top of page

Off Periods

The 2020 Kyowa Kirin care partner survey showed that while nine out of ten Parkinson's care partners are optimistic about Parkinson's treatments, just as many feel that managing medication, gauging when it stops, working, and knowing how to help with pharmacological treatments can be significant challenges.

Everyone with Parkinson's responds to medications differently, and your person's routine is unique to them. However, knowing that Carbidopa/Levodopa is the gold-standard treatment for Parkinson's, we want to offer advice about how to help your loved one get the most out of it if it's part of their medication regimen.

For more about Parkinson's medications - the most current, in-depth lists of drug names, side effects, contraindications, and additional information - be sure to head to the Medications section of this site under Treatments and Therapies.

Levodopa and ON Times

Levodopa acts to help with slowness, stiffness, and tremor and can be used in conjunction with other medications to address the same symptoms. Carbidopa is almost always combined with levodopa to enable more levodopa to reach the brain. It is also added to control nausea, which is a side effect of levodopa.

Although the terms ON and OFF have been used to describe responses to levodopa therapy for more than 50 years, there is still no universally agreed-upon definition for the term OFF. OFF periods occur when a person's Parkinson's medication isn't working optimally, and their motor and non-motor symptoms return. OFF is much more nuanced than this, but understanding its scientific causes can help you help your person with Parkinson's minimize it in their daily life.

Levodopa - a central nervous system agent - helps minimize symptoms because it is converted to dopamine in the brain. OFF times take place when levodopa is no longer working well enough to suppress Parkinson's symptoms. What, though, causes levodopa to stop working optimally, and what can you do to help your loved one with Parkinson's get the most from their medicine? Here, we explore some of the science behind "OFF" times and strategies that will help maximize "ON" times so your loved one can live their best life with Parkinson's.

Water and ON Times

To make its way from the mouth to the brain, levodopa must travel from a person's stomach to their small intestine, where it is absorbed by an extensive neutral amino acid active carrier system. A similar transport system transfers levodopa across the blood-brain barrier to the brain, where it is metabolized to produce dopamine. The more quickly levodopa reaches the small intestine, the faster it passes through the intestinal walls and the brain's carrier system. The quicker it converts to dopamine, the more quickly your person with Parkinson's will feel ON.

Movement disorder specialist Cherian Karunapuzha, MD says the key to minimizing delayed and partial ON times is to take levodopa on an empty stomach with a full glass of water. The water "flushes" the medicine quickly to the small intestine, and the absence of food in the stomach means nothing can slow its emptying. (Tip: crushing or chewing carbidopa/levodopa or drinking it with sparkling water can also speed the process.) Ideally, your person with Parkinson's would take each dose of levodopa one hour before a meal (to give it time to move from the stomach to the small intestine) or two hours after (the amount of time it takes for food to empty in the stomach). because this is not always possible, especially as a person's Parkinson's progresses and they take levodopa more often, encourage your loved one to take each dose at least 30 minutes before or 30 minutes after a meal--and, again always with a tall glass of water.

Protein and ON Times

The system that transports levodopa from the small intestine to the brain is the same system that transports amino acids. Both levodopa and amino acids must enter the bloodstream through the intestinal wall and then cross the blood-brain barrier to compete" with the amino acids for absorption, and it won't enter the carrier system quickly. Similarly, some amino acids compete with levodopa for absorption in the brain. Their presence when levodopa makes its way to the blood-brain barrier will delay the time it takes for the brain to transform the medication to dopamine and therefore, decrease the medication's efficacy. This, too, can lead to delayed or only partial ON times.

In the stomach, protein is broken down into amino acids, which then travel to the small intestine. For a person's levodopa to work most effectively, it should enter their small intestine when few amino acids are present; this gives it easy access to the carrier system and fewer obstacles to crossing the blood-brain barrier. To maximize ON times, your person with Parkinson's should try to avoid eating protein close to when they take their levodopa.

Constipation and ON Times

Constipation can also play a significant role in levodopa absorption and ON/OFF fluctuations. In the digestive system, food makes its way from the mouth to the large intestine through the alimentary canal esophagus, stomach, and small and large intestines). When a person's intestines aren't being emptied regularly, the levodopa they take won't make its way through the digestive system as it should, and it cannot control dietary changes that will minimize constipation. Having regular bowel movements means an in-depth look at how to manage constipation, a very common non-motor symptom of Parkinson's.

Parkinson's Progression and ON/OFF Fluctuations

Although the half-life of levodopa is short (one to one-and-a-half hours), in the first stages of Parkinson's, there is sufficient synthesis and storage of dopamine in the brains striatal neurons to keep Parkinson's symptoms at a minimum despite few doses of levodopa. However, as Parkinson's progresses, the brain produces less dopamine. This means it must rely entirely on levodopa to control Parkinson's symptoms. Yet as Parkinson's progresses, many people begin to experience fewer benefits from the medications, and the benefits may also be less consistent. This can increase wearing OFF periods and ON/OFF fluctuations.

As a care partner, you should talk with your person's physicians about how their Parkinson's -- including the frequency and severity of OFF times - has changed over time. In addition to dietary modifications, various adjustments can be made to their medication regimen to limit ON/OFF fluctuations and extend ON times. For some people, deep brain stimulation (DBS) or other surgical therapies can be effective ways to reduce OFF times as Parkinson's progresses. Ask your person's physicians what options might work for your person.


The Davis Phinney Foundation. Page 69. My person with Parkinson's has more frequent off periods than they did a few years ago .How can I help? Every Victory Counts for Care Partners. "Manual." Sixth Edition, 2021.

bottom of page