By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Reducing Mental Load: Practical Tips to Help Patients Declutter Their Mind

1. Introduction to Emotional Wellbeing
2. Reducing Mental Load
3. 4 Key Messages to Relay to Patients
4. 5 Practical Strategies You Can Teach Your Patients
5. Conclusion
6. Resources

What is Emotional Wellbeing?

Emotional wellbeing is an umbrella term that is used to describe the “overall positive state of one’s emotions, life satisfaction, sense of meaning and purpose and ability to pursue self-defined goals.”¹

Clinically, poor emotional wellbeing is linked to adverse mental health outcomes.^3–5 For practitioners, understanding emotional wellbeing opens opportunities for early intervention and holistic care. Promoting emotional wellbeing is not ancillary to clinical practice; it is central to improving patient outcomes, adherence and overall quality of life.

Reducing Mental Load and Mental “Decluttering”

Many patients describe feeling “wired and tired,” “mentally overloaded” or “unable to turn my brain off at night.” Clinically, this often reflects cognitive or emotional overload rather than a mood disorder.

What is Mental Load?

The ongoing, often invisible cognitive and emotional work of planning, tracking details, anticipating needs, managing others’ needs and self-monitoring, is continuous, boundaryless and rarely “done.” High mental load is associated with elevated perceived stress, sleep disturbances, role strain and lower wellbeing.^6,7

Mental load is not just “a busy schedule.” It’s internal vigilance: remembering appointments, monitoring others’ moods, preventing conflict and emotional caretaking. This is especially common in caregivers and working parents and is strongly linked to burnout and emotional exhaustion.⁷

Decluttering or Cognitive Offloading to Reduce Mental Load

Mental decluttering or cognitive offloading is the process of moving tasks, worries, decisions, reminders and unresolved thoughts out of working memory and into an external system (e.g., lists, calendars, notes, shared task boards and voice memos) so the brain is not holding them on constant “standby.”⁸ This process reduces cognitive load, frees attention and is associated with less rumination and better task performance.⁸ Clinically, offloading also supports sleep initiation, because pre-sleep rumination is often driven by unclosed loops (e.g., “Don’t forget to…,” “What if…,” “I still haven’t emailed…”). Patients who externalize those loops tend to fall asleep more easily and report less pre-bed hyperarousal.⁹

Clinical Goal: For emotional wellbeing, the goal is not to “empty the mind” in a spiritual sense. The clinical goal is to reduce relentless cognitive and emotional demands so that self-regulation systems (e.g., mood, sleep and stress response) can recover. Collaboration with a life coach or expanding your knowledge of tools to help patients “declutter their mental load” can support their emotional wellbeing. You can frame this for patients as: “We’re going to clear mental bandwidth so your nervous system can downshift.”

4 Key Messages to Relay to Patients

1. A persistent cluttered mental environment keeps the stress system (HPA axis) in a semi-activated state. Patients feel on alert, even at rest. This can impair sleep and mood stability.⁹
2. Decluttering the mind is not avoidance. It is structured processing plus externalizing: notice → name → park it somewhere reliable.
3. Cognitive or emotional load is often invisible labor. Validating it, especially in caregivers, women and high-responsibility professionals, is therapeutic and reduces shame.^6,7
4. Reducing mental load supports sleep quality, which supports emotional regulation, stress resilience and positive affect. Poor sleep is consistently linked to increased negative mood and decreased positive mood the next day.⁹

5 Mental Decluttering Strategies You Can Teach Your Patients

These strategies are appropriate for most patients and do not require advanced psychotherapy training to be introduced.

1. Nightly Brain Download (“Parking the Thoughts”)

Before bed, ask the patient to spend five minutes writing down unfinished tasks, unsent messages, unresolved conversations, worries, “what if” loops or tomorrow’s priorities. Include only the top one or two, not 20.

The instruction is: “You do not have to solve any of it right now. You’re just placing it in a holding area so your brain doesn’t have to rehearse it all night.” This is essentially cognitive offloading. Offloading reduces working memory demands and subjective workload, which in turn lowers perceived stress and improves cognitive performance.⁸

Clinically useful language: “We are telling your nervous system: you are allowed to power down.”

2. Externalize Responsibilities, Don’t Mentally Juggle Them

Recommend a shared calendar, task board or responsibility map for households, teams or co-parents. This is especially important for patients carrying a high “anticipatory load” in keeping track of who needs what and by when. Research on mental load shows that this anticipatory, emotional caretaking work is ongoing, boundaryless and associated with emotional fatigue and decreased wellbeing, especially in women managing work and caregiving simultaneously.⁷

Framing for the clinician: Moving invisible tasks into a shared system is not “being controlling,” it is redistributing cognitive and emotional labor.

3. Limit Unfinished Loops During the Day

Ask patients to notice “micro-rumination spirals,” e.g., mentally replaying a conversation, rehearsing an argument or repeating a worry.
Coach them on a brief containment script:

1. Name it (e.g., “I am worrying about X”).
2. Decide if it is actionable now.
3. If it’s not actionable now, write it down and schedule a review block, even if it is10 minutes tomorrow.

What you are doing here is teaching cognitive reappraisal and structured containment, which have been shown to reduce cognitive load associated with emotional rumination and supports adaptive regulation rather than ongoing perseveration.¹⁰

4. Create One “White Space Block” Daily

Ask the patient to incorporate a short, non-screen, nonproductive (five-to-ten-minute block once per day. No email, no scrolling and no multitasking. The point is for their nervous system to downshift. Even brief unstructured pauses are associated with reduced sympathetic arousal and allow emotional states to surface and resolve rather than stack. This supports both mood stability and a clearer internal state.

5. Tie Mental Decluttering to Sleep Hygiene

Have patients pair their cognitive offloading with their pre-bed wind-down routine. Sleep quality is tightly linked to emotional regulation and next-day positive affect. Inadequate or fragmented sleep increases negative affect and blunts positive mood the next day.​9​ Helping the mind “power down” protects both sleep and emotional resilience.

Guidance for Clinicians

• Validate first. Acknowledge that invisible mental load is legitimate, has physiological effects and is commonly carried by people in caregiving or leadership roles.
• For patients in high-load caregiving or high-responsibility roles, “declutter” does not mean “drop responsibilities.” The intervention is redistributing cognitive responsibility across systems and people and introducing scheduled mental rest states.
• Avoid framing this as a need for better time management or organization. Instead, frame it as “your nervous system has been carrying too much for too long; let’s design supports so your brain can rest.”
• Teach externalization early. Getting thoughts or tasks out of working memory is often the fastest relief lever for patients.
• Reinforce that this is not about perfection or minimalism. The goal is to create enough cognitive space so that self-regulation (e.g., mood control, impulse control and boundary setting) can be restored.
• If the patient’s “mental clutter” contains trauma, intrusive thoughts or self-harm ideation, that is outside general lifestyle work and warrants referral to a licensed mental health professional.

Conclusion

Emotional wellbeing is both a reflection and a regulator of overall health. Helping patients reduce mental load is not about “doing less” but about creating the cognitive and emotional space necessary for recovery, balance and self-regulation. When you teach patients to declutter their minds, you are empowering them to rebuild resilience, protect sleep and reconnect with a sense of calm and purpose that supports healing on every level.

Resources

For more information, including diet and lifestyle recommendations for supporting emotional wellbeing, refer to the resource listed below: 

Emotional Well-Being Protocol^‡: Developed with our clinician partners to support emotional well-being through foundational health, targeted interventions, and lifestyle strategies.^‡

1. Park CL, Kubzansky LD, Chafouleas SM, et al. Affect Sci. 2023;4(1). doi:10.1007/s42761-022-00163-0
2. Gallup Inc. State of the World’s Emotional Health 2025. Gallup.com. 2025. Accessed November 5, 2025. https://www.gallup.com/analytics/349280/state-of-worlds-emotional-health.aspx
3. Ryff CD. Persp Psychol Sci. 2018;13(2). doi:10.1177/1745691617699836
4. Chida Y, Steptoe A. Psychosom Med. 2008;70(7). doi:10.1097/PSY.0b013e31818105ba
5. Kubzansky LD, Huffman JC, Boehm JK, et al. J Am Coll Cardiol. 2018;72(12). doi:10.1016/j.jacc.2018.07.042
6. Kelloway EK, Dimoff JK, Gilbert S. Ann Rev Org Psychol Org Beh. 2023;10(1):363-387. doi:10.1146/annurev-orgpsych-120920-050527
7. Dean L, Churchill B, Ruppanner L. Comm Work Fam. 2022;25(1). doi:10.1080/13668803.2021.2002813
8. Morrison AB, Richmond LL. Cogn Res Princ Implic. 2020;5(1). doi:10.1186/s41235-019-0201-4
9. Tomaso CC, Johnson AB, Nelson TD. Sleep. 2021;44(6). doi:10.1093/sleep/zsaa289
10. Brockbank RB, Feldon DF. Educ Sci (Basel). 2024;14(8):870. doi:10.3390/educsci14080870

⁺Dr Ross is a paid consultant for Pure Encapsulations.

By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Berberine and Blood Sugar: Unlocking Clinical Potential with Enhanced Absorption

1. Introduction to Berberine
2. Berberine and Insulin Signaling and Glucose Metabolism
3. Bioavailability and Absorption Concerns
4. Pure Encapsulations Nutrient Solutions
5. Conclusion
6. Resources

Introduction to Berberine

Berberine is a bioactive isoquinoline alkaloid found in several botanicals, including barberry (Berberis vulgaris), Oregon grape (Berberis aquifolium), Indian barberry (Berberis aristata), Chinese goldthread (Coptis chinensis) and goldenseal (Hydrastis canadensis). Its oldest use dates back to 3000 BC,1 though it has been more commonly used for over 400 years as a traditional therapeutic agent in China, India and the Middle East and offers a wide array of health benefits.²

Researchers are interested in berberine for its capacity to reduce oxidative stress, modulate cytokine production, suppress adipogenesis and lipid accumulation, provide neuroprotection, restore the gut microbiome and regulate glucose metabolism and insulin signaling.^2,3

One key challenge of administering berberine is oral bioavailability. These pharmacokinetic constraints have driven the development of enhanced delivery systems. Among these, phytosome formulations have been investigated to improve absorption and clinical performance. Recent work has demonstrated improved pharmacokinetic profiles for food-grade berberine formulations.⁴ Randomized trials of berberine phytosome have reported favorable metabolic effects compared with standard preparations.⁵

This blog will focus on how berberine supports glucose metabolism and the clinical importance of choosing the right formulation to enhance absorption in your patients.

Berberine and Insulin Signaling and Glucose Metabolism

Berberine's clinical effects on glucose metabolism and insulin signaling are shaped by its pharmacological behavior. Although oral absorption is limited (less than 1%), berberine and its active metabolites primarily concentrate in the liver to govern glucose production and utilization.¹ Within the liver, berberine influences pathways that regulate gluconeogenesis. After entering circulation, berberine is rapidly and widely distributed to muscle, lung, brain, heart, pancreas, adipose and kidney tissue.¹

Mechanisms of Action

Berberine influences multiple, interconnected aspects of metabolic health, which helps explain its broad clinical relevance:

Glucose metabolism: Berberine affects glucose metabolism by stimulating glycolysis, the fundamental metabolic process for energy production. It also impacts gluconeogenesis, which is important since altered gluconeogenesis contributes to changes in fasting glucose states and insulin signaling. Furthermore, berberine enhances the production of GLP-1, thereby improving insulin signaling.²

Insulin signaling: After insulin is produced by the b-cells of the pancreas, it binds to insulin receptor sites on the cell surface. This process activates a chain reaction within the cell, known as the insulin signaling cascade. Insulin receptor substrate 1 (IRS-1) and protein kinase B (PKB, also known as Akt) are key messengers within cells. This promotes the translocation of the glucose transporter 4 (GLUT-4) protein to the cell surface, allowing glucose to be shuttled into the cells.

Berberine has been reported to have an impact on several areas of this chain reaction:

1. It reduces the inhibitory signal of IRS-1, thereby improving intracellular communication.⁶
2. It enhances Akt signaling and improves cellular glucose uptake.⁶
3. It promotes the movement of GLUT4 transporters to the cell surface. This enhances the ability of skeletal muscle cells to absorb glucose from the circulation and store it as glycogen, thereby improving whole-body glucose utilization.⁷
4. It activates AMP-activated protein kinase (AMPK), a central "energy sensor" in cells. AMPK activation redirects metabolism toward energy-efficient pathways, promoting glucose uptake and utilization while inhibiting processes that contribute to excess glucose production.^2,8 Further, there is an increased expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1), a key regulator of mitochondrial biogenesis.⁹
5. Berberine also upregulates SIRT1, a key regulator in adipose tissue, that contributes to insulin signaling, as well as promotes insulin secretion from b-cells.⁷

BERBERINE’S IMPACT ON INSULIN SIGNALING AND GLUCOSE METABOLISM

Additionally, berberine has an impact on other key mechanisms of action, including:

Lipid balance: Berberine reduces the liver's tendency to produce new fats from excess carbohydrates (a process known as de novo lipogenesis) and promotes fat burning for energy. Clinically, this supports fat metabolism within liver cells.¹⁰

Gut microbiota interaction: Berberine directly influences the gut microbiome in several ways. It encourages growth of beneficial bacteria, modulates the intestinal barrier and increases the production of bile acids (BA), short-chain fatty acids (SCFA), dopamine and branched-chain amino acids (BCAA), while reducing the production of trimethylamine (TMAO).¹¹

Healthy cytokine balance and antioxidant support: It has been reported that berberine supports healthy cytokine balance, inhibits leukocyte adhesion, suppresses oxidative stress and promotes immune regulation.^2,12

Notably, one study identified 22 pathways and molecular mechanisms that berberine impacts for glucose regulation alone, underscoring the depth of this topic, which extends beyond the scope of this blog.¹³

Phytosome^™ Technology for Increased Absorption

Phytosomes, also referred to as herbasomes, protect herbal extracts from digestive fluids and intestinal microbes, allowing them to enter the bloodstream, prolong circulation and delay clearance.²⁰ Phytosome^™ technology combines a botanical extract with phospholipids, improving membrane affinity, lymphatic uptake and resistance to P-gp efflux, which together enhance oral absorption and systemic exposure at a given dose.⁴ For berberine, this strategy aims to deliver higher effective concentrations to the liver and muscle, which are central to gluconeogenesis control, GLUT4-mediated uptake and overall glucose homeostasis, while potentially reducing GI intolerance seen with conventional forms.

Evidence for Enhanced Delivery

Berbevis^® is a form of berberine that utilizes Phytosome^™ technology. A pharmacokinetic study utilizing Berbevis^® showed significantly improved plasma exposure versus conventional berberine (chloride), confirming better absorption with the phospholipid complex.⁴ This led to further research, including:

• A double-blind, placebo controlled RCT reported that Berbevis^® (550 mg, twice daily) promoted healthy glycemic control and insulin signaling over placebo, while also supporting healthy lipid profiles.⁵
• Additional studies support similar promotion of healthy lipid profiles and cardiometabolic risk factors with Berbevis^® at a single dose of 500 mg per day.^21,22
• Two other studies using 550 mg twice daily of Berbevis^® reported support for healthy glucose metabolism and insulin signaling, with one study also showing significant support for cardiometabolic parameters.^23,24

Taken together, these data indicate that formulation matters. A phytosome form of berberine increases exposure, improves tolerability and results in clinically meaningful improvements in endpoints related to insulin signaling and glucose regulation, potentially at lower total daily doses than conventional berberine.

Pure Encapsulations Nutrient Solutions

Berberine UltraSorb^™ provides Berbevis^®, which is manufactured from Berberis aristata root extract. This berberine phytosome provides enhanced bioavailability that promotes healthy glycemic control, helps maintain healthy glucose levels already within normal ranges and promotes healthy insulin receptor function and signaling.⁴ Berberine UltraSorb^™ provides 550 mg of clinically studied berberine phytosome that is four times more bioavailable than standard berberine.

Suggested Dose: As a dietary supplement, take 1 capsule 1 to 2 times daily, with or between meals.

Conclusion

Berberine, a natural alkaloid with a long history of medicinal use, continues to demonstrate strong clinical relevance in modern metabolic care. While its low oral bioavailability has historically limited application, advances such as Phytosome^™ technology now offer improved absorption and greater clinical utility at lower and better tolerated doses.

By targeting multiple pathways simultaneously, berberine provides a multifaceted approach to restoring metabolic balance. For clinicians, berberine phytosome represents a promising adjunctive option for patients to support their metabolic health, particularly when combined with foundational nutrition and lifestyle strategies.^‡

Resources

For additional information that includes diet and lifestyle recommendations for supporting glucose regulation and insulin signaling, refer to the resources listed below:

Cardiometabolic Support Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support insulin signaling and glucose metabolism.

Berberine Webinar: Watch the webinar “Berberine Deep Dive: An Update to Evidence-Based Clinical Use for Cardiometabolic Applications^‡,” presented by Kelly Heim, Ph.D.

To learn more about the research on selected nutrient solutions, download the following:

• Berberine UltraSorb^™ Sales One Pager
• Berberine UltraSorb^™ Product Info Sheet

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.

1. Khoshandam A, Imenshahidi M, Hosseinzadeh H. Phytother Res. 2022;36(11). doi:10.1002/ptr.7589
2. Utami AR, Maksum IP, Deawati Y. Biology (Basel). 2023;12(7). doi:10.3390/biology12070973
3. Och A, Och M, Nowak R, Podgórska D, Podgórski R. Molecules. 2022;27(4). doi:10.3390/molecules27041351
4. Petrangolini G, Corti F, Ronchi M, Arnoldi L, Allegrini P, Riva A. Evid Based Complement Alternat Med. 2021;2021. doi:10.1155/2021/7563889
5. Rondanelli M, Gasparri C, Petrangolini G, et al. Eur Rev Med Pharmacol Sci. 2023;27(14). doi:10.26355/eurrev_202307_33142
6. Li A, Lin C, Xie F, Jin M, Lin F. Metab Syndr Relat Disord. 2022;20(8). doi:10.1089/met.2022.0017
7. Lv X, Zhao Y, Yang X, et al. Front Pharmacol. 2021;12. doi:10.3389/fphar.2021.720866
8. Bellavite P, Fazio S, Affuso F. Molecules. 2023;28(11). doi:10.3390/molecules28114491
9. Qin X, Jiang M, Zhao Y, et al. Br J Pharmacol. 2020;177(16). doi:10.1111/bph.14935
10. Cai Y, Yang Q, Yu Y, Yang F, Bai R, Fan X. Front Pharmacol. 2023;14. doi:10.3389/fphar.2023.1283784
11. Cheng H, Liu J, Tan Y, Feng W, Peng C. J Pharm Anal. 2022;12(4). doi:10.1016/j.jpha.2021.10.003
12. Wang K, Yin J, Chen J, Ma J, Si H, Xia D. Phytomedicine. 2024;128:155258. doi:10.1016/j.phymed.2023.155258
13. Han Y, Xiang Y, Shi Y, et al. Evid Based Complement Alternat Med. 2021;2021. doi:10.1155/2021/9987097
14. Kwon M, Lim DY, Lee CH, Jeon JH, Choi MK, Song IS. Pharmaceutics. 2020;12(9). doi:10.3390/pharmaceutics12090882
15. Solnier J, Zhang Y, Kuo YC, et al. Pharmaceutics. 2023;15(11). doi:10.3390/pharmaceutics15112567
16. Liu CS, Zheng YR, Zhang YF, Long XY. Fitoterapia. 2016;109. doi:10.1016/j.fitote.2016.02.001
17. Feng X, Wang K, Cao S, Ding L, Qiu F. Front Pharmacol. 2021;11. doi:10.3389/fphar.2020.594852
18. Tan XS, Ma JY, Feng R, et al. PLoS One. 2013;8(10). doi:10.1371/journal.pone.0077969
19. Moon JM, Ratliff KM, Hagele AM, Stecker RA, Mumford PW, Kerksick CM Nutrients. 2022;14(1). doi:10.3390/nu14010124
20. Kalaivani, P, Kamaraj, R. Cureus. 2024;16(8):e68180. doi:10.7759/cureus.68180
21. Cesarone MR, Hu S, Belcaro G, et al. Minerva Gastroenterol. 2024;70(1). doi:10.23736/s2724-5985.23.03540-4
22. Cesarone MR, Hu S, Belcaro G, et al. Minerva Med. 2025;116(4):285-291. doi:10.23736/S0026-4806.25.09637-5
23. Di Pierro F, Sultana R, Eusaph AZ, et al. Front Pharmacol. 2023;14. doi:10.3389/fphar.2023.1269605
24. Rondanelli M, Riva A, Petrangolini G, et al. Nutrients. 2021;13(10). doi:10.3390/nu13103665

⁺Kim Ross is a paid consultant for Pure Encapsulations.

By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Polyphenols in Practice: Targeted Strategies to Support Liver Health

1. Introduction
2. The Liver-Metabolic Health Connection
3. Polyphenols: Bergamot & Artichoke Extracts in Supporting Liver Health: A Summary of the Evidence
4. Pure Encapsulations Nutrient Solutions
5. Conclusion
6. Resources

Introduction to Liver Health

The liver is a central metabolic hub, responsible for nutrient processing, energy regulation and detoxification processes. With functions such as glycogen storage, lipid metabolism, bile production and clearance of endogenous and exogenous toxins, it plays a critical role in maintaining homeostasis. It also regulates circulating glucose and lipid levels, synthesizes essential proteins and processes hormones and cytokine mediators.¹

Given its pivotal role, changes to hepatic function have systemic consequences. When fat accumulation occurs within hepatocytes, it can lead to altered metabolic health and disrupt normal metabolic processes.²

Prevalence of Altered Metabolic Health and Fat Accumulation in the Liver³

The most vulnerable and at-risk populations include those who carry extra weight, have alterations in glucose and/or insulin regulation and cardiovascular concerns.

The Liver–Metabolic Health Connection

Body Fat Distribution

The liver is a central regulator of energy balance, integrating signals from dietary intake, adipose tissue and peripheral organs to maintain homeostasis. In states of energy excess, these finely tuned pathways become altered, contributing directly to systemic metabolic changes.

Central adiposity, measured via waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), consists of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).⁵

Visceral adiposity is of particular concern, since this becomes metabolically active tissue that drives higher levels of adipokines, cytokines produced by adipose tissue (i.e., TNF-α, IL-6) and is associated with increased changes in glucose and insulin regulation.6 Visceral adiposity promotes increased lipolysis, releasing free fatty acids (FFAs) directly into the portal circulation. The liver becomes flooded with FFAs, which are either re-esterified into triglycerides or incompletely oxidized.

Glucose and Insulin Metabolism

The liver stores glucose as glycogen during times of energy abundance and releases it via glycogenolysis during fasting. It also produces glucose through gluconeogenesis from substrates like lactate, glycerol and amino acids to maintain blood glucose levels.

When there is a consistent surplus of calories, the body experiences changes in insulin responses. Over time, this will impact the way the liver responds to insulin to reduce glucose production and continues to release glucose into the bloodstream, even when energy needs are already met.

While insulin fails to suppress gluconeogenesis, it activates pathways in the liver that convert excess carbohydrates into fat through a process called de novo lipogenesis. These newly created fats (triglycerides) are stored in liver cells, contributing to increased fat accumulation.

Lipid Metabolism

The liver plays a central role in regulating lipid balance, acting as the body's main processing center for fats. It packages triglycerides and cholesterol into very-low-density lipoproteins (VLDL) for delivery to other tissues, removes excess cholesterol from the bloodstream and helps break down dietary fats through bile acid production.

When the system becomes overwhelmed by a surplus of calories and circulating fats, the liver begins to store more fat than it can process or export. Over time, this leads to an accumulation of triglycerides within liver cells, reducing its efficiency and altering metabolic pathways.

As fat continues to accumulate, the liver produces more VLDL particles, contributing to an altered lipid profile.⁷ These changes affect not just liver health but also overall cardiometabolic risk, making lipid metabolism a critical link between liver function and systemic health.

Prevalence of Altered Metabolic Health and Fat Accumulation in the Liver³

Excess visceral fat = “Overflowing Delivery Trucks”-too many incoming deliveries (FFAs)

Imagine visceral fat as a fleet of delivery trucks constantly sending shipments of fat (free fatty acids) to the liver.

In excess weight, these trucks are working overtime, sending far more cargo than the liver’s “receiving docks” can handle. With nowhere else to go, the liver starts storing the excess inventory as fat.

Glucose/Insulin = “Mixed Messages from the Control Tower”

The liver is like a shipping control center that coordinates what gets produced and where it goes. Normally, insulin acts like a dispatcher, telling the liver to slow glucose production when supplies are sufficient and direct energy elsewhere.

But in states of energy surplus, the dispatcher’s messages get scrambled. The glucose “production line” keeps running at full speed, adding more cargo to already full warehouses, while the liver simultaneously ramps up fat production from excess carbs. The result? A backlog of stored products and a growing traffic jam in energy management.

Lipid Metabolism = “An Overloaded Shipping Hub” managing excess inventory

The liver functions as the body’s central shipping hub for fats. It receives cargo (free fatty acids from adipose tissue and dietary fats), processes it and packages triglycerides and cholesterol into VLDL particles for delivery throughout the body.

When too much cargo arrives too quickly, the hub becomes overloaded. This excess cargo is stored inside the “warehouse” (liver cells), slowing operations, while an increasing number of overflow packages spill into circulation.

Analogy created with the assistance of AI. Reference: OpenAI. ChatGPT [Large language model]. Version GPT-5. Published September 2025. Accessed September 2, 2025. https://chat.openai.com

Polyphenols: Bergamot & Artichoke Extracts in Supporting Liver Health: A Summary of the Evidence

Polyphenols are bioactive plant-derived compounds with antioxidant and metabolic-regulatory properties. In particular, BergaCynFF^®, a patented blend of bergamot flavonoids and artichoke (Cynara cardunculus) polyphenols, has demonstrated significant benefits for supporting lipid metabolism in the liver with the added benefits of promoting healthy uric acid levels, decreasing oxidative stress and supporting vascular endothelial health.^{8–11‡ 8–11‡}

A 12-week, randomized, placebo-controlled trial (n=102) assessed BergaCynFF^® (300 mg/day) in individuals with altered liver health. Compared to placebo, BergaCynFF^® significantly reduced hepatic fat measured by controlled attenuation parameter (CAP) score (P = .02). Subgroup analysis revealed the most pronounced benefit among participants aged >50 years and those with android adiposity (response rates: 78% vs 44%; P = .007).¹¹

Endothelial Function Improvement

A 12-week RCT of 32 adults with altered liver health and impaired endothelial function found that BergaCynFF^® supplementation significantly improved reactive hyperemia index (RHI) compared to placebo (P = .02). Improved endothelial reactivity supports the potential role of BergaCynFF^® in mitigating the heightened health risk factors.^12‡

Clinical Integration

BergaCynFF^® at 300 mg/day for 6–12 weeks may complement lifestyle interventions for liver health. Clinicians should monitor liver enzymes, CAP score, lipids, glycemic control and vascular markers to assess therapeutic response.^‡

Pure Encapsulations Nutrient Solutions

Lipid Support Complex is for patients seeking support for healthy fat metabolism. Lipid Support Complex supports hepatic fat metabolism with a combination of berberine and clinically studied BergacynFF^®, a patented extract blend of bergamot citrus and Cynara cardunculus. BergacynFF^® supports lipid metabolism in the liver, with the added benefits of promoting healthy uric acid levels, decreasing oxidative stress and supporting vascular endothelial health.^{8–11 ‡}

Suggested Dose: Take 2 capsules daily, with a meal.

Conclusion

The liver serves as a central hub for energy balance, nutrient processing and metabolic regulation. Disruptions in these pathways, driven by factors such as excess visceral fat, altered glucose handling and lipid imbalances, altered liver health.

Emerging evidence highlights the role of targeted nutraceutical strategies in supporting liver health. BergaCynFF^®, a patented combination of bergamot and artichoke polyphenols, demonstrates multi-faceted benefits, improvements in lipid profiles and glycemic control, enhanced antioxidant defenses and improved endothelial function.^‡

For clinicians, integrating BergaCynFF^® alongside foundational lifestyle interventions offers a promising approach to supporting liver function and broader metabolic health.^‡

Resources

For additional resources that include diet and lifestyle recommendations for supporting occasional anxiety, refer to the protocols listed below:

Hepatic Fat Metabolism Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support liver health

For more details on the research on the selected nutrient solutions, download the product information sheets: Lipid Support Complex

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.

1. Rhyu J, Yu R. World J Hepatol. 2021;13(11). doi:10.4254/wjh.v13.i11.1611
2. Rinella ME, Sookoian S. J Lipid Res. 2024;65(1). doi:10.1016/j.jlr.2023.100485
3. Younossi ZM, Kalligeros M, Henry L. Clin Mol Hepatol. 2025;31(Suppl):S32-S50. doi:10.3350/cmh.2024.0431
4. Chalasani N, Younossi Z, Lavine JE, et al. Hepatology. 2018;67(1). doi:10.1002/hep.29367
5. Nahorna A, Baur H. Obes Sci Pract. 2025;11(3):e70078. doi:10.1002/osp4.70078
6. Schousboe JT, Kats AM, Langsetmo L, et al. J Am Heart Assoc. 2018;7(16). doi:10.1161/JAHA.118.009172
7. Targher G, Byrne CD, Tilg H. Gut. 2020;69(9). doi:10.1136/gutjnl-2020-320622
8. Parafati M, Lascala A, Morittu VM, et al. Journal of Nutritional Biochemistry. 2015;26(9). doi:10.1016/j.jnutbio.2015.03.008
9. Musolino V, Gliozzi M, Bombardelli E, et al. J Tradit Complement Med. 2020;10(3). doi:10.1016/j.jtcme.2020.02.004
10. Ferro Y, Maurotti S, Mazza E, et al. Medicina (B Aires). 2022;58(12):1728. doi:10.3390/medicina58121728
11. Ferro Y, Montalcini T, Mazza E, et al. Front Endocrinol (Lausanne). 2020;11. doi:10.3389/fendo.2020.00494
12. Maurotti S, Pujia R, Ferro Y, et al. Nutrition. 2024;118. doi:10.1016/j.nut.2023.112294

⁺Kim Ross is a paid consultant for Pure Encapsulations.

Think Ahead: Cognitive Wellness Today for Tomorrow

By: Amy Doyle, MS, CNS⁺

1. Introduction
2. Age-Related Changes in the Brain
3. Oxidative Stress and Brain Health
4. Antioxidant Intake and Cognitive Function
5. Nutrient Solutions for Cognitive Function
6. Pure Encapsulations^® Nutrient Solutions for Cognitive Function
7. Summary
8. Resources
9. References

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 adults in the US age 65 and older experience memory loss, thinking difficulties and other cognitive changes that could interfere with daily life and activities.¹

By age 45, the risk of these types of cognitive changes is 1 in 5 for women and 1 in 10 for men.¹

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.^1,2

Age-related chemical and physical changes in the brain can include:³

• 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.⁴ 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.^5,6

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.⁴ Regulation of ROS in the brain is critical for memory consolidation and long-term potentiation.⁷

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.^8,9,10

In a 2023 meta-analysis of cohort studies, researchers sought to investigate the association of antioxidant intake with the risk of cognitive changes.¹¹

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.¹² In addition, the practitioner can support the brain’s resilience against oxidative stress with targeted nutrient solutions.

Magnesium L-threonate Animal research suggests that magnesium-l-threonate may promote synaptic plasticity and density in the regions of the hippocampus correlated with learning and memory.^13‡

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.^14‡

Phosphatidylserine supports cognitive function, emotional well-being and behavioral performance. It has also been shown to support healthy memory.^15,16‡

Resveratrol promotes cardiometabolic, neuronal and cellular health through a variety of effects on cell signaling, mitochondrial function and endogenous antioxidant defenses.^{17,18,19,20‡}

Omega 3 Fatty Acids encourage cardiovascular health by supporting lipid metabolism and healthy blood flow. ^21,22,23 In addition, studies indicate these oils help maintain healthy endothelial function.^24‡

Curcumin supports neuronal stability and function, in part, by promoting healthy cytokine balance and antioxidant defenses.^25‡

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.^26‡

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

1. ALZ.org. Facts and Figures 2024. Accessed May 14, 2024.
2. CDC.gov. Accessed May 14, 2024.
3. NCOA. Accessed May 12, 2024.
4. Song T et al. Ageing Res Rev. 2021;72:101503. doi:10.1016/j.arr.2021.101503
5. Bai R et al.  Ageing Res Rev. 2022;77:101619. doi:10.1016/j.arr.2022.101619.
6. Qin P, Sun Y, Li L.  Int J Mol Med. 2024;53(5):47. doi:10.3892/ijmm.2024.5371.
7. Serrano, F., & Klann, E.  Ageing Research Reviews, 2004. 3(4): 431–43. doi:10.1016/j.arr.2004.05.002.
8. Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB. Fruit and vegetable juices and Alzheimer's disease: the Kame Project. Am J Med. 2006;119(9):751-759. doi:10.1016/j.amjmed.2006.03.045
9. Barberger-Gateau P et al. Neurology. 2007. 69(20):1921-30. doi:10.1212/01.wnl.0000278116.37320.52.
10. Hughes TF et al. Am J Geriatr Psychiatry. 2010.18(5):413-20. doi:10.1097/JGP.0b013e3181c65250.
11. Zhao R et al. J Alzheimers Dis. 2024. 99(s1):S35-S50. doi:10.3233/JAD-220909.
12. Livingston G et al. Lancet. 2020. 396(10248):413-46. doi:10.1016/S0140-6736(20)30367-6.
13. Slutsky I, et al. Neuron. 2010 Jan 28;65(2):165- 77.
14. Kerner J, et al. Mech Ageing Dev. 2015 Jan;145:39-50.
15. Maggioni M, et al. Acta Psychiatr Scand. 1990 Mar;81(3):265-70.
16. Hirayama S, et al. J Hum Nutr Diet. 2013 Apr;27 Suppl 2:284-91.
17. Xia N, et al. Br J Pharmacol. 2017 Jun;174(12):1633-1646
18. Brito PM, et al. Atherosclerosis. 2009 Jul;205(1):126-34.
19. Pyo IS, et al. Molecules. 2020 Oct 12;25(20):4649.
20. Ghanim H, et al. J Clin Endocrinol Metab. 2010 Sep;95(9):E1-8.
21. Ottestad I, Hassani S, Borge GI, et al. PLoS One. 2012;7(8):e42550
22. Ebrahimi M, Ghayour-Mobarhan M, Rezaiean S, et al. Acta Cardiol. 2009 Jun;64(3):321-7.
23. Geleijnse JM, Giltay EJ, Grobbee DE, et al. J Hypertens. 2002 Aug;20(8):1493-9.
24. Khan F, Elherik K, Bolton-Smith C, et al. Cardiovasc Res. 2003 Oct 1;59(4):955-62.
25. Braidy N, et al. FEBS J. 2010 Jan;277(2):368-82.
26. Stough C, et al. Psychopharmacology (Berl). 2001 Aug;156(4):481-4.

By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Supporting Female Fertility with Nutrition

1. Introduction
2. The Role of Diet in Fertility
3. Nutrients that Support Fertility
4. Pure Encapsulations Nutrient Solutions
5. Conclusion
6. Resources

Introduction to Fertility Support

Over 15% of women between the ages of 25-49 are seeking fertility support from their healthcare providers.¹

Fertility refers to the natural ability to reproduce and conceive a child within 1 year of regular, unprotected intercourse. Successful fertility is dependent on factors impacting the male and female, including:

• Healthy production of sperm and eggs
• Unblocked fallopian tubes allowing the sperm to reach the egg
• Fertilization of the egg by the sperm
• Implantation of the fertilized eggs in the uterus
• Sufficient embryo quality

Female fertility also depends on healthy ovulation and reproductive anatomy as well as balanced hormones (estrogen, progesterone, luteinizing hormone, follicle-stimulating hormone). As women reach their 30s, they are about half as fertile as they were a decade before.² Unsuccessful conception resulting from factors impacting female, male or both partners’ health has resulted in as many as 1 in 6 people worldwide adapting their initial fertility plans.^2,3

This blog explores how diet and several key nutrients can impact fertility potential for women.

The Role of Diet in Fertility

Diet is a key modifiable factor influencing reproductive health. Research indicates that dietary patterns and specific nutrient intakes can affect fertility outcomes.⁴ Nutritional status can influence hormone production, ovulatory function and the quality of gametes and implantation environment. Clinically, maintaining a balanced diet and healthy body weight is often recommended as part of preconception care to optimize fertility.

Healthy dietary patterns rich in plant-based foods, such as the Mediterranean Diet, have been associated with higher chances of conception and improved outcomes in those undergoing assisted reproductive treatments. Similarly, a vegan/vegetarian diet, rich in plants and antioxidants, can positively impact fertility by reducing oxidative stress. A ketogenic diet, which reduces high-carbohydrate foods and increases quality fat, appears to be most beneficial for fertility outcomes in women who are overweight.⁴

In contrast, Western-style diets high in refined carbohydrates, saturated fats and processed foods impact fertility potentially through ovulation, changes in glucose and insulin regulation and increased cytokine production.⁴

General Dietary Guidelines:

There isn't one dietary pattern that is ideal for all women!

The best food plan will be one that your patient can adhere to with high compliance and includes personal food preferences and honors cultural beliefs and traditions while supporting overall health.

Nutrients that Support Fertility

Several micronutrients play specific physiological roles in female reproduction. Insufficient intake or deficiencies in these nutrients may impact ovarian function, egg quality or early embryonic development. Here are key nutrients, evidence for their roles in supporting female fertility and common dietary sources (Table A).

B Vitamins (B₆, Folate, and B₁₂)

Physiological role: B vitamins are critical for DNA synthesis, methylation reactions and hormone metabolism. Folate (vitamin B₉) and vitamin B₁₂ work together in one-carbon metabolism to support DNA replication in rapidly dividing cells (such as oocytes and early embryos). Vitamin B₆ acts as a coenzyme in amino acid metabolism and neurotransmitter synthesis, which can indirectly influence hormonal balance. Folate is also known for its important role in neural tube closure. Since this occurs around days 28-29 of pregnancy, usually before a woman knows she is pregnant, preconception consumption of adequate folate intake is critical.

Evidence: In the Nurses' Health Study II, women taking multivitamins with folic acid, as well as the intakes of B₆ and B₁₂, supported fertility.⁹ Another study found that adherence to a folate-rich, vitamin B₆–rich diet correlated with higher folate and B₆ levels in follicular fluid.⁴ Further, adequate folate and B₁₂ help support methylation and the amino acid homocysteine. Elevated homocysteine levels may impact fertility and pregnancy.¹⁰ These findings underscore the importance of B vitamins to support women's fertility.

Choline

Physiological role: Choline is an essential nutrient that supports cell membrane structure (as a component of phospholipids), neurotransmitter production (acetylcholine), and methylation pathways. In the context of fertility, choline is needed for proper neural tube closure and may support oocyte development and early embryogenesis.¹¹ It also has a role in one-carbon metabolism that complements folate. Choline also contributes to the synthesis of phosphatidylcholine in oocytes and embryos, which is important for cell division and signaling.

Evidence: While direct human studies on choline and female fertility are limited, emerging evidence points to its importance. For example, an animal study showed that supplemental choline supported ovarian follicle development.¹¹ In women, adequate choline status is thought to be beneficial during preconception and pregnancy, especially when folate intake is suboptimal, due to its role in reducing homocysteine.¹²

Iron

Physiological role: Iron is essential for oxygen transport (as a hemoglobin component) and cellular energy production. In women, iron requirements are high due to menstrual losses and even higher in pregnancy. From a fertility perspective, iron is required for proper ovulation and placental development; insufficient iron may impact ovulation and lead to poor oxygenation of reproductive tissues.

Evidence: Several studies link iron status with female fertility.¹³ For example, a recent clinical study in women with low iron showed that addressing iron status significantly supported fertility outcomes with an increase in conception rate (from 65% to 77%) and a higher live birth rate, as well as a lower miscarriage rate.¹⁴ A large prospective study of nurses found that women who used iron supplements supported ovulatory function.¹⁵ Caution should be exercised, as iron overload may negatively impact fertility outcomes.¹⁶

Zinc

Physiological role: Zinc is a trace mineral that acts as a cofactor for numerous enzymes and is vital for cell division, DNA synthesis and antioxidant defense. In female reproduction, zinc plays a critical role in oocyte development. A sufficient zinc concentration in the maturing oocyte is necessary to complete meiosis and form a fertilization-competent egg.¹⁷ Zinc also plays a unique role in the fertilization process, known as the "zinc spark," which is the moment of sperm-egg fusion that blocks additional sperm from the egg and activates the embryo.¹⁷ Furthermore, adequate zinc is needed in the early embryo for cell division and implantation.

Evidence: A comprehensive review highlighted that low zinc levels in females leads to changes in oocyte quality and other reproductive functions.¹⁷ Population studies have noted that women with suboptimal zinc levels may experience a longer time to pregnancy, likely due to subtle impacts on ovulation and egg viability.¹⁸

Vitamin D

Physiological role: Vitamin D functions as a steroid hormone in the body, regulating gene expression in numerous tissues, including the reproductive organs. Vitamin D receptors and metabolizing enzymes are present in the ovaries, endometrium and placenta, suggesting direct effects on reproductive processes. In ovarian tissue, vitamin D may influence follicular development and steroidogenesis (e.g., progesterone production). In the uterus, it may promote an optimal endometrial environment for implantation. Adequate vitamin D is also important for immune modulation during pregnancy.^19–22

Evidence: Low levels of vitamin D deficiency is common in women of childbearing age. Studies have found that sufficient vitamin D levels are associated with supporting fertility by supporting healthy, regular menstrual cycles and ovulation while reducing cytokine production.^23–26 Additionally, maintaining sufficient vitamin D during pregnancy is important for optimal outcomes.²⁷

Selenium

Physiological role: Selenium is an essential trace element that is a component of selenoproteins, including antioxidant enzymes like glutathione peroxidases and thyroid deiodinases. Through these enzymes, selenium helps protect cells (including oocytes and sperm) from oxidative damage. Selenium may be most known for its role in thyroid health, which is closely linked to fertility. Thyroid hormones (TSH, T3, T4) are essential for producing and regulating reproductive hormones and organs. Further, selenium's antioxidant role is also important in the ovarian environment, where oxidative stress can impact follicular development and embryo quality.²⁸

Evidence: Women with higher selenium levels tend to have better reproductive outcomes. In one study low plasma selenium in women was linked to a longer time to become pregnant compared to those with selenium levels in a typical range. These findings are consistent with broader observations that low selenium levels may be associated with certain pregnancy-related complications.^{18, 29}

Iodine

Physiological role: Iodine is crucial for synthesizing thyroid hormones (T3 and T4), which regulate metabolism and play a significant role in reproductive health. In women, proper thyroid function is necessary for regular menstrual cycles, ovulation and sustaining early pregnancy. Adequate iodine in the preconception period helps ensure the thyroid can meet the increased hormonal demands of pregnancy, supporting fetal neurodevelopment in the first trimester.³⁰

Evidence: A notable prospective study in the United States found that women with moderate-to-severe low iodine levels had significantly lower odds of conceiving. In fact, these women had about half the per-cycle chance of becoming pregnant compared to women with sufficient iodine levels. They also tended to take longer on average to achieve pregnancy.³¹ These findings are concerning given that approximately 30% of women of childbearing age in the study had iodine levels below recommended concentrations. This is further compounded by 75% of obstetricians not recommending iodine supplementation and about 50% of all prenatal vitamins not containing iodine in their formulation.³²

Omega-3 Fatty Acids

Physiological role: In reproductive health, omega-3s are thought to help with ovarian function and the uterine environment by reducing oxidative stress. They can influence hormone production and may promote better blood flow to reproductive organs. During the early stages of pregnancy, omega-3s support placental development and are critical for fetal brain development, but even prior to conception, they appear to be beneficial for the quality of oocytes and embryos.^33,34

Evidence: Multiple studies have reported on the benefits of omega-3s for women of reproductive years, such as supporting egg quality and endometrial health and increasing the number of follicles and follicular fluid.^35-38

In summary, research suggests that preconception supplementation of multiple micronutrients (via a multivitamin/mineral) supports fertility.^40,41

Pure Encapsulations Nutrient Solutions

PreNatal Nutrients is a multivitamin/mineral complex for women of childbearing age that provides essential vitamins, minerals and nutrients based on scientific evidence that supports maternal and fetal health. Features include Metafolin^® L-5 MTHF, the naturally occurring, universally metabolized form of folate and vitamin D derived from an algae source. It is best when combined with EPA/DHA essentials.^‡

Suggested Dose: Take 2 capsules daily, with a meal.

EPA/DHA essentials is an ultra-pure, microfiltered fish oil concentrate source from sardines and anchovies off the coast of Chile or Norway that supports daily wellness.^‡

Suggested Use: Take 1-2 softgels daily, with a meal.

DHA Ultimate is sourced from sardines and anchovies from the Pacific Ocean off the coast of Chile. The DHA fish oil is produced in a low-temperature, oxygen-free, solvent-free supercritical CO2-based extraction, resulting in a pure, clean and safe product.

Suggested Use: Take 2 capsules daily, with a meal.

Conclusion

Optimizing nutrition is a fundamental aspect of supporting female fertility. The micronutrients discussed (B vitamins, choline, iron, zinc, vitamin D, selenium, iodine and omega-3 fatty acids) contribute uniquely to the complex physiology of reproduction.

An evidence-based understanding of these nutrients helps clinicians guide women in making dietary choices or taking supplements (when appropriate) to address gaps. For integrative health practitioners, assessing nutritional status and ensuring adequacy of these key nutrients should be part of preconception care. While nutrition does not guarantee pregnancy, it lays the groundwork for hormonal balance, healthy ovulation and a receptive environment for pregnancy.

Resources

For additional resources that include diet and lifestyle recommendations for supporting fertility, refer to the protocols listed below:

Women's Fertility Support Protocol^‡: Designed by our scientific and medical advisors to help you deliver the most effective care and support for your patient's fertility.

For more details on the research on the selected nutrient solutions, download the product information sheets:

• PreNatal Nutrients
• EPA/DHA essentials
• DHA Ultimate

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.

1. Chandra A, Copen CE, Stephen EH. Natl Health Stat Report. 2013;(67).
2. Pfeifer S, Butts S, Fossum G, et al. Fertil Steril. 2017;107(1). doi:10.1016/j.fertnstert.2016.09.029
3. World Health Organization. April 4, 2023. Accessed February 29, 2024. https://www.who.int/news/item/04-04-2023-1-in-6-people-globally-affected-by-infertility
4. Cristodoro M, Zambella E, Fietta I, Inversetti A, Di Simone N. Biology (Basel). 2024;13(2). doi:10.3390/biology13020131
5. Stephens T V., Payne M, Ball RO, Pencharz PB, Elango R. J Nutr. 2015;145(1). doi:10.3945/jn.114.198622
6. Gorczyca AM, Sjaarda LA, Mitchell EM, et al. Eur J Nutr. 2016;55(3). doi:10.1007/s00394-015-0931-0
7. Blumfield M, Mayr H, Vlieger N De, et al. Molecules. 2022;27(13). doi:10.3390/molecules27134061
8. Crinnion WJ. Alternat Med Rev. 2010;15(1).
9. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Fertil Steril. 2008;89(3). doi:10.1016/j.fertnstert.2007.03.089
10. Ogawa S, Ota K, Takahashi T, Yoshida H. Nutrients. 2023;15(17). doi:10.3390/nu15173730
11. Jaiswal A, Dewani D, Reddy LS, Patel A. Cureus. Published online 2023. doi:10.7759/cureus.48538
12. Zeisel SH. Annu Rev Nutr. 2006;26.doi:10.1146/annurev.nutr.26.061505.111156
13. Holzer I, Ott J, Beitl K, et al. Front Endocrinol (Lausanne). 2023;14. doi:10.3389/fendo.2023.1173100
14. Tulenheimo‐Silfvast A, Ruokolainen‐Pursiainen L, Simberg N. Acta Obstet Gynecol Scand. 2025;104(4):738-745. doi:10.1111/aogs.15046
15. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Obstet Gynecol. 2006;108(5). doi:10.1097/01.AOG.0000238333.37423.ab
16. Zhang J, Su T, Fan Y, Cheng C, Xu L, LiTian. Life Sci. 2024;340. doi:10.1016/j.lfs.2023.122370
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19. Grzesiak M, Tchurzyk M, Socha M, Sechman A, Hrabia A. Int J Mol Sci. 2022;23(22). doi:10.3390/ijms232214137
20. Voulgaris N, Papanastasiou L, Piaditis G, et al. Hormones. 2017;16(1). doi:10.14310/horm.2002.1715
21. Jeon GH. Nutrients. 2024;16(1). doi:10.3390/nu16010096
22. Grundmann M, von Versen-Höynck F. Reprod Biol Endocrinol. 2011;9. doi:10.1186/1477-7827-9-146
23. Várbíró S, Takács I, Tűű L, et al. Nutrients. 2022;14(8). doi:10.3390/nu14081649
24. Meng X, Zhang J, Wan Q, et al. Reprod Biol Endocrinol. 2023;21(1). doi:10.1186/s12958-023-01068-8
25. Yang M, Shen X, Lu D, et al. Front Endocrinol (Lausanne). 2023;14. doi:10.3389/fendo.2023.1148556
26. van Tienhoven XA, Ruiz de Chávez Gascón J, Cano-Herrera G, et al. Int J Mol Sci. 2025;26(5):2256. doi:10.3390/ijms26052256
27. Liu CC, Huang JP. J Formos Med Assoc. 2023;122(7). doi:10.1016/j.jfma.2023.02.004
28. Brown EDL, Obeng-Gyasi B, Hall JE, Shekhar S. Int J Mol Sci. 2023;24(12). doi:10.3390/ijms24129815
29. Pieczyńska J, Grajeta H. J Trace Elem Med Biol. 2015;29. doi:10.1016/j.jtemb.2014.07.003
30. Kuehn B. JAMA. 2018;319(8). doi:10.1001/jama.2018.1291
31. Mills JL, Buck Louis GM, Kannan K, et al. Hum Reprod. 2018;33(3). doi:10.1093/humrep/dex379
32. Panth P, Guerin G, DiMarco NM. Biol Trace Elem Res. 2019;188(1). doi:10.1007/s12011-018-1606-5
33. Stanhiser J, Jukic AMZ, McConnaughey DR, Steiner AZ. Hum Reprod. 2022;37(5). doi:10.1093/humrep/deac027
34. Saldeen P, Saldeen T. Obstet Gynecol Surv. 2004;59(10). doi:10.1097/01.ogx.0000140038.70473.96
35. Nehra D, Le HD, Fallon EM, et al. Aging Cell. 2012;11(6). doi:10.1111/acel.12006
36. Al-Alousi TA, Al-Allak MMA, Aziz AA, Al Ghazali BS. Biomed Pharmacol J. 2018;11(4). doi:10.13005/bpj/1605
37. Abodi M, De Cosmi V, Parazzini F, Agostoni C. Eur J Obstet Gynecol Reprod Biol. 2022;275. doi:10.1016/j.ejogrb.2022.06.019
38. Trop-Steinberg S, Gal M, Azar Y, Kilav-Levin R, Heifetz EM. Heliyon. 2024;10(8):e29324. doi:10.1016/j.heliyon.2024.e29324
39. Schaefer E, Nock D. Clin Med Insights Womens Health. 2019;12. doi:10.1177/1179562x19843868
40. Keen CL, Clegg MS, Hanna LA, et al. J Nutr. Vol 133; 2003. doi:10.1093/jn/133.5.1597s
41. Gunabalasingam S, De Almeida Lima Slizys D, Quotah O, et al. Eur J Clin Nutr. 2023;77(7). doi:10.1038/s41430-022-01232-0

⁺Kim Ross is a paid consultant for Pure Encapsulations.

By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Cortisol: How It Shapes Occasional Anxiety and Mood

1. Introduction
2. Overview of the HPA Axis
3. Spotlight on Cortisol -The Master Stress Hormone
4. Recognizing Symptoms of High Cortisol
5. Pure Encapsulations Nutrient Solutions
6. Conclusion
7. Resources

Introduction

Stress and occasional anxiousness are increasingly common experiences in today's high-demand world. A poll conducted in 2024 by the American Psychiatric Association revealed that 43% of adults in the United States experience increased feelings of anxiousness, with 53% of those polled attributing this feeling to stress.¹ Although short-term stress responses are adaptive and essential for survival, dysregulated stress responses can significantly impact mood and mental clarity. Central to this physiological stress response is the hormone cortisol.

This blog highlights how cortisol, particularly when levels fluctuate, becomes an underlying driver of changes in mood and emotion. It will also provide targeted, evidence-based interventions that healthcare providers may consider for patients experiencing occasional anxiousness due to stress.

Overview of the Hypothalamus-Pituitary-Adrenal (HPA) Axis

The HPA axis is the body's primary neuroendocrine pathway for responding to stress, governed by a multi-layer negative feedback system. Signaling begins in the hypothalamus, which consolidates internal and external signals to determine the overall "threat" to the body. The hypothalamus releases corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in response to a perceived, physical or emotional stressor.

Next, CRH stimulates the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). The pituitary gland comprises the posterior, intermediate and anterior lobes, each responsible for releasing multiple hormones.

Finally, the release of ACTH prompts the adrenal glands to produce cortisol and dehydroepiandrosterone (DHEA) in the adrenal cortex and to release two catecholamines, epinephrine (adrenaline) and norepinephrine (noradrenaline), from the adrenal medulla.

Once the "threat" (stress) is removed, a negative feedback loop reduces CRH and ACTH production, lowering cortisol levels and returning the system to homeostasis.

While this system is adaptive in the short term, chronic activation of the HPA axis leads to sustained cortisol production, as seen in prolonged stress states. Over time, this can impair receptor sensitivity and disrupt the negative feedback loop, resulting in cortisol fluctuation. Long-term, this fluctuation has been associated with emotional lability, poor resilience, fatigue, cognitive fog, increased cytokine production, changes of glycemic control and circadian rhythm disturbances.^2,3

Spotlight on Cortisol: The Master Stress Hormone

Cortisol is a steroid hormone, specifically a glucocorticoid, synthesized in the zona fasciculata of the adrenal cortex. It exerts its effects by binding to glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), which are widely distributed throughout the central nervous system and peripheral tissues.⁴

Cortisol prepares the body for a "fight or flight" response. It increases blood glucose levels, enhances alertness and temporarily suppresses non-essential processes like digestion and reproduction. DHEA, also produced in the adrenal cortex, is a modulating hormone that buffers the effects of increased cortisol.^3,4

Functions of Cortisol

Cortisol plays a vital role in many physiological processes since most cells in the body have glucocorticoid receptors (GRs).²

Diurnal Cortisol Rhythm

Cortisol follows a distinct circadian rhythm governed by the suprachiasmatic nucleus (SCN) of the hypothalamus. This rhythm includes:^2,4

• A sharp increase within 30 – 45 minutes after waking (the cortisol awakening response, or CAR). A healthy cortisol awakening response can cause a 35-60% rapid increase in cortisol production, followed by a decline within 60 minutes.
• A gradual decline continues throughout the day, reaching its lowest point near midnight.

Of importance, cortisol has an inverse relationship with melatonin, commonly called the sleep hormone.

When Cortisol Fluctuates: Its Impact on Mood

When cortisol regulation changes, either through hypersecretion, receptor desensitization or circadian misalignment, the consequences of mood regulation can be profound.

Elevated cortisol patterns have been linked to³:

• Changes of the HPA axis leads to ongoing elevations in cortisol.
• Disruptions in the production of the inhibitory neurotransmitters GABA and serotonin, which are responsible for creating a sense of calmness.
• Changes in brain structure and function, particularly in the area responsible for mood regulation.
• Hypersensitivity to stressors with increased vigilance and threat perception, leading to increased anxious feelings

The Bi-Directional Relationship Between Cortisol and Occasional Anxiety

Prolonged psychological or physiological stress activates the HPA axis, leading to sustained cortisol secretion. The ongoing elevation of cortisol can cause changes to key brain regions involved in mood and emotional regulation, heightening vigilance, worry and symptoms of anxiousness. This state of occasional anxiousness, in turn, acts as a persistent internal stressor, perpetuating further HPA axis activation and continued cortisol release.

The result is a self-reinforcing feedback loop.

Recognizing Symptoms of High Cortisol

Biomarker assessment (e.g., salivary cortisol curve including CAR) may help evaluate diurnal rhythm and identify disruptions. Integrating this data with symptom patterns can help guide personalized nutrition and lifestyle strategies to support healthy HPA axis function.

Pure Encapsulations Nutrient Solutions

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. Research highlights include a significant reduction in perceived stress after 8 weeks of KSM-66^® and a reduction of occasional anxiousness after 4 weeks of Suntheanine^®.^6,7‡

Suggested Dose: Take 1 capsule two times daily, between meals.

Rapid Calm provides rapid-acting support (<1 hour) for occasional anxiety. It combines vitamin B6 with two clinically researched ingredients, Zembrin^®, a patented extract of Sceletium tortuosum, and Suntheanine^® l-theanine, to help moderate feelings of stress and occasional anxiety. This formula is ideal for as-needed relief from occasional everyday stressors. Research highlights that a single dose of 25 mg Zembrin^® reduced perceived anxiety levels and moderated fear responsivity.^{8,9 ‡}

Suggested Use: Take 1 capsule, as needed, with or between meals.

Cortisol Calm combines vitamin D3, Sensoril^® ashwagandha extract, Rhodiola rosea extract, Magnolia officinalis extract and l-theanine to promote relaxation and a healthy cortisol response. It provides support for occasional stress, calm and emotional well-being. Sensoril^® promotes relaxation and a healthy cortisol response as well as the reduction of perceived stress scale score and plasma cortisol and ACTH levels.^{10,11 ‡}

Suggested Use: As a dietary supplement, take 1 capsule in the morning and 1 capsule in the evening, with meals.

Amino Replete contains a blend of free-form amino acids, provided in the ratios found naturally in high biological value (BV) protein sources, made with high-quality vegetarian ingredients. It enhances healthy neurotransmitter synthesis with amino acid precursors to support cognitive function and positive mood.^‡

Suggested Use: As a dietary supplement, take 1 scoop daily, mixed with 8 ounces of water or juice, between meals, or as directed by a health professional.

Conclusion

Cortisol plays a central role in the body's adaptive response to stress, exerting wide-reaching effects on metabolism, immune function, circadian regulation and mood. For healthcare practitioners, understanding the bi-directional relationship between cortisol and mood and the symptoms of high cortisol is essential for comprehensive assessment and early intervention to interrupt the self-reinforcing cycle of stress and anxiousness.

Resources

For additional resources that include diet and lifestyle recommendations for supporting occasional anxiety, refer to the protocols listed below:

Positive Mood Protocol: Designed by our scientific and medical advisors in collaboration with Dr. James Greenblatt to help you deliver the most effective care and support for your patient's mood and emotional well-being.

For more details on the research on the selected nutrient solutions, download the product information sheets:

• Daily Calm
• Rapid Calm
• Cortisol Calm
• Amino Replete

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.

1. 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. Jones C, Gwenin C. Physiol Rep. 2021;8(24):e14644. doi:10.14814/phy2.14644
3. Sic A, Cvetkovic K, Manchanda E, Knezevic NN. Diseases. 2024;12(9):220. doi:10.3390/diseases12090220
4. Guilliams T. Principles and Protocols for Healthcare Professionals. Point Institute; 2018.
5. Azmi NASM, Juliana N, Azmani S, et al. Int J Environ Res Public Health. 2021;18(2). doi:10.3390/ijerph18020676
6. Salve J, Pate S, Debnath K, Langade D. Cureus. Published online 2019. doi:10.7759/cureus.6466
7. Hidese S, Ogawa S, Ota M, et al. Nutrients. 2019;11(10). doi:10.3390/nu11102362
8. Reay J, Wetherell MA, Morton E, Lillis J, Badmaev V. Hum Psychopharmacol. 2020;35(6). doi:10.1002/hup.2753
9. Terburg D, Syal S, Rosenberger LA, et al. Neuropsychopharmacology. 2013;38(13). doi:10.1038/npp.2013.183
10. Auddy B, Hazra J, Mitra A, Abedon B, Ghosal S. Journal of the American Nutraceutical Association. 2008;11(1).
11. Pandit S, Srivastav AK, Sur TK, Chaudhuri S, Wang Y, Biswas TK. Nutrients. 2024;16(9):1293. doi:10.3390/nu16091293

⁺Kim Ross is a paid consultant for Pure Encapsulations.

By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Fueling Focus: Optimizing Acetylcholine for Sharper Attention and Cognitive Performance

1. Introduction
2. Acetylcholine and the Cholinergic System
3. Optimizing Acetylcholine Through Diet and Lifestyle
4. Nutrient Solutions to Optimize Acetylcholine
5. Pure Encapsulations Nutrient Solutions
6. Conclusion
7. Resources

Introduction

Did you know?

• 1 in 25 adults have difficulty maintaining attention and focus.¹
• Nearly half of individuals feel their attention span isn't what it used to be.²

Attention and cognitive performance are fundamental to daily functioning, influencing productivity, learning and decision-making. Unfortunately, focus-related difficulties are increasingly prevalent, affecting individuals across all age groups leading to an upward trend in adults seeking support to improve their focus and concentration. The growing prevalence of digital distractions, stress and inadequate nutrition exacerbates attention-related challenges.

This blog highlights the role of the cholinergic system and acetylcholine optimization in enhancing cognitive performance and sustaining mental clarity through integrative strategies, including nutrition, lifestyle factors and targeted nutrient support. 

Acetylcholine and the Cholinergic System

The cholinergic system is a complex system involved in various peripheral and central nervous functions. Its most significant roles include:^3,4

1)    The transmission of signals across nerve cells for muscle activation, memory, learning, neuronal signaling, synaptic plasticity and sensory processing. 

2)    The synthesis and release of the neurotransmitter acetylcholine (ACh).

Acetylcholine is a primary neurotransmitter that, as the name implies, is synthesized from acetyl-coenzyme A (acetyl CoA) and choline. This neurotransmitter is essential for memory formation, learning and sustained attention. It acts at both nicotinic and muscarinic receptors throughout the brain, particularly in the prefrontal cortex and hippocampus, which are critical for executive function and memory recall.⁴  ACh is broken down into acetate and choline. Choline can then be recycled for use by nerves or can be converted back to phosphatidylcholine, a major component of cellular membranes.^3,4   

Studies show that individuals with higher acetylcholine activity demonstrate superior cognitive flexibility, faster reaction times and enhanced working memory. ^5–7 Conversely, acetylcholine depletion is associated with reduced attention span, slower cognitive processing and impaired recall ability.⁸

Nutrition and Lifestyle Interventions for Acetylcholine Optimization

Several factors can influence acetylcholine levels, including poor dietary intake of choline, lack of physical activity and chronic stress. Given acetylcholine's role in cognitive performance, strategic interventions aimed at preserving and enhancing cholinergic function should be a focus of clinical care.

Consuming foods high in choline is crucial since this nutrient is needed to synthesize acetylcholine. 

Key dietary sources include:

• Egg yolks (one of the highest sources of dietary choline)
• Beef and chicken liver
• Fish (rich in both choline and omega-3s)
• Soybeans and legumes
• Wheat germ and bran
• Vegetables (though smaller amounts compared to animal sources) 

Additionally, a Mediterranean-style diet, abundant in healthy fats, polyphenols, and antioxidant-rich foods, has been linked to improved cognitive performance, memory and executive function.⁹

Regular aerobic and strength exercise supports acetylcholine production by:

1. Increasing brain-derived neurotrophic factor (BDNF), which is directly involved in acetylcholine release and synapse maintenance.¹⁰
2. Increasing the release of nitric oxide (NO), which works synergistically with acetylcholine to enhance vasodilation.¹¹

Clinical Pearl: In older adults, low choline intake is associated with reduced gains in strength and muscle quality during resistance training, suggesting that adequate choline is important for muscle function and possibly acetylcholine-related neuromuscular activities.¹²

Mind-body practices can help promote increased focus, attention and cognitive performance; however, there isn't evidence to suggest a direct impact on acetylcholine production. 

1. Controlled breathing exercises, such as pranayama or diaphragmatic breathing, may help regulate cholinergic signaling, vagal tone and enhance parasympathetic nervous system activity, supporting cognitive clarity.¹³
2. Mindfulness meditation has been shown to enhance attention processing and emotional regulation through improved brain connectivity and neuroplasticity.^14,15
3. Time in nature ("green therapy") may support acetylcholine balance by reducing stress hormones.¹⁶

Clinical Pearl: Engage in physical activity in nature for an extra win!

In the digital age, one of the most pervasive disruptors of focus and cognitive efficiency is the constant influx of notifications, multitasking and screen time. Research indicates that frequent digital interruptions can lead to attention fragmentation, reducing the brain's ability to engage in sustained, deep work.¹⁷

To mitigate these effects, healthcare professionals can recommend structured digital detox strategies, such as: 

• Establishing technology-free blocks during the day
• Turning off notifications
• Using "do not disturb" settings during cognitively demanding tasks
• Implementing screen-free morning and evening routines
• Encouraging periods of boredom, creative play and real-world sensory engagement, such as connecting with others in real life, walking in nature or journaling. 

Nutrient Solutions to Optimize Acetylcholine

Targeted nutrient supplementation offers an evidence-based approach to supporting acetylcholine levels and cognitive function. 

Choline is a direct precursor to acetylcholine, which is involved in attention and cognitive performance. Supplemental and dietary intake is associated with healthy memory, attention and learning. Not all forms of choline may provide the same benefits.^18‡ Research suggests GPC and CDP-choline (citicoline) are bioavailable forms that efficiently cross the blood-brain barrier and support acetylcholine synthesis.¹⁸ Cognizin^®, a patented citicoline, increases choline and phospholipid composition in the brain.¹⁹ Studies in children, middle-aged adults and elderly adults indicate that it supports healthy cognition across a wide age range. In two studies, one involving adolescent boys and another involving middle-aged women, 250-500 mg Cognizin^® citicoline offered statistically significant support for daily mental task performance.^20,21

Acetyl-L-Carnitine (ALC) is an ester of the trimethylated amino acid L-carnitine. It plays a dual role in supporting cognitive function: it facilitates acetyl-CoA uptake to enhance acetylcholine production and supports mitochondrial energy production in neurons. Clinical trials suggest that ALC supplementation promotes mental clarity, reduces brain fog and supports focus in individuals with cognitive fatigue.²²

American Ginseng (Panax quinquefolius) has been shown to modulate acetylcholine release and thereby promote learning and working memory.²³ Its active components, known as ginsenosides, also possess protective properties that moderate oxidative stress-induced changes to cholinergic signaling.²⁴

Phosphatidylcholine: choline is a precursor to phosphatidylcholine, a key phospholipid found in cell membranes and serves as a reservoir for choline needed for acetylcholine synthesis.²⁵ 

Phosphatidylserine is a phospholipid critical for synaptic function and neuronal membrane integrity. Multiple studies indicate that supplementation helps support mental acuity, behavioral and cognitive parameters.^26–28

Omega-3 Fatty Acids: The long-chain omega-3 fatty acids EPA and DHA promote healthy cognition, support the release of neurotransmitters and help protect against oxidative stress. One systematic review concluded that omega-3 fatty acid intake (1-2 grams daily) promoted executive function, word and memory recall and cognitive performance.²⁹ 

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 the health of  your patients.^‡

Rapid Mental Energy is a non-stimulant formula that combines two clinically studied extracts, Alpinia galagna(enXtra) and American ginseng (Cereboost^®), to support alertness and sharpen working memory, without interfering with sleep.^{23,30–33‡}

Suggested Use: Take 1 capsule, as needed, with or between meals. It can be used in combination with caffeine.

Phosphatidylcholine (sunflower) is a phospholipid-bound choline that supports cellular function, cognitive function and liver health. It acts as a precursor for phospholipids and acetylcholine, the neurotransmitter involved in attention, memory and neuromuscular function.^‡

Suggested Use: Take 2 capsules daily, with a meal

CogniPhos contains a blend of clinically researched Cognizin^® citicoline, acetyl-L-carnitine, SharpPS^® phosphatidylserine and cofactors to promote daily cognitive performance and mental sharpness while supporting cellular energy and optimal neuronal function. ^21,27‡

Suggested Use: Take 2 capsules, 1-2 times daily, with meals or as directed by a healthcare professional

O.N.E™ Omega provides 1,000 mg of triglyceride-form EPA/DHA produced through a unique solvent-free, supercritical, CO₂-based extraction method to support a healthy inflammatory response.^‡

Suggested Use: Take 1 capsule daily, with a meal

Conclusion

Acetylcholine is a key neurotransmitter involved in attention regulation, memory formation and cognitive flexibility. Clinicians can provide integrative solutions to support acetylcholine production, including a choline-rich diet, regular physical activity, stress management techniques and key nutrients such as choline, phosphatidylcholine, acetyl-L-carnitine and omega-3 fatty acids to support sharper focus and cognitive performance in their patients. 

Resources

Cognitive Performance Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support for your patient.

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. National Institute of Mental Health. National Institute of Mental Health. Accessed March 26, 2025. https://www.nimh.nih.gov/health/statistics
2. Duffy B, Thain M. The Policy Institute. Published online February 2022.
3. Tizabi Y, Getachew B, Tsytsarev V, et al. In: Acetylcholine - Recent Advances and New Perspectives; 2023. doi:10.5772/intechopen.112447
4. Bekdash RA.Int J Mol Sci. 2021;22(3). doi:10.3390/ijms22031273
5. Newman EL, Gupta K, Climer JR, et al. Front Behav Neurosci. 2012;(JUNE). doi:10.3389/fnbeh.2012.00024
6. Dautan D, Huerta-Ocampo I, Gut NK, et al. Nat Commun. 2020;11(1). doi:10.1038/s41467-020-15514-3
7. Ballinger EC, Ananth M, Talmage DA, Role LW. Neuron. 2016;91(6). doi:10.1016/j.neuron.2016.09.006
8. Decker AL, Duncan K. Curr Opin Behav Sci. 2020;32. doi:10.1016/j.cobeha.2020.01.013
9. Fu J, Tan LJ, Lee JE, Shin S. Front Nutr. 2022;9. doi:10.3389/fnut.2022.946361
10. Wang Q, Cui C, Zhang N, et al. J Orthop Translat. 2024;46:91-102. doi:10.1016/j.jot.2024.03.007
11. Kingwell BA. The FASEB Journal. 2000;14(12). doi:10.1096/fj.99-0896rev
12. Lee CW, Lee T V., Galvan E, et al. Nutrients. 2023;15(18). doi:10.3390/nu15183874
13. Herhaus B. Psychoneuroendocrinology. 2024;160. doi:10.1016/j.psyneuen.2023.106751
14. Calderone A, Latella D, Impellizzeri F, et al. Biomedicines. 2024;12(11):2613. doi:10.3390/biomedicines12112613
15. Prakash RS. Archives of Clinical Neuropsychology. 2021;36(7). doi:10.1093/arclin/acab053
16. Shuda Q, Bougoulias ME, Kass R. Complement Ther Med. 2020;53. doi:10.1016/j.ctim.2020.102514
17. Duke É, Montag C. Addictive Behaviors Reports. 2017;6. doi:10.1016/j.abrep.2017.07.002
18. Kansakar U, Trimarco V, Mone P, et al. Front Endocrinol (Lausanne). 2023;14. doi:10.3389/fendo.2023.1148166
19. Silveri MM, Dikan J, Ross AJ, et al. NMR Biomed. 2008;21(10). doi:10.1002/nbm.1281
20. McGlade E, Locatelli A, Hardy J, et al. Food Nutr Sci. 2012;03(06). doi:10.4236/fns.2012.36103
21. McGlade E, Agoston AM, DiMuzio J, et al. J Atten Disord. 2019;23(2). doi:10.1177/1087054715593633
22. Pennisi M, Lanza G, Cantone M, et al. Nutrients. 2020;12(5). doi:10.3390/nu12051389
23. Scholey A, Ossoukhova A, Owen L, et al. Psychopharmacology (Berl). 2010;212(3). doi:10.1007/s00213-010-1964-y
24. Zhu Y, Wang Z, Yu S, et al. Molecules. 2022;27(22):7824. doi:10.3390/molecules27227824
25. Tan W, Zhang Q, Dong Z, et al. J Agric Food Chem. 2020 Dec 16;68(50):14884-14895. doi: 10.1021/acs.jafc.0c06383.
26. Hirayama S, Terasawa K, Rabeler R, et al. Journal of Human Nutrition and Dietetics. 2014;27(SUPPL2). doi:10.1111/jhn.12090
27. Kato-Kataoka A, Sakai M, Ebina R, et al. J Clin Biochem Nutr. 2010;47(3). doi:10.3164/jcbn.10-62
28. Richter Y, Herzog Y, Lifshitz Y, et al. Clin Interv Aging. 2013;8. doi:10.2147/CIA.S40348
29. Dighriri IM, Alsubaie AM, Hakami FM, et al. Cureus. Published online 2022. doi:10.7759/cureus.30091
30. Shin K, Guo H, Cha Y, et al. Regulatory Toxicology and Pharmacology. 2016;78. doi:10.1016/j.yrtph.2016.04.006
31. Bell L, Whyte A, Duysburgh C, et al. Eur J Nutr. 2022;61(1). doi:10.1007/s00394-021-02654-5
32. Ossoukhova A, Owen L, Savage K, et al. Hum Psychopharmacol. 2015;30(2). doi:10.1002/hup.2463
33. Srivastava S, Mennemeier M, Pimple S. J Am Coll Nutr. 2017;36(8). doi:10.1080/07315724.2017.1342576

⁺Kim Ross is a paid consultant for Pure Encapsulations.

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
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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
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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