Bipolar Disorder

Contributing Factors

Contributing factors are substances, contexts or conditions that have roles in the causation or promotion of bipolar disorder.


Eating an unhealthy diet is known to lead to nutrient deficiencies, which, in turn, can negatively affect brain function.

Foods that promote good brain health:

  • whole, fresh foods
  • eat sufficient good quality protein (w/fish 3x week) animal + plant-based
  • good-quality fats
  • minimal amounts of starches
  • antioxidant-rich vegetables and fruit

Substances that are bad for brain health:

  • sugar-containing foods and snacks
  • high glycemic foods (sugars and starches)
  • processed fats (processed plant oils, hydrogenated fats)
  • artificial ingredients (colours and preservatives)
  • fast food meals

Diet and bipolar disorder

  • People with bipolar disorder typically consume more sugar, carbohydrates, desserts, alcohol, and sweetened beverages, and processed foods (Lopresti & Jacka, 2015)
  • Biological processes that are negatively affected in bipolar disorder by diet include (The Bipolar Diet, 2019): 
    • neurotransmitter activity
    • inflammatory processes
    • oxidative stress
    • mitochondrial function
    • growth and regeneration of neurons

Low-inositol diet and bipolar disorder

  • People with bipolar disorder can have altered levels of inositol in brain. (Yu & Greenberg, 2016).
  • Overactive inositol signalling in the brain is implicated in setting off mania (Tomioka et al., 2018).
  • Consuming a diet low in sources of inositol may be useful in some bipolar patients (Shaldubina et al., 2006). In a trial, consumption of a low-inositol diet was beneficial for 10 of 15 patients (Gaby, 2011).
  • Medications commonly used for treating bipolar disorders work by reducing brain inositol levels (Lepore et al., 2021), so restricting food dietary inositol may be a strategy for improving the effects of lithium. However, this approach should only to be approached with qualified guidance.

Healthy diets for supporting bipolar disorder

Mediterranean diet

  • ​​The mediterranean diet is considered a good model for a healthy diet. It includes foods that are beneficial, and also reduces or eliminates foods that promote mental health issues.
  • General components of the mediterranean diet include:
    • plenty of vegetables and fruit
    • healthy fats including olive oil
    • regular consumption of seafood
    • poultry, beans, and small amounts of red meat
    • small amounts of dairy as yogurt and cheeses
    • whole grains instead of refined grains

More information and menu plans:

(Mediterranean Diet 101, 2021)

Paleo diet

Foods to eat:

  • meat, fish, eggs
  • vegetables, fruits
  • nuts, seeds
  • healthy fats and oils
  • herbs, spices

Foods to avoid:

  • sugar, high-fructose corn syrup
  • grains
  • legumes and beans
  • Dairy products
  • vegetable oils, and transfats
  • artificial sweeteners
  • processed foods

More information and menu plans:

(The Paleo Diet — A Beginner’s Guide + Meal Plan, 2018)


Caffeine is a molecule that acts as a stimulant in the central nervous system. It is commonly found in coffee, black tea, energy drinks, soda drinks, chocolate, some medications, as well as guarana and yerba maté.

Effects of caffeine

  • Effects of excessive caffeine consumption can include nervousness, irritability, palpitations, insomnia as well as increased heart rate, body temperature, blood flow, and blood sugar levels.
  • Caffeine depletes nutrients that are important for mental health such as B vitamins, vitamin C, potassium, magnesium, calcium, zinc (Scott, 2011).
  • Caffeine increases adrenal production of epinephrine and norepinephrine, which over time, can weaken the adrenal glands (Levi, 1967)
  • Excess caffeine makes the way the body responds to hypoglycemia worse (hypoglycemia is a risk factor for schizophrenia).

Caffeine and mental health

  • Excess caffeine makes the way the body responds to hypoglycemia worse (hypoglycemia is a risk factor for depression).
  • Restricting caffeine consumption can promote decreased hostility, suspiciousness, anxiety, and irritability in people with psychiatric conditions who drink excessive amounts of coffee (“Effects of Caffeine in Chronic Psychiatric Patients,” 1979).

Caffeine and bipolar disorder (Frigerio et al., 2021):

  • A limited amount of research shows a relationship between amounts of caffeine consumed and severity of bipolar symptoms.
  • Caffeine has been shown to cause manic symptoms and trigger bipolar disorder onset.
  • Caffeine suppresses the action of lithium treatment.
  • People switching to the manic state tend to drink excessive amounts of caffeinated products.
  • An abrupt increase in the amount of caffeine consumed may promote manic symptoms (Richards & Smith, 2016; Rizkallah et al., 2011).

CAUTION: abrupt elimination of caffeine while on high-dose lithium medication may induce significant lithium toxicity (Frigerio et al., 2021). It is important to be carefully monitored if drastically altering caffeine levels.


Inflammation is a normal part of the body’s defense to injury or infection. However, inflammation is damaging when it occurs in healthy tissues or lasts too long (months or years).

Causes of chronic inflammation include (Inflammation, n.d.):

  • environmental chemicals
  • poor nutrition and nutritional deficiencies
  • imbalanced microbiome (dysbiosis)
  • sleep issues
  • stress
  • personal environment

Additional sources of Inflammation (Berk et al., 2013):

• consuming the Standard American diet
• environmental toxins
• low grade infections
• sedentary lifestyle
• allergies

Inflammation and mental health

Inflammation plays a mediating role in both the risk and progression of depression (Berk et al., 2013).

Depression is a symptom of inflammation. Symptoms include (Greenblatt, 2018) :

  • lethargy/malaise/fatigue
  • decreased concentration
  • decreased appetite
  • decreased interest in pleasurable things
  • weakness

Cytokines and Depression

Depressed patients have been found to have (Huang & Lee, 2007):

  • higher levels of pro-inflammatory cytokines (TNF- α & CRP) than healthy patients
  • lower levels of anti-inflammatory cytokines than healthy patients

Pro-inflammatory cytokines are responsible for activating indoleamine 2,3-dioxygenase (IDO), a tryptophan and serotonin-degrading enzyme (Müller & Schwarz, 2007). Increased levels of IDO, and increased consumption of tryptophan and serotonin, results in a reduction in serotonergic neurotransmission (Müller & Schwarz, 2007) (Greenblatt, 2018).

Inflammation and bipolar disorder

  • Bipolar depression and manic episodes may be accompanied by increased pro-inflammatory signalling and T-cell immune activity (Anderson & Maes, 2015).
  • Reduced of the protective brain-derived neurotrophic factor (BDNF) is common in bipolar disorder patients. Reduced BDNF is associated with increased inflammatory signaling (Goldstein et al., 2011).
  • Lithium is beneficial for treating bipolar symptoms, in part due to its anti-inflammatory actions (Anderson & Maes, 2015).

Sleep loss and inflammation

  • In a 12-day study a moderate reduction in sleep duration was associated with a significantly increased amount of inflammatory compounds (Vgontzas et al., 2004).

Trauma and inflammation (Danese et al., 2009):

  • immune function is affected in a pro-inflammatory way by childhood maltreatment, abuse, social isolation, and economic hardship.
  • people who had stress in childhood are twice as likely to suffer chronic inflammation.

Inflammation and suicide

  • In psychiatric patients increased inflammation is associated with increased suicidal ideation (Greenblatt, 2018).
  • Patients with depression and high suicidal idealation have been shown to have significantly higher markers of inflammation including TNF-α, IL-6, and C-reactive protein (O’Donovan et al., 2013).

IDO, cytokines (inflammation mediators), and neurotransmission

    • Pro-inflammatory cytokines (cell-signalling molecules) increase the activity of Indoleamine 2,3-dioxygenase (IDO) – an important enzyme in tryptophan metabolism.
    • IDO degrades tryptophan to kynurenine thereby decreasing amounts of tryptophan available for production of serotonin, and melatonin (important for mood and sleep).
    • the kynurenine metabolite quinolinic acid increases excitatory glutamate neurotransmission.
    • higher concentrations of kynurenine and a higher kynurenine to tryptophan ratio have been found in overweight and obese versus normal weight people. Obesity is associated with an increased inflammatory state in the body (Fellendorf et al., 2021).

Tryptophan, kynurenine metabolites, and bipolar disorder

  • Blood and cerebral spinal fluid concentrations of kynurenine and its metabolites, as well as the kynurenine to tryptophan ratio have been found to be higher in subjects with bipolar disorder versus healthy controls subjects (Anderson & Maes, 2015; Trepci et al., 2021).
  • tryptophan degredation by IDO, as driven by a pro-inflammatory state, was found to be more active in bipolar disorder (Fellendorf et al., 2021).

Anderson, G., & Maes, M. (2015). Bipolar Disorder: Role of Immune-Inflammatory Cytokines, Oxidative and Nitrosative Stress and Tryptophan Catabolites. Current Psychiatry Reports17(2), 8.

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Frigerio, S., Strawbridge, R., & Young, A. H. (2021). The impact of caffeine consumption on clinical symptoms in patients with bipolar disorder: A systematic review. Bipolar Disorders23(3), 241–251.

Goldstein, B. I., Collinger, K. A., Lotrich, F., Marsland, A. L., Gill, M.-K., Axelson, D. A., & Birmaher, B. (2011). Preliminary findings regarding proinflammatory markers and brain-derived neurotrophic factor among adolescents with bipolar spectrum disorders. Journal of Child and Adolescent Psychopharmacology21(5), 479–484.

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Rizkallah, E., Bélanger, M., Stavro, K., Dussault, M., Pampoulova, T., Chiasson, J.-P., & Potvin, S. (2011). Could the use of energy drinks induce manic or depressive relapse among abstinent substance use disorder patients with comorbid bipolar spectrum disorder? Bipolar Disorders13(5–6), 578–580.

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Trepci, A., Sellgren, C. M., Pålsson, E., Brundin, L., Khanlarkhani, N., Schwieler, L., Landén, M., & Erhardt, S. (2021). Central levels of tryptophan metabolites in subjects with bipolar disorder. European Neuropsychopharmacology43, 52–62.

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