By Amy Doyle, MS, CNS⁺

Supporting Motility and Bowel Regularity: A Step-by-Step Approach

1. Introduction
2. Step One: Foundational Assessments and Identification of Subtype
3. Step Two: Investigation of Key Drivers
4. Step Three: Individualized Care
5. Step Four: Track Outcomes and Adjust
6. Pure Encapsulations® Nutrient Solutions
7. Conclusion
8. Resources

Introduction

Altered gastrointestinal motility is one of the most prevalent symptoms of functional bowel GI concerns encountered in clinical practice.¹ Despite its frequency, altered motility remains challenging to address due to its heterogeneity and the influence of gut–brain interactions.

A clinically useful lens for understanding motility concerns involves shifting the focus from symptom suppression to addressing physiology across multiple systems, including digestion, absorption, immune signaling, barrier integrity, microbial ecology and neuroendocrine regulation.

Patient care can differ significantly depending on the patient’s predominant clinical presentation: occasional diarrhea, occasional constipation or mixed bowel patterns - primarily occasional constipation with intermittent episodes of diarrhea.

Rather than being defined by structural changes, motility-related functional bowel concerns are characterized by symptom clusters that reflect shifts not only in motility but also potentially in other core physiological processes, including²:

• Visceral sensitivity
• Mucosal or immune activation patterns
• Changes within the gut microbial ecosystem
• Alterations in central nervous system processing influencing digestive function

This blog outlines a stepwise care strategy to support your decision-making in practice.

Step One: Foundational Assessments and Identification of Subtype

Functional bowel GI concerns can share similar clinical patterns with other health concerns.³ The first step is to perform a comprehensive functional assessment to confirm that the patient’s symptoms are not due to structural changes, non-beneficial microbial exposure or underlying metabolic, enzymatic or molecular contributors.⁴ Additional indications that advanced assessments may be needed include, but are not limited to, unintended weight loss, nocturnal symptoms, changes in iron levels, symptom onset after age 50 and family history.⁴

Step Two: Investigation of Key Drivers

While no single causative factor has been isolated for functional bowel GI concerns, several key drivers have been identified.

Additional assessments can help uncover contributors and support a personalized plan of care. For more information about foundational and supplemental assessments, refer to our Functional Bowel GI Health Protocol^‡.

Step Three: Individualized Care

Unique dietary triggers, stress, mood, sleep and exercise can strongly impact symptom levels, making nutrition, lifestyle and targeted supplementation essential components of care.¹⁰

Nutrition directly influences microbial fermentation, motility, immune signaling and epithelial integrity, making it foundational to supporting motility.⁹ For example:

• Occasional diarrhea: A short-term low-FODMAP diet can reduce fermentative load, osmotic activity and gas production, often improving stool urgency and frequency.¹¹
• Occasional constipation: Gradual introduction of soluble fiber supports stool hydration and colonic transit without excessive mechanical irritation.

Dietary changes should be used therapeutically and often temporarily, with structured reintroduction to prevent unnecessary restriction, nutrient depletions and unfavorable microbiome changes.

To explore more dietary strategies that support motility and bowel regularity, refer to our Functional Bowel GI Health Protocol^‡.

Lifestyle considerations include acknowledging stress, mood and the gut-brain connection. Patients with functional bowel GI concerns often present with a broad range of somatic concerns—such as fatigue, sleep disturbances, diffuse musculoskeletal discomfort and cardiopulmonary sensations—that may arise in the absence of identifiable structural changes.¹² Patterns of mood disturbance, including low mood, occasional anxiety and somatic preoccupation can influence how patients process and respond to visceral and extraintestinal signals.¹³

Any stress-management technique that supports physiological downregulation and enhances the body’s relaxation response can help patients feel more empowered in managing their symptoms and can promote greater parasympathetic activity.

Targeted nutraceutical support also differs depending on subtype but should focus on supporting digestion, microbial balance, intestinal barrier integrity and function, cytokine balance and motility.

Step Four: Track Outcomes and Adjust

Clinical outcomes should be tracked for 4-6 weeks at a time and include:

• Stool frequency and form (Bristol scale)
• Abdominal discomfort
• Bloating and gas
• Urgency or incomplete evacuation
• Sleep quality
• Energy levels
• Cycle-related symptom shifts (in women)

Structured dietary and supplement recommendations should be adjusted every 8-12 weeks, based on your patient’s response to care. Laboratory assessments can be completed every 3-6 months as necessary.

Ongoing assessment and refinement of diet, lifestyle and supplement strategies ensure that care remains responsive to changing clinical needs. Compassionate, individualized guidance can help patients build greater resilience, improve daily functioning and experience meaningful progress over time.

Pure Encapsulations Nutrient Solutions

PureGG 25B contains Lactobacillus rhamnosus GG, which is well known for its favorable effects on bowel function, particularly abdominal comfort, bowel motility and occasional diarrhea.^‡
Suggested Dose: 1 capsule daily, with or between meals

Epi-Integrity Powder promotes healthy modulation of mucosal immune responses to support GI integrity in a great-tasting powder.^‡
Suggested Dose: 1 scoop, 1-2 times daily. Add 1 serving to 8 oz of water or juice. Shake or stir until dissolved.

Conclusion

Altered gastrointestinal motility requires a personalized, systems-based approach—one that moves beyond symptom suppression to address the interconnected physiological processes that shape digestive function. By identifying each patient’s predominant symptom pattern, investigating key drivers and applying targeted nutrition, lifestyle and supplement strategies, clinicians can create highly individualized care plans that meaningfully reduce symptom burden and improve daily functioning.^‡

Resources

For more comprehensive recommendations on supporting functional bowel concerns, refer to:

• Functional Bowel GI Health Protocol^‡
• Barrier Builders: Nutrients to Support Mucosal Immune Responses and the Intestinal Barrier
• Unraveling the Complexity of Functional GI Concerns: Understanding Types, Causes and Solutions
• Is It a Leaky Gut? Defining What Lurks Beneath a Patient’s Symptoms
• Nutrient Solutions to Complement the 5R Protocol: A Comprehensive Approach to Maintaining Gut Health

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

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

1. Bharucha AE, et al. Mayo Clin Proc. 2016 Aug;91(8):1118 1132
2. American Gastroenterological Association. Accessed February 9, 2026
3. Chen M, Ruan G, Chen L et al. Front Endocrinol (Lausanne). 2022;13:817100. doi:10.3389/fendo.2022.817100.
4. Lacy BE, Pimentel M, Brenner DM et al. Am J Gastroenterol. 2021;116(1):17 44. doi:10.14309/ajg.0000000000001036.
5. Schiller LR. Cleve Clin J Med. 2020;87(8):501 507. doi:10.3949/ccjm.87a.19102.
6. Su Q, Tun HM, Liu Q, et al. Gut Microbes. 2023;15(1):2157697. doi:10.1080/19490976.2022.2157697
7. Jeffery IB, Das A, O'Herlihy E, et al. Gastroenterology. 2020;158(4):1016-1028.e8. doi:10.1053/j.gastro.2019.11.301
8. Pozuelo, M., Panda, S., Santiago, A. et al. Sci Rep 5, 12693 (2015). https://doi.org/10.1038/srep12693
9. Robles A, Perez Ingles D, Myneedu K, et alNeurogastroenterol Motil. 2019;31(12):e13718. doi:10.1111/nmo.13718
10. Radziszewski M, Smarkusz Zarzecka J, Ostrowska L. Nutrition, 2023;15(16):3662. Available from: https://www.mdpi.com/2072-6643/15/16/3662
11. Varjú P, Farkas N, Hegyi P, et al. PLoS One. 2017;12(8):e0182942. Published 2017 Aug 14. doi:10.1371/journal.pone.0182942
12. Ohlsson B. Ther Adv Gastroenterol. 2022;15. doi:10.1177/17562848221114558
13. Grover M, Kolla B, Pamarthy R, Mansukhani M. et al. PLoS One. 2021;16. doi:10.1371/journal.pone.0245323.
14. Guandalini et al. J Pediatr Gastroenterol Nutr, 2000:30(1), 54-60.

⁺Amy Doyle, MS, CNS is an employee of Pure Encapsulations.

By Kim Ross, DCN, CNS, LDN, IFMCP⁺

How to Evaluate Suspected Histamine Intolerance

1. Introduction
2. What is Histamine?
3. What is Histamine Intolerance?
4. Six Evaluation Techniques
5. Pure Encapsulations® Nutrient Solutions
6. Conclusion
7. Resources

Introduction

Self-reported food intolerances, including histamine intolerance, affect between 15-20% of individuals.¹ A challenge clinicians face is that patients can experience a wide range of symptoms, often mimicking food allergies or other health concerns, compounded by the lack of a validated diagnostic test for a histamine intolerance.¹ Current guidelines therefore emphasize a careful history, exclusion of other causes and a structured dietary “test and retest” approach.^1,2

This blog will describe histamine and histamine intolerance and focus on six evaluation techniques to employ when you suspect a patient has a histamine intolerance.

What is Histamine?

Histamine is a bioactive amine that is synthesized from the amino acid histidine. It is primarily synthesized and stored in basophils and mast cells, as well as within cells of the gastrointestinal tract, lymph nodes and thymus.

The two main pathways by which it is metabolized involve the enzymes diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT). Intestinal DAO is a class of enzymes that helps eliminate histamine from the body, specifically histamine ingested from food.

Histamine is involved in many functions of the body, including multiple immune mechanisms, cytokine production and neurotransmission.³

What is Histamine Intolerance?

Histamine intolerance (HIT) is a practical label clinicians use to describe the accumulation of histamine at a rate that exceeds the body’s ability to eliminate it.4 As a result, patients with a histamine intolerance may report a repeatable group of symptoms after eating histamine-rich foods, such as wine, cheese, spinach, fermented foods, some fish and meat.⁴

Because histamine receptors are widely distributed, symptoms can span multiple systems and may include, but are not limited to^1–3:

• Abdominal discomfort
• Occasional constipation or diarrhea
• Bloating
• Dizziness
• Headaches
• Nasal congestion and sneezing
• Flushing
• Itchy skin
• Skin rashes

Six Evaluation Techniques

1. Track the Symptom Pattern and Timing

Pattern recognition is an important evaluation technique. The first step is to encourage patients to track symptoms in relation to meals and timing. If symptoms occur within 20-30 minutes and resolve within a few hours, a histamine-related mechanism becomes more plausible.³

Ask your patients to track:

• Their symptoms, rating scale and frequency as accurately as possible
• The time from first bite to the onset of the symptoms, as well as the time to resolution
• Co-factors that may worsen symptoms, such as alcohol, exercise, heat, poor sleep and stress. Alcohol can interfere with histamine degradation.²

2. Identify Exposure Sources and Amplifiers

Histamine content of food varies greatly with maturity, storage time and processing. Some patients tolerate foods when fresh but react when aged or eaten as leftovers, suggesting it could be more about the way the food is aged or prepared rather than the food itself.⁵ Histamine content increases as food ripens and in leftovers.

Cooking methods also can alter histamine levels. For example, grilled seafood has higher histamine levels over raw or boiled seafood, while boiling helps decrease histamine levels.⁶

Therefore, as your patients track foods and symptoms, it is beneficial to also have them notate how the food was cooked, prepared and stored.

3. Review Medications and Decide When to Refer to a Specialist

Review a patient’s medications, both prescribed and over the counter, as some inhibit the function of the DAO enzyme.^2,4 This may also rule out high-histamine foods as the potential culprit.

Refer to a specialist if there is a history of anaphylaxis, airway symptoms, decrease in blood pressure or other rapidly progressive symptoms. For chronic conditions, refer to a specialist when there are unexplained changes in symptoms such as weight loss or persistent fevers. These symptoms may be indicative of a more serious issue.

4. Work the Differential on Purpose

Guidelines recommend ruling out alternative explanations before labeling symptoms as histamine related.² If it is within your scope of practice, it can be helpful to rule out food or environmental allergies, malabsorption concerns or other reasons mast cell activation may be present. If diagnostics are not within your scope of practice, refer accordingly.

5. Use Testing Strategically and Set Expectations

Patients may expect a definitive “histamine test.” Despite the availability of some testing options, these can produce false negatives and generally have low sensitivity and specificity.⁵ The 2021 guideline states there is no reliable procedure or test to confirm adverse reactions to ingested histamine, and determination must be made based on symptoms after other causes are excluded.² Testing for genetic polymorphisms that encode the DAO enzyme has the potential to uncover the genetic etiology of histamine intolerance.³

6. The Most Practical Evaluation Tool: A Structured Diet Trial and Re-challenge

Because biomarkers are limited, a time-limited histamine-reduced trial followed by systematic reintroduction is the most actionable evaluation tool.^2,4,7 Rather than promoting generalized or highly restrictive food lists, it is recommended to personalize food restrictions and emphasize nutrient optimization. Inform your patients that the goal is to identify patterns that influence symptoms and minimize unnecessary restriction.

• Baseline 7 days: During this time, have the patient follow their usual diet while keeping a diary as detailed in steps 1-2 above (food, timing, symptoms, stress, sleep, alcohol).
• Histamine-reduced/avoidance trial: For up to 4 weeks, emphasize fresh foods and minimize the foods, sources or amplifiers the patient identified in steps 1-2. Keep the diet broad for nutrient adequacy.
• Re-challenge: Reintroduce smaller and larger portions of one histamine-rich food category at a time over the next 1-6 weeks, notating any adverse reactions and frequency of symptoms if they return.

If symptoms improve and recur with re-challenge, shift from restriction to tolerance building and address amplifiers (food storage habits, alcohol, sleep, stress). If there is no meaningful change, revisit the differential rather than tightening the diet indefinitely.

Pure Encapsulations Nutrient Solutions

DAO Enzyme: An estimated 1-3% of the population cannot digest dietary histamine efficiently, often because of low intestinal diamine oxidase (DAO), an enzyme in the gastrointestinal (GI) tract that normally breaks down histamine.³ Supplementation with DAO enhances DAO activity in the GI tract, promoting breakdown of dietary histamine and reducing gastrointestinal discomfort (e.g., occasional diarrhea, bloating and gas) associated with sensitivity to histamine-rich foods.⁸ DAO may also reduce skin symptoms associated with high intestinal histamine levels.^9‡

Suggested Dose: As a dietary supplement, take 1 capsule, 2-3 times daily with meals or as directed by a healthcare professional.

Hist Reset: This formula promotes healthy mast cell stabilization and supports healthy histamine metabolism. Quercetin, luteolin and rutin are flavonoids known to exhibit antioxidant and immune modulating activity.^10–12 Bromelain supports healthy T-cell function and cytokine production.¹³ Riboflavin, niacinamide and molybdenum are included as cofactors for aldehyde dehydrogenase, a key enzyme in the breakdown of histamine. Preliminary research suggests that supplementation with vitamin C modulates bronchial responsiveness to histamine in sensitive subjects.14 Optimal vitamin C serum levels have been associated with lower blood histamine levels.¹⁵ NAC promotes immune and lung defense through mucolytic and antioxidant actions. It acts as a free radical scavenger by supporting glutathione production.^16‡

Suggested Use: As a dietary supplement, take 2 capsules daily, between meals or as directed by a healthcare professional.

Seeking medical advice from a professional may be appropriate for managing more serious symptoms and/or cases. Dietary supplements are not intended to replace the use of medications or alternative treatment.

Conclusion

Suspected histamine intolerance is best approached as a clinical pattern recognition problem. Because symptoms can overlap with food allergy, malabsorption concerns and other drivers of mast cell activation, your most valuable tools for assessment include a detailed history, intentional differential thinking and a structured “test and retest” plan that links symptoms to specific exposures and co-factors. When you guide patients to track timing, preparation methods, storage habits, alcohol intake, stress and sleep, you often uncover that the issue is not simply the food itself, but rather the combination of histamine load and the rate of histamine clearance that varies day to day.

With this structured approach, supportive tools such as meal-timed DAO and targeted antioxidant and flavonoid blends can be positioned as adjuncts within an individualized plan, while keeping the focus on sustainable dietary patterns, realistic next steps and appropriate referral when red flags are present.

Resources

For additional information, including diet and lifestyle recommendations for supporting histamine intolerance, refer to the resources listed below:

Histamine Intolerance Protocol^‡: Designed by our scientific and medical advisors to help you deliver the most effective care and support histamine intolerance.

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

• DAO Enzyme
• Hist Reset

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

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

1. Jackson K, Busse W, Gálvez-Martín P, Terradillos A, Martínez-Puig D. Int J Mol Sci. 2025;26(18). doi:10.3390/ijms26189198
2. Reese I, Ballmer-Weber B, Beyer K, et al. Allergologie. 2021;44(10). doi:10.5414/ALX02269
3. Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Biomolecules. 2020;10(8). doi:10.3390/biom10081181
4. Jochum C. Nutrients. 2024;16(8). doi:10.3390/nu16081219
5. Eade G. J Evol Health. 2018;2(1). doi:10.15310/2334-3591.1054
6. Chung BY, Park SY, Byun YS, et al. Ann Dermatol. 2017;29(6). doi:10.5021/ad.2017.29.6.706
7. Rentzos G, Weisheit A, Ekerljung L, van Odijk J. Eur J Clin Nutr. 2024;78(8). doi:10.1038/s41430-024-01448-2
8. Schnedl WJ, Schenk M, Lackner S, Enko D, Mangge H, Forster F. Food Sci Biotechnol. 2019;28(6). doi:10.1007/s10068-019-00627-3
9. Yacoub MR, Ramirez GA, Berti A, et al. Int Arch Allergy Immunol. 2018;176(3-4). doi:10.1159/000488142
10. Kimata M, Shichijo M, Miura T, Serizawa I, Inagaki N, Nagai H.Clinical and Experimental Allergy. 2000;30(4). doi:10.1046/j.1365-2222.2000.00768.x
11. Weng Z, Zhang B, Asadi S, et al. PLoS One. 2012;7(3). doi:10.1371/journal.pone.0033805
12. Theoharides TC, Stewart JM, Hatziagelaki E. Front Neurosci. 2015;9(JUN). doi:10.3389/fnins.2015.00225
13. Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R. Biomed Rep. 2016;5(3). doi:10.3892/br.2016.720
14. Bucca C, Rolla G, Oliva A, Farina JC. Ann Allergy. 1990;65(4).
15. Johnston CS, Solomon RE, Corte C. J Am Coll Nutr. 1996;15(6). doi:10.1080/07315724.1996.10718634
16. Raghu G, Berk M, Campochiaro PA, et al. Curr Neuropharmacol. 2020;19(8). doi:10.2174/1570159x19666201230144109

⁺Dr. Ross is a paid consultant for Pure Encapsulations.

By Kim Ross, DCN, CNS, LDN, IFMCP⁺

Evidence-Based Strategies for Clinicians: Addressing the Four Key Factors of Sleep Disturbances

1. The Importance of Sleep for patients
2. The Four Underlying Factors of Sleep Disturbances
3. Sleep Interventions
4. Pure Encapsulations Nutrient Solutions
5. Conclusion
6. Resources

The Importance of Sleep

Sleep is not a passive state. It is an active period of metabolic regulation, memory consolidation, immune signaling and cellular repair. Insufficient sleep has been associated with impaired glucose tolerance, reduced insulin sensitivity, altered cytokine signaling, decreased cognitive performance and increased vulnerability to mood changes.^1–3

Humans should spend an average of one-third of their lives asleep; however, 50-70 million Americans suffer from chronic sleep disturbances.⁴ According to the Centers for Disease Control, approximately 35% of adults in the U.S. report sleeping fewer than seven hours per night. Of concern, about 40-50% of your patients are likely to report significant sleep disturbances.⁵

Improving sleep enhances resilience to stress, improves emotional regulation and supports mood stability and should be considered a nonnegotiable intervention for your patients.⁶ This blog will focus on the four underlying causes of sleep disturbances and provide practical tips to help your patients achieve restorative sleep.

The Four Underlying Factors of Sleep Disturbances

Circadian Rhythm Dysregulation

Circadian rhythms are daily cycles that regulate everything from body temperature to hormone levels. They’re primarily controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus. The SCN is a tiny region of nerve cells that uses light information from the retina to synchronize our internal clocks with the outside world. Among its functions, the SCN modulates body temperature, cortisol rhythm, melatonin secretion and sleep timing.⁷ The SCN has two main clocks: a central one that controls sleep and wake cycles, and an external one that is synchronized with the environment. These two clocks work together to help us fall and stay asleep at night and wake up in the morning.

Glycemic Control

Maintaining stable blood glucose and supporting healthy insulin sensitivity are important for promoting uninterrupted, restorative sleep. Fluctuations in glucose, particularly in the evening, can trigger nocturnal dips and trigger a cortisol response that increases nighttime waking and reduces sleep efficiency.

Stress

Stress is an adaptive physiological response intended to maintain homeostasis by activating the hypothalamic-pituitary-adrenal (HPA) axis and releasing cortisol.

Psychological stress and pre-sleep cognitive arousal are among the most common contributors to fragmented sleep and delayed sleep onset. Healthcare providers often focus on supplements or sleep hygiene first, but addressing stress physiology and mental load may produce the most meaningful improvements for some patients.

• Rumination
• Worry about next-day tasks
• “Mental clutter”
• Difficulty disengaging from work, caregiving or digital stimuli

Together, these factors create a state known as pre-sleep cognitive arousal, which interferes with sleep onset and/or sleep efficiency.

Poor Sleep Hygiene Practices

Sleep hygiene is often misunderstood as basic advice. In reality, it is a targeted set of environmental and behavioral strategies that strengthen the circadian signal, reduce nighttime arousal and improve sleep efficiency.

Four Underlying Factors of Sleep Disturbances^8–15

Other Root Causes of Sleep Disruptions

Sleep Interventions

To determine the best intervention, begin with a clinical assessment of sleep that considers both sleep onset (how long it takes to fall asleep) and sleep efficiency (the proportion of time in bed that is spent asleep). Additionally, take the time to uncover the root cause(s) of your patients’ sleep disturbances.

Realigning Circadian Rhythm

Light exposure remains the primary synchronizer of the circadian rhythm. Research reinforces that both timing and spectral quality of light matter.^16,17

• Adequate daytime (especially morning) light exposure supports more robust circadian entrainment, reduced sleep latency and improved subjective sleep quality.
• Evening or pre-bed exposure to bright or blue-enriched light is associated with delayed sleep onset, reduced sleep quality and poorer next-day alertness.

For individuals with shift work or irregular schedules, strategic light management (bright light during wake periods; dim or filtered light before sleep) can partially re-align the circadian system and mitigate some of the metabolic and sleep-related risks associated with misalignment.¹⁸

Restoring Glycemic Control and Enhancing Dietary Intake

Dietary patterns play a meaningful role in sleep quality, circadian stability and next-day energy regulation. Address one or more of the following dietary factors with your patients, as needed.

Managing Stress

Clinicians sometimes feel uncertain about initiating stress management counseling. It is important to acknowledge and normalize the stressors patients experience. Rather than focusing on excluding or reducing stress, consider strategies to help your patients manage the stress they have.

There are many stress management techniques to consider, so work with your patient to determine which strategies are easiest for them to implement.

Stress Management Strategies to Support Sleep^25–27

Improving Sleep Hygiene Practices

Most sleep hygiene practices, properly applied, are a high-yield, low-risk intervention set.

Pure Encapsulations Nutrient Solutions

Circadian Rhythm and Sleep Support

Melatonin supports the body’s natural sleep cycle^‡ and helps facilitate the onset of sleep, as well as promotes sleep efficiency^‡.²⁹ Available options include Melatonin 0.5 mg, Melatonin-SR, Melatonin 3 mg and Melatonin liquid 30 ml

Suggested Dose: Melatonin 0.5 mg, Melatonin-SR and Melatonin 3 mg: 1 capsule, 30-60 minutes before bedtime; Melatonin Liquid: 1 ml (full dropper), 30-60 minutes before bedtime

Melatonin Dosing: Clinical use of supplemental melatonin ranges widely depending on the intended use. For sleep, doses of 0.3-3 mg are the most studied, with a consensus to start low and increase the nightly dose as needed.²⁹

Pure Sleep is for patients requesting a melatonin-free product to promote sleep quality^‡. Pure Sleep combines Suntheanine^® along with three clinically studied botanical extracts, KSM-66^® ashwagandha, valerian root and Affron^® saffron, to help patients fall asleep, stay asleep and experience the restorative, restful sleep they need without morning grogginess.

Suggested Use: 2 capsules, 30-60 minutes before bedtime

Best Rest Formula contains valerian, passionflower, chamomile, lemon balm and hops, which act to calm and relax the central nervous system; melatonin to facilitate the onset of sleep and promote sleep efficiency; and GABA and l-theanine to promote alpha wave production in the brain, an indication of relaxation.^29–32

Suggested Use: 2 capsules, 30-60 minutes before bedtime

Glucose Regulation Support

Metabolic Xtra provides a combination of nutrients to support healthy glucose metabolism and insulin receptor function and signaling^‡. It contains 350 mg berberine HCl per capsule, which has been shown to provide statistically significant support for healthy glucose and lipid metabolism.³³

Suggested Use: 1 capsule, 1-3 times daily, with meals

Occasional Stress Support

Daily Stress Formula is a blend of botanicals, herbs and other nutrients that supports the body’s resilience when faced with occasional stress.^‡ Chamomile and lemon balm promote calmness and relaxation^‡, rhodiola supports physical and mental stress^‡, and Eleutherococcus senticosus is an adaptogen that helps bolster adrenal function and stress resilience^‡.

Suggested Use: 3 capsules daily, with or between meals

Cortisol Calm promotes relaxation and healthy cortisol response^‡, may support healthy sleep, positive mood and cognitive function^‡ and provides support for occasional stress, calm and emotional well-being^‡. This formula contains vitamin D and a blend of herbal extracts, including Sensoril ashwagandha, rhodiola, magnolia and l-theanine.^‡.

Suggested Use: 1 capsule in the morning and 1 capsule in the evening, with meals

Conclusion

Sleep disturbances are common and often driven by four core factors: circadian rhythm disruption, glycemic changes, occasional stress and mental overload, and poor sleep hygiene. By addressing these root contributors through light exposure, nutrition, stress management and targeted lifestyle changes, clinicians can help patients achieve more restorative, resilient sleep.

Resources

For additional information, including diet and lifestyle recommendations for supporting optimal sleep, refer to the resources listed below:

Protocols:

• Sleep Protocol^‡: Designed by our scientific and medical advisors to help you deliver the most effective care and support for sleep.
• Emotional Wellbeing Protocol^‡: Designed by our scientific and medical advisors to help you deliver the most effective care and support for emotional wellbeing.

Webinar:

• “Optimizing Restful Sleep: Strategies and Tips for Supporting Overall Sleep Quality^‡,” presented by Peter Bongiorno, ND

Blogs:

• Reducing Mental Load: Practical Tips to Help Patients Declutter Their Minds
• Cortisol: How It Shapes Occasional Anxiety

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

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. Pinheiro MC, Costa HE, Mariana M, Cairrao E. Endocrines. 2025;6(4):49. doi:10.3390/endocrines6040049
2. Banks S, Dinges DF. . Journal of Clinical Sleep Medicine. 2007;3(5). doi:10.5664/jcsm.26918
3. Garbarino S, Lanteri P, Bragazzi NL, Magnavita N, Scoditti E. . Commun Biol. 2021;4(1). doi:10.1038/s42003-021-02825-4
4. Patel AK, Reddy V, Araujo JF. StatPearls [Internet]. 2020;3(Stage 3).
5. Benca RM, Bertisch SM, Ahuja A, Mandelbaum R, Krystal AD. . J Clin Med. 2023;12(7):2498. doi:10.3390/jcm12072498
6. Lo Martire V, Berteotti C, Zoccoli G, Bastianini S. . Curr Sleep Med Rep. 2024;10(1). doi:10.1007/s40675-024-00274-z
7. Kvetnoy I, Ivanov D, Mironova E, et al.. Int J Mol Sci. 2022;23(3):1835. doi:10.3390/ijms23031835
8. Steele TA, St Louis EK, Videnovic A, Auger RR. Neurotherapeutics. 2021;18(1). doi:10.1007/s13311-021-01031-8
9. Reid KJ, Abbott SM Sleep Med Clin. 2015;10(4):523-535. doi:10.1016/j.jsmc.2015.08.006
10. Depner CM, Melanson EL, Eckel RH, et al. Current Biology. 2019;29(6):957-967.e4. doi:10.1016/j.cub.2019.01.069
11. Yang Y, Zhao L hua, Li D dan, et al. Diabetol Metab Syndr. 2021;13(1):102. doi:10.1186/s13098-021-00720-w
12. Ring M. . Am J Med. 2025;138(10):1451-1463. doi:10.1016/j.amjmed.2025.05.044
13. Guidi J, Lucente M, Sonino N, Fava GA. . Psychother Psychosom. 2021;90(1). doi:10.1159/000510696
14. Knezevic E, Nenic K, Milanovic V, Knezevic NN. Cells. 2023;12(23). doi:10.3390/cells12232726
15. McEwen BS, Akil H. Journal of Neuroscience. 2020;40(1). doi:10.1523/JNEUROSCI.0733-19.2019
16. Didikoglu A, Mohammadian N, Johnson S, et al. . Proc Natl Acad Sci U S A. 2023;120(42). doi:10.1073/pnas.2301608120
17. Siraji MA, Spitschan M, Kalavally V, Haque S. Sci Rep. 2023;13(1). doi:10.1038/s41598-023-39636-y
18. Zhao C, Li N, Miao W, He Y, Lin Y. . Sci Rep. 2025;15(1). doi:10.1038/s41598-024-83789-3
19. Lin YS, Weibel J, Landolt HP, et al. Front Nutr. 2022;8. doi:10.3389/fnut.2021.787225
20. Ebrahim IO, Shapiro CM, Williams AJ, Fenwick PB. Alcohol Clin Exp Res. 2013;37(4). doi:10.1111/acer.12006
21. Lyons PM, Truswell AS. American Journal of Clinical Nutrition. 1988;47(3). doi:10.1093/ajcn/47.3.433
22. Lindseth G, Lindseth P, Thompson M. West J Nurs Res. 2013;35(4). doi:10.1177/0193945911416379
23. Lindseth G, Murray A. West J Nurs Res. 2016;38(8). doi:10.1177/0193945916643712
24. Saidi O, Rochette E, Del Sordo G, et al. Nutrients. 2022;14(24). doi:10.3390/nu14245299
25. Morrison AB, Richmond LL. . Cogn Res Princ Implic. 2020;5(1). doi:10.1186/s41235-019-0201-4
26. Zaccaro A, Piarulli A, Laurino M, et al. Front Hum Neurosci. 2018;12. doi:10.3389/fnhum.2018.00353
27. Meneo D, Curati S, Russo PM, Martoni M, Gelfo F, Baglioni C. Clocks Sleep. 2024;6(3). doi:10.3390/clockssleep6030031
28. Chevance G, Minor K, Vielma C, et al. Sleep Med Rev. 2024;75. doi:10.1016/j.smrv.2024.101915
29. Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Nutrients. 2022;14(19). doi:10.3390/nu14193934
30. Kimura K, Ozeki M, Juneja LR, Ohira H. Biol Psychol. 2007;74(1). doi:10.1016/j.biopsycho.2006.06.006
31. Yoto A, Murao S, Motoki M, et al. Amino Acids. Published online 2012. doi:10.1007/s00726-011-1206-6
32. Kenda M, Kočevar Glavač N, Nagy M, Sollner Dolenc M. Molecules. 2022;27(18). doi:10.3390/molecules27186021
33. Zhang Y, Li X, Zou D, et al. Journal of Clinical Endocrinology and Metabolism. 2008;93(7). doi:10.1210/jc.2007-2404

⁺Dr. Ross is a paid consultant for Pure Encapsulations.

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
17. Garner TB, Hester JM, Carothers A, Diaz FJ. Biol Reprod. 2021;104(5). doi:10.1093/biolre/ioab023
18. Grieger JA, Grzeskowiak LE, Wilson RL, et al. Nutrients. 2019;11(7). doi:10.3390/nu11071609
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
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⁺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.