What comes to mind when you think of eating for bipolar disorder?
Bipolar affective disorder, or manic-depressive disorder, is a psychological disease leading to sometimes extreme fluctuations of mood and energy. The United States leads the world in bipolar diagnoses at approximately 3% of the population (1, 2).
“Hippocrates was the first to distinguish between different dispositions or humors–melancholic, choleric, phlegmatic, sanguine–but it was Jules Farley in 1854 who first described “folie circulaire” or the alternating cycle of euphoria and melancholia” (2)
Common factors found in bipolar disorder include:
- increased risk of insulin resistance
- food sensitivities
- disordered eating based on mental state
- drug/nutrient interactions
- underlying inflammation
These tendencies likely mean bipolar disorder can be influenced by nutritional recommendations. But what causes bipolar disorder in the first place?
The spectrum of bipolar disorder
Like many diagnoses, there are multiple forms of bipolar disorder. These include:
- bipolar I
- bipolar II
- bipolar III
- bipolar disorder not otherwise specified
These forms likely exist on a spectrum of mental health diagnoses.
Other conditions like impulse disorders, substance abuse, eating disorders, or childhood behavioral disorders are sometimes considered part of the bipolar spectrum.
While bipolar disorder is one of the most heritable psychiatric disorders, genes alone are not responsible for the disease. Currently, research shows that contributors include genetic predisposition combined with environmental factors like diet and psychosocial stressors.
Other factors leading to diagnosis may include:
-
- circadian clock dysfunction
- catecholamine (dopamine, adrenaline, noradrenaline) imbalances
- serotonin dysregulation
- activity of inositol monophosphate
- neuroinflammation
- loss or lack of neurotrophic factors, polypeptides that assist in the development and regeneration of the nervous system
- problematic glycogen synthase kinase 3 beta activity, a physiologically widespread enzyme that, as all kinases, transfers a phosphate group from ATP to another molecule (3)
This blog will explore the possibility of nutritional interventions, or eating for bipolar disorder, in the context of these many contributors and triggers.
Let’s start with the high prevalence of insulin resistance in those with bipolar disorder.
Insulin resistance & eating for bipolar disorder
Staggeringly, insulin resistance is found in over 50% of bipolar disorder patients, which may contribute to the progression of the disease.
Other metabolic disorders are also more commonly found in those with bipolar, including type II diabetes, high blood pressure, obesity, and dyslipidemia or an imbalance in blood lipids (4).
What is insulin resistance, exactly?
Insulin resistance is when cells resist the actions of insulin, a hormone produced by the pancreas. Insulin is a potent signaling hormone that sets off a chain of events leading to the cellular uptake of glucose, aka blood sugar (5).
It’s easy to deduce the result of cells that aren’t receptive to insulin: increased glucose in the blood.
And, over time, this is exactly what occurs, commonly alongside increases in blood lipids and blood pressure. This progression is reflected in the diagnoses of type II diabetes and other metabolic disorders that often occur in people with bipolar disorder.
Insulin resistance and bipolar disorder share a major underlying contributor: Inflammation.
Since the 1950s, observational research has pointed to a connection between insulin resistance and inflammatory states (6). However, more recent research has revealed the complex biochemical mechanisms they share.
Studies exploring the role of neuroinflammation in bipolar disorder discuss contributions from both the innate and adaptive immune systems:
“Knowledge about the neurobiology of bipolar disorder is increasing steadily and evidence from several lines of research implicates immuno-inflammatory mechanisms in the brain and periphery in the etiopathogenesis of this illness and its comorbidities” (7).
The inflammatory links between insulin resistance and bipolar disorder create a web of pathogenic cross-talk.
Other inflammatory-mediated health concerns seemingly unrelated to these issues increase in prevalence:
- Cardiovascular disease is the leading cause of death for bipolar patients—they are 2.3 times more likely to develop CVD versus the general population (4).
- Insulin resistance may lead to blood-brain barrier dysfunction and mark the transition of systemic inflammation into neuroinflammation, creating a feedback loop of continuing damage to the blood-brain barrier and the progression of bipolar disorder.
- One research group questions if bipolar disorder is actually a “multi-system inflammatory disease” due to the high rates of co-occurring medical disorders associated with the diagnosis (8).
Additionally, bipolar patients with insulin resistance or type II diabetes are 8.4 times more likely to respond poorly to lithium, the gold standard pharmaceutical treatment. Responses to lithium worsen as insulin resistance progresses (4).
Are increasing rates of pediatric insulin resistance related to increasing rates of pediatric bipolar disorder?
Unfortunately, there may be a link.
In the past, metabolic syndrome—also called insulin resistance syndrome—was almost exclusively seen in adults (9).
Though the diagnosis of insulin resistance differs based on the applied definition (10), it seems that rates of both metabolic syndrome and insulin resistance have increased in children over the past decade…possibly by as much as 50% (11, 12).
Unfortunately, the diagnosis rates of mania and bipolar disorder have also been steadily increasing, which does not seem to be explained by more diagnostic attention (13).
To be clear, insulin resistance does not cause bipolar disorder. But in those who are genetically susceptible, it may trigger or contribute to the disease.
Insulin resistance and bipolar disorder: Solutions
In 2022, a research group investigated the effects of metformin on treatment-resistant bipolar disorder.
In a randomized, placebo-controlled trial, 45 bipolar patients with insulin resistance were split into a treatment group (2000 mg/day) or a placebo group. After 14 weeks, 10 patients in the metformin group and 1 in the placebo group no longer met the criteria for insulin resistance (14).
But how did treatment with metformin affect symptoms of bipolar disorder?
“HAM-A (P = .022 at week 14 and .019 at week 26) and CGI-BP change scores (P = .046 at 26 weeks) significantly favored converters over non-converters.
Effect sizes were large for the MADRS and GAF (Cohen d > 1 at 14 and 26 weeks) and large for the HAM-A and CGI-BP at 26 weeks.
Transient gastrointestinal side effects occurred under both treatment conditions” (14).
Pay special attention to the reported effect sizes—the metformin group experienced a large and clinically useful improvement on the MADRS and GAF scales, indicating a much more stable mental state.
While the study was small, the outcomes are incredibly promising and indicate the usefulness of dietary and lifestyle techniques for influencing insulin resistance.
For instance, bitter melon, a traditional Ayurvedic herb that is sold as both a whole food and supplement, has been widely researched for its beneficial effects on metabolic disturbances, including insulin resistance and diabetes (15).
Antioxidant-rich foods, such as berries, clove, potatoes, beans, artichoke, strawberries, red cabbage, and most all colorful fruits and vegetables, are also therapeutic foods for those with insulin resistance (16).
Aerobic and resistance exercises are backed by 100s of studies showing their effectiveness in improving insulin sensitivity and metabolic health.
“Resistance training can result in dramatic improvements in both insulin sensitivity and glucose uptake.” (17).
Eating for bipolar disorder means eating for metabolic health—the two go hand in hand.
Food reactions and eating for bipolar disorder
Gluten and casein may be problem proteins for people with bipolar disorder. Foods containing these proteins include:
Gluten:
- wheat
- barley
- rye
- spelt
- couscous
- some oats and other grains based on processing
Casein:
- milk
- cheese
- butter
- yogurt
- sour cream
- all dairy foods contain casein, with the exception of isolated protein sources such as whey and ghee (clarified butter)
You might wonder if this applies to you, especially if you don’t have a diagnosis of celiac disease or wheat allergy.
Amazingly, the link between gluten and mood disorders has been explored since the 1950s. In 1956, a series of case studies were published on those without celiac disease who experienced gluten-associated psychiatric symptoms. Amusingly, the paper is titled “Bread and Tears—Naughtiness, Depression, and Fits Due to Wheat Sensitivity” (18).
More recent research has found increased levels of gluten-related antibodies in those with bipolar disorder. Mania, specifically, is associated with increased levels of gliadin antibodies, a glycoprotein found within gluten (19).
In one study examining those with known celiac disease, the prevalence of bipolar disorder is 4.3% versus 0.4% in the healthy control group. The authors state:
“… a screening for CD in people with affective disorders and showing key symptoms or family history of CD is recommended” (20).
This means that if you are someone with bipolar who also experiences the classic symptoms of celiac disease, such as nausea, diarrhea, constipation, bloating, gas, or foul-smelling stools, or have a family history of celiac disease…then get tested.
The underlying pathophysiological connections between bipolar disorder and gluten reaction, be it wheat allergy, non-celiac gluten sensitivity, or celiac disease, are multi-factorial and may include (21):
- issues with tryptophan absorption leading to decreased central serotonin synthesis (remember that serotonin dysregulation is an issue that may contribute to bipolar disorder)
- the influence of inflammatory cytokines (small proteins that the immune system uses to communicate) on regions of the brain related to mood regulation
The link between casein and bipolar disorder isn’t as straightforward. I could find only a few applicable studies.
One, a 2010 examination of 75 bipolar patients for anti-casein IgG antibodies, suggested strong casein reactivity in those with bipolar disorder (22).
However, the study had some weak points. The confidence interval for each result was extremely wide, usually indicating that the sample size was too small to know the most accurate connection between the two factors.
Additionally, IgG antibodies are often elevated due to frequent or increased consumption of any food, not simply foods that lead to reactions. However, the authors state:
“Changes in epitope recognition patterns may underlie these findings, suggesting that food antigens are processed differently by [bipolar] patients, and that immunoglobulin G (IgG) increases are not simply a function of increased exposure to certain foods.”
This leads to a logical question—if you or one of your patients is eating for bipolar disorder, how do you know if gluten or casein contributes to symptoms?
It’s a fair and clinically essential question.
My suggestion is not complex, but sometimes difficult: Eliminate gluten and casein for a time and see if your symptoms improve.
As I said, food elimination is not complex. The main components of an elimination protocol are a timed, strict avoidance of certain foods and then the reintroduction of those foods, one by one, in a controlled way, once the period has passed. Forty days is a generally accepted period for elimination.
The difficulty comes with strictly adhering to the protocol and avoiding ingestion. For some people, such as those with suspected celiac disease, total elimination of gluten is paramount. Even tiny amounts of gluten can trigger an immune response and perhaps worsen psychological symptoms.
Working with an experienced practitioner can make the process much easier and more reassuring.
One final caveat critical for those with bipolar disorder is the appeal of replacing gluten and casein with high glycemic and processed gluten and casein-free foods. Gluten-free bagels, quick dairy-free snacks like alternative milk ice cream, or even soy-cheese pizza on cauliflower crust are for occasional consumption only.
As outlined above, a whole food, metabolically-supportive diet rich in antioxidant nutrients can be a game-changer for people with bipolar disorder.
Nutrient imbalances and bipolar disorder
My curiosity about nutrient imbalances in bipolar disorder is how this blog came to be.
I often work with mercury-toxic clients, and one particular client stood out due to her diagnosis of bipolar disorder, accompanied by imbalanced copper and, surprisingly, undetectable levels of lithium, even with a long history of prescribed lithium. I was shocked to see that undetectable levels of lithium appeared on her hair tissue mineral analysis.
She also dealt with anemia, keratosis pilaris, and extreme constipation. Thankfully, she benefited from a gradual shift to a whole-food, gluten-free diet, digestive support, lithium orotate, and caffeine elimination, a possible cause of decreased lithium levels (23). (Other causes of reduced lithium include pregnancy and mania.)
Clinically, I have noticed low lithium levels in people with mercury toxicity. This observation makes me wonder if there is a connection between mercury, lithium, and possibly other nutrient imbalances and bipolar disorder.
Could the toxic effects of mercury create a cycle of lithium depletion/nutrient imbalance and oxidation -> heightened bipolar symptoms -> furthered imbalance -> mitochondrial and neurological dysfunction (24)?
Lithium is needed to compensate for the damage done by mercury; in fact, lithium may act as a cofactor for glutathione and superoxide dismutase synthesis.
This connection isn’t well studied, but a similar pattern appeared in a recent case study (25). In this scenario, a 12-year-old boy with behavioral defiance was found to have high mercury levels and low lithium levels. After rebalancing his minerals with supplemental lithium and the removal of mercury fillings, his behavior drastically improved.
Adjacent to this experience, a 2012 study found an incredibly strong connection between the lifetime prevalence of bipolar disorder and Wilson’s disease, the diagnosis of congenital copper accumulation (26). The authors state:
“Indeed, recent studies indicate that higher levels of copper, similar to several other trace elements such as zinc, cadmium, and thallium, may play a role in the pathophysiology of bipolar disorder, which is consistent with the neurodegenerative hypothesis of such a disorders” (26).
Other nutrients are also worth mentioning. For instance, the Institute for Functional Medicine lists mitochondrial support and EPA-dominant omega-3 supplementation as worthwhile solutions for those with bipolar disorder (27).
However, they cite research that NAC, a popular compound used for increasing the size and number of mitochondria within cells, was ineffective in bipolar disorder compared to placebo treatment. Equivocal outcomes of other studies reflect these findings (28, 29).
Additionally, B vitamins, specifically B6, folate, and B12 may be helpful for some bipolar patients. While not all research agrees, some studies show a positive link between mental health and the relief of psychiatric symptoms (30).
And in some bipolar patients, these vitamins may positively influence the effects of high homocysteine levels, technically known as hyperhomocysteinemia, due to homocysteine’s interactions with the dopaminergic system.
A fantastic review of homocysteine’s role in psychiatric disorders (31) also lists two medications commonly prescribed for bipolar disorder, sodium valproate and lamotrigine, as possible disruptors of homocysteine metabolism.
“Considering that increased levels of Hcy are observed in bipolar patients, and folate is a cofactor involved in both Hcy metabolism and monoamine synthesis, Baek et al suggest that folate supplementation could normalize monoamine synthesis and correct mood stabilizer–associated functional folate deficiency” (31).
Vitamin B-rich foods include well-sourced liver, red meat, chickpeas, kidney beans, adzuki beans, dark green vegetables, eggs, and many nuts and seeds.
Eating for bipolar disorder means doing your best to balance
The highs and lows experienced by those with bipolar disorder can make balanced nutrition difficult.
For instance, did you know that approximately 33% of people with bipolar have an eating disorder (32)?
Times of mania can lead to undereating, along with the characteristic symptoms of sleeplessness, distractibility, and heightened energy, while depressive episodes might mean more calorie-rich but nutrient-deficient foods, such as processed or sugary snacks.
It’s critical that these food choices are not judged; rather, we can notice patterns and do our best to bring balance not only to the symptoms but to the choices they encourage.
There is no one right or researched way to accomplish this. A suggestion from my clinical work is to offer easy-to-access information on the links between mood highs and lows with certain foods and allow my clients to educate themselves.
The internal motivation that education can bring is a powerful force for change.
Corticosteroids and bipolar disorder
The use of certain drugs, such as prescribed digitalis, antihypertensives, and corticosteroids, but also street drugs, such as cocaine and heroin, can lead to psychiatric symptoms (33).
These side effects are known as substance-induced mood disorders and are especially apparent in cases of bipolar disorder after the use of corticosteroids. Interestingly, bipolar symptoms after steroid use are more prevalent in females and those with systemic lupus erythematosus (34).
The onset of bipolar symptoms, generally mania, usually begins just a few days after routinely taking the drug.
Consider this case study of a 43-year-old woman who was prescribed corticosteroids for Behçet’s disease, a rare inflammatory diagnosis requiring the long-term use of prednisone.
She reported symptoms of both mania and depression that worsened as the amount of prednisone was increased. When the dose was decreased, her psychological symptoms lessened; unfortunately, she had to maintain a moderate dose of the drug to control the symptoms of Behçet’s.
But why does this happen?
The most definitive answer is that we’re not sure.
Some evidence points to a connection between high doses of steroids and receptor activation imbalance in the hypothalamic-pituitary-adrenal (HPA) axis (36). This imbalance can lead to cognitive impairment and emotional disturbances, sometimes resulting in steroid-induced bipolar disorder.
But there is possibly another, more indirect reason behind bipolar disorder resulting from corticosteroids: Insulin resistance due to steroids’ interference in insulin signaling.
Even steroid-induced diabetes can result from the hyperglycemia and insulin resistance commonly associated with corticosteroid use.
Bipolar symptoms may also be more likely, as discussed in the first part of the blog.
However, remember that steroid use is sometimes unavoidable—at this point, eating for bipolar disorder and blood sugar stability becomes critical. Consuming macronutrient-balanced meals with a focus on colorful, fibrous foods is the most foundational place to start.
From there, seek out foods that lessen inflammation, such as chia, flax, hemp, well-sourced fish, and seaweeds rich in omega-3 fatty acids.
And remember that commonly reactive foods might be contributing to underlying inflammation. Consider working with a clinician to maintain dietary variety while exploring an elimination diet.
References
- https://www.nimh.nih.gov/health/statistics/bipolar-disorder
- https://www.ncbi.nlm.nih.gov/books/NBK558998/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413749/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185298/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1204764/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246086/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701682/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498820/
- https://www.nhlbi.nih.gov/health/metabolic-syndrome
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530262/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246086/
- https://www.nature.com/articles/0803317
- https://journalbipolardisorders.springeropen.com/articles/10.1186/s40345-014-0010-0
- https://pubmed.ncbi.nlm.nih.gov/35120288/
- https://pubmed.ncbi.nlm.nih.gov/25488547/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138814/
- https://journals.lww.com/nsca-scj/fulltext/2011/10000/exercise_programming_for_insulin_resistance.5.aspx#:~:text=Resistance%20training%20can%20result%20in,times%20per%20week%20(3).
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1889136/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266949/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763959/
- https://autoimmunhighlights.biomedcentral.com/articles/10.1007/s13317-014-0064-0
- https://onlinelibrary.wiley.com/doi/10.1111/j.1399-5618.2010.00879.x
- https://pubmed.ncbi.nlm.nih.gov/7748990/
- https://www.frontiersin.org/articles/10.3389/fpsyt.2020.586083/full
- https://ndnr.com/anxietydepressionmental-health/low-dose-lithium-an-effective-treatment-for-mood-disorders/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419066/
- https://www.ifm.org/news-insights/nut-role-nutrition-mental-health/
- https://pubmed.ncbi.nlm.nih.gov/33354859/
- https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-10-91
- https://biomedscis.com/fulltext/the-consequences-of-b-vitamins-on-mental-health-and-cognitive-function-a-literature-review-study.ID.000432.php
- https://journals.sagepub.com/doi/full/10.1177/2326409817701471
- https://journals.sagepub.com/doi/10.1177/1049732320956267
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181154/
- https://pubmed.ncbi.nlm.nih.gov/12847167/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953074/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827500/