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Immunomodulation for Mental Health: A Focus on Positive Mood

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....

11 / 26 / 2024
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Using Amino Acids and OPCs in a Functional Medicine Model for Positive Mood

Pure Encapsulations Pro Blog

Watch the Webinar

Using Amino Acids and OPCs in a Functional Medicine Model for Positive Mood

Presented by Dr. James Greenblatt, MD+

 

Mainstream models often fail to address mood effectively due to biological factors and biochemical individuality. Functional medicine seeks to identify all mood influencers, including biology, neurochemistry, diet, and lifestyle.


Join Dr. James Greenblatt as he discusses functional medicine for mood and explores two key interventions: amino acids and OPCs. Attendees will gain clinical, evidence-based recommendations to enhance their therapeutic toolkit. 

Learning objectives

  • Compare traditional vs. functional medicine models for mood
  • Understand amino acids' roles in enzyme and neurotransmitter production
  • Explain how amino acids support brain function, digestion, and mood
  •  Identify two neuroprotective mechanisms of OPCs
  •  Discuss documented mood-supporting mechanisms of curcumin

About the Speaker

James M. Greenblatt, MD, is a pioneer in the field of integrative medicine and has treated patients since 1988. He was the Chief Medical Officer at Walden Behavioral Care in Waltham, MA for 21 years and is an Assistant Clinical Professor of Psychiatry at Tufts University School of Medicine and Dartmouth College Geisel School of Medicine. An acknowledged integrative medicine expert, Dr. Greenblatt regularly lectures on the scientific evidence for nutritional interventions in psychiatry, has authored eight books, and is the founder of Psychiatry Redefined, an educational platform dedicated to the personalized, evidence-based treatment of mental health. Dr. Greenblatt helped co-develop the PureSYNAPSE™ exclusive.  

 

 

+Dr. Greenblatt is a paid advisor for Pure Encapsulations. 

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Immunomodulation for Mental Health: A Focus on Positive Mood

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

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

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 LearningClinical 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

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

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 LearningClinical 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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