Vitamin B3 (Niacin)

When a Nutrient Deficiency Looks Like Mental Illness

Vitamin B3, also known as niacin, is rarely part of conversations about mental health. When it is mentioned, it is usually framed as a cholesterol-lowering nutrient or the vitamin known for causing uncomfortable flushing at high doses.

What is often missing from the conversation is this:

Vitamin B3 is essential for brain energy, neurological stability, and emotional regulation.

Niacin is required to produce nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), molecules that sit at the center of cellular energy production, mitochondrial function, oxidative stress regulation, and DNA repair (Bogan & Brenner, 2008; Kirkland, 2021).

When these pathways are compromised, the brain is often one of the first organs to signal distress. Historically, that distress was often misinterpreted. In fact, a deficiency in vitamin B3 once led thousands of people, especially women, to be institutionalized for what doctors believed was mental illness.

They were not insane.
They were nutrient deficient.

That condition was called pellagra.

Understanding pellagra is not about revisiting a medical curiosity. It is about recognizing how easily nutrient-driven brain dysfunction can be misunderstood, especially when symptoms appear emotional, behavioral, or psychiatric in nature. This history matters today, particularly in conditions like PMDD, where symptoms are severe, cyclical, and often minimized.

What Is Vitamin B3 (Niacin)?

Vitamin B3 is a water-soluble B vitamin that exists primarily as nicotinic acid (niacin) and nicotinamide (niacinamide). Inside the body, niacin is required to form NAD and NADP, which act as electron carriers in hundreds of enzymatic reactions.

These reactions regulate:

• Cellular energy production (ATP)

• Mitochondrial respiration

• Neurotransmitter synthesis

• Oxidative stress and redox balance

• Immune signaling

• Hormone and steroid metabolism

The brain has an exceptionally high energy demand and limited energy reserves. Disruptions in NAD-dependent pathways impair neuronal signaling, synaptic plasticity, and stress tolerance, which can present as mood instability, anxiety, cognitive changes, or emotional dysregulation (Kirkland, 2020; Trammell & Brenner, 2013).

Niacin can be obtained from food or synthesized from tryptophan, but this conversion is inefficient. Approximately 60 mg of tryptophan is required to generate 1 mg of niacin, and the process depends on adequate vitamin B6, riboflavin, and iron (Gropper et al., 2017). Chronic stress, inflammation, hormonal fluctuations, and gut dysfunction further reduce efficiency.

Why the Brain Is Often the First Organ Affected

Neurons rely heavily on oxidative metabolism and are particularly sensitive to mitochondrial dysfunction and oxidative stress. When NAD availability declines, ATP production falls, reactive oxygen species accumulate, and neuroinflammatory signaling increases (Rajman et al., 2018; Kirkland, 2021).

The brain does not signal nutrient stress with pain. It signals through:

• Mood changes

• Irritability

• Anxiety

• Cognitive slowing

• Sleep disruption

• Reduced stress resilience

This is why early niacin deficiency often looks psychological rather than nutritional.

Pellagra: When Niacin Deficiency Was Mistaken for Mental Illness

Pellagra is the disease caused by severe niacin deficiency. It was once widespread in Europe and the United States, particularly among populations consuming monotonous or protein-poor diets.

Pellagra is classically described by the “three Ds”:

• Dermatitis

• Diarrhea

• Dementia

If untreated, it progressed to a fourth D: death (Hegyi et al., 2004).

Crucially, neuropsychiatric symptoms often appeared before skin or gastrointestinal signs. Depression, paranoia, hallucinations, confusion, aggression, and cognitive decline were common. Many individuals were institutionalized, and pellagra became one of the leading causes of death in U.S. psychiatric hospitals in the early 20th century.

This was not because the disease was rare. It was because the nutritional cause was not recognized.

Pellagra Is Not Just History

Despite food fortification, pellagra has not disappeared.

Modern case reports continue to document niacin deficiency presenting with dermatologic, gastrointestinal, and neuropsychiatric symptoms, often after prolonged restrictive diets or malabsorption.

A 2025 case report described a woman with progressive dermatitis, weight loss, gastrointestinal symptoms, and neuropsychiatric decline who was initially treated for autoimmune disease. Only after dietary history revealed chronic restriction was pellagra diagnosed. Treatment with nicotinamide led to rapid clinical improvement (Ryali et al., 2025).

These cases highlight a critical point: niacin deficiency is still missed because clinicians no longer expect to see it.

What Pellagra Teaches Us About PMDD

PMDD is not pellagra. That distinction matters.

There are no studies showing PMDD is caused by niacin deficiency. However, PMDD is characterized by severe neuropsychiatric symptoms that occur in response to normal hormonal fluctuations, often in the absence of abnormal standard lab findings.

Hormonal shifts increase oxidative stress, mitochondrial demand, and neurotransmitter turnover. Niacin-dependent NAD pathways play a central role in managing these processes (Kirkland, 2020; Rajman et al., 2018).

From a physiological standpoint, PMDD represents a state of increased metabolic vulnerability, where nutrient demand may exceed supply even without overt deficiency.

What We Often See on the Organic Acids Test (OAT)

There is no routine serum marker that reliably reflects functional niacin status in the brain. This is where functional testing, such as the Organic Acids Test (OAT), can offer valuable context.

The OAT does not diagnose niacin deficiency. Instead, it highlights patterns related to:

• Mitochondrial energy production

• Oxidative stress

• Neurotransmitter metabolism

• Redox balance

Niacin-dependent NAD pathways are central to all of these processes (Trammell & Brenner, 2013).

Common OAT Patterns Suggesting Increased Niacin Demand

Clinically, increased niacin demand or impaired utilization may be suggested by:

• Markers of impaired carbohydrate metabolism

• Accumulation of glycolytic intermediates

• Indicators of mitochondrial inefficiency

• Elevated oxidative stress markers

• Neurotransmitter metabolite imbalances

These findings are not diagnostic, but they provide context when symptoms, diet history, and hormonal timing align.

Why Niacin Is Rarely Screened For

Niacin deficiency is rarely identified because:

• There is no widely used clinical biomarker

• Symptoms overlap with psychiatric diagnoses

• Functional insufficiency occurs before classic deficiency

• Nutrition is often siloed from mental health care

This mirrors the historical failure to recognize pellagra.

The Bigger Lesson from Pellagra

Pellagra reminds us that:

• Nutrient deficiencies can present as psychiatric illness

• Women’s symptoms are often misattributed

• Absence of research does not equal absence of relevance

• Clinical patterns matter

Biology does not wait for randomized controlled trials.
The brain does not distinguish between psychiatric and nutritional stress.

Symptoms are data.
Patterns matter.

Want help understanding whether vitamin B3 or other nutrient patterns may be part of your picture?

This is one of the most common questions I work through with clients navigating PMDD, ADHD, perimenopause, fatigue, or chronic stress. Using symptoms, history, and functional lab patterns, we look beyond diagnoses and toward what the brain and body may actually need.

Understanding nutrients like vitamin B3 is not about adding another supplement. It is about understanding how your body works.

References

Bogan, K. L., & Brenner, C. (2008). Nicotinic acid, nicotinamide, and nicotinamide riboside: A molecular evaluation of NAD precursor vitamins in human nutrition. Annual Review of Nutrition, 28, 115–130. https://doi.org/10.1146/annurev.nutr.28.061807.155443 

Gropper, S. S., Smith, J. L., & Carr, T. P. (2017). Advanced Nutrition and Human Metabolism (7th ed.). Cengage Learning.

Hegyi, J., Schwartz, R. A., & Hegyi, V. (2004). Pellagra: Dermatitis, dementia, and diarrhea. International Journal of Dermatology, 43(1), 1–5. https://doi.org/10.1111/j.1365-4632.2004.01959.x 

Kirkland, J. B. (2020). Niacin and carcinogenesis. Nutrients, 12(6), 1603. https://doi.org/10.3390/nu12061603 

Kirkland, J. B. (2021). Cellular functions of NAD+. International Journal of Molecular Sciences, 22(16), 9009. https://doi.org/10.3390/ijms22169009 

Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic potential of NAD-boosting molecules. Cell Metabolism, 27(3), 529–547. https://doi.org/10.1016/j.cmet.2018.02.011 

Ryali, H., Elgezeri, H., Ahmed, H., Keith, D., & Thandi, C. (2025). Steroid-resistant rash with neuropsychiatric deterioration and weight loss: A modern-day case of pellagra. Cureus, 17(9), e92437. https://doi.org/10.7759/cureus.92437 

Trammell, S. A. J., & Brenner, C. (2013). Targeted, LCMS-based metabolomics for quantitative measurement of NAD+ metabolites. Analytical Biochemistry, 443(2), 159–168. https://doi.org/10.1016/j.ab.2013.09.018