THE PCCA BLOG

GLP-1: The Naturally Produced Hormone

Wed, 04 Sep 2024 17:00:00 GMT

You’re likely familiar with semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) used in commercially available prescription medicines for treatment of type 2 diabetes and obesity. Are you aware that GLP-1 — the hormone semaglutide is designed to induce — is naturally produced by the body to help promote healthy blood sugar levels, curb cravings and maintain a healthy weight? Or aware of the bacterium in the gut microbiota that induces natural production of GLP-1?

GLP-1: Key to Blood Glucose Homeostasis

GLP-1 is part of a group of metabolic hormones — called incretin hormones — that help decrease blood glucose levels. The majority of GLP-1s are produced by L-cells lining the small intestine and colon; smaller quantities are secreted by the pancreas and the central nervous system.

In the pancreas, GLP-1 stimulates the release of insulin, increases the amount of insulin-producing pancreatic cells (beta cells) and reduces the release of glucagon — a hormone that raises blood sugar levels. GLP-1 also signals appetite centers in the brain, indicating a sense of fullness during and between meals by slowing gastric emptying.

Primarily triggered by food consumption, GLP-1 release occurs 10 – 15 minutes after eating. Although it remains in the blood system for several hours, nerve activity and other hormones can affect GLP-1 production and levels. For example, somatostatin, a hormone principally produced in the nervous and digestive systems, reduces GLP-1 production; dipeptidyl peptidase-4, an enzyme expressed on the surface of cells, terminates the blood glucose lowering action of GLP-1.^1,2

Remarkably, GLP-1 is glucose-dependent — it reduces blood glucose levels only after a person eats; it does not reduce glucose levels on its own. In clinical studies, GLP-1 administered intravenously to fasting patients failed to reduce blood sugar levels compared with patients who consumed a meal. This inability to induce hypoglycemia, or low blood sugar levels, in IV-administered GLP-1 led to the development of GLP-1 receptor agonists.²

Gut Microbiota Affects GLP-1

The human gut, commonly known as the gastrointestinal (GI) tract, possesses more than 1,000 microbial species that form a complex ecological community known as the gut microbiota. Composed of bacteria, viruses, yeast, fungi and other microorganisms, the gut microbiota plays a pivotal role in health and disease. It serves several functions, including fermentation of food, protection against pathogens, immune response stimulation and vitamin production. Composition, proportion and diversity of an individual’s gut microbiota are affected by genetics, lifestyle (diet), drugs (frequency/use of antibiotics), aging and other factors.^3-5

Microbial metabolites, such as secondary bile acids, short-chain fatty acids, lipopolysaccharide and others within the gut microbiota, trigger GLP-1 secretion. Eating certain foods — eggs, nuts (almonds, pistachios and peanuts), high-fiber grains (oats, barley and whole wheat), avocados, olive oil and vegetables (Brussels sprouts, broccoli and carrots) — has shown to support GLP-1 levels.^5-7

Multiple studies have linked gut dysbiosis — a change or imbalance in the diversity, composition and functions of the microbiota — to reduced GLP-1 levels. Reduced GLP-1 levels are directly associated with development of metabolic disorders, including type 2 diabetes and obesity.^3-8

Probiotics Support Gut Health

In addition to eating GLP-1-supportive foods, specific strains of probiotics can significantly alter the gut microbiome and increase GLP-1 production. For example, the probiotic Akkermansia muciniphila (A. municiphila) secretes a protein that induces natural production of GLP-1. A unique strain of A. municiphila, AH39, targets the mucosal layer of the gut, which is critical for retaining gut barrier integrity and promoting healthy inflammatory markers. It also promotes healthy systemic metabolic outcomes within the gut lining.^9,10

The Bifidobacterium animalis HN019 strain promotes the production of short-chain fatty acids in the gut microbiota. It also supports the intestinal barrier function and promotes healthy inflammatory markers.

The Bifidobacterium animalis B420 strain aids in weight management and supports metabolic health by influencing gut microbiota composition and promoting the production of short-chain fatty acids that support energy metabolism and contribute to GLP-1 secretion.

Lactobacillus rhamnosus GG is believed to support gastrointestinal health and immune balance. It may help promote the structural and functional integrity of the gut barrier. It also supports the composition and activity of the gut microbiome, promoting an increase in beneficial bacteria and the production of short-chain fatty acids. These actions may help maintain a healthy intestinal environment, promote healthy inflammatory markers and support metabolic functions.

Clostridium butyricum nourishes the gut lining, promotes healthy inflammatory markers and supports healthy barrier function. Clostridium butyricum 10 is known for its butyrate-producing capabilities. Butyrate is a primary energy source for colonocytes, supporting their health and promoting a robust intestinal barrier. It also supports the healthy expression of tight junction proteins, further enhancing barrier integrity.¹⁰

Many misrepresent the naturally occurring GLP-1 hormone with GLP-1 RA. It’s important, however, to recognize the distinctions. For individuals who cannot tolerate or afford GLP-1 RAs, options, including dietary food choices and probiotic nutritional supplements, are available.

References

Society for Endocrinology. Your Hormones: Glucagon-like peptide 1. Last reviewed July 2021. Accessed August 2024 at https://www.yourhormones.info/hormones/glucagon-like-peptide-1/
Nadkarni P, Chepurny OG, Holz GG. Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014;121:23-65. https://doi:10.1016/B978-0-12-800101-1.00002-8
Tomaro-Duchesneau C, LeValley SL, Roeth D, et al. Discovery of a bacterial peptide as a modulator of GLP-1 and metabolic disease. Sci Rep. 2020; 10:4922. https://doi.org/10.1038/s41598-020-61112-0
Zeng Y, Wu Y, Zhang Q, et al. Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio 15:e02032-23. https://journals.asm.org/doi/10.1128/mbio.02032-23
Afzaal M, Saeed F, Shah YA, et al. Human gut microbiota in health and disease: Unveiling the relationship. Front Microbiol. 2022; 13:999001. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.999001
Wang Q, Lin H, Shen C, et al. Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling. Gut Microbes. 2023; 15(2). https://doi.org/10.1080/19490976.2023.2274124
Pederson T. What Foods Increase GLP-1 Levels? Healthline. 2024. Medically reviewed by Adam Bernstein, MD, ScD. Accessed August 2024 at https://www.healthline.com/health/foods-that-increase-glp-1
Li HY, Zhou DD, Gan RY, et al. Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review. Nutrients. 2021;13(9):3211. https://doi:10.3390/nu13093211
Rodrigues VF, Elias-Oliveira J, Pereira ÍS, et al. Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front Immunol. 2022;13:934695. https://doi:10.3389/fimmu.2022.934695
Wellness Works. Metabolic Probiotic with Akkermansia Product Data Sheet. 2024. Accessed August 2024 at https://beta.pccarx.com/prod_data/10444-Metabolic-Probiotic-with-Akkermansia.pdf

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.

Essential Supplements for Adults

Wed, 01 May 2024 19:37:37 GMT

In today's fast-paced world, maintaining optimal health can be a challenge. Despite the best intentions, many adults struggle to meet their nutritional needs through diet alone — that's where supplements can play a crucial role.

by Stephanie Allen, ASIN, DCN, DSS, CPES, Wellness Works Manager

Here are five supplements that adults should consider incorporating into their daily routine:

Multivitamin: According to the CDC, most Americans fall short of meeting their nutrient needs through diet alone. A high-quality multivitamin can help fill in the gaps, providing essential vitamins and minerals necessary for overall health and well-being.^1,2
Probiotic: A balanced microbiome in the gut is essential for digestive health, a robust immune system and even mood regulation. Probiotic supplements can help support the diversity of beneficial bacteria in the gut, promoting optimal gut function and overall wellness.^3-5
Fish Oil: Rich in omega-3 fatty acids EPA and DHA, fish oil supplements have been associated with numerous health benefits. The American Heart Association recommends a daily intake of at least 250 to 500 milligrams of EPA+DHA to support heart health and overall well-being.⁶
Vitamin D: Often referred to as the “sunshine vitamin,” vitamin D plays a crucial role in bone health, immune function and mood regulation. However, an estimated 88% of the population doesn't receive enough vitamin D from sunlight alone. Supplementation can help ensure adequate levels, especially for those who spend limited time outdoors or live in regions with limited sunlight.⁷
Magnesium: This essential mineral is involved in over 300 biochemical reactions in the body, including muscle function, nerve function and energy production. Despite its importance, studies suggest that approximately 75% of American adults don't meet the recommended daily intake of magnesium. Supplementation can help bridge this gap and support overall health and vitality.^8,9

While these supplements can be beneficial for many individuals, it's essential to remember that they are not a substitute for a balanced diet and healthy lifestyle. Additionally, it's always advisable to consult a healthcare professional before starting any new supplement regimen.

References

CDC. (Updated 2021). Only 1 in 10 Adults Get Enough Fruits or Vegetables. Accessed April 2024 at https://www.cdc.gov/nccdphp/dnpao/division-information/media-tools/adults-fruits-vegetables.html
U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020 - 2025. Accessed April 2024 at https://www.dietaryguidelines.gov/sites/default/files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf
Olvera-Rosales, L. B., Cruz-Guerrero, A. E., Ramírez-Moreno, E., et al. (2021). Impact of the Gut Microbiota Balance on the Health-Disease Relationship: The Importance of Consuming Probiotics and Prebiotics. Foods (Basel, Switzerland), 10(6), 1261. Accessed April 2024 at https://doi.org/10.3390/foods10061261
Appleton J. (2018). The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integrative Medicine (Encinitas, Calif.), 17(4), 28–32. Accessed April 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469458/
Hemarajata, P., & Versalovic, J. (2013). Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therapeutic Advances in Gastroenterology, 6(1), 39–51. Accessed April 2024 at https://doi.org/10.1177/1756283X12459294
Williamson, L. (2023). Are you getting enough omega-3 fatty acids? American Heart Association News Stories. Accessed April 2024 at https://www.heart.org/en/news/2023/07/05/are-you-getting-enough-omega-3-fatty-acids
NIH Office of Dietary Supplements. (Updated 2023). Vitamin D Fact Sheet for Health Professionals. Accessed April 2024 at https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Schwalfenberg, G. K., & Genuis, S. J. (2017). The Importance of Magnesium in Clinical Healthcare. Scientifica, 2017, 4179326. Accessed April 2024 at https://doi.org/10.1155/2017/4179326
DiNicolantonio, J. J., O'Keefe, J. H., & Wilson, W. (2018). Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart, 5(1), e000668. Accessed April 2024 at https://doi.org/10.1136/openhrt-2017-000668

These statements have not been evaluated by the Food and Drug Administration. Products referenced in this article are not intended to diagnose, treat, cure or prevent any disease.

Detoxification in the New Year

Wed, 03 Jan 2024 15:37:00 GMT

by Stephanie Allen, ASIN, DCN, DSS, CPES, Wellness Works Manager

Toxic Exposure

Everything from clothing and furniture to the air and soil has some level of chemical contaminants that can be harmful to health. Many of these are deemed “safe” individually and in very small volumes, but they build up over time. Multiple exposures to combinations of many different chemical toxins can lead to health problems such as metabolic syndrome.

Toxins are often stored in the adipose tissues and released back into circulation during weight loss, increasing autoimmune responses and leading to feelings of fatigue, increased allergies and illness. Therefore, a quality detoxification protocol is also an important part of any weight loss program.

To lessen the exposure and subsequent toxic load in the body, adopting a healthful diet that is low in processed foods, preservatives and pesticides is a good first step. Choose organic fruits and vegetables whenever possible. Decreasing any unnecessary over-the-counter medications, limiting alcohol intake and avoiding any nicotine products are very important steps to lessen the burden on the body. We are also unnecessarily exposed to foreign chemicals through our personal-care products. The United States allows more than 1,600 chemicals in personal care products that are banned in most of Europe due to health concerns.¹ We should regularly review used hygiene products, cosmetics and fragrances that may increase toxic exposure.

The Environmental Working Group is a great resource and contains lists of fruits and vegetables with the least and most pesticide, as well as information on toxins in personal care and cosmetic products. The regularly updated lists can be viewed on their website at ewg.org.

Boosting the Body’s Natural Processes

Lessening exposure to environmental toxins and chemicals is only part of decreasing our toxic load for optimal health. Boosting the body’s natural ability to process and eliminate toxins is another necessary step. Processes and metabolic systems of the kidneys, skin, liver and lungs, for example, rid the body of foreign chemicals. Movement and exercise, especially activities that generate sweat, are a great way to help promote clearing through increased lymph flow and cleansing through the pores in the skin. Steam baths and warm showers are a great way to destress and detox too, and increased water consumption helps eliminate broken-down toxins from the body.

Diet is also crucial. Cruciferous vegetables contain indole-3-carbinol (I3C), a strong antioxidant shown to improve detoxification processes and promote healthy metabolic pathways. Increased consumption of colorful vegetables also provides beneficial antioxidants that counteract free radicals formed when toxins break down. Some great dietary additions include blueberries, broccoli and Brussels sprouts. Herbal teas that contain dandelion, milk thistle, ginger, rooibos, green tea and burdock — or any combination of these — will provide chemicals and compounds that assist in detoxification. Beware of detox teas that contain large amounts of senna. Senna is a natural laxative and may lead to dehydration or poor absorption of needed nutrients if used too often or in too large a dose.

Adding Nutritional Supplements

Ingesting enough fiber is also paramount for clearing foreign materials. The Wellness Works combination product, Colon Health Support (WW #10370), is a proprietary blend of fibers, fructooligosaccharides (FOS), pectin and detoxifying herbs, as well as ingredients that support the detoxifying and cleansing pathways. Glutathione is a powerful antioxidant that helps clear free radicals that form during the breakdown of toxins, as well as supports the regeneration of antioxidants in the body. The liposomal form available in Liposomal Glutathione (WW #10325) — provided in a purified phosphatidylcholine delivery system — helps protect glutathione bonds from degradation during digestion. The liposomal delivery system also offers enhanced absorption due to the hydrophilic nature of the phospholipids. Studies have shown that the Setria^® glutathione, available in L-Glutathione Reduced (WW #10389), supports enhanced immune cell function and increases levels of glutathione in the blood. Liposomal Glutathione and L-Glutathione Reduced are good options to add into a detoxification routine or for daily use.

Milk thistle provides silymarin, a highly active botanical that works to protect the liver from free radical damage and supports glutathione concentrations. In addition to herbal teas, milk thistle is also available in Milk Thistle Plus (WW #10110). Our supplement provides 175 mg of milk thistle extract and is standardized to contain a minimum of 80% silymarin.

During the holidays, it is also common to overindulge in alcohol. For those looking to specifically provide the body with the depleted nutrients caused by excessive drinking or limit its impact with nutrients prior to alcohol consumption, we offer Alcohol Detox (WW #10395). Our Alcohol Detox formula combines micronutrients and cofactors essential to supporting healthy liver function and proper alcohol metabolism.²

References

Zhou, L., Martiner, J. (2022, Oct. 25) Personal care product chemicals banned in Europe but still found in U.S. Accessed November 2022 at https://www.ewg.org
Lieber C. S. (2003). Relationships between nutrition, alcohol use, and liver disease. Alcohol Res Health. 2003;27(3):220-231. (3), 220–231. Accessed November 2022 at https://pubmed.ncbi.nlm.nih.gov/15535450/

These statements have not been evaluated by the Food and Drug Administration. Products referenced in this article are not intended to diagnose, treat, cure or prevent any disease.

The Role of NAD in Healthy Aging

Thu, 19 Oct 2023 15:05:07 GMT

Functional medicine, a biology-based approach that focuses on identifying and addressing the root cause of diseases, is a popular topic. And so is healthy aging. It’s no wonder, especially when we consider our desire to understand the root cause of diseases and sustain health throughout life’s many stages.

In previous decades, growing old equaled a diminished quality of life, where many pathologies associated with aging were unavoidable. We now understand that limiting stress, maintaining energy levels, striving to achieve a balanced immune system and performing DNA repair are just a few ways that may support a healthy aging process.

NAD: Central to Metabolism & Aging

Functional medicine practitioners recognize how nicotinamide adenine dinucleotide (NAD), a coenzyme required to metabolize carbohydrates, fats and amino acids to energy, influences healthy aging. NAD is found in all living cells and is comprised of two dynamic, energy exchanging forms: NAD+, the oxidized form, and NADH (H for hydrogen), the reduction form. NAD+ is a critical metabolic intermediate that serves as a universal electron acceptor in hundreds of oxidation/reduction reactions reduced to NADH.

NAD+ is used as a co-substrate by several different types of enzymes, such as sirtuins (SIRTs), adenosine diphosphate (ADP), ribose transferases (ARTs) and the cyclic ADP-ribose (cADPR) synthases. Through these activities, NAD+ metabolism and its intermediate metabolites regulate a broad spectrum of cellular functions, such as energy metabolism, DNA repair, regulation of epigenetics and inflammation (see image below).¹ Maintaining a healthy ratio of coenzymes NAD+/NADH affects many aspects of cellular health, including the dynamics between metabolism and immune cell functions.

However, NAD+ levels and NAD+/NADH ratios decline with age. These lower levels are associated with many of the symptoms that were previously considered an unavoidable part of aging. Many now recognize the relationship between NAD+ and insulin sensitivity, stress management, circadian rhythm and neurodegeneration.²

Impact of NAD Levels & Deficiencies

Energy & Mitochondrial Function
Production of adenosine triphosphate (ATP), the energy currency of the body related to mitochondria metabolic processes, is impacted by NAD+ levels and the ratio of NAD+/NADH. NAD deficiency is associated with lower energy levels and mitochondrial dysfunction or damage.³
Sirtuins & DNA Repair
Sirtuins, a group of proteins involved in the metabolism and aging of cells, serve as cellular responses to oxidative and genotoxic stress. Appropriate levels of NAD+ and NAD+/NADH ratios are necessary for sirtuins and sirtuin activity. Maintaining adequate levels of NAD+ can positively impact DNA regeneration and repair through NAD+’s capacity as a substrate for the sirtuins as well as the poly (adenine diphosphate-ribose) polymerases (PARPs).^4-7
Cognitive Support
Restoring NAD+ levels proved beneficial in animal models, with study results indicating NAD+ may play a role in the prevention of neurodegeneration and protection against free radicals. Multiple NAD+-dependent processes are involved in neuroplasticity — where neurons in the brain develop new learning and memory pathways — when previous synaptic junctions were damaged or lost.6,7 The effects of NAD+ availability may also help improve sleep and subsequently mental clarity.⁸
Insulin Sensitivity
NAD+ and NAD+-dependent sirtuins also modulate insulin sensitivity and glucose homeostasis. An overexpression of SIRT1 reportedly improved glucose intolerance and dyslipidemia. SIRT1 was shown to regulate glucose and lipid metabolism, as well as increase NAD+ contents and SIRT1 activity in adipose tissue to help prevent diet-induced insulin resistance.⁹
Immune Balance and Inflammation
NAD+ is an intermediate for many immune responses and its availability can have impacts on resolution of inflammatory conditions. While more research is needed, most studies show that increased NAD+ levels have anti-inflammatory effects. Inflammageing, an age-related increase in pro-inflammatory markers for chronic inflammation, decreased in many cases by increasing the availability of NAD+ through NAD+ precursors.¹⁰Recent studies also show NAD+ contributes to anti-tumor T-cell responses.¹¹

Recognition of maintaining healthy NAD levels is growing. Many practitioners now recommend this important coenzyme as an oral supplement or administered intravenously during office visits.

New Product from Wellness Works

Wellness Works is pleased to announce a new product: NAD+Vitality. Our nutritional supplement contains Bioenergy RiaGev®-WS™, a proprietary combination of Bioenergy Ribose® and nicotinamide ascorbate (vitamin B3). A triple-blind, randomized, placebo-controlled pilot study showed a nicotinamide and d-ribose combination of the new RiaGev increased NAD+ levels in the blood, reduced waking cortisol, showed improved glucose levels and enhanced circulating antioxidants. No reports of skin flushing, which occurs in many NAD+ precursor supplements, were reported. In addition, NAD+ Vitality resolves the need to break down the combination and conversion of NAD+, like many other precursor supplements on the market.11

These statements have not been evaluated by the Food and Drug Administration. Products referenced in this article are not intended to diagnose, treat, cure or prevent any disease.

References

Navarro, Maria N., Gomez de las Heras, MM., Mittelbrunn, M. (2021) Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing. British J Pharma, 179, 9, 1839–1856. Open access publication. Accessed 09/2023 at https://doi.org/10.1111/bph.15477
Ruszkiewicz, J. A., Bürkle, A., Mangerich, A. (2022) Fueling genome maintenance: On the versatile roles of NAD+ in preserving DNA integrity. J Bio Chem, 298(6). Accessed 09/2023 at https://doi.org/10.1016/j.jbc.2022.102037
Diaz-Vegas, A., Sanchez-Aguilera, P., Krycer, J.R., et al. (2020) Is mitochondrial dysfunction a common root of noncommunicable chronic diseases? Endo Reviews, 41(3). Accessed 09/2023 at https://doi.org/10.1210/endrev/bnaa005
Grabowska, W., Sikora, E, Bielak-Zmijewska, A. (2017) Sirtuins, a promising target in slowing down the ageing process.” Biogeron, 18(4) 447–476, Accessed 09/2023 at https://doi.org/10.1007/s10522-017-9685-9
Amjad, S., Nisar, S., Bhat, A.A., et al. (2021) Role of NAD+ in regulating cellular and metabolic signaling pathways. Mol Met 49. Accessed 09/2023 at https://doi.org/10.1016/j.molmet.2021.101195
Imai, S., Guarente, L. (2014) NAD+ and sirtuins in aging and disease. Trends Cell Bio, 24(8) 464–471. Accessed 09/20233 at https://doi.org/10.1016/j.tcb.2014.04.002
Wilk, A., Hayata, F., Cunningham, R., et al. (2020) Extracellular NAD+ Enhances PARP-Dependent DNA Repair Capacity Independently of CD73 Activity. Nature News/Scientific Reports. Accessed 09/20233 at https://www.nature.com/articles/s41598-020-57506-9
Conlon, N. J. (2021) The role of nad+ in Regenerative Medicine. Plas & Recon Sur, 150. Accessed 09/20233 at https://doi.org/10.1097/prs.0000000000009673
Yamaguchi, S., Yoshino, J. (2017) Adipose tissue nad+ biology in obesity and insulin resistance: From mechanism to therapy.” BioEssays, 39(5), 1600227. . Accessed 09/20233 at https://doi.org/10.1002/bies.201600227
Navarro, M. N., Gomez de las Heras, M.M., Mittlebrunn, M. (2021) Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing. British J Pharma 179(9) 1839–1856. Accessed 09/20233 at https://doi.org/10.1111/bph.15477
Xue, Y., Shamp, T., Nagana Gowda, et al. (2022). A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD+ Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Clinical Trial. Nutrients, 14(11), 2219. Accessed 09/20233 at https://doi.org/10.3390/nu14112219