Amare Global Research White Paper

Modulation of the Gut-Heart-Brain-Axis Improves Mood, Metabolism, and Mental Wellness

Shawn M. Talbott, PhD

As the Chief Science Officer for Amare Global (“The Mental Wellness Company”), one of the most frequent questions that I get from Amare customers and Brand Partners is related to “the research” – where to find it, what it means, and how to apply it to everyday life?

I thought I would use this blog to expand on the hundreds of published papers and patents on our individual ingredients, as well as the dozens of “resource” documents on Amare finished products, by outlining some of our targeted research and how it is all coordinated toward advancing our overall objective of helping people to “Level Up”. 

I wrote a similar overview about 3 years ago, but the timing for an update is perfect, as a number of organizations such as the United Nations (UN), the Global Wellness Institute (GWI), and the Wall Street Journal (WSJ) have recently released reports about the explosion of “mental wellness” and features about how the gut/microbiome is at the center of a fundamental shift in how we understand (and influence) every aspect of human health and performance. Key among these reports is the recent World Happiness Report (2024) which paints a dismal picture and describes a vicious cycle of stress/anxiety/unhappiness that is destroying the quality of life for millions of people around the world (a problem that is particularly acute among our younger demopgraphics).

TL;DR – the key takeaways from these special reports and feature articles can be summarized as:

1. Most of us don’t feel the way we want to feel in terms of stress (too high), mood (too low), mental well-being (feeling “meh”), motivation (lacking), focus (foggy), and performance (don’t even get me started).
2. The COVID pandemic has had some obvious detrimental impacts on stress, mood, and mental wellness – but there is a “positive” aspect where people are beginning to prioritize their mental wellness because they realize that there is no physical health without mental health.
3. The microbiome and entire Gut-Heart-Brain-Axis play prominent roles in determining both our mental wellness and physical health – and science is leading the way to help us balance our microbiome and optimize how we feel and perform.
4. Amare Global was established as “The Mental Wellness Company” to address mental wellness in a comprehensive and holistic/natural way. Our approach centers around the most cutting-edge science incorporating the Microbiome-Gut-Heart-Brain-Axis to improve various aspects of psychological mood state. We use only the highest-quality research-supported individual ingredients, thus ensuring purity, potency, and proof of mental wellness benefits. We also go to the “next-level” by developing our own ingredients and blends, partnering directly with suppliers around the globe, and conducting/publishing/presenting clinical trials on many of our finished formulations.

“The research” can mean a lot of different things to many different people. 

At Amare, we use a lot of “branded” ingredients in our products – not “generic” herbs or “generic” probiotics – but specific plant extracts and DNA-verified probiotic strains that have been uniquely validated in human clinical trials. This is expensive, but we do it to ensure ingredient potency/purity and overall quality and effectiveness of the finished products. This also means that we have literally hundreds of studies and dozens of patents on the specific ingredients found in our products. 

Sometimes by “the research” people are curious about our where we get our ingredients (“sourcing”) – or how we test our ingredients (“quality”). In terms of sourcing, I have personal relationships with growers around the world, often visiting the farms and extraction facilities in remote corners of the globe to ensure sustainable, safe, and fair-trade practices. On the quality side of things, Amare performs over 7,500 different analytical tests every month to ensure that our products are potent (that they contain the right amount of active ingredients) and pure (that they do not contain contaminants like pesticides, heavy metals, pathogens including mold, genetically modified ingredients, allergens including gluten, and contaminants such as antibiotics, hormones, or pharmaceutical drugs).Very few companies in the entire nutraceutical industry have a similar level of commitment to ingredient sourcing and quality.

Because of the complexity of “the research”, we really go out of our way to explain the science of our ingredients and our finished formulas by providing educational videos  – including short highlight videos on every product page at http://Amare.com and longer “deep dive” videos on my YouTube page, as well as Product Information Pages (PIPs), Powerpoint decks, and extensive Technical Data Sheets (TDS) on the specific research-backed ingredients in our products – which can all be found in the “Resources” section at http://Amare.com and in the “back office” for Amare Business Partners. If you want to see “even more research” – you can check out my page on ResearchGate.

Typically by “the research” – people are asking for evidence that the products do what we say they do – so we also go the extra mile to conduct research on our final finished products – and as “The Mental Wellness Company” – we do our research in a unique and coordinated way, which has resulted in several peer-reviewed scientific journal publications, more than a dozen patent applications, and over two dozen invited presentations at scientific and policy conferences (which I’ll outline below). 

It’s important to note that as a mid-stage, fast-growth, international natural products company, we also do a lot of research that is never published or presented (as is the case with most innovative biotech companies). Some of those studies might be related to proving out our proprietary blends; confirming the purity/potency of a particular active ingredient; determining an optimal delivery method; clarifying a mechanism of action; and many other aspects of building a new pioneering type of cutting-edge mental wellness company to improve the lives of millions of people around the world.

Amare Global started in mid-2016 as “The Mental Wellness Company” with our first products launched at the end of 2017 – and has since been a finalist for numerous NutraIngredients and NEXTY awards (sort of like the Oscars and Grammys for the nutrition industry), including…

• Startup of the Year (2018 & 2019 Finalist for Amare Global)
• Best New Finished Product (2018 “NutrAward” for Fundamentals Pack)
  • -which contains our flagship product, Mentabiotics
• Botanical of the Year (2018 Finalist for Mood+)
• Probiotic of the Year (2019 for Kid’s Fundamentals)
• Best New Supplement (2022 Finalist for Edge)
• Probiotic of the Year (2023 Finalist for GBXFit)
• Another one for one of our major products that will be announced in June 2024

Over the years, we have shown that specific blends of nutritional ingredients (our formulas) can deliver meaningful improvements in overall well-being and psychological mood states – including reductions in “negative” factors such as stress, fatigue, depression, and anxiety – and accompanied by improvements in “positive” factors such as vigor, well-being, focus, mood, sleep-quality, and others. These “mental wellness” benefits are manifested through well-defined biological and biochemical mechanisms of action including improved microbiome balance, strengthened gut barrier integrity (i.e. reduced gut permeability or “leaky gut), lowered inflammation, primed immune function, increased heart rate variability, better cardiac risk profiles, balanced blood sugar, elevated neurotransmitter signaling, and reduced stress hormone exposure (among others).

Our individual studies – and the overall project as a coordinated research platform – demonstrate that natural nutritional interventions very well may be the most impactful solution to one of our most pressing global epidemics – and one that is open and accessible to all without the high cost, marginal benefits, and severe side effects of existing synthetic options. 

This white paper summarizes just a portion of our studies, many of which are on-going in areas such as immune health, leaky gut, cognition, metabolism, and the aging process. The overall objective is to expand our understanding of using natural nutritional interventions to help people “level up” from feeling “bad” to experiencing “wellness” and further toward exuding “flourishing.”

Background – A New Mental Wellness Solution – Our Three Brains

We used to think that mental wellness was “just” related to the brain and various influences of neurotransmitters like serotonin and stress hormones such as cortisol. Eventually, science advanced enough, and especially rapidly over the last decade, to inform us that the microbiome (the collection of trillions of gut bacteria) creates up to 90% of our body’s neurotransmitters – and has a dramatic influence on our mood, motivation, and resilience. Even more recent are the scientific and medical observations that the heart, through electro-magnetic signals sent to the brain, plays an equally influential role in determining our mental well-being.

The “first” brain in our head, is networked with both the gut (our “second” brain) and with the heart (our “third” brain). Each of our three brains sends and receives a wide range of signals to and from each other. It is the coordinated action of our three brains – and the interplay between them – that ultimately determines our overall mental wellness. 

Note: for a wide-ranging discussion of the influence of the microbiome and Gut-Heart-Brain-Axis on mental wellness, my recent book, “Mental Fitness” provides a primer…

Our three brains “talk” to each other through a complex network of nerves, cells, and biochemicals. This network—referred to as the Gut-Heart-Brain-Axis—includes nearly 100 trillion bacteria that live in our gastrointestinal system (our “microbiome”) and the cloud of electrical and magnetic signals generated by our heart. Coordination between these helpful bacteria and coherent heart signals are instrumental in modulating the function of our immune system, optimizing the body’s inflammatory response, and supporting many other aspects of our mental wellness and physical health.

An overarching theme between studies and across the entire research platform has been that a wide range of natural ingredients (probiotics, prebiotics, postbiotics, phytonutrients, and herbal extracts including nootropics and adaptogens) can help to restore balance within the interconnected “Gut-Heart-Brain-Axis” – to dramatically and dynamically improve numerous interconnected mental wellness parameters.

Among the numerous lines of evidence and intellectual property that we developed, there are three key studies that describe the arc of this research and Amare Global’s leadership position in the mental wellness space (each of these studies is appended to the end of this White Paper).

• Study 1 (Gut-Brain-Axis): assessed microbiome parameters (e.g. Lactobacillus, Bifidobacterium, Akkermansia, etc) and correlated those levels to psychological outcomes (e.g. depression, anxiety, stress). 

• Study 2 (Heart-Brain-Axis): measured heart efficiency (heart rate variability) and correlated those levels with mental/physical energy parameters (e.g. energy, focus, vigor).

• Study 3 (Mental/Physical Health): showed how improvements in mental wellness (brain), brought about by balancing gut and heart parameters, were also linked to improvements in physical health (blood glucose, cholesterol, cardiac risk, cortisol).

Across these studies (and others – see list below), we confirmed that targeted nutritional interventions could reliably and predictably improve both mental wellness and physical health parameters simultaneously and in a coordinated fashion.

Objective: This research platform intended to investigate the close multi-directional relationship between mental wellness parameters (mood, focus, energy, resilience) and physical health status (body weight, blood sugar, cardiac risk) – and show how these may be dramatically and simultaneously modified through natural nutritional regimens targeting the microbiome and the Gut-Heart-Brain-Axis with a coordinated supplementation regimen combining pro/pre/postbiotics and phytonutrients such as polyphenols, nootropics, and adaptgogens.

Methods: In more than 100 healthy moderately-stressed subjects, we examined interventions of 4-6 weeks duration on various outcomes, such as microbiome balance (Lactobacillus, Bifidobacteria, Akkermansia, and others); biomarkersincluding blood lipids, glucose, cortisol, and butyrate kinase; heart efficiency/variability and psychological mood state(Depression, Tension, Fatigue, Anger, Confusion, and Vigor).

Results: Following supplementation (see individual study for specific findings), we found significant and meaningful increases in populations of “good” bacteria (~8% Bifidobacterium, ~33% Lactobacillus, ~62% S. Thermophilus, ~90% Akkermansia) as well as improvements in bacterial ratios associated with healthier metabolism (~+6% composite score, ~-11% Firmicutes, ~+6% Bacteroidetes, ~-14% F/B ratio). Metabolites associated with stress and glycemic control improved post-supplementation (~-11% cortisol; ~+89% butyrate kinase, ~-6% glucose), as did body fat (~-2%) and blood lipids (~-8% total cholesterol, ~-5% LDL, ~+3% HDL, ~-23% triglycerides, ~-7% TC/HDL). Heart efficiency was improved as indicated by ~15% increase in heart rate variability. Psychological indices were significantly improved post-supplementation for both positive (~+17% Global Mood; ~+23% Vigor) and negative mood states (~-38% Depression; ~-41% Tension; ~-42% Fatigue; ~-31% Confusion; ~-39% Anger).

Conclusions: These results demonstrate, across multiple coordinated studies, the close relationship between microbiome balance, systemic metabolism, heart function, and psychological parameters – and the utility of targeted nutritional supplementation to optimize the entire Gut-Heart-Brain-Axis for not only improved metabolism, but also enhanced mental wellness and physical health.

Amare Global Peer-reviewed Scientific Presentations & Publications

• Several peer-reviewed scientific publications – including Functional Foods for Health & Disease, EC Nutrition, FASEB Journal, and others.

• More than two dozen peer-reviewed scientific presentations – including American College of Nutrition (ACN), American College of Sports Medicine (ACSM), Experimental Biology (EB), HealCon, American College of Lifestyle Medicine (ACLM), International Society of Nutrition Psychology Research (ISNPR), and others.

• More than a dozen patents-issued and patents-pending for the use of natural nutrition interventions for improving various aspects of mental wellness.

Selected Peer-reviewed Publications

• Modulation of Gut-Brain-Axis Improves Microbiome, Metabolism, and Mood. Functional Foods in Health & Disease Journal. 2020; 10(1): 37-54.
• Effect of Coordinated Probiotic/Prebiotic/Phytobiotic Supplementation on Microbiome Balance and Psychological Mood State in Healthy Stressed Adults. Functional Foods in Health & Disease Journal. Vol 9, No 4 (2019)
• Astaxanthin Supplementation Reduces Depression and Fatigue in Healthy Subjects”. EC Nutrition 14.3 (2019): 239-246. 
• Effect of Astaxanthin Supplementation on Psychophysiological Heart-Brain Axis Dynamics in Healthy Subjects. Functional Foods in Health & Disease Journal. Vol 9, No 8 (2019)
• Astaxanthin Sources: Suitability for Human Health and Nutrition. Functional Foods in Health and Disease (July 2019).
• Effect of Astaxanthin Supplementation on Cardiorespiratory Function in Runners”. EC Nutrition 11.6 (2017): 253-259.

Selected Scientific Presentations

• The Impact of Immune Health (on Mental Wellness) in the Post-Pandemic Environment and Understanding the Shift in Consumer Behavior (Wageningen, Netherlands) Sept. 2022
• Priming Dynamic Immune System Function with Functional Foods Improves Quality of Life Parameters. 29th International Conference on Functional Foods and Bioactive Compounds to Reduce the Risk of Diseases (April 29-30, 2021)
• The Brain-Body-Biome – How Mental Wellness Drives a Multi-Faceted Impact on Physical Health. HealCon – Complementary Medicine Conference -Newport CA, (May 2020)
• The Brain-Body-Biome – How Mental Wellness Drives a Multi-Faceted Impact on Physical Health. International Academy of Colon Hydrotherapists – Kissimmee FL June 2020)
• Dual Role of Gut-Brain-Axis Modulation in Obesity and Depression – Functional Food Center – 28th Conference on Functional Foods for Longevity (San Diego, CA Aug 2020)
• Targeted Dietary Supplementation Improves Mental Performance in Children. Experimental Biology / American Physiological Society (April 2020, San Diego, CA)
• Optimization of Heart-Brain-Axis Signaling Improves Mental and Physical Performance. American College of Sports Medicine (June 2020, San Francisco, CA)
• Effect of Coordinated Probiotic/Prebiotic/Phytobiotic Supplementation on Microbiome Balance and Psychological Mood State in Healthy Stressed Adults – portions of dataset presented at:
  • American College of Nutrition (Nov 2017 – Alexandria VA)
    • “Outstanding Research Award”
  • Experimental Biology (April 2018 – San Diego, CA)
  • American College of Sports Medicine (May 2018 – Minneapolis, MN)
  • Mental Health America – Fit for the Future Conference (June 2018 – Wash, DC)
  • Microbiome Movement – Gut Brain Axis (Nov 2018 – Boston, MA)
  • American Mental Wellness Awareness Association (Nov 2018 – Hershey, PA)
  • International Society for Nutritional Psychiatry Research (Nov 2019 – London UK)
• Development of a consumer-oriented microbiome tracker – American College of Sports Medicine (May 2018, Minneapolis MN)
• Effect of natural astaxanthin on mental wellness parameters – American College of Lifestyle Medicine (Oct 2018, Tucson AZ)
• Effect of Astaxanthin Supplementation on Cardiorespiratory Function in Runners – American College of Sports Medicine (May 2017 Denver CO)
• Natural Astaxanthin Improves Mental Wellness – American College of Nutrition (Nov 2017, Alexandria VA)
• Nrf-2 Activation by Palm Fruit Bioactives. American College of Sports Medicine Annual Scientific Conference – Denver, June 2017.
• Effect of Astaxanthin Supplementation on Cardiorespiratory Function in Runners. American College of Sports Medicine Annual Scientific Conference – Denver, June 2017.

Selected Patents & Applications

• Issued = NUTRITIONAL SUPPLEMENTS AND METHODS OF NUTRITIONAL SUPPLEMENTATION AFFECTING MICROBIOME METABOLISM – for coordinated support of microbiome, metabolism, and mood (Mentabiotics, Kids Fundamentals, Happy Juice).
• Issued = NUTRITIONAL SUPPLEMENTS AND METHODS OF NUTRITIONAL SUPPLEMENTATION AFFECTING MOOD AND FOCUS IN CHILDREN – unique blend of saffron, rosemary, clove, oregano, and holy basil to support mood, focus, and behavior (Kid’s Mood+).
• Issued = NUTRITIONAL SUPPLEMENTS AND METHODS OF NUTRITIONAL SUPPLEMENTATION AFFECTING HEART/BRAIN AXIS – unique blend of astaxanthin, palm fruit bioactives, CoQ10, and bergamot fruit extract shown to uniquely improve mood and mental/physical energy levels (MentaHeart).
• Issued = NUTRITIONAL SUPPLEMENTS AND METHODS OF SUPPLEMENTATION AFFECTING THE ENDOCANNABINOID SYSTEM – unique blend of hemp oil, black cumin seed oil, black pepper oil, and white frankincense to fully support the entire ECS (endocannabinoid system) for improvements in pain, mood, stress, and sleep. Works via a previously unknown mechanism of priming ECS receptors and activating ECS receptors for overall superior benefits (HempGBX+).
• Pending = NUTRITIONAL SUPPLEMENTS AFFECTING GUT-BRAIN-AXIS BALANCE AND MENTAL WELLNESS (GBX Proprietary Blend) for signaling support across the entire gut-brain-axis and found in several Amare products (FundaMentals Pack; MentaBiotics; MentaFocus; Energy+; VitaGBX; Kid’s VitaGBX).
• Pending = NUTRITIONAL SUPPLEMENTS AND METHODS OF NUTRITIONAL SUPPLEMENTATION AFFECTING MENTAL WELLNESS AND/OR MOOD – unique 5:1 ratio of EPA:DHA plus lavender oil to promote mental wellness (OmMega).
• Pending = many others for forthcoming products…

Why is this Work Important?

The biggest health problems today are not physical ailments such as heart disease, cancer, and diabetes – but are rather mental conditions related to lifestyle such as depression, anxiety, chronic fatigue, sleep deprivation, and everyday stress. These are not “diseases” but are actually quite normal psychological states that every one of us experiences on a regular basis. For example, just as cholesterol is not a disease (like heart disease) and inflammation is not a disease (like arthritis), so too is depression not a disease (like major depressive disorder, MDD), and anxiety is not a disease (like generalized anxiety disorder, GAD), and leaky gut is not a disease (like Hashimoto’s thyroiditis and other auto-immune conditions).

• When we’re stressed, we’re more likely to crave junk food and store belly fat – but when we’re resilient, we don’t succumb to stress-eating and we make better dietary choices. 

• When we’re tired, we’re less likely to exercise or meditate – but when we have good sleep quality and metabolism, we have abundant energy levels that can fuel an active lifestyle. 

• When we’re depressed or anxious, we’re less likely to take care of ourselves or interact positively with others – but when we have a good mood and a resilient outlook, we’re more likely to love ourselves and apply that love to others. 

The World Health Organization (WHO) has identified stress and depression as global epidemics and the leading causes of disability worldwide. In North America alone, there are hundreds of millions of people who spend hundreds of billions of dollars every year on “feel different” remedies such as antidepressant and anti-anxiety drugs, opioid painkillers, drugs for ADHD, drugs for sleep, and an unending array of energy drinks and junk food that we use to self-medicate in response to being tired, stressed, and depressed.

Unfortunately, while many of these approaches will change how we feel, typically by helping people feel “less bad” – none of them help us “feel good.” These synthetic approaches generally take us from feeling bad in one way to feeling bad in a different way – while utterly failing to help us feel truly good in the ways that we want to feel. 

Our coordinated “Psycho-Nutrition” research platform has spanned several years (and continues) focusing on the links between nutrition, biochemistry, and psychology (e.g. the emerging scientific field of “Nutritional Psychology” investigating how and why nutrients make us feel a certain way). Now we find ourselves at an exciting time in history where we can finally use traditional natural options, many with thousands of years of historical evidence (including traditional Chinese medicine, TCM; and traditional Indian medicine, Ayurveda) – in a science-supported way – to address many of today’s modern mental wellness challenges. These breakthroughs in our understanding of ancient/traditional medicine, natural supplements, and functional foods provide us with a wide array of scientifically validated tools that can dramatically improve how we feel and perform in every aspect of our lives.

• Numerous international organizations, including the Global Wellness Institute, have identified “Mental Wellness” as a segment of the health industry that is expected to experience exponential growth in the coming years (e.g. ~13% CAGR and $330-Billion+ by 2027). 

Further Reading…Wall Street Journal (WSJ) – The Future of Everything Report:

WSJ: “Modern Life is Messing with Our Microbiomes, but Science is Fighting Back“

WSJ; “Forget What You Think Happiness Is“

WSJ; “COVID-19’s Lasting Effects on Mental Health – for Good and Bad“

Final Words

Without overstatement, “Mental Wellness” is, by any measure, both the most urgent need and the most compelling growth opportunity within the broader wellness space – encompassing functional foods, dietary supplements, and numerous aspects of the natural products industry. Amare Global’s leadership in spearheading these studies – and educating about the category in general – is establishing an important foundation on which numerous companies and individuals will be able to build meaningful businesses to support mental wellness for millions of people around the world.

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