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
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.
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). Also, the relative efficiency of conversion of
the 18-C precursors will be compared to the 20-C precursors with respect to their metabolic
endpoints. 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.
;
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