Phenylketonuria (PKU) is a rare genetic disorder that results in excessive accumulation of the amino acid phenylalanine and reduced levels of the amino acid L-tyrosine in the blood.¹ If untreated, high levels of phenylalanine can cause severe mental retardation, behavioral disturbances, and other neurological problems. Eczema, sensitivity to sunlight, light skin, and a body odor described as "mousy" are also characteristic in individuals with PKU.

Fortunately, newborn screening programs now identify most cases of PKU in the United States and other countries. Early diagnosis and treatment is the key to reducing or preventing PKU-related conditions.² Gene therapy is currently being researched as a possible cure.^{3 4} Research is also being conducted on methods to decrease levels of phenylalanine in the blood through the use of certain enzymes⁵ and amino acids.⁶

The effects of elevated phenylalanine appear to be less severe in older children and adults than in newborns and young children, in whom the nervous system is still developing. This, combined with the difficulties inherent in following a strict life-long diet, have caused researchers to examine whether the dietary regimen may be relaxed as children get older. While some of the research suggests that relaxation of dietary measures may not be harmful,^{17 18 19} this has not been found to be true in all studies.²⁰ Therefore, more research is needed to resolve this issue.^{21 22} In a survey of 111 PKU treatment centers, 87% favored life-long dietary restriction of phenylalanine.²³

PKU during pregnancy (maternal PKU) is of particular concern. Excessively high or low levels of phenylalanine may occur during pregnancy, both of which may adversely affect the fetus.²⁴ Maternal PKU can lead to fetal malformations, including small head size (microcephaly), cardiac abnormalities, intrauterine growth retardation and mental retardation.²⁵ Adverse effects on the offspring can be reduced by family planning²⁶ and by careful dietary control both prior to and during pregnancy.^{27 28 29}

Breastfeeding, as opposed to formula feeding, appears to confer some benefits in children born with PKU but not treated until 20–40 days of age. In a preliminary study, children with PKU who had been breastfed rather than formula fed prior to receiving dietary treatment scored significantly higher on IQ testing.³⁰

A PKU diet is low in protein, providing no more than the minimum amount of phenylalanine needed by the body. All high-protein foods, such as dairy products, eggs, fish, meats, poultry, legumes, and nuts, are usually eliminated.³¹ Lower protein foods, such as fruits, vegetables and some grain products, are allowed in measured amounts, along with specially prepared phenylalanine-free or nearly phenylalanine-free foods. This diet is supplemented with an amino acid formula to increase protein intake without adding more phenylalanine than is nutritionally required.

Consultation and follow-up visits with medical and nutritional specialists are necessary for effective monitoring and dietary guidance in PKU. Phenylalanine levels fluctuate as a consequence of changes in diet, health, and growth; therefore, levels must be checked regularly.³² A nutrition specialist can also provide information on homemade and specially prepared PKU foods, including infant formulas, low protein pastas, breads, crackers, and other foods.

Individuals with PKU who are not following the PKU diet can become deficient in biotin, a water-soluble B vitamin. This is because phenylalanine blocks biotin metabolism. In a controlled study of children with PKU, elevated phenylalanine levels resulted in biotin-deficiency seborrheic dermatitis, which was corrected by a return to the phenylalanine-restricted diet.³³

There is debate about whether it is safe for people with PKU to consume aspartame, a low-calorie sweetener that contains about 50% phenylalanine. In one study, blood levels of phenylalanine increased only slightly after people with PKU ingested a 12-ounce soft drink sweetened with aspartame.³⁴ However, that study did not address long-term effects of regular aspartame consumption.

In PKU, phenylalanine accumulates in the blood as the result of a deficiency or malfunction of the enzyme phenylalanine hydroxylase, which under normal conditions converts phenylalanine to L-tyrosine.³⁵ Consequently, individuals with PKU are low in L-tyrosine,³⁶ which may contribute to behavior problems.^{37 38} In addition, low L-tyrosine levels in pregnant women with PKU may contribute to fetal damage.³⁹ In some,⁴⁰ but not all,⁴¹ double-blind studies, keeping tyrosine levels in the normal range by adding supplemental tyrosine to the diet improved behavior. In a preliminary study, plasma L-tyrosine levels were found to undergo significant fluctuations in individuals with PKU, suggesting a need for careful laboratory monitoring of individuals receiving tyrosine supplementation.⁴²

In a controlled trial, regular use of branched-chain amino acids (BCAAs) by adolescents and young adults with PKU improved performance on some tests of mental functioning.⁴³

Individuals with PKU may be deficient in a number of nutrients, due to the restricted diet which is low in protein and animal fat. Deficiencies of long-chain polyunsaturated fatty acids (LC-PUFA’s),^{44 45 46} selenium,^{47 48 49 50} vitamin B12,⁵¹ and vitamin K may develop on this diet.⁵²

Selenium is important for normal antioxidant function. Research suggests that selenium deficiency and decreased antioxidant activity may contribute to the neurological disorders associated with PKU.⁵⁵ In two preliminary studies on selenium-deficient individuals with PKU, supplementation with selenium in the form of sodium selenite corrected the deficiency,⁵⁶ whereas supplementation with selenium in the form of selenomethionine did not.⁵⁷

Because the PKU diet is low in animal products, fat intake is also significantly reduced. The results of a preliminary study on children with PKU suggested this reduced fat intake may impair the absorption of vitamin K from the diet, possibly resulting in a deficiency of this vitamin. In that study, children with PKU on a strict diet had low levels of certain vitamin K-dependent proteins that are needed for normal blood clotting.⁵⁸

Vitamin B12 is a nutrient found primarily in foods of animal origin, which are restricted on the PKU diet. Individuals on the PKU diet who are inconsistent in their use of a vitamin B12–containing PKU supplement may become deficient in this vitamin. In a survey of 37 young adult PKU patients, 12 of 37 (32%) were found to have low or low-normal blood levels of vitamin B12.⁵⁹

Information about the effects of a particular supplement or herb on a particular condition has been qualified in terms of the methodology or source of supporting data (for example: clinical, double blind, meta-analysis, or traditional use). For the convenience of the reader, the information in the table listing the supplements for particular conditions is also categorized. The criteria for the categorizations are: "Primary" indicates there are reliable and relatively consistent scientific data showing a health benefit. "Secondary" indicates there are conflicting, insufficient, or only preliminary studies suggesting a health benefit or that the health benefit is minimal. "Other" indicates that an herb is primarily supported by traditional use or that the herb or supplement has little scientific support and/or minimal proven health benefit.

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