Dr. Vliet’s Health Tip~ Silent Sabotage: How Modern Life Depletes Nitric Oxide & Damages Your Gut”

Did you know nitric oxide (NO) plays a major role in maintaining gut health?  Most doctors don’t mention it.  Most people never heard about nitric oxide beyond “it helps lower blood pressure.”  Yet this simple molecule is actually a quiet workhorse that links your gut, your immune system, your heart and blood vessels, your brain, and plays a major role in whether you remain healthy with zest and vitality as you age. In addition to all you have heard about nitric oxide’s role in cardiovascular health and erectile function, this powerful vasodilator molecule helps keep blood flowing to your intestinal lining, supports your immune defenses, and influences how “leaky” or resilient your gut barrier is. When the gut barrier breaks down due to vascular and endothelial damage, more toxins and inflammatory molecules slip into the bloodstream, and your body pays the price over time.

Today’s world makes this problem worse due to many sources of silent sabotage: 1) the standard American diet—packed with ultra‑processed foods, sugar, and unhealthy fats—chips away at gut health day after day. 2) Viral and bacterial infections, 3) COVID and other vaccines, 4) many of today’s medications, 4) repeated medical interventions, and 6) environmental toxins (herbicides, pesticides, endocrine disruptors, microplastics, etc) damage the good bacteria that protect your gut and help your body make and use nitric oxide properly. Then add in aging, chronic stress, poor sleep, sitting too much, and constant exposure to chemicals in the sky and you get a perfect storm where the critical beneficial gut microbes die off, nitric oxide signaling declines, and inflammation quietly rises. That combination doesn’t just affect digestion; it can shape your heart health, brain function, hormone balance, and overall resilience as you age.

In my original Health Tip: Nitric oxide Master Molecule & Super Optimizer of Health I introduced nitric oxide (NO) as nature’s super optimizer of health. This amazing little molecule dilates vessels, improves blood flow throughout the body, stimulates formation of new blood vessels for tissue repair and wound healing, and regulates platelet aggregation and reduces the risk of blood clots. Nitric oxide used to be thought of as simply the “foundation of heart health” until we realized it’s “master” effects on blood vessels throughout the brain and body as a vasodilator controlling blood flow to help support healthy blood flow pressure and health of the endothelium lining of blood vessels.

Today’s health tip focuses on nitric oxide’s role in gut health, inflammation and insulin resistance, and provide specific steps you can take to optimize your nitric oxide levels and reap its wide range of health benefits. But first, let’s review a summary of the key functions of nitric oxide throughout the body and important key points.

SUMMARY OF KEY FUNCTIONS OF NITRIC OXIDE: NO is synthesized in the body through a process of converting L-arginine (a “semi-essential” amino acid) into nitric oxide and citrulline. Once synthesized, NO is released to diffuse freely across cell membranes to execute its functions:

1. Vasodilation – relaxing and widening of blood vessels to help blood flow, to better deliver oxygen and nutrients to muscles and organs and regulating blood pressure.
2. Angiogenesis – the formation of new blood vessels important for tissue repair and wound healing.
3. Platelet function – Helps to regulate platelet aggregation to prevent blood clots and maintain heart health.
4. Relaxation of smooth muscle in gastrointestinal tract, airways, urinary bladder, uterus, etc.…) to regulate the processes of digestion, breathing, urination, menstruation and pregnancy.
5. Immune response – Helps to regulate inflammation and can also be made by the immune cells to kill bacteria, viruses and parasites.
6. Neurotransmission – Serves as a signaling molecule for the brain and peripheral nervous system.
7. Mitochondrial regulation – Modulates mitochondrial respiration and energy production in cells.
8. Gene expression regulation – Acts as a signaling molecule within cells to regulate gene expression and other cellular processes including cell proliferation (cell growth and division), differentiation (cell specialization), and apoptosis (programmed cell death).

IMPRESSIVE HEALTH BENEFITS OF NITRIC OXIDE:
Male Hormones and Erectile Dysfunction

• Testosterone – Nitric oxide (NO) and testosterone have a complex, bidirectional relationship: Testosterone can positively regulate NO production, while NO can also influence testosterone secretion.
• Erectile Dysfunction – NO is a key mediator of penile erection by stimulating the relaxation of smooth muscle cells in the erectile tissue leading to increased blood flow for the attainment of erection.
• Sexual Arousal – Both testosterone and NO levels increase during sexual excitation/arousal, and there’s a correlation between both testosterone and NO levels and sexual behavior.

Female Hormones and Sex

• Estrogen (in particular, 17-beta estradiol, the primary pre-menopausal estrogen) and nitric oxide work together to maintain healthy blood vessels, reducing risk of stroke, protecting the brain and cognitive function, and maintaining healthy blood pressure. Loss of estradiol at menopause leads directly to declining NO production and is one of the main reasons menopausal women have higher blood pressure, and also experience memory loss, mood dysregulation, sleep and concentration problems.
• Increased NO production – 17β-Estradiol increases expression and activity of nitric oxide synthase (NOS), the enzyme responsible for NO production.
• Sexual Function – NO is involved in sexual arousal and function, with links to improved blood flow to the genital area.

Brain and Cognitive Health

Nitric oxide (NO) plays a multifaceted role in brain function, acting as a signaling molecule with both neuroprotective and neurotoxic effects. It’s involved in regulating cerebral blood flow, synaptic plasticity, learning, memory, and even influences the sleep-wake cycle.

PTSD

Nitric oxide (NO) plays a significant role in the development and progression of PTSD, particularly in the context of fear and memory. Studies suggest that alterations in NO signaling, especially involving the enzyme neuronal nitric oxide synthase (nNOS), are linked to PTSD symptoms and related behaviors. Furthermore, manipulating NO levels, such as through nitrous oxide inhalation has shown promise as a potential therapeutic approach for some individuals with PTSD.

Heart Health

NO plays a critical role in protection against the onset and progression of cardiovascular disease through blood pressure regulation, maintaining vascular tone, inhibiting platelet aggregation and leukocyte adhesion, and prevention of smooth muscle cell proliferation (leading to thickening of blood vessel walls). Low NO levels are linked to hypertension, atherosclerosis, cardiomyopathy, congestive heart failure and heart attacks fundamentally via endothelial dysfunction, impaired blood flow and oxygen delivery to heart and lungs.

Diabetes

Nitric oxide is a critical molecule in glucose metabolism. In diabetes, dysregulation of nitric oxide pathways can contribute to complications like kidney disease and blindness. NO deficiency impairs blood vessel function and reduces insulin sensitivity which in turn leads to more gain in body fat and difficulty controlling glucose.

COPD

Studies show L-arginine metabolism is disturbed in individuals with COPD. With less L-arginine available for nitric oxide synthase (NOS) activity, less nitric oxide is produced. Supplementing with L- arginine and liposomal vitamin C can improve shortness of breath and the ability to perform daily activities in individuals’ chronic obstructive pulmonary disease.

ADDITIONAL NITRIC OXIDE BENEFITS:

• Hair and skin health, repair and even protection from sun damage.
• Improved exercise performance, including endurance, delayed fatigue, better muscle recovery and growth, less muscle soreness.
• Reduced inflammation throughout the body.
• Improved immune function.

Role of Nitric oxide Gut Health, Inflammation and Insulin Resistance
Nitric oxide acts like a switchboard for gut health, inflammation, and insulin sensitivity.  At the right level and from the right sources, NO protects. When NO is overproduced in the wrong places, it quietly drives inflammation and damage. It is important to understand the Nitric oxide basics: the “good” and “bad” streams.

Nitric oxide (NO) is made from the amino acid l‑arginine by enzymes called nitric oxide synthases (NOS).  There are three main types:

• Endothelial NOS (eNOS) – lives in blood vessel lining cells and produces low, steady amounts of NO to help vessels relax, regulate blood flow, and support insulin delivery into tissues.
• Neuronal NOS (nNOS) – lives in nerve cells and produces NO as a messenger to help nerves communicate and coordinate gut motility and other functions.
• Inducible NOS (iNOS) – mostly in immune and inflamed tissues; it normally stays quiet but can turn on strongly during inflammation, flooding tissues with much higher and more sustained NO.

Think of eNOS/nNOS as your “background maintenance crew,” making gentle pulses of NO that keep circulation, nerves, and basic defenses running smoothly

Think of iNOS is more like a fire hose: when inflammation ramps up, iNOS produces a large burst of NO intended to kill invaders or clear damage—but when this stays chronically elevated, it becomes toxic to your own cells.

Let’s review the many ways nitric oxide works in your gut. Bear with me, this may be a little technical but I feel it is important to demonstrate all the nuances to fully appreciate what goes on in our body and understand the complex connections throughout our body. If this gets to be more detail than you need, jump ahead to my summary and ACTION PLAN at the end!

1. NO in gut barrier, motility, and mucosal defense
In the gastrointestinal (GI) tract, NO is a key regulator of the gut barrier—the thin epithelial layer that separates the contents of your intestines from the rest of your body.
Physiologic (healthy) levels of NO:

• Increase microvascular blood flow to the mucosa, ensuring oxygen and nutrients reach the gut lining.
• Support mucus secretion, which acts as a protective coating separating bacteria and food particles from epithelial cells.
• Aid epithelial restitution, meaning the rapid repair and regrowth of cells when the lining is slightly injured.
• Relax smooth muscle in the gut wall to coordinate motility, helping food move along at the right pace.

At this “maintenance level,” NO is cytoprotective—it helps cells survive and recover—and promotes healing in the stomach and intestines.
However, both too little and too much NO can predispose to mucosal injury, depending on context:

• Too little NO (e.g., impaired eNOS activity, poor blood flow) can reduce mucosal perfusion, weaken barrier repair, and make the gut lining more vulnerable to irritants and toxins.
• Too much NO, especially from iNOS during chronic inflammation, can overwhelm local antioxidant defenses, producing reactive nitrogen species that injure cells, disrupt tight junctions (the “rivets” between gut cells), and promote barrier breakdown.

So NO in the gut is a “Goldilocks” molecule: you want enough to maintain blood flow, mucus, and repair, but not the chronic, high‑flux production that accompanies ongoing inflammation.

2. NO and gut inflammation: dual roles
NO plays a classic double role in gut inflammation:

• At lower, regulated levels (mostly eNOS/nNOS), it can be anti‑inflammatory: improving microcirculation, supporting barrier integrity, and limiting excessive immune activation.
• At high, sustained levels from upregulated iNOS, it becomes pro‑inflammatory and tissue‑damaging.

3. NO and the gut microbiome
Nitric oxide also shapes the gut microbiome—the community of bacteria and other microbes living in the intestines.

• At physiologic levels this can help maintain balance, discouraging overgrowth of certain pathogens.
• In inflammatory states, higher NO and peroxynitrite levels can reduce overall diversity and shift the ecosystem toward more stress‑tolerant, often less beneficial species.

In practical terms, the NO status of the gut helps decide “who lives there,” reinforcing either a healthy ecosystem or an inflammatory, dysbiotic one.

4. The oral–gut nitrate–NO axis
Beyond NOS, you have a dietary route to NO: the nitrate–nitrite–NO pathway.  Here’s how it works:

1. Dietary nitrate from vegetables enters the bloodstream after absorption.
2. Salivary glands concentrate nitrate in saliva.
3. Oral bacteria on the tongue and in the mouth reduce nitrate to nitrite.
4. When you swallow, nitrite enters the acidic environment of the stomach, where it can be chemically converted into NO and other nitrogen oxides.
5. Some NO acts locally in the stomach and upper GI tract; some products are absorbed and contribute to systemic NO availability independent of eNOS.

This pathway is important because it provides an alternative source of NO, particularly when endothelial NO production is impaired. It has documented relevance for:

• Vascular health and blood pressure regulation.
• Endothelial function.
• Metabolic health and exercise performance.

Several everyday factors can disrupt this oral–gut nitrate–NO axis:

• Antiseptic mouthwashes that kill nitrate‑reducing bacteria reduce nitrite formation and downstream NO.
• Very limited chewing (e.g., relying heavily on liquids or smoothies) reduces contact time with oral bacteria and the mechanics of chewing that signal this conversion.
• Chronic high‑dose proton pump inhibitor (PPI) medicines use reduces gastric acidity, making nitrite‑to‑NO conversion less efficient.

When this axis is impaired, dietary nitrate from vegetables no longer converts as effectively into NO, potentially contributing to endothelial dysfunction, higher blood pressure, and worsening cardiometabolic profiles.

5. NO, inflammation, and systemic insulin resistance
Systemic insulin resistance often emerges in the setting of low‑grade, chronic inflammation in metabolic tissues: adipose tissue, liver, and skeletal muscle.  In these tissues:

• Inflammatory signaling induces iNOS expression, especially in adipose tissue macrophages and hepatocytes.
• iNOS produces high levels of NO that react with other molecules to form reactive nitrogen species.
• These reactive species cause post‑translational modifications of insulin pathway proteins, particularly S‑nitrosylation (attachment of an NO group to cysteine residues), which alters protein function.
• The protein’s ability to transmit the insulin signal is reduced.
• Glucose uptake in skeletal muscle falls.
• Hepatic glucose production becomes less tightly controlled.
• Adipose tissue becomes more lipolytic and pro‑inflammatory.

Over time, this leads to insulin resistance across liver, muscle, and fat tissue, even if pancreatic insulin output is initially normal or elevated.

In short, chronic iNOS‑driven NO and nitrosative stress in metabolic organs are one of the biochemical “wrenches” thrown into the gears of insulin signaling.

6. eNOS vs iNOS in metabolic regulation
There is a clear distinction between:

• eNOS‑derived NO – generally protective in metabolic regulation.
• iNOS‑derived NO – often damaging in the context of obesity and insulin resistance.

Reduced eNOS activity or NO bioavailability in the endothelium is associated with endothelial dysfunction, insulin resistance, hypertension, and broader cardiometabolic disease. Blood vessels lose their ability to dilate appropriately, nutrient delivery to muscles and other tissues is impaired, and insulin’s ability to reach and act on target cells declines.

Upregulated iNOS and high flux of nitrogen oxides promote inflammation and insulin resistance in liver, muscle, and adipose tissue. Animal models with increased iNOS show worse metabolic profiles, while iNOS knockout or pharmacologic suppression often improves insulin sensitivity.
This gives us a practical therapeutic focus:

• Enhance eNOS and its physiologic NO to improve vascular and metabolic function.
• Limit chronic iNOS activation and its high‑flux nitrosative output, especially in inflamed gut and metabolic tissues.

7. Nitrosative stress and metabolic complications
When NO—particularly from iNOS—is produced in excess and the antioxidant system is overwhelmed, several damaging processes occur:

• NO reacts with superoxide to form peroxynitrite, a potent oxidant.
• Peroxynitrite drives nitrosative stress, which overlaps with oxidative stress but specifically involves nitrogen‑containing reactive species.
• Lipid peroxidation damages cell membranes and lipoproteins.
• Mitochondrial proteins and DNA are injured, impairing energy production.
• Enzymes in metabolic pathways are modified, leading to functional impairment.

Clinical and experimental data connect this nitrosative stress to:

• Worsening insulin resistance.
• Diabetic complications (e.g., neuropathy, nephropathy, vascular damage).
• Dyslipidemia and disturbed glucose homeostasis.

SUMMARY: Protect your gut–metabolic axis!

• Gut inflammation and dysbiosis drive high iNOS activity, the same nitric oxide chemistry that should protect you becomes part of a loop that damages the barrier, disrupts microbes, and worsens insulin resistance.
• Supporting healthy eNOS‑driven NO with diet, movement, and vascular care, while calming chronic iNOS activation, helps keep that loop from spinning out of control and causing damage.

We want to nourish “green light” NO through vegetables, exercise, and oral–gut health and avoid flipping on chronic “red light” NO by reducing inflammation, processed foods, and gut barrier injury.

YOUR NITRIC OXIDE-GUT OPTIMIZING ACTION PLAN
Our Action Plan is designed to keep your gut and nitric oxide system on the same team.  It helps digestion and also supports blood flow, metabolism, brain health and hormone balance as you age, and lowers risk of chronic illness.

Step 1: Understand the NO–gut–metabolism connection

Think of nitric oxide (NO) as a “smart messenger” that helps:

• Keep blood flowing smoothly to your gut and other organs
• Protect your gut lining so it isn’t “leaky”
• Support healthy blood sugar, blood pressure, and energy

When the gut is unhealthy—too many “bad” bacteria, not enough “good” ones, and a damaged gut lining—more toxins (like LPS-lipopolysaccharide a known as endotoxin from bacteria) leak into the bloodstream. That leakage turns on a more aggressive form of NO (from iNOS) and related “nitrosative stress,” which can:

• Injure the gut lining further
• Upset the microbiome balance
• Interfere with insulin and promote inflammation

At the same time, the helpful form of NO (from eNOS in your blood vessels) often goes down with aging, stress, and poor lifestyle habits. So, the goal is simple:

• Boost the protective NO that supports circulation and barrier health
• Dial down the inflammatory NO that keeps your gut and metabolism “on fire”

Step 2: Spot what quietly drains your nitric oxide: “NO saboteurs”

• Getting older – Our natural NO‑producing enzymes slow down with age.
• Declining estradiol in women and testosterone in men: Seek to optimize your hormones!
• Not moving enough – Sitting most of the day means less blood‑flow signal to make NO.
• Standard American diet – Lots of processed food, sugar, and unhealthy fats lower NO and raise inflammation.
• Too few leafy greens and beets – These foods are the main nitrate sources your body uses to make NO.
• Daily antibacterial mouthwash – It kills the mouth bacteria that turn food nitrates into usable NO.
• Frequent antibiotics – disturb the gut and mouth microbes that help with NO pathways.
• Long‑term acid blockers (PPIs) – They interfere with how nitrates are turned into NO in the stomach.
• Regular use of NSAIDs and certain other meds – Some drugs can damage blood vessels or disrupt NO signaling.
• Obesity, high blood pressure, high blood sugar – All stress your blood vessels and reduce NO.
• Smoking and toxins – create oxidative stress that destroys NO.
• Chronic stress and poor sleep –  raise stress hormones and inflammation that blunt NO production.
• Genetic factors affecting methylation/BH4 – In some people, NO‑making enzymes simply are not working efficiently.

You don’t have to fix all of these at once. Start by circling the ones that apply most to you and BEGIN THERE!

Step 3: Eat in a way that builds NO and calms gut inflammation

A simple food pattern can help both your gut and your nitric oxide:

• Load your plate with nitrate‑rich vegetables to feed the “nitrate–nitrite–NO” pathway, supporting better blood flow, energy, and metabolic balance.
• Aim to eat more foods like beets, beet greens, spinach, arugula, bok choy, kale, celery, cabbage, and other leafy or cruciferous veggies.
• Protect the mouth–gut NO pathway
  • Chew your food well and don’t rely only on smoothies; this gives your oral bacteria a chance to work with food nitrates.
  • Use strong antiseptic mouthwash only when clearly needed, not as a daily routine.
  • If you’re on long‑term acid blockers, ask your clinician whether they’re still necessary and if lower doses or alternatives are possible.
• Feed the “good” bacteria in the gut to help grow beneficial microbes that support nitrate metabolism and reduce the inflammatory triggers that crank up iNOS.
  • Regularly include prebiotic‑rich foods: beans, lentils, onions, garlic, asparagus, oats.
  • Add colorful, polyphenol‑rich foods: berries, dark and unsweetened cocoa, green tea, and a variety of vegetables.
• Cut back on gut and metabolic “fire starters” promote gut leakiness, liver and fat tissue inflammation, and the kind of NO (iNOS) that damages rather than protects.
  • Minimize ultra‑processed snack foods, fast food, sugary drinks,
  • Reduce intake of saturated fats.

Step 4: Use movement as a daily nitric oxide “ON switch” for protective NO production

• Aim for regular, moderate aerobic activity
  • Brisk walking, cycling, swimming, or similar movement most days of the week.
  • Even shorter “movement snacks” (5–10 minutes multiple times per day) help.
• Add resistance training to help blood vessels make more of the right form of NO and improve blood glucose regulation
  • Light weights, resistance bands, or body‑weight exercises a few times per week strengthen muscles and improve insulin sensitivity.
  • Every time you are moving around, you get your blood flowing, you’re teaching your vessels to produce more protective NO.

Step 5: Clean up habits that damage NO and the gut – small changes have big impact

• Keep alcohol intake to moderate amounts 1-2 times a week, not daily
• Avoid tobacco.  Both excess alcohol and any tobacco use damage blood vessels, raise oxidative stress, and push NO in the wrong direction.
• Improve stress management and sleep duration/quality
  • Chronic stress and poor sleep raise inflammatory and hormonal signals that suppress NO and harm the gut.
  • Simple routines—breathwork, mindfulness, light evening stretching, consistent bedtimes—can calm this down.

These steps not only help nitric oxide but also support your gut barrier, microbiome, and overall resilience.

Step 6: Consider targeted supplements

These are tools, not magic bullets, and should be used working with a clinician who knows your history and medications:

• For supporting protective NO
  • L‑arginine or L‑citrulline: amino acids that can help NO production.
  • Nitrate‑rich concentrates (e.g., beet products): may boost NO, blood flow, and performance.
• For calming inflammatory NO and nitrosative stress
  • Plant polyphenols (cocoa flavanols, resveratrol, green tea catechins): can support healthy NO, reduce oxidative stress, and reduce inflammatory signaling.
  • Antioxidant nutrients (vitamin C and E): help protect NO from being destroyed and may modestly improve vessel function.
  • Botanicals such as quercetin and berberine help reduce “overactive” inflammatory pathways that drive iNOS and nitrosative stress.
  • Probiotic and prebiotic combinations: support a healthier microbiome and lower gut‑derived toxins, indirectly reducing iNOS activity and improving insulin sensitivity.

Optimizing Benefits of L-Arginine Supplementation:

• I recommend our TruNitricOxide SR™ which has a unique patented extended-release form of L-arginine to prolong bioavailability of L-arginine to make NO.
• TruNitricOxide SR™ also contains ACTINOS2®, a mixture of both high- and low-molecular weight fractions of proteins and peptides that activate NOS to boost nitric oxide production, enhance transcription of the NOS gene and support its role in reducing the negative feedback mechanism for NO production.
• Studies found ACTINOS2 increases NO production in human endothelial cells in vitro from 9.5 to 12.7 times compared to a control.

I also selected our TruNitricOxide SR™ product because it is manufactured in the United States using the highest purity (>98.0%) of L-arginine alpha Ketoglutarate that is commercially available. This formulation is designed to deliver L-arginine alpha ketoglutarate in a controlled manner over a period of approximately 4-6 hours.