Questions and Answers about LNAA Use

by Prof. John Christodoulou, Head, Genetic Metabolic Disorders Service and Director, Western Sydney Genetics Program, The Children’s Hospital at Westmead, Sydney, Australia

From the Winter 2008 issue of National PKU News

There are a number of LNAA products recently on the market. They include Lanaflex (Nutricia/SHS International), PheBloc (Applied Nutrition), and PreKUnil and NeoPhe (both from Solace Nutrition). Each of the US distributors of LNNA products emphasizes that combining traditional PKU formula with a strict low protein diet is the best way to treat PKU. The LNAA products are an option to be used only as a “last resort”: that is, when blood phe levels are chronically excessively elevated despite formula and a low protein diet, or when the person is off the diet and is not able to return to it.

Your editor asked the three US distributors of LNAA products a series of questions to help dispel confusion over their use. Following on page 3 is a compilation of their responses:

Q: Are the LNAA products FDA- approved?

They are considered a PKU “medical food,” which does not require FDA approval. Thus, while the product are deemed “safe” for consumption, there are no guarantees of effectiveness for treating PKU.

Q: Do you need a prescription for purchasing the LNAA products? Will insurance companies reimburse the cost?

Patients have to be under medical supervision. Pharmacies will most likely ask for a prescription, but a prescription in the strict sense is not needed. These products are covered by insurance, just like traditional PKU formula, but reimbursement will depend on the specific policy and state; if patients order directly from any of the companies, they will need on file an updated consent form or prescription form from your clinician.

Q: Are there major differences between the various LNAA products?

Form and nutrient composition. All of the LNAA products except Lanaflex are in pill form. Lanaflex comes as an orange flavored powder to be mixed in water. Lanaflex is the only LNAA product containing vitamins, minerals and trace elements. Two stick packs provides the majority of vitamins and minerals recommended for adults.

In summer 2007, PreKUnil was reformulated to contain the amino acid, lysine (it was formerly deficient) as well as folic acid, vitamin B6, vitamin B12, and biotin.

The same amino acids are included in these preparations, but the concentrations vary.

PheBloc is virtually identical to PreKUnil but has a different coating that makes it easy to swallow.

Clinical response. Lanaflex has been clinically shown to have a “positive impact on brain function.” Clinical research studies on PreKUnil have shown a decrease in the influx of phe to the brain. Additionally, studies on PKU mice given PreKUnil showed a decline in blood phe concentrations. NeoPhe is the one LNAA product that has been clinically proven in humans to inhibit the transport of phe from the gut into the blood, causing blood phe levels to decrease somewhat. For patients who consume large amounts of natural protein, however, no decrease in blood phe may occur.

Q: What is the typical dosage?

Lanaflex: Recommended dosage is 0.8 gm per kg body weight (three stick packs for most patients). More than 3 stick packs per day may be indicated for patients consuming increased amounts of whole protein. Clinicians who wish to prescribe more may do so with careful monitoring, i ncluding behavioral changes.

PheBloc and PreKUnil: Recommended dosage is weight-dependent, 0.5 tablet per kg/day. For example, 60 kg (132 lb.) X 0.5 = 30 tablets.

NeoPhe: Starting dosage is 1 tablet/kg/day, adjusted as needed, up to 2 mg/kg/day. For example, 60 kg (132 lb.) X 1-2 = 60- 120 tablets.

Q: What is the cost of the LNNA products?

Lanaflex. 40-15.8 gm stick packs, $119
PreKUnil. Each 550-tablet bottle, $250.
NeoPhe. Each 550-tablet bottle, $250.
PheBloc. Each 550-tablet bottle, $202. This may vary depending on how it is purchased.

Q: What are suitable ages for using the products?

PheBloc is recommended for age 13 and older. NeoPhe and PreKUnil are designed “for people who are able to swallow tablets.” The researchers feel that age 8 and older is appropriate. In Denmark, where there is most experience (with PreKUnil), recommended age is 18 and older.

Lanaflex is indicated for adults over age 18.

Q: Can pregnant women use LNAA products?

No. The LNAA products are not intended for use by pregnant women with PKU, where very low blood phe levels are imperative for optimal outcome in the baby.

The LNAA products can be used by women during childbearing age; however, it is strongly recommended that such women maintain their classic phe-restricted diet or use birth control.

Q: How often must LNAA products be taken?

Lanaflex. Each time a meal is consumed, with the tablets taken throughout the meal, dividing the dose into before the meal, during the meal, and after the meal (typically one stick pack with a meal three times per day). Take with meals containing food protein. Mix one stick pack with 2 fl. oz. cold water for a low-volume “shot.”

PreKUnil, NeoPhe, and PheBloc. Spread intake of the tablets throughout the day. The general recommendation is to divide the daily dose by 3 and take prior to each meal.

Q: How do you monitor LNAA effectiveness?

The main purported effect of LNAA therapy is reduction in brain phe levels for all of the products except NeoPhe (which also can reduce blood phe levels). The most direct way to monitor brain phe levels would be to use magnetic resonance spectroscopy (MRS). However, this method is reasonable only in patients with very high blood phe levels, as well as being very expensive and not readily available. Some clinicians have used indirect measures of effectiveness, using brain function and neuropsychological tests. However, the “bottom line” is that it is very difficult to measure effectiveness of these products.

Dr. Richard Koch says his research shows that it is helpful to maintain a blood phe level no higher than 15 mg/dl while taking the LNAA products, since when the level is above 20 gm/dl, the brain phe levels rise significantly. Too much dietary phe will limit the effectiveness of the LNAA preparations in reducing brain phe levels.

Q: Are there any known side effects?

There are no known side effects associated with the use of these products, except as described in the research story on page 3 (increased anxiety level in some patients). Side effects are not well studied, but are not anticipated because the LNAAs are a part of natural protein.

Lanaflex is not recommended for individuals taking “serotonergic” medications for depression or anxiety, since the relatively large tryptophan content might interact with psychotropic drugs in over stimulating the brain serotonin system.

Q: How are the LNAA preparations prescribed for individual patients?

The clinic will first calculate how much total dietary protein is required for health maintenance. They will then prescribe the recommended amount of the LNAA product, based on age and weight, which will be subtracted from the total dietary protein. The difference will determine how much food protein (the source of dietary phe) is required.

It is important to note that use of an LNAA preparation does NOT mean patients are allowed a total relaxation of the diet. It is imperative that the clinician carefully calculates how much food protein/phe is allowed in the diet. Too much food protein and phe will limit the effectiveness of the LNAA preparations in reducing brain phe levels.

The diet should be rich in fruits and vegetables, whole grains, and may include some dairy and limited intake of meat/fish. The diet recommendation will depend on phe tolerance of the individual. Some people have been able to decrease their blood phe levels to goal range after running high blood phe levels for years and also have been able to decrease low protein foods and traditional PKU formula.