Levodopa and Protein – What About It?
Kathrynne Holden, MS, RD (retired)
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.
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?
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. 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. 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 protein and levodopa?
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.