The grapefruit rule: how vitamin C affects ADHD medication

Step away from the orange juice, and no one gets hurt.

original image from inflow - a wooden table with citrus fruits (grapefruit, orange, lime, lemon) and a variety of pills

It’s well understood that drug interactions exist for just about every medication, but the specifics of ADHD medication interactions are widely unknown. There are plenty of warnings about the overuse 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 medication may not work in the way you expect, one of the most common explanations for ineffective ADHD medications is Vitamin C, or ascorbic acid. If you've heard of "The Grapefruit Rule", this is the scientific explanation you've been looking for.

Too long; didn’t read

Adderall and Vyvanse are amphetamine-based stimulant medications that are used to treat ADHD. Because amphetamine is a strong alkaline (base), it is susceptible to being hindered “ineffective” by vitamin C (ascorbic acid), which acts as a magnet for amphetamines.

Moral of the story: don’t ingest vitamin C within an hour (before and after) of taking your stimulant medication. I also made a video on the science of ADHD medication back when I was striving to be a YouTuber - for anyone that prefers watching videos to reading articles.

Looking for something else?

What is vitamin C?

Vitamin C, also known as ascorbic acid, is an important nutrient and antioxidant your body uses to synthesize connective tissues and strengthen your immune system, among other functions.[1] Vitamin C is not made or stored by your body, which is why it’s important to consistently include it in your diet.

Which foods contain vitamin C?

Vitamin C is mostly found in foods containing citrus (citric acid)[2], but other foods have this vitamin as well.

Common sources of vitamin C include:

  • Oranges and orange juice
  • Broccoli
  • Grapefruit and grapefruit juice
  • Lemons and lemonade
  • Cabbage
  • Tomatoes
  • Brussels sprouts
  • Strawberries
  • Kale
  • Bell peppers and chili peppers
  • Cantaloupe
  • Parsley
  • Kiwi
  • Papayas

ADHD medication and ascorbic acid

A person's hand holding a pill with orange slices in the background
Photo by Polina Tankilevitch

While it’s crucial to include vitamin C in your diet each day, it’s also important to be aware of when you consume foods containing this nutrient because ascorbic acid is known to negatively interact[3] with amphetamines - a drug commonly used to treat ADHD.

Which ADHD medications are affected by vitamin C?

To date, the only ADHD medications known to interact with vitamin C are those containing amphetamine and/or dextroamphetamine. This is due to the high alkalinity of amphetamine-based medications, as well as their tendency to be attracted to ascorbic acid.[4]

These medications include:

  • Adderall XR (extended release)
  • Adderall IR (immediate release)
  • Dexedrine
  • Evekeo
  • Vyvanse (Elvanse)*
  • ProCentra
  • Zenzedi
  • Adzenys XR-ODT
  • Dyanavel
  • Mydayis 

*The initial drug form (pro-drug) in Vyvanse is lisdexamfetamine; however, it's metabolized by the liver and "turned into" dextroamphetamine.

How does vitamin C interfere with amphetamines?

Chemistry 101: acids and bases

Gradient map titled "pH scale". The scale is from "0" on the left, to "14" on the right. "7" is in the middle. O is acidic, 14 is basic, and 7 is neutral. Above the gradient bar are "vitamin c" on the far left, and "amphetamines" on the far right "
pH scale: acids and bases. Photo by Inflow

Think back to your high school chemistry class, and you may recall lessons on acids and bases. Acids are on the lower end of the pH scale, while bases (alkalines) are on the higher end. In the middle of the scale is the number “7”, which indicates neutrality – neither basic nor acidic.

To simplify, strong acids neutralize strong bases, and vice versa.

Biology 101: Nutrient absorption into the bloodstream

Diagram. Title: human digestive system. Shows structures from esophagus to colon.
The human digestive system. Photo by Inflow

Now let’s think back to biology classes — recall anything about the digestive system? If not, here’s a quick review:

When we consume things (food, medicine, etc.) they're transported to the stomach to await complete digestion. Part of this digestion process involves the absorption of nutrients and/or chemicals into the bloodstream, which occurs through the walls of your digestive tract.

Once absorbed, nutrients and chemicals hitch a ride via the cardiovascular system (AKA your bloodstream), where they’re eventually transported to their destination.

Final destination: the Central Nervous System

Put simply, stimulant medications target your Central Nervous System, or CNS.[5] Each of the different types of stimulants may have their own mechanisms, but their final destination is the same - the brain. However, because the medications are first absorbed into the bloodstream, they don’t act on the CNS right away. (This is why it can take up to two hours for some people to feel the effects of stimulant medication.)

And before absorption, amphetamines travel along the digestive tract along with whatever else you may have in your system at the time, which leaves time for interactions.

Title = absorption: without vitamin c. Image 1: stomach with a pill inside. Image 2: blood vessel with pill inside. Image 3: Brain with pill near it. Image 4: Brain with sparkles around it.
Amphetamine medication absorption - without vitamin C. Photo by Inflow

Enter: vitamin C, a strong acid with the ability to attract bases — and neutralize them.

If the amphetamines come into contact with ascorbic acid molecules before they reach the adrenal glands or liver (or other bodily structures or organs involved with drug metabolism and the Central Nervous System), they will be unable to reach the brain and work effectively.

What’s left of the amphetamine may be able to have some effect on the brain, but most of it is transported to the kidneys and flushed out during your next bathroom visit.[6]

Title = absorption with vitamin c. Image 1: stomach with pill and orange inside. Image 2: orange using a magnet to attract pill. Image 3: kidneys with pill inside. Image 4: toilet.
Amphetamine medication absorption: with vitamin C. Photo by Inflow

How to make sure your ADHD medication is effective

As mentioned, vitamin C is a vital nutrient for your health, so it’s extremely unsafe to avoid it just for the sake of improving the effectiveness of your medication.[7] But there are ways to take your medicine and still get the recommended amount of vitamin C.

Here are a few tips for taking ADHD medication with food:

  • If you take your vitamins in capsules/pills, 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
  • When you take your medication, wait at least one hour before consuming anything with vitamin C

Other ADHD medications

Other ADHD medications (i.e. those that do not contain amphetamines) are not  likely to be affected by ascorbic acid in the same way that Adderall is. However – like with all information presented here – it’s always a good idea to check with your doctor before making any decisions about your diet or treatment regimen.

Methylphenidate-based stimulants

Methylphenidate medications are also stimulants, but they are more acidic than amphetamines, making them less susceptible to the hindrance effect of vitamin C.

Common methylphenidate medications used to treat ADHD include:

  • Ritalin
  • Concerta
  • Daytrana
  • Quillivant
  • Methylin
  • Aptensio
  • Jornay PM
  • Contempla

Non-stimulant medication

Because non-stimulant medications use an entirely different mechanism to treat ADHD, their efficacy is unlikely to be immediately affected by vitamin C.

Common non-stimulants that are used to treat ADHD include[8] (but are not limited to):

  • Wellbutrin
  • Strattera
  • Guanfacine
  • Clonidine

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