Psychobiotics Going Mainstream?

Last week, the science journal/magazine, Science (one of the leading scientific publications on the planet) ran an excellent article on the “Psychobiome” (gut bacteria – aka the “microbiome” – that are involved in psychological effects such as stress, mood, and anxiety).

Since I’ve been researching and writing about this area for many years – and developing natural products to optimize the microbiome for improved mood, reduced stress, and enhanced mental fitness (aka “nutritional psychology”), I found this article to be just what the doctor ordered for the stressful times we’re all living in – I hope you do as well?

You can read the full original article here and see a highlighted version with my notes below.

Bacterial residents of the intestines may influence neurons and the brain through several routes.

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Meet the ‘psychobiome’: the gut bacteria that may alter how you think, feel, and act
By Elizabeth Pennisi (May. 7, 2020)

CAMBRIDGE, MASSACHUSETTS—Katya Gavrish is searching for new brain drugs in a seemingly unlikely place: human stool samples. An earnest and focused microbiologist who trained in Russia and loves classical music, she’s standing in front of a large anaerobic chamber in a lab at Holobiome, a small startup company here. She reaches into the glass-fronted chamber through Michelin Man–like sleeves to begin to dilute the sample inside. That’s the first step toward isolating and culturing bacteria that Gavrish and her Holobiome colleagues hope will produce new treatments for depression and other disorders of the brain and nervous system. (DocTalbott note = it’s difficult to over-emphasize how much impact the microbiome has on the brain)

The eight-person company plans to capitalize on growing evidence from epidemiological and animal studies that link gut bacteria to conditions as diverse as autism, anxiety, and Alzheimer’s disease. Since its founding a mere 5 years ago, Holobiome has created one of the world’s largest collections of human gut microbes. The company’s CEO, Phil Strandwitz, cannot yet say exactly what form the new treatments will take. But the targeted ailments include depression and insomnia, as well as constipation, and visceral pain like that typical of irritable bowel syndrome—conditions that may have neurological as well as intestinal components. Strandwitz, a mild-mannered Midwesterner with a Ph.D. in microbiology, isn’t prone to visionary statements, but neither is he short on ambition: He predicts the first human trial will start within 1 year. (DocTalbott note = our group has already conducted/presented/published several human trials showing how specific probiotic/prebiotic/phytonutrients can dramatically improve mood states including depression, anxiety, tension, and others)

The allure is simple: Drug development for neuropsychiatric disorders has lagged for decades, and many existing drugs don’t work for all patients and cause unwanted side effects. A growing number of researchers see a promising alternative in microbe-based treatments, or “psychobiotics,” a term coined by neuropharmacologist John Cryan and psychiatrist Ted Dinan, both at University College Cork. “This is a really young and really exciting field with a huge amount of potential,” says Natalia Palacios, an epidemiologist at the University of Massachusetts, Lowell, who is looking into connections between gut microbes and Parkinson’s disease.

Some researchers prefer a less hurried approach focused on understanding the underlying biology. But Holobiome and a few other companies are eager to cash in on the burgeoning, multibillion-dollar market that has already sprung up for other microbial therapies, which aim to treat conditions including intestinal disorders, allergies, and obesity. Those companies are pushing ahead despite many unresolved questions about how psychobiotic therapies might actually work and the potential dangers of moving too fast. “There’s a gold rush mentality,” says Rob Knight, a microbiologist at the University of California (UC), San Diego.

OVER THE PAST 20 YEARS, the recognition that the microbes living inside us outnumber our body’s own cells has turned our view of ourselves inside out. The gut microbiome, as it’s known, weighs about 2 kilograms—more than the 1.4-kilogram human brain—and may have just as much influence over our bodies. Thousands of species of microbes (not only bacteria but also viruses, fungi, and archaea) reside in the gut. And with as many as 20 million genes among them, those microbes pack a genomic punch that our measly 20,000 genes can’t match. Gut bacteria can make and use nutrients and other molecules in ways the human body can’t—a tantalizing source of new therapies.

The brain is the newest frontier, but it’s one with an old connection to the gut. The ancient Greeks, for example, believed mental disorders arose when the digestive tract produced too much black bile. And long before microbes were discovered, some philosophers and physicians argued that the brain and gut were partners in shaping human behavior. “What probably happens is that our brain and our gut are in constant communication,” says Cryan, who over the past decade has helped drive efforts to decode those communications. (DocTalbott note = think of all the terminology that we use everyday about having “gut feelings” or “trusting your gut” – and the new science of the microbiome is teasing out these effects that we’ve been observing since the beginning of time)

Epidemiological researchers have turned up intriguing connections between gut and brain disorders. For example, many people with irritable bowel syndrome are also depressed, people on the autism spectrum tend to have digestive problems, and people with Parkinson’s are prone to constipation.

Researchers have also noticed an increase in depression in people taking antibiotics—but not antiviral or antifungal medications that leave gut bacteria unharmed. Last year, Jeroen Raes, a microbiologist at the Catholic University of Leuven, and colleagues analyzed the health records of two groups—one Belgian, one Dutch—of more than 1000 people participating in surveys of their types of gut bacteria. People with depression had deficits of the same two bacterial species, the authors reported in April 2019 in Nature Microbiology.

Researchers see ways in which gut microbes could influence the brain. Some may secrete messenger molecules that travel though the blood to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Bacterial molecules might relay signals to the vagus through recently discovered “neuropod” cells that sit in the lining of the gut, sensing its biochemical milieu, including microbial compounds. Each cell has a long “foot” that extends outward to form a synapse-like connection with nearby nerve cells, including those of the vagus.

Indirect links may also exist. Increasingly, researchers see inflammation as a key factor in disorders such as depression and autism. Gut bacteria are key to proper immune system development and maintenance, and studies show that having the wrong mix of microbes can derail that process and promote inflammation. And microbial products may influence what are known as enteroendocrine cells, which reside in the lining of the gut and release hormones and other peptides. Some of those cells help regulate digestion and control insulin production, but they also release the neurotransmitter serotonin, which escapes the gut and travels throughout the body. (DocTalbott note = because of all these interacting factors, we also need to look beyond “just” the microbiome to also include each layer of the entire Gut-Brain-Axis, which gives us targets at the level of the microbiome, and at the level of the gut environment, and the level of the gut lining, and the immune system, and the inflammatory cascade, etc)

Although the mechanisms remain elusive, animal studies by Cryan and others have bolstered the idea that gut microbes can influence the brain. Rats and mice given fecal transplants from people with Parkinson’s, schizophrenia, autism, or depression often develop the rodent equivalents of those problems. Conversely, giving those animals fecal transplants from healthy people sometimes relieves their symptoms. The presence or absence of certain microbes in young mice affects how the mice respond to stress as adults, and other mouse studies have pointed to a role for microbes in the development of the nervous system.

At their lab, Cryan, Dinan, and their colleague Gerard Clarke think the amino acid tryptophan, which some gut bacteria produce, could be a causal link. Microbes or the body’s own cells can convert tryptophan into serotonin, a neurotransmitter implicated in depression and other psychiatric disorders. Cells also turn tryptophan into a substance called kynurenine, which reacts further to form products that can be toxic to neurons. Changes in the microbiome might tip the production of those various substances in a way that impairs mental health, Cryan says. Research has shown, for example, that people with depression convert tryptophan into kynurenine more readily than into serotonin.

Cryan’s group has amassed scores of papers and reviews that have helped solidify the case for microbial effects on several psychological and neurological disorders. But teasing effective fixes out of those links will be difficult, Clarke says: “It is one thing to know that a particular aspect of host physiology is influenced by our gut microbes and quite another to bend this influence to our will.”

Clarke’s group collaborates and consults with many companies and has tested some potential psychobiotics for stress management in healthy volunteers. But he sees a long road to treatments. “It will be important to understand better and more precisely the mechanisms at play.”

HOLOBIOME ISN’T AS PATIENT. Strandwitz founded the company in 2015 while still a graduate student in Kim Lewis’s microbiology lab at Northeastern University. “He very politely told me that he would join the lab only if I helped him start a company once he graduated,” recalls Lewis, who is famous for discovering and working to commercialize new antibiotics from soil microbes. Lewis agreed, but he figured it would be 10 years or more before Strandwitz would have his own company. Lewis was wrong: It only took 4 years.

At Northeastern, Strandwitz learned what he calls the “art of cultivation” from Gavrish, who was working with Lewis on isolating soil microbes. At the time, only about 25% of gut bacteria could be grown in the lab. Gavrish, who specializes in isolating and describing new microbial species, taught Strandwitz to manipulate nutrients and use antibiotics to give slow-growing, picky bacteria a chance to survive in culture instead of being outcompeted by more aggressive species. He began to track down growth factors to keep recalcitrant species going. Now, Strandwitz says, “We have in culture about 70%” of the known human gut microbes. If true, it’s a figure few other labs can match.

One growth factor Strandwitz identified turned out to be the key to launching his entrepreneurial dreams. He and colleagues isolated a bacterium that couldn’t survive on typical culture media and required an amino acid called gamma-aminobutyric acid (GABA) to thrive. GABA is a neurotransmitter that inhibits neural activity in the brain, and its misregulation has been linked to depression and other mental health problems.

The researchers reasoned that if this gut microbe had to have GABA, some other microbe must be making it. Such GABA producers might be a psychobiotic gold mine. Strandwitz and colleagues began to add gut microbes one at a time to petri dishes containing the GABA eater. If the GABA eater thrived, the scientists would know they’d found a GABA producer. They discovered such producers among three groups of bacteria, including Bactereroides. They quickly filed a patent for packaging those bacteria—or their products—to treat people with depression or other mental disorders.

Before publishing those findings, the group teamed up with researchers at Weill Cornell Medicine who were doing a brain scan study of 23 people diagnosed with depression. They found that people with fewer Bacteroides bacteria had a stronger pattern of hyperactivity in the prefrontal cortex, which some researchers have associated with severe depression. The collaboration reported its findings on 10 December 2018 in Nature Microbiology, along with the discovery of GABA-producing bacteria. (DocTalbott note = one of our very recent trials showed a substantial increase in Bacteroidetes – leading to not just improvements in mood and overall well-being, but also in body fat levels, metabolism, and cardiovascular health)

Holobiome further discovered that the bacteria produce GABA in the rat digestive tract, which may increase GABA levels in the brain. And it found that GABA producers reduced learned helplessness—a symptom of depression—in those animals. One of Strandwitz’s co-authors, microbial ecologist Jack Gilbert at UC San Diego, is also testing the therapeutic potential of GABA-producing bacteria in rats. His group and Holobiome have both observed that treated rats are more likely to stay longer on an uncomfortably warm surface—a test of visceral pain tolerance—perhaps because elevated GABA calms them. The findings are unpublished, but they’ve persuaded Gilbert to investigate whether those bacteria can also reduce anxiety in rats. “It’s clear they do have a neuromodulatory effect,” he says.

GABA is too big to reach the brain by slipping across the blood-brain barrier, a cellular defense wall that limits the size and types of molecules that can get into the brain from blood vessels. Instead, the molecule may act through the vagus nerve or the enteroendocrine cells. Some researchers might question why bacteria would be any more beneficial than GABA-boosting drugs. But Strandwitz says the bacteria may do more than simply boost GABA. He notes that they produce molecules that may have other effects on the brain and body, thereby addressing other symptoms of depression. (DocTalbott note = getting your microbiome to produce more GABA is a great way to reduce stress, tension, and anxiety – but what if you could also get your microbiome to make more dopamine so you’re more energized and motivated – or more serotonin so you’re happier and more content – or more norepinephrine so you can concentrate and focus – the list of potential benefits goes on and on – and most of them are achievable naturally)

He and Gilbert are unfazed by those uncertainties. “If we can show an influence, without any side effects, I don’t see any reason for not going forward with clinical trials,” Gilbert says.

At Holobiome, Strandwitz and colleagues have identified and ranked 30 promising GABA-producing bacteria, including the ones Gilbert is testing. Now, the company is enlisting an outside manufacturer to figure out which GABA-producing bacteria are best suited to produce in large enough quantities to test in people. The researchers hope to complete regulatory and ethical reviews in time to start human trials by early 2021. “We’ve been able to progress at this rate because we know our microbiology,” Strandwitz says. The initial target conditions are insomnia and irritable bowel syndrome with constipation.

Ultimately, Holobiome does not know whether its best products will be a single bacterial species, a group of species, or a compound made by bacteria. “For now, live bugs work the best,” Strandwitz says. He suggests a consortium of bacteria that includes a wider range of species than typical probiotics will be more versatile and able to treat multiple aspects of, say, depression.

HOLOBIOME IS ALREADY LOOKING beyond GABA producers. Thousands of newly isolated microbes wait in frozen vials at the company’s headquarters for their psychobiotic potential to be explored. “Whenever we see someone publishes a new paper on the microbiome, we can check if we have those bacteria and replicate the experiments,” says Holobiome’s Stephen Skolnick, who recently joined the company.

A key tool for those experiments is a “gut simulator,” a series of flasks connected by tubing, with several portals for adding microbes and for monitoring what’s happening inside. By allowing a mock microbiome to develop from different combinations of bacteria, sometimes with mammalian cells in the mix, the researchers can investigate newly isolated microbes and their products. If the scientists see promise, they can quickly pivot to thinking about additional products to develop.

Skolnick took the lead on obtaining a patent for Holobiome’s use of queuine—a vitamin-like molecule only produced by certain gut microbes—to improve mental well-being. The body uses queuine to build neurotransmitters such as dopamine, serotonin, and melatonin. Whether adding queuine producers or the molecule itself to the gut might help people with mental illness isn’t clear, but Strandwitz says he’s excited about the idea.

“It’s been amazing to witness the tremendous growth in the microbiome gut-brain field,” says UC Los Angeles biologist Elaine Hsiao. Like Strandwitz, she is an enthusiast, having helped start two companies to develop microbial therapies for several disorders, including epilepsy and autism.

Other researchers fear entrepreneurship is outracing science. Knight says venture capitalists are funding startups developing almost any microbiome-based therapies. Some concepts are “very promising and are supported by a lot of evidence,” he says, but others aren’t, and they’re still getting money. Knight says investors see an opportunity in eager patients. (Raes says he gets almost daily emails from depressed people seeking help.)

Microbial therapies won’t necessarily meet the same standards of efficacy as regular drugs. To be marketed as a pharmaceutical, a treatment has to pass muster with the U.S. Food and Drug Administration, or its equivalent in other countries, through clinical trials that prove its effectiveness against specific diseases. Most microbiome treatments so far are marketed as probiotics, for which regulatory thresholds are lower, at least in the United States—as are limits on the health claims that a manufacturer can make. Holobiome is developing both types of products.

The field still faces considerable scientific questions, too. Besides the correlative nature of much of the research and the usual questions of whether animal studies will translate to humans, there’s also the sheer complexity of the human microbiome, says Beatriz Peñalver Bernabé, a systems reproductive biologist at the University of Illinois, Chicago. “I don’t think that it will be ‘one thing fits all.’ We will need to look for specific strains and dosages for different people.” And, she adds, new theories and models are needed to predict how those strains will affect the individual’s particular microbiome community. (DocTalbott note = imagine the day where we can quickly, easily, and inexpensively measure your own personal microbiome – and provide you with a customized approach to microbiome modulation that is trackable over time to help you toward your goals or better mood – or less stress – or improved sleep – or weight loss – or anti-aging, etc. Those days are closer than you may think…)

Despite the obstacles, Gavrish remains confident that some strains she’s growing in the anaerobic chamber will lead to treatments. After all, she says, the connection between gut microbes and the human brain has deep evolutionary roots. “I truly believe you can harness the power of a million years of signaling by gut bacteria to help people.” (DocTalbott note = Agreed – the future of health is ancient)

Microbiome, Stress, and Immunity

Please join me and Michael Quach TONIGHT at 6pm PT for a discussion about how supporting your Microbiome can act as a “stress vaccine” to improve both Mental Wellness (stress, anxiety, depression, burnout) and Physical Health (immune protection, inflammation, and overall wellness).

Zoom = https://zoom.us/j/9292793215

Amare Facebook = https://www.facebook.com/groups/1bewell/

DocTalbott Facebook = https://www.facebook.com/doctalbott

2020ConferenceCall-ScienceofAmare-April9.jpg

Kid’s Mood+ Clinical Study

These last few days (April 4-7) should have been the annual scientific conference known as Experimental Biology in San Diego, CA.

Unfortunately, EB was cancelled due to the COVID-19 pandemic – so many of us are uploading our research to a central database that will be made available to the public in the coming days. The research abstracts will still be published in the FASEB Journal in the coming months – but I also wanted to get this information out to people ASAP, so I recorded my presentation via Zoom and posted the video to YouTube.

Here is the abstract of the study – notice our overall conclusions in red below:

Targeted Dietary Supplementation Improves Mental Performance in Children

Andrea Armstrong DC1, Michelle Massa MD2, Jessica Royston CHHC2, Markham McHenry DO3, and Shawn Talbott PhD4

1Armstrong Chiropractic and Family Wellness Center

2Advanced Natural Medicine of Jupiter, Inc.

3Elevate Health AZ

4Amare Global

Background: Saffron (Crocus sativus) dried flower stigma is the world’s most expensive spice and has been used in traditional medicine for alleviating depression, stress, anxiety, and insomnia. Saffron stigma contains more than 160 bioactive compounds including lepticrosalides (safranal, crocin, crocetin, picrocrocin) and numerous flavonoids and terpenes that have been associated with relaxation, positive mood, and mental & physical balance. At least seven controlled clinical trials have shown the antidepressant activity of saffron.

Objective: Building on the well-described “mood” benefits of saffron, our objective was to assess the benefits of saffron stigma combined with complementary brain-supporting spices (Holy Basil, Rosemary, Clove, and Oregano) on measures of mental focus and mental performance in healthy children who had not been diagnosed with either depression or ADHD.

Methods: Ten healthy children (ages 6-12 years of age) participated in this study. We used the validated NICHQ Vanderbilt Assessment Scales (National Institute for Children’s Health Quality) that are routinely used by healthcare professionals to help diagnose ADHD in children 6-12 years and are part of the American Academy of Pediatrics (AAP) Resource Toolkit for Clinicians Caring for Children with ADHD (3rd edition, 2019). Parents administered the NICHQ survey before and after 30-days of supplementation with a multi-nutrient blend intended to improve mental focus, mood, and stress resilience (Kid’s Mood+; Amare Global). The NICHQ assessment scales have 2 components: Symptom Assessment (in 5 areas: inattention, hyperactivity, defiance, conduct, and anxiety/depression) and Performance Assessment (including school performance on reading, writing, and math; as well as social relationship performance with parents, siblings, and peers including on organized teams).

Results: Following 30-days of supplementation, we found dramatic improvements on assessments of both Symptoms (e.g. focus, attention, mood, listening, tension, and irritation) and Performance (e.g. overall school work, math, reading, writing, and social relationships). All participants (10/10) demonstrated benefits in response to supplementation, with average Symptom scores 29% lower (23.4 pre versus 16.6 post) and Performance scores improved 18% (2.24 pre versus 1.83 post).

Conclusions: Previous human trials in children and teenagers have shown equivalence of saffron to fluoxetine (Prozac) for depression and methylphenidate (Ritalin) for ADHD. This is the first study in a population of normal healthy (“non-diagnosed”) children showing improvements in not just mental focus attributes, but also mental performance (academically and socially) subsequent to targeted supplementation. This study provides compelling evidence for safe and effective natural approaches as potential first-line therapy for improving focus, mood, and mental performance in children.

Stress Balance for the Whole Family

Last night, I held an online seminar about how families can naturally manage stress – for parents and kids – to help everyone feel better during these trying times…

Video is HERE on YouTube

Video is also HERE on Facebook

Slides are here = Talbott Amare Stress Focus 033120

Immune Boosting Super Foods

On April 1 (no joke!), I joined the hosts of Fresh Living on Utah’s CBS Channel 2 (virtually, of course) to discuss some of the most effective foods for supporting immune system protection.

The video is here on KUTV and here on YouTube – and below are the recipes for the smoothie and the shot that I discussed…

immune foods kutv

Immune Boosting Smoothie and Shot

With all the concern about corona virus, I will be presenting my top 10 foods for boosting immunity and helping to protect us from viruses.

Some of the top 10 foods include:

-Citrus/Kiwi (vitamin C)

-Berries (flavonoids)

-Yogurt (probiotic/beneficial bacteria)

-Seeds (prebiotic fiber)

-Mushrooms (glucans)

-Garlic (sulfur)

-Spinach (carotenoids)

-Turmeric/Ginger (turmerones/gingerols)

 

Smooth Immune (2 servings)

-2 cups of Almond milk

-1 cup of frozen berries

-1 cup vanilla yogurt

-1 cup spinach

-2 scoops Amare GBX Protein (Vanilla)

-2 scoops Amare SeedFiber (mushrooms, seed fibers)

-2 scoops Amare SuperFood (fruit/vegetable extracts)

 

Immunity Shot

-1 small orange

-1 small lemon

-1 garlic clove

-1/4 cup chopped turmeric (peeled or unpeeled)

-1/4 cup chopped ginger (peeled of unpeeled)

-Blend garlic, turmeric, ginger together first

-Add orange and lemon and blend all ingredients together into a juice

-Optional = strain pulp (I prefer to keep all the healthy fiber/pulp, but personal preference)

 

Webinar Tonight – 6pm PT

Please join me TONIGHT at 6pm PT for an overview of Amare products and the science behind improving mental wellness, optimizing gut-brain-axis balance, reducing stress, and bolstering immune protection.

 

I’ll be live on Zoom (if you want to ask questions) with simultaneous streaming to Facebook Live (if you just want to watch) – please join me at the links below…

 

Join Zoom Meeting

https://zoom.us/j/9292793215

 

Meeting ID: 929 279 3215

 

One tap mobile

+16699006833,,9292793215# US (San Jose)

+13462487799,,9292793215# US (Houston)

 

Facebook = https://www.facebook.com/groups/1bewell/

 

Gut microbiome linked to sleep quality and immune function

Interesting article and study published recently showing the close link between sleep (both quantity and quality) and the balance of the gut microbiome. Please see my highlighted version below…

The Sleep+ product that we have at Amare is the only natural approach to improving sleep quality – with ~40% more time spent in Deep Sleep (where our body rejuvenates) and REM Sleep (where our brain recovers).

With everyone these days under so much psychological stress AND wanting to improve immune system protection, any option to improve sleep quality is welcome to improve mental wellness and physical health.

Sleep quantity and quality may contribute to gut microbiota diversity

Original summary article is here = https://www.gutmicrobiotaforhealth.com/en/sleep-quantity-and-quality-may-contribute-to-gut-microbiota-diversity/

Original research study is here = Smith RP, Easson C, Lyle SM, et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS ONE. 2019; doi.org/10.1371/journal.pone.0222394

We already know there is a connection between sleep deprivation and a higher risk of suffering from diseases such as diabetes, obesity and cancer. Now, a new study by scientists at Nova Southeastern University (NSU) in Florida (USA) goes on to show that poor sleep is also linked to poor gut microbiota diversity, which in turns affects overall health.

“Sleep is pretty much the ‘Swiss Army Knife of health’. Getting a good night’s sleep can lead to improved health, whereas a lack of sleep can have detrimental effects,” explains Jaime Tartar, research director at NSU’s College of Psychology and co-author of the study, published in Plos One.

“Getting a good night’s sleep can lead to improved health, whereas a lack of sleep can have detrimental effects,”

The researchers undertook an experiment with 40 young healthy male volunteers, who were asked to wear a connected watch for 30 days. The device objectively monitored aspects of the quality and quantity of their sleep, taking into account factors that included bedtime, time spent in bed, total sleep time or the number of awakenings during the night.

Researchers also extracted DNA from participants’ fecal samples to examine gut microbiota diversity. We know that a more diverse gut microbiota seems to be associated with better overall health. And in this regard, Tartar highlights, a lack of gut microbiota diversity has been associated with diseases such as Parkinson’s, depression and autoimmune diseases.

After analyzing the fecal samples, the team found that the subjects who slept well had a more diverse gut microbiota and, inversely, that poor sleep was associated with decreased microbiota diversity.

A lack of gut microbiota diversity has been associated with diseases such as Parkinson’s, depression and autoimmune diseases.

“We were completely fascinated to see such strong correlation between different sleep measurements and gut microbiota diversity,” explains Tartar. “The next step is to try and understand if lower gut microbiota diversity causes poor sleep or whether, conversely, poor sleep leads to lower gut microbiota diversity. Right now we are planning a study to solve this question.”

The answer could lead to the development of potential interventions to improve gut microbiota diversity and thus, sleep quality and overall health.

Abstract of the Study:

The human gut microbiome can influence health through the brain-gut-microbiome axis. Growing evidence suggests that the gut microbiome can influence sleep quality. Previous studies that have examined sleep deprivation and the human gut microbiome have yielded conflicting results. A recent study found that sleep deprivation leads to changes in gut microbiome composition while a different study found that sleep deprivation does not lead to changes in gut microbiome. Accordingly, the relationship between sleep physiology and the gut microbiome remains unclear. To address this uncertainty, we used actigraphy to quantify sleep measures coupled with gut microbiome sampling to determine how the gut microbiome correlates with various measures of sleep physiology. We measured immune system biomarkers and carried out a neurobehavioral assessment as these variables might modify the relationship between sleep and gut microbiome composition. We found that total microbiome diversity was positively correlated with increased sleep efficiency and total sleep time, and was negatively correlated with wake after sleep onset. We found positive correlations between total microbiome diversity and interleukin-6, a cytokine previously noted for its effects on sleep. Analysis of microbiome composition revealed that within phyla richness of Bacteroidetes and Firmicutes were positively correlated with sleep efficiency, interleukin-6 concentrations and abstract thinking. Finally, we found that several taxa (Lachnospiraceae, Corynebacterium, and Blautia) were negatively correlated with sleep measures. Our findings initiate linkages between gut microbiome composition, sleep physiology, the immune system and cognition. They may lead to mechanisms to improve sleep through the manipulation of the gut microbiome.

The Immune Miracle – Chapter 6 – Priming: The Next Frontier of Immune Support (and References)

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

Chapter 6

Priming: The Next Frontier of Immune Support

The last chapter outlined some of the steps you can take to protect your body from infections by using diet, exercise, and dietary supplements. A detailed discussion of one particular dietary supplement was intentionally “saved” for its own chapter – that being an overview of the whole-gluco-polysaccharides (WGPs) that have been briefly mentioned throughout previous chapters.

Often, specific WGPs are referred to by their “generic” name of “beta-glucan.” This can pose a problem for consumers wanting to find the right type of supplement to help prime immune system function, i.e. protection from disease and improvement of vigor and quality-of life. Beta-glucan molecules can be extracted from almost any plant source. Yet, some forms extracted from cereal grains may be quite effective at lowering cholesterol, but have no positive benefit on immune system priming.

The specific type of beta-glucan that I am referring to when I use the term WGP is technically a “beta-1,3/1-6-linked polyglucose” which is a polysaccharide (long chain of sugar molecules) found in the cell walls of yeast cells. Purified beta-glucan has been shown in a wide variety of animal and in vitro studies to have general immuno-priming properties. Among its many beneficial effects are macrophage activation, tumor inhibition, and decreased infection rates. Certain WGPs are patented and protected, by more than 40 U.S. patents or patents pending, for general immune system support as well as for general anti-cancer and specific anti-tumor activity.

Commercial “beta-glucan” products are highly variable in their total content of beta-glucan, ranging from highly purified WGP extracts to less purified “mixed” blends of beta-glucan with other polysaccharides, to completely unknown “generic” versions of beta-glucan with suspect purity or potency.

As described in earlier sections, the body’s first line of defense is the “innate” immune system consisting of soluble blood factors (such as cytokines and complement) and the immune cells (monocytes/macrophages, neutrophils, and natural killer cells) that circulate throughout the body and identify and destroy foreign intruders. WGP has been shown to significantly increase the percent of active (“primed”) immune cells and the level of chemical messengers in the blood that regulate the body’s immune response. Because of its highly purified nature, the WGP form of beta-glucan has also been shown to contain significantly more of the molecular 1,3/1,6 glucose linkages that activate immune cells than any other nutritional supplement on the market.

A series of radioactive labeling studies in humans have shown orally administered WGP to be taken up by gastrointestinal macrophages (immune cells that are the body’s first line of defense), and shuttled to reticulo-endothelial tissues and bone marrow. Within the marrow, the macrophages degrade the WGP particles into smaller fragments that are secreted and eventually bound to specific receptors (CR3) on immune cells, priming their defense mechanisms for immediate action when presented with a pathogen.

In a July 2004 issue of The Journal of Immunology, WGP was shown to prime the immune system with increased plasma cytokines (INF-y and TNF-a), which play an important role in regulating the body’s immune response, but without increase in cytokine IL-1 (which can cause the fever, chills, and muscle aches which have been associated with other immune-enhancing supplements, such as echinacea and arabinogalactan).

Maintaining robust immune system function has emerged as a worldwide health concern – with food, beverage, and supplement manufacturers quick to jump on the bandwagon by touting new products to “boost” or “support” or “stimulate” immune function. Given all the “noise” across the immune support category, the challenge for health professionals and consumers alike lies in evaluating the research behind the increasing number of ingredients and products that claim to enhance immune system function.

According to a survey (2008) by IFIC (the International Food Information Council), nearly 90% of North Americans currently consume, or are interested in consuming, foods and beverages that improve immune system function – and many people will have questions about which products are supported by scientific evidence.

Most of the “immune” products on the market are touting immune health claims based on vitamin content. But, just because a product contains some vitamin A or C or E – or minerals such as selenium or zinc (all of which are certainly needed for optimal immune function), it does not mean it has any bearing on whether or not that product would truly “support” immune function, especially when your body might need it most (e.g. following immune suppression by stress, sleep loss, or close contact with sick/infected individuals).

When out of balance (high or low), the immune system not only fails to protect the body from invading pathogens (bacteria and viruses) but can even attack it, the body mistaking its own cells for dangerous pathogens, resulting in autoimmune diseases such as lupus and rheumatoid arthritis. Allergies can result when the immune system is “overactive” and mistakes an innocuous and harmless particle (such as pollen or cat dander) for an invading pathogen. Another side effect of an out-of-balance immune system is chronic low-grade inflammation, which can increase risks for cancer, heart disease, and other chronic diseases related to elevated inflammation.

As described earlier, and worth repeating, is that the human immune system has two “parts” – the innate and the adaptive immune responses. The innate system is fast-acting and is considered the body’s first line of defense against any foreign invaders. The part of the immune system that most people understand to be the “immune response” is the “adaptive” system, which is a very specific, but delayed, response. Each of the two parts of the immune system work and interact with each other to coordinate protection of the body. For example, the innate system includes physical barriers to infection (such as our skin and mucous membranes), as well as chemical barriers (such as acidic environments and enzymes that kill pathogens or prevent their growth). Another part of the innate system includes the “complement” proteins that help to kill pathogens directly (via lysis) or mark them (opsonization) for later destruction (phagocytosis) by specific immune cells (phagocytes). Natural Killer (NK) cells are another important part of the innate system because of their ability to target and kill viral-infected cells and tumor cells.

In concert with the innate system, the “adaptive” portion of the immune system is a delayed response that is dependent on the innate system for activation. Although initially a delayed response, the adaptive system has “memory” – so the second time the body is exposed to the same pathogen, the response is almost immediate. The main adaptive cells are the “T” and “B” lymphocytes, which work together in a coordinated fashion to recognize (and kill) virus-infected cells and also to help activate other cells in the immune system (via chemical signaling by cytokines).

Obviously, having an immune system response that is either under-active or weakened will increase susceptibility to infections and disease. Unfortunately, our immune system is constantly under attack – not only from pathogens, but also from common everyday physical and emotional stress, sleep deprivation, and environmental insults. In attempts to combat these daily “stresses” on the immune system, consumers are bombarded by a dizzying array of pharmaceuticals and nutraceuticals sold as immune “boosters” (which are probably not what most people really need, based on the simple fact that keeping the immune system in a constant state of stimulation would be expected to result in the detrimental side effects associated with overstimulation, and possibly allergies and autoimmune/inflammatory diseases. Immune system function needs to be balanced – not boosted or suppressed.

The specific WGP form of beta-glucan is known to activate or “prime” innate immune cells to perform their primary protection function: increased ability of macrophages to phagocytose, i.e. engulf and destroy foreign challenges when present. It is important to note that WGP does not automatically “stimulate” immune activity; it only activates immune function when a pathogen is present (e.g. tumor, anthrax, influenza, etc.). In contrast, certain plant-derived or fungi-derived polysaccharides (e.g. echinacea, arabinogalactan, reishi/maitake/shiitake mushrooms) are known to immediately stimulate immune activity, irrespective of the presence of pathogens – a situation that can result in inappropriate levels of inflammation and cytokine release leading to fever, chills, and general malaise.

Scientific Support

There exists a wide-ranging and rich body of research on the mechanism and benefits of specific WGP beta-glucans as biological response modifiers (BRMs) against cancer and infectious diseases. Unfortunately, a major problem with many studies of generic or poorly-defined beta-glucans is the unknown nature of the complex mixtures of partially-purified extracts of mushrooms, yeast, and other plant biomass (which can often include compounds that interfere with immune function or cause undesired side effects).

As documented in The Journal of Immunology (2004), researchers from the Memorial Sloan-Kettering Cancer Center and the Department of Immunology at the University of Louisville School of Medicine demonstrated a clear mechanism by which orally-administered WGP beta-glucans enhance tumoricidal (anti-tumor) activity – by activation of granulocytes (neutrophils and eosinophils), monocytes, macrophages, and NK cells. When consumed orally, WGP particles perform much like a “pro-drug” where they are taken up by gastrointestinal macrophages (via the Peyer’s patches in the small intestine) and shuttled to reticulo-endothelial tissues and bone marrow. Within the marrow, the macrophages degrade the WGP and secrete small, soluble, biologically active fragments that bind to CR3 of mature bone marrow granulocytes. Once recruited from the bone marrow by an inflammatory stimulus, these granulocytes with WGP-primed CR3 can rapidly and specifically target tumor cells for destruction.

These data show us the mechanism by which dietary supplementation with WGPs could legitimately be viewed as a novel anti-cancer therapy, by harnessing immune system activity to help destroy existing tumors and maintain the vigilance of tumor surveillance (catching and destroying cancerous cells before they develop into problematic tumors). In some ways, this “immune sensitizing” or “priming” effect of WGP is reminiscent of the activity of monoclonal antibody therapy (Herceptin, Rituxan, Campath-1H, and Erbitux) that is now being used to treat patients with metastatic breast carcinoma, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and metastatic colon carcinoma, respectively. Additional studies have shown that adding WGP beta-glucan to the immune system (via oral or injection routes) can help to leverage the body’s existing immune mechanisms to target any pathogen or tumor cell.

It’s important to repeat and emphasize that the term “beta-glucan” can be used to describe a wide rage of polysaccharide molecules derived from yeast, fungi, seaweed, and a variety of cereals and other plants. WGP is a specific (patented) form of beta-glucan that is described as a “linear glucose molecule with a ‘beta-1,3/1,6’ branch point extended by a long beta 1,3 oligosaccharide.” The slight molecular differences between WGPs and other forms of beta-glucan are subtle, but important when it comes to specificity, bioactivity, efficacy, and safety. The U.S. Food and Drug Administration considers yeast-derived WGP (from baker’s yeast = Saccharomyces cerevisiae), to be “GRAS” (Generally Recognized As Safe) because of its long history of safe consumption as part of the food supply. Ongoing FDA-monitored clinical trials are investigating a soluble (injected) version of WGP beta-glucan as an adjunct therapy to chemotherapy in cancer treatment.

As discussed in Chapter 3, it is well-known that any type of “over-stress” may lead to increased susceptibility to upper respiratory tract infections. For example, both physical and psychological stressors can result in measurable immune challenges with reductions in key immune system components, such as neutrophils, natural killer (NK) cells, T cells, and B cells. The net effect of an ongoing immune challenge is a weakened immune system, which often results in URTIs as well in generalized reductions in energy levels, mood, and quality of life. Lifestyle factors, such as improved coping with daily stress and getting adequate hours of nightly sleep, may influence the immune response and improve a range of immune system parameters, including immune cell populations, antibody production, and cytokine response. Biological response modifiers such as WGP are effective at enhancing the innate immune response and improving the microbicidal activity of neutrophils, macrophages, and natural killer cells against a variety of pathogens. In several studies, WGP has been shown to reduce the risk of URTIs after stressful events, as well as reduce postoperative infection rates and shorten intensive care unit stay duration among hospitalized patients.

A recent study published in the Journal of Sports Science and Medicine (2009) showed that WGP beta-glucan is able to reduce URTIs (upper respiratory tract infections) and improve overall mood state in over-stressed subjects. In this study, marathon runners were used as a model of over-stress, with results showing a clear reduction in URTI symptoms in the subjects taking WGP beta-glucan versus those taking a placebo. Subjects also showed a significant improvement in measures of overall health and psychological well-being including reduced fatigue and increased vigor (physical and mental energy). During the course of the four-week treatment period, subjects in both treatment groups, 250mg and 500mg beta-glucan, reported fewer URTI symptoms, better overall health, and a more positive mood state compared to placebo.

A wide range of efficacy studies have been conducted on purified WGP beta-glucan, with results showing convincingly that daily supplements of 250-500mg are able to effectively reduce URTIs (upper respiratory tract infections) and improve mood state (energy/fatigue/vigor) under various conditions of physical and psychological stress. Due to problems with purity and bioactivity, however, it is unlikely that “generic” or “mixed” beta-glucan supplements would generate the same efficacy at such a low daily dose — making it important for consumers and health professionals to look for specific yeast-derived WGP beta-glucans that contain the research-proven “1,3/1,6” branching structure.

Illness and stress impact the immune system in both physical and psychological ways. The ability to naturally prime our immune system function back toward optimal levels of functioning represents both the next frontier of immune system support, and also the next frontier of how we think about our overall wellness and quality of life.

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The Immune Miracle – Chapter 5 – Eating for Immunity

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

 

Chapter 5

Eating for Immunity

The first thing to keep in mind when it comes to supporting the immune system with lifestyle interventions such as diet, exercise, stress management, and dietary supplements, is that they’re ALL important in their own specific way. You can’t neglect one and expect the others to “pick up the slack” or expect a supplement to “make up” for a poor diet. That said, dietary supplements can be an easy, safe, and effective way to help your immune system “get an edge” when you’re under stress or find your systems depleted or run down.

When it comes to dietary supplements, we need to also consider that there is a huge difference between chronic supplementation (to support the immune system on a regular basis) and acute supplementation (to bolster immune system activity to battle an existing infection). For example, the popular immuno-stimulant herb echinacea appears to be quite effective (when standardized for the right compounds) in stimulating immune system activity to battle a new infection – but it is not recommended for prolonged or continuous use, due to concerns over cellular toxicity. Likewise, vitamin C and zinc would be appropriate at low doses for chronic “protection”; whereas, higher levels are effective on a short-term basis for direct activity against invading pathogens.

You might remember from the Introduction of The Immune Miracle, that the primary key to bolstering immunity is, of course, to protect our bodies from infection in the first place. The last chapter (Chapter 4) gave an introduction to the concept of immune system priming. The next chapter (Chapter 6) goes into even more detail about how to most effectively prime our immune system function for optimal health and wellness. Some of the supplements covered in this chapter help to maintain normal immune system function, while others actively promote or stimulate immune function above normal levels. The latter approach is one that should not be undertaken lightly, and then only for a short period of time, because as indicated in earlier sections, a chronically stimulated immune system can be just as bad as a chronically suppressed immune system: both can lead to myriad health problems.

When it comes to protection (or prevention), we’re primarily talking about strengthening the immune system. It is always a good idea to keep your immune system “humming” throughout the year (not just when cold and flu season comes rumbling into town). The sections that follow provide a number of points to consider for supporting immunity, including nutrition, exercise, rest, fluid intake, and exposure to pathogens.

Exposure to pathogens

Viruses cause colds and flu; bacteria can cause all sorts of unpleasant effects (gastrointestinal cramps, fever, diarrhea, etc.). Probably the most effective way to reduce your exposure to any pathogens is to wash your hands as frequently as possible. One of the primary ways that viruses and bacteria are transferred between people is through “secondary contact” – someone with the “bug” touches something, like a handrail or doorknob; then, you touch the same object and pick up the “bug” there. Frequent hand washing can reduce the chance that you’ll transfer those pathogens from your hand to your eyes or nose, where they’ll enter and begin to infect your body.

Fluid intake

Why is it that our mothers and grandmothers always made us drink more fluids when a cold came on? Mostly, it’s because your body needs that extra fluid to “flush out” the infection – via several routes, including increased mucous production. With the more severe influenza infections, dehydration can result from fluid lost from vomiting and diarrhea; so, be sure to replace all losses plus drink a bit extra for good measure.

Exercise

Regular physical activity is a vital part of maintaining optimal immune function: those who exercise at a moderate level at least a couple of times each week are far less likely to get sick compared to sedentary individuals. On the other hand, be aware that extremes of exercise – whether extremely intense or extremely long in duration (such as marathons or triathlons) – have been associated with reduced immune protection and increased risk of infection (primarily in competitive athletes).

Nutrition

When it comes to optimal nutrition, any significant nutrient deficiency can impair functioning of the immune system. As such, it is always wise to include a complete multivitamin supplement as part of your total immune system support. In a multivitamin, be sure to look for one that supplies at least the recommended daily allowance (RDA) levels for the nutrients listed below. Many popular products contain some of them; so, check the labels and add additional amounts as needed to reach the suggested intake. To round out your nutrient armory, consider adding additional amounts of key amino acids such as N-acetyl-cysteine (1-2 grams per day) or glutamine (1-5 grams per day) – both of which have been linked to elevated immune system responses. Finally, there are a number of immune-stimulating herbs and herbal blends available,  the most effective of which seem to be echinacea, goldenseal, and astragalus.

Immune-friendly Nutrients

Nutrient Daily Value (Adults) Optimal Intake for Immune Support
Vitamin A 5,000 IU 5,000 IU with at least 50% derived from beta-carotene (women who are pregnant, or who may become pregnant should NOT exceed the RDA for pre-formed vitamin A unless directed to do so by a personal physician)
Vitamin C 60 mg 250 – 1,000mg
Vitamin E 30 IU 30 IU from natural mixed sources including both tocopherols and tocotrienols
Vitamin D 600 IU 1,000 – 2,000 IU
Mixed Carotenoids 5-6 mg 5 – 50 mg
Iron 18 mg 18 mg
Selenium 62 mcg 100 – 200 mcg
Zinc 15 mg 15 – 45 mg

 

Astragalus has been used as an herbal “tonic” for centuries in Traditional Chinese Medicine (TCM) and in Native American folk medicine. As a tonic, astragalus is used primarily as a “prevention” herb throughout the cold and flu season – a different usage than the more popular echinacea, which is best used for early stage treatment as soon as you feel a cold or flu coming on. Research studies have shown that astragalus can help fight bacteria and viruses by enhancing various aspects of the body’s normal immune response, i.e. enhanced function of specific immune system cells such as T cells, lymphocytes, and neutrophils. In TCM, astragalus is often combined with other “tonic” herbs such as ginseng, cordyceps, or ashwagandha, to keep the immune system “humming” during periods of high stress; each of these appear to be somewhat effective in increasing energy levels and (possibly) enhancing the immune-stimulating effects of astragalus.

Echinacea is the “King” of the immune function herbs (with over 300 scientific studies attesting to its immune enhancing effects). It is important to note that the primary use of echinacea is in the acute (short-term) treatment of the common cold – NOT for prolonged use (past a few weeks) as general immune system support. Also, echinacea is generally not recommended for use by individuals with autoimmune disorders (such as multiple sclerosis or rheumatoid arthritis) due to its immune stimulating properties. The best use of echinacea is immediate consumption following acute exposure to an infected individual (meaning that as soon as Aunt Mary coughs on you, you should reach for the echinacea capsules).

Goldenseal is a popular herbal remedy for immune system stimulation, due to its high content of berberine. Because of the “endangered” status of goldenseal, however, many consumers (and supplement manufacturers) are turning to other berberine-containing herbs such as barberry and Oregon grape, which also appear to be quite effective alternatives for immune system support. Berberine has been shown to block the adherence of various infectious bacteria (such as streptococci) to the body’s respiratory linings. However, berberine-containing herbs are known to cause uterine contractions, so they should be avoided during pregnancy.

A number of mushrooms are used in TCM to support immune system strength. Among the more popular are Shiitake, Maitake and Reishi – all of which contain various polysaccharide and amino acid components that may help stimulate immune cell activity and get the immune system “ready” to do battle with invading pathogens. Although they are not completely understood, current theory suggests that the complex polysaccharides and small protein structures present in herbs such as astragalus and in mushrooms act as immuno-modulators, because of similarities between these compounds and the cellular surfaces of pathogenic bacteria (though the herbs lack the infectivity that pathogens have).

Nettle leaf is an herbal treatment used for symptoms of hay fever and other mild allergic conditions. It may act as a gentle antihistamine, helping to alleviate sneezing, nasal congestion, and itchy, watery eyes without many of the common side effects of synthetic antihistamines (nervousness, insomnia, drowsiness).

Probiotics, which are also called “beneficial bacteria”, are quite effective for supporting immune function. The most popular varieties used in dietary supplements, Lactobacillus acidophilus and Bifidobacteria bifidum, have been shown in hundreds of studies to “boost” immune function via their effects on increasing white blood cell numbers, activity, and effectiveness. Used in conjunction with pre-biotics (indigestible carbohydrates that “feed” the growth of friendly bacteria in the intestines) such as fructo-oligosaccharides (FOS), probiotic organisms can displace certain pathogenic microbes in the intestines to help prevent disease. Typical dosage recommendations are in the 2-4 billion organisms/day range. Be careful to select a product that is fresh and has been transported and stored under proper conditions (refrigeration is best).

Vitamin C is the perennial immune-booster and cold-fighter. Despite the exaggerated old wives’ tale of vitamin C preventing the common cold, it is clear that regular consumption of higher than RDA amounts of vitamin C (500mg to 2 grams daily) can help reduce the duration and severity of colds. In fact, clinical studies now suggest that about 1 gram of vitamin C consumed on a regular basis throughout the cold and flu season can reduce cold incidence by about 20% and cold duration by almost 40%. Vitamin C can also act as a natural antihistamine to help open up congested airways. In some people, however, high doses (500mg or more) can produce mild diarrhea or gas, so you may need to experiment to find the most effective dose for you (reduce intake until symptoms disappear).

Often used in conjunction with vitamin C are a wide variety of bioflavonoids, such as quercetin, rutin, hesperidin, and a number of  catechins and polyphenols found in green tea, grape seed, and pine bark extracts. All possess powerful antioxidant functions that can both strengthen immune system cells and protect healthy body tissues from damage; some, such as quercetin, may also work as an antihistamine. Taken separately, or in combination in “mixed bioflavonoid” complexes, these phytochemical compounds can be taken at dosages of several hundred milligrams per day to help prevent infections and alleviate mild symptoms of colds, flu, and allergies such as hay fever.

Vitamin A is an effective immune system nutrient because it helps keep bacteria and viruses from penetrating the protective mucous membranes (mouth, nose, stomach, lungs) and gaining a foothold in the body. Since vitamin A is a fat-soluble vitamin, people on low-fat diets may be limiting their consumption of foods rich in vitamin A (liver and dairy) and should consider a supplement. For men and postmenopausal women, vitamin A is considered relatively safe up to 25,000 IU (7,500 mcg of “retinol equivalents” – or RE) per day, but it is best to avoid dietary supplements with more than 5,000 IU of “pre-formed” vitamin A in favor of supplements that provide at least half of their vitamin A content in the form of natural beta-carotene. In pregnant women, or in those who could become pregnant, less than 10,000 IU (3,000 mcg RE) per day is more prudent, as high-dose vitamin A is linked to birth defects and other damaging effects in the developing fetus. All women considering becoming pregnant should discuss vitamin supplementation with a personal physician – especially for vitamin A supplements. A safer alternative may be to consider a mixed-carotenoid supplement, because beta-carotene can be converted into vitamin A in the body, but only at levels which the body requires.

Selenium is a building block of the body’s key antioxidant enzymes, glutathione peroxidase (GPx). GPx is also thought to play a key role in helping immune system cells protect us from invading viruses and bacteria. Selenium has shown positive results as an important immune system nutrient in studies of cancer (some forms of which may be caused by viruses), AIDS, and chronic fatigue syndrome. When combined with zinc, these two nutrients provide a boost to general immunity. Since few Americans get the recommended amounts of either selenium or zinc from their diets, a dietary supplement may be needed – especially during the cold and flu season. To achieve intake levels associated with enhanced immunity, consider a supplement providing selenium (200mcg/day) and zinc (15-30mg/day) together.

Zinc lozenges have become one of the most popular natural approaches to treating the common cold, and there is actually some good scientific evidence to support their use. Zinc lozenges appear to reduce cold symptoms, such as sore throats, hoarseness, and coughing – and may even be able to shorten the duration of colds by a full day or so. Like vitamin C, zinc is an essential nutrient for optimal functioning of the immune system; both offer significant antiviral activity when consumed at elevated levels for a short period of time. It appears, however, that some forms of zinc lozenges may be more effective than other forms, due to the total amount of ionized zinc that the lozenge actually releases into the mouth and throat. At least one study has shown that lozenges containing zinc gluconate plus citric acid, sorbitol, or mannitol may not deliver high enough levels of ionized zinc; whereas, lozenges which contained glycine (an amino acid) appeared to deliver a higher quantity of ionized zinc.

Vitamin D is a fat-soluble vitamin that acts as a steroid hormone (the body can make its own vitamin D from cholesterol in the skin after being triggered by the sun’s UVB rays). Thus, factors such as sun exposure, use of sunscreen, geographic location, gender, age, race, and others will influence a person’s vitamin D status. Vitamin D, as a steroid hormone, influences virtually every tissue system in the body, including our bones, intestines, pancreas, brains, muscles, cardiovascular system, and cell growth cycles (which are related to cancer risk). In addition to the long list of biological functions of vitamin D listed above, vitamin D also acts as an immune system modulator – preventing excessive expression of inflammatory cytokines and increasing the “oxidative burst” potential of macrophages. Vitamin D dramatically stimulates the expression of potent anti-microbial peptides which exist in neutrophils, monocytes, and NK cells – as well as in the epithelial lining of the respiratory tract where peptides play a role in protecting the lung from function.

According to research published in the New England Journal of Medicine (2007), most of us (as many as 1 billion people worldwide) have a vitamin D deficiency. Some of the most common risk factors for vitamin D deficiency include:

  • Living at Northern latitudes (anywhere above San Francisco or Philadelphia or London – no vitamin D is made in the skin at a latitude of 52-degrees-N from October to March, because the atmospheric ozone filters out the UVB rays of the sun)
  • Failure to get at least 15 minutes of direct sun exposure daily
  • Being dark-skinned or African-American
  • Being elderly (those over 50 make only 25% of the vitamin D of a 20-year-old)
  • Being overweight.

A “normal” range of vitamin D in the blood is 30-74mg/mL – and an “optimal” level suggested by most research is 50-70mg/dL (for protection from heart disease and cancer). Being in full sun for 15-30min in the summer will produce approximately 20,000IU of vitamin D, which is released into the circulation within 48 hours (assuming person is light-skinned, non-elderly, and of normal body weight).

Vitamin D reduces cell proliferation and increases cell differentiations. It also slows the growth of new blood vessels and reduces inflammation – each of which can reduce the risk for certain cancers. In numerous studies, higher intakes of vitamin D and higher vitamin D status have been linked with reduced rates of cancer. A study from Creighton University showed a 77% reduction in cancer diagnoses (with 1,100IU/day of vitamin D in postmenopausal women). Another, the Health Professionals Follow-up Study (HPFS), showed a reduction by half in colon cancer rates  when comparing the subjects with the highest to the lowest vitamin D concentrations.

Scientific evidence also suggests that vitamin D deficiency is responsible for immune-related conditions including autism and asthma. For example, the seasonal vitamin D deficiency that spikes during the winter months (when sun exposure is reduced) has been associated with immune system dysfunction, including autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, rheumatoid arthritis, and autoimmune thyroid disease. Many scientists have even suggested that the vitamin D deficiency in the winter months may be the seasonal trigger for influenza outbreaks around the world.

Flu epidemics rear their heads in the winter (when vitamin D levels are low) and retreat in the summer (when vitamin D levels are higher); this is despite the fact that influenza viruses are found in the population year-round (but epidemics do not “break out” until vitamin D levels fall). Vitamin D levels are lowest (in the Northern hemisphere) from November through May (7 months) and highest (enough to prevent flu outbreaks) in from June through October (5 months).

Why Vitamin D Supplements Are Needed

Only a very few foods are a good source of vitamin D, including fortified dairy products and breakfast cereals, fatty fish, beef liver (too high in vitamin A for vitamin D to be absorbed), and egg yolks. Cod liver oil is also a good source of vitamin D, but also tends to contain too much vitamin A, which can interfere with the absorption and activity of vitamin D in the body. Researchers from Creighton University have estimated that 3,000IU/day of vitamin D (total intake including food and supplement sources) is required to assure that 97% of Americans will achieve desired blood levels of 35ng/mL.

The two forms of vitamin D found in dietary supplements are D2 (ergocalciferol) and D3 (cholecalciferol). D3 is the preferred form because it is chemically equal to the form of vitamin D produced by the body, and is 2-3 times more effective than the D2 form at raising blood levels of vitamin D. A daily dose of 2,000IU of vitamin D3 would be expected to raise blood levels by 20mg/mL – which is about the amount of “deficiency” that the average person might expect to have (especially during the winter months in a Northern-latitude city in the USA).

 

The Immune Miracle – Chapter 4 – Priming Your Immune System

The Immune Miracle

The all-natural approach for better health, increased energy, & improved mood.

Shawn M. Talbott, PhD, CNS, LDN, FACSM, FAIS, FACN

 

Chapter 4

Priming Your Immune System

As discussed in the last chapter, the relationship between stress and decreased immune function is well-established by researchers around the world. Chronic stress can cause deleterious effects on the immune system by reducing the responsiveness of the innate and adaptive systems (so we get sick more frequently) and increasing inflammatory mediators (so we’re likely to experience daily fatigue, moodiness, and pain). Psychological stress reduces immune cell populations, lowers antibody production, and alters cytokine responses — though these are biochemical changes that none of us “feel” in our bodies on a day-to-day basis.  What we “feel” is whether or not we’re sick, whether or not we have energy or are in a good or bad mood,  whether or not we feel motivated to get up and get things done. With a dysfunctional immune system, we tend to feel tired, moody, confused, irritable, tense, and simply “off” of our best game. But, with a properly primed immune system, we’re less likely to get sick, and we’re more likely to have the high levels of vigor that most of us describe as feeling energetic, happy, clear-headed, motivated, and “in the zone” when it comes to our mental and physical performance.

Sounds great, right? But how do you take your stress-suppressed immune system and “prime” it back into an optimal state of function? A variety of dietary supplements have been studied for the prevention and treatment of both experimentally-induced and naturally-occurring colds, including: Echinacea, vitamin C, ginseng, vitamin E, and zinc. You can read about these and others in Chapter 5.

In a recent research study conducted by SupplementWatch, the physical and psychological effects of a natural yeast extract containing “whole beta-1,3/1,6-gluco-polysaccharide” (the WGP mentioned earlier) were studied in a group of “stressed out” volunteers.  In previous clinical trials, WGP has been shown to reduce the severity and duration of upper respiratory tract infections (URTIs) in both stressed and non-stressed subjects. In laboratory studies, WGP has also been shown to enhance the microbicidal activity of innate immune cells (to directly destroy viruses and bacteria) as well as to increase the survival time of animals challenged with a variety of pathogens in vivo.

Therefore, WGP already has a good track record for being effective in reducing the incidence or severity of URTI in humans whose immune systems have been affected by chronic stress. In the most recent study, SupplementWatch reported the effects of using WGP on the physical and psychological well-being of healthy women under moderate levels of psychological stress. The study employed a series of subject self-assessment questionnaires that addressed overall health status and URTI symptoms. In addition to evaluation of subjects for physical health, a psychological assessment known as the Profile of Mood States (POMS) was conducted. A key objective of the study was to explore how 12 weeks of WGP supplementation (versus a placebo) affected URTI symptoms and indices of well-being under conditions of moderate psychological stress.

The study used a randomized placebo-controlled, double-blind design. Seventy-seven women (average age: 41 years old) were screened for “moderate” levels of stress and randomly assigned to take either 250 mg/day WGP or a look-alike placebo. Subjects self-administered the allotted capsule once daily in the morning for 12 weeks.

Results showed that women supplementing with WGP had significant improvements in measurements of their physical health as indicated by a reduction in URTI symptoms, such as sore throat, stuffy or runny nose, and coughing – by more than half! See Figure 1 below.

Figure 1.  URTI Symptoms

 

When psychological health was measured, women in the WGP group had a significant 29% increase in overall mood and well-being – indicating that they simply “felt better” in a variety of ways (energy, mood, mental function) as a result of their superior immune system function. See Figure 2 below.

Figure 2.  Global Mood State Score (POMS)

 

This recent study of WGP supplementation in stressed women shows us that a stress-suppressed immune system can effectively be primed back to normal levels of activity, resulting in better physical health (fewer episodes of cold symptoms) and better mental health (improved measures of vigor and well-being). During the course of the 12-week supplementation period, subjects adding WGP to their diets (250mg/day) reported fewer URTI symptoms (indicating better physical health – see Figure 1) and higher overall Global Mood State (indicating superior psychological health – see Figure 2) compared to moderately stressed subjects taking a daily placebo.

As indicated in earlier chapters, WGP has been shown to bind to specific receptors of innate immune cells (CR3), priming them to be more effective in killing foreign challenges.  This binding site preferentially recognizes WGP over other forms of polysaccharides, resulting in a significantly higher level of immune system activation as compared to other immune modulators.  The specificity of the activation mechanism and preferential binding of WGP on the CR3 receptor site of innate immune cells also explains the lack of effect on URTI symptoms reported with other types of WGP supplementation (such as the generic “beta-glucans” that can be extracted from cereals).

This most recent study shows that improving immune system function with specific yeast-derived WGP has a noticeable effect on maintaining health and positive mental attitude in psychologically stressed individuals.  Daily supplementation with WGP reduced the incidence of symptoms associated with URTIs and improved psychological well-being.