Dr. Koz’s Corner

July 4 2024

Sugar Alcohols Linked to Heart Disease – Part 2

Friends:

Ideally, understanding safe limits is a primary directive to clarify the ingestion of sugar alcohols, or any nutrient for that matter, before an individual inadvertently stumbles into a “red zone” of potential health risks and harm with habits of overconsumption.

The notable axiom in biochemistry states, “Poison is in the Dose.”

However, the field of nutrition and product development certainly needs better guidelines to recommend and clarify the amounts and frequencies of sugar alcohol in the diet so that one can more fully, confidently, and safely exploit its numerous beneficial functional health merits.

Both xylitol, a five-carbon, and erythritol, a four-carbon sugar, are created endogenously by our metabolism. They are no strangers to our biochemistry, evolution, and physiology.

Also, sugar alcohols and other polyols have broad distributions in health-engendering fruits and vegetables, though in relatively small percentages compared with other accompanying sugars.

The recently published science study from the Cleveland Clinic, very similar to the first about erythritol back in 2023, underscores our current understanding that xylitol blood levels (and other sugar alcohols) increase in hyperglycemia and diabetes, reflecting a marker of underlying sugar/insulin metabolic dysfunction.

Their team of scientists conducted various studies that extrapolated and warned, though still veiled with many
unknowns, of the possible higher risk of MACE ( major cardiac event and blood clots) with an undefined standard of excessive use and amounts of xylitol ( or erythritol) as a sweetener.

Thus, as mentioned in the study, those with underlying, already predisposed blood sugar dysfunction or a lower expression of sugar-alcohol rate-limiting enzymes are even more vulnerable to adverse thrombotic events and more
significant spontaneous platelet aggregation; even those fasting are more likely and, as a logical continuation, the study conjectures more prone to exacerbation and risk of
a significant cardiac event (MACE) with the use of polyols for sweetness.

Though concerns are warranted and sincere, this, from my perspective, seems a bit early, too linear, and presumptive in drawing what feels more like a conclusion with so many other variables still to factor in.

However, platelet aggregation is complex and nuanced, with different activation sites depending on the substance, meaning all the mechanisms of action still need to be fully understood.

One study noted that the GLUT-3 granules in platelets and the presence of glucose allow for platelet contraction, like a muscle fibril in bringing them together for aggregation.

This is a very interesting but reasonable theory since both tissues are mesodermal in their origin.

As the platelets pull together or contract, this is an early step in forming a clot, which is normal and essential when within limits.

However, platelet aggregation is not a blood clot, though this differentiation appeared murky throughout the study.

Accompanying obesity, diabetes, hyperglycemia, and frequent sugar consumption, the significant incretin hormone GLP-1 from the L-cells of the small intestines is blunted and less effective in its metabolic roles with hyperglycemia, obesity, and diabetes.

But as a preview of many of the functional benefits of xylitol or erythritol, these sugar alcohols are still effective, not blunted, as potent GLP-1 independent agonists in the face of this crucial metabolic dysfunction.

Also, as sucrose load increases over time in people who consume high-sugar diets, the system becomes less responsive to releasing GLP-1, engendering greater risk for inflammation, higher blood lipids, hyperglycemia, and Type 2 diabetes.

But the following question has not been explored to the best of my knowledge, but as a side thought: could it perhaps be that the endogenous increase in alcohol sugars is not only a marker but also a safety valve and off-ramp for survival via a more activated PPP pathway rather than sustaining the far more damaging oxidative, metabolic, and glycation effects of hyperglycemia?

In my philosophy and use of ingredients, I have formulated sugar alcohols in very prudent, calculated, and restricted amounts to capture some of the sweetness but, even more importantly, its functional health contributions.

Nature presents and proves the map and model when constructing a formulation—sugar alcohols are never alone but in conjunction with other sugars and nutrients.

For example, a medium-sized apple contains about 19 g of sugar ( sucrose, fructose, glucose, with about 3% xylose, sorbitol, etc.), and it is proven healthy and good for you, diabetics, and for weight management.

Yes, the skin contains abundant nutrients and antioxidants, which significantly contribute to its healthful and protective properties.

Still, apples also have glucosidase-inhibitory features, which block and slow down simple sugar absorption along the brush border, even with their relatively high sugar content and a small presence of sugar alcohols.

The scientific literature cites that polyols, xylitol, and erythritol also have glucosidase inhibition properties.

These sugar alcohols can actually contribute a similar and safe mode of purpose as the pharmaceutical drug Ozempic, GLP-1 agonist, which is eagerly sought for blood sugar balance, diabetes, appetite control, and fat metabolism and making a financial killing in the pharmaceutical industry.

It was interesting to me that some of the research scientists, in their parting comments as an aside, said that if they had to choose between sucrose or an alcohol sugar, they would opt for sugar over the less-studied sugar alcohols and their largely unknown long-term effects.

So, is this to be Hobson’s choice? Which kind of sugar generates the least fear or harm?

Excess sugar ( sucrose) is one of the major, extremely well-studied culprits in multiple chronic diseases and conditions.

It induces higher rates of cardiovascular disease, syndrome X, hyperlipidemia, obesity, fatty liver, inflammation, fuels some cancers, candidiasis, sticky platelets, and dental caries.

Sugar is far more scientifically established and has largely proven life-shortening, health-damaging, and untoward outcomes than our present and limited understanding of polyols in human health.

So, with these facts on the table, what are some significant additional merits of xylitol and erythritol if used modestly, carefully, and not excessively, which are absent with sucrose?

–GLP-1 agonist in the face of hyperglycemia
–Bacterial biofilm disruption–significant for immune and dental health
–Erythritol enhances vascular endothelial elasticity and lowers BP in several studies
–Promotes bone remineralization; xylitol is considered an ally in fighting osteoporosis in some studies
–Acts as an alpha-glucosidase. inhibitor–thus helping to slow down and blunt the absorption of sugar and helps to manage blood sugar
–Anti-inflammation properties–erythritol helps reduce gut inflammation in high-fat diets.
–Erythritol antioxidant properties again OH radical, xylitol appears to raise intracellular glutathione.
–Some early and limited studies demonstrated that erythritol lowered HbA1C.
Armed with these facts, you could improve your sugar composition and make it more healthful by mixing sucrose with some sugar alcohols, as found in Nature.

In Nature, multiple kinds of sugars, sugar alcohols, and rare sugars work together naturally with antioxidants, fiber, and other nutrients—they are not isolated and should not be overconsumed individually in a healthy, balanced diet.

With this kind of synergistic interrelationships, we can find the most significant dividends for health and safety while keeping in mind the following criteria:

Every food or ingredient follows a “bell-shaped” curve where there is little problem or effect, a certain amount balances the good, and too much creates stress on metabolism and health. Moderation and balance remain the central pivot points for more optimal health and nutrition, polyols included.

Science and industry should ideally establish a clearer “dose-response” curve–that means how much and at what amount one begins to see an actual adverse and causal event, factoring in health, age, and predisposing health tendencies for specific markers. Also, more and statistically larger prospective and retrospective population studies cross-correlated with various health factors and consumption patterns. Polyol research has made some good progress in this area, but as the early Clevland Clinic studies demonstrate, many questions remain open, only scratching the surface, and there is a yearning for much more creative and enlightening work.

Thus, the prime directive for supplementation, whether with unusual or regular foods or nutrients, is to establish a “happy zone” for maximum safety, tolerance, and optimal dosage.

April 1 2024

Small Intestine Microbiome Considerations and Sporebiotics

Friends:

When most people hear the word “microbiome,” they think about our gut with its vast array of competing and synergistic bacteria. The microbiome is essential for a healthy life, ground zero for many aspects of our health, and when it goes wrong, it is the origin of many diseases.

This subject is massive, and indeed, having been in the industry and health for years, most of us should have a deep appreciation and some awe of its influence on our health, vitality, immunity, longevity, and even mental health.

But our concept and assumptions are open to some enlightenment and surprises because when we think about “gut health,” we may be unaware of the role and unique environment of the small intestines—significant differences in conditions, needs, population, and kinds of bacteria and their roles.

It’s like visiting Europe and then popping over to North Africa—different environments, different needs, and what works in one place does not fit or is even right in another. The culture and people are different; the weather and landscape are different. What works in the lower intestine differs from the small intestines.

However, though the microbiome is present in both places ( including the unique oral environment), the populations and the people who make up those populations differ!

Thus, as we will soon discuss, the most ideal and effective forms of probiotics can differ in what is emphasized.

Think of the lower gut, especially the cecum, where trillions of bacteria are present, more than the number of cells, making your body like a densely super-populated “urban area” while the small intestines with a less dense and far less populated, very dynamic, rural environment.

If the same level or somewhat the same population existed in the small intestines, it would be a significant disease leading to very harsh symptoms and consequences from bleeding, multiple nutritional deficiencies, osteoporosis, severe gastrointestinal distress, and possible death.

This manifestation of excess bacteria in the small intestines is called SIBO (Small Intestinal Bacterial Overgrowth). Remember that a healthy colon contains a factor to the power of more than thousands and thousands of times more bacteria than the small intestines.

SMALL INTESTINES

Low diversity and density of gut bacteria

Digestive secretions–many digestive enzymes, including “lactase,” sit along its brush border where nutrients are processed and then absorbed

Nutrient-rich environment
Shorter transit time

Long tube, about 21 feet. 2-3 cm diameter

Huge surface area for nutrient absorption–about the size of a tennis court

COLON

High diversity and density of gut bacteria

No digestive secretions

Nutrient-poor environment ( relative)

Longer transit time

Short, wide tube–about 6 feet and 6-8 cm wide–much smaller and thicker walled surface area.

From Briticana: “Although the small intestines are only 3 to 4 cm in diameter and approximately 7 meters in length ( about 21 feet), it
has been estimated that its total absorptive surface area is approximately 540 SQUARE FEET. This enormous absorptive surface is
provided by the unique structure of the MUCOSA, which is arranged in concentric folds with the appearance of transverse ridges. “

COLONIZATION VS GERMINATION

Colonization: Making this very simple, when probiotics are taken that are “alive” and must be kept viable through refrigeration, and
if they survive the digestive juices ( most do not), they will adhere to the intestinal membrane and colonize the intestinal tract. Most
typically, in the lower intestines, they will be set up through their communication system ( quorum sensing as discussed in previous
Dr. Koz columns) to establish their presence amongst your flora for a reasonably long time. So again, only with “Live bacteria.” For
edification, the following:

Live–Viable cells that can reproduce and colonize.

Active–Full probiotic cell intact but no longer alive, no colonization capability.

Post Bitoic–Broken apart cell and its constituents

Prebiotic–Just the food for the bacteria they can metabolize–no cells, but invaluable for the growth of a healthy flora.

Germination is most typical of Sporebiotics. Once these bacteria hit the small intestines, they grow rapidly in numbers but
ultimately do not adhere and do not form colonies. They are in and out of your system typically in less than a month.

SPOREBIOTICS VS PROBIOTICS

An excellent excerpt from her blog Nutrition by Nathalie“:

“Enter sporebiotics. Sporebiotics are soil-based probiotics, meaning they consist of bacteria (typically Bacillus rather than Lactobacillus or
Bifidobacterium) natively found in our soil. These strains of bacteria found in nature, on fruits, roots, and tubers, were consumed by our
ancestors and functioned as the “original” probiotic (pretty cool, right?).

Sporebiotic supplements are usually a blend of Bacillus spores, highly resistant structures in harsh environments (like the stomach) thanks
to a natural protein shell, and active in favorable environments (like the large intestine).”

“While probiotics are meant to re-colonize the gut, meaning they multiply and form a stable, replicating population, sporebiotics
recondition the gut by increasing microbial diversity and promoting the growth of health-promoting bacteria.

Sporebiotics stay in the gut for about 21-28 days, using quorum sensing to read the microbial environment and scan for pathogenic and
beneficial bacteria.

Amazingly, they can both target and kill harmful gut bacteria and produce metabolites that encourage the re-growth of helpful bacteria.
After 21-28 days, the bacterial spores leave the body through your poop and transition back to their dormant state, ready to be used again
(how incredible is mother nature?).”

Another feature of sporebiotics that I really gravitate to and that is quite unique is that upon germination in the small intestines,
where digestion starts the absorption of nutrients and sugars, they create an explosion of digestive enzymes, from lactase to digest
milk to proteolytic enzymes to better absorb amino acids and antibiotic-like compounds.

There are many key recognized sporebiotics. Many different strains can represent each bacterium, and some are toxic, like
Clostridium, which creates food poisoning.

I like Bacillus coagulans and Bacillus subtilis in moderation in my formulations for health, improved digestion, and better immunity.

These bacteria can be used safely and intelligently in functional foods and beverages, including those that first target the more
oxygen-rich small intestines before they descend into the required anaerobic conditions of the large intestines that is required for
the traditional probiotics.

February 1 2024

H.pylori the Underestimated Infection

Friends:

Not that much is discussed about this, but this stomach bacteria called H. Pylori, is a significant health issue. Helicobacter pylori, a spiral-shaped Gram-negative bacterium, has been classified as a class I carcinogen by the World Health Organization and recognized as the causative agent for peptic ulcers, duodenal ulcer, gastritis, mucosa-associated lymphoid tissue lymphomas, and gastric cancer. Owing to their alarming rate of drug resistance, eradication of H. pylori remains a global challenge. H. pylori is a resilient bacteria strain that can be difficult to eliminate. Due to increased resistance, it may respond poorly to antibiotics, the only conventional medicine option available.

This bacterium lives exclusively in the human stomach and is the only known bacteria able to survive and grow in such an acid environment. As much as 80% of all gastro-duodenal ulcers are caused by H. pylori infections, although the infection is asymptomatic in most cases (70 to 80%).

It is also mildly contagious and can be food/water-borne.

In other words, Helicobacter pylori infections should be taken seriously.

Migraines, cardiovascular problems, and immune system conditions have also been linked to helicobacter pylori infections.

It is clearly a significant problem, given that 25% of Western populations are believed to be infected.

Charité and McGill University quantify the association between Helicobacter pylori and Alzheimer’s disease, infection. It is theorized to increase risk by about 11%-24% for those over 50 infected over a period of around 10 years: Prof. Antonios Douros, a pharmacoepidemiologist at Charité and the first author of the study. “Nearly one-third of all people in Germany are infected with this type of bacteria. An infection can be asymptomatic, but the bacteria can also cause inflammation of the stomach lining or even stomach cancer. Numerous lab studies have also found a link between H. pylori and many neurological issues.” Continuing, “We know that the bacterium can reach the brain via various routes, potentially causing inflammation, damage, and the destruction of neurons.

When the stomach has been damaged by these microbes, it is also no longer able to absorb Vitamin B12 or iron effectively, which also increases the risk of dementia”.

The good news is that a specific and fairly large range of probiotics and some key botanical compounds, i.e., Mastic Gum, Broccoli extract compounds, Cinnamon, spirulina, chlorella, AFA, etc., can compete directly with H. pylori, inhibits its adhesion to stomach tissues, and helps to restore the gut microbial environment.

As for the probiotics, these living microorganisms are comparatively more effective than the standard triple antibiotic regimen in managing symptoms related to pathogenic bacteria. The need for alternative therapy is better explained by the increasing rate of antibiotic resistance and the lowering of patient compliance with the standard treatment.

THE PROBIOTIC SPECIAL FORCES

Very special duties, abilities, and why:

Bacillus coagulans; Bacillus subtilis
These are hearty, acid-resistant, stabile spore bacteria that germinate in the upper GI tract and cover a lot of specific and general health territory on a temporary basis, which is good–they do their service, get out of the way, and don’t hang around for a long time in your gut. They create a burst of digestive enzymes, healing compounds to the GI membranes, and natural antimicrobial compounds inhibitory to lethal to a number of potential problem gut bacteria such as H.pylori, Escherichia Coli, Shigella, and Desulfovibrio with its gut/brain implications (linked to Parkinson’s).

Proprietary Tested Formula with introduction:

“After colonization, Helicobacter pylori will secrete toxins, causing damage to the body, lesions, and diseases. Due to the influence of many factors such as strain cross-infection, the resistance of Helicobacter pylori (H. pylori) to antibiotics increases, and the long-term unreasonable use of antibiotics has related adverse effects on the gastrointestinal micro-ecosystem, causing gastrointestinal dysfunction and gastrointestinal disorders—adverse reactions such as dysbacteriosis. Therefore, it is of great significance to seek natural non-toxic substances to prevent and treat diseases caused by Helicobacter pylori“.

“Domestic and foreign studies have shown that probiotics metabolize antibacterial substances such as lactic acid, hydrogen peroxide, bacteriocin, etc.

Probiotics also secrete H. pylori anti-adhesion compounds to down-regulate adhesion receptor sites, stimulate the expression of
mucins, and stabilize gastric mucosa.

A healthy and enhanced gastrointestinal tract generally better inhibits colonization of Helicobacter pylori (H. pylori).

At the same time, the following probiotics can regulate the host’s immune response by adhering to epithelial cells, and can also stimulate the body to produce IgA (immunoglobulin), which has an immune clearance effect on Helicobacter pylori (H. pylori)”. (1) Lactobacillus plantarum Lp05 has good resistance to gastric acid, inhibits the growth and proliferation of H. pylori, and significantly reduces the adhesion of H. pylori to SGC7901 (human gastric cancer cells), GES1 (human gastric epithelial cells), AGS (human gastric cancer cells) and MKN45 (human gastric cancer cells), creating conditions for the eradication of H. pylori. Studies have shown that the use of the described inhibitor made of Lactobacillus plantarum against H. pylori infection does not make H. pylori resistant and does not cause adverse reactions in patients during treatment.

(2) Lactobacillus acidophilus LA85 can effectively balance the intestinal flora, competitively exclude harmful bacteria after entering the body, and produce a variety of bacteriocins to inhibit pathogenic bacteria, with a broad-spectrum antibacterial effect. For people with intestinal flora disorders, oral administration can help balance intestinal flora quickly, inhibit the proliferation of spoilage bacteria, and enhance the intestinal mucosal barrier, while the bacteria can also help improve immunity.

(3) Bifidobacterium longum BL21 has excellent extracellular polysaccharide-producing properties and has immune-enhancing effects. It has been shown that endogenously produced (i.e., produced by intestinal flora) hydrogen has antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective effects, and this strain possesses some hydrogen-producing properties, indicating its potential application in anti-inflammatory conditions.

(4) Lactobacillus reuteri LR08 is a strong acid producer, which can effectively antagonize the growth of pathogenic bacteria. In addition, this strain can also remove pathogenic bacteria by adsorbing them to form co-precipitates and then excreting them with excretion. Also forms antimicrobial compound against H.pylori, “reuterin”.

(5) Bifidobacterium lactis BLa80 can effectively adhere to intestinal mucosal epithelial cells, forming a microbial protective layer to resist the colonization of the intestine by foreign harmful bacteria and inhibit the growth of harmful bacteria, in addition to enhancing the content of short-chain fatty acids, which are the main source of energy for colonic mucosal cells and promoting the proliferation of epithelial cells.

(6) Lactobacillus casei LC89 can produce short-chain fatty acids at high levels, which can not only directly provide energy to intestinal mucosal cells, but also regulate intestinal pH and improve inflammatory bowel disease of the organism. Its lactobacillus preparation can effectively improve the host’s inflammatory bowel disease and relieve the symptoms of abdominal pain, diarrhea, and loss of appetite caused by inflammatory bowel disease through animal tests and human tests.

In conclusion, the smart use of specific probiotics and botanicals, either alone or in conjunction with antibiotics, is the system of health and medicine, called Complimentary

December 15 2023

D-Ribose and Beyond – Part 3

Friends:

As discussed in my previous article, AGEs (Advanced Glycation End products) are the inevitable byproducts of nonenzymatic glycation and oxidation of sugars onto proteins and lipid oxidants that can potentially create a variety of damaging cellular and metabolic dysfunctions, inflammation, and oxidative stress.

This is called “cross-linking”–the components of the glycation process get hooked into one another before becoming final disruptive
and harmful particles.

Our earlier discussion centered on the use of D-ribose sugar.

To review; it is tricky in that not only do our bodies make it, but there is too much when we are diabetic and even prediabetic that subjects our cells to form dangerous AGE too much and too rapidly.

However, D-ribose as an intelligent and prudently used nutraceutical for most healthy people can potentially offer important, specific, immediate-acting health benefits and relief, especially in addressing certain cardiovascular events.

And though there are possbile roles in performance enhancement and recovery, it is cautioned, that it also has a “dark” side and risks if used too much and too frequently.

This is the condrum in human studies which was mentioned before as limited in addressing this question–what is too much and what is too often? However, apart from D-ribose, AGEs are ubiquitous in humans and accumulate widely in all tissues to form a very high molecular weight substance that is not easily degraded. AGE is increasingly recognized as a culprit or co-culprit in aging, heart, and degenerative diseases including Alzheimer’s, and even wrinkles and dark skin spots to name just a few of the nasty outcomes! According to an online science text, “AGEs can be crosslinked through side chains with body proteins or proteins from cooking.”

Keeping it simple, as AGE particles accumulate on cell receptor sites, they can be a stressor and create pro-inflammatory, disease precursor actions called RAGE–appropriately rhymes, right?

These receptor sites, if not overwhelmed, also have the capacity to help divest the system of AGE particles, so it’s a balance between
the forces of stress reduction vs stressor promotion. When stressors are in a state of overwhelmingly winning, we refer to this stage as RAGE– the term makes sense!

The first steps are the molecules from sugars, specifically saccharides that have various binding or hooking-up tendencies, depending on the type of saccharide, to glycate with amino acids, and form the first transitional compound called Maillard Compounds (MC)–browning effect when heated.

Ironically, to confound the picture, early-formed MC has some antioxidant functions and benefits, like what is found in beer, but it can also change to become irreversible AGE in time.

Ample evidence has found that excessive consumption of mature, well-bonded, advanced glycation end products (AGEs) are harmful compounds.

Cooking foods at high temperatures, AGEs can accumulate in the body as a significant contributor to inflammation that can increase the risk of insulin resistance and type 2 diabetes.

There are different and 3 sequential stages to the final cross-linking with the first two, including Maillard Compounds are much more easily reversible with proper diet, nutraceuticals, and exercise ( probably assists in making cells more insulin sensitive and better controlling blood glucose levels).

Sugary foods and highly processed and prepackaged products also are high in AGEs.

Cooking methods that use high temperatures to brown or char foods, such as grilling, roasting, and broiling, greatly impact the number of AGEs consumed–darn, but they taste so good!

Modifying Cooking Methods:

Modifying cooking methods is the most effective way to reduce the intake of foods high in AGEs.

In a study published in the June 2010 issue of the Journal of the American Dietetic Association, they compared different types of cooking methods and found that dry heat promoted AGE formation by more than 10- to 100-fold above uncooked foods in all food categories.

After cooking, carbohydrate-rich foods such as fruits, vegetables, and whole grains maintained low AGE levels.

Foods cooked with moist heat, shorter cooking times lower temperatures, and acidic ingredients such as vinegar or lemon juice produced the least amount of AGEs.

January 2022 issue of Diabetes Care showed that “overweight women who ate foods cooked at high temperatures had much higher biological markers of insulin resistance than those who ate foods prepared by boiling or steaming.”

Some Examples of Compounds Helpful In the Fight Against AGE Formation:

Spirulina, micro-algae, beer compounds, carnosine, phenolic antioxidants, pigmented berries, teas ( black and green), many herbal teas–most all fruits and vegetables, etc.

As for commercially available products, some online, I do like “Balance of Nature”, “Field of Greens”, and “Brickhouse Nutrition” but there are many other well-formulated botanicals, mushrooms, and microalgae products available at the health food stores.

Revista Română de Medicină de Laboratory Vol. 30, Nr. 2, Aprilie, 2022 201 Exogenous antioxidants and endogenous antioxidants work together to protect the body from free radicals. Antioxidants originating from natural sources such as bacteria, algae, and plants are known as exogenous antioxidants (6).

Blue-green algae or cyanobacteria are a storehouse of bioactive chemicals with well-established antioxidant properties. Phycobiliproteins are the most abundant proteins among the wide range of bioactive compounds produced by cyanobacteria and are promising tools in diagnostics, biomedical research, and therapeutic applications.

Current Diabetes Reports showed that because AGEs are associated with oxidative stress, and as mentioned, they’re of particular concern to patients with diabetes and prediabetes.

The researchers found that subjects who consumed a meal with a high AGE content had an increased circulation of AGEs in the body and that lowering dietary AGE intake could improve hyperinsulinemia by about 40% in type 2 diabetes patients.

Excessive intake of dietary AGEs and AGE provocative sugars, which have the potential to be controlled by our own keener self-management, can be risk-enhancing accelerators in precipitating diabetes–that is really important to understand and appreciate!

This is “an area of major clinical relevance,” the study concluded.

So, in summary, where does this leave us?

AGE is inevitable and normal, but we can be in charge to help manage its production and adverse effects.

My recommendation friends, is to have lots of fresh fruit and vegetables as the major percentage of your diet.

Have minimal to moderate high-temperature cooked flesh proteins, but use liquid when cooked when possible– slow-cooked or lower heat cooked when also possible.

Include nutraceuticals, B vitamins, and antioxidants that can help deter the body from creating irreversible AGE cross-linking.

Regular and ideally daily physical exercise is a very important component in how your underlying blood sugar and insulin sensitivity behave–not to be underestimated!

If taking D-ribose, which I may do infrequently in special circumstances, my preference as it works for me, but perhaps yours is different, is to typically use less than 5 g/dose, and I always accompany it with loads of protective antioxidants!

Enjoy and explore what works for you!

October 17 2023

D-Ribose: The intriguing but Tricky Sugar – Part 2

Friends:

I am starting section 2 with the ending of the first section:

“Herein lies the question in human applications of what is too much, too long, and where are the endpoints? What are the possible consequences and cautions of exceeding the endpoints of chronic dosing? “

Below is a progression of some of the many features that display good effects with smaller or optimal amounts or for a limited time of use, to the harmful effects of excess–again, this is all relative and a function of one’s biochemical individuality, and again, the expression, timing, and order of one factor listed below is merely a guide and is not necessarily contingent upon the preceding factors.

GENERAL CONCEPT OF D-RIBOSE PROGRESSION FROM GOOD TO HARMFUL ( TOP TO BOTTOM)

WHEN SAFE AND BALANCED AMOUNTS ARE USED THE BODY CAN HANDLE AND METABOLIZE

Cardiac synergist

Promoting Anti-Fatique and synthesis of ATP

Improves Cardiac ischemia

Promotes insulin release and lowers blood sugar

Weakens immune suppression caused by viruses

May help relieve muscle pain syndrome

CROSSING THE THRESHOLD OF SAFE AMOUNTS AND SAFE FREQUENCY INTO THE ZONE OF VARIOUS DEGREES OF POSSIBLE HARM Nausea and dizziness Dehydration Aggravation of blood sugar disturbances and diabetes AGE accumulation and eventual cell dysfunction Increased inflammation and autoimmune exacerbation Cell structure damage: glomerular membrane; kidney disease, heart, blood vessel lining, brain, and nerve tissue

My major concern personally about D-ribose ( and other reducing sugars, including less severely, even the alcohol sugars and even to a slightly lesser extent fructose and glucose ) is their rapid creation of AGE ( Advanced Glycation Endporudcts) and RAGE (the receptor sites for the AGE molecules).

AGEs are the products of nonenzymatic glycation and oxidation of sugars to proteins and lipid oxidants that can create a variety of damaging cellular and metabolic dysfunctions. This chemical reaction with sugars that creates AGE is called a “maillard reaction”. For example, it’s also part of the browning and tasty outcome of frying and BBQ–delicious, but too much may create excessive AGE risks–darn it!

‘NUTRIENTS” 2010 Dec; 2(12): 1247–1265.

Published online 2010 Dec 13.

“Advanced glycation end products (AGEs) are a heterogeneous, complex compound formed mainly via the Maillard reaction. The Maillard reaction occurs when reducing sugar reacts in a non-enzymatic way with amino acids in proteins, lipids, or DNA”.

As mentioned but important to emphasize, these dangerous molecules can be formed in the body by our metabolism, especially if we have high blood sugar, as well as sources from the diet and our methods of cooking ( that to be more deeply explained in Dr. Koz’s next article)

RAGE was initially identified as a receptor for advanced glycation end products. RAGE showed that this receptor is most abundantly expressed in skeletal muscle, lung, and heart, creating inflammation and dysfunction.

However, the body can eliminate AGE molecules pretty well if not chronically excessive and prior to more permanently damaged organs and blood vessels.

Exercise also helps to rid us of early-developing AGE molecules.

Diabetics are far more susceptible to creating AGE molecules as well as those who are prediabetic, however, AGE is not limited to diabetics; can happen and accumulate in healthy individuals so don’t become complacent!

Remarkably, diabetics and prediabetics will metabolize and create more polyols and D-ribose from various sugar metabolism pathways than non-diabetics!

However, these body-made molecules are ironically fairly easily subject to glycation, which is the basis for much of the diabetic damage to all tissues.

When molecules are glycated, they become inflammatory and can create metabolic dysfunction in the brain, heart, muscles, and kidneys.
Several compounds may have the ability to help prevent and reverse glycation and its deleterious effects.

Benfotiamine ( a synthesized form of fat-soluble Thiamin–Vitamin B1) and carnosine have demonstrated anti-glycation activity that
may also help slow aging.

From our diet, fruits, veggies, and things like dark chocolate and tea, have powerful antioxidants that help protect cells from glycation.

Specifically, blueberries, pomegranate, and tea are super antioxidants. A regular supply of these in your diet helps save your skin from the effects of AGEs.

However, roasted coffee has lots of “maillard compounds”, that give a rich taste and flavor, but it also has many wonderful and special health benefits– my advice, consume it in moderation, and you should be fine.

So, what do I do personally?

Though I am in excellent physical health, my blood sugar has been stubborn all my life, on the high side, and thus will pay particular attention if I wish to take some D-Ribose.

I am not suggesting this may be your prescription, but when I do take some D-Ribose, usually when anticipating some extra stamina needed for extra exertion and recovery ( intense bike ride, gym, or a tough hike) it is very occasional, about one gram, with plenty of accompanying antioxidants, and sometimes I will also include a small capsule of Benfotiamine.

Even so, with all the prep, I still have some of the AGE “monkey on my back,” wondering if I covered all the bases!

More of AGE and RAGE will be my next Dr. Koz column– so stay tuned!

September 12 2023

D-Ribose: The intriguing but Tricky Sugar – Part 1

Friends:

Let me begin by saying supplement D-Ribose powder works typically immediately on one’s sense of energy and vitality–quite
impressive!

I can attest to this personally–however, as we expand our discussion, there are some cautions, caveats, and wisdom that should be
kept in mind for your health and safety–more of this is discussed in Part 2 of this topic.

In the current nutrition industry, the big, trending buzz terms target anti-inflammation, microbiome enhancement, and immunity.

Well, D-Ribose supplementation primarily deals with ATP depletion, and the manifestations of ATP energy depletion, and it is not
really and primarily connected directly with immunity, microbiome, and inflammation.

However, outside of its very specific and dramatic and positive cardiac effects, I would cautiously say in rehabilitation and recovery
from acute or chronic disease or injury ( must avoid if diabetic!), organs, muscles, and tissues that may become exhausted when still
suboptimal in their vitality, could for the short term perhaps benefits from extra and temporary D-Ribose supplementation to
elevate cellular and tissue ATP energetics.

D-Ribose is a simple, natural, 5- carbon sugar and carbohydrate with molecular formula C5H10O5. It’s made by our bodies from glucose. The naturally-occurring form, d-ribose, is a component of the ribonucleotides from which RNA is built, and so this compound is necessary for coding, decoding, regulation, and expression of genes. As a supplement as mentioned, it’s powerful and should not be underestimated. and in my opinion, but not alone, should not be used excessively, indefinitely, or in excess! However, “Excessive” is a relative and still being researched term as well as “indefinitely”-we are still not clear if and when consequences may kick in for humans.

And then again, each of us has our own biochemical individuality and range of sensitivity based on age, health, genes, etc.

Most of the research is in small mammal studies to date, but there is gathering research and data for short-term acute dosing, in
humans, but not yet really in long-term chronic dosing, large populations, or those of racial diversity over long and very long periods
of time to really understand the full scope of this ingredient in humans.

Even so, there is prudent messaging of considering implementing a time limit–nothing really established as end-points, but one to
exercise being prudent and cautious in using something so active and powerful.

So parenthetically, this quietly begs the question, is this to be considered a dietary supplement or really a medicine/drug when used
in the application and intervening, for instance in minor to significant cardiac symptoms? Also, noted in being effective regarding
findings of pain relief in fibromyalgia and headaches ( the relief by virtue of raising the ATP levels).

Typically, a d-ribose supplement is in the form of a scoopable, white powder–it is pleasantly sweet, easy to measure, and quickly
dissolves in liquids.

As for its effect on energy and uses in health and medicine, the following excerpt nicely summarizes.

Feb 12, 2023, “Very Well” D-Ribose expands the pool of vital ATP. it is made naturally in our bodies from glucose ( ed:
sometimes too little but can be too much and detrimental creating metabolic harm in some states of diabetes). ATP also
supports muscle contraction (the tightening, shortening, and lengthening of muscles) and your body’s nerve signals. Also
known as D-ribose, it is marketed as a nutritional supplement to reduce fatigue and improve athletic performance. It’s also
been studied for people with heart failure for that reason, D-ribose can be instrumental in treating a myriad of
cardiovascular problems including arrhythmia, angina, heart failure, peripheral vascular disease, statin-induced myalgia,
and the rescue of any muscle tissue that is starving for oxygen”.

This is significant and could be life-saving for those that would have an acute cardiac episode. The following excerpt differentiates
and alludes a bit more if one is outside the red zone of an urgent cardiac situation:

Exp Ther Med. 2021 May; 21(5): 496.

D-ribose: Potential clinical applications in congestive heart failure and diabetes, and its complications (Review)
Shuai Li,1,* Juanjing Wang,2,* Yutian Xiao,1,* Li Zhang,1,* Jinren Fang,1 Nanyang Yang,1,3 Zhixia Zhang,1Moussa Ide Nasser,4 and
Hui Qin1,3

“….Therefore, D-ribose may improve the recovery of myocardial ATP content following ischemia by increasing the de novo synthesis
rate of adenine nucleotides. In addition, following myocardial ischemia, D-ribose improves distal myocardial function. Furthermore,
D-ribose supplementation may also efficiently target the ‘hibernating’ myocardium and reduce cardiomyocyte loss of ATP
attributed to ischemia in patients with coronary artery disease, as well as enhance early diastolic filling and the respiratory
performance of patients with CHF. However, the effects of D-ribose as a myocardial protective agent prior to ischemia have
remained to be assessed, to the best of our knowledge. “

Herein, lies the question in human applications of what is perhaps too much, too long, and where are the endpoints? What are the
possible consequences and cautions of exceeding too long the endpoints of chronic dosing? This is to be discussed more in Part 2.

August 28 2023

Parkinson’s Disease and Gut Bacteria – Part 2

Recent discoveries have implicated the gut microbiome in the progression and severity of Parkinson’s disease; however, how gut
bacteria affect such neurodegenerative disorders remains unclear. Now we can report that the Bacillus subtilis probiotic strain
PXN21 inhibits α-synuclein aggregation and clears preformed aggregates in an established Caenorhabditis elegans model ( those
roundworms again in Part One) of synucleinopathy. This protection is seen in young and aging animals.

Multiple B. subtilis strains trigger the protective effect via both spores and vegetative cells, partly due to a biofilm formation in the
worms’ gut and the release of bacterial metabolites. Research has identified several host metabolic pathways differentially regulated
in response to probiotic exposure.

Findings provide a basis for exploring the disease-modifying potential of B. subtilis as a dietary supplement!
The accumulation of misfolded α-syn into pathological aggregates plays a central role in the pathogenesis of PD and other
synucleinopathies (Synucleinopathies are a subgroup of neurodegenerative diseases characterized by impairment of alpha-
synuclein (αSyn) metabolism, producing abnormal intracellular deposits(namely progressive aggregation of insoluble fibrillary αSyn
in neurons and glia).

Significant effort has been invested into finding ways to suppress the formation or enhance the clearance of toxic α-syn aggregates
as a treatment for PD, though no such therapies are available yet. Previous studies suggest that the presence of distinct groups of
bacteria in the gut microbiome modulates PD pathology. However, deciphering the precise effect of individual bacterial species
remains challenging.

Studies now show that B. subtilis PXN21, a probiotic strain that is available for human consumption, both inhibits aggregation and efficiently removes preformed aggregates in a C. elegans model with ectopic expression of human α-syn. Previous studies report that the biofilm formation and NO (Nitric oxide) production by B. subtilis confer C. elegans ( research roundworms) with stress resistance and enhanced longevity ( Donato et al. 2017). “Our results reveal that while these pathways contribute to the suppression of α-syn later in life, the protective effect seen earlier in life is independent of these mechanisms. In young adults, the probiotic acts independently of gut colonization and triggers its protective effects partly by producing bacterial metabolites other than NO”.

Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in …Recent discoveries have implicated the gut microbiome in the
progression and severity of Parkinson’s disease–anti-aggregation properties of B. subtilis remain, to a large extent, distinct from its
anti-aging effects. Interestingly, based on autopsy observations, Braak and co-workers proposed the hypothesis that the primary
events of α-syn aggregation and spreading originate outside the brain, in the anterior olfactory nucleus and the dorsal motor
nucleus of the vagus, further propagating through the cranial nerves from the peripheral nervous system to the brain and the other
vulnerable areas in the central nervous system (CNS), including the striatum and substantia nigra.

Regardless of the direct (causal) involvement of α-syn spreading from the gut to the brain in the pathogenesis of PD, a growing body
of evidence now indicates the presence of alterations in the microbiota of PD patients.

However, the good news is probiotics, especially B. subtilis, are not alone–in comes the amazing and complimentary world of Mushrooms!

Comprehensive and alternative medicines have recently attracted scientific researchers’ attention for treating NDs. Edible
mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson’s and Alzheimer’s diseases.

It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-
amyloid-induced neurotoxicity. Medicinal functional mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and antioxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments.

Anti-Aging and Neuroprotective Properties of Grifola frondosa and Hericium erinaceus Extracts
Farida Tripodi 1, Ermelinda Falletta 2, Manuela Leri 3, Cristina Angeloni 4, Daniela Beghelli 5, Laura Giusti 6, Riccardo Milanesi 1,
Belém Sampaio-Marques 7 8, Paula Ludovico 7 8, Lorenzo Goppa 9, Paola Rossi 10, Elena Savino 9, Monica Bucciantini 3, Paola
Coccetti 1

Abstract

“… increasing evidence indicates that medicinal mushrooms have several beneficial effects. One of the main issues in Western
countries is represented by the challenges of aging and age-related diseases, such as neurodegenerative disorders. Among these,
Parkinson’s disease (PD) affects 10 million people worldwide and is associated with α-synuclein misfolding, also found in other
pathologies collectively called synucleinopathies. Here, we show that aqueous extracts of two edible mushrooms, Grifola frondosa,
and Hericium erinaceus, represent a valuable source of β-glucans and exert anti-aging effects in yeast. Their beneficial effects are
mediated through the inhibition of the Ras/PKA pathway, with increased expression of heat shock proteins and a consistent increase
of both mean and maximal lifespans. These fungal extracts also reduce the toxicity of α-synuclein heterologously expressed in yeast
cells, resulting in reduced ROS levels, lower α-synuclein membrane localization, and protein aggregation…..data suggests using G.
frondosa and H. erinaceus as a functional food to prevent aging and age-related disorders, (is valid) in further supporting the neuro-
healthy properties of these medicinal mushroom extracts.

In conclusion, we have a three-step sequence to help defuse, perhaps help to prevent, and to start to heal neurological structures
from the damaging alpha-syn proteins:

1. Use of “B subtilis” at the probiotic core
2. Mushroom adaptogens
3. Supportive additional adaptogens ( like olive, turmeric, etc) and key nutrients.

Keep healthy, curious, and active!
Dr. Koz

July 31 2023

Parkinson’s Disease and Gut Bacteria – Part 1

Special kudos to Megan Brooks for providing some background information on the gut bacteria Desulfovibrio and its gut/brain implications.

Friends:

Parkinson’s Disease is all too common, on the increase, and potentially becomes a tragic neurological disease, especially as we age. What to do and how to be proactive is what the next two installments of Dr. Koz are all about.

ABOUT PARKINSON:

Parkinson’s disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment at this time.

A small study suggests that a common gut bacteria may play a role in the development of (PD) by causing aggregation of the alpha-synuclein protein, a key feature in the pathology of PD.

Environmental factors and genetics are also suspected to play a role in PD etiology, although the exact cause remains unknown.

ABOUT OUR MICROBIOME:

“Our findings indicate that specific strains of Desulfovibrio bacteria are likely to cause Parkinson’s disease,” study investigator Per Erik Saris, Ph.D., from the University of Helsinki, Finland, says in a news release.

The study was online on May 1 in Frontiers in Cellular and Infection Microbiology.

It builds on earlier works by researchers that showed that Desulfovibrio bacteria were more prevalent and abundant in quantity in patients with PD, especially patients with more severe disease, than in healthy individuals.

Desulfovibrio is a genus of gram-negative bacteria commonly found in aquatic environments where levels of organic material are elevated and waterlogged soils.

Saris and colleagues looked for Desulfovibrio species in fecal samples from 10 patients with PD and their healthy spouses.

Isolated Desulfovibrio strains were fed to a strain of Caenorhabditis elegans roundworms that expressed human alpha-syn fused with a yellow fluorescent protein.

They found that worms fed Desulfovibrio bacteria from patients with PD harbored significantly more and larger alpha-syn aggregates than worms fed Desulfovibrio bacteria from healthy individuals or worms fed E.Coli

Noteworthy observations, worms fed Desulfovibrio strains from patients with PD died in significantly higher quantities than worms fed E coli bacteria.

“Taking into account that aggregation of alpha-syn is a major hallmark of PD, the ability of Desulfovibrio bacteria to induce alpha-syn aggregation in large numbers and sizes, as demonstrated in the present study, provides further evidence for the pathogenic role of Desulfovibrio bacteria in PD, as previously suggested,” they add.

The findings highlight the potential for screening and targeted removal of harmful Desulfovibrio bacteria, Saris suggests in the news release.

Reached for comment, James Beck, Ph.D., chief scientific officer at the Parkinson’s Foundation, cautioned that “this research is in a very early stage, uses a nonvertebrate animal model, and the number of participants is small”.

“Understanding the role of the gut microbiome in influencing PD is in its infancy. These are important steps to determining what ― if any ― link may be between gut bacteria and PD,” Beck told Medscape Medical News.

“Right now, there are no implications for the screening/treatment of carriers,” Beck said.

“It seems that many people, whether with PD or not, harbor Desulfovibrio bacteria in their gut. More research is needed to understand the difference between the Desulfovibrio bacteria of people with PD vs. those who do not have PD,” Beck added.

However, a very recent news break is regarding findings and new assays as marker precursors for PD by the Michael J. Fox Foundation for Parkinson’s Research Foundation.

“Parkinson’s cure ‘inevitable’ after biomarker breakthrough”

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has announced what it says is the ‘most significant breakthrough yet’ in the search for a Parkinson’s biomarker: a biological test for Parkinson’s disease. The test demonstrates high diagnostic accuracy, differentiates molecular subtypes, and detects disease in individuals before cardinal movement symptoms arise.

A paper on the test was published in The Lancet Neurology journal by leaders of the Parkinson’s Progression Markers Initiative (PPMI), the Parkinson’s biomarker study sponsored by the MJFF.

Now things are getting very interesting as they begin to connect!

Their press release:

“The new Parkinson’s test, known as the alpha-synuclein seed amplification assay (αSyn-SAA), heralds the ability for research to define Parkinson’s disease biologically, offering a critical tool for clinical trial design and assessment of treatment effects and for early detection of disease pathology.

The PPMI authors said the test detects alpha-synuclein pathology, one of the two biological hallmarks of Parkinson’s disease (alongside dopaminergic transport dysfunction, which can be visualized using DaTScan). As a result, for the first time since James Parkinson first characterized the disorder in 1817, researchers and clinicians can use biology (as opposed to clinical assessments and patient-reported outcomes) to identify, define and monitor Parkinson’s objectively, based on cellular pathology in the body”.

A new era in Parkinson’s disease research

“Validation of this biomarker launches a new, biological era in Parkinson’s research,” said Kenneth Marek, PPMI principal investigator, president, and senior scientist at the Institute for Neurodegenerative Disorders.

“Using αSyn-SAA, we are already unlocking a new understanding of Parkinson’s, which will transform every aspect of drug development and clinical care. We will rapidly be able to test new therapies in the right populations, target the right therapy to the right patient at the right time, and launch studies of agents that can potentially prevent Parkinson’s disease altogether. PPMI was built to do this, and we are especially grateful to the thousands of study participants whose contributions have enabled this watershed moment.”

So let’s review the sequence in a “nutshell” as we conclude Part One–a specific gut bacteria creates a special protein that is toxic to the brain in specific places of the brain (dopamine sites) that creates neurological damage that is being recognized and can now be measured as a major culprit for Parkinson’s’ ( and perhaps other Neurological Diseases (ND).

Part Two will be some fascinating interventions with specific agents from our nutraceutical industry that have promising impacts on disease origin, progression, and health restoration.

( Author comment) It’s significant when “aggregation” is mentioned; check with earlier Dr. Koz articles about “quorum sensing” and virulence. Again, having a lurking “bug “that goes “bad” is far less of an issue than its number. Once reaching a large number, an ” aggregation” becomes a critical mass population and thus makes communication, in what appears to be “decisions” in how it grows and the nuances of activity in its metabolism.)

July 2 2023

Natural Biofilm Disruptors and Oral health

Friends:

As we have explored and discussed in the past several columns, Quorum Sensing helps bacteria communicate and coordinate their
behavior.

Many diseases of humans, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this
communication to control the diseases caused by bacteria. The most immediate and conspicuous example of this process is right in
our mouths. Every day we deal with plaque, tartar, and gum sensitivities. When the bacteria first adhere to the surfaces on the
enamel and gum crevices, they start to proliferate when obtaining a certain amount of critical population growth.

Being fed, particularly sugar is like “growth-hormone steroids” for them!

As in the mouth, I assume high sugar or refined carbohydrate diet offers a similar principle of overgrowth in the intestines to certain
unwanted bacteria and yeasts–like in Candidiasis.

The process of “adhesion” is the first major initial step whether in the mouth or the gut wall. If no adhesion, no significant bacterial
population growth.

Dental plaque, with the initial step being the adhesion of bacteria to dental surfaces, is the etiologic factor for periodontitis. Dental plaque is in the form of a bio-film and is difficult to eliminate completely. Currently, the treatment of periodontitis is based on mechanical removal of the biofilm by scaling, root planing, and adjunctive use of antibiotics. The problem with this approach is that the bio-film formation is stubborn and persistent–it restarts immediately after the mechanical cleaning has finished, and antibiotics cannot and should not be used continuously. Though periodontal pathogens communicate through quorum sensing, new approaches to treating periodontal disease using quorum sensing inhibition must be explored.

Quorum quenching or quorum sensing inhibition:

Peres, M.A.; Macpherson, L.M.D.; Weyant, R.J.; Daly, B.; Venturelli, R.; Mathur, M.R.; Listl, S.; Celeste, R.K.; Guarnizo-Herreno,
C.C.; Kearns, C.; et al. Oral diseases: A global public health challenge. Lancet 2019, 394, 249–260

The biofilm formation can be disrupted by disturbing the quorum sensing mechanism utilized by the various species of bacteria
forming the plaque bio-film together.

The inhibition of quorum sensing is commonly referred to as “quorum quenching.”

It initially meant stopping quorum-sensing autoinducers (ai) which turn on the bacteria or viruses to proliferate,

Quorum quenching is now commonly used in a more general sense to refer to any inhibition of quorum sensing due to the use of
enzymatic or non-enzymatic molecules.

Quorum sensing can be blocked by stopping the signal molecule production, destroying the signal molecule, and
preventing the signal molecule from binding to its receptor.

Quorum sensing blockage by molecules is produced by various plants, algae, and other organisms.

Various plants, algae, fungi, etc. produce molecules that might inhibit quorum sensing in bacteria. Some of the very impressive list is cited below which interesting and different mechanisms of action. There are many more with even more and more being recognized all the time:

Horseradish
Garlic
Turmeric-curcumin
Citrus flavonoids-flavonine naringenin
Sponge Agelas oroides-alkaloid oroidin
Red marine alga
Grapefruit extract-furocoumarins, carotenoids,
limonoids, pectin, and coumarin

Nutmeg
Sweet basil-muscarinic acid
Garlic-disulfides and trisulphides
Clove extract-eugenol6
Clove extract-hexane and methanol
Piper nigrum
Coffee extract-caffeine

Other notable ones have different mechanisms of action of how they create quorum quenching.

For instance, cranberries–anti-inflammatory and inhibits the matrix building of the biofilm.

The cranberry proanthocyanins seem to exert anti-inflammatory effects in the oral cavity, through different mechanisms. They
appear to be able to inhibit the production of pro-inflammatory cytokines.

Luteolin is a flavone contained mainly in carrots, fennel, and pepper. In vitro and in vivo studies have shown that luteolin inhibits
the production of IL-6, TNF-α, and prostaglandin D2 by gingival fibroblasts.

Quercetin is found in grapes, apples, onions, etc., and greatly impacts inflammation and biofilm disruption. Furthermore, in vitro
studies show that quercetin inhibits the synthesis of TNF-α by oral macrophages. These beneficial actions demonstrate quercetin’s
protective role in countering inflammatory oral diseases.

Curcumin–the main polyphenol in turmeric, is often used as a natural remedy in the treatment of periodontal diseases due to its
anti-inflammatory power; therefore in the market, there are several curcumin-based toothpastes and mouthwashes
Epigallocatechin gallate (EGCG), the main polyphenol in green tea, seems to have an important antioxidant action, countering ROS
generation and exerting a powerful scavenger of free radicals in periodontitis. At the same time, ECGC stimulates antioxidant
defenses. A study by Hrishi et al. highlighted how the daily use of green tea-based toothpaste should increase glutathione-S-transferase activity in the gingival crevicular fluid of patients with CPD.

Genistein, the main isoflavone in soy, appears to be a powerful antioxidant and an inhibitor of nitric oxide synthesis. A study has
shown how injections of 20 mg/kg of body weight of genistein, in mouse models with periodontitis, protect cells from mitochondrial
damage and ROS accumulation and reduce the inflammatory cytokine levels in periodontal tissue.

Also related are compounds protecting against periodontal diseases including green and black teas, lycopene antioxidants as in
tomatoes, and the remarkable antioxidant resveratrol found in various botanicals and of course red wine.

Importantly, the very popular alcohol sugars, xylitol, and erythritol. most common examples are significant bio disrupters in bacteria
forming the oral biofilm by bacteria in the mouth.

Let the following abstract be our closure and a preview of the topic in our next installment:

Xylitol and erythritol inhibit real-time biofilm formation of Streptococcus mutans
June 2020
BMC Microbiology 20(1)

Background: Regular consumption of xylitol decreases the number of cariogenic streptococci in dental plaque. Both xylitol and
erythritol inhibited real-time biofilm formation by all the nine tested S. mutans strains. The sensitivity of the strains to inhibition
varied: some were more sensitive to xylitol and some to erythritol. Xylitol also modified the expression levels of gbpB, gtfB, gtfC, and
gtfD genes that are important in polysaccharide-mediated adherence of S. mutans. Conclusion: The erythritol- and xylitol-induced
inhibition of biofilm formation was only partly explained by a decrease in the number of viable S. mutans cells or the number of
polysaccharides in the biofilm matrix, suggesting that in addition to reduced proliferation also the matrix composition and thereby
the surface attachment quality of biofilm matrix may be altered by the polyols.

Over the past 3 articles, we explored the role and importance of microbial self-synthesizing biofilms as a crucial factor in health and
disease. Incorporating an understanding of the use of natural biofilm disruptors should not be taken as a singular panacea; the
inexorable adverse biofilms will still happen, and perhaps be more moderated depending on an individual’s dietary practices, but it
can offer broader, more proactive, optimizing nutritional strategies for our better overall health and immunity. Thank you.

May 8 2023

Biofilm/QS – Focus on Serratiopeptidase – Part 3

Friends:

In these past two articles, we explored biofilms and the unique, fascinating, and relatively less-known form of its communication intelligence called “quorum sensing.”

Why not discuss ingredients and leave this background science behind?

The reason is that many “ingredients” go beyond typical ingredient description when positioning their features and how it relates and interacts with the microbiome, oral health, and the biofilm challenge.

We are just scratching the surface of our understanding, which is awesomely complex!

Once when one somewhat better appreciates how things connect, then interrelationships and therapeutic and health strategies are better understood–this is a sequential process, and the biofilm structure and its microbial communication are not random.

From Joe Cohen in “Self-Hacked,” for some review:

“When many bacteria gather in one place, enough to form a “quorum” as in the number of members needed to vote on an issue in parliamentary procedure, they can communicate with one another via chemical messages, or “quorum sensing” (QS).

Quorum sensing allows the bacteria to work en masse (as though together they made up one organism) to change their behavior and adapt to their present environment.

QS operates as “strength in numbers” for the bacteria to expand their territory, construct biofilm shields, defend against antimicrobial agents, and make necessary changes to improve their survival.

However, aside from bacterial biofilms, there are viral ones. The difference is that the bacteria will make their own and the viral biofilm recruits materials from the host cells.

From a newsletter from the Pasteur Institute:

“Like the formation of biofilms in bacteria and viruses, a collection of viruses has formed. This viral accumulation may support the virus in chronic infection. Despite the similarities between bacterial and viral biofilms, they have differences, one of the important differences being that the matrix of normal biofilm formation is mainly made by the microbe itself, while the matrix of viral assemblies is produced by the infected cell.”

The objective against deleterious microbes ( i.e., bacteria, viruses, and some yeasts) is to “jam” these communication signals, and thus, it becomes harder to form biofilms and survive.”

Also, some compounds will not directly destroy certain microbes but can disrupt the biofilm, such as cyanobacteria, spirulina/chlorella. the polyols include xylitol and green-lipped mussel with its omega-3 anti-inflammatory capacity(especially good for stiff joints), serratiopeptidase, etc.

A number of natural compounds are good for jamming signals or disrupting biofilms to the point the underlying infection, or bacterial mass, is more susceptible to our immune system and therapeutics ( to be discussed more in detail next issue).

There are some exotic hybrid amino acids, such as Acyl homoserine lactone, and some natural compound superstars, such as Serratiopeptidase, which I will focus on for the remainder of this article.–

Serratiopeptidase is a proteolytic enzyme derived from silkworms ( from the friendly bacterium Serratia-E15) or can be synthesized through fermentation protocols,

It is a very available bulk ingredient or as a dietary supplement.

Serratiopeptidase: An Integrated View of Multifaceted Therapeutic Enzyme

Charu Sharma, 1 Niraj Kumar Jha, 2 M. F. Nagoor Meeran

“Serratiopeptidase is a proteolytic enzyme with immense applications in therapeutic areas,

which have been validated by several in vitro, in vivo, clinical studies, and through anecdotal evidence.

These applications are attributable to their versatile properties, including anti-inflammatory,

anti-biofilm, potent disruptor, analgesic, anti-endemic, and fibrinolytic effects.

The significant impact of serratiopeptidase reported needs to be backed by more scientific data.

This review encompasses the therapeutic applications of serratiopeptidase based on available in vitro, in vivo,

and clinical studies. We found some strong evidence regarding the efficacy of serratiopeptidase”.

“Serratiopeptidase, A Serine Protease Anti-Inflammatory, Fibrinolytic, and Mucolytic Drug, Can Be a Useful Adjuvant for the Management in COVID-19

Charu Sharma, 1 Niraj Kumar Jha, 2 M. F. Nagoor Meeran, 3 Chandragouda R. Patil, 4 Sameer N. Goyal, 5 and Shreesh Ojha 3,

The management of COVID-19 has continued to rely on drugs repurposed based on their pharmacological effects, including antiviral, antibiotic, anti-inflammatory, and or immunomodulatory, along with the availability of numerous vaccines against SARS-CoV-2 in the past few months (Fan et al.–2020).

“Repurposing of drugs has gained enormous attention over identifying novel drug candidates due to known safety, potency, and multi-targeted pharmacological action as an immunomodulatory, anti-inflammatory, and antimicrobial, fibrinolytic ( dangerous, spontaneous clotting) agent.”

Serratiopeptidase Doses, Safety, and Adverse Effects

SEPD ( serratiopeptidase) is generally well tolerated, with few exceptions of rare adverse effects. It is available alone or in combination with anti-inflammatory agents as a tablet, mostly as enteric-coated tablets or capsules. SEPD is distributed to the tissues and bioavailable in plasma and lymph following binding to alpha-2-macroglobulin in the blood, thus devoid of allergenicity and retains its enzymatic activity at the systemic and cellular level within 1 h.

In most human studies, the usual doses of SEPD range from 10 to 60 mg/day in divided doses, with the most preferred dose of 10 mg thrice daily on an empty stomach. Usually, it is used for 2–4 weeks, depending on the aim of therapy and outcome.

The dose of 10 mg equals 20,000 units of enzyme activity.

Therefore, many researchers and medical experts cite that 10 mg thrice daily could be examined as an adjuvant for COVID-19.

Using SEPD can be virtuously justified, being safe and effective and devoid of side effects that commonly develop with conventional mucolytics that may cause sedation, euphoria, gastrointestinal disturbances, respiratory irritation, and constipation, probably due to the absence of any interaction with receptors.

In my personal approach to nutritional and supplement protection, taking into account the constant, silent battle of adverse biofilm challenge and subclinical inflammation and unwanted spontaneous clotting risk from resiual spike protein since I did have a mild bout of a Covid variant (and who knows when next one will hit next?), I now include a minimal dose for some extra protection with SEPD on an empty stomach no more than several times per week–but that’s me, and you would decide how to use it based on your knowledge and, best yet, a discussion with your professional health provider.

In my next sequel article, I will discuss other easily available and potent natural blockers of QS and biofilms and additional attention concerning dental and periodontic health against oral biofilms.