Fatty Acid Metabolism Clinical Trial
Official title:
Essential Fatty Acid Metabolism in the Newborn: Equivalence of Precusors and Mediators in the Synthesis of Long Chain Polyunsaturated Fatty Acids of the n-6 and n-3 Series
| Verified date | July 13, 2010 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
We will test the following hypotheses:
1. The activity of the desaturating/elongating enzymes assessed by the in vivo conversion
of deuterated a-linolenic and linoleic acids to DHA and AA, respectively, will be
related to the duration of gestation and to postnatal age.
2. Dietary w-3 and w-6 LCPUFAs in human milk or DHA and AA supplemented formula will
inhibit the desaturation/elongation of deuterated a-linolenic and linoleic acids
demonstrating in vivo inhibition of the metabolic pathway by respective products.
Present evidence suggests that the parent essential fatty acids (EFA), linoleic acid (18:2
w-6) and a-linolenic acids (18:3 w-3) are insufficient to fully satisfy EFA nutrition during
early life in the human. A possible need for long chain (LC, longer than 18 C chain length)
EFAs in the human is suggested by the accretion rates of elongated and desaturated products
in the developing fetus; the altered plasma and red cell fatty acid patterns, and the
abnormal visual function observed in infants receiving solely the parent EFAs; and by the
relatively high concentration of LC EFAs in human milk. Most milk formula, as compared to
human milk, are lower in oleic acid, higher in linoleic, have little a-linolenic acid and
virtually no LC w-3 or w-6 polyunsaturated FA (LC PUFA). This study will evaluate the
capacity of human infants to form w-3 and w-6 LCPUFAs from the parent EFAs as affected by
developmental stage and dietary EFA supply. The precursors will be labeled with deuterium and
the products analyzed by gas chromatography / mass spectrometry GC/MS. The main products of
the desaturation / elongation pathway are docosahexaenoic (DHA) and arachidonic (AA) acids
for the w-3 and w-6 series, respectively. Infants will be fed human milk or formulas with or
without supplemental LCPUFAs as part of a study to evaluate the effect of EFAs on CNS
functional development. Infants included in this study of the effect of developmental stage
on EFA desaturation/elongation will be 2-5 days of age (before any fat is administered
enterally or parenterally) and 28, 32, 36 or 40 weeks gestation. In addition, infants born at
28 and 40 weeks gestation will be studied 2 and 6 weeks postnatally after dietary fat has
been provided for at least 7 days and energy intake is sufficient to assure growth. To
evaluate the effect of dietary EFA on DHA and AA formation we will assess elongation/
desaturation in infants receiving 3 diets: human milk (which contains w-3 and w-6 LCPUFAs);
cow milk based formula providing 18:2 w-6 and 18:3 w-3 but no LCPUFAs; or formula
supplemented with added LCPUFAs (DHA and AA). This study should provide new information on
the effects of developmental stage and w-3 and w-6 LCPUFA supply in determining the activity
of EFA elongation/desaturation in the human. This knowledge may help in improving early
neonatal nutritional practices to assure meeting the EFA needs of the developing CNS.
| Status | Completed |
| Enrollment | 110 |
| Est. completion date | July 13, 2010 |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A and older |
| Eligibility |
- INCLUSION CRITERIA: Newborns with birth weights appropriate for their gestational age born at 28, 32, 36 and 40 weeks gestation that are recovering from common neonatal morbidity will be recruited to enter the study before 5 days of age. This disease condition will not be life threatening at the time of study. The typical disease conditions expected based on the pilot phase of study are infants recovering from asphyxia, infants recovering from transient tachypnea, infants recovering from suspect pneumonia, infants recovering from hyaline membrane disease. Hyperbilirubinemia in conjunction with disease condition will not be a reason for exclusion. Newborns with birth weights below the tenth percentile of the weight distribution for a given gestational age born at 30-34 and 36-38 weeks gestation. Will include infants born at 28 to 40 weeks who are free of major neonatal morbidity and will be recruited to enter the study at 10 days of age. EXCLUSION CRITERIA: Maternal factors which may affect their fatty acid metabolism of the neonate. - Vegetarian or vegan diet during pregnancy - Metabolic disease which may affect essential fatty acid status of the fetus (hyperlipidemia, diabetes) Postnatal factors: Birth weight inadequate for gestational age (birth weight below the 10th percentile or above the 90th percentile for gestational age) Significant acute neonatal morbidity which interferes with normal lipid metabolism during the study period. Infants who are recovering from common neonatal morbidities that do not have obvious effects on elongase/desaturase activity will not be excluded. Feeding other than prescribed for the study. |
| Country | Name | City | State |
|---|---|---|---|
| Chile | Clinica Presbiteriana Madre Hijo | Santiago | |
| Chile | Hospital Luis Tisne | Santiago |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute on Alcohol Abuse and Alcoholism (NIAAA) |
Chile,
Glomset JA. Fish, fatty acids, and human health. N Engl J Med. 1985 May 9;312(19):1253-4. — View Citation
Lee AG, East JM, Froud RJ. Are essential fatty acids essential for membrane function? Prog Lipid Res. 1986;25(1-4):41-6. — View Citation
Sprecher H. Biochemistry of essential fatty acids. Prog Lipid Res. 1981;20:13-22. — View Citation
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