Providing the Right
Fuels for FOD’s
Elaina Jurecki, MS, RD
Regional Metabolic Nutritionist
Kaiser Permanente Medical Center
Oakland, CA
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
The Body’s Energy Sources
Glycogen
Fats
Protein
Fatty Acids
Amino Acids
Glucose
Ketone Bodies
The Body’s Energy Sources
Glycogen
Fats
Protein
Fatty Acids
Amino Acids
Glucose
Ketone Bodies
Fatty Acid Oxidation
During Fasting
Adipose Tissue
Heart
Skeletal
Muscle
Fatty Acids
Liver
Brain
Ketones
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
Fatty Acid Oxidation
During Fasting
Adipose Tissue
Cardiomyopathy
Arrhythmia
Fatty Acids
Liver
Steatosis
Muscle
dysfunction
Poor Tone
Myoglobinuria
Muscle pain
Loss of
Consciousness
↑Ammonia
Ketones
Fat as an Energy Source
Carnitine
Substrate
Mitochondria
Fatty Acids
Carnitine
Waste
Energy
(ATP)
Beta Oxidation
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
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
Fat as an Energy Source
Carnitine
Substrate
Fatty Acids
Long Chain Fats
Medium Chain Fats
Short Chain Fats
Acetyl
CoA
Acetyl
CoA
Acetyl
CoA
Mitochondria Beta Oxidation
Carnitine
Waste
Energy
(ATP)
Fat as an Energy Source
Carnitine
Substrate
Fatty Acids
Long Chain Fats
Medium Chain Fats
Short Chain Fats
Acetyl
CoA
Acetyl
CoA
Acetyl
CoA
VLCAD
Mitochondria Beta Oxidation
Carnitine
Waste
Energy
(ATP)
Fat as an Energy Source
Carnitine
Substrate
Fatty Acids
Long Chain Fats
Medium Chain Fats
Short Chain Fats
Acetyl
CoA
Acetyl
CoA
Acetyl
CoA
LCHAD
Mitochondria Beta Oxidation
Carnitine
Waste
Energy
(ATP)
Fat as an Energy Source
Carnitine
Substrate
Fatty Acids
Long Chain Fats
Medium Chain Fats
Short Chain Fats
Acetyl
CoA
Carnitine
Waste
MCAD
Acetyl
CoA
Acetyl
CoA
Mitochondria Beta Oxidation
Energy
(ATP)
Fat as an Energy Source
Carnitine
Substrate
Fatty Acids
Long Chain Fats
Medium Chain Fats
Short Chain Fats
Acetyl
CoA
Acetyl
CoA
SCAD
Acetyl
CoA
Mitochondria Beta Oxidation
Carnitine
Waste
Energy
(ATP)
Fat as an Energy Source
Carnitine
Substrate
Fatty Acids
Long Chain Fats
Medium Chain Fats
Short Chain Fats
Acetyl
CoA
Acetyl
CoA
Acetyl
CoA
Mitochondria Beta Oxidation
Carnitine
Waste
Energy
(ATP)
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
Treatment Strategies
Acute
Acute Treatment
Emergency Care Letter
IV Fluids
High dose IV glucose
Carnitine to excrete toxic metabolites.
Use of insulin to suppress catabolism.
Treatment Strategies
Avoidance of Fasting
Fat Restriction
Energy Supplementation
- Carbohydrates and Proteins
- MCT Oil
- Cornstarch
Prevent Catabolism
Carnitine Supplementation
Healthy Diet promotes growth & development
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
Relation of Fatty Acids to
Blood Sugar During Fasting
4.5
4
3.5
3
2.5
2
1.5
Fatty acids
Glucose
1
0.5
0
4 hrs
8 hrs
12 hrs 16 hrs
Stanley, et al, JIMD, 1989.
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
Exercise
Increase metabolic
tolerance
Gradually achieve
conditioned state
Snacking is important
The body will adapt to
alternative energy
sources.
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
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
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.
Essential Fatty Acids
in Edible Oils
Soybean
Walnut
Peanut
Flax
Coconut
Linoleic
Linolenic
Canola
500
450
400
350
300
250
200
150
100
50
0
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.
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)
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.
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
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
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.
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.
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.
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
Providing the Right
Fuels for FOD’s
Elaina Jurecki, MS, RD
Regional Metabolic Nutritionist
Kaiser Permanente Medical Center
Oakland, CA