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05. Rationale for Micronutrient Supplementation in Mental Illness

Published on January 1, 2023 Expired on January 1, 2026

Amelia Villagomez, M.D.

Assistant Professor of Psychiatry - University of Arizona

Key Points

There is strong evidence that poor nutrient intake from diet is:
- Epidemic in the United States.
- Correlated with mental disorder symptoms.
- A risk factor for the emergence of mental disorder symptoms.
Correcting poor nutrient intake can improve mental health.
A good diet may not be enough to optimize nutritional factors related to mental health.
Most Americans are not consuming sufficient amounts of vitamins and minerals.

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Slides and Transcript

Slide 1 of 18

A good diet may not be enough to optimize nutritional factors related to mental health.

Rationale for Micronutrient Supplementation in Mental Illness Slide 1 of 18

Slide 2 of 18

Nobel prize winner, Linus Pauling, in 1968 hypothesized that what is probably inherited in mental disorders are genes that regulate brain metabolism of essential nutrients. As a result, some people have a congenital need for more than typical amounts of co-factors for optimal enzymatic activity.

References:

Downing, D. (1994). Linus Pauling. Journal of Nutritional Medicine, 4(4), 387-388.

Rationale for Micronutrient Supplementation in Mental Illness Slide 2 of 18

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Slide 3 of 18

As we discussed previously, enzymes combined with co-factors, in other words vitamins and minerals, result in the transformation of chemical A to chemical B.

References:

Ames, B. N., Elson-Schwab, I., & Silver, E. A. (2002). High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased km): Relevance to genetic disease and polymorphisms. The American Journal of Clinical Nutrition, 75(4), 616-658.

Rationale for Micronutrient Supplementation in Mental Illness Slide 3 of 18

Slide 4 of 18

Polymorphisms in a gene can result in a decreased binding affinity for co-factors which in turn lowers the reaction rate.

References:

Ames, B. N., Elson-Schwab, I., & Silver, E. A. (2002). High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased km): Relevance to genetic disease and polymorphisms. The American Journal of Clinical Nutrition, 75(4), 616-658.

Rationale for Micronutrient Supplementation in Mental Illness Slide 4 of 18

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Slide 5 of 18

Dr. Bruce Ames has hypothesized that adding vitamins at high doses could increase the intracellular co-factor concentration and thereby activate a defective enzyme. In his 2002 paper cited below, he identified that about 50 human genetic diseases due to defective enzymes can be remedied or ameliorated by the administration of high doses of the vitamin component of the corresponding co-factors which at least partially restores enzymatic activity.

References:

Ames, B. N., Elson-Schwab, I., & Silver, E. A. (2002). High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased km): Relevance to genetic disease and polymorphisms. The American Journal of Clinical Nutrition, 75(4), 616-658.

Rationale for Micronutrient Supplementation in Mental Illness Slide 5 of 18

Slide 6 of 18

Along the same vein, Dr. Eugene Arnold has written about how certain individuals with ADHD benefit from omega-3 supplementation. He says the high heritability of ADHD is multifactorial, of course, but it seems conceivable that one of the genetic factors or more precisely one of the gene-by-environment interactions may be vulnerability to long-chain omega-3 deficiency.

References:

Gordon, H. A., Rucklidge, J. J., Blampied, N. M., & Johnstone, J. M. (2015). Clinically significant symptom reduction in children with attention-deficit/hyperactivity disorder treated with micronutrients: An open-label reversal design study. Journal of Child and Adolescent Psychopharmacology, 25(10), 783–798.

Rationale for Micronutrient Supplementation in Mental Illness Slide 6 of 18

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Slide 7 of 18

Is it possible that some individuals with mental disorders also have a vulnerability to micronutrient deficiency because of polymorphisms of various enzymes and that potentially adding in micronutrients would increase enzymatic activity resulting in improvement in symptoms? We will examine this hypothesis and research supporting it shortly.

References:

Johnstone, J. M., Hughes, A., Goldenberg, J. Z., Romijn, A. R., & Rucklidge, J. J. (2020). Multinutrients for the treatment of psychiatric symptoms in clinical samples: A systematic review and meta-analysis of randomized controlled trials. Nutrients, 12(11), 3394.

Rationale for Micronutrient Supplementation in Mental Illness Slide 7 of 18

Slide 8 of 18

I want to take a moment to talk about the RDA or recommended dietary allowance. The RDAs were initially established during World War II to determine at the time of possible shortage what levels of nutrients would prevent symptomatic nutrient deficiency in most people and by most people specifically 97.5% of people, not all people. If 100 people were to get exactly the RDA level of vitamin C, then 2.5 of that 100 could be at a risk for developing scurvy, for example.

References:

Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. (1997). Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. National Academies Press (US).

Rationale for Micronutrient Supplementation in Mental Illness Slide 8 of 18

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Slide 9 of 18

Additionally, mental health symptoms were not considered when developing RDA values. They were focused mainly on physical ailments. So, RDAs may not give us the best picture of what is optimal for mental health.

References:

Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. (1997). Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. National Academies Press (US).

Rationale for Micronutrient Supplementation in Mental Illness Slide 9 of 18

Slide 10 of 18

The Institute of Medicine has written that intake at the level of the RDA or AI which is adequate intake would not necessarily be expected to replete individuals previously undernourished nor would it be adequate for disease states marked by increased requirements.

References:

Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. (1997). Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. National Academies Press (US).

Rationale for Micronutrient Supplementation in Mental Illness Slide 10 of 18

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Slide 11 of 18

Given the high metabolic needs of the brain, often the first signs of dietary deficiency are psychological.

References:

Johnstone, J. M., Hughes, A., Goldenberg, J. Z., Romijn, A. R., & Rucklidge, J. J. (2020). Multinutrients for the treatment of psychiatric symptoms in clinical samples: A systematic review and meta-analysis of randomized controlled trials. Nutrients, 12(11), 3394.
Benton, D. (2010). The influence of dietary status on the cognitive performance of children. Molecular Nutrition & Food Research, 54(4), 457-470.

Rationale for Micronutrient Supplementation in Mental Illness Slide 11 of 18

Slide 12 of 18

Some individuals are genetically predisposed to require greater amounts of micronutrients for optimal mental functioning and nutrient intakes at the recommended dietary allowance may be insufficient for some individuals based on polymorphism differences in enzymes, receptors, and other cell organelles.

References:

Johnstone, J. M., Hughes, A., Goldenberg, J. Z., Romijn, A. R., & Rucklidge, J. J. (2020). Multinutrients for the treatment of psychiatric symptoms in clinical samples: A systematic review and meta-analysis of randomized controlled trials. Nutrients, 12(11), 3394.
Benton, D. (2010). The influence of dietary status on the cognitive performance of children. Molecular Nutrition & Food Research, 54(4), 457-470.

Rationale for Micronutrient Supplementation in Mental Illness Slide 12 of 18

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Slide 13 of 18

Another problem that compounds the issue of micronutrient insufficiency is that the nutrient density of plants has diminished over the past 50 years. This study looked at the mineral content of 20 fruits and 20 vegetables in the 1980s compared to the 1930s. There were several marked reductions in mineral content. The mineral content of fruits are illustrated in light blue and vegetables in dark blue. There were statistically significant reductions in the levels of calcium, magnesium, copper and sodium in vegetables, and magnesium, iron, copper and potassium in fruit. The water content increased significantly and dry matter decreased significantly in fruit.

References:

Mayer, A. (1997). Historical changes in the mineral content of fruits and vegetables. British Food Journal, 99(6), 207-211.

Rationale for Micronutrient Supplementation in Mental Illness Slide 13 of 18

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Well, what might account for these changes? On the environmental front, the use of herbicides and pesticides that diminish essential nutrients and crops through chelation of minerals, an emphasis on high-yield crops at the expense of nutrient density and even the increase in atmospheric CO2 have all been identified as contributors to the reduced nutrient density of plants.

References:

Johnstone, J. M., Hughes, A., Goldenberg, J. Z., Romijn, A. R., & Rucklidge, J. J. (2020). Multinutrients for the treatment of psychiatric symptoms in clinical samples: A systematic review and meta-analysis of randomized controlled trials. Nutrients, 12(11), 3394.

Rationale for Micronutrient Supplementation in Mental Illness Slide 14 of 18

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Slide 15 of 18

Key points. There is strong worldwide evidence that poor nutrient intake from diet is epidemic in the US, is correlated with mental health symptoms, is a risk factor for the subsequent emergence of mental health symptoms.

Rationale for Micronutrient Supplementation in Mental Illness Slide 15 of 18

Slide 16 of 18

There is strong worldwide evidence that poor nutrient intake from diet when corrected results in improved mental health. A good diet may not be enough to optimize nutritional factors related to mental health.

Rationale for Micronutrient Supplementation in Mental Illness Slide 16 of 18

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Slide 17 of 18

What we eat matters for mental health and most Americans are not consuming sufficient amounts of vitamins and minerals.

Rationale for Micronutrient Supplementation in Mental Illness Slide 17 of 18

Slide 18 of 18

Rationale for Micronutrient Supplementation in Mental Illness Slide 18 of 18

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Next Section

06. An Introduction to Research Types for Micronutrient Supplementation

Learning Objectives:

After completing this activity, the learner will be able to:

Describe the connection between dietary patterns and mental health.
Discuss the available evidence about using BSMs for mental health conditions.
Recognize patients who can benefit from BSM supplementation.

Original Release Date: January 1, 2023

Review and Re-release Date: March 1, 2024

Expiration Date: January 1, 2026

Expert: Amelia Villagomez, M.D.

Medical Editor: Paz Badía, M.D.

Relevant Financial Disclosures:

None of the faculty, planners, and reviewers for this educational activity have relevant financial relationships to disclose during the last 24 months with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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