The Gut-Brain Axis

Sugar’s Toxicity on Your Squash

BY DR. BAYNE FRENCH, MD DC

Tell Me Something I Care About:

• This article will further detail the toxicity of sugar from the intestinal tract to distal organs. This time, your brain.
• Our gut flora communicates directly with the brain through various mechanisms.
• High sugar consumption impairs brain functions in many ways, including by disrupting our gut bacterial balance.
• Endurance athletic fueling "experts", professional athletes, and anyone else who promotes high sugar consumption forfeit any merit and credibility.

The Toxicity of Sugar. A Refresher:

In my Pulitzer-worthy tome Sugar, Leaky Gut and Liver Disease. Let’s Do Some Lumberjacking! I detail how sugar damages our intestinal lining, distorts gut flora, and damages our liver. If you haven’t read it, you should. It’s a hoot. I also detail a sugary trip through the bowel of a coward who trolled me.

So much of what determines health or disease starts at our intestinal lining. This is where numerous products inside our intestine directly interact with, well, us.

Food compounds, toxins like sugar, bacteria, and bacterial-derived products directly interface with our intestinal lining and thus our immune, nervous, and circulatory systems.

When intestinal sugar is low and our gut flora healthy, our intestinal lining is robust. When intestinal sugar is high, and our gut flora is distorted (dysbiosis), the intestinal lining becomes leaky. In my previous large article, I explained how this directly damages our liver. Sorry, brain, you are next.

Both components of sugar (glucose and fructose) lead to disease over time in different ways. Fructose is particularly damaging to our gut bacteria and the proteins that control the integrity of our gut lining. Proteins that keep it tight, and highly selective as to what passes through.

This damage then leads to leak and toxic substances directly flowing to our liver. So how does the brain get affected you might ask? Pipe down. I’m getting there.

Recall that true sugar is sucrose. It is composed of a molecule of glucose and a molecule of fructose.

Glucose spikes blood sugar. This is directly toxic to all tissue, especially the brain. Glucose sticks to our tissues, creating toxic Advanced Glycation Endproducts which I’ve written about before.

Chronically elevated blood sugar also leads to arterial disease, directly impairing oxygen to the brain and leading to dementia over time.

Brain tissue forms and releases BDNF (Brain-derived Neurotrophic Factor). This compound protects brain nerve cells and helps with learning and memory. Monteni et al. (Neuroscience. 2002) was able to show in mice that those rodents eating the most sugar had the least BDNF. They were just dumber mice. If that’s possible.

Higher sugar = lower BDNF, thus impaired learning and memory. A sugary cycle of getting dumber. Maybe that’s why those that promote and recommend high sugar consumption, continue to do so…

Ever hear of beta-amyloid? If you read my articles you would have. It’s the nasty protein aggregates that form in the brain of those with Alzheimer’s disease. The formation of beta-amyloid is directly linked with insulin resistance. Insulin resistance is the pandemic problem arising from chronically elevated blood sugars.

And then there’s fructose. Fructose is likely biochemically more harmful than glucose. It does not spike blood sugar, which is why it was considered a healthier sweetener decades ago.

Fructose is particularly potent at damaging our intestinal lining and disrupting intestinal flora. Both these problems lead to liver damage. Fructose also directly enters the blood stream and is taken up by the liver. This leads to further toxicity and greatly enhanced fat formation, called lipogenesis.

Fructose is a potent driver of uric acid formation. Uric acid can cause gout. It also leads to weight gain, elevated blood pressures, and is directly toxic to the liver.

Perhaps you’re starting to see how both components of sugar are toxic to your brain. In Sugar and its Role in Dementia. Avoid Getting Stupiderer, I attempt to consolidate studies implicating sugar as a cause for getting dumb. Here’s a summary:

• Sugar-sweetened beverage consumption increased dementia risk (Chen et al. Am J Clin Nutr. 2023).
• The highest sugar consumers had the smallest brains and worst memory (Pase et al. Alzheimers Dement. 2017).
• The highest sugar consumers scored the worst on the Mini Mental Status Exam (Chong et al. Clin Interv Aging. 2019).
• Zhang et al. studied 210,832 humans. That’s a lot of mammals. Multiple types of sugar were studied. True sugar, sucrose, was most robustly associated with all-cause dementia and Alzheimer's disease. The highest consumers of sucrose had the highest incidence of dementia.
• Individuals studied over 7 years who consumed the most sugar were twice as likely to develop dementia (Agarwal et al. J Affect Disord. 2022). Agarwar et al. also determined that for every 10% increase in calories from sugar, dementia risk increased by 40%.

Think about this for a moment in the setting of two endurance athletes. Both fuel with sugar, which is super stupid, but at very different amounts:

1. Emple Gummyjar just wants to compete. So much so that he missed the birth of his daughter while in Spain competing in the Mediterranean Epic. His wife said she didn’t mind which is complete crap. Anyway, Emple trains and competes for about 8 hours in an average week, and fuels with 90 grams of sugar per hour. That’s 720 grams of sugar consumed per week.
   
   
2. Preston Potatocannon was bitten by a rattlesnake in middle school. Three of his fingers necrosed and fell off. Professional dodgeball dreams over. Preston found that since he possessed all his toes, he could run quite well. He too trains and competes 8 hours per week, and consumes much lower amounts of sugary crap, about 40 grams per hour. That’s 320 grams of toxicity per week.

Mr. Gummyjar consumes 125% more sugar than Mr. Potatocannon. Recall that Agarwar et al. determined that for every 10% increase in calories from sugar, dementia risk increased by 40%. This then means that Emple Gummyjar, over his 7-year career, has increased his risk of dementia by 500%.

Keep in mind that Preston Potatocannon’s risk is also considerable higher than if he chose to fuel with lower amounts of a complex (non-sugar) carb source.

Asker Jeukendrop is a Ph.D., which probably means he’s hard-working and cognitively up there. How he can promote high sugar consumption for the benefit of the Gatorade Sports Science Institute befuddles me. This is my befuddled face.

Not only does high sugar consumption impair optimal human performance in numerous biochemical ways (see my article, Sugar. The Antithetic Performance Enhancer) it is metabolically damaging and drives cancer, heart disease, fatty liver, and brain disease. It gets worse…Dr. Jeukendrop actually educates athletes on how to “train” the gut to accommodate and tolerate massive amounts of sugar. So as not to crap themselves.

I would love to see an article from Dr. Jeukendrop refuting sugars toxicity to our gut flora, intestinal lining, liver, metabolic wellness, power-to-weight ratio, cardiovascular wellness, contribution to cancer, and brain health.

Micro-talk:

It seems like every author has a different definition of the organisms that inhabit us. Below are definitions that make sense to me:

• Microorganism. These are the wee (microscopic) critters that reside on and in us, comprised of fungi, viruses, archaebacteria, protozoa, and predominantly bacteria.
• Microbiota. The entire collection of organisms we pack around with us. These are the residents of a body-wide community.
• Microbiome. This is a population of organisms and their specific environment. The critter and its ecosystem. Gut microbiome. Skin microbiome. Etc.
• Dysbiosis. An imbalance between beneficial and harmful microbiota. I view dysbiosis as a primary driver of disease.

Microorganisms live in almost every nook and corner of the human body, and their numbers are vast, measuring in the tens of trillions. This is about how many grams of sugar Dr. Jeukendrop and his disciples consume per year.

These human microorganism numbers makes the ratio of human and microbial cells about 1:1 (Kho et al. Front Microbiol. 2018). Meaning we have as many microorganisms as we have cells.

The diversity of these organisms is ever-changing. They are always fighting for supremacy and probably don’t enjoy the company of others that don’t look like them. Sound familiar?

Hibbing et al. (Nat Rev Microbiol. 2010) understands this microscopic xenophobism and describes is a “competitive exclusion strategy”. These are the collective actions that bacteria employee to exert nutrient competition and other competitive metabolic interactions to hamper the growth of other bacteria. This is precisely how beneficial bacteria beat down harmful bacteria. And how harmful ones get out of hand.

Some of these organisms are inherently toxic. Most are innocuous, and many helpful. These helpful microorganisms cause problems when they migrate into other areas:

SUPER COOL TANGENT #1: One of the most common examples of “normal” bacteria going rogue is a bladder infection. Many bladder infections are caused by E. coli. Patients are abhorred to learn that their urine culture grew E. coli. “E. coli!?”. This bacteria is largely helpful when it remains in the colon. In the bladder, however, an infection ensues.

Kandpal et al. (Microorganisms. 2022) reports that disrupted microbiota correspond with numerous disease states including inflammatory bowel disease (like Crohns disease), Alzheimer's disease, Parkinson's disease, fatty liver disease, allergies, and cancers. They state: "Therefore, it is of the utmost importance to investigate the function of microbiota and normal physical and pathological conditions to aid the development of therapeutics against them".

Therapueutics against them? I suggest that one of the most potent "therapeutics against them" is to simply disallow sugar from becoming a staple.

SUPER COOL TANGENT #2: Excessive carbohydrate, especially sugar consumption, alters our gut flora, leading to dysbiosis. Distorted gut bacteria then ferment this carbohydrate producing excess amounts of oxalate. The most common type of kidney stone is calcium oxalate… and doctors tell kidney stone suffers just to consume less calcium and avoid oxalate containing foods like spinach. Seriously?

By far, most microbiota live in our intestinal tract, with a collective weight of about 4.5 pounds (2.1 kg for you Canadians). Over 70% of all our microbiota reside specifically in the colon (large intestine).

The genetic material and thus the spectrum of compounds they are able to produce (because that’s what the genome does by providing a blueprint to make stuff) is vast, possessing 50-100 times more information than the human genome (Anwar et al. Parasit Microbiol Res. 2020). Grice et al. (Annu Rev Geom Hum Genet. 2012) even called the gut microbiota our “second genome”. A bit freaky right? That the bacteria in and on us is genetically much more complicated than we are. Don’t fight it, nurture it.

SUPER COOL TANGENT #3: One of the largest phyla of bacteria in/on us is Bacteroidetes. Within this phylum are numerous species of Bacteroides. These bacterial species possess genes that allow for the formation of over 260 enzymes (called hydrolases) that help us with the digestion of carbohydrates. This is far more enzymes than our own genome is capable of producing. Are you following? The bacteria in our colon makes hundreds of enzymes that help us digest food. More than we make on our own!

Results of human and animal studies are increasingly showing that disruption of intestinal microbiota impacts the development of our brains, leads to neurological disorders and results in behavioral change, like feeling less happy and more stressed-out. Yes, our gut flora greatly impacts how we behave, our actions, and how we feel (Park et al. Exp Mol Med. 2021).

Kandpal et al. (Metabolites. 2022) compiled in massive amount of data detailing how distorted gut flora plays a pivotal role in leading to neurological disorders. “One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial make up".

SCFAs:

These enzymes, hydrolases, formed from our healthy (non-dysbiotic) gut microbiota as described above form short-chain fatty acids (SCFAs) from our diet.

SCFA’s are a rich energy source for us, providing upwards of 10% of the total human energy requirement per day (Beslen et al. Lipid Res. 2013). Meaning, when we have healthy gut flora, they actually produce energy for us. Energy to make us run faster and farther. Energy to lean over and pick up our grandchildren. Energy to harvest apples, drag out a Whitetail deer, procreate, and think! Regular/high sugar consumption directly interferes with our flora’s ability to make SCFAs.

SCFAs are absolutely critical for our health and especially that of our brain. Summary of their benefits:

• Provides nutritional energy for the body.
• Nurtures the colon lining, providing the intestinal cells themselves energy and protecting against colorectal cancer and inflammation (Gonvalvesa et al. Porto Biomed. 2016).
• Cause satiety (feeling full), improved blood sugar metabolism, and insulin sensitivity (Canfora et al. Nat. Rev. Endocrinol. 2015).
• Higher intestinal production of SCFAs (like in those people that don’t consume much sugar) is associated with having a lean body weight, reduced inflammation, and feeling less hungry (Boulange et al. Genome Med. 2016).
• SCFAs influence eating habits and host metabolism acting to prevent excessive food intake and a lower incidence of obesity (Dahiya et al. Front. Microbiol. 2017).
• Decreases glucose production from the liver, thereby reducing elevated blood sugar levels and resultant insulin resistance and obesity (den Besten et al. J. Lipid Res. 2013).
• Communicates with the brain, resulting in a lower appetite (Frost et al. Nat. Commun. 2014).
• Decrease gut permeability by bolstering the tight junctions between cells of the intestinal lining. This protects the gut barrier function (Miyoshi et al. Nutrition. 2008).
• Influence nerve function of the gut itself. This improves motility, secretion, inflammation and lowers tumorgenesis (formation of tumors) (Soret et al. Gastroenterology. 2010).
• Lower the pH of the gut, creating a more acidic environment. This further nurtures a favorable gut flora.
• Sugar, and especially fructose, alters SCFA formation by causing gut flora dysbiosis.

Gut-Brain Axis:

This refers to a bidirectional communication network connecting our gastrointestinal tract and central nervous system. This means there is a reciprocal transmission of messages, intestine to brain and brain to intestine.

This communication occurs via different mechanisms. These include direct nerve connections, hormones, our immune system, and molecules directly released by gut flora that travel to the brain through nerves (not by electrical impulses, but by using nerves as a conduit).

The primary neurological route occurs through the vagus nerve. We have 12 cranial nerves that exit our brain and brain stem, on each side of our head. The vagus nerve is cranial nerve #10, and is primarily the “rest and digest” nerve of our autonomic nervous system. It connects the brain with numerous organs, including the intestine.

SUPER COOL TANGENT #4: Campylobacter jejuni is a nasty bacteria. It can create unimaginable diarrhea, capable of absolutely ruining a 14-day Dall sheep and caribou hunt in the Brooks Range of Alaska. I had to burn the tent. Anyway, Dr. Lisa Goehler and her chums came up with a hilarious idea late one night in a pub. They decided to infect their lab mice with Campylobacter. At least they didn’t feed them sugar. The brains of these mice were then studied, as if crapping themselves wasn’t bad enough. Chemical abnormalities were noted in several different brain regions of these mice. These findings suggested that there was direct communication between intestinal mayhem and altered brain chemistry. The vagus nerve, transmitting pathological messages from the intestine to the brain.

Blood Brain Barrier (BBB):

This barrier is a highly selective “filter” made up of numerous tightly adherent cell types that line blood vessels in the brain. The BBB is a gatekeeper, allowing essential items like oxygen and nutrients (and some medicines) to enter the brain, but blocking almost everything else.

Sharon et al. (Cell. 2016) reported in their research that gut microbiota governs numerous brain and nervous system functions including the integrity of the blood-brain barrier.

I cannot underscore how important this is, which is why I’m going on and on about gut flora.

If your gut microbiota is distorted, then your brain is leaky. This then results in mood and behavior troubles but also increases the risk of neurodegenerative diseases like dementia, Parkinson’s, and others. One of the surest ways to disrupt gut flora is through the regular consumption of sugar.

SUPER COOL TANGENT #5: Liu et al. killed off all bacteria in their mice, resulting in them being “germ-free”. At least they didn’t have diarrhea. Anyway, these mice were found to have leaky brains. In an act of kindness, Dr. Liu and cronnies then gave their mice probiotic (healthy bacteria). Leaky brain resolved!

Strategies to Prevent Dysbiosis:

In my Pulitzer-snubbed tome Sugar, Leaky Gut and Liver Disease. Let’s Do Some Lumberjacking! I describe the absolutely real condition of Leaky Gut syndrome and how it damages your liver. Are you seeing parallels between Leaky Gut and Leaky Brain?

SUPER COOL TANGENT #6: Have you seen Avatar: Fire and Ash yet? I watched it recently, the 10:30 AM matinee. I held hands with my 83-year-old mother, to whom I owe all credit for anything of merit I have accomplished, or ever will. Anyway, in the movie, they must’ve said hear my words a dozen times. Readers and interested parties in your metabolic wellness, hear my words: There is compelling evidence that high sugar consumption damages gut microbiota. This then directly and indirectly damages the brain in numerous ways.

Ever hear of quercetin? I’ve written about it before. It’s useful for many things, including lowering uric acid. It also increases beneficial gut microbiota, including one called Facklamia. Seriously, I couldn’t make that up. Facklamia. Anyway, improved gut microbiota (like Facklamia. I just like saying it) result in higher levels of BDNF (Brain-derived Neurotrophic Factor), thus improved learning and memory (Sharma et al. Neuropharmacol. 2019). Facklamia.

Zheng et al. and his entourage fed their mice an unhealthy diet. Numerous dysbiotic metabolic abnormalities were discovered. These problems were rectified, and healthy gut flora restored, by the supplementation of N-Acetylcysteine (NAC). NAC is an antioxidant, with anti-inflammatory properties, and has known positive effects on blood sugar metabolism. Add improved poop germs to the list.

I know of no single dietary habit that would benefit the brain, metabolism, and overall health and disease risk mitigation as profoundly as consuming sugar very rarely, and in small amounts. And never fuel with it for athletic pursuits. This is the polar opposite of what Dr. Jeukendrup recommends and is actually teaching.

Ike Dweck, aside from having a cool name, is an excellent singer/songwriter. In Blood Runs Hot he sings:

The buried damned don’t get a…
Second chance to come clean.
So who am I to mutter “life is low”
When fresh blood runs hot in me.

Hopefully it’s clear now that an unhealthy intestinal bacterial community has far reaching health consequences. It may also be apparent that purveyors and promoters of incredibly unhealthy advice infuriate me. As a student of anthropologic biology and ancient happenings I know that my time here is fleeting. I want to impart messages of healthful living in the time that I have hot blood.

I urge you, fellow mammal, to take complete responsibility for your health and metabolic wellness. Come to understand basic nutritional principles, identify areas of improvement in your health, and enact a plan. Shuck terrible and biased advice like a cloak. You can do it. Fresh blood is still running hot in you.