Essential Fatty Acids and the PKU Diet

By Anita MacDonald, Consultant Dietitian in Inherited Metabolic Disorders, Birmingham Children’s Hospital, Steelhouse Lane, Birmingham, UK

From the Fall 2007 issue of National PKU News

I would like to report on an international study that was led by Dr Margaret Cleary, Consultant Pediatrician, who is now working at Great Ormond Street Hospital for Sick Children in London. PKU centers from France and from the UK recruited patients into this study. It aimed to investigate if essential fatty acids added to non-phenylalanine protein substitute (PKU formula) could improve the important longer chain fatty acid status in PKU. Longer chain fats are important for brain and retinal (eye) function. First, some background information on fatty acids.

Fatty Acid Primer

Fat is essential in the diet. It is a necessary component of cell membranes in the brain, immune cells, and most other body tissues. Fatty acids are the building blocks of fat or lipid. Two fatty acids, linoleic acid (an omega-6 fatty acid) and alpha-linolenic acid (an omega-3 fatty acid) and are considered essential because they cannot be synthesized by humans. These essential fatty acids are converted to important longer chain fatty acids, providing they are eaten in the diet in the right amounts and proportions. Linoleic acidis converted to arachidonic acid and remains in the omega -6 family of fatty acids. Alpha-linolenic acid is converted to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and remains in the omega-3 family.

What is the Role of Essential Fatty Acids?

Fats are found in complex chemicals such as triglycerides, phospholipids, sphingolipids, and glycolipids. They have several functions:

  • They are important structural components. Phospholipids are part of the membranes that surround all cells in the body.
  • The brain phospholipids contain a high proportion of DHA, suggesting that it is important in central nervous system function. Animal studies have indicated that depletion of DHA in the brain may cause learning deficits.
  • DHA is found in very high concentrations in retinal cell membranes, suggesting it plays an important role in visual function.
  • They are important for the production of hormone-like substances called eicosanoids that regulate numerous body functions including inflammation, pain, and swelling. They also have a role in controlling blood pressure and blood clotting, and are important for allergic reactions.

    • Where are These Essential Fatty Acids Found?

    Omega-6 fatty acids

  • Linoleic acid (omega-6 family) is found in seeds, nuts, grains and legumes. Good sources, especially for the PKU diet, are corn oil, safflower oil, soybean oil, sunflower seed oil, and peanut oil.
  • Arachidonic acid is found in animal fats. Egg yolk contains small amounts of arachidonic acid. Butterfat contains trace amounts.


    • Omega-3 fatty acids

  • Alpha-linolenic acid is found in the green leaves of plants, including algae and in selected seeds, nuts and legumes. Flax oil, rapeseed (canola) oil, walnut oil, and soy oil are all sources of this fatty acid.
  • EPA and DHA are found in mackerel, salmon, herring, sardines, sable fish (black cod), anchovies, albacore tuna (and fish oil), and wild game, none of which are PKU-friendly.

    • Do People with PKU Get Enough Essential Fatty Acids?

    Studies have shown that children with PKU have lower intakes of fat in their diet compared with children on normal diets. There also is evidence that children with PKU take plenty of linoleic acid but small amounts of alpha-linolenic acid. This means that the balance between intake of linoleic and alpha-linolenic acid is suboptimal. Ideally, children should have 5 parts of linoleic acid to 1 part alpha-linolenic acid. Inadequate intake of alpha-linolenic acid may compromise the conversion of alpha-linolenic acid to the longer chain fatty acid, EPA. In addition, sources for the longer chain fatty acids (e.g. EPA and DHA) are limited in low phenylalanine diets. There have now been a few studies which have shown that blood levels of DHA are low in children on the PKU diet.

    Our Study

    There has been much debate on how best to supplement essential fatty acids in the PKU diet. Since the protein substitute is taken three times daily, it would appear a good medium to add essential fatty acids.

    Traditionally, protein substitutes in the UK have not contained fat. However, a protein substitute has been introduced that contains both linoleic acid and alpha-linolenic acid in the recommended proportions of 5:1 linoleic acid to alpha-linolenic acid. This is called Periflex Junior and Advance in the U.S., or Minaphlex or Anamix in the UK and Europe (name differs between countries). Designed for children ages 1-10 years, we evaluated efficacy in our international study.

    Fifty-three children with PKU ages 1-10 years were recruited from four UK and three French metabolic centers. For 20 weeks, half of the children were given a phenylalanine-free protein substitute that contained the essential fatty acids (Group 1); and half were given their usual protein substitute without the essential fatty acids (Group 2). Forty four children completed the study.

    Fat intake increased in Group 1 (the children taking the supplemented protein substitute). Group 1 children had a higher fat intake, providing 32% of calories. Group 2 children (control group) had a fat intake that only provided 24% of their calorie intake. The average fat intake for non-PKU children in the UK is 36% of calories. The children in Group 1 had a higher total intake of alpha-linolenic acid than Group 2, with a ratio of linoleic acid to alpha-linolenic acid of 6.5:1 compared to 10:1 in the control group, including all dietary fat sources. The ideal ratio is estimated to be 5:1.

    At the start of the study, blood fatty acid levels were similar in both groups. Both groups had low amounts of the longer chain fatty acids, arachidonic acid and DHA, in their red blood cell membrane phospholipids compared to normal ranges. In Group 1, after 20 weeks on the protein substitute supplemented with fatty acids, their median DHA red cell membrane phospholipids increased by 19%, but the control group (Group 2) remained unchanged. Although there was an improvement in DHA concentrations in Group 1, it was still less than normal ranges. Median arachidonic acid levels increased by 0.5% in the group supplemented with essential fatty acids. Growth and blood phenylalanine control were satisfactory in all subjects. This protein substitute is now available in the UK, US, and throughout Europe so is easily used as a way of improving essential fatty acid intake.

    Other Ways of Improving Essential Fatty Acid Intake on a Low Phenylalanine Diet

    Some oils are naturally higher in alpha-linolenic acid and are good to use in every day cooking and salad dressings in low phenylalanine diets. These include rapeseed (canola), walnut, and soybean oils. Corn, sunflower, and safflower oils are rich in linoleic acid but not alpha-linolenic acid.

    Other researchers have tried to give fish oil supplements rich in DHA or capsules containing DHA and arachidonic acid for PKU. These appear to improve long chain polyunsaturated fat status, but the ideal dose and ratio of DHA and arachidonic acid has not yet been defined.

    Conclusions

    Supplementing the PKU diet with a balanced blend of the essential fatty acids (both linoleic acid and alpha-linolenic acid) improved DHA status without compromising arachidonic acid. In this study we decided to add essential fatty acids rather than directly adding the longer chain fatty acids (e.g. DHA) to the protein substitute. This was because the longer chain fatty acids are commonly based on fish oils and may adversely affect the taste of the protein substitutes and, ultimately, diet compliance. Therefore, based on our study results, adding essential fatty acids to non-phe- containing protein substitute is a useful way to improve essential fatty acid status of children and others on the diet.

    Table 1: Oils containing high proportions of alpha-linolenic acid

    OilLinoleic Acid % Alpha-Linolenic Acid %Ratio of Omega 6:3
    Linseed/Flax 16 54 1:3.4
    Rapeseed/Canola 19.7 9.6 2:1
    Walnut 58 12 5:1
    Soybean 54 7 7.7:1

    Last update: February 2008
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