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Immunomodulation for Mental Health: A Focus on Positive Mood

  • Nov 26, 2024
Pure Encapsulations Pro Blog
Discover the link between immune health and mood regulation. Learn how immunomodulation could offer new hope for those experiencing low mood.

Immunomodulation for Mental Health: A Focus on Positive Mood

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

Introduction 

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

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

Immunological Basis of Mood and Mental Health

Immune System Activation and the Brain

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

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

Image created with BioRender®.Image created with BioRender®.

Cytokines and Neurotransmitter Balance

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

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

Lifestyle Components to Support Positive Mood Through Cytokine Modulation

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

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

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

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

Nutrient Solutions to Support a Positive Mood Through Cytokine Modulation

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

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

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

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

Pure Encapsulations® Nutrient Solutions

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

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

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

Pycnogenol® 100 mg supports cognitive function and cardiovascular health‡

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

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

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

Conclusion

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

Resources

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

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

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

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

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

References

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

Building Resilience: A Guide to Personalized Care for Stress

  • Oct 30, 2024
Pure Encapsulations Pro Blog

Building Resilience: A Guide to Personalized Care for Stress

Key Points

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

Table of Contents:

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

The Importance of a Personalized Approach to Stress Management

More than one-third of adults don’t know where to begin to manage their stress. For some, their healthcare practitioner may be the only person they talk to about their stress.[1] While stress is a universal experience with profound impacts on each patient’s overall health, its manifestation and effects are unique to everyone, necessitating a personalized approach . A customized strategy can address a wide range of stress symptoms and causes while also improving patient involvement and results.

Understanding Individual Differences in Stress Responses

Each patient's experience of stress is shaped by numerous factors including genetic predisposition, environmental factors, personal coping mechanisms and even the specific stressors themselves. A personalized approach allows the healthcare practitioner to address these distinctions, enabling more precise identification of stress triggers and the development of effective, individualized strategies.

Building Resilience Against Stress

The following infographic is a guide to providing comprehensive care for your patient that addresses the physiological and psychological mechanisms associated with the stress response, along with thorough assessment recommendations, diet, exercise, sleep adaptogenic and nutrient support. Infographic displaying 3 stages of adaptation and related assessments, and diet, exercise and supplement recommendations  

The Three Stages of Stress Adaptation: Expanding Your Knowledge

The 3 stages of stress adaptation are a framework that describes how the body responds to stress in three stages: alarm, resistance and exhaustion. A thorough understanding of the progression of these stages and how their presentation can vary between individuals is vital for supporting a patient’s response to stress and for promoting resilience to it.Explore our educational videos below to enhance your knowledge of the 3 stages of stress adaptation, the intricate relationship between stress, the hypothalamic-pituitary-adrenal (HPA) axis and the long-term effects of stress.

 

Additional Resources

Stress Management & Relaxation Protocol‡: developed with James Greenblatt, MD, a pioneer in the field of integrative medicine for mental health, this protocol offers nutrition and lifestyle recommendations to support stress management and relaxation.‡ Drug-Nutrient Interaction Checker: provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements. PureInsight™: Our streamlined platform easily collects patient data and provides valuable, personalized recommendations to help achieve their unique health goals. Virtual Dispensary: our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory.  

References

[1] American Psychological Association
Blog

The Role of Neurotransmitters in Attention, Focus and Behavior

  • Sep 24, 2024
Pure Encapsulations Pro Blog
 

The Role of Neurotransmitters in Attention, Focus and Behavior

 

Key Points:

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

Table of Contents:

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

Introduction

For many, maintaining focus is a daily struggle that affects productivity and overall well-being. The prevalence of focus and attention issues is approximately 6.76%, or around roughly 366.33 million, adults globally. What causes these challenges with focus? One crucial factor is the brain’s neurotransmitters. Focus involves the ability to sustain attention on a particular task or goal, while ignoring distractions. It is essential for effective work, learning and daily functioning. Maintaining focus can be difficult for many people, leading to decreased productivity and increased stress. In this blog, we’ll explore how neurotransmitters impact our ability to focus, the role they play in managing focus-related tasks and provide some lifestyle solutions to support focus.

Key Neurotransmitters Involved in Focus

Dopamine: is essential for motivation, attention and reward processing. It helps regulate how we perceive and respond to stimuli, influencing our ability to stay focused on tasks. Low levels of dopamine can impair our ability to concentrate, stay organized, manage time effectively and may lead to challenges in maintaining attention on tasks.1 Norepinephrine: affects alertness and arousal. It helps the brain stay alert and responsive to stimuli, which is essential for maintaining focus. Norepinephrine has been shown to alter network activity in attention and working memory through arousal activation of the frontoparietal network, which is critical for sustained attention and alertness.2 Serotonin: influences mood, impulse control and overall cognitive function. It plays a role in managing emotional responses and maintaining a steady focus. Changes in serotonin levels can affect our emotional stability and our ability to maintain focus, leading to increased distractibility and impulsive actions.3 Acetylcholine: governs memory, learning, motivation and attention. Synthesized from choline, acetylcholine is the chief neurotransmitter of the parasympathetic nervous system and has a significant impact on muscle function, sleep, cognitive processes and mental performance.4 Fluctuations of acetylcholine can affect short-term memory, processing speed and word recall and can lead to learning difficulties and symptoms like brain fog.

Natural Ways to Support Neurotransmitter Balance‡

By understanding how neurotransmitters play a role in focus, attention and mood, you can better provide guidance on lifestyle changes that support neurotransmitter balance.

Diet and Nutrition

A balanced diet rich in essential nutrients can support neurotransmitter production and function. Foods high in omega-3 fatty acids and certain nutrients, such as vitamin D, magnesium and zinc, support the synthesis of neurotransmitters or assist their functioning.5 Very few research studies have investigated specific dietary patterns on focus or attention outcomes in randomized clinical trials. However, there is available evidence to provide broad recommendations, such as consuming nutrient-dense foods and limiting excessive added sugars as beneficial for attention problems. Mediterranean diets, rich in omega-3s and plant-based foods compared to Western diets, have also been associated with better mental health and mood.6

Exercise

Regular physical activity has been shown to boost levels of dopamine, norepinephrine and serotonin, which can enhance mood and improve concentration. In fact, in children who have problems with attention, exercise interventions improved overall executive function when participating in exercise.7 Additionally, there is a robust body of scientific evidence demonstrating positive outcomes on brain function in adults from long-term exercise. Several studies have shown positive effects of exercise on cognitive functioning, specifically on prefrontal cortex-dependent cognition. Even acute, short bursts of exercise have been shown to improve mood and emotional status.8  

Supplements

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

Conclusion

Understanding the relationship between neurotransmitters and focus offers valuable insights into managing focus-related challenges. By addressing neurotransmitter imbalances through lifestyle changes and supporting supplements, individuals can help improve their ability to concentrate and enhance their overall focus and attention.

Resources

Mood Protocol: Developed in collaboration with our scientific and medical advisors to support mood.‡ Drug-Nutrient Interactions Checker:  provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements. PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help patients achieve their health goals. Virtual Dispensary: Our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory. You can also explore Pure Encapsulations® to find On-Demand Learning, Clinical Protocols, and other resources developed with our medical and scientific advisors.

References

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

Aging Gracefully: Harnessing NAD+ for Healthy Aging

  • Sep 3, 2024
Pure Encapsulations Pro Blog

Aging Gracefully: Harnessing NAD+ for Healthy Aging

 

Table of Contents

1.Introduction 2.Definition and Mechanisms of NAD+ 3.The Making of NAD+ 4.NAD+ and Implications for Health and Aging 5.Approaches to Restore NAD+ 6.Nutrient Solutions to Restore NAD+ and Cellular Health 7.Pure Encapsulations Nutrient Solutions 8.Summary 9.Resources

Introduction

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

Definition and Mechanisms of NAD+

NAD+ is ubiquitous in every living cell and is found in pools within the cytoplasm, mitochondria and nucleus. Operating primarily as a coenzyme, NAD+ facilitates enzymatic reactions that involve transferring hydrogen atoms in oxidation-reduction processes.[1] In its reduced form, known as NADH, it acts as an antioxidant, playing a vital role in neutralizing free radicals and protecting cellular structures.1 While a crucial player in redox reactions, NAD+ is also involved in:[2],[3]
  • Cellular aging
  • Energy metabolism
  • DNA repair
  • Formation of new mitochondria
  • Calcium homeostasis
  • Immune regulation
  • Circadian rhythm
  • Vascular activity
  • Gene expression
There are three primary classes of enzymes that utilize NAD+: glycohydrolases, sirtuins and PARPs (poly-ADP-ribose polymerases). In their consumption of NAD+, these three classes of enzymes generate nicotinamide (NAM) as a byproduct, which can be recycled back into NAD+ to help maintain intracellular levels.1 Sirtuins are also key regulators implicated in aging processes, while PARP-1 plays a significant role in DNA repair and cell survival under stress conditions.1,[4] While these three groups of enzymes rely on NAD+, more than 300 enzymes in the body depend on NAD+ for their activity.1

The Making of NAD+

Due to its high demand, NAD+ must be continuously synthesized, catabolized and recycled in the cell to maintain steady intracellular levels. Intracellular NAD+ levels are sustained in 3 ways:
  • de novo biosynthesis using l-tryptophan via the kynurenine pathway
  • de novo biosynthesis via the Preiss-Handler pathway, using dietary sources of nicotinic acid, or nicotinic acid mononucleotide from the kynurenine pathway
  • recycling of nicotinamide phosphoribosyltransferase (NAMPT) into NAD+ via the salvage pathway
Image adapted from Paro R, Grossniklaus U, Santoro R, et al. Introduction to Epigenetics [Internet]. Cham (CH): Springer; 2021. Chapter 9, Epigenetics and Metabolism. 2021 Mar 24. Available from: https://www.ncbi.nlm.nih.gov/books/NBK585707/doi: 10.1007/978-3-030-68670-3_9. Creative Commons license. KEY: Nicotinic acid phosphoribosyltransferase (NAPRT), Nicotinic acid mononucleotide (NAMN), Nicotinic acid adenine dinucleotide (NAAD), Nicotinamide mononucleotide adenylyltransferase (NMNAT1-3), 2-amino-3-carboxymuconate semialdehyde (ACMS), Nicotinamide phosphoribosyltransferase (NAMPT), Nicotinamide mononucleotide (NMN) These pathways collectively regulate the intracellular levels of NAD+, which are essential for maintaining cellular functions and metabolic balance. Understanding the intricacies of NAD+ synthesis and consumption pathways is essential for exploring strategies aimed at modulating cellular metabolism and promoting health.

NAD+ and Implications for Health and Aging

Maintaining optimal levels of NAD+ is crucial for sustaining tissue and metabolic homeostasis throughout life. As we age, however, levels of NAD+ naturally decline and many of the enzymes responsible for the degradation and biosynthesis of NAD+ are altered. This can lead to NAD+ degradation exceeding the cells' capacity for de novo synthesis or efficient recycling and salvage of NAM (nicotinamide).1 The age-associated decline in NAD+ may have implications for overall cellular health and longevity.

Approaches to Restore NAD+

Naturally occurring NAD+ decline and altered NAD+ metabolism have been implicated in various processes associated with aging.1 Decreased NAD+ levels can affect cognitive function and have other unwanted health outcomes that extend to the cardiovascular, endocrine and immune systems.1,3 Approaches to restore NAD+ levels can support health and vitality in the aging patient. ‡ The decline in NAD+ levels associated with aging underscores its importance in healthy aging. By understanding and potentially influencing NAD+ levels, healthcare practitioners can explore new avenues in promoting cellular health and longevity.‡

Nutrient Solutions to Support NAD+ and Cellular Health

Nutrients that enhance the biosynthesis and activity of NAD+ can promote restoration of tissue levels of NAD+ and support overall cellular health. ‡ Resveratrol supports metabolic health by promoting healthy activity of the key enzyme AMP kinase (AMPK)and SIRT1 activity which are positively associated with mitochondrial function.[1],[2],7,8 Nicotinamide riboside chloride (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+), a key driver of cellular energy production.1,[3],[4],[5],[6],[7]‡ Sulforaphane is one of the most effective activators of phase II detoxification, which occurs primarily in the gut and the liver.[8],[9] Acetyl l-carnitine supports healthy mitochondrial function and cell membrane stability.[10]‡ Alpha lipoic acid is a key component of the metabolic process, alpha lipoic acid produces energy in muscles and directs calories into energy production.[11] are unique natural metabolites of intestinal bacteria that are produced by commensal microbiota after consuming foods rich in ellagitannins and ellagic acid — major health promoting constituents of pomegranates, nuts and berries. These unique polyphenols undergo metabolism by intestinal bacteria to small, highly absorbable metabolites called urolithins, which mediate the widely acclaimed health benefits of pomegranates and other ellagitannin-rich foods.[12],[13]‡ Pyrroloquinoline Quinone, or PQQ provides B vitamin-like activity with unique antioxidant properties. PQQ supports mitochondrial, neuronal and cellular function, at least, in part, by activation of Nrf2 and antioxidant gene expression. Preliminary research suggests that PQQ promotes mitochondrial biogenesis by targeting SIRT1 and PGC-1α.[14]‡

Pure Encapsulations® Nutrient Solutions

  Pure Encapsulations® provides uniquely formulated products made with high-quality, pure ingredients backed by verifiable science to complement your plan of care and support healthy aging in your patients.‡   NR Longevity™: specially designed to target biological processes that decline with age, such as the body’s natural ability to make energy, build new mitochondria and protect cells from oxidative stress.1 Nicotinamide riboside (NR), resveratrol and sulforaphane promote healthy aging by replenishing NAD+, enhancing mitochondrial function and providing antioxidant support, respectively.‡  Suggested use: 2 capsules, 1-2 times daily, with or between meals   RENUAL® enhances mitochondrial renewal to support energy output/energy production Features Mitopure™ Urolithin A to power muscle function, increase cellular energy and promote healthy aging.‡ Suggested use: Take 2 capsules, 1-2 times daily, with or between meals.   Ubiquinol-QH 100mg is the active antioxidant form of CoQ10. It supports the production of ATP for energy, promotes cardiovascular health and provides antioxidant support.‡ Suggested use: Take 1 capsule, 1-2 times daily, with meals.   RevitalAge™ Ultra is a scientifically researched combination of acetyl-l-carnitine (ALC) and alpha lipoic acid (ALA) offered with antioxidant and mitochondrial support cofactors. It promotes healthy aging through mechanisms involving gene expression, mitochondrial function, cellular energy production and antioxidant protection. Also contains Nicotinamide riboside (NR) to promote the synthesis of NAD+, a key driver of cellular energy production‡ Suggested use: Take 2 capsules daily, with meals.   Ultra B-Complex w/PQQ combines essential B vitamins with PQQ to support mitochondrial bioenergetics and function. Also provides alpha lipoic acid and luteolin for enhanced antioxidant and cellular support‡ Suggested use: Take 1 capsule, 1-2 times daily, with meals.  

Summary

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

Resources

Mitochondrial Health Protocol‡: designed by our clinician partners to help you deliver the most effective care and support for your patients. It includes foundational recommendations for overall health and focused interventions to address common clinical objectives related to mitochondrial function.‡ Drug-Nutrient Interaction Checker:  provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements. PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals. Virtual Dispensary: our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory. [1] Covarrubias AJ, Perrone R, Grozio A, Verdin E. Nat Rev Mol Cell Biol. 2021;22(2):119-141. doi:10.1038/s41580-020-00313-x [2] Ying W. Antioxid Redox Signal. 2008;10(2):179-206. doi:10.1089/ars.2007.1672 [3] Xie N, Zhang L, Gao W, et al. Signal Transduct Target Ther. 2020;5(1):227doi:10.1038/s41392-020-00311-7 [4] Xu W, Li L, Zhang L. Front Physiol. 2020;11:901. doi:10.3389/fphys.2020.00901 [5] Timmers S, et al. Cell Metab. 2011 Nov 2;14(5):612- 228 [6] Ghanim H, et al. J Clin Endocrinol Metab. 2010 Sep;95(9):E1-8 [7] Conze D, Brenner C, Kruger CL. Sci Rep. 2019 Jul 5;9(1):9772 [8] Trammell SA, Schmidt MS, Weidemann BJ, et al. Nat Commun. 2016 Oct 10;7:12948 [9] Janssens GE, Grevendonk L, Perez RZ, et al. Nat Aging. 2022 Mar;2(3):254-263 [10] Chu X, Raju RP. Metabolism. 2022 Jan;126:154923 [11] Clement J, et al. Rejuvenation Res. 2019 Apr;22(2):121-130 [12] Zhang Y, et al. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403. 2 [13] Karen-Ng LP, et al. Asian Pac J Cancer Prev. 2011;12(5):1161-6 [14] Kerner J, et al. Mech Ageing Dev. 2015 Jan;145:39-50 [15] Kishi Y, et al. Diabetes. . 1999 Oct;48(10):2045-51 [16] Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F. Evid Based Complement Alternat Med. 2013;2013:270418 [17] Heim KC. In: Antioxidant Polymers: Synthesis, Properties, and Applications. Cirillo G, Iemma F, eds. Taylor and Francis, c. 2012 [18] Harris CB, et al. Nutr Biochem. 2013 Dec;24(12):2076-84
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Think Ahead: Cognitive Wellness Today for Tomorrow

  • Jul 29, 2024
Pure Encapsulations Pro Blog

Think Ahead: Cognitive Wellness Today for Tomorrow

Table of Contents

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

Introduction

As we age, supporting brain health and cognitive function increasingly becomes a focal point of our health. Mild memory deficits and slower cognitive processing are a normal part of aging. It has been estimated that 1 in 9 Read on to discover how you can proactively target metabolic processes and related pathways to support your patients’ brain health and cognitive function throughout their lifetime.

Age-Related Changes in the Brain

Changes in brain neurons can begin 20 years or more before cognitive symptoms develop, with the prevalence of these changes doubling every five years after age 65.1,[1] Age-related chemical and physical changes in the brain can include:[2]
  • Changes in vascular makeup, reduced blood flow and oxygen
  • Decline in production of hormones and neurotransmitters
  • Decreased antioxidant defenses
While these underlying brain changes can occur for decades, one factor is emerging as a significant player in the development and occurrence of cognitive changes: oxidative stress.

Oxidative Stress and Brain Health

Oxidative stress occurs when there’s an imbalance between free radicals and antioxidants in the body resulting in greater reactive oxygen species (ROS) production.  Free radicals are a natural byproduct of many physiological processes, but they can also be introduced by external sources like diet, toxins and environmental factors. While free radicals play essential roles in cellular signaling and immune function, an excess can lead to cellular damage, an immune response and mitochondrial dysfunction that can progress to adverse effects on brain function.[3] Highly metabolic, the brain is a large consumer of oxygen and is rich in polyunsaturated fatty acids. These characteristics combined with its high production of ROS and low levels of antioxidant enzymes make it particularly vulnerable to oxidative damage.[4],[5] When ROS production overwhelms the brain’s antioxidant defenses, oxidative stress damages proteins, DNA and cell membranes, disrupts neuronal cell functions and triggers neuronal cell death. Regulation of ROS in the brain is critical for memory consolidation and long-term potentiation.[6]  

Antioxidant Intake and Cognitive Function

Several prospective studies have found that people who consume an antioxidant rich diet of fruits and vegetables can reduce their risk of cognitive changes.[7],[8],[9] In a 2023 meta-analysis of cohort studies, researchers sought to investigate the association of antioxidant intake with the risk of cognitive changes. The meta-analysis included 17 articles with 98,264 participants. Of the total, 7,425 participants had cognitive changes after 2-3 years of follow up, that interfered with their daily living. Studies included participants from Europe, Asia and North America.  The studies considered antioxidant intake from diet, supplements or both.  The antioxidants studied included vitamin A, vitamin C, vitamin E and flavonoids. Additional subgroup analyses were conducted based on the participants’ kind of nutrition, diet and supplement, geographical region and study quality. Overall, the researchers determined that a high antioxidant diet or supplement intake significantly decreased the incidence of cognitive changes that interfere with daily living by 16% (RR =.084, 95% CI 077.-091(pt <0.001). In subgroup analysis by nutritional type, high dietary and supplement intake of vitamin C or vitamin E alone significantly reduced risk of cognitive changes (RR= 0.81, 95% CI 0.70-0.94, I2 = 37.9%, p = 0.097), and (RR=0.77, 95% CI 0.64-0.92, I2=54%, p=0.013), respectively. Both vitamin A and flavonoid intake were also shown to decrease risk of cognitive changes, however results were not statistically significant. High dietary and supplement antioxidant intake demonstrated a greater risk reduction with statistical significance in North American populations (RR=.083, 95% CI 0.75-0.93, I2=47.3%, p=0.003), compared to European populations, where although risk was reduced, results were not statistically significant. The authors concluded that consuming fruits and vegetables rich in antioxidants or antioxidant supplements can have a protective effect on cognitive function and reduce risk of cognitive changes.

Nutrient Solutions for Cognitive Function

It is important to educate patients about modifiable risk factors associated with mild, age-related cognitive decline like an antioxidant-rich diet, physical activity, managing stress, prioritizing sleep and engaging in social and mental stimulation.[10] In addition, the practitioner can support the brain’s resilience against oxidative stress with targeted nutrient solutions. Animal research suggests that magnesium-l-threonate may promote synaptic plasticity and density in the regions of the hippocampus correlated with learning and memory.[11]‡ Acetyl-L-carnitine supports the availability of acetyl-CoA, an important energy-generating metabolite. In addition, it supports healthy mitochondrial function and cell membrane stability.[12]‡ Phosphatidylserine supports cognitive function, emotional well-being and behavioral performance. It has also been shown to support healthy memory.[13],[14]    ‡ Resveratrol promotes cardiometabolic, neuronal and cellular health through a variety of effects on cell signaling, mitochondrial function and endogenous antioxidant defenses.[15],[16],[17],[18], ‡ Omega 3 Fatty Acids encourage cardiovascular health by supporting lipid metabolism and healthy blood flow. [19],[20],[21], In addition, studies indicate these oils help maintain healthy endothelial function. [22]‡ Curcumin supports neuronal stability and function, in part, by promoting healthy cytokine balance and antioxidant defenses. [23]‡ Bacopa monnieri has been utilized traditionally for centuries in Ayurvedic medicine to support the nervous system, cognitive capacity and memory. A three-month trial conducted by Australian scientists suggests that bacopa may support learning, moderate stress and support memory. [24]‡ Luteolin promotes neuronal health through antioxidant, immunomodulating and mast cell stabilizing actions, helping to moderate the release of immune mediators.‡ Ginkgo biloba helps sustain the strength and elasticity of blood vessels and capillaries.  It may also promote the flow of oxygen and blood to the brain. ‡ With oxidative stress and related metabolic shifts occurring early in the development of changes in cognitive function, identifying and addressing these processes can be crucial for healthy function.

Pure Encapsulations® Nutrient Solutions for Cognitive Function

As the most trusted brand and leader in the professional supplement space, Pure Encapsulations® is committed to helping healthcare professionals understand and apply personalized, evidence-based nutrition to achieve optimal patient outcomes. The following supplements can support neuronal health, vascular integrity, memory, mental sharpness and overall cognitive function.‡ Memory Pro promotes neural health, cognitive function and memory. Also supports vascular integrity and promotes relaxation.‡ Suggested use: As a dietary supplement, take 3 capsules daily, with or between meals. BenfoMax is a fat-soluble vitamin B1 (thiamine) derivative that maintains healthy advanced glycation end (AGE) product activity to support vascular, nerve, retinal and kidney cellular health. It also promotes healthy glucose metabolism.‡ Suggested use: As a dietary supplement, take 1 capsule, 1-3 times daily, with meals. O.N.E. Omega contains triglyceride form EPA and DHA from fish oil produced through a unique solvent free, supercritical, CO2-based extraction method. Encourages cardiovascular health by supporting lipid metabolism and healthy blood flow.  Also helps maintain healthy endothelial function. ‡ Suggested use: As a dietary supplement, take 1 capsule daily, with a meal. CurcumaSorb Mind contains Meriva® bioavailable curcumin phytosome; support for mood, memory and mental sharpness.‡ Suggested use: As a dietary supplement, take 2 capsules, 1-2 times daily, with meals CogniMag  promotes cognitive function, learning ability and working memory. Also supports optimal brain magnesium levels.‡ Suggested use: As a dietary supplement, take 2 capsules, twice daily, with a meal and at bedtime. Brain Reset promotes concentration, mental clarity and memory with a multi-faceted blend of nutrients and herbal extracts. Promotes neuroimmune health by supporting cellular function, neuroprotection and immune mediator balance.‡ Suggested use: As a dietary supplement, take 2 capsules daily, between meals. AntiOxidant Formula  supports the body’s natural defense mechanism against free radicals.‡ Offers a synergistic, broad spectrum of antioxidants, including essential vitamins and minerals like vitamin A, E and B complex vitamins. Suggested use: As a dietary supplement, take 1 capsule, 1-2 times daily, with meals. Ester-C® & Flavonoids offers a blend of Ester-C ® and flavonoid compounds to provide vitamin C support for healthy immune and cellular function as well as blood vessel integrity. ‡ Suggested use: As a dietary supplement, take 1 capsule, 1-2 times daily, with or between meals.

Summary

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

Resources

Mild Age-Related Cognitive Decline Protocol‡: Developed in collaboration with our scientific and medical advisors to support cognitive health in older adults‡ Drug-Nutrient Interactions Checker:  provides valuable information on potential interactions between your patients’ prescriptions, over-the-counter medications and nutritional supplements. PureInsight™: Our streamlined platform easily collects patient data and provides valuable recommendations to help achieve their health goals. Virtual Dispensary: our Pure Patient Direct program provides account holders FREE access to our virtual dispensary to help simplify patient sales and reduce in-office inventory. You can also explore Pure Encapsulations® to find On-Demand Learning, Clinical Protocols, and other resources developed with our medical and scientific advisors.

References

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

  • Jul 25, 2024
Pure Encapsulations Pro Blog
Learn how to mitigate age-related muscle decline. Discover ways to help aging patients support their muscle mass and strength for sustaining mobility and independence.

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

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.

Prevalence and Symptoms of Age-Related Muscle Decline

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.[1]  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.[1] 

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 dysfunctional mitochondria through mitophagy. 

Mitophagy is a selective autophagy process that serves as the mitochondria’s own quality-control mechanism and involves removing and recycling dysfunctional mitochondria.[2] 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 [3],[4],[5],[6] 

When mitophagy is altered, it can lead to the accumulation, rather than clearance, of less-functional 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,[7],[8]

Created with BioRender.com

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.[1]

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,[1],[2],[3]

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.[1] 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”[Ma1]  and muscle loss.[2] In addition, changes in mitochondrial function that also occur with aging can contribute to oxidative stress and favor catabolism of the muscle.[3],[4],[5]  

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.[6] 

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.[7] 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 improved20  

Nutrients to Support Age-Related Muscle Decline

Along with adequate protein, a phytonutrient rich diet and exercise, f[Sa1] [AD2] ocusing 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.[1],[2]  Urolithin A also supports muscle function in preclinical models, improving endurance and exercise capacity in both young and age-related models of muscle decline. [3]

 

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.[4],[5] Proper intake of amino acids is important for the synthesis, repair and metabolism of muscle, cells and tissues.‡ 

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® and Douglas Laboratories® are Pure Encapsulations partner brands.

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.‡

Douglas Laboratories has been dedicated to meeting the needs of healthcare professionals for over 65 years. As a globally recognized leader in innovative, science-based nutritional supplements, we strive to support healthcare professionals as they help their patients discover the potential for healthy living, today and in the future.

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 and dysfunctional mitochondria. Resveratrol offers support for longevity, metabolic health, and mitochondrial function.[1],[2] CoQ10 is a key nutrient used in the energy production pathway.[3]‡

Suggested use: 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 use: Take 1 capsule, 1-2 times daily, with meals.

Muscle Health

Muscle Protect with HMB supports healthy muscle mass and function, provides anabolic muscle building support attenuates muscle protein breakdown and preserves lean muscle mass in aging adults. Formulated with clinically studied HMB® and Amino 9™, a leucine-rich blend of essential amino acids (EAAs) combined with vitamin D3 and glutamine.‡

Suggested use: 1 scoop, 1-2 times daily

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 use: 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® [De1] enzymes are included to break down protein for increased amino acid absorption and to ease digestion, along with Sunfiber® for gastrointestinal health.‡   

Suggested use: 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.[1] ‡

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

Drug-Nutrient Interactions Checker: Offers scientifically supported, clinically relevant information along with relevant product suggestions.

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

References

[1] 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.

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Supporting Menopausal Comfort and Healthy Aging: Expert Advice from an Integrative OBGYN

  • May 13, 2024
Pure Encapsulations Pro Blog










Supporting Menopausal Comfort and Healthy Aging: Expert Advice from an Integrative OBGYN






TABLE OF CONTENTS


1. Symptoms of Menopause


2. What Is Going On During Menopause?


3. What Most Practitioners Miss When Supporting Menopause Symptoms


4. Four Steps to Supporting Menopause and Healthy Aging


5. Resources



SYMPTOMS OF MENOPAUSE



Menopause is a natural part of life, but that does not mean it’s an easy one. In fact, 90% of women seek
medical support during their menopause transition.1 Common but significant symptoms can include hot
flashes, cold or night sweats, low energy, sleep disturbances, palpitations, weight gain, mood disturbances,
inability to concentrate and vaginal dryness.


The loss of ovarian-produced estrogen and progesterone is predominantly responsible for the effects of menopause.
Restoring these hormones to physiologic, premenopausal levels using conventional interventions is a common
clinical objective. Unfortunately, recreating the exact ovarian function and hormonal rhythms of a healthy
premenopausal woman is not currently possible, and for some women, these interventions may not be appropriate.
For these reasons, additional modalities are often needed to support female health throughout the menopausal
years.


Dr. Felice Gersh, M.D.,+ a board-certified OB/GYN and Integrative Medicine practitioner, says,
“The unique health issues faced by women are often minimized and overlooked; the most egregious example is
menopause. But no longer can we view menopause as simply the loss of fertility and periods. It is the beginning
of a huge metabolic shift, which we must recognize and address to support the health and well-being of the woman
for years to come.”



WHAT IS GOING ON DURING MENOPAUSE?



It is important to understand the physiological changes that drive symptoms in menopausal women. Instead of
picturing menopause like a finish line women must cross, it is better to consider it as a process that is
different for all who go through it.


Dr. Felice Gersh says, “Historically, they say [menopause] is when a woman has not had a spontaneous period
for 12 consecutive months, which is arbitrary. There’s nothing special about 12 months. It’s a
process. So, I want you to think differently … [Menopause] is a process of ovarian senescence, the aging
and decline of ovarian production of estrogen and progesterone.”


Dr. Gersh points out the inversion of the hormones responsible for driving fertility cycles in women. Prior to
the onset of menopause, estrogen is high and progesterone is low. As the process continues into the menopause
transition, these hormones and others, including LH, FSH, and inhibin B, begin to invert, which triggers the
symptoms listed above. As the process continues and the hormones stabilize, progesterone is elevated and
estrogen remains low.2


The inverse relationship of hormone levels before, during and after menopause drives many practitioners to
suggest hormone replacement therapy (HRT) to help restore balance. While HRT may work for some menopausal women,
there are some contraindications to taking these pharmaceuticals, and even with perfect dosing, it will not be
able to recreate the hormonal status of a healthy premenopausal woman.


Certain therapies, such as HRT, may be appropriate and should be used under the recommendation of a qualified
healthcare professional for managing menopause symptoms. Dietary supplements are not intended to replace the use
of such therapies or pharmaceuticals.


However, if looking for a way to potentially manage menopause symptoms, the following protocol and supplement
recommendations mentioned later in the blog, may be appropriate.






WHAT MOST PRACTITIONERS MISS WHEN SUPPORTING MENOPAUSE SYMPTOMS



Hormones take center stage when menopause support is initiated, and for good reason. Other hidden risks of
menopause are often overlooked and must also be addressed.


Estrogen receptors are found all over the body and play vital roles in regulating countless physiological
functions. The fluctuations of estrogen during menopause have additional health
implications,3 including but not limited to:



  • Weight gain and increased visceral fat

  • Changes in metabolic health

  • Musculoskeletal effects

  • Cardiovascular health

  • Neurological health

  • Cellular health (breast, colon)

  • Autoimmunity

  • GI concerns like occasional heartburn, malabsorption and motility


Dr. Gersh points out, “There are receptors for estrogen on virtually every organ system in the body. So,
when you lose ovarian-produced estrogen, you lose the optimal, healthy functioning of all the organ systems of
the body, leading to these myriad problems.”


Two important health concerns to note are cardiometabolic concerns and bone health.


Cardiovascular health can become a risk factor for menopausal women, with postmenopausal women experiencing
cardiovascular concerns 4 times the rate of premenopausal women.5


The menopause transition brings with it unfavorable shifts in body fat distribution, lipids and lipoproteins and
alterations in the structural and functional measures of vascular health.6


The Study of Women’s Health Across the Nation (SWAN) study investigated chronological aging versus
reproductive aging and the results showed changes in total cholesterol, LDL-C and apolipoprotein B levels during
the menopausal transition. These changes were found to be independent of the effect of chronological aging
alone. Additionally, the menopausal transition was independently associated with adverse changes in body
composition and increases in visceral adipose tissue, both of which contribute to cardiometabolic
function.7


Changes in bone metabolism are 4 times more likely to affect women than men, especially women over 50 years of
age. Studies have shown that women can lose up to 20% of their bone density during the five to seven years
following menopause.



4 STEPS TO SUPPORTING MENOPAUSE AND HEALTHY AGING



It is important to support your patients through the menopausal transition and let them know that it does not
have to be a difficult or negative experience.


Dr. Felice Gersh, in collaboration with Pure Encapsulations®, has co-developed a four-step protocol that
connects lifestyle changes with targeted supplement protocols to help guide your patients through this stage of
life.





To learn more about Dr. Gersh’s approach and the Pure Encapsulations® products designed to
support menopausal women, explore the resources listed below.‡



RESOURCES



Webinar: “A Woman’s Guide
to Healthy Aging: Supporting Menopausal Comfort & Healthy Longevity”‡ with
Dr. Felice L. Gersh, M.D.


PureWoman
Exclusive and PureWoman
Brochure


Drug-Nutrient Interactions
Checker: Offers scientifically supported, clinically relevant information and relevant
product suggestions.


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


REFERENCES



  1. Guthrie JR et al. Climacteric 2003; 6:112–117

  2. Davis, S., Lambrinoudaki, I., Lumsden, M., et al. Nat Rev Dis Primers 1, 15004 (2015).

  3. Adapted from Exper Rev Endocrinol Metab® 2011 Expert Reviews Ltd

  4. Centers for Disease Control and Prevention, National Center for Health Statistics. Accessed October
    15, 2021.

  5. Davezac M et al. Front Aging. 2021 Sep 24;2:727380. doi: 10.3389/fragi.2021.727380. PMID: 35821994;
    PMCID: PMC9261451.

  6. El Khoudary SR et al. Circulation. 2020 Dec 22;142(25):e506-e532. doi: 10.1161/CIR.0000000000000912. Epub
    2020 Nov 30. PMID: 33251828.)

  7. El Khoudary SR. Menopause. 2019;26(10):1213-1227

  8. National Osteoporosis Foundation. What Women Need to Know. Accessed June 2021.

  9. BHOF.
    Accessed on April 18, 2024.




+Dr. Felice Gersh, M.D. is a retained advisor for Pure Encapsulations®.




Blog

Thyroid Health: Looking Beyond TSH and T4

  • May 3, 2024
Pure Encapsulations Pro Blog










Thyroid Health: Looking Beyond TSH and T4






TABLE OF CONTENTS


1. Thyroid Health: Functions and Common Symptoms


2. Thyroid Hormone Metabolism: Looking at the Whole Pathway


3. Inhibitors of T4 to T3 Conversion


4. Looking Beyond TSH and T4



  • 3.1. Free T3 and Free T4

  • 3.2. Reverse T3

  • 3.3. Thyroid Antibodies

  • 3.4. Adrenal Panel


5. Nutrients to Support Thyroid Function‡


6. Pure Encapsulations® Nutrient Solutions


7. Summary


8. Resources


Standard assessments may overlook factors that underlie a patient’s thyroid concerns. Learn more about
looking beyond TSH and T4 to support your patient’s thyroid hormone metabolism and overall health.



THYROID HEALTH: FUNCTIONS AND COMMON SYMPTOMS



An optimally functioning thyroid is essential for maintaining body homeostasis. Thyroid hormones influence nearly
every organ system in the body, encompassing the heart, central nervous system, autonomic nervous system,
skeletal structure, gastrointestinal tract, and metabolism.


The rate of thyroid concerns has more than doubled in the past twenty years, with women affected at a prevalence
five to eight times that of men.1, 2 More than half of individuals with symptoms are unaware they are
related to
their thyroid.1 Thyroid symptoms can vary between individuals and can
include:



  • Fatigue

  • Occasional constipation

  • Weight gain, difficulty losing weight

  • Intolerance to cold, cold hands and feet

  • Dry skin

  • Dry, thinning hair or hair loss

  • Mood concerns

  • Joint and muscle discomfort

  • Heavy or irregular menstrual cycles, fertility concerns

  • Slowed heart rate

  • Low libido



THYROID HORMONE METABOLISM: LOOKING AT THE WHOLE PATHWAY



Four hormones have been identified to be secreted by the thyroid, T1, T2, T3, and T4. The two primary hormones are
thyroxine (T4), a prohormone, and triiodothyronine (T3), which is 300 times more biologically active than
T4.3


Once T4 is secreted, it is bound to transport proteins and carried to the cells and tissues where it passes
through a series of metabolic transformations and is either converted to T3 or inactivated into reverse T3
(rT3). T3 is utilized by mitochondria and contributes to metabolism of glucose and lipids, regulates metabolic
responses according to energy intake, controls thermogenesis and basal and oxidative
metabolism—essentially affecting all tissues in the body.4


Successful conversion of T4 to T3 relies heavily on transport proteins, along with nuclear receptors and
selenium-dependent enzymes known as deiodinases. These three players are crucial to homeostasis at the cellular
level as they coordinate the uptake, activation and deactivation of thyroid hormone within the cell.5
Conversion
of T4 to T3 occurs primarily in the liver and kidneys, but also within the gut, bones, muscles, adipose tissue,
heart and CNS.6, 7, 8





Created with BioRender.com




INHIBITORS OF T4 TO T3 CONVERSION



Eighty percent of the T3 found in circulation is produced by peripheral conversion from T4.4 A number
of lifestyle, environmental, and dietary factors can inhibit
this conversion and lead to symptoms.4, 9, 10, 11, 12






T4 to T3 conversion influences all tissues within the body, as they are dependent on T3 for normal cell
function.4



LOOKING BEYOND TSH AND T4



In line with standard practices, practitioners commonly rely on TSH and T4 levels to screen for thyroid concerns.
While these markers play important roles, they don’t tell the whole story. Getting to the root of an
individual’s symptoms requires investigating what is occurring further down the thyroid hormone pathway at
the cellular level, and why. This begins with understanding that although TSH and T4 levels can provide insight
into thyroid gland function, they don’t reflect:



  • Alterations in cellular sensitivity to thyroid hormones

  • Inadequate peripheral conversion of inactive T4 to metabolically
    active T3



  • Poor uptake of thyroid hormones into the mitochondria

  • Activity of rT3, anti-thyroid antibodies or environmental factors
    which can displace thyroid hormones and prevent their binding to cellular receptors.


Any one of these factors along with impaired T4 to T3 conversion, or fluctuation in T3 and rT3 levels can trigger
changes in an individual long before TSH or T4 are outside their respective reference ranges.


Expanding the assessment of thyroid function beyond TSH and T4 can provide insight into what is happening
peripherally to T4.


The following markers can provide evidence of suboptimal thyroid function:


FREE T3 AND FREE T4


Measuring total thyroid hormones provides the sum of both the free thyroid
hormone and thyroid hormone bound to a protein; however, it does not differentiate how much of that hormone is
available for uptake by the cells. A hormone bound to a protein is inactive. Only the free T4 and free T3 tests
measure the levels of thyroid hormones in circulation that are available to cells.


REVERSE T3


rT3 can be produced in response to physical or emotional stress. Free T3 and rT3 can both bind to thyroid receptors on the cell. When rT3 binds to thyroid receptors, it
inactivates them and prevents the metabolically active hormone T3 from binding to receptors.


THYROID ANTIBODIES


Thyroid peroxidase antibodies (TPO antibodies) and thyroglobulin antibodies
(TG antibodies) can be produced when the body begins to lose “self-tolerance”. Thyroid antibodies
can be present long before aberrations are seen in TSH and T4.


ADRENAL PANEL


Elevated urinary cortisol metabolites have been associated with diminished
peripheral thyroid hormone metabolism.14 Examining the role stress plays in thyroid
function in each patient is foundational for any thyroid care plan.



NUTRIENTS TO SUPPORT THYROID FUNCTION



Various nutrients participate in the synthesis, metabolism, and mechanisms of action of thyroid hormones.


Curcumin helps to neutralize free radicals that may affect iodothyronine
5’-monodeiodinase enzyme activity, the limiting factor in the conversion of T4 to the more active T3
hormone.14‡


Vitamins A and D help to maintain healthy thyroid cell metabolism and support triiodothyronine
(T3) and thyroxine (T4) hormone function.15, 16


Ashwagandha helps maintain healthy thyroid function and relaxation as suggested in preliminary
research.17‡


Forskolin in coleus extract has been shown to support thyroid hormone metabolism in preclinical
models, potentially by promoting adenylate cyclase activity.18‡


Zinc and Selenium help to maintain healthy thyroid cell metabolism and support triiodothyronine
(T3) and thyroxine (T4) hormone function.19, 20 Selenium has also been shown to help to neutralize free radicals
that may affect iodothyronine 5’-monodeiodinase enzyme activity, the limiting factor in the conversion of
T4 to the more active T3 hormone.13‡


Probiotics support healthy intestinal microflora to promote digestive and immune
health.‡



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 thyroid and overall health support. You’ll find Pure Encapsulations® offers nutrients
individually and in combination to meet all your patients’ unique needs.


COMPREHENSIVE SUPPORT



  • Thyroid
    Support Complex‡     is a comprehensive thyroid support
    formula that contains vitamins, minerals, and herbal extracts to nourish and support thyroid gland
    function.‡ Suggested use: Take 2 capsules daily, with a meal.


IMMUNE SUPPORT



  • Zinc 30 provides broad physiological support including immune
    function and emotional wellness.‡ Suggested use: Take 1 capsule, 1-2 times daily, with meals.

  • Selenium (citrate) supports antioxidant defenses and cellular
    health and provides immune system support.‡ Suggested use: Take 1 capsule daily, with a
    meal, or as directed by a health professional.

  • Vitamin D3 125 mcg (5,000 IU) supports musculoskeletal,
    cardiovascular, neurocognitive, cellular, and immune health.‡ Suggested use: Take 1-5 capsules daily, or as directed by a health professional. Consume with food.


DETOXIFICATION SUPPORT



  • Curcumin 500 with Bioperine®
    supports the body’s natural detoxification system and helps maintain healthy hepatic function. Helps maintain healthy cell cycle
    function and supports antioxidant defenses.‡ Suggested use: Take 1 capsule, 1-3 times daily, between meals.


MICROBIAL BALANCE



  • Probiotic 50B offers seven researched probiotic strains that
    promote healthy intestinal ecology to support gastrointestinal and immune health.‡ Suggested
    use: Take 1 capsule daily, with or between meals.



SUMMARY



Environmental, genetic, lifestyle, and nutritional factors can affect the thyroid hormone pathway in
different ways for different individuals. While laboratory tests can be critical tools, the absence of markers
mentioned in thyroid testing does not equate to optimal function.


Personalized medicine addresses the whole person, which requires exploration of the unique mediators,
triggers, and antecedents that may be impacting each patient’s thyroid hormone function and presenting symptoms.



RESOURCES



Thyroid Support Protocol: Developed in collaboration with our scientific and medical
advisors to support thyroid health.‡


Drug-Nutrient Interactions Checker: Offers scientifically
supported, clinically relevant information along with relevant product suggestions.


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


REFERENCES



  1. American Thyroid Association. Accessed on March 18, 2024.

  2. Wyne KL, Nair L, Schneiderman CP, et al. J Endocr Soc. 2022 Nov 10;7(1):bvac172. doi: 10.1210/jendso/bvac172.

  3. Abdalla SM, Bianco AC. Defending plasma T3 is a biological priority. Clin Endocrinol (Oxf). 2014;81(5):633-641. doi:10.1111/cen.12538

  4. Severo JS, Morais JBS, de Freitas TEC, et al. The Role of Zinc in Thyroid Hormones Metabolism. Int J Vitam Nutr Res. 2019;89(1-2):80-88. doi:10.1024/0300-9831/a000262.

  5. Sabatino L, Lapi D, Del Seppia C. Factors and Mechanisms of Thyroid Hormone Activity in the Brain: Possible Role in Recovery and Protection. Biomolecules. 2024;14(2):198. Published 2024 Feb 7. doi:10.3390/biom14020198

  6. Sabatino L, Vassalle C, Del Seppia C, Iervasi G. Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions. Endocrinol Metab (Seoul). 2021;36(5):952-964. doi:10.3803/EnM.2021.1198

  7. Fröhlich E and Wahl R. Trends Endocrinol Metab. 2019 Aug;30(8):479-490. doi: 10.1016/j.tem.2019.05.008. Epub 2019 Jun 27. PMID: 31257166.

  8. Samuels, MH. J Clin Endocrinol Metab. 2008. 85(4):1388-93.

  9. Mancini A, Di Segni C, Raimondo S, et al. Mediators Inflamm. 2016;2016:6757154. doi:10.1155/2016/6757154

  10. Roti E et al. Int J Obes Relat Metab Disord. 2000;24 Suppl 2:S113-S115. doi:10.1038/sj.ijo.0801293

  11. Farasat T et al. Journal of Diabetes and its Complications. 2012. 26(6):522-25. doi:10.1016/J.JDIACOMP.2012.05.017

  12. Gillam MP et al. Curr Opin Pediatr. Aug 2001.13(4):364-72. doi: 10.1097/00008480 200108000 00014. PMID: 11717564.

  13. Vantyghem MC et al. J Endocrinol Invest. 1998.21(4): 219-25.

  14. Mahmoodianfard S et al. J Am Coll Nutr. 2015;34(5):391-9.

  15. Farhangi MA et al. J Am Coll Nutr. 2012. Aug;31(4):268-74.

  16. Mazokopakis EE et al. Hell J Nucl Med. 2015.18(3):222-27.

  17. Chandrasekhar K et al. Indian J Psychol Med. 2012. Jul-Sep; 34(3): 255–262.

  18. Godard MP et al. Obes Res. 2005 Aug;13(8):1335-43.

  19. Kilic M. Neuro Endocrinol Lett. 2007 Oct;28(5):681-5.

  20. Combs GF Jr et al. Am J Clin Nutr. 2009 Jun;89(6):1808-14.




Blog

Moving the Needle with PMS: Three Areas to Focus On

  • Apr 12, 2024
Pure Encapsulations Pro Blog










Moving the Needle with PMS: Three Areas to Focus On






TABLE OF CONTENTS


1. Symptoms and Prevalence of PMS


2. Potential Hormone Fluctuations Seen in PMS


3. Underlying Contributors to PMS



  • 3.1. Stress

  • 3.2. Blood Sugar Regulation

  • 3.3. Gut Health


4. Assessments for PMS


5. Nutrition and Lifestyle Support for PMS‡



  • 5.1. Diet

  • 5.2. Exercise

  • 5.3. Stress


6. Nutrient Support


7. Pure Encapsulations® Nutrient Solutions


8. Summary


9. Resources



SYMPTOMS AND PREVALENCE OF PMS



The menstrual cycle reflects a woman’s overall health status and has been considered her fifth vital
sign.1 For some women, their menstrual cycle is a dreaded time of the month, bringing with it a
cyclic pattern of pain and discomfort that impacts their daily life.


In fact, approximately 90% of cycling females report that they experience at least one mood related or physical
symptom in the luteal phase of their menstrual cycle.2


When a woman experiences one or more symptoms in the five days prior to the onset of her menses, this is known as
PMS, or premenstrual syndrome.3


Up to 30% of reproductive-age women experience PMS and report a number of emotional and physical
symptoms:3












POTENTIAL HORMONE FLUCTUATIONS SEEN IN PMS



While the cause of PMS is multifactoral, the fluctuation of estrogen and progesterone levels during the menstrual
cycle play a role. In some individuals, excess or depletion of these hormones can contribute to symptoms.











Since progesterone is required to balance estrogen’s activity, elevated estradiol should be viewed relative to
progesterone levels. The natural fluctuation of estrogen can contribute to PMS symptoms and can occur
when:4



  • Progesterone is low

  • Both estrogen and progesterone are in normal ranges, but estrogen is higher than progesterone

  • Phase I detoxification metabolites are elevated

  • Estrogen is elevated outside the luteal phase


While hormonal fluctuations can be a contributing factor to PMS symptoms, research suggests that in some women
PMS may be caused by a heightened sensitivity to the normal rise and fall of estrogen and progesterone during
the luteal phase of the menstrual cycle, impacting the serotonergic and GABAergic systems.2, 5



UNDERLYING CONTRIBUTORS TO PMS



Owing to the complex interactions between the hormones, body tissues, cells and the gut microbiome that
coordinate the menstrual cycle, a practitioner may be uncertain which system to address first in patients with
PMS. While there are many approaches, there are three underlying contributors and strategies that can help move
the needle in caring for patients with PMS: stress, blood sugar regulation and gut health.


STRESS


High stress is a contributing factor to PMS symptoms, as a bidirectional relationship exists between the
hypothalamic-pituitary-gonadal (HPG) axis and hypothalamic-pituitary-adrenal (HPA) axis.


The paraventricular nucleus in the brain, which contains several neurons that regulate the HPG axis and
expression of gonadotropin-releasing hormone (GnRH), also contains neurons which regulate the HPA axis and
expression of corticotropin-releasing-factor (CRF).6 This area of the brain is also ubiquitous with
GABAergic and serotonergic neurons. The neural overlap of these regulating systems is one contributing factor to
their interactions, as both the HPG and HPA axes are vulnerable to hormones produced by the other.6,
7


In animal studies, various stress models and exogenous cortisol have been shown to suppress GnRH and luteinizing
hormone (LH) secretion.6 Corticotropin-Releasing Factor, released in response to stress, can increase aromatase
production in the brain and promote increased estrogen levels.8 Conversely, progesterone and its
metabolite, allopregnanolone, are able to modulate HPA axis function due to their interaction with GABAergic
neurons.6 Estradiol can positively and negatively impact HPA axis reactivity, hypothesized to be due
to the distribution of both Erα and ERβ receptors in the parts of the brain responsible for HPA axis
regulation.6, 7








Credit: Schweizer-Schubert S et al. Front Med (Lausanne). 2021 Jan 18;7:479646. doi:
10.3389/fmed.2020.479646. PMID: 33585496; PMCID: PMC7873927.






A controlled study conducted by Hou et al. attempted to determine basal HPA axis activity in women with PMS by
measuring salivary cortisol levels mid-follicular and mid-luteal phase. Compared to healthy controls, women with
PMS exhibited an attenuated cortisol awakening response, a potential indicator for HPA axis dysregulation when
combined with markers of HPA axis function and other factors.9, 10 These findings align with previous
experiments in women with premenstrual symptoms that found hypoactivity of the HPA axis in response to
stress.11, 12


BLOOD SUGAR REGULATION


Fluctuations with glucose metabolism may occur during the luteal phase in some women with PMS. Decreased tissue
sensitivity to insulin and a worsening of glycemic control in the luteal phase have been reported in women with
higher estradiol or progesterone levels, compared to the follicular phase.13, 14, 15, 16


Higher circulating levels of insulin can impact production of Sex Hormone Binding Globulin, or SHBG, and can
elevate estrogen production by increasing aromatase.17 A transport protein, SHBG binds to sex
hormones like estrogen and testosterone and regulates their bioavailability. When SHBG production is decreased,
more hormones are available in their active form to reach target tissues and cause symptoms. In addition, low
plasma SHBG can be an early indicator of insulin resistance.18











GUT HEALTH


In a survey examining premenstrual emotional and GI symptoms in 156 healthy women, over 70% of the women surveyed
listed one or more GI symptom in the five days prior to their menses, including pain, bloating and altered bowel
habits—typically in the form of occasional diarrhea.19


Fluctuations in prostaglandins and hormones throughout the menstrual cycle can impact numerous functions of the
gut, including motility, pain sensitivity and immune function, contributing to the common GI symptoms seen in
PMS.











Sex hormones in the gut also communicate with neurotransmitters involved in signaling along the gut-brain axis,
often leading to co-existing emotional and GI symptoms in women with PMS.18


The gut microbiome plays a critical role in the regulation of estrogen metabolism. Microbes in the gut encode
enzymes responsible for the biotransformation of estrogen and its elimination through the stool. Altered gut
microbiota can increase activity of β- glucuronidase enzymes that engage in deconjugation of estrogens and
restore their biological activity.20 Reactivated estrogens can then be reabsorbed into the
bloodstream where they are free to reach target tissues.


The relationship between the gut microbiota and estrogen is bidirectional, however; estrogen levels can influence
the composition and diversity of the gut microbiota, and reduced diversity of gut microbiota can affect estrogen
levels.19



ASSESSMENTS FOR PMS



Assessments for PMS should explore hormone levels during the luteal phase, gut health, blood sugar regulation,
HPA axis function, nutrient status and neurotransmitter function.












NUTRITION AND LIFESTYLE SUPPORT FOR PMS



Nutrition and lifestyle play crucial roles in managing PMS because they can influence hormonal balance, energy,
mood and overall well-being. Making positive changes in diet, stress management and physical activity may help
alleviate the severity of PMS symptoms for many individuals.


DIET


Diet plays a significant role in moving the needle for individuals with PMS.


Cross-sectional studies have identified that most women experience food cravings during their luteal cycle,
particularly for high-calorie, high-sugar, high-fat, and high-salt foods, and that severity of PMS symptoms is
positively correlated with intake of these types of foods.21, 22


Due to the influence of insulin, stress, and the gut microbiome on menstrual health, a phytonutrient-rich,
preferably organic, whole foods diet should be emphasized for women with PMS. The Mediterranean diet, comprised
of a high intake of fruits and vegetables, whole grains, legumes, nuts and olive oil can be beneficial for women
with PMS.


A 2022 cross-sectional study examined dietary patterns and PMS symptoms in 262 women ages 20-49. A lower
prevalence of PMS was found in women who adhered to a Mediterranean diet, and a higher prevalence of PMS was
found in women who had low adherence to a Mediterranean diet and higher intake of snacks and
breads.23 The consumption of sugar has also been significantly associated with an increase in nervous
tension symptoms in PMS.24


Encouraging fermented foods and adequate fiber can support motility, stool consistency, and balance in the
patient’s gut microbiome, as well as support the excretion of excess estrogen.


EXERCISE


Regular physical activity can have a positive effect on both emotional and physical PMS symptoms. Exercise
increases endorphins, helps regulate cortisol and ovarian hormone levels, and can reduce prostaglandin
levels.2, 25 A randomized, controlled trial examined the effects of 20 minutes of aerobic exercise
three times a week on PMS symptoms in 65 women and found that the intervention group experienced a significant
reduction in headaches, nausea, bowel changes and appetite changes after 8 weeks, compared to
controls.26 In a systematic review of 17 randomized and nonrandomized studies that included over
8,800 women, regular exercise was shown to reduce nervous tension, anger, general pain and occasional
constipation symptoms.27 Forms of exercise included strength training, yoga, Pilates and aerobic
exercise. While many studies have demonstrated significant improvement in PMS symptoms after 8 weeks, some women
may experience a benefit after just one menstrual cycle, especially if they are new to exercising.28


The American College of Obstetricians and Gynecologists endorses routine exercise to help manage physical and
affective premenstrual symptoms and highlights yoga as a beneficial option to reduce overall PMS
symptoms.2


STRESS


In a 2022 meta-analysis of 77 studies that examined factors associated with prevalence and severity of
menstrual-related symptoms, stress was determined to be significantly associated with prevalence of
PMS.24 Stress in a patient raises cortisol, impacts glycemic control and insulin sensitivity and
increases prostaglandins.24, 29


There are numerous recommendations the practitioner can make for a patient needing to manage stress, including
relaxation techniques, aerobic exercise, meditation and yoga. Interestingly, Cognitive Behavioral Therapy (CBT)
has been the most studied psychosocial practice for addressing PMS symptoms and is endorsed by the American
College of Obstetrics and Gynecologists as a recommended option. CBT has been shown to provide statistically
significant reductions in symptom scores compared to controls in nervous tension, low mood, negative behavioral
changes, symptom intensity and interference with daily life.21



NUTRIENT SUPPORT



Along with dietary and lifestyle changes, nutrients that support blood sugar balance, emotional well-being, GI
health and healthy prostaglandin and eicosanoid levels can help improve patient outcomes.30, 31, 32, 33,
34


Vitamin B6 has a positive effect on premenstrual mood and may enhance the effect of
magnesium.30‡


Healthy intracellular magnesium levels have been associated with maintaining positive mood
during the luteal phase.31 Magnesium also plays an important role in nervous system sensitivity,
providing support for muscle comfort, breast comfort and emotional well-being associated with the menstrual
cycle.32


Calcium promotes healthy smooth muscle function and menstrual comfort.33


Vitamin D supports healthy smooth muscle function and menstrual comfort, due to its ability to
promote healthy calcium levels, cyclic hormone function and neurotransmitter activity.34‡


Omega-3 Fatty Acids moderate prostaglandin and leukotriene production, supporting healthy
connective tissue.35 Research suggests that omega-3 fatty acids may also play a role in maintaining
gastrointestinal cell health by supporting healthy eicosanoid production.‡


Eleuthero is a highly recognized adaptogen thatpromotes physiological balance and
moderatesoccasional stress. In part, it helps moderate the production of adrenocorticotrophic hormone (ACTH) and
corticosterone activity.36‡


Rhodiola supports energy and mental function.37


Chaste tree/Vitex has been traditionally used and clinically studied for the beneficial support
it provides to the hypothalamus and pituitary.38‡


l-Theanine may be helpful for premenstrual support and promote alpha wave production in the
brain, an indication of relaxation.39, 40‡



PURE ENCAPSULATIONS® NUTRIENT SOLUTIONS



Pure Encapsulations provides products designed to complement your supplement plans for patients who need overall
support. We offer nutrients individually and in combination to meet all your patient’s unique needs when it
comes to supporting healthy stress response, moderating food cravings, encouraging healthy mood, and promoting
healthy GI and cyclic hormone function. Pure Encapsulations can help you move the needle toward your patient’s
overall menstrual comfort.‡


PMS Essentials
supports the health and activity of the adrenal glands and promotes physiological balance and moderates
occasional emotional stress. It also promotes optimal energy reserves and healthy immune function.‡


O.N.E.TM
Multivitamin supports overall wellness with vitamins, minerals and
antioxidants.‡


O.N.E.TM Omega
promotes joint and connective tissue integrity and cardiovascular health.‡


Magnesium
(glycinate) encourages healthy cognitive and neuromuscular function and helps with calcium
metabolism and bone mineralization.‡


l-Theanine promotes
relaxation without causing drowsiness and offers premenstrual support, including supporting a healthy
mood.‡


CarbCrave Complex
moderates carbohydrate intake and helps lessen appetite by supporting neurotransmitter function.‡


Phyto-ADR supports adrenal
gland health and promotes physiological balance and moderates occasional emotional stress. Supports optimal
energy reserves and promotes immune function. May help to moderate mild fatigue under stressful
conditions.‡


Best-Rest Formula
provides support for occasional sleeplessness, encourages the onset of sleep as well as healthy sleep quality
and supports natural relaxation of the nervous system.‡


PureGG 25B is our highly
researched Lactobacillus rhamnosus GG supplement that supports immune, G.I. and overall health across all ages.
Our PureGG 25B is a human origin strain, selected for its resistance to gastric acidity, adhesion properties and
ability to support healthy gut microflora.‡


Pure Encapsulations only uses premium ingredients backed by verifiable science, so you can be confident you are
recommending products with quality, purity, and potency.



SUMMARY



There is moderate evidence that supports the use of pharmaceuticals like SSRIs for the treatment of PMS symptoms.
The rate of relapse is high in patients that stop SSRIs and most patients need to maintain use of them until
menopause.2


Certain medications, such as SSRIs, may be appropriate and should be used under the recommendation of your
healthcare professional for managing chronic, long-term, and/or more serious symptoms related to PMS. Dietary
supplements are not intended to replace the use of such medications.


However, if looking for a way to potentially manage common PMS symptoms, the supplement recommendations mentioned
may be appropriate, along with other dietary and lifestyle changes.


The practitioner who can provide support and lifestyle recommendations that address the root causes of patient
specific PMS symptoms can provide care that makes a difference for female patients, while also improving their
overall health.



RESOURCES



PMS
Protocol:‡ This protocol offers focused interventions to support menstrual
comfort in patients with premenstrual syndrome.‡


Nutrient
Solutions to Complement the 5R Protocol: This blog post covers nutrient solutions that
supplement the 5R Protocol and addresses factors related to leaky gut and other GI concerns.


Drug-Nutrient Interactions
Checker: Offers scientifically supported, clinically relevant information that’s easy to
understand with product suggestions based on verifiable science.


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


REFERENCES



  1. NIH.
    Accessed on February 20, 2024.

  2. Clinical
    Practice Guidelines    . American College of Obstetricians and Gynecologists. Dec 2023. 
    Accessed on February 20, 2024.

  3. Trout KK, Teff KL. Curr Diab Rep. 2004 Aug;4(4):273-80. doi: 10.1007/s11892-004-0079-4. PMID:
    15265470.

  4. Dutch Interpretive Guide. Precision Analytical. 2023: 45-51.

  5. Schweizer-Schubert S, Front Med (Lausanne).Jan 18 2021.18(7):479646. doi: 10.3389/fmed.2020.479646.

  6. Handa R and Weiser M. Front Neuroendocrinol. 2014 April ; 35(2): 197–220.
    doi:10.1016/j.yfrne.2013.11.001.

  7. Acevedo-Rodriguez A et al. J Neuroendocrinol. 2018 Oct;30(10):e12590. doi: 10.1111/jne.12590. Epub
    2018 Aug 7.

  8. Dickens MJ et al. J Neuroendocrinol. 2013 Apr;25(4):329-39. doi: 10.1111/jne.12012.

  9. Hou L et al. Stress, 22:6, 640-646, DOI:10.1080/10253890.2019.1608943

  10. Stadler T et al. Psychoneuroendocrinology. 2016; 63: 414-432

  11. Huang et al. Stress. 2015. 18(2):160-168. DOI: 10.3109/10253890.2014.999234

  12. Klatzkin RR et al. J Psychosom Res. 2014 Jan;76(1):46-55. doi: 10.1016/j.jpsychores.2013.11.002.
    Epub 2013 Nov 12. PMID: 24360141; PMCID: PMC3951307.

  13. Escalante Pulido JM et al. Arch Med Res. 1999 Jan-Feb;30(1):19-22. doi:
    10.1016/s0188-0128(98)00008-6. Erratum in: Arch Med Res 1999 May-Jun;30(3):265. PMID: 10071420.

  14. Yeung EH et al. J Clin Endocrinol Metab. 2010 Dec;95(12):5435-42. doi: 10.1210/jc.2010-0702. Epub
    2010 Sep 15. PMID: 20843950; PMCID: PMC2999972.

  15. Valdes CT et al. J Clin Endocrinol Metab. 1991 Mar;72(3):642-6. doi: 10.1210/jcem-72-3-642. PMID:
    1997519.

  16. Zarei S et al. Clin Exp Reprod Med. 2013 Jun;40(2):76-82. doi: 10.5653/cerm.2013.40.2.76. Epub 2013
    Jun 30. Erratum in: Clin Exp Reprod Med. 2013 Sep;40(3):141. PMID: 23875163; PMCID: PMC3714432

  17. Daka B et al. Endocr Connect. 2012 Nov 19;2(1):18-22. doi: 10.1530/EC-12-0057. PMID: 23781314;
    PMCID: PMC3680959.

  18. Chen C et al. Minerva Endocrinol. 2010 Dec;35(4):271-80. PMID: 21178921; PMCID: PMC3683392.

  19. Bernstein MT et al. BMC Womens Health. 2014 Jan 22;14:14. doi: 10.1186/1472-6874-14-14. PMID:
    24450290; PMCID: PMC3901893.

  20. Hu S. et al.  Gut Microbes. 2023 Jan-Dec;15(1):2236749. doi: 10.1080/19490976.2023.2236749.
    PMID: 37559394; PMCID: PMC10416750.

  21. Meneghesso et al. Int J Nutrology. 2022. doi.org/10.54448/ijn2236

  22. Hashim MS et al.  Nutrients. 2019 Aug 17;11(8):1939. doi: 10.3390/nu11081939. PMID: 31426498;
    PMCID: PMC6723319.

  23. Kwon YJ et al. Nutrients. 2022 Jun 14;14(12):2460. doi: 10.3390/nu14122460. PMID: 35745189; PMCID:
    PMC9230049.

  24. AlQuaiz A et al. Int J Womens Health. 2022 Dec 16;14:1709-1722. doi: 10.2147/IJWH.S387259. PMID:
    36561605; PMCID: PMC9766474.

  25. Mitsuhashi R et al. Int J Environ Res Public Health. 2022 Dec 29;20(1):569. doi:
    10.3390/ijerph20010569. PMID: 36612891; PMCID: PMC9819475.

  26. Mohebbi Dehnavi Z et al. BMC Womens Health. 2018 May 31;18(1):80. doi: 10.1186/s12905-018-0565-5.
    PMID: 29855308; PMCID: PMC5984430.

  27. Yesildere et al. Complement Ther Med. 2020 Jan;48:102272. doi: 10.1016/j.ctim.2019.102272. Epub
    2019 Nov 27. PMID: 31987230.

  28. Samadi Z et al. Iran J Nurs Midwifery Res. 2013 Jan;18(1):14-9. PMID: 23983722; PMCID: PMC3748549.

  29. Yaribeygi H et al. EXCLI J. 2022 Jan 24;21:317-334. doi: 10.17179/excli2021-4382. PMID: 35368460;
    PMCID: PMC8971350.

  30. De Souza MC et al. J Womens Health Gend Based Med. 2000 Mar;9(2):131-9.

  31. Facchinetti F et al. Obstet Gynecol. 1991 Aug;78(2):177-81.

  32. Fathizadeh N et al. Iran J Nurs Midwifery Res. 2010 Dec; 15(Suppl1): 401–405.

  33. Ghanbari Z et al. Taiwan J Obstet Gynecol. 2009 Jun;48(2):124-9

  34. Khajehei M et al. Int J Gynaecol Obstet. 2009 May;105(2):158-61.

  35. Bartram HP et al. Gastroenterology. 1993 Nov;105(5):1317-22.

  36. Gaffney BT et al. Life Sci. 2001 Dec 14;70(4):431-42

  37. Kalman DS et al. Nutr J. 2008 Apr 21;7:11.

  38. Berger D et al. Arch Gynecol Obstet. 2000 Nov;264(3):150-3

  39. Kimura K et al. Biol Psychol. 2007 Jan;74(1):39-45.

  40. Timmcke JQ et al. FASEB J. 2008. 22; 760.




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