There’s been a lot of talk about the importance of vitamin B12, B6, and folate for mental health. Although this is well deserved, let’s not overlook thiamine, or vitamin B1—the original B vitamin.

Thiamine is an essential micronutrient that plays a critical role in the production of energy in every cell of the human body.  Classically, severe thiamine deficiency is associated with chronic alcoholism. It results in devastating problems such as heart failure, nerve damage, ocular abnormalities, gut dysfunction, memory loss, confusion, psychosis, and death. Without thiamine, brain cells die quickly, and in cases of severe deficiency, high-dose thiamine is promptly needed to prevent catastrophic outcomes (1).

Less dramatic but more common in otherwise healthy appearing individuals is subclinical deficiency, or marginal thiamine status. The presentation is insidious and overlooked as it masquerades as other common conditions such as depression.

The organ most affected by lack of thiamine is the brain. The brain takes up only 2% of the human body by volume but demands 20% of the body’s total energy expenditure to send endless streams of electrical signals, synthesize neurotransmitters, and form new connections.

Maintaining a healthy mood requires a lot of cellular energy, so it’s easy to see why even marginal thiamine status can produce deleterious effects on mental health long before the more obvious classic symptoms of severe deficiency appear. Early signs of low thiamine include depressed mood, irritability, anxiety, fatigue, poor concentration, low appetite, and sleep disruption (2). Sound familiar?

Major Depressive Disorder, or Subclinical Thiamine Deficiency?

Several observational studies have shown an inverse relationship between thiamine status and severity of depression (3–5). A randomized double-blind placebo-controlled study of 120 healthy college students showed that supplementation with 50mg of thiamine daily for two months was associated with reports of being more clearheaded, composed, and energetic (6). A similar study of 80 healthy elderly Irish women showed that taking 10mg of thiamine daily for 6 weeks led to significant improvement in appetite, fatigue, sleep, and mood compared to placebo. Eighty-eight percent of subjects who took thiamine reported a “cheerier” and “brighter” mood at the end of the study (7). Another small study of 51 hospitalized patients with severe depression showed that adding 300mg of thiamine to the antidepressant fluoxetine (Prozac) led to faster clinical improvement when compared to fluoxetine alone (8).

Thiamine has direct effects on mood, sleep, and cognition primarily through its major role in the synthesis of the neurotransmitter acetylcholine. The synthesis of other mood regulating neurotransmitters—serotonin, norepinephrine, and GABA—also depends on thiamine (9). Thiamine may exert protective effects on mental health by reducing systemic inflammation, which contributes to every major psychiatric illness; this is conceptualized as “the brain on fire.” Thiamine reduces inflammation via its role in the formation of NADPH, a ubiquitous compound used by every cell in the human body for redox reactions. These redox reactions are the chemical reactions that extinguish the proverbial fire within us, keeping inflammation in check (10).

Why Aren’t We Getting Enough Thiamine?

Thiamine deficiency is common, affecting 30% of psychiatric patients, 38% of pregnant women, 20% of patients entering the emergency room for any reason, 29% of obese patients, 40% of the elderly, 55% of cancer patients, and a whopping 76% of patients with diabetes (11). What’s more, these statistics likely underestimate the prevalence due to the low sensitivity of conventional lab testing.

Thiamine must be obtained from the diet. Food sources include pork, beef, liver, fish, eggs, legumes, whole grains, and nuts. In the developed world, food is abundant, so why is thiamine status still a concern? People from developed nations are not lacking in calories or food, but in proportional levels of micronutrients, such as thiamine, needed to convert food into a form of energy that can be used to keep the brain operating smoothly, a situation coined “high-calorie malnutrition.” (10) It is like having a car with a tank full of gas, but you can’t start the engine because you don’t have the key.

Excessive consumption of refined carbohydrates and ultra processed foods is the norm in the modern diet. Refined carbs deplete thiamine because its resulting glucose load disproportionately increases demand for thiamine relative to the meager amount that it provides. Thiamine is depleted in the process of regulating blood glucose levels and in converting glucose into cellular energy.

The ability of glucose to deplete thiamine is demonstrated by the prevailing teaching in medical schools and in medical textbooks that if thiamine deficiency is suspected in a hospitalized patient, thiamine should be given before administering IV glucose to avoid precipitating catastrophic neurological injury. Over time, we’ve become more flexible with this rule: if a patient urgently needs glucose, IV glucose shouldn’t be delayed, but thiamine should be given concurrently or promptly after (12).

Despite government-mandated fortification of refined grains, many people are still not getting enough thiamine to compensate for the consumption of excess refined carbs as well as other environmental factors. Coffee, tea, alcohol, and plant foods that are high in oxalates block gut absorption of thiamine (13,14). Commonly prescribed medications, such as those used to treat diabetes, high blood pressure, allergies, acid reflux and depression, antagonize thiamine absorption and function. Aging, chronic emotional stress, and environmental toxins in our food system impair the gut’s ability to absorb thiamine and other B vitamins.

The body only stores 30mg of thiamine, and it only takes 18 days of deprivation to completely drain body stores. When 80% of body stores are lost, symptoms of neurological injury appear (11). An acute medical illness can dramatically increase demand for thiamine and precipitate a deficiency within a few days. It is difficult to accurately measure thiamine status because 90% is stored inside cells. Whole blood levels may appear normal even in the setting of symptomatic deficiency states.

Who should consider supplementing with thiamine?

Supplementation should be considered when any one of the following is present: mood symptoms, fatigue, brain fog, forgetfulness, vegetarian/vegan diet, older age, diabetes, obesity, bariatric surgery, chronic gastrointestinal symptoms, alcohol use, and the use of any medication that interferes with thiamine uptake or function.

Lack of reliable lab testing and highly variable presentations of thiamine deficiency make definitive diagnosis difficult. Fortunately, thiamine supplementation is cheap, safe, and well-tolerated even when given in excess. It’s water-soluble and doesn’t accumulate in the body. I have not seen any negative side effects in the hundreds of patients I’ve treated with thiamine, even in fragile elderly patients who required high dose IV thiamine. The safety of thiamine behooves us to consider empiric supplementation at doses above the RDA in a comprehensive approach to treating mood symptoms. Thiamine is best given in the setting of adequate potassium intake through the consumption of whole foods, and alongside supportive cofactors such as magnesium and other B vitamins.

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References:

1.   Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome: under-recognized and under-treated. Psychosomatics. 2012;53(6):507–16.

2.   Fattal-Valevski A. Thiamine (Vitamin B1). J Evid-Based Complement Altern Med. 2011 Jan 1;16(1):12–20.

3.   Carney MWP, Williams DG, Sheffield BF. Thiamine and Pyridoxine Lack in Newly-Admitted Psychiatric Patients. Br J Psychiatry. 1979 Sep;135(3):249–54.

4.   Pepersack T, Garbusinski J, Robberecht J, Beyer I, al  et. Clinical relevance of thiamine status amongst hospitalized elderly patients. Gerontology. 1999 Apr;45(2):96–101.

5.   Zhang G, Ding H, Chen H, Ye X, Li H, Lin X, et al. Thiamine Nutritional Status and Depressive Symptoms Are Inversely Associated among Older Chinese Adults. J Nutr. 2013 Jan 1;143(1):53–8.

6.   Benton D, Griffiths R, Haller J. Thiamine supplementation mood and cognitive functioning. Psychopharmacology (Berl). 1997 Jan 1;129(1):66–71.

7.   Smidt LJ, Cremin FM, Grivetti LE, Clifford AJ. Influence of Thiamin Supplementation on the Health and General Well-being of an Elderly Irish Population With Marginal Thiamin Deficiency. J Gerontol. 1991 Jan 1;46(1):M16–22.

8.   Ghaleiha A, Davari H, Jahangard L, Haghighi M, Ahmadpanah M, Seifrabie MA, et al. Adjuvant thiamine improved standard treatment in patients with major depressive disorder: results from a randomized, double-blind, and placebo-controlled clinical trial. Eur Arch Psychiatry Clin Neurosci. 2016 Dec 1;266(8):695–702.

9.   Plaitakis A, Hwang EC, Van Woert MH, Szilagyi PIA, Berl S. Effect of Thiamin Deficiency on Brain Neurotransmitter Systems. Ann N Y Acad Sci. 1982;378(1):367–81.

10. Dhir S, Tarasenko M, Napoli E, Giulivi C. Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults. Front Psychiatry [Internet]. 2019 Apr 4;10.

11. Lonsdale D, Marrs C. Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition. Academic Press; 2017. 358 p.

12. Schabelman E, Kuo D. Glucose before Thiamine for Wernicke Encephalopathy: A Literature Review. J Emerg Med. 2012 Apr;42(4):488–94.

14. Vimokesant S, Kunjara S, Rungruangsak K, Nakornchai S, Panijpan B. Beriberi Caused by Antithiamin Factors in Food and Its Prevention. Ann N Y Acad Sci. 1982;378(1):123–36.

Medical Disclaimer: The information mentioned in this article is not intended to diagnose, treat, cure, or prevent any disease. The information provided is for educational purposes only and is not intended to replace the relationships with your medical provider(s). Before initiating any treatment, please first consult with your licensed medical provider.