Aspirin, Caffeine, Orphenadrine & Nutrient Depletion
Also searched as Norgesic Forte, Invagesic, Invagesic Forte. What the clinical evidence reports, what it may mean, and what to discuss with your pharmacist.
Aspirin, Caffeine, Orphenadrine 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, Orphenadrine long-term, worth raising with your pharmacist or healthcare provider.
Take more than one medication? Open the checker with Aspirin, Caffeine, Orphenadrine pre-loaded and add the rest to see overlapping nutrient signals.
Reported nutrient depletions with Aspirin, Caffeine, Orphenadrine
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 uses to build new cells and keep DNA healthy. Some research done in lab settings suggests that aspirin, because it contains a carboxylic acid structure, might interfere with certain enzymes that depend on folate, but this has not been shown to matter in real patients. The evidence here is simply too limited to know whether this combination has any meaningful effect on your folate levels in practice. If you take this medication long term and have concerns, it is worth mentioning to your pharmacist or doctor at your next visit.
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.
Vitamin C is something your immune cells and connective tissues depend on, and aspirin, the active pain reliever in this combination, can nudge your body to excrete more of it through the urine while also reducing how much gets absorbed in the gut. That said, this effect tends to be dose-related, meaning it matters most at high, long-term aspirin doses rather than the lower amounts typically found in combination products like this one. For most people, this is considered an insignificant depletion and no supplement is needed. If you take high-dose aspirin regularly or have concerns, it is worth a quick conversation 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)
- 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.
Caffeine belongs to a chemical family called methylxanthines, and one known effect of these compounds is that they can nudge potassium, a mineral your muscles and heart depend on for normal rhythm and function, to shift from the bloodstream into your cells. This can quietly lower the amount of potassium circulating in your blood. At normal doses the effect is usually modest, but it is worth paying attention to if you already have other reasons your potassium might run low. Long-term users, or anyone with kidney concerns or taking other medications that also affect potassium, would do well to mention this to their 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 it is worth paying attention to. Regular aspirin use has been linked in clinical studies to a higher chance of low B12 levels compared to people who do not take it, though the exact reason is not fully settled. Some researchers think aspirin may interfere with how the stomach processes and absorbs B12 from food over time. Because this is rated as a moderate concern, long-term users of this combination should bring it up with their pharmacist or doctor, since some people do end up needing a supplement.
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
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 Aspirin, Caffeine, Orphenadrine
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.
Aspirin, Caffeine, Orphenadrine & nutrients: FAQs
Does Aspirin, Caffeine, Orphenadrine deplete FOLIC ACID?
Should I take a supplement because I take Aspirin, Caffeine, Orphenadrine?
Should I stop taking Aspirin, Caffeine, Orphenadrine?
Where does this information come from?
Questions about Aspirin, Caffeine, Orphenadrine and your nutrition?
Ask a licensed pharmacist — free, no appointment needed.
Sources & How We Checked
Nutrient depletion records for Aspirin, Caffeine, Orphenadrine 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.