Depression, Anxiety, B12, B vitamins, Omega 3s, Essential fatty acids, diet/nutrients

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Bastyr Student Case Report

A Case of Depression and Anxiety

By Katharine Chang

Abstract

This case report is written to demonstrate the importance of micronutrients and the fundamentals of health in mental disorders such as depression and anxiety. Through a well-balanced diet, proper nutrient supplementation, and healthy relational dynamics, human beings are able to not only step away from their diagnoses but also thrive and step into who they are meant to be. There are a handful of research articles already written on the benefits of omega-3 fatty acids on major depressive disorder.¹ Likewise, researchers have found a significant decrease in depressive symptoms measured by the Hamilton Rating Scale for Depression (HAM-D) in depressed subjects who had additional intervention in the form of a B12 injection.² Since the brain is mainly composed of fat through the form of myelin sheaths, it has been proven that consuming omega-3 fish oils modulate signal transduction and decrease the inflammatory state of the brain which occurs during depression.³ Studies have demonstrated that the biochemical involvement of omega 3 polyunsaturated fatty acids decreases inflammatory cytokines such as IL-1 and TNF-α through the inhibition of nuclear factor-kB, a transcription factor involved in inflammatory signaling pathways.³ Since certain nutrients and fatty acids are depleted in those suffering with depression, especially if they are not consuming a nutrient-dense diet, it is only logical that getting to the underlying cause of disease as well as replacing what is depleted will improve disease outcome. After a month-long follow up with a patient diagnosed with bipolar disorder and depression, there was significant improvement in mood stability and anxiety through dietary intervention and supplementation.

Introduction

Depression is a disease that many experience worldwide and impacts an estimated number of 350 million people.³ Results from the World Mental Health survey show that about 1 in 20 people reported a depressive episode in the previous year. Moreover, it is one of the leading causes of disability on a global scale with high-income countries like the United States and Japan ranking highest, 17% and 3%, respectively.³ According to the World Health Organization, 300 million people worldwide have depression with 16.2 million adults in the United States. Of those 16.2 million, 10.3 million adults experienced at least one episode resulting in severe impairment. Since depression is highly associated with suicide, it is of great importance to research interventions ranging from natural alternatives to conventional pharmaceuticals in order to improve the health outcomes of depression. As stated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), five or more of the listed symptoms have to have been present in the same two week time period and include a change from normal functioning with one of the symptoms being either loss of interest/pleasure or depressed mood. Some symptoms include depressed mood most of the day or almost every day, diminished pleasure or interest in all or most activities, notable unintentional weight loss or weight gain, insomnia, fatigue, feelings of worthlessness/guilt, inability to concentrate, psychomotor agitation or increasing thoughts of suicide or death. Before diagnosing, other substances or medical conditions that may cause similar depressed symptoms must be ruled out.

Depression is a brain disorder that involves imbalanced neurotransmitters and overall systemic inflammation.⁴ Those with depression may experience symptoms including lethargy, mood swings, irritability, difficulty concentrating, lack of motivation, suicidal thoughts, loss of interest, anxiety, insomnia, and sadness. There have been many interventions that have combined pharmaceutical drugs such as selective serotonin reuptake inhibitors (SSRIs), including sertraline, fluoxetine, citalopram, with alternative measures like cognitive behavioral therapy and counseling. SSRIs are known to come with side effects such as sexual dysfunction, weight gain, sleep disturbances, headache, and appetite changes; and studies have shown that the need for natural alternatives to treat depression and mood disorders has formally surfaced especially for those currently taking these drugs.^5,6 Omega-3 fatty acids have been shown to be beneficial in the treatment of depression.⁷ It is already well known through several studies that those who consume a diet rich in omega-3 fatty acids are less susceptible to developing depression, which includes prenatal and bipolar depression.⁴ Compared with the rest of the world, the Western diet is saturated with omega-6 fatty acids, which contribute to many inflammatory pathways in the body when consumed in excess.³ In addition to fatty acids, B vitamins especially B6, folate (B9), and B12 have been well known to play an essential role in cell metabolism and biochemical processes in the human body.⁸ These vitamins play a role in building neurotransmitters along with other nutrients such as protein and lipids.⁹ Researchers have studied the effect of multivitamins on mood and neurocognitive function and found not only emotional improvement but also biochemical changes in the serum.⁹ With natural interventions such as these, the trajectory of those dealing with depression is positive due to the ability of not only improving but sustaining long-term health. Thus, this all leads to the question: To what degree can appropriate supplementation of omega-3s and multivitamins improve depressive symptoms and mood disorders?

Case Description

A.P. is a 34-year-old Caucasian male that presented to our clinic with a chief concern of stabilizing mood and addressing depression. He has a history of bipolar disorder diagnosed in 2016, anxiety, insomnia, and drug and alcohol abuse. His main symptoms were low energy, wanting to sleep, and a decreased appetite. He works at a jet fuel company and has a very stressful relationship with his boss, mentioning multiple times that he feels anxious at work. He leaves work often wanting to sleep, not due to fatigue but because he does not like his job. The only medication he is on is lamotrigine (100 mg) to manage his bipolar disorder. He was prescribed and currently taking lithium orotate (5 mg 1-2 times/day)

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a ProOmega 2000 (2000 mg/day) and magnesium glycinate (20 mg/each, 3 caps at night). In office, review of systems came back negative except for the fact that he experiences mood swings every day; however, he stated that he is able to manage it well due to being on Lamictal and the lithium orotate. His previous in-office Patient Health Questionnaire-9 (PHQ-9) total scores came back none-mild and an in-office PHQ-9 during his most recent visit was a 5, which is mild. His most recent labs were done in January 2018 and all lab values were within normal limits (refer to Table 1).

Table 1: Patient Lab Values

Future labs we have considered were salivary cortisol, vitamin D and vitamin B12 levels, a male hormone panel, and thyroid labs since many of his symptoms such as irregular mood, low energy, and insomnia can overlap with depression and bipolar disorder. We have considered checking his cortisol rhythms because he reported having a spurt of excitement around 8:30-9:00 pm. After considering the patient’s entire symptom picture including social and past medical history, a working diagnosis of nutrient depletion was made. The patient is not on a multi-vitamin, his diet is sub-optimal, he works inside a warehouse with jet fuel exposure, and he does not take his omega-3 fatty acids consistently. We made sure to take into consideration his current work situation and life circumstances that could have also been perpetuating his mood instability and depression as well. We inquired every visit about his social support network, and he stated that he feels comfortable reaching out to his girlfriend and friends in times of need.

We prescribed D-Mulsion Citrus Vitamin D drops at 2000 IUs per day, a men’s multivitamin by Vitamin Code at 2 capsules twice a day, and a recommendation to take his fish oils regularly at 2000 mg per day, especially since he has external stressors from his occupation and is anxious in preparation for an upcoming move.

A conversation regarding transitions was brought up to make space for his thoughts in regards to moving away. The patient reported he would feel relief due to leaving his current job but does not know how smoothly he will transition into another environment with the pressure of finding a new job and making new friends. In office, we reminded him about the excitement, challenges, and possible discomfort of transitioning into an entirely different community, which the patient was open to discussing. He was aware and reported feeling a little more comfort knowing his girlfriend will be going alongside him. We also educated him on consuming a variety of nutrients including proteins and healthy fats and suggested that he substitute his morning coffee with Teecino herbal blends since caffeine can inhibit tryptophan conversion into serotonin. The patient moved out of state shortly after the appointment and quit his job, which was a major source of his stress and a trigger to his depressive symptoms. We followed up with him after a month and the patient reported experiencing increased stability of mood and less anxiety, although he was experiencing more stress from looking for a new job.

Discussion

The differential diagnosis list for the patient included stressful relational dynamics at work, nutrient deficiencies of B vitamins (B6, folate, B12), vitamin C, and omega-3 fatty acids, which are all nutrients commonly depleted in depression. The patient did report negative changes in mood and stress when he was around his old boss; therefore, it was important to take external stressors such as work environment into consideration. Through a more biochemical lens, B vitamins are heavily involved in cellular functioning and serve as essential cofactors that ultimately lead to production of neurotransmitters like serotonin, GABA, and dopamine.⁹ In depression, even minor deficiencies of B vitamins like B6 downregulate serotonin and GABA production, which contribute to symptoms such as irregular sleep patterns and behavioral changes.⁸ Furthermore, the study performed by White et al., demonstrated that supplementation with multivitamins including 500 mg/day of vitamin C showed mood benefits and specifically reductions in depressed mood.⁹ The patient’s diet does not consist of foods that are particularly high in vitamin C, which can potentially be contributing to his low mood. Likewise, foods he frequently eats such as quinoa, black beans and rice do not possess high levels of healthy fats such as omega-3 fatty acids. An imbalanced diet was also on the differentials list since he eats very carbohydrate heavy meals, though mostly vegan (quinoa, rice, black beans, pasta, and granola). Furthermore, he is not consuming enough protein (at least 56g/day based on body his weight) and healthy fats which are essential in the production of neurotransmitters.⁹ Other differentials of lower priority were male hormone imbalance and hypothyroidism since symptoms of depressed mood and low energy can be seen in these processes as well.

In a study performed by Mocking et al in 2016, it was found that supplementation with omega-3 fatty acids has a positive effect in those suffering with major depressive disorder (MDD).⁷ Researchers also found that higher EPA doses were associated with a better response whereas DHA did not have a significant effect on MDD symptoms.⁷ In another study performed in Rotterdam, researchers found that individuals who had lower concentrations of omega-3 fatty acids experienced severe symptoms of depression; therefore, supplementing or increasing dietary omega-3 fatty acids has been and is increasingly being studied for benefiting depression.¹⁰

The formation of neurotransmitters and prostaglandins is affected by omega-3 and omega-6 fatty acid proportion, which is very important in the maintenance and regulation of normal functioning of the brain. Thus, ensuring that an individual has optimal omega-3 levels is crucial, especially for those dealing with depression. In addition to supplementing with these fatty acids, many foods such as salmon and mackerel are often recommended due to their rich source of omega-3 fatty acids. Ever since omega-3 oils have been shown to improve depressive symptoms, there have been more studies done that show the effect of omega-3 oils in other mental health disorders such as bipolar disorder, schizophrenia, and dementia.⁴ Likewise, other studies assessing the military diet have demonstrated the possibility of reducing psychiatric disorders like suicide and impulsive aggression by increasing omega-3 fatty acids.⁴

The role of multivitamins, including B vitamins, has also been in the spotlight for not only improving depressive symptoms but also inflammatory lab biomarkers. In a randomized, double-blinded study performed by White et al, supplementing with a multivitamin significantly improved mood in a matter of four weeks. This was concluded by reduced scores according to the depression-dejection scale of the Profile of Mood State. Researchers also found that increasing B vitamins decreased homocysteine levels in young healthy adults. Other research has undoubtedly shown the role of multivitamins, especially B vitamins, in improving stress and mood and decreasing risk for neurodegenerative diseases like Alzheimer’s disease. Another randomized controlled trial that specifically studied vitamin B12 and its effect on treating major depressive disorder demonstrated that having a B12 injection along with taking antidepressant medication had significant impact on depressive symptoms.² Researchers screened 199 depressed patients in total and out of that, 73 patients had a low to normal B12 level. They randomized 34 patients to the treatment group and 39 to the control group. After three months, 100% of the treatment group taking antidepressants along with receiving B12 injections showed a 20% decrease in their HAM-D rating score, whereas only 69% of the control group taking only antidepressants showed 20% reduction in their scores.

The research studies up to date, although convincing, still reveal much conflicting evidence. Since the therapeutic dose of omega-3 fatty acids in supplement form, usually 9 grams, is sometimes hard to achieve due to the concern of causing gastric pain, it is difficult to truly understand the potency and efficacy of it. Also, the different forms of supplemental fish oils used in the studies are not specifically stated since the synthetic ethyl ester (EE) form differs in efficacy and safety compared with the natural triglyceride (TG) form. Likewise, the source of these fish oils is hard to control between studies as well. Furthermore, there is also a need to take the genetic variability among different participants into account. More research needs to be done to support the claim of fish oils on depression and a greater population size needs to be obtained. It would be beneficial to study the specific interaction between antidepressants and the EPA component of fish oils and the possibility of enhancing drug effect. There should be more consistency across the studies in regards to taking into account participant dietary status, health history, sex, age, and lifestyle habits, including smoking, and drug and alcohol use.

Conclusion

The beneficial effects of omega-3s and natural interventions have been researched and shown to have substantial effects on human mood; however, a more universal claim needs to be made on its efficacy. There is a lot of variability seen in clinical trials involving the testing of omega-3s; but since depression can have many causes other than a lack of omega-3s in the diet, more targeted and comprehensive trials need to be undertaken. Supplementation and implementing food as medicine to support the patient is warranted especially in cases when social and environmental factors are not under the patient’s control and cannot be removed within a certain time period. Depression involves the increased presence of pro-inflammatory cytokines and higher omega-6 to omega-3 ratios thus, increasing omega-3 fatty acids not only enhances cognitive function but also decreases symptoms of depression.^4,10 The balance of neurotransmitters, essential fatty acids, and B vitamins is essential and heavily involved in maintaining normal brain function and stability of mood.^2,4 It can be inferred that including more foods that contain B vitamins (organ meats, eggs, beans, lentils, sunflower seeds, broccoli, spinach) and omega-3 fatty acids (sardines, chia seeds, walnuts, Brussels sprouts) could be a simple, preventive measure against mood instability, especially for those dealing with mental health concerns like depression, anxiety, and bipolar disorder. It is warranted to investigate deeper into the cause of mood instability and assess if certain underlying factors can be removed; this can range from unhealthy relational dynamics to true micronutrient depletion from an inadequate diet.

Although many biochemical factors can contribute to symptoms of depression, meeting the patient where they are in their health journey and helping them establish strong foundations of health, which includes exploring topics such as their sense of well-being and past traumas, takes priority. It is critical to give equal opportunity and weight to mind, body, and spirit and not end treatment after addressing a lab value that is out of range, especially when working with mental health disorders. Each individual has unique genetic profiles, social and medical history, and determinants of health; thus, individualized, personalized treatment is of utmost importance when it comes to patient care.

References

1. Bastiaansen JA, et al. The efficacy of fish oil supplements in the treatment of depression: food for thought. Transl Psychiatry. 2016;6(12):e975.

2. Syed EU, Wasay M, Awan S. Vitamin B12 Supplementation in Treating Major Depressive Disorder: A Randomized Controlled Trial. The Open Neurology Journal. 2013;7:44-48.

3. Grosso G, et al. Omega-3 Fatty Acids and Depression: Scientific Evidence and Biological Mechanisms. Oxidative Medicine and Cellular Longevity. 2014;2014.

4. Wani AL, Bhat SA, Ara A. Omega-3 fatty acids and the treatment of depression: a review of scientific evidence. Integr Med Res. 2015;4(3):132-141.

5. Ferguson JM. SSRI Antidepressant Medications: Adverse Effects and Tolerability. Prim Care Companion J Clin Psychiatry. 2001;3(1):22-27.

6. Necyk C, et al. Study of natural health product–drug adverse reactions (S.O.N.A.R.) in patients seeking mental health services. Current Medical Research and Opinion. 2016;32(8):1335-1343.

7. Mocking RJ, et al. Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Transl Psychiatry. 2016;6(3):e756.

8. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy–A Review. Nutrients. 2016;8(2):68. Published 2016 Jan 28.

9. White DJ, et al. Effects of Four-Week Supplementation with a Multi-Vitamin/Mineral Preparation on Mood and Blood Biomarkers in Young Adults: A Randomised, Double-Blind, Placebo-Controlled Trial. Nutrients. 2015;7(11):9005-17.

10. Tiemeier H, et al. Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam study. Am J Clin Nutr. 2003;78:40–46.

Katherine Chang is a fourth-year naturopathic medical student at Bastyr University in San Diego, California. She obtained her bachelor’s degree in Hispanic studies while studying pre-medicine and always possessed a desire to help people. Growing up, she experienced the power of nutrition and natural medicines firsthand and wholeheartedly believes she was divinely called to this profession. Her clinical interests include mental health, oncology, autoimmunity, and pain management. After graduating in spring 2019, she looks forward to joining a naturopathic medical practice and promoting naturopathic medicine within the greater Los Angeles community. She has received advanced training in regenerative joint injections, nutraceutical formulation, IV therapy, and PRP aesthetics. Her long-term aspirations are to do a lot of community work with school-aged children in low-income neighborhoods to prevent childhood obesity and mental health disorders. Besides medicine, she enjoys gardening, nature walks, family time, and practicing Chinese calligraphy.