Nutritional and Lifestyle Interventions for Positive Mood: A Quick Guide for Providers

“How are you feeling?” It’s a question we’re asked almost every day, and according to the statistics, many of us are not feeling so well. In the United States more than 50% of Americans will need support for their mental health at some point in their lifetime.^{1, 2} The good news is that there are many lifestyle factors we can incorporate in our daily lives to support our mood:

1. Reduce and manage stress. Stress is impossible to completely remove from our lives, but we can manage it by setting firm boundaries, making time for your needs, asking for help where you need it and engaging in rituals such as journaling, meditation and breathing techniques.

2. Exercise and movement. Moving your body has many mood enhancing benefits including reduced stress hormones, increased endorphins and improved sleep and digestion.³  You don't have to only go to a gym — dancing, walking and playing with your kids all count too. The key to consistent movement is making sure you enjoy it.

3. Ensure adequate sleep. Sleep is truly the foundation of health because it’s during sleep that our body clears out the debris, rebuilds and heals. A 2021 study found a link between sleep and mood through the glymphatic system which is highly active during sleep and clears metabolic waste out of the brain through fluid exchange.⁴

4. Exposure to sunlight and nature. Daily sunlight helps regulate our circadian rhythms which supports sleep and boosts mood by increasing serotonin. It’s also a source of vitamin D. Getting out into nature further reinforces that serotonin boost.^5‡

5. Connection and community. Connection is a fundamental human need and in our technological age we’re getting much less. Having a supportive community where you feel like you belong can reduce the incidence of anxiety and depression.⁶ Engage in recreational sports, volunteering and other group activities to enhance your mood.

6. Consume a healthy diet. A diet focused on whole foods that’s lower in sugar, and higher in protein, healthy fats and complex carbohydrates provides the necessary amino acids, fats and nutrients that support the creation of mood supporting hormones and neurotransmitters.

7. Supplement as needed. Sometimes we need extra support, and this is where supplements can play a significant role in helping the body obtain the necessary nutrients to support mood. Taking a synergistic approach to supplementing for mood tends to yield the best results since there are many contributing factors. Below are some potential options:

• Multivitamin: A high quality multivitamin delivers many of the nutrients needed to support neurotransmitter synthesis, including zinc and B vitamins.^‡
• Omega 3 Fatty Acids: Omega 3 fatty acids are called essential fatty acids because your body needs them but can’t produce them. In observational and epidemiological studies, higher plasma levels of EPA have been associated with healthy mood. ^{7, 8‡}
• Magnesium: Magnesium has many systemic benefits. In a cross-sectional study involving 210 elderly individuals, optimal magnesium intake was associated with positive mood.^9‡
• Probiotics: Gut health plays an important role in mental health. Probiotics encourage healthy gut bacterial ecology and intestinal integrity.^{10, 11‡.}
• Curcumin: The antioxidant and immune-modulating properties of curcumin have been implicated in mood, relaxation and neuronal health.^{12, 13}
• B Vitamins: Folate, vitamin B6 and vitamin B12 promote methylation, nerve support and cellular energy production. Folate plays important roles in emotional well-being.^‡
• Rhodiola: Rhodiola is an adaptogenic herb that has been used for hundreds of years to help lessen mental and physical stress.^{16, 17, 18‡}
• L-theanine: L-theanine is the active component of green tea that promotes relaxation without causing drowsiness.^19‡

Supporting mood and stress resilience is critical as a foundation for health. It is essential that clinicians assess stress levels as part of the bigger picture so that appropriate measures can be taken.

Pure Encapsulations’ Mood Protocol and mood support formulas provide research-backed solutions for your patients’ needs.^‡

References

1. Kessler RC, et al. World Psych. 2007;6(3):168-176.
2. Key Substance Use and Mental Health Indicators in the United States: Results from the 2015 National Survey on Drug Use and Health. Rockville, MD: Center for Behavioral Health Statistics and Quality. 2016.
3. Cooney, GM, Dwan K, Mead G. JAMA. 2014 Jun 18;311(23):2432-3
4. Yan T, et al. Front Psychiatry. 2021; 12: 658340.
5. Bum-Jin Park, et al. Int J Environ Res Public Health. 2020 Jun; 17(12): 4348.
6. Schaefer S, et al. PLoS One. 2013; 8(11): e80329.
7. Féart C, et. al. Am J Clin Nutr. 2008 May;87(5):1156-62.
8. Samieri C, et. al. Am J Clin Nutr. 2008 Sep;88(3):714-21.
9. Barragán-Rodríguez L, et al. Magnes Res. 2008 Dec;21(4):218-23.
10. Arseneault-Bréard J, et al. Br J Nutr. 2012 Jun;107(12):1793-9.
11. Rao AV, et al. Gut Patho. 2009 Mar 19;1(1):6.
12. Braidy N, et al. FEBS J. 2010 Jan;277(2):368-82.
13. Bhutani MK, et al. Pharmacol Biochem Behav. 2009 Mar;92(1):39-43.
14. Menon V, et al. Indian J Psychol Med. 2020 Jan-Feb; 42(1): 11–21.
15. Young L, et al. Nutrients. 2019 Sep; 11(9): 2232.
16. Spasov AA, et al. Phytomedicine. 2000 Apr;7(2):85-9.
17. Maslova LV, et al. Eksp Klin Farmakol.1994 Nov-Dec;57(6):61-3.
18. Stojcheva E, et al. Molecules. 2022 Jun; 27(12): 3902.
19. Juneja LR, et al. Trends in Food Science & Technology.1999. 10; 199-204.

Nutritional Support for Athletic Recovery

As a healthcare practitioner, it's essential to recognize the significance of athletic recovery for your patients. Whether they are professional athletes or just enjoy exercising regularly, recovery plays a critical role in their overall health and performance. In this blog post, we'll discuss the importance of athletic recovery and provide tips on promoting it.^‡

The Benefits of Athletic Recovery

Athletic recovery is the process of allowing your body to rest and heal after physical activity. It's essential for preventing injuries, reducing inflammation and improving performance. Here are some of the benefits of athletic recovery:

• Reduced risk of injury: When your body is fatigued, you're more likely to get injured. Recovery helps reduce the risk of injury by allowing your body to repair and rebuild.
• Improved performance: Recovery is essential for improving performance. When your body is well-rested, you can perform at your best.
• Inflammation management: Inflammation is a natural response to physical activity. The key is maintaining a balanced inflammatory response. Effective recovery techniques help to promote balanced inflammatory responses.
• Prevention of overtraining: If you aren't paying attention, overtraining can strike without notice, negatively impacting performance, sleep, energy, motivation and eating patterns.

Factors of Recovery

When looking at the actual factors associated with recovery, it is important to understand the underlying physiology to effectively monitor objective markers that can quantify whether or not a patient is recovering from their efforts. Some of the factors include:

• Normalization of physiological functions like blood pressure and heart rate
• Restoration of energy stores (blood glucose and muscle glycogen)
• Replenishment of cellular energy enzymes

Nutritional Strategies Promoting Athletic Recovery

As a healthcare practitioner, you can help your patients promote athletic recovery by providing them with the right strategies. Here are some recommendations:

Stress Management

• Ashwagandha – An Ayurvedic herb that has been used for over 4,000 years and has been shown to moderate occasional stress.^1‡
• B-Vitamins – Promote cognitive function and positive mood in addition to supporting the body’s nutrient needs during stress.^{2, 3‡}
• Multivitamins – Under stressful states, the body has an increased need for many micronutrients and a multivitamin can be helpful to support the body’s increased needs.^4‡

Promote Healthy Cytokine Balance

• Curcumin – Curcumin has been the subject of over 3,000 studies over the past 30 years and has an extensive history of use. The remarkable breadth of applications of curcumin stem from its multifocal mechanisms involving diverse intracellular signaling pathways and the regulation of hundreds of genes involved in cytokine balance, detoxification and cellular health.^{5, 6, 7, 8, 9‡}

Promote Muscle Recovery

• Creatine – Creatine is an energy carrier that is naturally present in muscles, brain and other organs. By increasing the rate of creatine phosphorylation, ammonia and lactate levels in the blood are lowered resulting in faster recovery from exercise. It is also important for vegan and/or vegetarian athletes.¹⁰
• Magnesium – Magnesium is important for hundreds of processes throughout the body and supports muscle function and recovery. Additionally, athletes can have up to 20% increase in needs for this nutrient versus normal populations.^{11, 12, 13}

Promote Connective Tissue Repair

• Collagen – Collagen has been shown to support musculoskeletal health to help optimize performance and mobility and supports healthy cartilage and joint tissues.¹⁴
• Vitamin C – Supports the healthy production of collagen and the health of connective tissue.¹⁵

Conclusion

Athletic recovery is essential for preventing injuries, improving performance and promoting overall health. As a healthcare practitioner, you can help your patients promote athletic recovery by providing them with the right tools and information. Encourage rest days, provide stretching and mobility exercises, recommend proper nutrition, suggest massage and other recovery techniques and monitor progress. By doing so, you can help your patients achieve their fitness goals and live a healthier life.

References

1. Lopresti AL, Smith SJ. J of Herb Medi. 2021;28:100434.
2. Cohick PL, et al. Eur J of Clin Nutr. 2011;65, 4234.
3. Young LM, Pipingas A, White DJ, et al. Nutrients. 2019;11(9):2232.
4. Schlebusch L, Bosch BA, Polglase G, Kleinschmidt I et al. Suid-Afrikaanse tydskrif vir geneeskunde. 2022;90(12).
5. Zhang F, Altorki NK, Mestre JR, et al. Carcin. 1999 Mar;20(3):445-51.
6. Santos-Parker JR, Strahler TR, Bassett CJ, et al. Aging (Albany NY). 2017 Jan 3;9(1):187-208.
7. James MI, Iwuji C, Irving G, et al. Cancer Lett. 2015 Aug 10;364(2):135-41.
8. Bundy R, Walker AF, Middleton RW, Booth J. J Altern Complement Med. 2004 Dec;10(6):1015-8.
9. Panahi Y, Rahimnia AR, Sharafi M, et al. Phytother Res. 2014 Nov;28(11):1625-31.
10. Wax B, Kerksick CM, Jagim AR, et al. Nutrients. 2021 Jun 2;13(6):1915.
11. Reno AM, Green M, Killen LG, et al. J Strength Cond Res. 2022 Aug 1;36(8):2198-2203.
12. Nielsen FH, Lukaski HC. Magnes Res. 2006 Sep;19(3):180-9.
13. Vernon WB. Magnesium. 1988;7(5-6):234-48.
14. Clark KL, Sebastianelli W, Flechsenhar KR, et al. Curr Med Res Opin. 2008 May;24(5):1485-96.
15. DePhillipo NN, Aman ZS, Kennedy MI, et al. Orthop J Sports Med. 2018 Oct 25;6(10):2325967118804544.

Four Underlying Factors for Quality Sleep

We all know how important sleep is. It plays a central role in our health, emotional well-being and performance at work or school. Yet so many people experience occasional sleeplessness. Did you know that 43% of adults report that stress has caused them to lose sleep in the last month, more than one third of adults use medication or other aids to help with sleep, and the productivity losses of fatigued workers adds up to about $136 billion?^{1, 2, 3} Here are a few of the underlying causes of occasional sleeplessness:

1. Circadian Rhythm
2. Glycemic Regulation
3. Stress
4. Sleep Hygiene

Circadian Rhythm

Circadian rhythms are daily cycles that regulate everything from our body temperature to hormone levels. They’re primarily controlled by the suprachiasmatic nucleus (SCN) in the hypothalamus. The SCN is a tiny region of nerve cells that uses light information from the retina to synchronize internal clocks with the outside world. This helps us sleep when it’s dark and wake when it’s light.⁴ The SCN has two main clocks: a central one that controls sleep and wake cycles, and an external one that’s synchronized with the environment. These two clocks work together to help us fall asleep at night, stay asleep during the night and wake up in the morning. When circadian rhythms are disrupted, it can have serious effects on our health.⁵ Shift workers and jet lag are two common examples of this phenomenon.⁶

Glycemic Regulation

Glycemic fluctuations can significantly impact falling asleep and staying asleep throughout the night.⁷ Blood sugar fluctuations can lead to waking up at night due to impacts on cortisol, which is generally seen as a “stress” hormone. One of the impacts of cortisol is the release of stored blood sugar in response to a fluctuation. When cortisol is elevated, it becomes a challenge to fall asleep or get back to sleep, as it is a hormone that boosts alertness.⁸ The sleep impacts of blood sugar fluctuations are, unfortunately, a feed-forward cycle, which shows that when someone is not sleeping appropriately this can have a further influence on insulin sensitivity and glucose homeostasis.⁹

Stress

Stress is all around us and difficult, if not impossible, to fully remove from modern life. Unfortunately, stress can have a disproportionate effect on sleep, whether this be from the worry that comes along with it, or the hormone and neurotransmitter impacts. As discussed, elevated cortisol doesn’t only impact glycemic regulation, it can also be related to melatonin secretion.¹⁰ Stress results in the activation of the HPA resulting in the release of cortisol, noradrenaline and adrenaline, all of which are excitatory neurotransmitters, important to the waking hours, but very impactful if levels are increased when one is trying to get a good night’s sleep.

Sleep Hygiene

Pursuing the right lifestyle changes and behaviors can have a much bigger impact on sleep quality than one may think. Below is a “punch list” to refer to every day that, when followed appropriately, will promote high-quality, restful sleep.

• No screens for 30-60 min prior to bed – The bright light from screens disrupts our normal sleep-wake schedule.
• Keep the same bedtime and wake-up time – Our body responds well to a fixed schedule, keeping to a regular sleep/wake routine will help your body to stay on track.
• Avoid caffeine and alcohol for 4-6 hours prior to bed– Both have larger deleterious effects on sleep than you realize, either from the obvious response to stimulants or due to the metabolism needs of alcohol.
• Have a pre-sleep routine – Try out some relaxing activities like reading, meditation, stretching or peaceful music.
• Finish exercise at least 2 hours prior to bedtime – You need to relax after exercise, and this can take some time.
• Find the right temperature – The Sleep Foundation suggests a sleeping temperature between 60-67 degrees Fahrenheit as optimal.¹¹
• Improve your sleeping environment – Comfortable bedding, complete darkness and removing distracting noises can go a long way.

Nutrient/Herb Recommendations

Once the primary impact on sleep quality has been determined, it becomes straightforward to prioritize appropriate recommendations, based on the unique needs of the patient. Below is a summary of potential options which can help to support the personalized needs of patients.

Conclusion

Promoting healthy sleep onset is important for and needed by many patients. Having a clear understanding of why a patient is experiencing occasional sleeplessness is the starting point. Once that is identified and prioritized, one can determine the appropriate course of action aligned with both the goals of the patient and the underlying physiology responsible for the patient’s concerns. Check out our latest Sleep Protocol and sleep support formulas!

References

1. American Psychological Association. (2013, January 1). Stress and sleep. Retrieved from: https://www.apa.org/news/press/releases/stress/2013/sleep
2. Maust DT, Solway E, Clark SJ, et al. Am J Geriatr Psychiatry. 2019;27(1):32-41.
3. Ricci JA, Chee E, Lorandeau AL, Berger J. J Occup Environ Med. 2007;49(1):1-10. doi:10.1097/01.jom.0000249782.60321.2a
4. Fukuhara C, Tosini G. Front Biosci. 2003;8:d642–651.
5. Radziuk, J. M. 2013;62(4), 1017-1019.
6. Waterhouse J. J R Soc Med. 1999;92(8):398-40
7. Shoji S, Shoji Y. Nihon Rinsho. Nihon Rinsho. 2009 Aug;67(8):1525-31.
8. Hirotsu C, Tufik S, Andersen ML. Sleep Sci. 2015;8(3):143-152.
9. LeBlanc ES, Smith NX, Nichols GA, et al. BMJ Open Diabetes Res Care. 2018 Dec 26;6(1):e000604.
10. Mohd Azmi NAS, Juliana N, Azmani S, et al. Int J Environ Res Public Health. 2021;18(2):676.
11. The Best Temperature for Sleep. Sleep Foundation. Retrieved from: https://www.sleepfoundation.org/bedroom-environment/best-temperature-for-sleep

Are Multivitamins Really That Important?

Written by Chris Oswald, DC, CNS*

This article offers an up-to-date overview on multivitamins and if it is beneficial to take this supplement.

A healthy diet consisting of a variety of foods can be quite beneficial to your health. If you are not eating enough fruits, veggies, beans (legumes), whole grains, nuts (high in magnesium), and other foods containing valuable nutrients, it may be beneficial to take a supplement. Unfortunately, most American adults are not meeting recommended daily intake levels of key nutrients through diet alone.^{1, 2, 3}

These nutrients, and others, are key contributors to many health-promoting functions throughout the body, like immune function,⁵ energy production,⁶ and overall wellness.⁷ Researchers have examined the benefits within certain health areas, such as cognition⁸ and cardiovascular health,⁹ and concluded that multivitamins don’t work. However, it’s important to note that the purpose of these studies was to test the impact of a multivitamin against a specific disease state, but multivitamins are not designed to treat any diseases. Multivitamins are there to fill the nutritional gaps in one’s diet.

As noted above, American adults are not getting enough of the critical nutrients essential to the healthy and optimal function of the human body. The collection of ingredients in a high-quality multivitamin is designed to work in concert to deliver overall wellness benefits by supporting many basic functions throughout the body. Some of the ingredients with their purpose are as follows:

• Fully chelated minerals and antioxidants to support optimal health.^10‡
• Bioavailable nutrients like methylated B-vitamins.^10‡
• Lutein and zeaxanthin to support eye health.^12‡
• Choline and inositol, which are essential to neuronal function.^{13, 14‡}
• Vitamin D provides broad overall support for cellular health.^15‡

While pursuing a well-balanced diet and acquiring all the necessary vitamins and minerals from diet should be everyone’s goal, it is important to realize the current state of many of your patients and clients. Even with the best of intentions, it is difficult to get all the nutrients needed from diet alone, and the data that continuously comes out of NHANES supports the possibility that many of your patients can benefit from the consistent use of a multivitamin. It is also important to realize that multivitamins are not intended to treat any disease or health condition, but meant to provide a sort of “vitamin and mineral insurance” to help ensure that patients meet the recommended daily intake levels necessary to support healthy function throughout the body.

Pure Encapsulations® offers our best-selling O.N.E. Multivitamin, providing support for overall wellness with vitamins, minerals, and antioxidants.^‡ Learn more here.

References

1. Office of Dietary Supplements - Nutrient Recommendations and Databases. NIH Office of Dietary Supplements. https://ods.od.nih.gov/HealthInformation/nutrientrecommendations.aspx. Accessed December 23, 2022.
2. WWEIA Data Tables. WWEIA Data Tables: USDA ARS. https://www.ars.usda.gov/northeast-area/beltsville-md-bhnrc/beltsville-human-nutrition-research-center/food-surveys-research-group/docs/wweia-data-tables/. Accessed December 23, 2022.
3. NHANES- National Health and Nutrition Examination Survey. https://www.cdc.gov/nchs/nhanes/index.htm. Published November 29, 2022. Accessed December 23, 2022.
4. Office of Dietary Supplements - Nutrient Recommendations and Databases. NIH Office of Dietary Supplements. https://ods.od.nih.gov/HealthInformation/nutrientrecommendations.aspx. Accessed January 13, 2023.
5. Crawford C, Brown LL, Costello RB, Deuster PA. Nutrients. 2022;14(21):4604.
6. Tardy AL, Pouteau E, Marquez D, et al. Nutrients. 2020;12(1):228. 8
7. McKay DL, Perrone G, Rasmussen H, et al. J Am Coll Nutr. 2000;19:613-621
8. Young LM, Gauci S, Arnoldy L, et al. Nutrients. 2022;14(23):5079.
9. Sesso HD, Rist PM, Aragaki AK, et al. Am J Clin Nutr. 2022;115(6):1501-1510.
10. McKay DL, Perrone G, Rasmussen H, et al. J Am Coll Nutr. 2000;19:613-621
11. Prinz-Langenohl R, Brämswig S, Tobolski O, et ak. Br J Pharmacol. 2009 Dec; 158(8): 2014–2021
12. Hammond BR, Fletcher LM, Roos F, et al. Invest Ophthalmol Vis Sci. 2014 Dec 2;55(12):8583-9.
13. Knott V, de la Salle S, Choueiry J, et al. Pharmacol Biochem Behav. 2015 Apr;131:119-29.
14. Lucas CT, Call FL 2nd, Williams WJ. J Clin Invest. 1970 Oct;49(10):1949-55
15. Hossein-nezhad A, Spira A, Holick MF. PLoS One. 2013;8(3):e58725.

*Chris Oswald, DC, DNS is an employee of Atrium Professional Brands, Inc.

The Renewable Energy Within: Remodeling Mitochondrial Networks through Diet and Lifestyle Strategies

Webinar: "The Renewable Energy Within: Remodeling Mitochondrial Networks through Diet & Lifestyle Strategies" with Dr. Kelly Heim, Ph.D.

VIEW THE WEBINAR

This blog explains the process and importance of mitochondrial health and the various supplemental process to support cellular energy.

Throughout a typical day, everyone deals with their own individual routines and how to go about performing specific tasks during this time. Generally, most tasks we perform require mental energy, and some require a lot of physical energy. But regardless of the tasks, both will require a good amount of ATP (adenosine triphosphate), the chemical energy all our cells use to sustain life and keep us healthy. Specifically, ATP is vital for the health and of certain organs such as the brain, muscles and other tissues that demand a lot of energy. One interesting fact about ATP is you use half your body weight worth of ATP every day, which a lot of it getting regenerated and some being made from scratch by our bodies.

ATP, indirectly, comes from the food we eat every day with cells converting caloric energy into ATP. Theoretically the more calories you eat, the more ATP you can make but you might rethink this after further study. A lower calorie diet rich in phytochemicals may help you create more cellular energy and ATP, which is a good thing for our bodies.

ATP is created by mitochondria, the energy powerhouses of the cells and essential organelles that generate this high-energy molecule. Glucose, fatty acids and certain amino acids that we consume are metabolized by the TCA cycle, or also known as the Krebs Cycle, in addition to other pathways. The end result is NADH, which carries an electron to the electron transport chain. Ultimately, this simulates ATP Synthase, the enzyme that makes ATP from ADP, a low-energy phosphate.

There are hundreds to thousands of these structures inside each cell, depending on the tissue. It’s even been suggested that about 10% of our body weight is mitochondria, but this is hard to measure¹.

Loss of mitochondrial quality or quantity has been associated with several phenotypes, including loss of grey matter, fewer cardiomyocytes, slower detoxification, and smaller, weaker muscles. Aging tends to occur more rapidly in organs that are highly dependent on mitochondria, such as the brain, muscles, and heart. A common opinion in the medical literature is that a cell with more mitochondria, or better functioning ones, is typically a healthier one. It’s probably also a younger one, since as we age the quality and quantity of mitochondria decline as we grow older. This pattern is a feature of AACD, or Age-Associated Cellular Decline, which describes the constellation of cellular and bioenergetic hallmarks of normal human aging.

Why would you want to enhance the quality or quantity of mitochondria? There are 3 clinical areas why this makes a lot of sense:

• Muscle strength and stamina
• Cardiovascular health
• Neurocognitive health

As we get older, the mitochondria diminish in function, energy output and membrane output. Older or damaged mitochondria not only make less ATP, but contribute to cellular degeneration and apoptosis. Together these two factors contribute to the decline in cellular function as we age.

The process to building new mitochondria is called mitochondrial biogenesis, which is highly responsive to diet and lifestyle. Research shows you can build new mitochondria by restricting calories and eating a low energy diet. Reducing caloric intake by eating less can create more ATP for your cells.

Urolithin A (UA) is a unique molecule which is derived from ellagitannins found in pomegranates and certain berries and nuts. A study published in Nature Medicine (2016) reported that urolithin A stimulated mitophagy in preclinical models and improved muscle function and exercise capacity in rodent models while also increasing muscle strength in C. elegans, a preclinical paradigm of aging.^2‡

In the first human clinical trial, four weeks of urolithin A supplementation in healthy, sedentary elderly subjects (at doses of 500 mg and 1000 mg per day), confirmed that UA is safe, orally bioavailable, and effective in increasing mitochondrial gene expression in skeletal muscle and improving mitochondrial biomarker profiles.^3‡

Urolithin A is a first-in-class mitophagy modulator for cellular energy & muscle health.⁴ It works, at least in part, by promoting mitochondrial renewal, which is a key factor in cellular energy production, muscle health and healthy aging.^‡

Renual, which contains urolithin A, coenzyme Q10 and trans-resveratrol, supports cellular energy and muscle health and is designed for middle-aged and older adults.^‡

Pure Encapsulations offers other products to support mitochondrial health, including Mitochondria-ATP, which supports cellular energy and mitochondrial health with a newly updated formulation that includes NMN (nicotinamide mononucleotinamide) to support NAD+, a key cofactor in cellular energy production.^‡

Learn more about these products by visiting our Energy and Fitness Health Category today!

We have a webinar based on this topic for you to listen, conducted by Dr. Kelly Heim, Ph.D.* You can watch here: https://blog.pureencapsulationspro.com/view-our-webinar-recording-the-renewable-energy-within-remodeling-mitochondrial-networks-through-diet-and-lifestyle-strategies/

Works Cited

1. Nisoli E., Carruba MO. J Cell Sci. 2006.119(Pt 14) 2855-62.
2. Ryu D, et al. Nat Med. 2016;22(8):879-888
3. Andreux PA, et al. Nat Metab 1:595-603
4. As of 11/2/2020 in the healthcare practitioner channel

*Dr. Kelly Heim is an employee of Atrium Innovations, Inc.

Vitamin B₁₂: How to Optimize Based on Individual Needs and Health Goals

Webinar: “The Renewable Energy Within: Remodeling Mitochondrial Networks through Diet & Lifestyle Strategies” with Kelly Heim, Ph.D.

VIEW THE WEBINAR

This article offers an up-to-date overview on the different forms, functions, and benefits of vitamin B₁₂ with special attention to personalization and genetic and laboratory assessments.

Overview of the Forms and Functions of B₁₂

What Is B₁₂?

Vitamin B₁₂ is a water-soluble micronutrient that exists in several different forms, collectively called cobalamins. Cobalamins contain a cobalt molecule within a complex ring system that can bind to different ligands. These ligands, also known as side chains, determine what form vitamin B₁₂ is in.

There are four forms of cobalamin. Hydroxocobalamin and cyanocobalamin are precursors to the active forms, methylcobalamin and adenosylcobalamin. Methylcobalamin is involved in homocysteine metabolism and the methylation pathway.° Adenosylcobalamin plays a central role in the mitochondria and supports energy production, muscle, and nerve health.^‡

What Are the Benefits of B₁₂?

There is a wide range of clinical applications for vitamin B₁₂, especially if you're trying to address metabolic, neurological, and cognitive needs. The active forms of B₁₂ serve as coenzymes in reactions that support red blood cell function, DNA synthesis, homocysteine metabolism, energy production, ATP formation, neurological function, muscle health, and cognition.^‡

How Do We Get Vitamin B₁₂?

Vitamin B₁₂ is naturally bound to proteins within animal products, and upon ingestion, is broken down by stomach acid and pepsin. B₁₂ is transported through the gastrointestinal tract by forming a complex with transcobalamin I and is eventually absorbed in the small intensive or terminal ileum. It then is transported to the liver where most of it is stored. Interestingly, some B₁₂ is secreted back into the gut where it needs to be absorbed again through a process called enterohepatic recirculation. The remaining fraction that doesn't get stored in the liver or recirculated forms a complex with transcobalamin II and goes through the bloodstream, eventually crossing the cell membrane via endocytosis.^‡

Once in your cells, B₁₂ gets to work. One way in which B₁₂ is used by the body is through methylcobalamin’s role in the methylation pathway. Methylation is a ubiquitous process with big implications. It entails the donation of a methyl group (CH₃) to a molecule, which acts as a “green light” for subsequent reactions to occur. When methylation is going well, the process helps repair your DNA, regulates hormones, produces energy, supports detoxification, keeps your immune system healthy, supports the protective coating along your nerves, and strengthens the nervous system. The whole point of the methylation pathway is to generate SAMe, which is a methyl donor. A central step in generating SAMe is the conversion of homocysteine to methionine, which is performed by an enzyme called methionine synthase, which requires methylcobalamin as a cofactor.^‡

The second function of vitamin B₁₂ is in the form of adenosylcobalamin, which operates in the mitochondria as a critical cofactor for an enzyme called methylmalonyl-CoA-mutase or MCM, which converts methylmalonyl COA to succinyl-CoA in the Krebs cycle or the TCA cycle. The Krebs Cycle drives the formation of cellular energy in the form of ATP. If there is inadequate adenosylcobalamin to drive this cycle, it slows down, and you get a buildup of methylmalonyl COA and methylmalonic acid. This buildup is a key way to test as a marker of intracellular, mitochondrial, B₁₂ status.^‡

Personalization

Now that we’ve reviewed the benefits of B₁₂, we need to talk about what happens when you don’t have enough B₁₂ to support optimal function.

Common Signs of Low B₁₂

• Occasional fatigue
• Occasional irritability, apathy, mood changes
• Changes in tongue appearance
• Patients often complain about occasional burning or prickling sensation—primarily in the extremities—that results from low B₁₂

Patient Populations at Risk for Low B₁₂

Older people should remain aware of B₁₂ levels and think beyond just consuming adequate amounts of animal products. This is important because while they may be taking in enough B₁₂, they may have difficulty absorbing B₁₂ since stomach acid production and enzyme secretion both decline with age.

Vegetarians and vegans should also be monitored for signs and symptoms of low B₁₂. Because the primary source of B₁₂ is through consuming animal products, individuals abstaining from eating meat will likely not be taking in sufficient vitamin B₁₂. One caveat is that fermented products do contain small amounts of B₁₂ due to the bacteria present in these foods. Vegetarians and vegans' symptoms of low B₁₂ tend to gradually develop over years, so while you may not be seeing any overt symptoms, it is important to test them regularly to assess their status.

Patients with intestinal conditions also require vigilance on vitamin B₁₂ status. These individuals may not be absorbing enough vitamin B₁₂ to maintain adequate body stores, and also might excrete more B₁₂ because their gut may not adequately reabsorb it after enterohepatic recirculation.

The profound inter-individual variability in vitamin B₁₂ requirements indicates the importance of taking a personalized approach to helping your patients achieve optimal B₁₂ levels.

Laboratory and Genetic Assessments for B₁₂

If you have a patient who you would like to monitor for B₁₂, there are five main methods that are helpful for assessing B₁₂ status.

Initial assessment of B₁₂ status should include a complete blood count and serum test for vitamin B₁₂ levels. These assessments will give you a birds-eye view to confirm B₁₂ absorption, but it does not offer details pertaining to intracellular status.

Serum homocysteine can be used in conjunction with these tests to give you a better indication of a vitamin B₁₂ assimilation and overall methylation competence, because it also takes into account folate and vitamin B₆. If you have normal homocysteine levels, that means methylation is going quite well, but there is a possibility that folate and B₆ may be doing the heavy lifting, thereby camouflaging a potential issue with B₁₂.

Methylmalonic acid (MMA) is a test that is more specific to the intracellular status of B₁₂ because it indicates absorption and transport status. This is a specific B₁₂ biomarker that inversely correlates with mitochondrial assimilation; if you have high MMA levels, it means that you have lower B₁₂ status. This is indicated when serum levels are in the low end of the normal range. In cases such as this, be on the lookout for neurological symptoms that suggest that B₁₂ might be low. This test is not widely used but can be an important tool in assessing a patient’s B₁₂ status.

The fourth method is holo-transcobalamin II (holoTCII), which is also helpful in assessing absorption and transport status of B₁₂. Transcobolamin II is one of the important transporters of B₁₂ and is responsible for carrying B₁₂ through the bloodstream and delivers it to cells that need it. While this test is not widely available, it should be reserved if you have a refractory case of low B₁₂ that is not responding, and you've already performed these other assessment methods.

Ordering a genetic test alongside labs testing can be helpful in guiding further assessment and personalization. Genetic tests are available for less than $100 and can be a cost-effective way to identify potential underlying challenges in absorption, transport and assimilation. These three insights not only pertain to B₁₂, but to other vitamins and nutrients as well, such as folate and B₆, which help paint a larger picture of what may be happening with your patients. Remember, it is important to understand both genotype and phenotype, so running a genetic test in conjunction with your lab assessments is key to guiding further personalization and dosages.

The genetic markers of relevance are:

• FUT2 (rs602662: GG, GA) is an enzyme that participates in the regulation of the microbiome and host microbe interactions, which plays a role in B₁₂ uptake. This variant reduces the function of this enzyme and reduces B₁₂ absorption.
• TCN2 (rs1801198: CG, GG) transport is affected by variations in the TCN2 gene, which codes the transcobalamin transport carrier protein.
• MTR (rs1805087: GG, GA) and MTRR (rs1801394: GG, GA) are important for assimilation. These polymorphisms affect methionine synthase, which is encoded by the MTR gene and MTRR, which supports the regeneration of methyl and affects the methylation cycle.

Conclusion

In conclusion, vitamin B₁₂ has many benefits, and is essential for maintaining metabolic, neurological, and cognitive processes. It can exist in four forms, with methylcobalamin and adenosylcobalamin being the two active forms. Methylcobalamin is important for supporting the methylation pathway and is particularly involved in cognitive and neurological functions. Adenosylcobalamin is involved in ATP production in the mitochondria and is important for optimal muscular and cellular health, as well as neuronal health.^‡

Low doses of B₁₂ are obtained from consuming a diet containing animal products. Patients who do not consume animal products may develop low B₁₂ and should be assessed regularly. Older individuals are also at risk of developing low B₁₂ because absorption function naturally declines with age. Patients with GI conditions that affect absorption should also be routinely checked for adequate B₁₂ levels. If patients are on acid-blocking medications or Metformin, there is strong evidence that shows a connection with long-term use of these drugs and decreases B₁₂ status.

There are a variety of methods used to assess vitamin B₁₂ in your patients, but the important note is that personalization is key, and using a genetic test in conjunction with lab testing can help elucidate an individual’s needs relating to B₁₂ status.

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