Providing the Right Fuels for FOD s. Elaina Jurecki, MS, RD Regional Metabolic Nutritionist Kaiser Permanente Medical Center Oakland, CA
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1 Providing the Right Fuels for FOD s Elaina Jurecki, MS, RD Regional Metabolic Nutritionist Kaiser Permanente Medical Center Oakland, CA
2 Providing the Right Fuels for FOD s The Body s Use of Energy Fat As An Energy Source Energy Blocks because of FOD s Treatment Strategies: Acute vs. Chronic The Future - Questions
3 The Body s Energy Sources Glycogen Protein Glucose Amino Acids Fats Fatty Acids Ketone Bodies
4 The Body s Energy Sources Glycogen Glucose Protein Amino Acids Fats Fatty Acids Ketone Bodies
5 Fatty Acid Oxidation During Fasting Adipose Tissue Heart Skeletal Muscle Fatty Acids Liver Brain Ketones
6 Fasting: Infants & Children More difficulty adapting to fasting: higher energy needs more effort to maintain body temp. higher rate of brain metabolism body does not produce energy sufficiently enough
7 Fatty Acid Oxidation During Fasting Adipose Tissue Cardiomyopathy Arrhythmia Liver Steatosis Ammonia Fatty Acids Muscle dysfunction Poor Tone Myoglobinuria Muscle pain Loss of Consciousness Ketones
8 Fat as an Energy Source Carnitine Substrate Mitochondria Carnitine Waste Fatty Acids Beta Oxidation Energy (ATP)
9 Fat as an Energy Source Long Chain Fats: C16 - C18: CCCCCCCCCCCCCCCCCC-OH Medium Chain Fats: C6 to C8 CCCCCCCC-OH Short Chain Fats: C2 to C4: CCCC-OH
10 Fat as an Energy Source Fatty Acids - C18 CCCCCCCCCCCCCCCCCC-OH + Carnitine Carnitine-Specific Enzymes Needed Mitochondria CCCCCCCCCCCCCCCCCC-CoA CCCCCCCCCCCCCCCCCC + CC-CoA Beta Oxidation ATP Carnitine Shuttling Scavenging
11 Fat as an Energy Source Carnitine Substrate Long Chain Fats Medium Chain Fats Short Chain Fats Carnitine Waste Fatty Acids Acetyl CoA Acetyl CoA Acetyl CoA Mitochondria Beta Oxidation Energy (ATP)
12 Fat as an Energy Source Carnitine Substrate Long Chain Fats Medium Chain Fats Short Chain Fats Carnitine Waste Fatty Acids Acetyl CoA Acetyl CoA Acetyl CoA VLCAD Mitochondria Beta Oxidation Energy (ATP)
13 Fat as an Energy Source Carnitine Substrate Long Chain Fats Medium Chain Fats Short Chain Fats Carnitine Waste Fatty Acids Acetyl CoA Acetyl CoA Acetyl CoA LCHAD Mitochondria Beta Oxidation Energy (ATP)
14 Fat as an Energy Source Carnitine Substrate Long Chain Fats Medium Chain Fats Short Chain Fats Carnitine Waste Fatty Acids Acetyl CoA Acetyl CoA MCAD Acetyl CoA Mitochondria Beta Oxidation Energy (ATP)
15 Fat as an Energy Source Carnitine Substrate Long Chain Fats Medium Chain Fats Short Chain Fats Carnitine Waste Fatty Acids Acetyl CoA Acetyl CoA Acetyl CoA Mitochondria Beta Oxidation SCAD Energy (ATP)
16 Fat as an Energy Source Carnitine Substrate Long Chain Fats Medium Chain Fats Short Chain Fats Carnitine Waste Fatty Acids Acetyl CoA Acetyl CoA Acetyl CoA Mitochondria Beta Oxidation Energy (ATP)
17 Symptoms of FOD s Low blood sugar Decreased ketone production Increased blood ammonia Increased toxic fatty acids Liver and muscle dysfunction Altered consciousness Rhabdomyolysis Retinal tissue and nervous system problems
18 Treatment Strategies Acute
19 Acute Treatment Emergency Care Letter IV Fluids High dose IV glucose Carnitine to excrete toxic metabolites. Use of insulin to suppress catabolism.
20 Treatment Strategies Avoidance of Fasting Fat Restriction Energy Supplementation - Carbohydrates and Proteins - MCT Oil - Cornstarch Prevent Catabolism Carnitine Supplementation Healthy Diet promotes growth & development
21 Avoidance of Fasting Tolerance to fasting extremely variable Modifying factors can change one s tolerance More muscular - more tolerant Fatty acids increase before blood sugar drops What is the time period allowed without eating? - continuous night time feeding? - middle of the night feedings? - fast for the duration of the night? Infants < 4 hours Children < 8 hours
22 Relation of Fatty Acids to Blood Sugar During Fasting hrs 8 hrs 12 hrs 16 hrs Fatty acids Glucose Stanley, et al, JIMD, 1989.
23 Avoidance of Fasting Tolerance to fasting extremely variable Modifying factors can change one s tolerance More muscular - more tolerant Fatty acids increase before blood sugar drops What is the time period allowed without eating? - continuous night time feeding? - middle of the night feedings? - fast for the duration of the night? Infants < 4 hours Children < 8 hours
24 Exercise Increase metabolic tolerance Gradually achieve conditioned state Snacking is important The body will adapt to alternative energy sources.
25 Fat Restriction Less fat - less toxic fatty acids to accumulate. Lower fat diet help to maintain more normal carnitine levels. Does the fatty acids cause the damage or is it because of a lack of energy production? How restricted should the fat intake be? Consequence of fat restriction - - Essential fats - Fat soluble vitamins - Source of energy
26 Consequences of Fat Restriction Fat is an important energy source. Still oxidized to form ATP Some overlap in the enzymes to oxidize Oxidation in other cells - peroxisomes Fat has an important role in the diet. Satiety Helps enhance aroma, flavor, and mouth feel Unrestricted fat intake resulting in minimal consequences - infants with MCAD do well on regular formulas
27 Essential Fatty Acids Precursors for prostaglandins & leucotrienes. Signs of essential fatty acid deficiency usually not seen (dry skin, dermatitis, hair loss, poor growth). α-linoleic 18:2, the omega-6 fats γ-linolenic 18:3, the omega-3 fats 3 to 5% of total calories; ratio of linoleic to linolenic of 4 : 1. National Institute of Medicine recommends children, 4-8 yrs., consume 10 grams linoleic acid and 0.9 grams linolenic acid per day.
28 Essential Fatty Acids in Edible Oils Linoleic Linolenic Canola Coconut Flax Peanut Walnut Soybean
29 Docosahexaenoic Acid Supplementation with Docosahexaenoic Acid. Very long chain fatty acid - C22:6 - found in fish and can be synthesized from linolenic acid. Adequate intake of DHA in infants for optimal development of brain and eye. Low levels of DHA seen in LCHAD even with adequate linolenic intake. Did not improve retinal pigment problems in LCHAD Dosage Recommendations: 65 mg. DHA for children < 40 lbs. 120 mg. for children > 40 lbs.
30 Fat Soluble Vitamins Low fat diets - increased risk of low intake of vitamins A, D, K and E. Vitamin A, D, K and E. Dietary intake looked at in 10 children with LCHAD: Vitamin A and D - primary source in foods was nonfat milk. Low intakes of vitamin K and E due to low intakes of green leafy veggies and nuts. Multivitamin/mineral supplement generally recommended for these diets. (Gillingham, Mol Genet Metab, 2003)
31 Energy Supplementation Use of carbohydrates and proteins instead of fat in the diet to ensure adequate calories. Compensate for increased needs due to illnesses or stressed states.
32 Use of Cornstarch Source of a complex carbohydrate digested slowly for gradual release of glucose. May be beneficial to maintain blood sugar levels Can keep in fed state and prevent body fat release. Useful at bedtime & before exercise Should not be cooked or mixed in citrus juice Dosage: 1/2 to 1 tbsp. per every 10 lbs. of body weight. May cause G.I. Upset and not well digested in infants
33 MCT Supplementation MCT oil: manufactured from fractionation of coconut oil. Can use in cooking, salad dressings, beverages. Infant formulas containing MCT oil: Pregestimil Portagen Dietary MCT is used as immediate energy source. Bypasses long chain disorders and enters mitochondria without need of carnitine
34 MCT Supplementation MCT supplementation - suppresses long chain fatty acid oxidation and prevents accumulation of toxic metabolites. Providing 10-20% of calories in a diet has more of an impact than fat restriction. Study of 50 patients with LCHAD found improved metabolic control with use of MCT (den Boer, Peds, 2002). Cell studies show patients with long chain defects can oxidize these fats as an energy source.
35 Use of Odd Chain Fats as Supplements Ongoing study by Dr. Roe at University of Texas. Use of fats 7 vs. 8 carbon chain length. Attempt to restore energy production and improve organ function with these fats. Study of 22 patients with FOD s showed initial improvements in heart and liver function and increased muscle strength. No evidence of chemical toxicity from these fats. Diarrhea and weight gain seen in older patients. Need to see if better than MCT Oil.
36 Carnitine Supplemention Conjugates toxic fats for excretion Restores free CoA Low blood and tissue levels seen in patients with FODs Higher fat diets may increase carnitine losses Will it cause accumulation of toxic fatty acids in the mitochondria? 50 LCHAD patients on carnitine did not decrease frequency of metabolic decompensation. No improvement in fasting tolerance in MCAD infants.
37 What Does the Future Hold? Increasing numbers of patients living to adulthood. Newborn screening will detect patients before presenting with symptoms. Ongoing controlled treatment studies - - How much fat to restrict - Alternate energy sources - Carnitine Identifying adults with milder forms of the disorder Additional new disorders to be found
38 Providing the Right Fuels for FOD s Elaina Jurecki, MS, RD Regional Metabolic Nutritionist Kaiser Permanente Medical Center Oakland, CA
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