Something s Fishy in Depression Treatment: The Potential of Cod Liver Oil as a Treatment for Major Depressive Disorder. Pilar Curtis 05/03/2010

Transcription

1 Something s Fishy in Depression Treatment: The Potential of Cod Liver Oil as a Treatment for Major Depressive Disorder Pilar Curtis 05/03/2010 Science B-23: Human Organism Section Leader: Diane Gilbert-Diamond 1

2 Abstract Major depressive disorder (MDD) is the most common mental illness in the United States, affecting over 6% of Americans yearly. While placebos have been proven to be relatively effective in treating mild to moderate cases of MDD, traditional treatment for the depressive symptoms associated with the disorder typically involves a combination of antidepressant drugs and psychotherapy. Unfortunately, most antidepressants are both costly and tend to be associated with negative side effects; therefore, many people affected by MDD are looking for natural alternative treatments. Much research has been devoted to the therapeutic potential of cod liver oil, and particularly the omega-3 fatty acids it contains. While cod liver oil is often advertised as an effective treatment for mood disorders, the current body of research in the field does not provide concrete empirical support for these claims. Many studies support the role of omega-3 fatty acids in treatment for MDD, but many others provide evidence that is not in accord to this hypothesis. Until further well-designed studies are conducted, the true therapeutic potential of cod liver oil will be unknown. However, I argue that since the ingestion of cod liver oil is very safe, and some studies have shown therapeutic effects, physicians should continue to recommend its use to patients. If patients believe that cod liver oil will aid their symptoms, they may be helped solely by the placebo effect. As long as this practice maintains close monitoring by physicians, it should be endorsed as an intermediate treatment for MDD. 2

3 In order to lead a healthy life, a person needs to have both physical and mental wellbeing. One of the most common disruptions to mental health in America is an affective disorder called major depressive disorder (MDD). MDD is characterized by recurrent episodes of depressive symptoms that disrupt daily activities. According to the National Institute of Mental Health (NIMH, 2010), 14.8 million Americans over the age of 18 suffer from MDD every year. In addition to its high prevalence in the United States, MDD is of major concern to healthcare professionals due to the high number of people affected by the disorder who resort to committing suicide. Mental Health America (2010) cites major depression as the main factor contributing to the over 30,000 suicides that occur every year in the United States. In fact, suicide is the 8 th leading cause of mortality in the country (Andrew, 2010). Due to MDD s high cost for the American population, much attention has been paid to the development of treatments for the disorder. Antidepressants and psychotherapy have already been established as relatively effective treatments for MDD (WebMD, 2010). However, paralleling a recent focus on nutrition in the country, nutritional supplements have also begun to be recommended to patients. One such supplement is cod liver oil. This paper aims to dissect recent research investigating the possible mental health benefits afforded by cod liver oil in order to determine whether its use in the treatment of MDD has garnered enough empirical support for the justification of the practice. A recent post on the website HarvardFML, which serves as an outlet for frustrating events in student s lives, states: Today, I went to UHS [Mental Health Services] because of my depression; I can t wake up in the mornings and have zero motivation. They prescribed fish [expletive] oil. FML. (HarvardFML, March 4 th, 2010). This post not only indicates that some patients expect a traditional treatment when they seek the help of healthcare professionals, but also that those who receive a recommendation for the use of cod liver oil do not appreciate its 3

4 potential medicinal benefits. In order to understand physicians motivation in prescribing alternative treatments for MDD, the traditional methods and their potential downsides must first be understood. Throughout the past few decades, the healthcare industry has made much advancement in the treatment of major depressive disorder (MDD). Several classes of antidepressants have been developed to treat the symptoms of the mental illness, including monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (WebMD, 2010). These medications, as indicated by their names, influence the production or reabsorption of specific enzymes and neurotransmitters in the body, allowing hormonal imbalances in the brain to be at least partially resolved. There are also various schools of psychotherapy that have proven to be effective in the treatment of MDD; for example, cognitive behavioral therapy aims to change the way patients perceive their environments and the way that they react in different situations (NACBT, 2007). With this two-pronged approach, both the distal causal factors and proximate symptoms of MDD can be treated simultaneously. However, patients seldom respond optimally to the same regimen as other patients. Instead, treatment often requires many trials and errors before an effective treatment is found for a patient. Many antidepressants are also associated with a variety of negative side effects, including weight gain, fatigue, anxiety, and sexual dysfunction (Mayo Clinic, 2010). Additionally, certain studies claim that the use of antidepressants in the treatment of mild or moderate cases of MDD is no more effective than the use of a placebo (Tuzzo & Ferran, 2010). Therefore, the use of a nutritional supplement such as cod liver oil in treatment is an enticing option either for intermediate periods between traditional treatments, or to treat mild cases of MDD. 4

5 While many nutritional supplements are thought to have effects on mood, much of the research in the field has been devoted to the study of cod liver oil. The primary components of cod liver oil are vitamin A, vitamin D, and omega-3 fatty acids (Fallon & Enig, 2009). Some interest in the effects of vitamin D on depressed persons has arisen, largely due to the role of sunlight in both vitamin D absorption and mood alteration in seasonal affective disorder (SAD), a type of depressive disorder (Young, 2009). However, most of the studies that have investigated the effects of vitamin D on depression have had faulty designs and therefore hold little academic credibility. Instead, the primary focus of research on cod liver oil is devoted to omega-3 fatty acids. Omega-3 s are essential fatty acids; these polyunsaturated fatty acids cannot be produced by the human body, but are necessary for good health (University of Maryland Medical Center, 2009). The two most important for brain functions such as neurotransmitter reception and signal transmission are EPA and DHA, both of which are contained in cod liver oil (Leung & Kaplan, 2009). Omega-3 fatty acids have been associated with many benefits to overall health, including decreased inflammation. Some studies have also indicated that omega-3 fatty acids may reduce the risk of certain illnesses, such as cardiovascular disease and some cancers. However, studies that support the health effects of omega-3 fatty acids are often contested by others that find no such results. This pattern is also true of the effect of omega-3 fatty acids on mood and depression. Marleen Freeman s (2009) paper Complementary and Alternative Medicine (CAM): Considerations for the Treatment of MDD provides a salient introduction for the debate surrounding the use of cod liver oil as an antidepressant. Freeman gives a broad overview of the use of non-pharmaceutical medicine in the treatment of the mental illness, focusing on MDD. She states that the enticing over-the-counter availability of alternative treatments such as cod 5

6 liver oil, coupled with the wide array of information accessible by the public over the Internet, can lead to unreported cases of MDD. The paper specifically discusses the ability for websites to exaggerate the amount of empirical support that any alternative medicinal practice has obtained, which can be misleading to people seeking treatment for depression. Freeman emphasizes that MDD is a serious mental illness, and the onus of diagnosis and treatment of depression should not be on the patient. Without drawing firm conclusions in either direction, Freeman discusses the available treatments for MDD, but emphasizes the need for adequate evaluation and monitoring by a physician for any treatment program. Without demonizing alternative treatments, Freeman s editorial illustrates the necessity of both further research in the field and a thorough analysis of the available data. Through a review of existing studies and their results, it may be possible to illuminate the true potential of depression treatment with cod liver oil, and to identify certain characteristics of individual cases that could indicate cod liver oil as an effective treatment. One of the most commonly cited sources of support for the benefits of cod liver oil on depression is a study conducted in Norway by Raeder, Steen, Vollset, and Bjelland (2007). These researchers wanted to explore the relationship between regular use of cod liver oil supplements and symptoms of depressive episodes in the general population. In order to do so, Raeder et al. analyzed the data recovered from the Hordaland Health Study. This national survey collected health-related data from a representative sample of 21,835 Norwegians between the ages of and Researchers specifically analyzed depressive symptoms reported by participants, which were measured by a standardized Hopsital Anxiety and Depression Scale. They also analyzed the use of cod liver oil by both asking participants to list the medications and nutritional supplements that they had taken on the previous day, and asking them to report cod liver oil use 6

7 in the past year. The results of the study showed that while 3.8% of respondents who did not use cod liver oil reported depressive symptoms, only 2.5% of their counterparts reported daily use of cod liver oil suffered from these indicators of MDD. Therefore, researchers concluded that the daily use of cod liver oil is negatively correlated with feelings of depression. This study is very important in supporting the hypothesis that omega-3 fatty acids and cod liver oil have an important preventative or therapeutic effect on symptoms of depression. However, there are limitations to this study that are addressed by its researchers. Since the study did not utilize a randomized controlled trial design, there are certain individual factors for which the analysis of the results cannot account. For example, the diet of respondents was not monitored, and may be a confounding variable in omega-3 fatty acid intake if participants eat varying amounts of fish or plan sources. In addition, the study only includes people of very specific age ranges, which could affect its results. Another strong body of evidence for the use of cod liver oil to treat MDD comes from a review done by Leung and Kaplan (2009), which discussed studies investigating the association between omega-3 fatty acids and perinatal depression. Perinatal depression occurs in mothers either during pregnancy (antenatal depression) or shortly after they have given birth to their children (postpartum depression). Many studies implicate major hormonal fluctuations associated with pregnancy and giving birth in the causation of perinatal depression, including the dysregulation of cortisol. While this disorder is not entirely paralleled by MDD, the symptoms of the two mental illnesses are similar enough to suggest that any effect of cod liver oil on the depressive symptoms of one would also be relevant to the other. Leung and Kaplan report that many studies indicate that a deficiency in the dietary intake of omega-3 fatty acids is a risk factor for the development of perinatal depression. However, the majority of these studies show only 7

8 low levels of omega-3 fatty acids in people with perinatal depression, or lower levels of the disorder among populations whose diet includes high DHA intake. Therefore, these results are primarily correlational in nature, and are not often randomized controlled trials. Kaplan and Leung also discuss studies that do not report the same pattern. They conclude that nutritional deficiency of omega-3 fatty acids in pregnant women may be a factor contributing to the risk of perinatal depression, and that further controlled studies on the topic are necessary. In essence, these findings are in accord with Freeman s (2009) recommendation of further study and supporting evidence for the use of cod liver oil as an alternative therapy for the depressive symptoms of MDD. In order to provide evidence of the therapeutic validity of natural remedies for depressive disorders, Mischoulon (2009) discusses several studies in the field in his paper Update and Critique of Natural Remedies as Antidepressant Treatments. Mischoulon reports that many controlled trial studies speak to the effectiveness of omega-3 fatty acids in the reduction of depressive symptoms. For example, one study indicated that an intake of roughly 5 times the normal recommended intake of omega-3 fatty acids is effective as an antidepressant regime. In addition, certain studies have found that those who have sought treatment for MDD but have proven to respond positively to treatment with omega-3 fatty acids. These patients experience a reduction in fatigue, sexual dysfunction, anxiety, and depressive symptoms on a significantly higher scale than those who are treated with a placebo. Therefore, Mischoulon concludes that the effects of omega-3 fatty acids validate their use as a complementary treatment for depression. Since their ingestion in large quantities is also completely benign, Mischoulon states that their use should not be discouraged. However, Mischoulon warns that the evidence supporting the use 8

9 of dietary supplements as primary antidepressant treatments is as of yet inconclusive, and must be monitored and researched by trained professionals. While the articles reviewed above discusses the limitations of previous research in the field and warns about its relatively inconclusive results, they generally promote the use of cod liver oil and omega-3 fatty acids it contains as a potential treatment for MDD. Other researchers, however, have not supported these findings. Milte, Sinn, and Howe (2009) review available research that investigates whether levels of polyunsaturated fats are abnormal in people with ADHD, depression, and Alzheimer s disease as compared to those with good mental health. They report that while many studies indicate a positive effect of omega-3 fatty acid supplementation on depression, there must be more focus on the baseline levels of polyunsaturated fatty acids before conclusions can be drawn. They discuss the possibility that the levels of EPA or DHA in the brain or blood may predetermine the effectiveness of treatment with omega-3 fatty acids. In so doing, Milte et al. do not discredit the potential benefits of cod liver oil for depressive symptoms; however, they suggest that the results of the studies claiming high effectiveness of the treatment are likely due to extenuating factors that must be controlled in future studies. Results from other studies urge some researchers to draw more radically negative conclusions about the potential antidepressant effects of the omega-3 fatty acids contained in cod liver oil. A study conducted by Astorg et al. (2009) aims to determine the predictive validity of omega-3 fatty acids on future depressive episodes in middle-aged French men and women. These researchers tested the plasma omega-3 fatty acid levels of participants upon first participation in the study, and then conducted a follow-up appointment 8 years later. The participants in the study were divided into two groups for analysis; the first included 444 people who reported 9

10 having been prescribed antidepressants or lithium at least twice since their baseline blood testing, and the second consisted of 371 people with no history of depressive symptoms or relevant prescriptions. Upon comparison of their baseline omega-3 fatty acid levels, Astorg et al. determined that they were not significantly different between participants with a history of depression and those without. The researchers concluded that the major predictive factors for depressive episodes in their population were socio-professional status and tobacco use, and that omega-3 fatty acid levels held no predictive validity. Therefore, Astorg et al. indicated that they were skeptical about the preventative qualities of omega-3 fatty acids against the depressive symptoms associated with MDD. The overall attitudes toward the strength of empirical evidence supporting the use of cod liver oil and omega-3 fatty acids as a treatment for MDD differ vastly in the aforementioned reviews and studies. However, the researchers involved in this debate tend to agree on one thing: there is simply not enough research to provide concrete conclusions on either side. In designing future studies in the field, researchers must aim on the improvement of several aspects of past experiments. For example, studies must investigate effects among a larger age range, and aim to have a fairly balanced gender representation in their participant pools. Furthermore, the fact that most studies take into account either the effects of plasma levels of omega-3 fatty acids or the therapeutic effects of omega-3 fatty acid supplementation, as opposed to both, is detrimental to garnering adequate knowledge on the topic. If studies were to account for both potential effects of cod liver oil on depressive symptoms, physicians could have a clearer frame of reference for the recommendation of the alternative treatment. Evidently, the exact status of cod liver oil as an effective alternative treatment for MDD will not be clarified until a large body of well planned research is conducted and reviewed. 10

11 However, many of those seeking treatment for depressive symptoms of MDD cannot be satisfied by this inconclusive decision of the merit of cod liver oil. Therefore, the question still stands: should physicians recommend the use of cod liver oil as an alternative treatment for MDD? The answer to this question has not been found in the heavily debated characteristics of either omega- 3 fatty acids or depression itself. Perhaps, then, it can be found in a proven characteristic of traditional treatment. One interesting aspect of treatment for depressive disorders is that the placebo effect is highly prevalent among mild and moderate cases (Rief et al., 2009). The placebo effect is a medical phenomenon in which a patient s belief that he or she is being treated effectively can lead to lessened symptoms of certain illnesses or ailments, even when actual treatment is not provided. Drug trials prove that up to 68% of the positive effects of antidepressants are due to the placebo effect as opposed to the true action of the medication. This characteristic of depression treatment is problematic for those producing the drugs, since it is difficult to market a drug whose effects are proven to be relatively similar to those of a sugar pill. However, the placebo effect can be very promising for physicians ability to help reduce their patients depressive symptoms. Practically nowhere in the body of research surrounding cod liver oil supplementation or treatment is there any mention of any deleterious effects of the substance. Even when ingested at 5 times the standard daily intake, the worst reported side effects of cod liver oil are a slightly fishy aftertaste and mild gastrointestinal discomfort (Mischoulon, 2009). In addition, it is known that cod liver oil has beneficial effects on overall health, no matter the validity of its use as an antidepressant. Therefore, the fact that physicians recommend that depressed patients take cod liver oil in hopes that it will lessen their symptoms causes no harm to these patients, as long as they are educated about the potential effects and limitations of the 11

12 supplement, and their progress continues to be monitored by professionals. The safety and benefits of cod liver oil, coupled with the therapeutic ability of a placebo in treating depression, may indicate that physicians should continue to recommend the use of cod liver oil to depressed patients in hopes that their belief in the supplement s antidepressant potential will work to alleviate their depressive symptoms. This use of cod liver oil could prove to be particularly useful as an interim treatment for cases of depression that prove to be resistant to traditional antidepressants, or on mild to moderate cases that are usually subject to the placebo effect. It may therefore be beneficial for physicians to continue to encourage these patients to take cod liver oil. In conclusion, the use of cod liver oil to treat MDD is highly debated within the field. The current body of research investigating the potential antidepressant effects of cod liver oil does not draw concrete conclusions for either the continuation or cessation of the practice. Flaws of design plague both studies that support the therapeutic effects of cod liver oil and omega-3 fatty acids on MDD and those that dispute these effects. Therefore, until future studies that control for confounding variables such as the difference between preventative and therapeutic uses of omega-3 fatty acids, the validity of cod liver oil as a treatment for MDD will remain uncertain. However, the relatively high probability of positive outcomes in MDD treatment being caused by the placebo effect may encourage the recommendation by physicians that their patients take cod liver oil. In order for this practice to take advantage of the placebo effect, physicians must thoroughly educate their patients about the benefits of omega-3 fatty acids on depression. Finally, it is of utmost importance that if physicians do have their patients take cod liver oil, they must also continue to monitor the progression of the illness. In so doing, patients 12

13 who do not experience alleviation of depressive symptoms will be able to be prescribed a new treatment plan within an appropriate time frame. 13

14 References Andrew, L.B. (2010, March 30). Depression and suicide. Retrieved April 20, 2010, from emedicine website: Anonymous. (2010, March 4). Retrieved on April 14, 2010 from HarvardFML website: Astorg, P. et al. (2009). Long-chain n-3 fatty acid levels in baseline serum phospholipids do not predict later occurrence of depressive episodes: A nested case-control study within a cohort of middle-aged French men and women. Prostaglandins, Leukotrienes and Essential Fatty Acids, 81, Fallon, S. & Enig, M.G. (2009, February 8). Cod liver oil basics and recommendations. Retrieved March 6, 2010, from the Weston A. Price Foundation website: Freeman, M.P. (2009). Complementary and alternative medicine (CAM): Considerations for the treatment of major depressive disorder. Journal of Clinical Psychiatry, 70[suppl 5], 4-6. Leung, B.M. & Kaplan, B.J. (2009). Perinatal depression: Prevalence, Risks, and the Nutrition Link A review of the literature. Journal of the American Dietetic Association, 109, Mayo Clinic Staff. (2010, February 11). Depression (major depression): Treatments and drugs. Retrieved from gs Mental Health America. (2007, December 11). Ranking America s mental health: An analysis of depression across the States. Thompson Healthcare: Washington, D.C. National Institute of Mental Health. (2010, April 30). The numbers count: Mental disorders in America. Retrieved from mental-disorders-in-america/index.shtml#kesslerprevalence Milte, C.M., Sinn, N. & Howe, P.R. (2009). Polyunsaturated fatty acid status in attention deficit hyperactivity disorder, depression, and Alzheimer s disease: Towards an omega-3 index for mental health? Nutrition Reviews, 67(10), Mischoulon, D. (2009). Update and critique of natural remedies as antidepressant treatments. Obstetrics and Gynecology Clinics of North America, 36, National Association of Cognitive-Behavioral Therapists. (2007, April 5). Cognitive behavioral therapy Retrieved from 14

15 Raeder, M.B., Steen, V.M., Vollset, S.E. & Bjelland, I. (2007). Associations between cod liver oil use and symptoms of depression: The Hordaland health study. Journal of Affective Disorders, 101, Rief, W., Nestoriuc, Y., Weiss, S., Welzel, E., Barsky, A.J. & Hofmann, S.G. (2009). Metaanalysis of the placebo response in antidepressant trials. Journal of Affective Disorders, 118, 1-8. Tuzzo, J. & Ferran, L. (2010, January 6). Study: Antidepressants, placebos near equally effective. Good Morning America: Healthy Living. Retrieved from: University of Maryland Medical Center. (2009). Omega-3 fatty acids. Retrieved from WebMD. (2010). What is depression? Retrieved from Young, S.N. (2009). Has the time come for clinical trials on the antidepressant effect of vitamin D? Journal of Psychiatry and Neuroscience, 34(1), 3. 15