Fatty Acid Status Of Metabolic Patients: To Supplement Or Not To Supplement?

From the Spring/Summer 2004 issue of National PKU News

Role Of DHA And LCPUFAS

The Food and Drug Administration (FDA) has recently approved two fatty acids- docosahexaenoic acid (DHA, an omega-3) and arachidonic acid (AA, an omega-6)-as supplements in infant formula, in order to mimic human breast milk. They are both classified as long chain polyunsaturated fatty acids (LCPUFAs). What is their importance?

DHA has a number of important roles. In infant brain and eye development, where a significant portion of the brain and retina contain high amounts of DHA, studies have shown that DHA is vital throughout pregnancy, especially during the last trimester when increased amounts are taken up by the fetus. Also, there is a rapid increase of DHA in the brain from birth to age two. There are studies that show formula-fed babies have lower amounts of DHA in their tissues and brains than breastfed babies. Animal studies show that low levels of DHA in the brain affect learning patterns.

Deficiencies in LCPUFAs and PKU were first seen in the 1960's, including one study that reported deficits of LCPUFAs in autopsied brains of individuals with PKU. A study in 1977 showed that myelin lipids from PKU brains contained reduced amounts of LCPUFAs compared to non-PKU brains. Several other studies since the 1990's reported deficiencies in blood DHA in PKU compared to controls. Our study in 2002 (Moseley et al) looked at fatty acid status in 27 PKU adults and adolescents. We found that they had elevated omega-6 fatty acids and significant deficiencies in DHA.

In several PKU studies, reductions in DHA have been implicated in the observed dysfunction of prefrontal lobe cognition ("executive function") sometimes seen in treated PKU. In untreated or poorly controlled PKU, high levels of blood phe block transport into the brain of tyrosine and tryptophan, amino acid precursors to the neurotransmitters dopamine and serotonin. These important neurotransmitters play a role in mood and learning. DHA is needed in their synthesis, a process that is already compromised when phe levels are high.

The intense interest in DHA is due to its important functions in the brain as well as to the known DHA deficiency associated with some other disorders. DHA has a role in regulating gene expression, maintaining membrane fluidity, regulating membrane-bound enzymes, and regulating neuron size. DHA deficiencies are seen in mitochondrial disorders, ADHD, dyslexia, schizophrenia, and depression. Many researchers are investigating the role of DHA in mood and learning disorders as well as Alzheimer's disease. There is still much that we don't know about DHA's role in human health.

LCPUFAS And Supplement Issues

A recent study of children who were either on regular formula, a formula supplemented with LCPUFAs (including DHA and AA), or breast milk after birth showed that the breastfed and supplemented groups had lower blood pressure at age six than the formula-fed group. Early exposure to LCPUFAs may thus reduce cardiovascular risk in later life. LCPUFA functions have a great impact on health through their effect on powerful hormones. These hormones regulate blood vessel leaking, lipid accumulation, and immune cell behavior.

Several researchers began supplementing PKU individuals with fish oil and LCPUFAs and reported normalization of blood LCPUFA levels, improved visual function, and no adverse effects.

A Complicated Balance

The issue of supplementation is not without complexity. The precursors to the powerful hormones affected by LCPUFAs are alpha- linolenic (ALA, an omega-3) and linoleic (LA, an omega-6). Sources of LA include safflower oil, corn oil, sunflower oil, and walnut oil. Sources of ALA include flaxseed oil, canola oil, and soybean oil. These are essential fatty acids: our bodies cannot make them so we must get them from our diet. ALA can make DHA but only in small amounts. DHA is found mainly in fish and meats.

These two fatty acids have opposing metabolic functions and their balance is of key importance. If there is too much of one, there will be less function of the other. The ratio of ALA to LA should be 1:1 or 2:1. However, the PKU medical food products contain high amounts of omega-6 and very little omega-3. Research studies support the idea that a proper balance of these fatty acids should lead to decreases in cardiovascular disease, diabetes, hypertension, and other chronic medical conditions.

To Supplement Or Not?

As a dietitian, my main goal is to make sure our patients are getting the recommended amounts of calories, protein, fat, and vitamins/minerals for optimal growth, development and health. I have the same goal for omega-3 fatty acids. Many on-diet persons with PKU may not get what they need from food or medical food products. In my view, there is enough evidence to suggest that omega-3 fatty acids are important for optimal health, and that supplementing the PKU diet is reasonable. I know of no adverse effects reported when supplements are given in recommended amounts. However, this is an issue to discuss with your PKU dietitian/doctor before you start any supplementation.

Listed below are the Adequate Intakes of Omega-3 and Omega-6 Fatty Acids for adults, as recommended by an expert panel (National Institutes of Health, 1999):

Fatty Acid Gm/Day % Energy* LA (omega-6) 4.40 2.0 ALA (omega-3 2.20 1.0 DHA (omega-3) 0.22** 0.1 * Based on a 2,000 calorie diet. ** Pregnant or lactating: 0.30 gm/day.

It is good to know your fatty acid profile before supplementing to determine any deficiencies. Kennedy Krieger Institute in Baltimore does this test routinely for about $200 US). See http://www.genetics.kennedy.krieger.org. Fasting red blood cell fatty acid testing gives the best assessment.

Martek manufacturers the DHA and AA that is currently supplemented in infant formulas. This product has a good balance of omega-3 fatty acids, and omega-6 fatty acids are already abundant in our diets. The Martek oils are made from fish algae and contain no toxins (such as mercury, which is high in certain species of fish). For more information go to: http://www.martek.com. The GNC health food stores have a similar supplement called EFA Complete, also made from fish algae. There may be other nontoxic supplements that are made from fish algae. Flaxseed oil, touted as a source of omega-3 fatty acids, doesn't contain DHA.

Editor's Note: Some clinicians are not sure that omega-3 fatty acid supplements are needed for most people with PKU. However, those on no-fat (or very low fat) formulas, definitely need an adequate source of essential fatty acids, which includes omega-3's. Whether or not the formula you are using contains fat, you might want to discuss with your doctor and/or nutritionist whether a supplement is desireable. It would be very difficult for PKU formulas to be supplemented with omega-3 fatty acids because of significant shelf-life reduction (due to rapid oxidation of the fatty acids), palatability issues, and cost to the consumer. As Kathyrn Moseley points out, supplementing the diet according to recommended amounts is considered safe (see her story above for recommended supplements). For the long-term health of our PKU population, there may be important benefits to omega-3 fatty acid supplementation. While there is some conversion of other fatty acids to omega-3 fatty acids, the conversion is limited and may not provide optimal intake.