Running on Empty: Subclinical Thiamine Deficiency is Common and Causes Depression

article by Michelle T. To, MD

There’s been a lot of talk about the importance of vitamin B6, B12, 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. It sits at the entry points of pathways that convert food into adenosine triphosphate (ATP)–chemical energy used to carry out nearly all cellular functions. Thiamine is therefore the gatekeeper of energy production. Due to factors associated with our modern lifestyle, suboptimal thiamine status is common but under-recognized.

Classically, thiamine deficiency, in its most severe form, is associated with chronic alcoholism. Severe deficiency 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 high dose thiamine is promptly needed to prevent catastrophic outcomes.¹

What is more common in modern times is subclinical deficiency, or marginal thiamine status, in otherwise healthy appearing individuals. The presentation is insidious and overlooked as it masquerades as other common conditions.

The organ most affected by lack of thiamine is the brain.

When we consider how energy demanding the brain is, it is easy to see why the brain requires so much. The brain takes up only 2% of the human body by volume but demands 20% of the body’s total energy expenditure. Most of that energy is needed to send endless streams of electrical signals, synthesize neurotransmitters, and form new connections. Maintaining a healthy mood requires a lot of cellular energy!

With the brain’s high energy demands, it is 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?

Could a subset of those diagnosed with Major Depressive Disorder be, in fact, suffering from subclinical thiamine deficiency?

Several observational studies have shown an inverse relationship between thiamine status and severity of depression.^3–5 A double blind randomized 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. Systemic inflammation 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

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. They are lacking 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 This is like having a full gas tank, but the car won’t start because the key to the ignition is missing.

Excessive consumption of refined carbohydrates and ultra processed foods is the norm in the modern diet. Think bread, pasta, rice, grains, and sugar. 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, IV thiamine should be given before administering IV fluids with glucose to avoid precipitating catastrophic neurological injury by depleting thiamine stores. Over time, we’ve become more flexible with this rule: if the patient is hypoglycemic and urgently needs glucose, IV fluids with 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 antagonize thiamine absorption and function, including those used to treat diabetes, high blood pressure, allergies, acid reflux and depression. 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. 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, diabetes, vegetarian/vegan diet, older age, 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 the 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’ve never seen an adverse reaction in the hundreds of patients I’ve treated with thiamine, even among fragile elderly hospitalized patients who were given high dose IV thiamine for acute confusional states. 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.