Safety and Efficacy of Omega-3 Free Fatty Acids in Adolescents With Obesity and Hypertriglyceridemia.
Safety and Efficacy of Omega-3 Free Fatty Acids in Adolescents With Obesity and Hypertriglyceridemia.
The primary objetive was to evaluate the safety and efficacy the 3 grams per day of omega-3
 in adolescents with obesity and hypertriglyceridemia ( ≥ 150 mg/dl and ≤ 1000 mg/dl) for 12
 weeks, compared with placebo. Half of subjects received 3 grams of omega 3, while the other
 half received placebo.
First of all, the omega-3 free fatty acids have an important effect for lowering
 triglycerides through three potential mechanisms such as:

 Inhibition of triacylglycerol synthesis as direct inhibition of diacyl glycerol acetyl
 transferase and phosphatidic acid phosphohydrolase results in lowering triacylgycerol
 production.

 Simulation of fatty acid oxidation through activation of peroxisome proliferation activated
 receptor stimulates hepatic mitochondrial and peroxisomal beta oxidation of fatty acids.
 Decreased availability of fatty acids for triacylgylcerol synthesis results in lowering
 plasma triacylgycerol levels Lipoprotein Lipase mediated clearance. One of the first
 randomized double blind placebo controlled clinical trials was managed by Harris in 1997 in
 adult subjects with an average age of 46 ± 11 years and severe hypertriglyceridemia (500-2000
 mg / dl) 20 subjects received placebo and 22 subjects 4 grams of omega-3. The mean percent
 change from baseline in the omega-3 group was -45 ± 23% and in the placebo group was -16 ±
 35% (p <0.0001).

 Also, more clinical trials have recently been conducted with similar results such as the most
 recent randomized, double-blind, placebo-controlled clinical trial that was conducted by
 Ta-Chen Su in Taiwan in adults with hypetriglyceridemia (200-1000 mg / dl). The first group
 received 4 grams of omega-3 (n = 84), the second group received 2 grams of omega-3 (n = 82)
 and the third group received placebo (n = 87). The mean percent change from baseline in the 4
 grams of omega-3 group was -32.1%, in the 2 grams group of omega-3 was -29.7% and in the
 placebo group was -5.4% (p <0.0001) What is more, the strongest scientific evidence in favor
 of supplementation of omega-3 acids fatty was determined by two meta-analysis, the first
 study was published by Harris in 1997 that included 72 placebo-controlled clinical trials,
 the study showed a reduction of 25-30% triglycerides levels with doses of 3-4 g omega-3
 compared with placebo in subjects with triglycerides levels ≥500mg / dl. The second
 meta-analysis by Balk that included 17 clinical trials (7,803 patients) with different doses
 of omega-3 (0.8-5.4 g). The net reduction in triglycerides levels was -27 mg / dl (IC95%
 22-30), p <0.0001 In addition, the American Heart Association based on the meta-analysis by
 Harris currently recommends the administration of 2 to 4 grams of omega-3 per day for the
 treatment of severe hypertriglyceridemia (≥500mg / dl) in adult patients.

 Secondly, the Task Force for the Management of Dyslipidaemias of the European Society of
 Cardiology (ESC) and European Atherosclerosis Society (EAS) currently recommends that if
 hypertriglyceridemia is not able to reduce with statins or fibrates the physician will
 prescribe 2-4 grams of omega-3 fatty acids to reduce triglyceride levels in adult patients.

 Finally, the Food Drug Administration (FDA) in 2004 authorized the administration of 2 to 4
 grams of omega-3 per day for the treatment of severe hypertriglyceridemia (≥500mg / dl) in
 adult patients.

 There is enough evidence that medical literature supports the use of omega-3 in adult
 patients for treatment of hypertrigyceridemia even the American Heart Association has made
 the recommendation in its Scientific Statement but unfortunately in children the information
 about the use of omega-3 for hypertriglyceridemia is insufficient to make clinical decisions.

 There are no specific recommendations and dosages of omega-3 in children and adolescents for
 the treatment of hypertriglyceridemia.

 A randomized, double-blind placebo controlled clinical trials are necessary to assess the
 efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in
 children and adolescents.

 Main objective:

 Assessing the efficacy and safety of supplementation of 3 grams of omega-3 fatty acids for 12
 weeks on serum triglycerides in adolescents with obesity and hypertriglyceridemia compared to
 a control group that received placebo.

 Secondary objective:

 Assessing the efficacy and safety of supplementation of 3 grams of omega-3 fatty acids for 12
 weeks on serum cholesterol, HDL-C, glucose and uric acid in adolescents with obesity and
 hypertriglyceridemia compared to a control group that received placebo.

 Study plan detailing the procedures.

 Visit 1 Enrollment:

 The subject was picked up by the Allergy Department and Obesity Clinic. Informed consent and
 informed assent. Demography (date of birth, gender) and evaluation of Inclusion/Exclusion
 criteria Medical. Surgical history physical examination and anthropometry (weight, height,
 body mass index, abdominal perimeter, waist and hip). Pulse and blood pressure. Pregnancy
 test. Fasting venous blood samples of 12 hours for the measurement of triglycerides and
 metabolic profile. Food recommendation was indicated by the Pediatric Clinical Nutrition
 Service. Physical activity was indicated with a 30-minute walk per day for seven days per
 week by the Pediatric Clinical Nutrition service.

 Visit 2 Randomization:

 Triglyceride levels were reviewed, in case of report ≥150 mg / dl and ≤ 1000 mg/dl the
 subjects were randomized.

 The type of randomization used was blocked randomisation, number of subjects per block were
 10 and number of blocks were 13. (130 subjects were randomized).

 Allocation of omega-3 or placebo capsules for all randomized subjects and beginning of the
 week 0 of treatment.

 Visit 3 Treatment week 4 Allocation of omega-3 or placebo capsules. Checking of adverse
 effects. Accounting of capsules. Supervision of compliance diary of omega-3 or placebo
 capsules. Supervision of compliance diary food recommendation. Supervision of compliance
 physical activity

 Visit 4 Treatment week 8 Allocation of omega-3 or placebo capsules. Checking of adverse
 effects. Accounting of capsules. Supervision of compliance diary of omega-3 or placebo
 capsules. Supervision of compliance diary food recommendation. Supervision of compliance
 physical activity.

 Visit 5 Treatment week 12 Checking of adverse effects. Accounting of capsules. Supervision of
 compliance diary of omega-3 or placebo capsules. Supervision of compliance diary food
 recommendation. Supervision of compliance physical activity.

 Follow-up telephone call week 16. A follow-up telephone was performed 4 weeks after the visit
 5. At the follow-up telephone call, the investigator checked adverse events.
Inclusion Criteria:

 -  Ages 10-16 years old

 -  Informed consent from a parent or legal guardian of minors or adult subject

 -  Written assent from the adolescent to participate in the study

 -  Obese patients (Body Mass Index ≥95th percentile according to the National Center for
 Health Statistics, Center for Disease Control and Prevention [CDC].

 -  Fasting Serum triglycerides ≥150 mg/dL and ≤1000 mg/dL.

 -  Cooperation to ingest capsules (omega-3 or placebo) and taking laboratories

 Exclusion Criteria:

 -  The subjects must not had received pharmacology treatment for hypertriglyceridemia six
 months before and at the time of enrollment.

 -  Treatment with medications that affect triglyceride levels, including oral
 hypoglycemic agents or insulin.

 -  Pregnancy or positive urine pregnancy test for those females who have begun
 menstruating.

 -  Known Bleeding Disorder or Coagulopathy or treatment with anticoagulant medications or
 low platelet counts, abnormal PT, or PTT.

 -  Subjects with mental delayed.

 -  Neurological disorder.

 -  Subjects with Cardiophaty

 -  Subjects with gastroesophageal reflux

 -  Endocrinopathies such as thyroid disorder, Hypothalamic disorder and Type 1 or 2
 diabetes or fasting glucose that is >=126 mg/dl.

 -  Subjects with liver disease

 -  Familial hypertriglyceridemia.

 -  Familial hypercholesterolemia

 -  Polycystic ovary syndrome

 -  Use of contraceptives by any way of administration 6 months before and at the time of
 enrollment.

 -  Use of vitamins 6 months before and at the time of enrollment.

 -  Allergy to fish oil.

 -  Allergy to soybean oil.

 Elimination criteria:

 -  Subject or parents´ subject either decision to discontinue of the study at any time
 without prejudice to further treatment.

 -  Serious adverse event.

 -  Safety reason as judged by the investigator.

 -  Pregnancy.