Levodopa molecule

Levodopa and Protein – What About It?

Levodopa and Protein – What About It?

Kathrynne Holden, MS, RD (retired)

levodopa molecule.

What is levodopa?

Levodopa is a precursor of dopamine. First discovered in fava beans in the early 1900s, today levodopa is a mainstay in Parkinson treatment. Why? By the middle of the 1900s, scientists realized that neurons in the brain produced dopamine, which then guided the body’s movements. Later they found that in some people these neurons were gradually dying off, leading to dopamine deficiency and Parkinson’s disease. They could give dopamine by mouth, but it could not cross the blood-brain barrier, so it was useless if swallowed.

By 1961, however, research showed that levodopa – a precursor to dopamine – could cross the blood-brain barrier. Once there, the brain converted the levodopa to dopamine, where it treated the symptoms of PD – tremor, slowed movement, poor balance, shuffling gait. All were improved by use of levodopa. A few years later, scientists developed a pill form of levodopa to treat PD and it was hailed as a miracle.

It was, and still is, the standard medication used to treat PD. It improved movement, balance, and walking ability; it decreased tremor, allowing people to continue their work and hobbies.

However, there were significant problems. Researchers soon learned that:

– its effects didn’t last long
– it caused severe nausea
– combining levodopa and protein was a problem – breakdown products of protein competed with levodopa for absorption from the small intestine.

Carbidopa molecule
After more research, scientists developed two compounds, carbidopa and benserazide, that, when combined with the levodopa, “protected” it to a large extent from competition with protein. So, in the mid-1970s, the pill was combined with carbidopa (in the United States) and benserazide (in Europe and other countries).

Since that time, new formulations continue to improve levodopa’s effectiveness. Sinemet CR is an extended-release form that can be taken with meals. Stalevo has an added COMT inhibitor that helps it last longer. Rytary (an extended-release form), Duodopa (delivery via pump directly into the small intestine), and Parcopa (does not need to be taken with water, it dissolves on the tongue) are some of the newer forms.

For some people, though, the levodopa and protein combination still can be a problem, even with the newer forms. Not everyone is protein-sensitive, especially in the early stages of PD. But some people are very sensitive to protein from the beginning of levodopa use; and for others, protein becomes more of a problem in later stages of PD. Let’s take a look at why this happens.

What exactly is protein?

Foods rich in protein
Foods rich in protein

Protein is a long strand of amino acids. Nine of these are called “essential amino acids.” They are essential for human life, because our liver cannot make them. Foods that contain the greatest amount of essential amino acids are animal foods – meat, poultry, fish, eggs, and dairy foods. These contain all the nine essential aminos needed for human life, and are called “complete protein.” Most plant foods contain some, but not all, of the essential aminos, and are called “incomplete protein.” However, combining different plant foods gives us complete protein. Eating a combination of legumes (beans, peas, lentils), grains, nuts and seeds will give us all the essential aminos needed for health.

Why is protein a concern for those using levodopa?

When we eat protein – meat, for example – the stomach grinds it up into tiny particles and sends it to the small intestine. Enzymes there break down the meat protein strands into their individual amino acids.

Twenty basic amino acids.
There are twenty standard amino acids.
Then, special carriers in the intestine attract the aminos and carry them across the intestinal wall to the bloodstream. There are different carriers for the different amino acids, and this is where the problem begins.

Levodopa is also broken down into individual molecules. The carriers for levodopa are the same as the carriers for the “large neutral amino acids” – leucine, isoleucine, valine, phenylalanine, tryptophan, tyrosine, methionine, histidine. The meat we ate contains a large number of these aminos, whereas a levodopa pill has a much smaller amount of levodopa molecules.

So, when you eat a hamburger at the same time as taking levodopa, the intestinal carriers receive an avalanche of large neutral aminos, but only a tiny amount of levodopa. The carriers can be swamped by all the aminos, so that the levodopa must wait its turn. And, because levodopa has a short lifespan, its useful life may be nearly over by the time it’s absorbed into the blood and arrives at the brain.

This is why the levodopa and protein combination can cause problems, and why many people need to take levodopa about 30 minutes before meals. It has a clear path through the stomach and out of the small intestine, before the aminos arrive.

Types of protein

Animal protein is often more of a concern than plant proteins, though not always. Each individual can be unusually sensitive to a particular protein. One person may be affected most by dark turkey meat, another by ham, another by beef, eggs or sausage.

There is one protein, however, that seems to block levodopa to a greater extent, and for a longer time than other types – milk protein.

Milk protein may block levodopa more severely than other proteins
Milk protein may block levodopa more severely than other proteins
Of all the people I’ve talked to in over twenty years of counseling, more people have named milk as the food that blocks levodopa absorption the most severely. Many say that if they have milk on their cereal in the morning, levodopa won’t work for the rest of the day. The protein in milk is especially rich in the large neutral amino acids, and this may be why it’s a greater concern.

What about the different kinds of milk?

Cows’ milk and milk from goats and sheep are the types of milk most often used. All three are high in large neutral aminos, although they have different proportions of each. It may be an individual matter whether one kind of milk affects a person more than another type.

Why are some people affected by protein more than others?

There is no perfect answer to this question. Some people are unaffected by any kind of protein, while others are sensitive to certain proteins, but not others. Still others have some degree of sensitivity to all kinds of protein. Why? We can only speculate. Perhaps some people have a higher number of intestinal carriers receptive to these aminos, and thus are not so sensitive to milk or other proteins blocking levodopa.

What’s the best way to manage levodopa and protein?

Many people experience nausea when they first start using levodopa. So at first, it’s best to take levodopa with food, either with a meal, or with some crackers and juice. Usually, our bodies adapt to the levodopa in a few weeks, and then most people can take their levodopa about 30 minutes before meals. If you find that protein in food doesn’t block levodopa, you can certainly take it with meals.

It’s also good to be aware, though, that PD can slow the movement – “peristalsis” – of the gastrointestinal tract. When the stomach’s peristalsis is slowed, food may remain there for an abnormally long time. A high-fat meal can take as long as four to six hours to exit the stomach. Any levodopa taken while the stomach is full of food will be unable to exit into the small intestine; the levodopa must wait until the stomach clears. This can cause “motor fluctuations” – periods of time when PD medications are not working. If this is the case, talk to your neurologist, or a dietitian who can help you plan lower-fat, smaller meals that clear the stomach quickly.

A last, scary, thought

One of the scariest questions I hear, over and over down through the years, is: “Can you give me a list of foods that contain protein so I can avoid them?”

Of course I could provide a list of foods with protein. But, because I’m a health professional, the answer must be ‘No.”

Such a list would be equivalent to a recipe for death. Protein is absolutely necessary for human life. Every day your body must build new cells – blood, skin, muscles (including the heart), hair, organs – and enzymes, such as the insulin you produce to store glucose from the food you eat.

You require about ½ gram of protein per pound (about 1 gram per kilogram) of body weight per day, to restore and repair these cells. Without protein, your body would begin to devour its own muscles and organs, a condition called “protein-energy malnutrition.”

Today’s medications are far improved over the early days of levodopa. Timing of levodopa and foods goes a long way toward eliminating or minimizing off times. If you have signs of gastroparesis (slowed stomach emptying), such as acid reflux, lack of appetite at normal meal times, feeling full after only a few bites of food, burping, or heartburn, ask your doctor to assess the possibility of gastroparesis, which can be treated.

You don’t need to overdo protein intake, which the western diet often does. You just need to eat enough protein to meet your daily needs, and time your levodopa so that it wins the race with protein to the small intestine.

If you have any questions or thoughts, put them in the “Comments” section on this page, and I’ll respond. I hope to hear from you.

Comments 26

  1. Nick B.
    January 8, 2017

    How about protein supplements like whey protein powder and similar products typically used when working out.

    I follow a pretty brutal workout regime to fight my PD and find that getting enough protein can be a challenge.

    1. khadmin
      January 9, 2017

      Good for you for choosing exercise to fight PD! Yes, you definitely need ample protein, and whey protein is a good source. Be aware, though, that whey is a concentrated source of three of the amino acids that compete with levodopa for absorption, particularly leucine. While this stimulates muscle protein synthesis, it may interfere with your Sinemet absorption. I would experiment cautiously; it may be necessary to take the whey protein well apart from levodopa, depending on your personal sensitivity to protein. Let us know how it works for you!

  2. Rob
    January 9, 2017

    Should someone with PD be eating large amounts of fava) broad beans?

    1. khadmin
      January 9, 2017

      Good question, Rob. Here is an article I wrote about fava beans that should help: http://nutritionucanlivewith.com/2016/06/fava-beans-levodopa-parkinsons-disease/
      Let me know if this did not answer your question.

  3. Ivor
    January 9, 2017

    I was wondering if the protein in milk products such as yoghurt and cheese are in the same category as milk?

    1. khadmin
      January 9, 2017

      The proteins are the same in yogurt – casein and whey; the milk sugars have been changed, but not the protein. .

      In cheesemaking, the whey is drawn off, so the remaining protein is largely caseins. There are some of the large neutral aminos – mainly alanine, glycine, valine, methionine, leucine and isoleucine.

      Some people find they can tolerate cheese better than milk, with regard to levodopa absorption; but this seems to be highly individual.

  4. Andrew
    January 9, 2017

    Thanks for the info. I wondered as to the reason for the LevaDopa/protein incompatibility, which I have noticed first-hand.

    1. khadmin
      January 9, 2017

      You’re very welcome, Andrew; and good for you for taking note of foods vs levodopa absorption. Diet can make a tremendous difference in motor fluctuations / off time, and you’re doing exactly the right thing in keeping track.

  5. Connie Swanson
    January 9, 2017

    Have you heard of the starch diet by Dr John a McDougall? I have PD and I’m considering doing this diet. What do you think?

  6. Karen Dean
    January 9, 2017

    Thank you KH for this detailed explanation.
    You do a wonderful job relaying the latest PD info.
    Thank you and HAPPY HEALTHY 2017.

    1. khadmin
      January 10, 2017

      Karen, you just made my day! I so appreciate your thoughts and kindness, and wish you a happy, healthy, and prosperous New Year!

  7. Lori
    January 14, 2017

    Thanks for sharing with with the RD community. Do you have any idea Kathryn about similar effects (diminished response) w Mirazipine (or Ropinerol) similar meds used for Restless Leg Syndrome?

    1. khadmin
      January 14, 2017

      Hi Lori, do you mean could protein be blocking absorption of mirtazapine and/or ropinerole? Protein should not have an effect on either medication. For restless leg, I would be certain the person has had complete testing for blood levels of iron; also would consider trying magnesium supplements if deficiency of Mg is a possibility.

  8. walaa
    January 24, 2017

    what about coconut oil?any benefit for Parkinson patients?

    1. khadmin
      January 25, 2017

      Hi — There is no research that is specific to PD; but virgin coconut oil appears to be heart-protective, and in animal studies, was protective against stress, which is very common in PD. It is a medium-chain triglyceride, which is metabolized differently than other types of saturated fats, and can be used directly for energy; it may be somewhat protective against Alzheimer’s disease, although there isn’t enough research to make any strong conclusions. However, it has been used for centuries in tropical countries as both food and medicine, believed to have antibacterial, antiviral, antioxidant, and immunostimulating properties. Used in moderation, it should be a fine addition to the daily diet.

  9. Jane
    January 28, 2017

    My husband takes sinemit every 2 hours during day. It is hard to get enough protein in diet since even small amounts affect his med absorption. Any suggestions? Jane

    1. khadmin
      January 29, 2017

      Hi Jane, this is a difficult situation for sure. First, has his neurologist discussed use of one of the longer-lasting forms of levodopa, such as Stalevo or Rytary? That would cut down on the number of times daily that he needed to take his levodopa, and make it easier to time his meals.

      Another thing that helps some people is use of “Liquid Sinemet.” Dissolving the sinemet makes it take effect much, much faster than swallowing the pill, so that meals can be eaten sooner. For the instructions on making liquid Sinemet, go to: http://www.parkinson.org/pd-library/books/medications

      You can order a copy of the booklet, or download the entire booklet as a pdf, or go to Appendix C page 73 and print out just the page with the “Formula for Liquid Sinemet.”

      Next, is the question – why does he need to take levodopa so often? Certainly this does happen as PD advances; but his doctor should also rule out:

      1) gastroparesis (slowed stomach emptying) which is very common in PD and makes food stay in the stomach longer than normal. This means that the next dose of levodopa cannot be absorbed, because it can’t pass by the food in the stomach. So motor complications occur, and the Sinemet is increased to compensate. But if gastroparesis is the problem, it can be managed by changing the diet.

      2) Prolonged constipation is also very common in PD, and can block levodopa absorption. If constipation lasts more than 3 days, ask his doctor about a laxative, such as Miralax, to relieve it. He may then find that his medications are more effective.

      Let me know if you have other questions, and my very best to you and your husband. -Kathrynne
      P.S. An article that might be of interest: Reconsidering Coenzyme Q10 in Parkinson’s Disease http://www.naturalmedicinejournal.com/journal/2016-02/reconsidering-coenzyme-q10-parkinsons-disease

  10. Tami Keith
    March 1, 2017

    Kathryn; I was actually ‘browsing’ your site when we had a patient who stated Rytary had gluten in it. I work at a Neurology clinic in Nashville Tennessee and we deal with Rytary alot. Never knew it had Gluten in it. My comment actually is that you have a person whom you communicate alot with ‘Michael’, who had stated that his Rytary was too expensive after Humana. I am wondering if he tried going to the MY RYTARY website and filling out the registration forms. We have all our patients do this and they can provide financial assistance to patients AFTER the insurance pays. BIG SAVINGS. The doctors office should have the forms to send to the manufacturer to get the process started. IMPAX is the manufacturer.

    Just wanted to help. Thank you Tami K. LPN

    1. khadmin
      March 2, 2017

      Tami, thanks so much for your comments. I have heard from a number of people that Rytary is too expensive for them. Thanks so much for the information on MY RYTARY, I will make sure everyone knows about this resource, it may make it possible for more people to obtain this useful medication.

      I was not aware that Rytary contained gluten — I have seen the list of inactive ingredients, and it does not appear there. If you see the patient again, could you find out where s/he obtained the information? I would definitely like to know if this is indeed the case, as quite a few people have leaky gut or gluten sensitivity.

      Thanks again for your very helpful comments, I hope to hear from you again! -Kathrynne

  11. John Tyne
    March 7, 2017

    Personally I haven’t had a problem with Sinemet or carbolev and protien. But what I have discovered is that cannabis, be it an oil taken orally or smoked, it is far more effective than any prescribed medication at controlling the symptoms of PD

    1. khadmin
      March 7, 2017

      Thanks for your comments, John — I’ve heard similar comments from others, and hope more study is given to the use of cannabis for PD.

  12. KT
    March 8, 2017

    How long should one wait after or before eating protein if they are taking carbidopa/levodopa. i just started March 1st and the instructions read ‘do not take with high protein foods. so, what’s considered ‘high’? is it best to take it on an empty stomach?

    1. khadmin
      March 9, 2017

      Usually, if you take levodopa with plenty of water/liquid 30 minutes before a meal, that’s enough time for the levodopa to dissolve and clear the stomach into the small intestine before the meal enters the stomach. For most people a snack of 5-6 grams of protein won’t interfere with levodopa. But a meal that has 20+ grams protein usually will interfere. You have started Sinemet quite recently — do you experience any nausea? If so, take the Sinemet with meals for awhile, until your body adapts; then take about 30 minutes before meals. I hope this is helpful. Let me know if this did not fully answer your question.

  13. Alice
    March 30, 2017

    Thank you for this! Best answer to the issues of protein and levodopa I’ve been able to find. Thank you for posting in Purely Parkinson’s!

    1. khadmin
      March 31, 2017

      You’re most welcome, Alice, I hope it’s helpful.

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