May 2025 Issue
Nutritional Psychiatry & Bipolar Disorder
By Sara Chatfield, MPH, RDN, LDN
Today’s Dietitian
Vol. 27 No. 5 P. 16
Recent Developments in Nutrition Applications
Bipolar disorder (BD) is a complex and often debilitating mental health condition characterized by marked fluctuations in mood and energy.1 People with BD tend to swing from depression to mania; manic episodes can include grandiose thinking, rapid speech, reduced need for sleep, impulsivity and risk taking, and possibly psychosis.1,2 BD is associated with impairments in functioning and cognition and a high risk of suicide.1,3-8 Individuals’ symptoms vary widely and subtypes of the disorder reflect differences in the severity of mania; bipolar I includes mania and often greater functional impairment, while bipolar II features milder, hypomanic episodes.2 BD affects about 4.4% of US adults in their lifetimes.3 The average age of onset is 25 years; BD begins most commonly in the adolescent or young adult years, but some individuals have onset later in adulthood.1,2,8,9
BD tends to co-occur with other mental health conditions and chronic physical illnesses. Common mental health comorbidities include anxiety, ADHD, PTSD, eating disorders, and substance use disorders.1,5,7,8,10 Common physical conditions include CVD, metabolic syndrome, type 2 diabetes, obesity, irritable bowel syndrome, neurological diseases, and respiratory diseases.2,5,6,8,10-12 Suicide and chronic physical comorbidities, particularly CVD, contribute to the significantly—about 20% to 30%—lower life expectancy of individuals with BD, compared with the general population.2,5,8,10-12
Etiology and Treatments
The etiology of BD is not clear, but recent research has uncovered potential genetic, epigenetic, and environmental contributors.1,2,4,8 Researchers have suggested that an interplay between oxidative stress, mitochondrial dysfunction, inflammation, and immune dysfunction may underlie the disorder.13,14 Elevated oxidative stress levels can damage cells, DNA, and mitochondria, and may contribute to immune and neurocognitive dysfunction in BD, including altered levels of neurotransmitters that affect mood.2,7,13 Mitochondrial disturbances, in turn, can increase oxidative stress and alter intracellular calcium levels, which are typically elevated in BD.2,13-15 Individuals with BD tend to have increased inflammatory markers, which can indicate high levels of inflammation systemically and neurologically.4,7,10,16,17 Additionally, some studies have found imbalances in the microbiota of people with BD, which can contribute to inflammation, oxidative stress, and immune dysfunction.2,7,14 Chronic inflammation and oxidative stress likely factor into the higher rates of chronic physical conditions in individuals with BD, including metabolic disorder, diabetes, and CVD.11,12,16
Typical treatments for BD include medications, psychotherapy, and complementary treatments.1 Commonly prescribed medications are antidepressants, antipsychotics, anticonvulsants, and lithium.7 Rates of medication nonadherence are high among people with BD and adverse side effects are common; the anticonvulsant valproic acid can lead to deficiencies of folate and vitamin B12, and some antipsychotics and anticonvulsants can lead to weight gain and metabolic dysfunction.7,10,18,19 There’s evidence that some medications reduce microbial diversity in the gut, which may contribute to metabolic alterations, although treatment with lithium may increase microbial diversity and help regulate calcium.7 It’s also important to note that lack of treatment and more manic episodes have been associated with an increased risk of CVD mortality, while treatment with lithium and other medications has been linked to a reduced risk of CVD mortality in people with BD.7,12 Individuals with BD frequently experience residual symptoms and recurrences despite treatment with medication, so finding effective complementary strategies such as nutrition and lifestyle changes could be vital to improved management of the disorder.4,16,19
Nutrition Strategies
Nutrition intersects with many of the physical and psychological complications associated with BD. Poor dietary habits can contribute to inflammation and oxidative stress and can impact the immune system, which may worsen BD progression and symptoms and raise the risk of chronic diseases.13 As more information on the potential benefits of nutrition strategies comes to light, it opens possibilities for helping people with BD. Improving nutrition intake can reduce inflammation and oxidative stress, and may help with symptom control and chronic disease prevention.2,11
People with BD are more likely to have poorer nutrition and lifestyle habits than the general population, including irregular eating patterns; higher intake of saturated fat, salt, and sugar; low fiber intake; higher intake of processed meats and snacks; and lower adherence to a Mediterranean diet pattern.2,6,7,10,12,16,18 Furthermore, a high percentage of individuals with BD—up to 30% in some studies—report binge-eating behaviors.10,12 Excess sugar intake and other poor dietary and lifestyle habits can contribute to problems frequently experienced by individuals with BD, such as chronic inflammation, oxidative stress, overweight, and metabolic dysfunction, including higher blood glucose and lipid levels.2,7,11,18 Sleep disturbances in BD may also increase inflammation and negatively impact immunity.7 Increasing physical activity may improve symptoms and functioning in people with BD; however, about 40% to 65% report that they are sedentary.7,12 The fluctuating energy levels and appetite common in individuals with BD may be closely tied to unhealthy habits.11,16,18
Nutrition research findings in this population typically reflect common challenges. Data from observational studies indicates that individuals with BD tend to have lower blood levels of the omega-3 fatty acids EPA and DHA, essential to neuronal function, and higher ratios of omega-6 to omega-3 fatty acids, which have been linked with higher levels of inflammatory markers.13,16 Additionally, some studies have found that individuals with BD had lower levels of many essential micronutrients, including iron, zinc, manganese, selenium, folate, vitamin B12, and vitamin D.16 Lower levels of the antioxidant vitamins A, E, and C have been associated with higher oxidative stress levels in individuals with BD.16 Research on how calcium intake and blood calcium levels affect BD is limited and has led to mixed findings, with evidence of both low and elevated blood calcium levels in participants with BD.2,13-16
Vida Velasco-Popov, MS, RD, CDN, dietitian at New York-Presbyterian Hospital and first author on a recent study on nutrition and BD, highlights these nutrition challenges: “Common dietary patterns observed in this population are high in calories, saturated fat, and sugar, which not only increase the risk for aforementioned comorbidities, but also increase risk for certain micronutrient deficiencies, including vitamin D, folate, vitamin B12, and vitamin B6 to name a few.” She recommends screening clients with BD for common deficiencies like folate and B12, particularly those who are taking valproic acid.
Anti-inflammatory
Strategies that increase the intake of anti-inflammatory and antioxidant compounds seem to hold the most potential for helping to manage BD. Observational studies have linked consumption of a Mediterranean diet high in anti-inflammatory compounds with a lower risk of BD.10 However, studies on the effects of individual nutrients and compounds on BD is limited and has led to mixed results. Fernanda Gabriel, MS, a Brazilian dietitian and PhD student focusing on nutrition and BD at the Faculty of Medicine of the University of São Paulo and first author on a recent study on the topic, believes that, while more research is needed, systematic reviews indicate that “a healthy food pattern could be more beneficial” for BD symptoms than focusing on individual nutrients. She notes that nutrition strategies providing broad antioxidant and anti-inflammatory support with adequate fiber may benefit patients with BD who are “usually in a state of more inflammation, dysbiosis, and oxidative stress.”
Velasco-Popov says, “Though further research on whole dietary patterns for patients with BD are needed to adequately develop effective standards of care for this population, nutrition strategies aimed at incorporating a Mediterranean diet with an emphasis on healthy fats seems most promising.”
Polyunsaturated Fatty Acids (PUFAs)
There’s evidence that altered PUFA levels in BD may increase inflammation and that this interaction may be mediated by certain genes.4 Overall, research indicates that increasing intake of omega-3 fatty acids may be beneficial for lowering inflammation levels and possibly reducing some symptoms in people with BD. Some international studies have linked greater seafood intake with lower rates of BD.2,16,18 One study including 83 individuals with BD determined that their reported intake of fatty fish was correlated with higher EPA and DHA levels and lower levels of one inflammatory marker.4 A 12-week randomized controlled trial including 82 participants with BD found that increasing dietary omega-3 fatty acid intake (to 1,500 mg of EPA and DHA daily) while lowering omega-6 intake significantly reduced their mood and energy fluctuations, but not impulsivity, compared with the control group following a typical American diet (with 150 mg of omega-3s daily).19 Additionally, some interventional studies providing omega-3 fatty acid supplements to participants with BD have found improved symptoms, generally with a small effect size, although other studies have not found significant results.16,20
According to the World Federation of Societies of Biological Psychiatry and Canadian Network for Mood and Anxiety Treatments Taskforce clinical guidelines, omega-3 fatty acid supplements including 1 to 2 g of EPA are “weakly” recommended as an adjunctive treatment for depression in BD.21
Micronutrient and Antioxidant Support
CoQ10 is a compound with antioxidant and mitochondrial energy production functions, found in greatest abundance in animal products like beef, fish, and poultry, and lower amounts in some plant oils, seeds, and nuts.2,20 Among the limited number of studies on the effects of CoQ10 supplementation in BD, some have found improvements in depression.2,20 One small trial including 69 participants with BD found that providing 200 mg CoQ10 supplements daily for eight weeks led to improvements in inflammatory markers and depression levels compared with participants taking a placebo.2
N-acetylcysteine (NAC) is a derivative of the amino acid L-cysteine and is a compound the body is capable of synthesizing from cysteine. Cysteine-rich foods include animal protein, whole grains like wheat and quinoa, and soybeans.2 NAC could potentially benefit people with BD by decreasing oxidative stress levels—through increased production of glutathione, an antioxidant—and altering neurotransmitter levels for antidepressant effects.2,7 Some studies have supported the antidepressant effects of NAC in participants with BD, while others have not found any positive results.2,13,16,20 One recent double-blind randomized controlled trial including 67 individuals with BD and depression found that participants with high levels of the inflammatory marker C-reactive protein who took 1.8 g of NAC daily for 12 weeks had significantly reduced symptoms of depression and reduced levels of C-reactive protein compared with those receiving a placebo.2,16
While evidence for the benefits of antioxidant supplements is preliminary, Velasco-Popov recommends that people with BD include foods high in CoQ10 and L-cysteine: “These antioxidants may play a supportive role in helping manage symptoms of depression in patients with BD. Foods such as fish, poultry, plant-based oils, as well as soybeans, and whole grains are high in CoQ10 and L-cysteine respectively.”
Despite evidence of lower micronutrient levels in people with BD, there is a lack of consistent data on the benefits of supplementation; limited studies in this population have found mixed results.16,20 Two small studies providing different multinutrient supplements including antioxidants to participants with BD, one over an eight-week period and the other—an open label trial—over six months, noted some improved symptoms.16 Some studies involving single nutrients have also found positive but inconsistent effects. One trial providing folic acid supplements to participants with BD for three weeks in combination with the medication valproate found improvements in their manic symptoms.16 However, an open trial with 10 participants with BD found that methylfolate supplements given for six weeks were associated with improved symptoms of depression but not mania.16 And two trials providing vitamin D to participants with BD for 12 weeks found no significant improvements in their symptoms, despite their lower vitamin D levels.16 Overall, limitations of these studies include their small sample sizes, lack of blinding, and shorter periods of supplementation; larger and longer-term trials may shed more light on the effects of supplementation in BD.
Probiotics
Probiotics may benefit individuals with BD through various mechanisms and some studies have linked them with improvements in depression.2,7,17 However, there is still very limited research in this area. One randomized controlled trial including 66 patients with BD admitted to an inpatient setting with mania found that supplementing the probiotics Lactobacillus rhamnosus GG and Bifidobacterium lactis for 24 weeks reduced their hospital stays and readmissions compared with controls.2
Ketogenic Diet
Researchers have theorized that the ketogenic diet (KD) may, by shifting the brain’s energy source from glucose to ketone bodies, support better mitochondrial function, which could improve BD.14,15 Currently, limited research on KDs in BD has revealed mixed results, although further studies are ongoing.2,14 In one small retrospective analysis, inpatients with BD provided with a KD (with 5% carbohydrate, 75% to 80% fat, and 15% to 20% protein) showed significant improvements in their well-being and symptom severity.14 Other small studies have found positive effects of the KD on BD symptoms, although most have been case studies or pilot studies.14 There are also potential concerns with following a restrictive KD. Individuals with BD may find it difficult to plan and follow the strict diet and it may lead to adverse effects like inadequate intake of essential nutrients—including some that already tend to be low in people with BD—and potentially serious side effects such as hyperlipidemia, hypertriglyceridemia, cardiovascular complications, kidney stones, and altered electrolyte levels.14 Therefore, individuals undertaking a KD should be carefully monitored by a health care team that includes an RD.14
Putting It Into Practice
RDs can play an important role in helping clients with BD find nutrition- and lifestyle-focused strategies to improve their quality of life. Assessing individuals with BD for nutrition risks and common nutrient deficiencies is key and, keeping in mind the challenges that their clients may face, RDs can help enable positive changes.
While working with clients with BD, Gabriel recommends that RDs “understand the pathophysiology of the disease—duration of episodes, variations, and symptoms.” She also advises: “It is essential to evaluate the complete individual.”
Velasco-Popov offers the following advice: “RDs should keep in mind that clients with BD may have difficulty committing to long-term dietary changes if psychological changes are not taken into account. Due to the cyclic nature of manic and depressive phases experienced by clients with BD, it seems most pertinent for RDs to work in collaboration with other members of the patient’s care team, including psychologists, to appropriately consider medical stability when working with clients with BD. Encouraging patients with BD to change their relationship with food and develop healthy nutritional habits should be part of a collaborative effort involving the patient, psychologist, and the RD for best health outcomes. Goal setting and one-on-one work with an RD should be targeted during euthymic states for best results.”
Clients with BD may have additional nutrition needs due to other chronic conditions. Velasco-Popov says, “RDs must also keep in mind that patients with BD are at increased risk for certain comorbidities such as obesity, type 2 diabetes, and CVD.”
Gabriel concurs: “Most of the patients also have metabolic comorbidities such as CVD, obesity, thyroid, and bone alterations.”
Both Velasco-Popov and Gabriel recommend that RDs work with individuals with BD to implement positive diet and lifestyle changes. Velasco-Popov says, “Encouraging clients with BD to follow a diversified diet rich in vegetables, fruits, lean protein sources, and healthy fats should be the first-line approach for effectively providing nutrition support for this population.”
Gabriel says, “As RDs, we need to stimulate a healthy lifestyle for this population, so they can benefit in a variety of forms: gut functioning, immune system, less inflammation, less cardiovascular risk, more glycemic and weight control—and, maybe, less symptoms and episodes!”
Final Thoughts
Velasco-Popov believes that ongoing research may shed more light on this complex disorder and identify the most effective nutrition strategies for individuals with BD: “Understanding the epigenetic effects of inflammation could prove a promising area of study for future nutrition research. Considering the role inflammation plays in BD and the potential of antioxidant-rich foods to reduce oxidative stress, I believe that future nutrigenomic research will likely be a key direction for advancing nutrition-based approaches to support patients with BD.”
— Sara Chatfield, MPH, RDN, LDN, is a Chicago-based freelance nutrition writer and consultant who has practiced dietetics in clinical and community settings.
References
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