Editor's note: This article was updated on September 21, 2023
It’s well understood that drug interactions exist for just about every medication, but the specifics of ADHD medication interactions are still a bit of a mystery. There are plenty of warnings out there about the overuse and abuse of such medications, but there’s not enough talk about the variables that can lower the effectiveness of drugs like Adderall, Ritalin, and Vyvanse.
While there are many reasons why your prescription medication may not work the way you expect, one explanation for ineffective ADHD meds? Vitamin C, or ascorbic acid. If you've heard of "The Grapefruit Rule" with regard to ADHD stimulants, this is the scientific explanation you've been looking for.
⚕️ Medical disclaimer: This article provides information only. It should not replace professional medical advice. Consult your healthcare provider before making changes to your medication regimen or considering supplements like vitamin C. Grapefruit and other citrus fruits can interfere with prescription medicines, which can lead to serious—sometimes life-threatening—health problems. Please consult a healthcare professional to determine if it's safe to consume grapefruit or other citrus products while taking your medication. The content may not include the latest research, and Inflow cannot be held responsible for any consequences resulting from the use of this information. Your reliance on this content is at your own risk.
Too long; didn’t read
- Grapefruit and grapefruit juice can interfere with some prescription medications, either by increasing or decreasing the absorption of the drug into the bloodstream.
- Grapefruit specifically is known to block the actions of certain enzymes that break down drugs in the body, which can be extremely dangerous.
- Medications containing amphetamine (such as Adderall) may be less effective if taken with foods or beverages containing vitamin C.
- If you take stimulant ADHD medication, hold off on your morning glass of orange juice for an hour to avoid ineffective treatment.
Grapefruit, CYP3A4, and drug interactions
Grapefruit juice can significantly impact the way your body breaks down (metabolizes) different drugs and medications taken orally. It can also reduce the effectiveness of certain medications.
Absorbing too much of a drug
Generally speaking, grapefruit juice increases drug absorption in the bloodstream by blocking the action of the enzyme CYP3A4 in the small intestine, which is responsible for metabolizing various medications. This increase in absorption is not a good thing.
Enzyme levels vary from person to person, meaning that everyone metabolizes drugs at different rates, and, as a result, grapefruit juice can have different effects on people, even if they take the same dose of the same drug. 1
⚛️ Science translation? Consuming grapefruit with certain medications makes your body process the meds differently. Instead of breaking it down, more of the drug enters your bloodstream and stays in your body longer, potentially leaving excessive amounts of the drug in your system.
Medications that may be prone to this effect include:
- Antiarrhythmics, like Cordarone (amiodarone; treat irregular heartbeats)
- Anticoagulants, like Coumadin (warfarin; blood thinners)
- Antiplatelet medications, like clopidogrel and ticagrelor (blood clot prevention)
- Anxiolytics, like BuSpar (buspirone; anti-anxiety medications)
- Budesonide (anti-inflammatory corticosteroids that treat Chron's or ulcerative colitis)
- Calcium channel blockers (treat high blood pressure)
- Cytotoxic drugs (used in cancer treatment)
- Immunosuppressive drugs, like cyclosporin, sirolimus, and tacrolimus
- Statins, like Lipitor (cholesterol-lowering drugs) 2
ℹ️ Looking for more information about grapefruit and its potentially dangerous effects on certain medications?
- Click here to view a resource provided by the FDA.
- Click here to view a resource provided by the NHS.
Not absorbing enough of a drug
As mentioned, grapefruit juice is known to interact with certain medications in a way that leads to higher levels of those drugs in the body. However, scientists have recently discovered a different effect with a few other medications:
Grapefruit can decrease absorption and reduce the effectiveness of some medications.
When we consume certain medications, transporters play a crucial role in helping them into our body's cells. But if you've recently had a glass of grapefruit juice, the transporters can be blocked, preventing them from delivering the full dose to the appropriate cells. Consequently, this will make the medication less effective.
And it's not just grapefruit juice that can reduce medication absorption; orange juice and apple juice can have similar effects, along with other foods and drinks containing higher amounts of vitamin C, aka ascorbic acid, as well as other chemicals in these juices, like glutathione. 3
Medications that may be less effective with vitamin C include:
- Amphetamines (ADHD medications like Adderall)
- Antihistamines, like Allegra (fexofenadine)
What is vitamin C?
Vitamin C, also known as ascorbic acid, is an important nutrient and antioxidant used to synthesize connective tissues and strengthen the immune system. Vitamin C is not made or stored by your body, which is why it’s important to include it in your diet on a daily basis.
Which foods contain vitamin C?
- Brussels sprouts
- Grapefruit and grapefruit juice
- Lemons and lemonade
- Oranges and orange juice
- Peppers (bell and chili)
- Seville oranges
Does vitamin C affect ADHD medication?
Consuming foods rich in vitamin C is important for a balanced diet. However, it's crucial to be mindful of the timing, as ascorbic acid may interact adversely with amphetamines, which are commonly used to treat ADHD.
Vitamin C has the potential to exhibit similar behavior to adrenergic compounds when it interacts with specific receptor regions in the body. 3 Adrenergic compounds are substances that affect the adrenergic system, which is related to adrenaline and norepinephrine. By interacting with these receptors, vitamin C may influence the functioning of amphetamine-based medications like Adderall, making them less effective. 4
Research suggests that ascorbic acid may decrease the effectiveness of Adderall and other amphetamines due to the way it interferes with the medication's absorption in the bloodstream. 4
The exact mechanism behind this interaction is still a topic of debate among scientists. One theory suggests that the acidity of ascorbic acid overrides the alkalinity of the medication, resulting in reduced efficacy. If this is true, it would mean that other stimulant medications containing methylphenidate, such as Ritalin and Concerta, would be similarly influenced by vitamin C.
Alternatively, some speculate that vitamin C has a magnetic effect on amphetamines and prematurely eliminates them from the body through urine.
Regardless of the specific mechanism, both hypotheses align on the same thing: Vitamin C can decrease the efficacy of stimulant medications used to treat ADHD. 4,5
So, I can't have vitamin C at all if I take Adderall?
Everyone should include vitamin C in their diet! However, if you're currently taking an ADHD medication that has amphetamine or dextroamphetamine, you should probably avoid drinking a big glass of orange juice with your morning dose. Otherwise, the effectiveness of your ADHD medication can be compromised, which is a concern for those who struggle with executive dysfunction every day.
💡 Pro tip! As a general rule of thumb, you should wait at least one hour before taking your medication if you've just had something high in vitamin C, and vice versa.
Worsened medication side effects
Scientists have also noted that ingesting too much vitamin C too close to the time Adderall is taken can increase the likelihood of experiencing common negative side effects of the drug.
ADHD medication side effects that can be exacerbated by too much vitamin C:
- Anxiety and nervousness
- Mood swings and irritability
- Difficulty falling and staying asleep
It's worth noting that these interactions aren't necessarily dangerous like those mentioned above in the CYPA34 section: Absorbing too much of a drug.
Vitamin C is a natural source of energy and is involved in the production of important neurochemicals and hormones, such as adrenaline. 6 By default, ascorbic acid is a good thing. In fact, taking vitamin C in modest doses - and at the right time - can offer benefits when it comes to amphetamine concentration in your bloodstream.
Ascorbic acid or vitamin C can:
- Help speed up the elimination of the drug from your system at the end of the day, which may be especially helpful for those who struggle with medication-induced insomnia.
- Effectively "flush out" any extra amphetamine salts in the blood, potentially reducing the likelihood of developing a drug dependence.
- Improve one's appetite (if the decreased appetite was originally caused by ADHD medication)
Tips and warnings
How to safely consume vitamin C
- Vitamin C is vital for your health, so it’s extremely unsafe to avoid it just for the sake of improving medication effectiveness. (Otherwise, you could end up with a vitamin C deficiency or scurvy!)
- Make sure to read the Drug Facts label on your medication. It should indicate if you need to avoid consuming grapefruit or other fruit juices while taking it.
- If you're unsure if you can consume grapefruit with your ADHD medication, ask your doctor or pharmacist. They can provide you with the necessary information and ensure your safety.
How to make sure your ADHD medication is effective
- If you take your vitamins in capsules or pills and they contain vitamin C, wait until midday or evenings to take them.
- Consider skipping the glass of orange juice on the mornings you take your stimulant medication.
- If you consume anything with vitamin C in the morning, wait at least one hour before taking your medication.
- After taking your medication, wait at least one hour before consuming anything with vitamin C.
Vitamin C and other ADHD medications
Other ADHD medications (i.e. those that don't contain amphetamines) are less likely to be affected by ascorbic acid in the same way as Adderall. However – like with all information presented here – it’s always a good idea to check with your doctor before making decisions about your diet or treatment regimen.
Methylphenidate medications, while also stimulants, have a higher acidity compared to amphetamines. If we consider the theory regarding bases and acids, it's highly probable that they're less affected by the inhibitory impact of vitamin C. However, you should still speak with your doctor if you have concerns.
Common methylphenidate medications used to treat ADHD include:
- Jornay PM
Nonstimulant medication and vitamin C
Because non-stimulant meds use a different mechanism to treat ADHD, their efficacy is unlikely to be negatively affected by vitamin C. In fact, vitamin C may even improve symptoms if taken with an antidepressant,7 which is the drug classification of several non-stimulants.
Common non-stimulants or antidepressants used to treat ADHD include (but are not limited to):
- Wellbutrin (bupropion)
- Strattera (atomoxetine)
- Guanfacine (brand name: Intuniv)
- Clonidine (brand names: Catapres and Kapvay)
1 Clinical Pharmacology and Therapeutics | Physiologically Based Pharmacokinetic Modeling of Bergamottin and 6,7-Dihydroxybergamottin to Describe CYP3A4 Mediated Grapefruit-Drug Interactions (2023)
2 Fabad Journal of Pharmaceutical Sciences | Interaction of Statins with Grapefruit Juice (2023)
3 International Journal of Molecular Sciences | Glutathione and Glutathione-Like Sequences of Opioid and Aminergic Receptors Bind Ascorbic Acid, Adrenergic and Opioid Drugs Mediating Antioxidant Function: Relevance for Anesthesia and Abuse (2020)
4 Dodson, William A. | ADHD Medication Information Sheet (2016)
5 Arh Hig Rada Toksikol | Effect of urine adulterants on commercial drug abusescreening test strip results (2020)
6 Nutrients | Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020)
7 Psychology & Psychotherapy | Effect of Ascorbic Acid on Mental Depression Drug Therapy: Clinical Study (2014)