By Amy Doyle, MS, CNS⁺

Putting Pep in Their Step: Supporting Patients with Age-Related Muscle Decline

1. Introduction
2. How Muscle Mass and Strength Change with Age
3. The Mitochondria’s Role in Muscle Health
4. Exercise and Nutrition Interventions for Age-Related Muscle Decline
5. Nutrients to Support Age-Related Muscle Decline
6. Pure Encapsulations® Nutrient Solutions
7. Summary
8. Resources

Introduction

Skeletal muscle is the predominant tissue in the human body, comprising 40% of overall body weight.¹ We rely on our skeletal muscle for numerous physiological functions including movement, maintaining posture, generating force, metabolism and respiration.¹

As people age, so do their skeletal muscles.

How Muscle Mass and Strength Change with Age

Age-related muscle decline can begin at age 30.³ More pronounced in sedentary individuals, muscle mass can be lost at a rate of 1% per year.² Loss of muscle mass can also be accompanied by atrophy of muscle fibers and reduced muscle function and strength. This gradual decrease can progress, with an individual losing up to one-third of their muscle mass by age 80.²

Loss of muscle mass and strength in older individuals could contribute to fall risk, reduced mobility, loss of independence, and ability to perform daily functions.²

The Mitochondria’s Role in Muscle Health

Skeletal muscle is a tissue with high energy demands and mitochondria are primarily responsible for meeting this demand. Mitochondria not only power muscle contraction by supplying ATP, they also undertake other critical functions, including moderating intracellular calcium, cell proliferation, apoptotic signaling, regulation of redox states and immune response.³

Well-functioning mitochondria are essential for maintaining cellular homeostasis and muscle health. Cellular mitochondrial health is maintained by growing the mitochondrial pool through mitochondrial biogenesis, through preserving fusion and fission and by ensuring the removal of altered mitochondria through mitophagy.

Mitophagy is a selective autophagy process that serves as the mitochondria’s own quality-control mechanism and involves removing and recycling altered mitochondria.⁴ Mitophagy helps preserve only healthy mitochondria for the mitochondrial pool.

Just as skeletal muscle function can change as the human body ages, mitochondria are also subject to the effects of aging, as shown in the illustration below. These age-associated changes in mitochondria can lead to altered mitophagy.^5,6,7,8

When mitophagy is altered, it can lead to accumulation, rather than clearance of altered mitochondria.

Accumulation of these mitochondria can contribute to energy deficit and changes in the balance between anabolic and catabolic processes — important determinants of muscle mass, function, motor neuron and muscle fiber health.^8,9,10

Mitochondria can quickly adapt to changing conditions triggered by systemic or cellular challenges.³

Supporting mitochondrial function helps reduce loss of muscle mass and function and benefit overall health, specifically by enhancing mitochondrial dynamics and mitophagy.³

Both sedentary and physically active are susceptible to age-related muscle decline, yet the degree of severity is highly variable and dependent upon multiple risk factors beyond mitochondrial health, including hormone and cytokine balance, malnutrition and degree of physical activity.¹¹

Exercise and Nutrition Interventions for Age-Related Muscle Decline

Lack of exercise is believed to be the leading risk factor for age-related muscle loss.¹¹ Both resistance and aerobic training have been shown to improve the health of skeletal muscle by impacting mitochondrial quality and increasing muscle strength and function in older patients.^11,12,13,14

Individually tailored exercise programs can support healthy aging and be a means of prevention and intervention for age-related muscle decline.

In clinical studies demonstrating the benefits of aerobic, resistance or combined exercises, exercise was performed at least 2-3 times per week, for 30-60 minutes each session, for at least 8-12 weeks.^12,13

When recommending exercise as a therapeutic option for patients, the duration of sessions, amount of weight, distance, and number of exercises should increase gradually based on each individual’s capability and improvement.

Forty percent of older individuals do not meet the recommended .8g/kg protein intake requirements in their diet.¹⁵ Poor protein intake, combined with decreased absorption and intake of other nutrients that are essential for muscle health like amino acids and vitamins and minerals, put older individuals at a greater risk of reduced muscle protein synthesis or “anabolic resistance” and muscle loss.¹⁶ In addition, changes in mitochondrial function that also occur with aging can contribute to oxidative stress and favor catabolism of the muscle.^17,18,19

Two ways to support age-related muscle decline in the older patient involve assessing their protein and antioxidant intake. Recommended adequate protein in the older patient is 0.8 gm/2.2 lbs of body weight up to age 65, and 1 gm/2.2 lb of body weight after age 65.²⁰

Adherence to a Mediterranean diet, which promotes a high intake of proteins, fibers and polyphenols, combined with an individualized exercise regimen can be an effective approach to age-related muscle changes in the aging patient.

Nutrients to Support Age-Related Muscle Decline

Along with adequate protein, a phytonutrient rich diet and exercise, focusing on nutrients that support cellular, mitochondrial and muscle health can help improve patient outcomes.

B vitamins are essential to basal mitochondrial function, serve as metabolic coenzymes and/or methyl donors.^‡

PQQ provides B vitamin-like activity with unique antioxidant properties. PQQ supports mitochondrial, neuronal and cellular function, at least in part, by activation of Nrf2 and antioxidant gene expression. PQQ may also help to maintain cytokine balance.^‡

Amino Acids are the building blocks for all proteins, making them essential for several body functions, including fluid balance, enzyme production, cellular repair and energy metabolism.^25,26 Proper intake of amino acids is important for the synthesis, repair and metabolism of muscle, cells and tissues.^‡

Creatine is an energy carrier that is naturally present in muscles, brain and other organs. It clinically studied to increase body strength, build muscle mass, and support recovery from strenuous exercise. Creatine also promotes growth factor signaling and glycogen storage to support gains in muscle strength.^‡

Pure Encapsulations^® Nutrient Solutions

Pure Encapsulations^® offers high-quality supplements that are FREE FROM unnecessary additives and many common allergens for patients who may need support for age-related muscle changes. We offer nutrients individually and in combination to meet all your patients’ unique needs.^‡

Klean Athlete^® is a Pure Encapsulations partner brand.

Klean Athlete^® is our dedicated sports nutrition brand designed to power peak performance through optimal health. By harnessing the science of sports nutrition, Klean Athlete^® delivers safe, NSF Certified for Sport^® supplements to support healthy, active lifestyles. Klean Athlete^® is trusted by over 350 professional and collegiate sports teams and is the preferred brand of many of the world’s top coaches, trainers and health professionals.^‡

Cellular Health

Renual enhances mitochondrial renewal to support energy output/energy production. Features Mitopure^™ Urolithin A to power muscle function, increase cellular energy and promote healthy aging. Research indicates that urolithin A enhances autophagy, the natural process of cellular renewal in which the body degrades and recycles cellular components, as well as mitophagy, the clearance and recycling of older mitochondria. Resveratrol offers support for longevity, metabolic health, and mitochondrial function.^27,28 CoQ₁₀ is a key nutrient used in the energy production pathway. ^29‡
Suggested Dose: Take 2 capsules, 1-2 times daily, with or between meals.

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

Muscle Health

Creatine supports muscle strength, performance and recovery^‡ It promotes growth factor signaling and glycogen storage to support gains in muscle strength and supports quick conversion of ADP to ATP energy.^‡
Suggested Dose: 1 1/2 tsp daily mixed with 8 oz of water or beverage of choice.

KLEAN Isolate^™ supplies 20 grams of high-quality whey protein isolate in each serving. The dietary protein provided by Klean Isolate^™ supplies essential amino acids, including branched chain amino acids that participate in many of the body’s metabolic and physiologic systems. With no additional flavorings or sweeteners, Klean Isolate^™ can easily be added to any beverage to enhance daily protein and amino acid intake.^‡
Suggested Dose: Adults take 1 scoop daily mixed with 10-12 oz. of water or other beverage (cool or room temperature), or as directed. For best results, take within 45 minutes after being active.

KLEAN Plant-Based Protein^™ by Klean Athlete^® supplies a blend of pea and organic brown rice protein to provide amino acids for muscle protein synthesis. ProHydrolase^® enzymes are included to break down protein for increased amino acid absorption and to ease digestion, along with Sunfiber^® for gastrointestinal health.^‡
Suggested Dose: 1 scoop daily mixed with 10-12 ounces of water or other beverage, or as directed by a trainer, coach or health professional.

Digestive Support

Digestive Enzymes Ultra w/ Betaine HCl contains an extensive profile of betaine HCl and digestive enzymes to support protein, carbohydrate, fat, fiber and dairy digestion while promoting enhanced nutrient bioavailability and absorption. Encourages optimal gastric pH with betaine HCl, which is important for the enhanced digestion of protein and other nutrients for daily wellness and healthy neurotransmitter synthesis.^‡
Suggested Dose: 2 capsules with each meal, or as directed by a health professional.

Summary

Loss of muscle mass and strength can significantly impact an individual’s well-being and ability to live independently. Providing patients with targeted, personalized nutrition and exercise interventions to enhance anabolic processes and cellular health can greatly influence their quality of life now, and as they age.

Pure Encapsulations^® provides uniquely formulated products made with high-quality, pure ingredients backed by verifiable science to complement your plan of care.

Resources

• Age Related Muscle Loss Protocol^‡

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. Najm A. et al. Int J Mol Sci. 2024 Apr 12;25(8):4300. doi: 10.3390/ijms25084300. PMID: 38673885; PMCID: PMC11050002.
2. Ali S. et al. Gerontology. 2014;60(4):294-305. doi: 10.1159/000356760. Epub 2014 Apr 8. PMID: 24731978; PMCID: PMC4112511.
3. Burtscher J. et al. Front Public Health. 2024 Jan 10;11:1330131. doi: 10.3389/fpubh.2023.1330131. PMID: 38269379; PMCID: PMC10806989.
4. Faitg J et al. Calcif Tissue Int. 2024 Jan;114(1):53-59. doi: 10.1007/s00223-023-01145-5. Epub 2023 Nov 5. PMID: 37925671; PMCID: PMC10791945.
5. Aging Cell. 2016. 15(6):1132-39.
6. J Orthop Translat. 2020. 23:38-52
7. A Gerontol A Biol Sci. 2018. 17:939-45
8. Ferri E et al. Int J Mol Sci. 2020 Jul 23;21(15):5236. doi: 10.3390/ijms21155236. PMID: 32718064; PMCID: PMC7432902.
9. Kubat GB et al. Mitochondrion. 2023 Sep;72:33-58. doi: 10.1016/j.mito.2023.07.003. Epub 2023 Jul 13. PMID: 37451353.
10. Drake JC et al. FASEB J. 2016 Jan;30(1):13-22. doi: 10.1096/fj.15-276337. Epub 2015 Sep 14. PMID: 26370848; PMCID: PMC6137621.
11. Dhillon RJ and Hasni S. Clin Geriatr Med. 2017 Feb;33(1):17-26. doi: 10.1016/j.cger.2016.08.002. PMID: 27886695; PMCID: PMC5127276.
12. Chen N. et al. Eur Rev Aging Phys Act. 2021 Nov 11;18(1):23. doi: 10.1186/s11556-021-00277-7. PMID: 34763651; PMCID: PMC8588688.
13. Ni HJ et al. Arch Gerontol Geriatr. 2022 Mar-Apr;99:104605. doi: 10.1016/j.archger.2021.104605. Epub 2021 Dec 2. PMID: 34922244.
14. Yarasheski KE et al. Am J Physiol. 1999 Jul;277(1):E118-25. doi: 10.1152/ajpendo.1999.277.1.E118. PMID: 10409135.
15. Morley JE et al. J Am Med Dir Assoc. 2010 Jul;11(6):391-6. doi: 10.1016/j.jamda.2010.04.014. PMID: 20627179; PMCID: PMC4623318.
16. Cochet C et al. Nutrients. 2023 Aug 24;15(17):3703. doi: 10.3390/nu15173703. PMID: 37686735; PMCID: PMC10490489.
17. Cedikova M et alPhysiol. Res. 2016;65:S519–S531. doi: 10.33549/physiolres.933538.
18. Prado CM et al. Clin Nutr. 2022 Oct;41(10):2244-2263. doi: 10.1016/j.clnu.2022.07.041. Epub 2022 Aug 7. PMID: 36081299.
19. Romani M et al. Nutrients. 2022 Jan 22;14(3):483. doi: 10.3390/nu14030483. PMID: 35276842; PMCID: PMC8838610.
20. Age and Aging. 2023;52:10.1093
21. Besora-Moreno M et al. Clin Nutr. 2022 Oct;41(10):2308-2324. doi: 10.1016/j.clnu.2022.07.035. Epub 2022 Aug 17. PMID: 36099667.
22. Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F. Evid Based Complement Alternat Med. 2013;2013:270418.
23. Heim KC. In: Antioxidant Polymers: Synthesis, Properties, and Applications. Cirillo G, Iemma F, eds. Taylor and Francis, c. 2012
24. Ryu D, et al. Nat Med.2016 Aug;22(8):879-88.
25. Flakoll PJ, et al. J Appl Physiol (1985). 2004 Mar;96(3):951-6.
26. Shimomura Y, et al. J. Nutr. 2006. 136(2); 529- 532.
27. Timmers S, et al. Cell Metab. 2011 Nov 2;14(5):612-22.
28. Goh KP, et al. Int J Sport Nutr Exerc Metab. 2014 Feb;24(1):2-13.
29. Zheng A, Moritani T. J Nutr Sci Vitaminol (Tokyo). 2008 Aug;54(4):286-90.
30. Yago MR, et al. Mol Pharm. 2013 Nov 4;10(11):4032-7.

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

By Amy Doyle, MS, CNS⁺

New Research on Clinical Strategies to Support Biological Age

Biological age isn’t the future of care — it’s already reshaping patient expectations today. Patients are prioritizing their health span, and the demand for biological age assessments is expected to triple over the next ten years.

Most patients already understand the value of good nutrition, quality supplements and a balanced lifestyle. But what if these habits could do more than support day-to-day wellness — what if they could actually slow down or even reverse biological age?

A new pilot study published in the ACNEM Journal (September 2025) explored exactly that. Over just 90 days, researchers tracked how structured nutrition, supplementation and lifestyle program affected participants’ biological age using advanced DNA methylation tests. The results were eye-opening: participants reduced their biological age by an average of 2–9 years, depending on the biomarker used.

Here’s what that means and why it matters.

Chronological Age vs. Biological Age: What’s the Difference?

Chronological age is how many years a person has been alive. Biological age, however, reflects how fast a person’s cells are aging.

Scientists measure this using “epigenetic clocks that read DNA methylation patterns. These chemical tags on your DNA change with lifestyle, stress, sleep and nutrition adjustments. Certain clocks estimate overall biological age (like Horvath and PhenoAge), while others measure the pace of aging or cellular changes.

In this study, four clocks were used:

• PC PhenoAge – predicts health span and risk
• DAMAge – measures DNA changes and cellular stress
• Intrinsic Epigenetic Age – cellular aging independent of immune changes
• DunedinPACE – rate of aging per year

What Did the 90-Day Study Involve?

Forty-one adults, aged 30–81, completed a three-month holistic protocol that included:

1. A structured whole-food nutrition plan

• 6 servings of vegetables per day (greens, cruciferous and colorful varieties)
• 1.6–2.0 g protein per kg ideal body weight
• No added sugars and a diet focusing on whole foods

2. Daily movement and strength training

• At least 30 minutes of exercise per day
• Strength training 3 times per week
• Stress-management practices (5–10 minutes daily)

3. Targeted supplement support
Participants received a blend of supplements including:

• Methylated B-complex (with L-5-MTHF and methylcobalamin)
• Resveratrol (100 mg/day)
• Ubiquinol (200 mg/day)
• A nutrigenomic detox complex (sulforaphane, NAC, ALA, curcumin)
• Nicotinamide riboside (100 mg/day)

These ingredients target core “hallmarks of aging,” including oxidative stress, mitochondrial decline, inflammation and epigenetic alterations.

The Results: Biological Age Dropped — Fast

PC PhenoAge

• Decreased 2.3 years on average in just 3 months
• (p = 0.0029; statistically significant)

• Decreased 8.8 years on average
• (p = 0.00019; highly significant)

• Showed small but positive improvements
• Not statistically significant, but directionally favorable

In short, participants became biologically younger and accumulated less cellular changes in just 90 days.

Why Did It Work? A Multi-Pathway Approach

This wasn’t a single “magic bullet”, it was a synergistic lifestyle approach that targeted multiple aging pathways:

Methylated B vitamins support DNA methylation, stress-hormone metabolism, and genomic stability. A vegetable-rich diet provides polyphenols that influence epigenetic regulation.^3‡

Resveratrol supports healthy cytokine balance, improves metabolic markers, and helps to scavenge free radicals which are responsible for skin aging--thanks to its antioxidant activity. Sulforaphane activates the Nrf2 pathway, improving detoxification and antioxidant capacity.^‡

Ubiquinol boosts energy production and reduces oxidative stress. Nicotinamide riboside increases NAD⁺, a coenzyme essential for DNA repair, mitochondrial function, and cellular resilience.^‡

This multi-modal strategy addressed key hallmarks of aging simultaneously, resulting in meaningful biological rejuvenation.

What This Means for Health and Longevity

If your patients already value supplementation and healthy living, this study reinforces something powerful:

Small, consistent daily habits can significantly influence how fast the body ages at the cellular level.

This research shows that:

• Biological age is modifiable
• Improvements can happen quickly
• A holistic approach is more powerful than isolated changes
• Supplements that support methylation, detoxification and mitochondrial health can meaningfully enhance results

While more research is needed, the message is clear; daily lifestyle choices are one of the most powerful tools available for extending health span.

For more comprehensive resources on biological age, refer to:

• The Consumer Longevity Revolution: Mapping the Future of Health, Wealth, and Wellness. Version 1.2. September 2025. LEMON – Dare to Imagine; in partnership with 40+Lab and Kompassium. Available from: https://kompassium.com/wp-content/uploads/2025/12/The-Consumer-Longevity-Revolution-text-29-09-2025.pdf
• Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role. Adv Nutr. 2012 Jan;3(1):21-38.
• Choi SW, Friso S. Modulation of DNA methylation by one-carbon metabolism: a milestone for healthy aging. Nutr Res Pract. 2023 Aug;17(4):597-615. doi: 10.4162/nrp.2023.17.4.597.
• Borsoi FT, Neri-Numa IA, de Oliveira WQ, de Araújo FF, Pastore GM. Food Chem (Oxf). 2022 Dec 13;6:100155.
• Wu Q, Xiao C, Ouyang B, Farag MA, Yuan Y, Simal-Gandara J, Cao H, Xiao J. Phytomedicine. 2025 Nov 25;148:157495.
• Xia N, Daiber A, Förstermann U, Li H. Antioxidant effects of resveratrol in the cardiovascular system. Br J Pharmacol. 2017 Jun;174(12):1633-1646. doi: 10.1111/bph.13492. Epub 2016 May 6. PMID: 27058985; PMCID: PMC5446570.
• Cao X, Liao W, Xia H, Wang S, Sun G. The Effect of Resveratrol on Blood Lipid Profile: A Dose-Response Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022 Sep 11;14(18):3755.
• Liu K, Zhou R, Wang B, Mi MT. Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr. 2014 Jun;99(6):1510-9.
• Fahey JW, Talalay P. Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. Food Chem Toxicol. 1999 Sep-Oct;37(9-10):973-9.
• Gomes, A. P., et al. Cell, vol. 155, no. 4, 2013, pp. 1624–1638.
• Trammell, S. A. J., et al. “Nicotinamide Riboside Is Uniquely and Orally Bioavailable in Mice and Humans.” Nature Communications, vol. 7, 2016, p. 12948.
• Vreones M, Mustapic M, Moaddel R, Pucha KA, Lovett J, Seals DR, Kapogiannis D, Martens CR. Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. Aging Cell. 2023 Jan;22(1):e13754.

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.

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22. Lindseth G, Lindseth P, Thompson M. West J Nurs Res. 2013;35(4). doi:10.1177/0193945911416379
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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.