Role of Omega-3 Fish Oil Fatty Acids on Depression Among HIV-seropositive Pregnant Pregnant Women in Nairobi: A Randomized Double-blind Controlled Trial

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].