Mental Health Care: Exploring the Microbiota-Gut-Brain Connection

By: Kim Ross, DCN, CNS, LDN, IFMCP

1. Introduction
2. What is the Microbiota-Gut-Brain Axis?
3. The Microbiota's Influence on the Gut-Brain Axis
4. The Microbiota-Gut-Brain Axis and Mood
5. Nutrition and Lifestyle Interventions to Support the Microbiota-Gut-Brain Axis
6. Nutrient Solutions to Support the Microbiota-Gut-Brain Axis
7. Pure Encapsulations Nutrient Solutions
8. Conclusion
9. Resources

Introduction

Mental health concerns are a growing global issue, with recent data indicating that nearly 1 in 8 individuals worldwide experience some form of emotional distress, including anxious feelings and mood fluctuations.¹ Evidence suggests that disruptions in gut microbiota composition, often influenced by modern diets, stress and environmental exposures, may play a role in these rising mental health concerns.²

By leveraging dietary strategies, stress management techniques and targeted nutrient support, clinicians can provide natural, sustainable solutions that optimize the microbiota-gut-brain axis to address mental health and emotional resilience.

This blog explores the underlying mechanisms of the microbiota-gut-brain axis, its role in mood regulation and evidence-based strategies, including dietary interventions, stress management techniques and targeted nutrients such as probiotics, prebiotics, ashwagandha and L-theanine to support a balanced and resilient gut-brain connection.^‡

What is the Microbiota-Gut-Brain Axis?

The microbiota-gut-brain axis is a bidirectional communication network between the gut microbiome, the central nervous system (CNS), autonomic nervous system (ANS), enteric nervous system (ENS) and the hypothalamus-pituitary-adrenal (HPA) axis.^3,4 This intricate system regulates cognitive function, mood and overall mental well-being. The gut microbiome, composed of trillions of microorganisms, influences neurotransmitter production, immune modulation and hormonal balance, all affecting neurological function and mental & emotional health.⁴

The Microbiota's Influence on the Gut-Brain Axis

The microbiota-gut-brain axis functions through several key pathways facilitating communication between the gut microbiota and the brain. These include neural, immune and endocrine pathways, each playing a distinct role in supporting mental health.

Neural Pathway

The vagus nerve is a primary conduit between the gut and brain, transmitting signals directly from the gut microbiota to the central nervous system.³ Sometimes called the “sixth sense,” the vagus nerve can sense the microbiota and transfer the information to the nervous system, where it integrates and responds appropriately.⁵ Additionally, the enteric nervous system, often called the "second brain," contains millions of neurons that interact with gut microbes to regulate neurotransmitter production and brain activity.

Immune Pathway

The gut microbiome plays a critical role in immune system regulation, influencing cytokine regulation.³ Beneficial microbes promote the release of anti-inflammatory cytokines, such as interleukin-10 (IL-10). Non-beneficial microorganisms can trigger the production of cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which have been implicated in neuro-immune responses and mood disturbances.⁶

Endocrine Pathway

The endocrine pathway is more commonly referred to as the neuroendocrine system. The gut microbiota modulates gut hormones and neurotransmitters made in the gut and activates the hypothalamus-pituitary-adrenal (HPA) axis. The HPA axis governs the body's stress response and is involved in mood and immune function.³ Gut bacteria produce neurotransmitters such as serotonin, dopamine and GABA, which are essential for maintaining emotional stability.⁷

The Microbiota-Gut-Brain Axis and Mood

Studies suggest that gut microbiota imbalances are linked to mood fluctuations through altered neurotransmitter production, increased intestinal permeability, HPA dysregulation and heightened cytokine production. Specific bacterial strains, such as Bifidobacterium longum and Lactobacillus helveticus, have been shown to exert anxiolytic and mood-stabilizing effects by modulating gamma-aminobutyric acid (GABA), serotonin, dopamine, tryptophan, cortisol and cytokines.⁷

Nutrition and Lifestyle Interventions to Support the Microbiota-Gut-Brain Axis

Optimizing gut health through targeted nutrition and lifestyle interventions can strengthen the microbiota-gut-brain axis and improve mood regulation.

Diet and Its Influence on the Microbiome

Diet is described as one of the most influential and rapid contributors to microbial changes.^3,4 A symbiotic relationship between fiber, polyphenols, prebiotics and fermented foods in the diet supports microbial diversity and enhances gut-brain communication.

• Fiber is a food source for beneficial bacteria and promotes short-chain fatty acid (SCFA) production. Among its benefits, SCFAs support the GI barrier, promote the production of serotonin and GABA, modulate the immune system and influence the gut-brain connection through the vagus nerve.⁸ Fruits, vegetables, legumes and whole grains are rich sources of dietary fiber.
• Polyphenol-rich foods like berries, apples, green tea, olive oil and dark chocolate may act as prebiotics.³ They have been shown to modulate the gut microbiome by increasing beneficial bacteria (i.e., Bifidobacterium, Firmicutes, Lactobacillus) and reducing harmful bacteria (i.e., Clostridium) while also supporting the body’s natural inflammatory processes and providing antioxidant and neuroprotective properties.⁹ Many polyphenol-rich foods are also a good source of fiber.
• Prebiotics found in foods like garlic, onions, leeks, bananas, apples, honey, chicory root, flaxseed and asparagus fuel the growth of beneficial bacteria. By default, many prebiotic foods are also a source of fiber and polyphenols.
• Fermented foods, including yogurt, kefir, kimchi, miso, cheese, vinegar and sauerkraut, provide beneficial probiotics that enhance gut microbiota composition and are a readily available source of SCFAs. Homemade fermented foods will provide the most probiotic diversity, and the fermentation process increases the polyphenol bioavailability.¹⁰

In contrast, a diet high in processed foods, refined sugars and artificial additives can disrupt the gut microbiome, contributing to mood fluctuations and an altered cytokine response.⁴

Stress, Physical Activity and Sleep: Their Influence on the Microbiome

Stress negatively impacts gut microbiota composition and vagal tone, increasing intestinal permeability and cytokine response.⁵ Conversely, gut microbiota diversity may influence how one handles stress, partially due to the influence on the production of GABA and serotonin.¹¹ Stress management techniques like meditation, deep breathing and cognitive behavior therapy can help restore microbial balance, reduce HPA overactivity and support emotional resilience.⁵

Physical activity, particularly aerobic exercise, fosters microbial diversity and enhances the production of beneficial short-chain fatty acids (SCFAs), improving HPA axis control and positive moods.¹²

Sleep and the microbiome have a complementary relationship. Sleep is essential for maintaining a healthy microbiome, and a diverse microbiome has been positively correlated with increased sleep efficiency and total sleep time. Sleep deprivation has been linked to shifts in microbial composition and increased cortisol levels.¹³

Nutrient Solutions to Support the Microbiota-Gut-Brain Axis

Targeted supplementation with specific nutrients and bioactive compounds can further enhance the gut-brain connection and promote positive mental health.^‡

Probiotics & Prebiotics

Probiotic supplementation has been extensively studied for its effects on gut health and mood regulation. More specifically, in 2013, the term 'psychobiotics' was coined, describing the beneficial bacteria that produce health benefits for mental health.⁷ Multiple probiotic strains have been shown to enhance GABA and serotonin receptor expression in the brain, reduce cortisol levels and reduce cytokine activation. (Table 1)^‡

The most extensive and compelling evidence to support emotional and mental health exists for Lactobacillus helveticus Rosell-52 (RO052) and Bifidobacterium longum Rosell-175 (RO175).⁷ In a randomized, double-blind, placebo-controlled trial, supplementation with this combination maintained healthy urinary cortisol levels, indicating the potential to lessen occasional stress.¹⁴ In a separate analysis, supplemented subjects reported positive mood, relaxation and enhanced cognitive function.¹⁵ Further, multiple human studies have reported positive mood effects with this specific combination of probiotic strains.⁷

Prebiotics works synergistically with probiotics. The various types of prebiotics include fructans, galactooligosaccharides, xylo-oligosaccharides, chitooligosaccharides, lactulose, resistant starch and polyphenols. Prebiotics modulate and support the growth of the gut microbiota, specifically Bifidobacteria and Lactobacilli, increase SFCA production, improve gut barrier function, modulate the immune system and positively influence mood.^16‡

Butyrate

Butyrate is one of the three most abundant short chain fatty acids (SCFAs) produced by anaerobic bacterial fermentation of polysaccharides/fiber in the colon, where it serves as an energy source for epithelial cells.¹⁷ Considered a functionally versatile molecule, butyrate provides support for maintaining gastrointestinal health and regulating the neuro-endocrine-immune pathways, in part due to its ability to cross the blood-brain barrier.^17,18‡

Ashwagandha

Ashwagandha (Withania somnifera) is an adaptogenic herb that modulates the HPA axis and maintains healthy cortisol levels. In a double-blind trial, 60 participants with high perceived stress scores were randomized to receive KSM-66 Ashwagandha^® extract (125 mg or 300 mg) or placebo twice daily for 8 weeks. A significant reduction in perceived stress scale (PSS) scores was observed with both doses of ashwagandha compared to the placebo group. Mean cortisol response decreased by 17% and 33% in the groups receiving 125 mg and 300 mg twice daily, respectively, after 8 weeks. Subjects receiving ashwagandha also exhibited significant improvements in sleep quality.^19‡

L-Theanine

L-theanine an amino acid found in green tea, may be most recognized for its ability to exert anxiolytic effects by modulating GABA activity and for its role in regulating the stress response. In a double-blind crossover trial, 30 healthy adults received l-theanine (200 mg Suntheanine^®/day) or placebo for 4 weeks. L-theanine significantly improved stress-related symptoms, including low-mood symptoms and occasional anxiety per validated questionnaires and sleep (Pittsburgh Sleep Quality Index; PSQI)^‡

Newer research also suggests that l-theanine influences the gut-brain connection by increasing beneficial bacteria, such as Lactobacillus, while also decreasing non-beneficial bacteria, such as Closterium.²¹

Pure Encapsulations^® Nutrient Solutions

Pure Encapsulations provides uniquely formulated products made with high-quality, pure ingredients backed by verifiable science to complement your plan of care and support microbiota-gut-brain axis in your patients.^‡

ProbioMood is a clinically researched combination of probiotic strains that promotes emotional well-being and relaxation. This formula contains the well-researched strains Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175. It was developed using an innovative, patented microencapsulation process designed to protect the probiotic strains from harsh conditions, including gastric acidity.^‡

Suggested Use: Take one (1) capsule daily, with or between meals

Poly-Prebiotic is a shelf-stable prebiotic formula that includes 1.5 g of clinically researched PreticX^™ XOS (xylo-oligosaccharides) that enhances the growth of Bifidobacteria. In contrast to FOS and other common prebiotics, studies on XOS report very low incidence of gas and bloating.^20,21

Suggested Use: Take three (3) capsules, 1-2 times daily, with or between meals

SunButyrate^™-TG liquid is a unique butyrate-rich triglyceride oil that allows for direct delivery of 875 mg of butyric acid (per serving) to the intestines. Benefits include supporting gut cell and barrier function and promoting cytokine balance.^‡

Suggested Use: As a dietary supplement, take 1 teaspoon, 1-3 times daily, with meals.

Daily Calm combines GABA with clinically backed saffron (affron^®), ashwagandha (KSM-66^®) and l-theanine (Suntheanine^®) to relieve feelings of occasional stress and anxiety. Together, these ingredients address common mental health needs while supporting mood and sleep quality with continued use.^‡

Suggested Use: Take one (1) capsule, two times daily between meals

Conclusion

The microbiota-gut-brain axis plays a pivotal role in supporting mental health. The gut microbiota communicates with the brain through neural, immune and endocrine pathways, influencing neurotransmitter production, stress response and cytokine regulation. Healthcare professionals can support gut health and enhance mental well-being by utilizing targeted nutrients such as probiotics, prebiotics, ashwagandha and l-theanine, in combination with diet and lifestyle strategies.

Resources

Microbiota-Gut-Brain Axis Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support for your patient's intestinal health.

Drug-Nutrient Interaction Checker:  Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight^™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

1. World Health Organization. Mental disorders. World Health Organization. June 8, 2022. Accessed February 12, 2025. https://www.who.int/news-room/fact-sheets/detail/mental-disorders
2. Foster JA, Rinaman L, Cryan JF. Neurobiol Stress. Published online 2017. doi:10.1016/j.ynstr.2017.03.001
3. Chakrabarti A, Geurts L, Hoyles L, et al. Cellular and Molecular Life Sciences. 2022;79(2). doi:10.1007/s00018-021-04060-w
4. Liu L, Huh JR, Shah K. EBioMedicine. 2022;77. doi:10.1016/j.ebiom.2022.103908
5. Bonaz B, Bazin T, Pellissier S. Front Neurosci. 2018;12(FEB). doi:10.3389/fnins.2018.00049
6. Tsvetanova F. Int J Mol Sci. 2024;25(5). doi:10.3390/ijms25052980
7. Ross K. Explore. Published online 2023. doi:10.1016/j.explore.2023.02.007
8. Silva YP, Bernardi A, Frozza RL. Front Endocrinol (Lausanne). 2020;11. doi:10.3389/fendo.2020.00025
9. Wang X, Qi Y, Zheng H. Antioxidants. 2022;11(6). doi:10.3390/antiox11061212
10. Leeuwendaal NK, Stanton C, O’toole PW, Beresford TP. Nutrients. 2022;14(7). doi:10.3390/nu14071527
11. Berding K, Bastiaanssen TFS, Moloney GM, et al. Mol Psychiatry. 2023;28(2). doi:10.1038/s41380-022-01817-y
12. Dalton A, Mermier C, Zuhl M. Gut Microbes. 2019;10(5). doi:10.1080/19490976.2018.1562268
13. Smith RP, Easson C, Lyle SM, et al. PLoS One. 2019;14(10). doi:10.1371/journal.pone.0222394
14. Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C. Gut Microbes. Published online 2011. doi:10.4161/gmic.2.4.16108
15. Messaoudi M, Lalonde R, Violle N, et al. British Journal of Nutrition. Published online 2011. doi:10.1017/S0007114510004319
16. Yoo S, Jung SC, Kwak K, Kim JS. Int J Mol Sci. 2024;25(9). doi:10.3390/ijms25094834
17. Facchin S, Bertin L, Bonazzi E, et al. Life. 2024;14(5):559. doi:10.3390/life14050559
18. Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. Neurochem Int. 2016;99:110-132. doi:10.1016/j.neuint.2016.06.011
19. Salve J, Pate S, Debnath K, Langade D. Cureus. Published online 2019. doi:10.7759/cureus.6466
20. Hidese S, Ogawa S, Ota M, et al. Nutrients. 2019;11(10). doi:10.3390/nu11102362
21. Lim SE, Kim HS, Lee S, et al. Front Nutr. 2024;11:1419978. doi:10.3389/fnut.2024.1419978
22. Finegold SM, Li Z, Summanen PH, et al. Food Funct. 2014;5(3). doi:10.1039/c3fo60348b
23. Childs CE, Röytiö H, Alhoniemi E, et al. British Journal of Nutrition. 2014;111(11). doi:10.1017/S0007114513004261

By: Kim Ross, DCN, CNS, LDN, IFMCP

1. Introduction
2. A Healthy Barrier and Its Functions
3. A Compromised Barrier
4. Factors that Impact GI Integrity and Lead to a Self-Tissue Response
5. Nutrition, Lifestyle and Health Components
6. Nutrient Solutions to Build the Intestinal Barrier
7. Pure Encapsulations Nutrient Solutions
8. Conclusion
9. Resources

Introduction

The intestinal barrier is more than just a digestive checkpoint - it's a key defender against non-beneficial microorganisms, toxins, and antigens while allowing the body to absorb vital nutrients. When this barrier is compromised, it can lead to a cascade of symptoms, including occasional bloating, abdominal discomfort, irregular bowel movements, and nutrient malabsorption.

One common consequence of a weakened barrier includes intestinal concerns, often triggered by self-tissue response. According to the CDC, over 3.1 million Americans experience intestinal immune concerns,¹ which can disrupt nutrient absorption and weaken overall immunity.

This article will explore the essential nutrients that support the mucosal immune system and strengthen the intestinal barrier, offering insights into how dietary interventions can help maintain gut integrity and overall health.

A Healthy Barrier and Its Functions

The intestinal barrier consists of a monolayer of specialized epithelial cells that line the gut lumen, forming a selectively permeable barrier. These epithelial cells are sealed together by tight junction proteins, including occludin, claudin-1, and zonula occludens-1 (ZO-1).^2,3 Tight junctions function as "gatekeepers," determining what substances can pass through the intestinal lining into the bloodstream while preventing the entry of harmful microorganisms, toxins, and antigens.

The intestinal barrier also includes a mucus layer, which provides physical protection by preventing direct contact between microbes and the epithelial cells. It contains antimicrobial peptides and secretory immunoglobulin A (sIgA), which neutralize non-beneficial microorganisms and contribute to immune defense. This layer is rich in immune cells such as macrophages, dendritic cells, and T-cells, which play key roles in maintaining immune homeostasis.³

The primary functions of the gut barrier include:⁴

• absorption of nutrients
• regulation of immune responses
• maintenance of intestinal homeostasis
• prevention of the translocation of harmful substances
• supporting bidirectional communication between the gut microbiota and the immune system

A Compromised Barrier

When the integrity of the gut barrier is compromised, it can lead to increased intestinal permeability, commonly called "leaky gut." Increased permeability allows larger molecules, such as undigested food particles, toxins, and microbes, to enter the bloodstream, potentially triggering an unbalanced state and immune activation. This, in turn, can lead to persistent intestinal distress and self-tissue response in the intestines, further exacerbating symptoms and contributing to systemic changes.

Factors That Impact GI Integrity and Lead to a Self-Tissue Response

The integrity of the intestinal barrier and the development of a self-tissue response in the intestines is rarely a result of one factor. Instead, it is a multifactorial process influenced by numerous factors, including the health of the microbiome, immune and cytokine responses, and nutrition, lifestyle, and health components.

The Health of the Microbiome

The gut microbiome is a complex ecosystem of nearly 100 trillion microorganisms that maintain mucosal health.² Beneficial microbes such as Bifidobacteria, Lactobacilli, enterococcus, and Clostridium produce short-chain fatty acids (SCFAs), which support tight junction integrity and signaling.²

Conversely, a microbial imbalance resulting from low microbial diversity or gastrointestinal infections can increase intestinal permeability and promote an increased immune response. Evidence suggests that individuals with a self-tissue response in the intestines have a reduction of beneficial bacterial species in the gastrointestinal tract.⁵

The Immune and Cytokine Responses in the Gut

The gut-associated lymphoid tissue (GALT) is an integral part of the immune system, responsible for responding to non-beneficial bacteria while maintaining tolerance to dietary antigens and commensal bacteria. Cytokines such as interleukin-10 (IL-10) promote immune tolerance, whereas excessive production of cytokines like IL-6 and TNF-α disrupt mucosal balance. Activation of these cytokines can perpetuate barrier and tissue changes, contributing to systemic immune activation.^6,7

Nutrition, Lifestyle & Health Components

Nutrition: The Standard American Diet (Western Diet) contains a high intake of refined sugars, processed carbohydrates, red or processed meat, omega-6 fatty acids, and alcohol, exacerbating the body's cytokine balance processes. The way of eating is also partially responsible for decreased bacterial diversity in the gut and contributes to inadequate intake of essential vitamins and minerals. Poor nutrient absorption is a common presentation for people with a self-tissue response in the intestines.^8,9

Conversely, a diet rich in fruits and vegetables, fiber, omega-3 fatty acids, fish, grains, and legumes protects and supports a healthy GI barrier. Studies have shown that eliminating some food groups, such as gluten and dairy or other known food allergies or intolerances, may help reduce GI symptoms and support a self-tissue response.⁹ Special attention should be given to replacing vitamins and minerals, such as B vitamins, vitamin D, electrolytes, and omega-3 fatty acids, as indicated.¹⁰

Lifestyle: Perceived stress that is uncontrolled or not well managed is considered a predictor of the exacerbation of GI symptoms and self-tissue response.¹¹ Poor sleep quality is associated with elevated levels of IL-6, TNF-α, nuclear factor-kB (NF-kB), and CRP (C-reactive protein), known markers of the immune system.¹²

Health Components: General health components such as a history of intake of medications, exposure to environmental toxins and genetic predisposition also play a role in the susceptibility to a compromised intestinal barrier and immune response.

Nutrient Solutions to Build the Intestinal Barrier

Glutamine is the most abundant amino acid in the body. It is the primary energy source for enterocytes (the cells that line the small intestine and colon), utilizing about 30% of total glutamine.^13,14 It also helps maintain healthy intestinal integrity by enhancing the intestine's protective mucosal lining and promotes tissue repair from metabolic stress.^14‡

Studies have demonstrated that L-glutamine supplementation reduces intestinal permeability and supports outcomes in patients with compromised barrier integrity.^13‡

Arabinogalactan, a fiber derived from larch trees, is a prebiotic that promotes the growth of beneficial gut bacteria. such as Bacteroidetes, Bifidobacterium, and Faecalibacterium praisnitzii, which are crucial for proper gut-associated lymphoid tissue (GALT) function and development.¹⁵ These bacteria produce SCFAs, including butyrate, which enhance epithelial integrity and modulate cytokine production.^‡

Arabinogalactan also has immunomodulatory properties, supporting the production of natural killer (NK) cells and promoting mucosal immunity.¹⁶ It may also promote healthy production of cytokines, which mediate cell-to-cell communication between cells involved in the immune response. Its dual role as a prebiotic and immune supporter makes it a valuable addition to protocols to restore gut health.^‡

Perilla (Perilla frutescens) is a traditional herb rich in polyphenols and rosmarinic acid. which promote cytokine balance and antioxidant effects. Its active compounds reduce the production of cytokines such as IL-6 and TNF-α, which are implicated in intestinal immune changes.^17‡

In a randomized, controlled trial involving 50 individuals, 150 mg of Benegut^® Perilla frutescens extract twice daily offered significant support for GI comfort.¹⁸ Perilla also stabilizes mast cells, reducing hypersensitivity reactions that can contribute to mucosal damage.^19‡

Additionally, its antioxidant properties help neutralize reactive oxygen species (ROS), protecting the intestinal lining from oxidative stress.²⁰

Astragalus (Astragalus membranaceus) is a well-known adaptogenic herb with a long history of use in Traditional Chinese Medicine (TCM). It promotes immunity by supporting B and T lymphocyte production, balancing Th1/Th2, and modulating cytokine response.²¹ It also protects the intestinal barrier by upregulating tight junction proteins and secretory IgA (sIgA) production. This key immune component coats the intestinal lining and prevents the adherence of non-beneficial microorganisms.²² Its adaptogenic properties further support resilience against stress, a contributing factor to a compromised intestinal barrier.^23‡

Deglycyrrhizinated licorice (DGL) supports the healing of the GI barrier and other mucous membranes by increasing blood supply to mucosa, increasing the production of mucus, which acts as a protective barrier for the intestinal lining and improves the life span of intestinal cells.^24‡

Pure Encapsulations^® Nutrient Solutions

Pure Encapsulations offers expertly crafted supplements made with high-quality, pure ingredients and supported by verifiable scientific research. These products are designed to complement personalized care plans.^‡

Epi-Integrity powder: is a carefully formulated blend of glutamine, prebiotic fiber, and herbal extracts that support the modulation of mucosal immune responses and promote gastrointestinal (G.I.) barrier integrity. It helps maintain a balanced microbiome, provides mucosal protection, and supports epithelial cell health for optimal gut function.^‡

Suggested Use: 1 scoop, 1-2 times daily. Add 1 serving to 8 oz of water or juice. Shake or stir until dissolved.

Conclusion

Restoring intestinal barrier integrity and supporting mucosal immune responses are essential for addressing symptoms associated with self-tissue responses in the gut. Healthcare providers can leverage evidence-based nutritional strategies to address the underlying factors contributing to a compromised barrier. Nutrients such as L-glutamine, arabinogalactan, perilla, Astragalus, and DGL offer targeted support for mucosal repair, cytokine modulation and immune balance.^‡

Resources

Gastrointestinal Self-Tissue Response Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support for your patient's intestinal health.^‡

Drug-Nutrient Interaction Checker:  Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight^™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

1. Center for Disease Control and Prevention. June 21, 2024. Accessed January 19, 2025. https://www.cdc.gov.
2. Fusco W, Lorenzo MB, Cintoni M, et al. Nutrients. 2023;15(9). doi:10.3390/nu15092211
3. Di Sabatino A, Santacroce G, Rossi CM, Broglio G, Lenti MV. Intern Emerg Med. 2023;18(6). doi:10.1007/s11739-023-03329-1
4. Ghosh S, Whitley CS, Haribabu B, Jala VR. CMGH. 2021;11(5). doi:10.1016/j.jcmgh.2021.02.007
5. Khan I, Ullah N, Zha L, et al. Pathogens. 2019;8(3). doi:10.3390/pathogens8030126
6. Ullah H, Arbab S, Tian Y, et al. Front Immunol. 2024;15:1413485. doi:10.3389/fimmu.2024.1413485
7. Tanoue T, Umesaki Y, Honda K. Gut Microbes. 2010;1(4). doi:10.4161/gmic.1.4.12613
8. De Castro MM, Pascoal LB, Steigleder KM, et al. World J Exp Med. 2021;11(1). doi:10.5493/wjem.v11.i1.1
9. Christensen C, Knudsen A, Arnesen EK, Hatlebakk JG, Sletten IS, Fadnes LT. Advances in Nutrition. 2024;15(5):100219. doi:10.1016/j.advnut.2024.100219
10. Balestrieri P, Ribolsi M, Guarino MPL, Emerenziani S, Altomare A, Cicala M. Nutrients. 2020;12(2). doi:10.3390/nu12020372
11. Edman JS, Greeson JM, Roberts RS, et al. Explore: The Journal of Science and Healing. 2017;13(2). doi:10.1016/j.explore.2016.12.005
12. Irwin MR, Opp MR. Neuropsychopharmacology. 2017;42(1). doi:10.1038/npp.2016.148
13. Abbasi F, Haghighat Lari MM, Khosravi GR, Mansouri E, Payandeh N, Milajerdi A. Amino Acids. 2024;56(1):60. doi:10.1007/s00726-024-03420-7
14. Kim MH, Kim H. Int J Mol Sci. 2017;18(5). doi:10.3390/ijms18051051
15. Cao Y, Shen J, Ran ZH. Gastroenterol Res Pract. 2014;2014. doi:10.1155/2014/872725
16. Dion C, Chappuis E, Ripoll C. Nutr Metab (Lond). 2016;13(1). doi:10.1186/s12986-016-0086-x
17. Pressi G, Rigillo G, Governa P, et al. Pharmaceutics. 2023;15(1). doi:10.3390/pharmaceutics15010240
18. Buchwald-Werner S, Fujii H, Reule C, Schoen C. BMC Complement Altern Med. 2014;14. doi:10.1186/1472-6882-14-173
19. Takano H, Osakabe N, Sanbongi C, et al. Exp Biol Med. 2004;229(3). doi:10.1177/153537020422900305
20. Adam G, Robu S, Flutur MM, et al. Antioxidants. 2023;12(3). doi:10.3390/antiox12030727
21. Wang XY, Wang RC, Qu ZY, Zhu YZ, Li YL. Frontiers in Natural Products. 2022;1. doi:10.3389/fntpr.2022.971679
22. Liang H, Tao S, Wang Y, et al. Front Nutr. 2024;11. doi:10.3389/fnut.2024.1364739
23. Park HJ, Hyun YK, Yoon KH, Kyung SK, Shim I. Korean Journal of Physiology and Pharmacology. 2009;13(4). doi:10.4196/kjpp.2009.13.4.315
24. Murray MT. In:Textbook of Natural Medicine.; 2020. doi:10.1016/b978-0-323-43044-9.00085-6

By: Kim Ross, DCN, CNS, LDN, IFMCP

1. Introduction
2. The Interconnected Web
2.1 The Role of Thyroid Hormones
2.2 The Hypothalamus-Pituitary-Thyroid-Adrenal (HPTA) Axis
2.3 Mood and Neurotransmitter Dysregulation
3. Lifestyle Components to Support Healthy Thyroid Function
4. Nutrient Solutions to Support Thyroid Function
5. Pure Encapsulations Nutrient Solutions
6. Conclusion
7. Resources

By: Kim Ross, DCN, CNS, LDN, IFMCP

Occasional stress and anxious feelings have implications for thyroid health. A poll conducted in 2024 by the American Psychiatric Association revealed that 43% of adults in the United States experience increased feelings of occasional anxiousness, with 53% of those polled attributing this feeling to stress.¹ The American Thyroid Association reports that approximately 12% of the U.S. population will experience changes in thyroid function at some point in their lives ², though the data on the prevalence varies from 4.6%-14.4%.³ Suboptimal thyroid function is characterized by compromised thyroid hormone production or conversion of thyroxine (T4) to triiodothyronine (T3). Thyroid antibodies may also be present, with or without changes in thyroid hormone levels, resulting in a self-tissue response. Low mood is a common symptom of changes in thyroid hormone levels, with 63% of adults with suboptimal thyroid function having some degree of anxious feelings.⁴

Conventional intervention approaches often focus on symptom management rather than addressing the root causes of stress, mood dysregulation and thyroid-related symptoms. For example, the most common medical intervention for thyroid support is the use of synthetic T4 medications, which may stabilize thyroid hormone levels but can exacerbate anxious feelings in some patients.⁵

Pharmaceuticals used for mood regulation have variable efficacy and carry risks that should be carefully considered.⁶ These limitations underscore the need for a nutrient-focused, integrative approach to supporting thyroid health, resilience and emotional balance.

It’s important to note that any recommendations are not meant to treat, cure, or prevent diseases or be a substitute for medical, diagnostic, and treatment options. Dietary supplements are not intended to replace the use of any medications prescribed.

It can be a challenge deciding optimal clinical recommendations when patients present with occasional stress, anxiousness and changes with thyroid function, with or without the presence of thyroid antibodies. It can be helpful to review the interconnected web between the three to help determine the appropriate and most optimal course of action.

The hypothalamus-pituitary-thyroid (HPT) axis is the neuroendocrine system that controls the production of thyroid hormones through a feedback loop. Thyroid stimulating hormone (TSH), is produced by the pituitary gland, which signals the thyroid gland to produce thyroid hormones, primarily thyroxine (T4). Once T4 is secreted, it is bound to transport proteins and carried to the cells and tissues where it passes through a series of metabolic transformations. It is then activated to triiodothyronine (T3) or inactivated into reverse T3 (rT3). This entire process is largely influenced by nutrient (in)sufficiency, stress and other lifestyle factors. However, loss of self-tolerance is another influential factor in this process. Thyroid antibodies may be present with or without abnormalities in the production of TSH, T4 and/or T3 and can contribute to a suboptimal thyroid. Genetics, cytokine dysregulation, diet and lifestyle factors are commonly noted as contributors to loss of self-tolerance.^7,8

Thyroid hormones play a role in the development, differentiation and metabolic maintenance of virtually all tissues, which is a topic that is beyond the scope of this blog. Of interest, thyroid hormones help regulate the body’s response to stress. Additionally, thyroid hormones directly influence the synthesis, release and degradation of key neurotransmitters associated with stress and mood regulation, including serotonin, dopamine and gamma-aminobutyric acid (GABA).

Suboptimal thyroid function often disrupts the hypothalamic-pituitary-adrenal (HPA) axis, which can alter one’s ability to maintain resilience to the stressors of life while also worsening occasional anxious feelings. There are two categories of stressors:

• External: Such as post-traumatic events, work, relationships and finances.
• Physiological: Such as nutrient insufficiencies, toxin burden, overactivation of the 
  immune system and cytokine function.

When an individual experiences stress, the HPA axis is activated, leading to increased production of cortisol. This is when the interconnected hypothalamic-pituitary-thyroid-adrenal (HPTA) axis becomes apparent. Elevated cortisol levels can inhibit the conversion of T4 to its active form T3, resulting in suboptimal thyroid function. Additionally, stress can lead to changes in production of reverse T3, which is biologically inactive and competes with T3 for cellular receptors.⁹ Finally, stress has been implicated as a trigger for loss of self-tolerance and an increased production of thyroid antibodies.¹⁰ The feedback loop in the HPTA axis creates a potential pathway through which stress and low functioning thyroid are interconnected. 

The relationship between stress and suboptimal thyroid can also contribute to the development of occasional anxious feelings. Thyroid hormones play a role in regulating the central nervous system (CNS) and the limbic system, which are critical for mood stabilization and emotional processing. Thyroid function in need of support can affect the synthesis and availability of  neurotransmitters such as serotonin, dopamine and gamma-aminobutyric acid (GABA), which are essential for maintaining a calm and balanced emotional state.¹¹ In fact, nutrients that are needed for the proper production of thyroid hormones also play a role as co-factors for the production of these neurotransmitters, including, but not limited to, B vitamins, zinc, vitamin C and the amino acid tyrosine.^‡

Nutrition: A nutrient-dense diet that supports thyroid health, neurotransmitter production, and modulates cytokine response can be effective in managing stress and emotional well-being. Emphasizing foods rich in selenium (e.g., Brazil nuts), iodine (e.g., seaweed, seafood, dairy, eggs, poultry) and zinc (e.g., pumpkin seeds, lean meats) should serve as a foundation. The Mediterranean Diet, known for its anti-inflammatory properties, has been shown to improve emotional regulation and support the neuroendocrine system.¹²

Exercise: Aerobic activities, such as walking or cycling, have been found to enhance the conversion of T4 to T3 and increase the sensitivity of cellular receptors to thyroid hormones. Additionally, yoga and tai chi, which integrate physical movement with mindfulness, have demonstrated efficacy in reducing stress and promoting thyroid health.¹³

Sleep: Suboptimal thyroid function may lead to sleep disturbances. Poor sleep aggravates occasional anxiety by impacting neurotransmitters and can lead to the increased production of stress hormones. Prioritizing 7-9 hours of restorative sleep per night, maintaining a consistent sleep schedule and creating a calming pre-sleep routine can help optimize thyroid function, modulate stress responses and promote a calm mood.

Stress Management: Mind-body practices such as mindfulness meditation, deep breathing exercises, guided imagery and progressive muscle relaxation have been shown to provide effectiveness on the psychological and physiological levels.¹⁴

Iodine is a vital nutrient for the synthesis of T4. While adequate iodine intake is essential for maintaining thyroid function, it should be approached cautiously, especially in individuals with a self-tissue response.^‡ 

Selenium is a critical cofactor for the enzyme deiodinase, which converts T4 to T3. Generally, individuals will consume enough of this nutrient in their diet. It is important to be aware of potential selenium toxicity from excess consumption.¹⁵

Zinc is an essential trace mineral involved in the conversion of T4 to T3 and is a needed cofactor for the regulation of neurotransmitters. B Vitamins particularly B6, B9 (folate) and B12, play a role in T4 production, and neurotransmitter synthesis. These vitamins also help improve the body’s response to stress.^‡

Myo-inositol is the primary form of inositol found in the central nervous system. It plays an important role in cell membrane formation and serves as part of the phosphatidylinositol secondary messenger system, supporting serotonin, norepinephrine and cholinergic receptor function.^16‡

Studies have shown that combined use of Selenium methionine and Myo-inositol can support feelings of well-being, thyroid hormone production and healthy TSH, TPO and TG antibody levels.^{17,18 ‡}

L-Tyrosine is an amino acid that serves as a precursor for the synthesis of thyroid hormones and the neurotransmitter, dopamine. 

GABA is an inhibitory neurotransmitter and amino acid that promotes calmness and relaxation. It plays a significant role in regulating the HPA axis and reducing the body's stress response. ^‡

L-Theanine, an amino acid found in green tea, has been shown to promote relaxation by modulating glutamate (the excitatory neurotransmitter) function, and possibly the GABA, system as well.^{19 ‡}

Ashwagandha (Withania somnifera) is an adaptogenic herb known for its ability to reduce stress and support thyroid health. Research indicates that ashwagandha can lower cortisol levels, support thyroid hormone production and enhance overall well-being.²⁰ 

Pure Encapsulations® provides uniquely formulated products made with high-quality, 
pure ingredients backed by verifiable science to complement your plan of care and support 
healthy aging in your patients.^‡

Thyroid Support Complex: Supports optimal thyroid gland function, healthy thyroid cell 
metabolism and thyroid hormone function^‡

Suggested Use: As a dietary supplement, take 2 capsules daily, with a meal.

Daily Stress Formula: Promotes mental relaxation and moderates the effects of 
occasional stress, supports the body’s resilience when faced with occasional stress and
helps moderate mild fatigue under stressful conditions^‡
 
Suggested Use: As a dietary supplement, take 3 capsules daily, with or between meals.

L-Theanine: Promotes relaxation, with Suntheanine®, without causing drowsiness^‡

Suggested Use: As a dietary supplement, children ages 8-18, take 1 capsule, 1-2 times 
daily, between meals. Adults, take 2 capsules, 1-3 times daily, between meals.

Zinc 30: Broad physiological support, including immune function and emotional wellness^‡

Suggested Use: As a dietary supplement, take 1 capsule, 1-2 times daily, with a meal.

Selenium (selenomethionine): Supports antioxidant defenses, immune function and 
cellular health^‡

Suggested Use: As a dietary supplement, take 1 capsule daily, with a meal, or as directed 
by a health professional.

GABA: Promotes relaxation and moderates occasional stress. May also support immune 
health during occasional stress.^‡

Suggested Use: As a dietary supplement, take 1 capsule daily, between meals, or as 
directed by a health professional.

DopaPlus 180’s: Promotes the production of dopamine to support daily cognitive function 
and performance on mental tasks while also supporting mood.^‡

Suggested Use: As a dietary supplement, take 3 capsules, 1-2 times daily, with low protein 
foods.

SeroPlus: Promotes serotonin synthesis to support relaxation, moderate occasional stress 
and maintain healthy eating behavior. Provides neurotransmitter precursors to help 
balance serotonin function and maintains healthy serotonin activity and reuptake.^‡

Suggested Use: As a dietary supplement, take 2 capsules, 1-2 times daily, between meals.

NeuroPure 120’s: Provides enhanced support for emotional balance and mood stability
while supporting overall neurotransmitter function and neuronal health.^‡

Suggested Use: As a dietary supplement, take 2 capsules, 1-2 times daily, between meals.

Inositol Complex: May support healthy mood, emotional wellness and behavior and helps 
lessen occasional nervous tension.^‡

Suggested Use: as a dietary supplement, take 1 capsule, twice daily with meals.

The intricate connection between stress, occasional anxiousness, and thyroid health underscores the importance of a holistic approach to wellness. By understanding the role of the HPT and HPTA axes, as well as the impact of lifestyle factors and nutrient support, individuals can take proactive steps to better manage their thyroid health and emotional well-being. Prioritizing a nutrient-dense diet, stress management techniques, quality sleep, and appropriate supplementation can create a foundation for resilience and balance. While navigating these interconnections can be complex, informed choices and integrative strategies offer a pathway to improved overall health

Thyroid Support Protocol^‡: Designed by our clinician partners to help you deliver the most effective care and support for your patient's thyroid.

Drug-Nutrient Interaction Checker:  Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

1. American Psychiatric Association. American Adults Express Increasing Anxiousness in Annual Poll; Stress and Sleep are Key Factors Impacting Mental Health. American Psychiatric Association. May 1, 2024. Accessed November 11, 2024. https://www.psychiatry.org/news-room/news-releases/annual-poll-adults-express-increasing-anxiousness
2. American Thyroid Association. Prevalence and Impact of Thyroid Disease. American Thyroid Association. Accessed November 11, 2024. https://www.thyroid.org/media-main/press-room/
3. Wyne KL, Nair L, Schneiderman CP, et al, 2009-2019. J Endocr Soc. 2023;7(1). 
   doi:10.1210/jendso/bvac172
4. Bathla M, Singh M, Relan P. Indian J Endocrinol Metab. 2016;20(4). doi:10.4103/2230-8210.183476
5. The American Society of Health-System Pharmacists. Levothyroxine. MedlinePlus. February 15, 2019. Accessed November 11, 2024. 
   https://medlineplus.gov/druginfo/meds/a682461.htm
6. Kirsch I. Front Psychiatry. 2019;10(JUN). doi:10.3389/fpsyt.2019.00407
7. Mikulska AA, Karaźniewicz-łada M, Filipowicz D, Ruchała M, Główka FK. Int J Mol Sci. 
   2022;23(12). doi:10.3390/ijms23126580
8. Klubo-Gwiezdzinska J, Wartofsky L. Pol Arch Intern Med. 2022;132(3). 
   doi:10.20452/pamw.16222
9. Sinha SR, Prakash P, Keshari JR, Kumari R, Prakash V. Cureus. Published online 2023. 
   doi:10.7759/cureus.50199
10. Markomanolaki ZS, Tigani X, Siamatras T, et al. J Mol Biochem. 2019;8(1):3-12.
11. Martin J V., Sarkar PK. Front Endocrinol (Lausanne). 2023;14. 
    doi:10.3389/fendo.2023.1210540
12. Barrea L, Verde L, Annunziata G, et al. J Endocrinol Invest. 2023;47(1):17-33. 
    doi:10.1007/s40618-023-02169-2
13. Pascoe MC, Thompson DR, Ski CF. Psychoneuroendocrinology. 2017;86. 
    doi:10.1016/j.psyneuen.2017.08.008
14. Toussaint L, Nguyen QA, Roettger C, et al. Evidence-based Complementary and 
    Alternative Medicine. 2021;2021. doi:10.1155/2021/5924040
15. MacFarquhar JK, Broussard DL, Melstrom P, et al. Arch Intern Med. 2010;170(3). 
    doi:10.1001/archinternmed.2009.495
16. Concerto C, Chiarenza C, Di Francesco A, et al. Curr Issues Mol Biol. 2023;45(2). 
    doi:10.3390/cimb45020113
17. Nordio M, Basciani S. Int J Endocrinol. 2017;2017. doi:10.1155/2017/2549491
18. Ferrari SM, Fallahi P, Di Bari F, Vita R, Benvenga S, Antonelli A. Eur Rev Med 
    Pharmacol Sci. 2017;21(2).
19. Shamabadi A, Kafi F, Arab Bafrani M, Asadigandomani H, A. Basti F, Akhondzadeh S. 
    J AIect Disord. 2023;333. doi:10.1016/j.jad.2023.04.029
20. Wiciński M, Fajkiel-Madajczyk A, Kurant Z, et al. Int J Mol Sci. 2023;24(22). 
    doi:10.3390/ijms242216513

By: Kim Ross, DCN, CNS, LDN, IFMCP

Positive mood and emotional well-being are essential to overall health, yet low mood affects a significant portion of the global population. According to the World Health Organization, 5% of adults (over 280 million people) worldwide experience some level of low mood or loss of pleasure and interest in activities. In comparison, it is estimated to affect about 10% of all adults in the United States.^1,2 Additionally, it is reported that low moods are 50% more common in women than men.²  

People struggling with low mood experience variable ranges of psychological and physical symptoms. These can include pervasive feelings of sadness or hopelessness, a lack of interest in activities, fatigue and difficulty concentrating. These symptoms are often accompanied by physical manifestations such as changes in appetite, sleep disturbances and decreased energy levels.2 Importantly, underlying immunological processes have been found to play a critical role in regulating mood states, opening avenues for innovative therapeutic approaches.¹

Immune System Activation and the Brain

An area of science called neuroimmunology has highlighted the deep, bidirectional connection and communication between the brain and immune system and its influence on mood regulation.^3–5 Immune cells, including microglia, astrocytes and cytokines, interact directly with neurons, contributing to the modulation of mood and cognitive function.^6,7

Studies suggest that systemic immune activation can affect the nervous system via production of cytokines, including  interleukin-1 beta (IL-1b), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α), which can cross the blood-brain barrier.¹ Alteration of the immune/brain interaction can affect neurotransmitter balance, affecting the production of serotonin, GABA, dopamine and norepinephrine, which are critical for mood stabilization.⁴

Cytokines and Neurotransmitter Balance

Cytokines can influence neurotransmitter balance by modulating key pathways responsible for serotonin, dopamine and glutamate/GABA synthesis and reuptake. For example, the cytokine interferon-gamma (IFN-g) can activate the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan, a precursor to serotonin, into kynurenine. This shift reduces serotonin availability, affecting mood regulation.8 However, some kynurenine metabolites have neuroprotective properties, reinforcing the importance of having a healthy cytokine balance within the body.⁸

Similarly, some cytokines (IL-1b, IL-6, IFN-g, and TNF-α) have been shown to decrease the transport of tyrosine (a non-essential amino acid produced from phenylalanine), which is needed for the synthesis of dopamine and catecholamines.9  Cytokines have also been implicated in increasing glutamate activity through quinolinic acid production.¹⁰

Nutrition: Diet plays a critical role in immune and mood regulation. A nutrient and polyphenol-dense Mediterranean diet is rich in vegetables, fruits, omega-3 fatty acids and fiber. It has been shown to modulate cytokine levels and promote mental well-being.^11,12 

Exercise: Regular, moderate-intensity physical activity has been shown to promote cytokine balance. Exercise also helps to reduce stress and provides neuroprotection through the antioxidant system.¹³

Sleep: Poor sleep quality is associated with elevated levels of IL-6, TNF-α, nuclear factor-kB (NF-kB), and CRP (C-reactive protein), important markers of the immune system.¹⁴ Prioritizing sleep hygiene and achieving 7 to 9 hours of restorative sleep can help restore immune balance and positively influence mood.

Mind-Body Practices: Yoga, meditation and mindfulness practices can reduce stress, improve sleep and promote a balanced immune response, including the modulation of cytokines.¹⁵

Polyphenols, including flavonoids, curcumin, epigallocatechin gallate (EGCG) and oligomeric proanthocyanidins (OPCs), are found in a variety of plant-based foods, such as vegetables, berries, green tea and dark chocolate.¹⁶

Curcumin, the active compound in turmeric, exerts its mood benefits by regulating cytokine activity, mainly by reducing levels of TNF-α and IL-6. By maintaining a healthy cytokine response, curcumin supports neurotransmitter balance, especially the monoamines, serotonin, norepinephrine and dopamine.¹⁷ Further, preclinical data suggest that curcumin may bind to NMDA receptors to balance glutamate/GABA signaling.^18‡

Green tea extract contains a high concentration of EGCG, a compound known for its antioxidant and cytokine-modulating properties. The catechins in green tea also help boost dopamine levels, while theanine modulates glutamate, GABA, serotonin and dopamine levels, enhancing a sense of calm and providing cytokine balance.19,20 Green tea extract also supports neurogenesis and promotes the release of brain-derived neurotrophic factor (BDNF), which plays a critical role in mood regulation.^19‡

Pycnogenol, derived from the bark of the French maritime pine tree, is another potent immunomodulator that shows promising cognitive-enhancing effects by reducing oxidative stress and enhancing neurotransmitter activity.²¹ Over 450 articles have been published highlighting the plethora of benefits of this compound in multiple areas of health.^22‡

Pure Encapsulations^® provides uniquely formulated products made with high-quality, pure ingredients backed by verifiable science to complement your plan of care and support healthy aging in your patients.^‡

CurcumaSorb Mind offers support for mental alertness, relaxation and occasional stress. Promotes emotional wellness by supporting healthy levels of serotonin and dopamine.^‡

Suggested Use: Take 2 capsules, 1-2 times daily, with meals.  

Pycnogenol^® 100 mg supports cognitive function and cardiovascular health^‡

Suggested Use: Take 1 capsule, 1-2 times daily, with or between meals.

Green Tea extract (decaffeinated) supports neurocognitive, cardiovascular and cellular health. Provides optimal cellular function and antioxidant protection^‡

Suggested Use: Take 1 capsule, 1-4 times daily, with meals.

The intricate relationship between the immune system and mood highlights the importance of cytokine modulation in mental health. By targeting key cytokines involved in mood regulation, it is possible to influence neurotransmitter pathways and foster positive emotional states.  Making lifestyle changes and using immune-modulating ingredients like pycnogenol and polyphenols offers a holistic approach to supporting mental well-being.

Positive Mood Protocol‡: Designed by our clinician partners to help you deliver the most effective care and support for your patient's mood.

Drug-Nutrient Interaction Checker:  Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.

PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols and other resources developed with our medical and scientific advisors.

1. Miller AH, Raison CL. Nat Rev Immunol. 2016;16(1). doi:10.1038/nri.2015.5
2. World Health Organization (WHO). Accessed June 29, 2024. https://www.who.int/news-room/fact-sheets/detail/depression
3. Zhou L, Foster JA. Neuropsychiatr Dis Treat. Published online 2015. doi:10.2147/NDT.S61997
4. Ross K. Explore. Published online 2023. doi:10.1016/j.explore.2023.02.007
5. Nutma E, Willison H, Martino G, Amor S. Clin Exp Immunol. 2019;197(3). doi:10.1111/cei.13279
6. Dantzer R.  Physiol Rev. 2018;98(1). doi:10.1152/physrev.00039.2016
7. Daëron M. Front Immunol. 2022;13. doi:10.3389/fimmu.2022.984678
8. Tsuji A, Ikeda Y, Yoshikawa S, et al.  Int J Mol Sci. 2023;24(6). doi:10.3390/ijms24065742
9. Mancini M, Natoli S, Gardoni F, Di Luca M, Pisani A.  Int J Mol Sci. 2023;24(6). doi:10.3390/ijms24065618
10. Ho TC, Teresi GI, Segarra JR, et al.  Front Psychiatry. 2021;12. doi:10.3389/fpsyt.2021.642976
11. Koelman L, Egea Rodrigues C, Aleksandrova K. Advances in Nutrition. 2022;13(1). doi:10.1093/advances/nmab086
12. Ventriglio A, Sancassiani F, Contu MP, et al. Clinical Practice & Epidemiology in Mental Health. Published online 2020. doi:10.2174/1745017902016010156
13. Docherty S, Harley R, McAuley JJ, et al. BMC Sports Sci Med Rehabil. 2022;14(1). doi:10.1186/s13102-022-00397-2
14. Irwin MR, Opp MR. Neuropsychopharmacology. 2017;42(1). doi:10.1038/npp.2016.148
15. Black DS, Slavich GM. Ann N Y Acad Sci. 2016;1373(1). doi:10.1111/nyas.12998
16. Winiarska-Mieczan A, Kwiecień M, Jachimowicz-Rogowska K, Donaldson J, Tomaszewska E, Baranowska-Wójcik E. Int J Mol Sci. 2023;24(3). doi:10.3390/ijms24032258
17. Peng Y, Ao M, Dong B, et al. Drug Des Devel Ther. 2021;15. doi:10.2147/DDDT.S327378
18. Ramaholimihaso T, Bouazzaoui F, Kaladjian A.  Front Psychiatry. 2020;11. doi:10.3389/fpsyt.2020.572533
19. Afzal O, Dalhat MH, Altamimi ASA, et al. Molecules. 2022;27(21). doi:10.3390/molecules27217604
20. Shamabadi A, Kafi F, Arab Bafrani M, Asadigandomani H, A. Basti F, Akhondzadeh S.  J Affect Disord. 2023;333. doi:10.1016/j.jad.2023.04.029
21. Simpson T, Kure C, Stough C. Front Pharmacol. 2019;10. doi:10.3389/fphar.2019.00694
22. Weichmann F, Rohdewald P.  Front Nutr. 2024;11. doi:10.3389/fnut.2024.1389374

Building Resilience: A Guide to Personalized Care for Stress

By: Amy Doyle, MS, CNS⁺

Key Points

1. Each patient's experience of stress is unique and shaped by multiple factors.
2. A thorough understanding and personalized approach to the three stages of stress response is essential for supporting patients in recovering from stress and building resilience.
3. A customized strategy not only addresses the diverse causes and symptoms of stress but also enhances patient engagement and outcomes.

Table of Contents:

1. The Importance of a Personalized Approach to Stress Management
2. Understanding Individual Differences in Stress Responses
3. Building Resilience Against Stress
4. The 3 Stages of Stress Adaptation: Expanding Your Knowledge
5. Additional Resources

The Importance of a Personalized Approach to Stress Management

Understanding Individual Differences in Stress Responses

Building Resilience Against Stress

Additional Resources

Stress Management & Relaxation Protocol^‡: developed with James Greenblatt, MD, a pioneer in the field of integrative medicine for mental health, this protocol offers nutrition and lifestyle recommendations to support stress management and relaxation.^‡

Drug-Nutrient Interaction Checker: provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements.

PureInsight™: Our streamlined platform easily collects patient data and provides valuable, personalized recommendations to help achieve their unique health goals.

Virtual Dispensary: our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

References

The Role of Neurotransmitters in Attention, Focus and Behavior

Key Points:

1. Approximately 6.76% of adults experience focus and attention related challenges.
2. Neurotransmitters such as dopamine, norepinephrine, serotonin and acetylcholine play crucial roles in managing focus-related tasks.
3. A balanced diet, regular exercise, and supplements can support neurotransmitter production and function. Consider food or supplements high in omega-3 fatty acids, vitamin D, magnesium and B vitamins for foundational support.^‡
4. Targeted supplements can support specific neurotransmitters that contribute to focus and attention: CogniPhos (acetylcholine), CurcumaSorb Mind (dopamine and serotonin) and DopaPlus (dopamine and norepinephrine).^‡

Table of Contents:

1. Introduction
2. Key Neurotransmitters Involved in Focus
3. Natural Ways to Support Neurotransmitter Balance
4. Conclusion
5. Resources

Introduction

Key Neurotransmitters Involved in Focus

Dopamine: is essential for motivation, attention and reward processing. It helps regulate how we perceive and respond to stimuli, influencing our ability to stay focused on tasks. Low levels of dopamine can impair our ability to concentrate, stay organized, manage time effectively and may lead to challenges in maintaining attention on tasks.¹

Norepinephrine: affects alertness and arousal. It helps the brain stay alert and responsive to stimuli, which is essential for maintaining focus. Norepinephrine has been shown to alter network activity in attention and working memory through arousal activation of the frontoparietal network, which is critical for sustained attention and alertness.²

Serotonin: influences mood, impulse control and overall cognitive function. It plays a role in managing emotional responses and maintaining a steady focus. Changes in serotonin levels can affect our emotional stability and our ability to maintain focus, leading to increased distractibility and impulsive actions.³

Acetylcholine: governs memory, learning, motivation and attention. Synthesized from choline, acetylcholine is the chief neurotransmitter of the parasympathetic nervous system and has a significant impact on muscle function, sleep, cognitive processes and mental performance.⁴ Fluctuations of acetylcholine can affect short-term memory, processing speed and word recall and can lead to learning difficulties and symptoms like brain fog.

Natural Ways to Support Neurotransmitter Balance^‡

Diet and Nutrition

Exercise

Supplements

• CogniPhos: A blend of clinically researched Cognizen^® citicoline, acetyl-L-carnitine, Sharp-PS^® phosphatidylserine and cofactors. Cognizen^® promotes daily cognitive performance and mental sharpness. ^9,10‡
• CurcumaSorb Mind: A curcumin and polyphenol blend to promote mood, memory and mental sharpness and support healthy levels of serotonin and dopamine. ^11‡
• DopaPlus: This formula provides the dopamine precursors L-tyrosine and L-DOPA (from Mucuna pruriens). DopaPlus supports dopamine production and maintains healthy reuptake for daily mental function and sharpness. ^{12, 13‡}
• Vitamin D + Magnesium: Vitamin D and Magnesium are both nutrients that play a role in the body’s nervous system. In a randomized-clinical trial, children supplemented with vitamin D and magnesium had a positive impact on and total difficulties compared to placebo after 8-weeks of supplementation.^14‡
• Fish oils:  are rich in omega-3 essential fatty acid. DHA, a fatty-acid in fish oil, is well recognized for its ability to support neural and cognitive function.  Epidemiological studies indicate that intake of DHA is associated with healthy cognitive function.^15‡
• Vitamin B₆: A coenzyme involved in the synthesis of neurotransmitters needed for synaptic transmission (e.g., dopamine, serotonin, GABA).^‡
• Pycnogenol®: A highly researched maritime pine bark extract, which contains a unique mixture of proanthocyanidins and other polyphenols. Clinical trials have shown that pycnogenol supports parameters related to attention in both children and adults. ^17-19‡

Conclusion

Resources

Mood Protocol: Developed in collaboration with our scientific and medical advisors to support mood.^‡

Drug-Nutrient Interactions Checker:  provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements.

PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help patients achieve their health goals.

Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations^® to find On-Demand Learning, Clinical Protocols, and other resources developed with our medical and scientific advisors.

References

1. Kessi M, Duan H, Xiong J, C, et al. Front Mol Neurosci. 2022 Sep 21;15:925049. doi: 10.3389/fnmol.2022.925049.
2. O'Donnell J, Zeppenfeld D, McConnell E, et al. Neurochem Res. 2012 Nov;37(11):2496-512. doi: 10.1007/s11064-012-0818-x. Epub 2012 Jun 21.
3. Jones LA, Sun EW, Martin AM, Keating DJ. Int J Biochem Cell Biol. 2020 Aug;125:105776. doi: 10.1016/j.biocel.2020.105776. Epub 2020 May 29.
4. Sam C, Bordoni B. Physiology, Acetylcholine. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557825/
5. Lange KW, Lange KM, Nakamura Y, et al. Curr Nutr Rep. 2023 Sep;12(3):383-394. doi: 10.1007/s13668-023-00487-8. Epub 2023 Jul 28.
6. Firth J, Gangwisch JE, Borisini A, et al. BMJ. 2020 Jun 29;369:m2382. doi: 10.1136/bmj.m2382.
7. Liang X, Li R, Wong SHS, et al. Int J Behav Nutr Phys Act. 2021 May 22;18(1):68. doi: 10.1186/s12966-021-01135-6.
8. Basso JC, Suzuki WA. Brain Plast. 2017 Mar 28;2(2):127-152. doi: 10.3233/BPL-160040.
9. McGlade E, et al. J Atten Disord. 2015 Jul 15.
10. McGlade E, et al. Food and Nutrition Sciences, 2012, 3, 769-773.
11. Bhutani MK, et al. Pharmacol Biochem Behav.2009 Mar;92(1):39-43.
12. Katzenschlager R, et al. J Neurol NeurosurgPsychiatry2004;75:1672-1677.
13. Ranjbar E, et al. Nutr Neurosci.2014 Feb;17(2):65-71.
14. Hemamy M, Pahlavani N, Amanollahi A,et al. BMC Pediatr. 2021 Apr 17;21(1):178. doi: 10.1186/s12887-021-02631-1. Erratum in: BMC Pediatr. 2021 May 12;21(1):230. doi: 10.1186/s12887-021-02683-3.
15. Jackson PA, et. al. Br J Nutr.2012 Apr;107(8):1093-8.
16. Calderón-Ospina CA, Nava-Mesa MO. CNS Neurosci Ther. 2020 Jan;26(1):5-13. doi: 10.1111/cns.13207. Epub 2019 Sep 6.
17. Belcaro G, Luzzi R, Dugall M, et al. J Neurosurg Sci. 2014 Dec;58(4):239-48. Epub 2014 Mar 28.
18. Luzzi R, Belcaro G, Zulli C, et al. Panminerva Med. 2011 Sep;53(3 Suppl 1):75-82.
19. Trebatická J, Kopasová S, Hradecná Z, et al. Eur Child Adolesc Psychiatry. 2006 Sep;15(6):329-35. doi: 10.1007/s00787-006-0538-3. Epub 2006 May 13.

Aging Gracefully: Harnessing NAD+ for Healthy Aging

By: Amy Doyle, MS, CNS⁺

Table of Contents

Introduction

In the intricate world of cellular metabolism, one molecule stands out for its pivotal role in energy production, cellular function, and healthy aging: Nicotinamide adenine dinucleotide, or NAD+. As a coenzyme, it plays a crucial role in facilitating redox reactions and serves as a mediator for vital cellular functions — adjusting to metabolic demands of the cell as needed.

Definition and Mechanisms of NAD+

NAD+ is ubiquitous in every living cell and is found in pools within the cytoplasm, mitochondria and nucleus. Operating primarily as a coenzyme, NAD+ facilitates enzymatic reactions that involve transferring hydrogen atoms in oxidation-reduction processes.[1] In its reduced form, known as NADH, it acts as an antioxidant, playing a vital role in neutralizing free radicals and protecting cellular structures.¹

• Cellular aging
• Energy metabolism
• DNA repair
• Formation of new mitochondria
• Calcium homeostasis
• Immune regulation
• Circadian rhythm
• Vascular activity
• Gene expression

There are three primary classes of enzymes that utilize NAD+: glycohydrolases, sirtuins and PARPs (poly-ADP-ribose polymerases). In their consumption of NAD+, these three classes of enzymes generate nicotinamide (NAM) as a byproduct, which can be recycled back into NAD+ to help maintain intracellular levels.1 Sirtuins are also key regulators implicated in aging processes, while PARP-1 plays a significant role in DNA repair and cell survival under stress conditions.^1,4

While these three groups of enzymes rely on NAD+, more than 300 enzymes in the body depend on NAD+ for their activity.¹

The Making of NAD+

Due to its high demand, NAD+ must be continuously synthesized, catabolized and recycled in the cell to maintain steady intracellular levels.

• de novo biosynthesis using l-tryptophan via the kynurenine pathway
• de novo biosynthesis via the Preiss-Handler pathway, using dietary sources of nicotinic acid, or nicotinic acid mononucleotide from the kynurenine pathway
• recycling of nicotinamide phosphoribosyltransferase (NAMPT) into NAD+ via the salvage pathway

Image adapted from Paro R, Grossniklaus U, Santoro R, et al. Introduction to Epigenetics [Internet]. Cham (CH): Springer; 2021. Chapter 9, Epigenetics and Metabolism. 2021 Mar 24. Available from: https://www.ncbi.nlm.nih.gov/books/NBK585707/doi: 10.1007/978-3-030-68670-3_9. Creative Commons license.

KEY: Nicotinic acid phosphoribosyltransferase (NAPRT), Nicotinic acid mononucleotide (NAMN), Nicotinic acid adenine dinucleotide (NAAD), Nicotinamide mononucleotide adenylyltransferase (NMNAT1-3), 2-amino-3-carboxymuconate semialdehyde (ACMS), Nicotinamide phosphoribosyltransferase (NAMPT), Nicotinamide mononucleotide (NMN)

These pathways collectively regulate the intracellular levels of NAD+, which are essential for maintaining cellular functions and metabolic balance. Understanding the intricacies of NAD+ synthesis and consumption pathways is essential for exploring strategies aimed at modulating cellular metabolism and promoting health.

NAD+ and Implications for Health and Aging

Maintaining optimal levels of NAD+ is crucial for sustaining tissue and metabolic homeostasis throughout life.

As we age, however, levels of NAD+ naturally decline and many of the enzymes responsible for the degradation and biosynthesis of NAD+ are altered. This can lead to NAD+ degradation exceeding the cells' capacity for de novo synthesis or efficient recycling and salvage of NAM (nicotinamide).¹

The age-associated decline in NAD+ may have implications for overall cellular health and longevity.

Approaches to Restore NAD+

Naturally occurring NAD+ decline and altered NAD+ metabolism have been implicated in various processes associated with aging.1 Decreased NAD+ levels can affect cognitive function and have other unwanted health outcomes that extend to the cardiovascular, endocrine and immune systems.^1,3

Approaches to restore NAD+ levels can support health and vitality in the aging patient. ^‡

The decline in NAD+ levels associated with aging underscores its importance in healthy aging. By understanding and potentially influencing NAD+ levels, healthcare practitioners can explore new avenues in promoting cellular health and longevity.^‡

Nutrient Solutions to Support NAD+ and Cellular Health

Nutrients that enhance the biosynthesis and activity of NAD+ can promote restoration of tissue levels of NAD+ and support overall cellular health. ^‡

Resveratrol supports metabolic health by promoting healthy activity of the key enzyme AMP kinase (AMPK)and SIRT1 activity which are positively associated with mitochondrial function.^1,2,7,8

Nicotinamide riboside chloride (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+), a key driver of cellular energy production.^{1,3,4,5,6,7‡}

Sulforaphane is one of the most effective activators of phase II detoxification, which occurs primarily in the gut and the liver.^8,9

Acetyl l-carnitine supports healthy mitochondrial function and cell membrane stability.^{10 ‡}

Alpha lipoic acid is a key component of the metabolic process, alpha lipoic acid produces energy in muscles and directs calories into energy production.¹¹

Urolithins are unique natural metabolites of intestinal bacteria that are produced by commensal microbiota after consuming foods rich in ellagitannins and ellagic acid — major health promoting constituents of pomegranates, nuts and berries. These unique polyphenols undergo metabolism by intestinal bacteria to small, highly absorbable metabolites called urolithins, which mediate the widely acclaimed health benefits of pomegranates and other ellagitannin-rich foods.^{12, 13 ‡}

Pyrroloquinoline Quinone, or PQQ provides B vitamin-like activity with unique antioxidant properties. PQQ supports mitochondrial, neuronal and cellular function, at least, in part, by activation of Nrf2 and antioxidant gene expression. Preliminary research suggests that PQQ promotes mitochondrial biogenesis by targeting SIRT1 and PGC-1α.^{14 ‡}

Pure Encapsulations® Nutrient Solutions

Pure Encapsulations® provides uniquely formulated products made with high-quality, pure ingredients backed by verifiable science to complement your plan of care and support healthy aging in your patients.^‡

NR Longevity™: specially designed to target biological processes that decline with age, such as the body’s natural ability to make energy, build new mitochondria and protect cells from oxidative stress.¹ Nicotinamide riboside (NR), resveratrol and sulforaphane promote healthy aging by replenishing NAD+, enhancing mitochondrial function and providing antioxidant support, respectively.^‡
Suggested use: 2 capsules, 1-2 times daily, with or between meals

RENUAL® enhances mitochondrial renewal to support energy output/energy production Features Mitopure™ Urolithin A to power muscle function, increase cellular energy and promote healthy aging.^‡
Suggested use: Take 2 capsules, 1-2 times daily, with or between meals.

Ubiquinol-QH 100mg is the active antioxidant form of CoQ₁₀. It supports the production of ATP for energy, promotes cardiovascular health and provides antioxidant support.^‡
Suggested use: Take 1 capsule, 1-2 times daily, with meals.

RevitalAge™ Ultra is a scientifically researched combination of acetyl-l-carnitine (ALC) and alpha lipoic acid (ALA) offered with antioxidant and mitochondrial support cofactors. It promotes healthy aging through mechanisms involving gene expression, mitochondrial function, cellular energy production and antioxidant protection. Also contains Nicotinamide riboside (NR) to promote the synthesis of NAD+, a key driver of cellular energy production^‡
Suggested use: Take 2 capsules daily, with meals.

Ultra B-Complex w/PQQ combines essential B vitamins with PQQ to support mitochondrial bioenergetics and function. Also provides alpha lipoic acid and luteolin for enhanced antioxidant and cellular support^‡
Suggested use: Take 1 capsule, 1-2 times daily, with meals.

Summary

NAD+ represents not just a coenzyme in redox reactions but a central player in cellular vitality and health. Its decline with age highlights its critical importance in maintaining cellular integrity and function. As research progresses, harnessing the potential of NAD+ may offer promising clinical strategies for enhancing both longevity and quality of life.

Resources

Mitochondrial Health Protocol^‡: designed by our clinician partners to help you deliver the most effective care and support for your patients. It includes foundational recommendations for overall health and focused interventions to address common clinical objectives related to mitochondrial function.^‡

Drug-Nutrient Interaction Checker:  provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements.

PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

References

1. Covarrubias AJ, Perrone R, Grozio A, Verdin E. Nat Rev Mol Cell Biol. 2021;22(2):119-141. doi:10.1038/s41580-020-00313-x
2. Ying W. Antioxid Redox Signal. 2008;10(2):179-206. doi:10.1089/ars.2007.1672
3. Xie N, Zhang L, Gao W, et al. Signal Transduct Target Ther. 2020;5(1):227doi:10.1038/s41392-020-00311-7
4. Xu W, Li L, Zhang L. Front Physiol. 2020;11:901. doi:10.3389/fphys.2020.00901
5. Timmers S, et al. Cell Metab. 2011 Nov 2;14(5):612- 228
6. Ghanim H, et al. J Clin Endocrinol Metab. 2010 Sep;95(9):E1-8
7. Conze D, Brenner C, Kruger CL. Sci Rep. 2019 Jul 5;9(1):9772
8. Trammell SA, Schmidt MS, Weidemann BJ, et al. Nat Commun. 2016 Oct 10;7:12948
9. Janssens GE, Grevendonk L, Perez RZ, et al. Nat Aging. 2022 Mar;2(3):254-263
10. Chu X, Raju RP. Metabolism. 2022 Jan;126:154923
11. Clement J, et al. Rejuvenation Res. 2019 Apr;22(2):121-130
12. Zhang Y, et al. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403. 2
13. Karen-Ng LP, et al. Asian Pac J Cancer Prev. 2011;12(5):1161-6
14. Kerner J, et al. Mech Ageing Dev. 2015 Jan;145:39-50
15. Kishi Y, et al. Diabetes. . 1999 Oct;48(10):2045-51
16. Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F. Evid Based Complement Alternat Med. 2013;2013:270418
17. Heim KC. In: Antioxidant Polymers: Synthesis, Properties, and Applications. Cirillo G, Iemma F, eds. Taylor and Francis, c. 2012
18. Harris CB, et al. Nutr Biochem. 2013 Dec;24(12):2076-84

Think Ahead: Cognitive Wellness Today for Tomorrow

By: Amy Doyle, MS, CNS⁺

Table of Contents

Introduction

As we age, supporting brain health and cognitive function increasingly becomes a focal point of our health. Mild memory deficits and slower cognitive processing are a normal part of aging. It has been estimated that 1 in 9

Read on to discover how you can proactively target metabolic processes and related pathways to support your patients’ brain health and cognitive function throughout their lifetime.

Age-Related Changes in the Brain

Changes in brain neurons can begin 20 years or more before cognitive symptoms develop, with the prevalence of these changes doubling every five years after age 65.1^,[1]

Age-related chemical and physical changes in the brain can include:^[2]

• Changes in vascular makeup, reduced blood flow and oxygen
• Decline in production of hormones and neurotransmitters
• Decreased antioxidant defenses

While these underlying brain changes can occur for decades, one factor is emerging as a significant player in the development and occurrence of cognitive changes: oxidative stress.

Oxidative Stress and Brain Health

Oxidative stress occurs when there’s an imbalance between free radicals and antioxidants in the body resulting in greater reactive oxygen species (ROS) production.  Free radicals are a natural byproduct of many physiological processes, but they can also be introduced by external sources like diet, toxins and environmental factors.

While free radicals play essential roles in cellular signaling and immune function, an excess can lead to cellular damage, an immune response and mitochondrial dysfunction that can progress to adverse effects on brain function.^[3] Highly metabolic, the brain is a large consumer of oxygen and is rich in polyunsaturated fatty acids. These characteristics combined with its high production of ROS and low levels of antioxidant enzymes make it particularly vulnerable to oxidative damage.^[4],[5]

When ROS production overwhelms the brain’s antioxidant defenses, oxidative stress damages proteins, DNA and cell membranes, disrupts neuronal cell functions and triggers neuronal cell death. Regulation of ROS in the brain is critical for memory consolidation and long-term potentiation.^[6]

Antioxidant Intake and Cognitive Function

Several prospective studies have found that people who consume an antioxidant rich diet of fruits and vegetables can reduce their risk of cognitive changes.^[7],[8],[9]

In a 2023 meta-analysis of cohort studies, researchers sought to investigate the association of antioxidant intake with the risk of cognitive changes.

The meta-analysis included 17 articles with 98,264 participants. Of the total, 7,425 participants had cognitive changes after 2-3 years of follow up, that interfered with their daily living. Studies included participants from Europe, Asia and North America.  The studies considered antioxidant intake from diet, supplements or both.  The antioxidants studied included vitamin A, vitamin C, vitamin E and flavonoids. Additional subgroup analyses were conducted based on the participants’ kind of nutrition, diet and supplement, geographical region and study quality.

Overall, the researchers determined that a high antioxidant diet or supplement intake significantly decreased the incidence of cognitive changes that interfere with daily living by 16% (RR =.084, 95% CI 077.-091(p_t <0.001).

In subgroup analysis by nutritional type, high dietary and supplement intake of vitamin C or vitamin E alone significantly reduced risk of cognitive changes (RR= 0.81, 95% CI 0.70-0.94, I² = 37.9%, p = 0.097), and (RR=0.77, 95% CI 0.64-0.92, I²=54%, p=0.013), respectively.

Both vitamin A and flavonoid intake were also shown to decrease risk of cognitive changes, however results were not statistically significant.

High dietary and supplement antioxidant intake demonstrated a greater risk reduction with statistical significance in North American populations (RR=.083, 95% CI 0.75-0.93, I²=47.3%, p=0.003), compared to European populations, where although risk was reduced, results were not statistically significant.

The authors concluded that consuming fruits and vegetables rich in antioxidants or antioxidant supplements can have a protective effect on cognitive function and reduce risk of cognitive changes.

Nutrient Solutions for Cognitive Function

It is important to educate patients about modifiable risk factors associated with mild, age-related cognitive decline like an antioxidant-rich diet, physical activity, managing stress, prioritizing sleep and engaging in social and mental stimulation.^[10] In addition, the practitioner can support the brain’s resilience against oxidative stress with targeted nutrient solutions.

Animal research suggests that magnesium-l-threonate may promote synaptic plasticity and density in the regions of the hippocampus correlated with learning and memory.^[11]‡

Acetyl-L-carnitine supports the availability of acetyl-CoA, an important energy-generating metabolite. In addition, it supports healthy mitochondrial function and cell membrane stability.^[12]‡

Phosphatidylserine supports cognitive function, emotional well-being and behavioral performance. It has also been shown to support healthy memory.^[13],[14]‡

Resveratrol promotes cardiometabolic, neuronal and cellular health through a variety of effects on cell signaling, mitochondrial function and endogenous antioxidant defenses.^{[15],[16],[17],[18],‡}

Omega 3 Fatty Acids encourage cardiovascular health by supporting lipid metabolism and healthy blood flow. ^{[19],[20],[21],} In addition, studies indicate these oils help maintain healthy endothelial function. [22]^‡

Curcumin supports neuronal stability and function, in part, by promoting healthy cytokine balance and antioxidant defenses. [23]^‡

Bacopa monnieri has been utilized traditionally for centuries in Ayurvedic medicine to support the nervous system, cognitive capacity and memory. A three-month trial conducted by Australian scientists suggests that bacopa may support learning, moderate stress and support memory. [24]^‡

Luteolin promotes neuronal health through antioxidant, immunomodulating and mast cell stabilizing actions, helping to moderate the release of immune mediators.^‡

Ginkgo biloba helps sustain the strength and elasticity of blood vessels and capillaries.  It may also promote the flow of oxygen and blood to the brain. ^‡

With oxidative stress and related metabolic shifts occurring early in the development of changes in cognitive function, identifying and addressing these processes can be crucial for healthy function.

Pure Encapsulations® Nutrient Solutions for Cognitive Function

As the most trusted brand and leader in the professional supplement space, Pure Encapsulations® is committed to helping healthcare professionals understand and apply personalized, evidence-based nutrition to achieve optimal patient outcomes.

The following supplements can support neuronal health, vascular integrity, memory, mental sharpness and overall cognitive function.^‡

Memory Pro promotes neural health, cognitive function and memory. Also supports vascular integrity and promotes relaxation.^‡
Suggested use: As a dietary supplement, take 3 capsules daily, with or between meals.

BenfoMax is a fat-soluble vitamin B1 (thiamine) derivative that maintains healthy advanced glycation end (AGE) product activity to support vascular, nerve, retinal and kidney cellular health. It also promotes healthy glucose metabolism.^‡
Suggested use: As a dietary supplement, take 1 capsule, 1-3 times daily, with meals.

O.N.E. Omega contains triglyceride form EPA and DHA from fish oil produced through a unique solvent free, supercritical, CO2-based extraction method. Encourages cardiovascular health by supporting lipid metabolism and healthy blood flow.  Also helps maintain healthy endothelial function.^‡
Suggested use: As a dietary supplement, take 1 capsule daily, with a meal.

CurcumaSorb Mind contains Meriva® bioavailable curcumin phytosome; support for mood, memory and mental sharpness.^‡
Suggested use: As a dietary supplement, take 2 capsules, 1-2 times daily, with meals

CogniMag  promotes cognitive function, learning ability and working memory. Also supports optimal brain magnesium levels.^‡
Suggested use: As a dietary supplement, take 2 capsules, twice daily, with a meal and at bedtime.

Brain Reset promotes concentration, mental clarity and memory with a multi-faceted blend of nutrients and herbal extracts. Promotes neuroimmune health by supporting cellular function, neuroprotection and immune mediator balance.^‡
Suggested use: As a dietary supplement, take 2 capsules daily, between meals.

AntiOxidant Formula  supports the body’s natural defense mechanism against free radicals.^‡ Offers a synergistic, broad spectrum of antioxidants, including essential vitamins and minerals like vitamin A, E and B complex vitamins.
Suggested use: As a dietary supplement, take 1 capsule, 1-2 times daily, with meals.

Ester-C® & Flavonoids offers a blend of Ester-C ® and flavonoid compounds to provide vitamin C support for healthy immune and cellular function as well as blood vessel integrity.^‡
Suggested use: As a dietary supplement, take 1 capsule, 1-2 times daily, with or between meals.

Summary

In the quest to maintain optimal brain health, understanding and addressing the role of oxidative stress is key to safeguarding your patient’s cognitive function

Resources

Mild Age-Related Cognitive Decline Protocol^‡: Developed in collaboration with our scientific and medical advisors to support cognitive health in older adults^‡

Drug-Nutrient Interactions Checker:  provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements.

PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals.

Virtual Dispensary: our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.

You can also explore Pure Encapsulations® to find On-Demand Learning, Clinical Protocols, and other resources developed with our medical and scientific advisors.

References