Omega-3 Supplementation and Depression Clinical Trial
Condition: Depressive Symptoms
MeSH terms: Depression
Study type: Interventional

Summary: 
      Fish oil omega-3 supplements provide essential nutrients for brain health and functioning.
      These nutrients have been proven to be effective in reducing depressive symptoms. They have
      also been found to be effective and well tolerated in reducing the bad fat accumulation among
      patients infected with human immunodeficiency virus (HIV)and are using highly active
      antiretroviral treatment. The role of this nutritional supplement in combating depression
      among pregnant women who are living with HIV infection has however not been established. Yet,
      currently, more than 2 million pregnant women are estimated to be living with HIV infection
      globally. In Kenya, about 9.0% of pregnant women are HIV-seropositive.

      In this study, it is hypothesized that there is no difference in the levels of depressive
      symptoms among HIV infected pregnant women who are taking omega-3 fish oil supplements and
      those taking a placebo.

      The study will therefore seek to ascertain that taking omega-3 fish oil nutritional
      supplement has a significant positive effect on depressive symptoms among HIV infected
      pregnant women, compared to a placebo.
    

Detailed description: 
      Background to the study: Fatty acids are the key building blocks of most fats and oils, both
      those in the body and in foods. Among the essential fatty acids that are required to maintain
      health, but must come from the diet, is omega-3. These omega-3 fatty acids are important
      constituents of all cell membranes and are involved in the movement of substances in and out
      of the cells. They also produce hormone-like substances which regulate many functions of the
      body. The omega-3 fatty acids occur naturally, and consist of shorter long-chain
      alphalinolenic acid (ALA) and the longer chain, eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA). The ALA is naturally found in green leafy vegetables, flax seed,
      soybean oil and walnuts. The long chain EPA and DHA are naturally found in dark muscles of
      sea fish such as salmon, mackerel and tuna. These nutrients must be consumed in the diet
      because they cannot be synthesized by humans[1]. Research on the health benefits of omega-3
      fatty acids dates back to 1929 when it was found to promote growth and prevent inflammation
      of the skin in rats [2, 3]. The essentiality of long-chain fatty acids for human health
      however emerged in 1970's when the first total parenteral nutrition which was fat-free was
      found to induce the essential fatty acid deficiencies among infants with volvulus, a bowel
      obstruction, at birth[4]. Further research in the 1970s on the health status of
      modern-hunter-gatherer Inuit Eskimos was also found to be related to their staple diet of
      fatty sea fish and fish eating marine mammals rich in long chain omega-3 fatty acids, EPA and
      DHA [5].

      It has been proven that omega-3 long chain fatty acids, EPA and DHA improve depressive
      symptoms [6, 7]. As a mood disorder, depression is characterized by feelings of unhappiness
      and hopelessness, and generally marked by altered mood. It is not a single disease, but a
      syndrome encompassing a spectrum of symptoms with multiple causes [8, 9]. Women experience at
      least one episode of minor or major depression during pregnancy and after childbirth. This is
      however often under-diagnosed, undetected and missed out due to lack of screening. Although
      screening for depression may not be a routine activity in antenatal care, studies that have
      screened for depression in pregnancy indicate that 20-30% of pregnant women are depressed
      [10, 11]. The prevalence of depression is high during the second and third trimesters of
      pregnancy [12] when maternal level of omega-3 fatty acids is depleted.

      Adequate intake of long chain omega-3 fatty acids is also essential, during pregnancy to
      support normal growth and maturation of many fetal organ systems, particularly the brain and
      eyes [13, 14]. Moreover, long chain omega-3 fatty acids are critical for the development and
      function of many different organ systems of the fetus, including the structure of the brain
      and retina of the eye [15]. Premature birth and its potential neurological complications may
      result from omega-3 deficiency [16]. Documented research findings on omega-3 fatty acids and
      human immune-deficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS) are mainly
      two-fold: one, on plasma triglycerides levels, and two, on the immune response parameters.
      Studies have shown that use of omega-3 fatty acids among HIV infected patients receiving
      highly active antiretroviral therapy is well tolerated and effective in reducing the plasma
      triglyceride levels [17-19]. The fish oil has therefore been recommended as second-line
      therapy for HIV patients with hypertriglyceridemia [12]. One of the metabolic end products of
      long chain fatty acids of omega-3 and omega-6, once eaten and absorbed by the body, are
      prostaglandin hormones which are responsible for the inflammation response. Research shows
      that omega-3 fatty acids produce less prostaglandin than omega-6 fatty acids, decreasing the
      inflammatory process [5]. Earlier research reported that omega-3 fish oil is
      immuno-suppressive as it significantly decreased various parameters of the immune response
      [20]. However, more recent studies have shown that dietary intake of omega-3 fatty acids
      increased the cluster of differentiation 4 (CD4) cell count [21] The role of long chain
      omega-3 fatty acids in combating depression among HIV-seropositive pregnant women has however
      not been established. The specific symptoms which may be more responsive to omega-3
      supplementation have also not been established. Currently, more than 2 million pregnant women
      are estimated to be living with HIV infection globally. In Kenya, about 9.0% of pregnant
      women are HIV-seropositive [22] and their health conditions as well as that of their unborn
      babies silently continue to deteriorate partly due to depression related comorbidities. This
      research will seek to ascertain that taking omega-3 fish oil supplement with higher EPA in
      relation to DHA can have a significant positive effect on depressive symptoms among
      HIV-seropositive pregnant women compared to a placebo. It will also monitor and identify
      those depressive symptoms that are more responsive to this nutrient among the
      HIV-seropositive pregnant women, and can be managed through nutrition supplementation.

      Conceptual Framework: The major risk factors for depression are genetic predisposition,
      hormonal imbalance and stressful events which could be of environmental, social or
      psychological origin as well as nutrition-related factors [11, 23-25]. Stressful events could
      however also cause hormonal imbalance, which, in the process can increase the stress hormone,
      cortisol, causing depression [23]. Both pregnancy and HIV infection status are also
      accompanied by high nutrient demand, in the presence of inadequate and inappropriate dietary
      intake as well as a high intake of saturated fats in fried food. This is likely to contribute
      to nutrient deficiencies, which also determines the neurotransmitter function and hormonal
      balance in mental health.

      Problem statement: This study seeks to ascertain that taking omega-3 fish oil supplement with
      higher EPA in relation to DHA have a significant positive effect on depressive symptoms among
      HIV-seropositive pregnant women. The level of omega-3 fatty acids rapidly declines during
      pregnancy as some of it is transferred to the fetus for the rapid formation of the fetal
      brain cells [13]. The resultant depletion in omega-3 might precipitate the occurrence of
      depression in pregnant women unless the nutrient deficit is met through dietary intake of
      omega-3 rich foods or supplementation. The modern diet is however inadequate in long chain
      omega-3 fatty acids [5]. About 40% of HIV-seropositive pregnant women are reportedly
      depressed [26, 27]. The depression in HIV-seropositive pregnant women is a significant public
      health problem due to its negative effects on both maternal and child health. It may
      adversely affect the quality of life and adherence to HIV/AIDS medication regimens [27, 28]
      which may subsequently affect disease progression and health outcome [29] of the women.
      Currently, more than 2 million pregnant women are estimated to be living with HIV infection
      globally [9]. In Kenya, about 9.0% of pregnant women are HIV-seropositive [22].

      Justification of the study: This study will contribute to the debate on nutritional support
      and management of depressive symptoms and related health complications in HIV infected
      pregnant women and other vulnerable populations, to improve their mental health, hence
      improve the quality of life. A reduction in the prevalence of depression could therefore
      influence nutrition and health agencies as well as policy makers to make omega-3 fatty acid
      nutritional supplement accessible to HIV positive pregnant women and other vulnerable
      populations.

      Overall aim: To ascertain that taking omega-3 fish oil supplement with higher EPA in relation
      to DHA have a significant positive effect on depressive symptoms compared to a placebo among
      HIV-seropositive pregnant women.

      Research questions: 1.Does taking omega-3 fish oil supplement with higher EPA in relation to
      DHA have a significant positive effect on depressive symptoms among HIV-seropositive pregnant
      women, compared to a placebo? 2. Is the change in depressive symptom levels among study
      participants related to the change in their omega-3 fatty acid status after intervention with
      omega-3 fish oil supplement and placebo? 3. Which depressive symptoms are more responsive to
      omega-3 fish oil supplement intervention?

      Study setting: The study will be conducted at health facilities in Nairobi, Kenya. According
      to the latest Kenya national population and housing census results of 2009, [30], Nairobi,
      which is the capital city of Kenya, is the most populated city in the country with about 3.1
      million people (about 1.6 million males and 1.5 million females) and an annual growth rate of
      about 4.1%[16]. The available sentinel survey data indicate that the prevalence of HIV/AIDS
      among pregnant women in Nairobi was 10.1% [31] in 2006.

      Methodology: This will be a double-blind, parallel randomized control trial (RCT) using
      omega-3 fish oil supplements and placebo. Both the study participants and the research
      administrators, including the principle investigator, will not know the difference between
      omega-3 supplement and placebo which will be of similar physical characteristics.
      Participants will be recruited from purposely sampled health facilities with highest
      attendance at the Prevention-of Mother-to-Child-Transmission (PMTCT) of HIV AIDS programs.
      The sampling frame will consist of pregnant women with known HIV-seropositive status and
      enrolled in PMTCT program at these health facilities. A total of 200 women who meet the study
      inclusion and exclusion criteria will be enrolled to participate in the study.

      Data Collection: Quantitative methods will be used to collect socio-demographic information,
      dietary intake data, and depressive symptoms, biological specimens of cheek cells, maternal
      weight, CD4 count, blood pressure and compliance with routine medication and study
      intervention. The primary measurement tool for efficacy of omega-3 fish oil will be the Beck
      Depression Inventory, Second Edition (BDI-II) scoring scale with a cut-off score for
      depression of 14 or more. Further understanding of depression in pregnancy and HIV/AIDS
      condition will be gained through qualitative methods. Cheek cell samples will be collected
      through mouth wash method for laboratory extraction of lipids for omega-3 analysis. The
      lipids will be extracted from the cheek cells using Bligh and Dyer methodology [32].
      Gas-liquid chromatography by the method of Gibson and Kneebone [33] will be used to determine
      per cent (%) levels of omega-3 fatty acids in the lipids before, during and after the
      intervention.
    

Intervention name(s): Soybean oil soft gels; Fish oil omega-3 EPA-rich soft gels
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Each participant will receive OmegaVia soybean oil soft gels to take orally, one soft gel taken three times per day in the morning, mid-day and in the evening after meals for a period of 8 weeks; A total of 3.0g of OmegaVia fish oil omega-3 EPA-rich soft gels will be taken orally per day as one soft gel in the morning, mid-day and evening after meals for 8 weeks with bi-weekly follow-up visits.
Other intervention name(s): OmegaVia Soybean oil soft gels; OmegaVia fish oil omega-3 EPA-rich soft gels
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Omega-3; EPA; Depression; HIV infected; Pregnant women