Clinical trial NCT03040856: The Effect of Alpha Linolenic Acid (ALA) Supplementation During Pregnancy
Official title: The Effect of Alpha Linolenic Acid (ALA) Supplementation on Essential Fatty Acids Profile During Pregnancy Compared to Common Supplements and the Epigenetic Effect on the Newborn
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Omega 3 Supplements During Pregnancy
Keywords: Omega 3
Supplements
Alpha Linolenic Acid
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2017-02-02
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Omega-3 fatty acids are "good fats," and are among the most important nutrients lacking in Western diets today. The average person in developing countries consumes less than 100 mg of DHA daily. With increasing awareness of the importance of DHA, many people realize that they need to make a change in their diet by adding DHA-rich foods or supplements.

The aim of this study is to learn the effect of different supplementations from the omega 3 group on the maternal and fetal fatty acid profile during pregnancy and to study their epigenetic influence.

Detailed description: DHA (Docosahexaenoic Acid ) is a long chain omega-3 fatty acid important for brain and eye development and function throughout life. It also supports heart health. DHA is the most abundant omega-3 in the brain and retina and is naturally found in breast milk. EPA (Eicosapentaenoic Acid ) is a long-chain omega-3 fatty acid important for overall health. However, unlike DHA, the body does not store EPA in significant quantities in the brain or retina (DHA is found in every cell throughout the body, EPA is not). These Omega 3 fatty acids are considered essential due to the inability of the human body to create them and the need to consume them from nutritional source. Food that is considered rich in omega 3 fatty acids are fat fish and green vegetables. Omega-3 fatty acids are "good fats," and are among the most important nutrients lacking in Western diets today. The average person in developing countries consumes less than 100 mg of DHA daily. With increasing awareness of the importance of DHA, many people realize that they need to make a change in their diet by adding DHA-rich foods or supplements.

Alpha Linolenic Acid (ALA) is a shorter-chain omega-3 that serves as a source of energy and as a building block for long-chain omega-3 fatty acids (DHA and EPA). This precursor for omega 3 fatty acid is abundant in falx seeds. The mother and the fetus has the metabolic mechanism that enables them to transform ALA into EPA,DHA endogenously.

Women during pregnancy are predisposed to a reduction in unsaturated long chain fatty acid (Polyunsaturated Fatty Acid = PUFA) from the omega 3 group . Lately, a new hypothesis claiming that a reduced level of this essential acids expose the fetus later in his adult life to a spectrum of metabolic and cardiovascular disease. New publication on animal models showed higher rates of obesity, insulin resistance diabetes and cardiovascular damage on mice exposed short chain fatty acids compared to those treated with enriched ALA diet supplementation. Different nutritional and gynecological health organization around the world including the FDA, recommend incorporating omega 3 fatty acids supplementation to daily diet and specifically in pregnant women in order to raise their blood levels for the developing fetus. However, normal fatty acid profile of the omega 3 group in mother and fetus haven't been described yet. Furthermore, the total effect and future benefit to fetus haven't been thoroughly studied and is based mainly on presumptions.

The aim of this study is to learn the effect of different supplementations from the omega 3 group on the maternal and fetal fatty acid profile during pregnancy and to study their epigenetic influence.

Study methods:

Women 12 weeks of gestation visiting high risk unit and fitting inclusion criteria will be offered to participate in the study. Demographic, medical and obstetrical information will be collected from medical files after giving signed informed consent .

Each participant will be randomly assigned to one of three arms of the study based on the order of being recruited (1- to first group, 2- to second group, 3 - to third group, 4- to first group, etc.). Randomization will be done by the principal investigator that is not one of the high risk unit team, and will be blinded to the participants and the treating doctor.

Group 1: Enriched diet with 2 capsules of ALA supplementation a day - 630 mg in each capsule. Total amount of 1260 mg (Daily recommended dose is 1-2 g).

Group 2: Enriched diet with 2 capsules of DHA+EPA supplementation a day (Each capsule consist of 240 mg DHA and 360 mg EPA) Group 3: Control group - Will receive 2 placebo capsule a day (All products will be supplied by the same company that is approved by the FDA and the Israeli health ministry) Follow up will take place on every visit to the high risk unit that is 3 and 2 weeks apart at the second and third trimester, respectively. On each visit one blood tube that include 5cc of blood will be taken for fatty acid profile analysis and on labor 2 blood tubes will be taken from the mother and from the umbilical cord after separation of the placenta : 1- for fatty acid analysis , 2- for PCR evaluation of mRNAs of genes that were found correlated in animal models to be influenced by maternal diet during pregnancy and are connected to metabolic syndrome pathologies in adulthood ( including - FASn, Elov6, PPAR (α, β/δ, γ), SCD1, Fads2, SREBP-1 Ppargc1alpha, Lpin1, Plin5 , MAPK/PGC-1α. (

Eligibility criteria: Inclusion Criteria:

* Age 18-42
* Singleton
* Gestational age 12-16 during first visit at the high risk unit

Exclusion Criteria:

* Liver Disease
* Dyslipidemia
* Twins
* Warfarin, LMWH, Heparin use ( Due to suspected drug interaction that has been reported however has not been proven yet)

Primary outcomes:
measure: Levels of Omega 3 fatty acids ( DHA, EPA, ALA)
timeFrame: Change in maternal levels of Omega 3 fatty acids ( DHA, EPA, ALA) from recruitment (12 week of gestation ) until delivery .
Secondary outcomes:
measure: Expression of messenger RNAs ( mRNAs) between the study groups
timeFrame: At delivery - Immediately after separation of the placenta ( Blood sample from the mother and from the umbilical cord)
Other outcomes:
Locations:
city: Ramat-Gan
country: Israel
facility: Dr. A Mohr-Sasson
Study officials:
affiliation: Department of Obstetrics and Gynecology ,Sheba Medical Center, Ramat Gan, Israel
name: Israel Hendler, M.D
role: STUDY_DIRECTOR
affiliation: Bert Strassburger Lipid Center, Sheba Medical Center, Ramat Gan, Israel
name: Alicia Leikin-Frenkel, M.D, Ph.d
role: STUDY_DIRECTOR
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