Wednesday, November 19, 2008

Protein and Levodopa Protein and Levodopa

Kathrynne Holden, M.S., R.D.

A combination of levodopa with carbidopa or benserazide, known as the brand name Sinemet, Madopar, and other names, is an important medication used in treating Parkinson’s disease. However, there are some barriers to absorption of regular (quick-release) Sinemet/Madopar by the body.

1) If you take your Sinemet with a meal, or just after a meal, it may take avery long time for the Sinemet to be absorbed.This is because the stomach takes about one to three hours to empty food. If Sinemet is mixed with food, it takes the same amount of time to clear the stomach as the food does.

2) A high-fat meal takes even longer to clear the stomach. Fat is digested very slowly compared to carbohydrate and protein. If Sinemet is taken with a high-fat meal, it is further delayed in clearing the stomach.

3) Protein in the meal is broken down in the intestine into amino acids.These aminos must travel across the intestinal wall to get into the blood.Then they must cross the blood-brain barrier to enter the brain. Sinemet also must transit the intestine and the blood-brain barrier using exactly the same carrier system as the amino acids.

Most meals contain a large amount of protein, and the amino acids use up all the “carriers.” The Sinemet must wait until the carriers are free again, in order to cross over into the bloodstream. The same thing happens when Sinemet tries to get to the brain, where it does its work. Once more, amino acids clog all the “carriers” and Sinemet can’t get through to the brain. Therefore, it’s best to take Sinemet 30 to 60 minutes before eating a meal. This allows the Sinemet to be quickly absorbed before the food can interfere.

PROBLEM: Many people experience nausea when they first begin to use Sinemet. This usually disappears after a few weeks, although some people continue to feel nausea as long as they use Sinemet.

SOLUTION: Take the Sinemet along with some foods that don’t contain protein. Ginger tea is a good choice for many people, because it often “settles the stomach.” A graham cracker or soda cracker along with the ginger tea may help, too — these are very low in protein, and should not interfere with the absorption of Sinemet. You can find ginger tea in health food stores. Ginger ale may also be helpful for some people. If your nausea is not relieved after a few weeks, discuss this with your doctor, who may wish to prescribe an anti-nausea medication. What about Sinemet CR/Madopar HBS?

Sinemet CR (“Controlled Release”) and Madopar HBS and their generic forms, are designed to be released slowly into the blood over a long periodof time, providing a continuous, smooth, supply of levodopa. It was also designed so that it can be taken with a meal. However, it requires more time to become effective than regular Sinemet, and taking it with food means it will be even longer before it takes effect. If you spend a great deal of time in an “off state” (time when medications are not working) then it may be best to take Sinemet CR 30-60 minutes before eating a meal, just as you do regular Sinemet.

On-off fluctuations. In the early stages of PD, the brain continues to produce dopamine, although in reduced amounts. Medications such as the levodopa in Sinemet boost this amount, so a steady supply of dopamine reaches the brain at all times. Later on, the brain ceases to produce dopamine in any significant amount, and must rely totally on Sinemet. This is when “on-off fluctuations” start to occur.

When levodopa begins to take effect and there is a good dopamine response, the person is said to be “on,” functioning and moving well. As the levodopa begins to lose its effect and movement becomes more difficult; the person is said to be “off” or experiencing a “wearing off” phenomenon. These on-off fluctuations are a common problem in patients who have taken Sinemet for several years.

New medications, such as the agonists ropinerole and pramipexole, and the COMT-inhibitor tolcapone, have greatly extended the effectiveness of levodopa, and decreased “off time.” Nevertheless, in advanced PD, fluctuations can still be a problem.

The nutritional concern at this point is the amino acids previously discussed. These must cross the cells of the intestinal walls to get into the blood, and then must cross the blood brain barrier to get into the brain. These amino acids use exactly the same pathway as levodopa to get into the bloodstream and the brain.

Therefore, a meal high in protein combined with Sinemet can seriously interfere with levodopa absorption, particularly at the level of the brain receptors. Research indicates that many people who experience "on-off" fluctuations can benefit by adjusting their protein intake.For those wishing to adjust their protein intake, there are three ways currently considered feasible.

1) Balanced protein plan. This is the plan I highly recommend. With the help of a registered dietitian, determine your protein needs; if you are otherwise healthy, this will be about 1/2 gram of protein per pound of body weight per day. Then, divide this amount equally among three meals, morning, midday, and dinner. For most people, this will result in less protein than the typical western diet provides; also, it will be evenly divided, providing for more consistent levodopa absorption. Be sure to take the levodopa at least 30 minutes before meals; if you need to eat snacks between meals, choose those with little or no protein – fruit, juices, etc.

2) Evening protein. I do not recommend you attempt this plan without the assistance of a registered dietitian. High-protein foods are eaten only in the evening, so that mobility is improved during the day. This plan is not ideal, however, because mobility is greatly reduced during the night time, and many people find they have difficulty turning in bed, or getting up at night. Some people then forego eating any protein in the evening, so as to have better control of PD symptoms throughout the night; such deprivation leads to protein starvation and illness, even hospitalization. If you are extremely protein-sensitive, ask for a referral to a registered dietitian, who can assess your protein needs and help you plan a safe and effective “evening protein menu.”

3) High-carbohydrate (high-carb) plan. Eat meals that consist of a ratioof five-to-seven parts carbohydrate to one part protein (5:1 to 7:1).

In the small intestine, carbohydrate breaks down into glucose, and enters the bloodstream. Protein breaks down into amino acids, which enter the blood stream with glucose. A high ratio of carbohydrate to protein causes a large amount of insulin to be released into the blood. Insulin removes some of the amino acids from the blood and may help lower the competition between aminos and Sinemet.

The high-carb meal plan appears to work well for about two-thirds of the people who try it. It allows small amounts of protein throughout the day, and a more natural menu. It has disadvantages, however:

- it is difficult to understand and plan meals and recipes in such a high ratio

- it is very difficult to devise a menu under 1800 calories per day, and this is too much food for some people

- it is difficult to eat meals away from home – restaurants, friends’ homes, and traveling all pose problems for those wishing to maintain a high-carb diet plan.

- furthermore, a high-carb diet could make some conditions, like diabetes, lung disease, and high serum triglycerides, much worse.

A high-carb menu plan should only be undertaken with the help of a registered dietitian. An RD can determine your individual protein needs, and provide accurate information on the amounts of protein and carbohydrate in foods. It should also be discussed with one's physician first. Some people find it so successful that they may need less levodopa, and your physician needs to work closely with you to determine the correct amount. Otherwise, you might find yourself over medicated.

Other protein-related information. Meat, poultry, fish, milk, cheese, and eggs are all very high in protein. For many people, milk in particular block slevodopa, to a greater extent than other protein-rich foods. To get better results from your Sinemet, use high-protein foods moderately, along with large helpings of fruits, vegetables, and grains.This means that at a meal you should eat a small portion (3-4 ounces) of meat, poultry, fish, cheese, or eggs, accompanied by fruit, vegetables, and bread, cereal, pasta, or other grains.

If milk is a problem for you, a good substitute is a “milk alternative” such as soy or rice milk. Be sure to choose the kinds that are fortified with calcium and vitamin D. Westsoy soy beverage has a fortified version. Rice Dream also carries a fortified version. You can get these products at larger grocery stores or at health food stores.

Carnation Instant Breakfast is inexpensive, and an Instant Breakfast Shakeworks well for most people, as long as it’s made using soy or rice milk, and some fruit. However, it contains a small amount of dried milk, and those who are very sensitive to milk protein may not be able to use Instant Breakfast.

Plant protein is a good choice for part of your protein needs. Plant protein (dried beans, nuts, and seeds) contains a high ratio of carbohydrates to protein, whereas meat, fish, and poultry contain no carbohydrate. It’s a good idea to eat several servings of cooked dried beans, peas, or lentils each week. Legumes have more fiber than any other food. Fiber helps with constipation and is heart-protective as well. Good choices are bean soup, refried beans, three-bean salad, and patties made from soy protein, like Morningstar Farms “Better’n Burgers” or Boca Burgers.You can find these and others in the freezer case at the grocery stores.

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