The grapefruit rule: how vitamin C affects ADHD medication

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

Jun 13, 2022
4
 min read
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 the way you expect, one explanation for ineffective ADHD meds? 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 used to treat ADHD.
  • Amphetamine is prone to increased renal extraction in the presence of vitamin C (ascorbic acid)
  • Amphetamine-based medication is more susceptible to being hindered “ineffective” when ingested with substances containing vitamin C.
Looking for something else?

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.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?

  • 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, you should also be aware of when you consume foods containing this nutrient because ascorbic acid can negatively interact2 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.3 This is due to the increased renal extraction of amphetamines when ascorbic acid is present in the system.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?

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

Let's think back to biology classes—recall anything about the digestive system?

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 chemicals into the bloodstream, occurring through the walls of your digestive tract.

Once absorbed, nutrients and chemicals hitch a ride via the cardiovascular system (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 have their own mechanisms, but their 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.)

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.

If the amphetamines come into contact with ascorbic acid molecules before reaching the adrenal glands or liver (or other organs involved with drug metabolism and the CNS), they'll be less likely 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 at your next bathroom visit.4

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

Vitamin C is vital for your health, so it’s extremely unsafe to avoid it just for the sake of improving medication effectiveness.6

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

  • If you take your vitamins in capsules or 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 don't contain amphetamines) are unlikely 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-based stimulants

Methylphenidate medications are also stimulants, but they're 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

Nonstimulant medication

Because nonstimulant meds use a different mechanism to treat ADHD, their efficacy is unlikely to be immediately affected by vitamin C.

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

  • Wellbutrin
  • Strattera
  • Guanfacine
  • Clonidine

Looking for support?

Inflow can help you thrive with ADHD and reach your full potential. Start your journey now.

Get started

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 the way you expect, one explanation for ineffective ADHD meds? 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 used to treat ADHD.
  • Amphetamine is prone to increased renal extraction in the presence of vitamin C (ascorbic acid)
  • Amphetamine-based medication is more susceptible to being hindered “ineffective” when ingested with substances containing vitamin C.
Looking for something else?

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.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?

  • 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, you should also be aware of when you consume foods containing this nutrient because ascorbic acid can negatively interact2 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.3 This is due to the increased renal extraction of amphetamines when ascorbic acid is present in the system.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?

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

Let's think back to biology classes—recall anything about the digestive system?

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 chemicals into the bloodstream, occurring through the walls of your digestive tract.

Once absorbed, nutrients and chemicals hitch a ride via the cardiovascular system (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 have their own mechanisms, but their 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.)

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.

If the amphetamines come into contact with ascorbic acid molecules before reaching the adrenal glands or liver (or other organs involved with drug metabolism and the CNS), they'll be less likely 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 at your next bathroom visit.4

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

Vitamin C is vital for your health, so it’s extremely unsafe to avoid it just for the sake of improving medication effectiveness.6

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

  • If you take your vitamins in capsules or 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 don't contain amphetamines) are unlikely 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-based stimulants

Methylphenidate medications are also stimulants, but they're 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

Nonstimulant medication

Because nonstimulant meds use a different mechanism to treat ADHD, their efficacy is unlikely to be immediately affected by vitamin C.

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

  • Wellbutrin
  • Strattera
  • Guanfacine
  • Clonidine

Looking for support?

Inflow can help you thrive with ADHD and reach your full potential. Start your journey now by taking our quiz.

Take the quiz