine?
No — never stop a prescribed medication because of a nutrient association. Aspirin, Caffeine is prescribed for good reasons, and nutrient considerations are usually manageable with monitoring or diet. Any change to your medication belongs in a conversation with your prescriber.
Where does this information come from?
The depletion records come from the Natural Medicines (Therapeutic Research Center) database — an evidence-graded clinical reference — and are displayed as published, with their citations. The plain-English context is written and reviewed by licensed HelloPharmacist pharmacists.

Questions about Aspirin, Caffeine and your nutrition?

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Sources

Sources & How We Checked

Nutrient depletion records for Aspirin, Caffeine are evidence-graded and sourced from the Natural Medicines database, and are displayed as published with their citations.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.