DHA is an omega-3 fatty acid that is highly concentrated in the fetal brain and nervous system.
Maternal transfer of DHA increases substantially during late pregnancy, when fetal brain and eye development are especially active.
Many pregnant patients do not meet seafood intake recommendations, making DHA intake an important point of assessment in prenatal nutrition counseling.
Prenatal dietary DHA intake may help support healthy birth weight and healthy pregnancy progression, in addition to its foundational role in fetal neurodevelopment.‡
Why DHA Matters During Pregnancy
Docosahexaenoic acid (DHA) is an omega-3 long-chain polyunsaturated fatty acid and the dominant omega-3 fatty acid in the brain, as well as the most abundant omega-3 fatty acid in the nervous system. Because of its central role in neural structure and function, consuming dietary DHA is especially important during pregnancy.
DHA is involved in placental development early in pregnancy and continues to accumulate in the fetal brain throughout gestation, with the most rapid accretion occurring from approximately weeks 29 to 40, a period of accelerated brain and retinal development. DHA is also critically involved in neuronal growth and synapse formation during fetal development and early life, which helps explain why maternal DHA status before conception, during pregnancy and during lactation is clinically relevant.1,2 ‡
Assessing and Recommending DHA Intake in Clinical Practice
A practical issue in clinical care is that many women enter pregnancy with suboptimal DHA status, often due to low seafood intake or a dietary fatty acid pattern that does not support adequate omega-3 status.1 Early assessment is therefore important. A brief review of seafood intake can help determine whether a patient is likely meeting DHA needs through food alone.
Pregnant women are advised to consume 8 to 12 ounces of low-mercury seafood per week.3–5 Salmon is a particularly rich source of DHA, providing approximately 1.2 grams per 3-ounce serving.5
For patients with low seafood intake, food aversions or inconsistent intake of DHA-rich foods, supplementation may be considered. Several professional groups suggest a minimum of 250 mg/day of DHA plus EPA during pregnancy, with some recommending an additional 100 to 200 mg/day of DHA and others suggesting 600 to 1,000 mg/day, ideally beginning by 20 weeks gestation.5
Clinical Takeaway
DHA warrants clinical consideration during pregnancy because it supports fetal brain, nervous system and eye development. It may also contribute to healthy pregnancy progression and birth outcomes. From a practice standpoint, assessing DHA intake early, encouraging regular consumption of lower-mercury seafood (8-12 ounces per week) and identifying whether additional dietary or supplemental DHA support is needed can help promote adequate intake, ideally by 20 weeks gestation.‡
Pure Encapsulations® Options for Targeted Nutritional Support‡
DHA Ultimate is a supercritical CO2 extracted DHA fish oil that supports healthy neural and cognitive function.‡ Epidemiological studies indicate that a high intake of DHA is associated with healthy cognitive function in adults as well as infants born to mothers with a diet high in DHA.6,7 Suggested Dose: 2 softgel capsules daily, with a meal
EPA/DHA Essentials is an ultra-pure, microfiltered fish oil concentrate that supports cardiovascular health and daily wellness.‡ Suggested Dose: 1-2 softgel capsules daily, with a meal
Resources
For additional information to help you deliver the most effective care for women’s health from preconception to postpartum, refer to the resources below:
Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.
Tahaei H, Gignac F, Pinar A, et al. Nutrients. 2022;14(3). doi:10.3390/nu14030518
About the Author
Dr. Kim Ross is a Doctor of Clinical Nutrition (DCN), Certified Nutrition Specialist (CNS®), Licensed Dietician Nutritionist (LDN), and a Functional Medicine Certified Practitioner (FMCP). She is an Associate Professor and the Director of Nutrition Programs for Sonoran University of Health Sciences. Dr. Ross has been in clinical practice (Ross Nutrition) since 2010, specializing in hormonal, mental, and gastrointestinal health, though she works with a broad range of health conditions.
+Dr. Ross is a paid consultant for Pure Encapsulations.
Dietary fiber may support weight management through several mechanisms. These include greater satiation and satiety, slower gastric emptying, healthy glycemic responses, and colonic fermentation that may influence appetite-related signaling.
Not all fibers behave the same way. Viscosity, fermentability dose, and food matrix all matter clinically. This helps explain variable patient responses.
A practical target for many adults is to consume 25 to 30 grams of fiber per day, or about 14 grams per 1,000 kcal. Increase intake gradually to improve gastrointestinal tolerance.
Literature now extends the conversation beyond "bulk and regularity". It now focuses on microbiota-mediated, metabolic and gut-brain mechanisms relevant to long-term weight management.
Mechanisms Tying Dietary Fiber to Weight Management
Fiber is a practical nutritional tool in weight management because it can improve the patient's experience with food. Meals built around fiber-rich foods are often more filling. They can help soften hunger intensity between meals and may also promote a healthy postprandial glucose response.1
Weight management is rarely about willpower and motivation.
It is shaped by whether a dietary pattern supports satiety, sustainability, adherence and metabolic regulation over time.
Dietary fiber influences weight management through several organs and physiological mechanisms.1–3
In the upper gastrointestinal tract, fiber can increase chewing time and meal volume. Depending on the type, fiber can also slow gastric emptying. These effects may support satiation during meals and satiety between meals, helping patients feel full sooner and remain satisfied longer.‡
In the small intestine, dietary fiber can slow nutrient absorption which may contribute to a more gradual postprandial glycemic response. This may support healthy blood glucose and insulin. It also supports more stable energy and appetite regulation.‡
In the colon, gut microbiota metabolizes fermentable fibers into short-chain fatty acids. These may participate in gut-brain and enteroendocrine signaling. This includes pathways involving hormones that modulate hunger and satiety, such as glucagon-like peptide-1 (GLP-1), peptide YY, cholecystokinin (CCK) and ghrelin.
These mechanisms suggest that fiber may support weight management not through a single effect, but through coordinated actions on digestion, healthy glycemic response, appetite signaling and energy intake.‡
Mechanisms Tying Dietary Fiber to Weight Management
Created with BioRender.com
Adapted from Ferri E et al. Int J Mol Sci. 202. 21:5236.
Dietary Fiber Characteristics That Influence Weight Management Outcomes
A key clinical takeaway is that fiber should not be viewed as a single intervention. Fibers differ in viscosity, fermentability, solubility, particle structure and food matrix. These characteristics influence their physiological effects.2,4
Soluble fibers, such as psyllium, beta-glucans, pectins and inulin, dissolve in water. This may affect gel formation, glycemic response and microbial fermentation. Insoluble fibers, such as flaxseed, wheat bran, cellulose and some hemicelluloses, often relate more to stool bulk and intestinal transit. Unfortunately, these categories do not fully predict physiological response.1,4
More viscous dietary fibers, such as psyllium, glucomannan and beta-glucans from oats and barley, are generally more relevant for gastric emptying, fullness and a healthy postprandial glycemic response. More fermentable fibers, such as inulin, fructooligosaccharides, resistant starch and some oligosaccharides, may exert greater effects in the colon through microbial metabolism and short-chain fatty acid production.1,4
Whole food sources, such as legumes, berries, chia seeds, vegetables and intact whole grains, deliver additional variables. These include food form, cellular structure and accompanying nutrients, all of which can modify physiological response.
These differences help explain why one patient may notice better satiety and appetite control, while another experiences more prominent effects on stool quality, glycemic response or digestive tolerance. Research suggests that baseline gut microbiota composition may also influence responsiveness to specific fibers, supporting growing interest in more personalized nutrition approaches.5,6
Not All Fibers Are the Same
Created with BioRender.com
Adapted from Ferri E et al. Int J Mol Sci. 202. 21:5236.
Clinical Application
Current guidelines suggest that adults benefit from consuming approximately 25 to 30 grams of fiber per day or about 14 grams per 1,000 kcal consumed. Notably, population intake remains well below recommended levels.4
Keep advice simple and direct for patients.
Encourage patients to build meals around fiber-rich foods such as legumes, vegetables, fruit, nuts, seeds and intact whole grains, increasing intake gradually to improve gastrointestinal tolerance.
Add one fiber-rich food to each meal as an initial step.
Set expectations appropriately. Fiber may support weight management, but it is not a stand-alone solution.‡
Fiber’s benefits are strongest when included in a diet that improves food quality, satiety and adherence. In that way, fiber helps support a healthy eating pattern for physiological and behavioral sustainability.‡
Pure Encapsulations® Options for Targeted Nutritional Support‡
Arabinogalactan (AG) is a fermentable prebiotic fiber found in high concentrations in North American larch trees.
Suggested Dose: 1 capsule, three times daily, between meals
PureLean® Satiety is designed to support relaxation and moderate appetite to promote healthy weight management†. It offers clinically researched DNF-10® to moderate caloric intake and promote satiety‡ Suggested Dose: 1 capsule, 1-2 times daily, with meals.
Resources
For additional information that includes diet and lifestyle recommendations for supporting weight management, refer to the resources listed below:
Weight Management Protocol: Designed by our scientific and medical advisors to help you deliver the most effective care and support weight management.
Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.
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
Created with BioRender.com
Adapted from Ferri E et al. Int J Mol Sci. 202. 21:5236.
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
Exercise
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.
Created in Canva
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.
Nutrition
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
In a systematic review of 19 observational studies and 9 randomized-controlled trials, Besora-Moreno et al revealed that a higher intake of antioxidant foods was associated with better muscle preservation outcomes.21 A meta-analysis of 4 randomized-controlled trials by the same authors found that that higher fruit and vegetable consumption and supplemental protein each significantly improved.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.
Urolithins are unique natural metabolites of intestinal bacteria that are produced by commensal microbiota after consuming foods rich in ellagitannins and ellagic acid — major health promoting constituents of pomegranates, nuts and berries. These unique polyphenols undergo metabolism by intestinal bacteria to small, highly absorbable metabolites called urolithins, which mediate the widely acclaimed health benefits of pomegranates and other ellagitannin-rich foods.22,23 Urolithin A also supports muscle function in preclinical models, improving endurance and exercise capacity in both young and age-related models of muscle decline.24‡
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.
Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.
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)
DAMAge (Cellular Clock)
Decreased 8.8 years on average
(p = 0.00019; highly significant)
Intrinsic Epigenetic Age & DunedinPACE
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:
Methylation and Nutrition Support
Methylated B vitamins support DNA methylation, stress-hormone metabolism, and genomic stability. A vegetable-rich diet provides polyphenols that influence epigenetic regulation.3‡
Polyphenols and Cellular Defense
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.‡
Mitochondrial Health
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:
This content is an adaptation and summary of Furness D, Taylor P, Three-Month Nutritional and Lifestyle Intervention Reduce Biological Age: A Pilot Study Using DNA Methylation Clock. ACNEM Journal 2025 Sep; Vol 44, No 3.
It is not authored, endorsed, or reviewed by the original researchers or publishers. The information is provided for educational purposes only and should not be relied upon as a substitute for professional advice, diagnosis, or treatment. Accuracy and completeness are not guaranteed. Always refer to the original source and consult a qualified professional for guidance specific to your situation.
Associated References:
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.
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.
Key Drivers of Functional Bowel Concerns 3,5,6,7,8,9
Occasional Diarrhea
Occasional Constipation
Increased levels of hydrogen and hydrogen-sulfide producing bacteria
Changes in bile acid absorption
Changes in carbohydrate absorption (FODMAPS, fructose, lactose)
Increased intestinal permeability
Previous or current non-beneficial microorganism exposure
Reduction in Bifidobacteria, Lactobacillus and butyrate-producing organisms
Mast cell activity and histamine signaling
Altered gut-brain axis and autonomic balance
Stress
Altered serotonin signaling in the enteric nervous system
Changes in motility related to previous non-beneficial microorganism exposure
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.
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:
Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.
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 to1–3:
Abdominal discomfort
Occasional constipation or diarrhea
Bloating
Dizziness
Headaches
Nasal congestion and sneezing
Flushing
Itchy skin
Skin rashes
Analogy of the Body’s Handling of Histamine
Think of the body’s histamine handling like a sink.
Symptoms can appear if the faucet runs faster (more histamine exposure or release) or the drain runs slower (reduced histamine breakdown).
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:
Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.
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.
Some cognitive and emotional contributors include:
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 Disturbances8–15
Image created in BioRender.com
While this blog addresses four underlying factors, many other root causes may be present.
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.
Glucose Homeostasis as a Foundation for Sleep Stability
Low-glycemic, whole-food patterns support insulin signaling during the day and night. Changes in glucose metabolism can activate counterregulatory hormones such as cortisol, epinephrine and glucagon, leading to abrupt awakening or restless sleep.
Supporting healthy blood glucose levels through balanced meals, pairing protein with fiber and limiting refined carbohydrates, particularly at dinner, can meaningfully improve sleep continuity.
Individuals who wake during the night due to a drop in glucose may benefit from consuming a small snack before bed to help stabilize glucose response during sleep. Similarly, a small snack upon waking may help promote the return to sleep.
Caffeine Timing
Caffeine is one of the most common dietary contributors to delayed sleep onset and reduced sleep efficiency. Its average half-life is approximately five hours but is variable based on genetics and other factors.19
Patients with sleep difficulty should avoid caffeine after noon, though some patients may require complete elimination. Energy drinks, pre-workout supplements and chocolate are often overlooked sources.
Alcohol and Sleep Fragmentation
Alcohol is sometimes used to self-induce relaxation, yet even moderate evening intake can decrease REM sleep, increase sympathetic activity and lead to early-night sedation followed by late-night fragmentation.20
Recommending that patients cease alcohol at least three hours before bedtime supports more stable sleep cycles.
Protein Intake and Amino Acid Availability
Protein intake throughout the day supports sleep-related neurotransmitter balance. Dietary sources of tryptophan and its cofactors (vitamin B6, magnesium and iron) contribute to melatonin synthesis, but the distribution of protein across meals also influences glycemic stability, which is critical for uninterrupted sleep.
Encouraging patients to prioritize protein at breakfast and lunch can support daytime satiety and reduce evening carbohydrate cravings that may otherwise disturb sleep.
Evening Meal Timing and Composition
Research has demonstrated that the consumption of higher protein, higher carbohydrate and higher fat diets is beneficial to sleep onset and efficiency, working in different mechanistic ways; therefore, personalizing dietary intake is important.21–24
Encourage patients to finish most of their intake earlier in the evening and reserve any late-night eating for truly necessary stabilization (e.g., a small snack for individuals with nocturnal drops in glucose).
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 Sleep25–27
Improving Sleep Hygiene Practices
Most sleep hygiene practices, properly applied, are a high-yield, low-risk intervention set.
Light
Exposure to bright morning light within 30 to 60 minutes of waking; avoid blue light one to two hours before bed; use blackout curtains; minimize LED lights in the bedroom.
Pre-bed mobile phone use and other blue light exposure predicted circadian phase delay, poorer sleep quality and worse memory/concentration the next day. Conversely, daytime exposure to bright light or daylight-simulating indoor lighting correlated with earlier sleep onset and better sleep quality.17
Temperature
Maintain a cool room, ideally 60 to 67°F.
Higher environmental and bedroom temperatures are generally associated with poorer sleep quality, including reduced sleep efficiency, increased awakenings and shorter sleep duration.28
Noise
Use white noise if needed; reduce household noise during sleep hours; avoid falling asleep with the television on.
Electronics
Remove TVs from the bedroom; charge phones outside the room; avoid screen use before bed.
Bedding
Choose a supportive mattress and pillows that allow neutral spinal alignment; avoid overly warm bedding.
Pets
Recommend pets sleep outside the bed if nocturnal disruptions occur.
Routine
Maintain consistent bed and wake times daily; create a calming pre-sleep routine; avoid large meals within two to three hours of bedtime.
Environment
Keep the bedroom uncluttered; use low, warm lighting after sunset; avoid working or studying in the bedroom.
Unsure where to begin?
Start with morning light exposure, a consistent wake time, reducing evening light exposure and optimizing bedroom temperature and environment.
Then layer in other support (nutrition, stress reduction and targeted supplements).
Reinforce that improving sleep is about progress, not perfection.
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.
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.
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
clinical perspective, emotional wellbeing represents a dynamic balance rather than simply the absence of distress. It reflects how effectively individuals adapt to stress, regulate mood and sustain motivation and connection. This area of health has gained increasing attention as rates of psychological distress, burnout and poor life satisfaction continue to rise globally. A 2025 Gallup global survey found that 39% of adults reported worrying for much of the previous day and described themselves as stressed, suggesting a broad deficit in emotional wellbeing.2
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
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
Decluttering the mind is not avoidance. It is structured processing plus externalizing: notice → name → park it somewhere reliable.
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
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
Created in BioRender
These strategies are appropriate for most patients and do not require advanced psychotherapy training to be introduced.
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.”
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.
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:
Name it (e.g., “I am worrying about X”).
Decide if it is actionable now.
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
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.
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.‡
References
Park CL, Kubzansky LD, Chafouleas SM, et al. Affect Sci. 2023;4(1). doi:10.1007/s42761-022-00163-0
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
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:
It reduces the inhibitory signal of IRS-1, thereby improving intracellular communication.6
It enhances Akt signaling and improves cellular glucose uptake.6
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
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
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:
Drug-Nutrient Interactions Checker: Provides valuable information on potential interactions between your patients' prescriptions, over-the-counter medications and nutritional supplements.
