"Sugar-Sugar.....And you've got me wanting you"

Trehalose is "the miracle sugar that saves life." Dr. William Seeds

We have all been taught that sugar or glucose is bad for you. “All things are poison, and nothing is without poison; the dose makes the poison.”– Paracelsus (1493–1541). When discussing sugar, I must change that famous quote to all sugars are poison….; but the structure makes the poison.

Trehalose: trehala manna, a substance produced by weevils that feed on plants. Plants and vegetables can also produce Trehalose during the dry season or under stress to maintain hydration and restore health. Trehalose is a disaccharide composed of two glucose molecules. “For where two or three are gathered in my name, there am I among them.” Matthew 18:20.

Glucose is a needed fuel, but as we all know, overconsumption causes harm. However, when glucose is bonded to another glucose, we have Trehalose ( two glucose molecules combined through a bond called 1,1-α-glycosidic bond)

Monosodium glutamate (MSG) was introduced in Japan to enhance food flavor. For those who know the character on YouTube, Uncle Roger (my favorite). He calls MSG “The King of Flavor.”

While MSG enhances the umami flavor profile however with the added glutamate, a primary excitatory neurotransmitter in the brain, can cause neurological inflammation if consumed in excess. To balance that, God gave us Gabapentin.

Like MSG, Trehalose began to gain recognition as a food preservative in the 1990s when advancements in enzymatic production methods made it commercially viable for widespread use. The Japanese company Hayashibara Co., Ltd. developed a cost-effective process for producing trehalose from starch using enzymes, leading to its approval for food applications. Trehalose is mainly used as a food preservative to increase the water content of food, making it fresher and last longer. By the early 2000s, trehalose was widely used as a food additive in various products, including baked goods, beverages, and frozen foods, especially in Japan and other parts of Asia.

When two is better than one:

As a disaccharide, Trehalose is around 40 percent less sweet than sugar. Due to its unique bond, it has numerous benefits for the human body, especially at the cellular level.

1. In healthy patients, blood glucose can spike after eating. It typically rises from a fasting level of ~70-100 mg/dL to 120-140 mg/dL within 30-60 minutes after consuming a meal rich in carbohydrates, depending on the carbohydrates' glycemic index.

   • Insulin levels also rise from fasting (~5-15 µIU/mL) to 40-60 µIU/mL after meals. For Longevity Science, we want insulin to be constantly low in the 2-6 µIU/mL.

   The spike generally occurs within 30-60 minutes after the meal. After blood glucose levels normalize, insulin levels decline, typically within 2-3 hours after the meal.

   One might not think it is a problem, but its cumulative effect over time can lead to Advanced Glycation End Products (AGE). Furthermore, the spike in Insulin can lead to cardiovascular disease. Ranging at the endothelial level, causing:

   A. Endothelial Dysfunction: Chronic high insulin levels reduce Nitric Oxide (NO) production and increase endothelin-1, a vasoconstrictor. This imbalance leads to artery stiffening, a precursor to atherosclerosis.

   B. Atherogenesis: Lipid Metabolism: Hyperinsulinemia promotes dyslipidemia by increasing low-density lipoprotein (VLDL) production and reducing high-density lipoprotein (HDL) levels. This encourages the development of atherosclerotic plaques.

   C. Oxidative Stress: High insulin levels increase oxidative stress, which damages endothelial cells and accelerates plaque formation.

   D. Hypertension: Sympathetic Nervous System (SNS) Activation: Hyperinsulinemia stimulates the SNS, increasing heart rate and vascular resistance, contributing to high blood pressure.

   E. Renal Sodium Retention: Insulin promotes sodium reabsorption in the kidneys, causing fluid retention and elevated blood pressure.

   F. Inflammation: Chronic hyperinsulinemia drives the release of inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), contributing to vascular inflammation and plaque instability.

   G. Prothrombotic State: Insulin resistance and hyperinsulinemia impair fibrinolysis (the breakdown of blood clots) by increasing plasminogen activator inhibitor-1 (PAI-1) levels, increasing the risk of thrombosis and acute cardiovascular events.

   H. Left Ventricular Hypertrophy: Insulin promotes the growth of cardiomyocytes. Chronic hyperinsulinemia can contribute to left ventricular hypertrophy, which is associated with heart failure and arrhythmias.

This leads back to the question of what causes cardiovascular disease: cholesterol or sugar? Based on my previous posts and The Mid-Western Doctor’s post, the answer is sugar and chronic high insulin. I don’t think it is just the Mid-Western Doctor and me; many physicians, including some Cardiologists, are now waking up to the lie that big pharma has been promoting that Cholesterol is the cause of Cardiovascular diseases. As of recent estimates, approximately 25% to 30% of adults aged 40 years and older in the United States are prescribed statins to manage cholesterol levels and reduce cardiovascular disease risk. This translates to roughly 40 million Americans using statins. The prevalence is higher among specific groups. In older adults, usage increases with age, with nearly 50% of adults aged 65 and older on statins. To me, statin is a toxin and should never be used, period!

“Sugar-Sugar, you got me wanting you.” Trehalose is increasingly recognized for its ability to modulate postprandial glucose and insulin responses. Studies consistently demonstrate its potential to attenuate rapid increases in blood sugar and insulin levels after meals compared to other carbohydrates such as glucose or sucrose. This modulation mainly benefits individuals managing diabetes or seeking better glycemic control.

2. Increasing intracellular hydration: According to Dr. William Seeds, when one loses 10-15 percent of intracellular water, the cell becomes acidic, leading to negative responses. Trehalose increases the osmolarity of extracellular water, pulling water into the cell through the ionic water channels surrounding it.

3. Stabilization of Proteins and Membranes: Trehalose helps stabilize proteins and lipid membranes, maintaining cell integrity during stress. Stabilizing the cellular membrane protects the cell, and stabilizing the mitochondria membrane protects the outer membrane of the mitochondria (MOM) from releasing reactive oxygen species into and outside the cell. Stabilization of proteins protects proteins from misfolding and aggregating into plaques. By preventing protein misfolding, Trehalose has been shown to protect neurons from damage, potentially aiding in the prevention of neurodegenerative diseases like Alzheimer's, Parkinson's, Multiple Sclerosis, ALS, or other neurological-degenerative disease.

4. Apoptosis and Autophagy Activation: most human cells divide 40-60 times, but this number can vary significantly based on cell type, environmental conditions, and genetic factors. After a cell is done with cell division, God designed it to go into a cellular death program called Apoptosis, the Sicario. When the sicario is done, The Cleaner comes in. Autophagy is a process that promotes cellular cleanup. This process is crucial for preventing age-related cellular decline. Trehalose plays a critical role in this. When this process is not optimized, one can have uncontrolled cellular division, leading to cancer. Senescent Cells can stay around forever, and Stem Cell Exhaustion can also occur.

5. Gut Microbiota Benefits: Trehalose is a substrate for beneficial gut bacteria, promoting their growth and activity. While not a traditional prebiotic, it can indirectly support a healthier gut microbiota balance.• Promotes Growth of Beneficial Bacteria: Certain strains of beneficial bacteria, such as Bifidobacteria and Lactobacilli, can metabolize trehalose. This contributes to a diverse and balanced gut microbiome. It also reduces pathogenic growth. By enhancing the growth of beneficial bacteria, trehalose suppresses the proliferation of harmful or pathogenic bacteria.*( a study (2018) published in Nature by Collins et al. found a relationship between Trehalose and Clostridium difficile (C. difficile). C. difficile is a bacterium that can cause severe diarrhea and colitis, particularly in individuals with disrupted gut microbiota (e.g., after antibiotic use). A closer look at the study showed that Trehalose does not cause C. difficile. However, when a patient develops C. difficile through multiple rounds of antibiotics, Trehalose metabolism can worsen that condition. So please don’t take it when you have C. difficile.

6. Anti-Inflammatory Agent: Modulates Immune Responses: Downregulates Pro-Inflammatory Cytokines: Trehalose reduces the expression of cytokines like TNF-α, IL-6, and IL-1β, which are central to chronic inflammation. It helps shift the immune response toward a more balanced and less inflammatory state. It upregulates Anti-Inflammatory Cytokines by enhancing the production of cytokines like IL-10, which suppress inflammatory pathways and promote tissue healing.

7. Reduces Oxidative Stress: Trehalose is also an antioxidant. Intracellular oxidative stress is a significant driver of diseases and aging. Trehalose helps mitigate oxidative damage by stabilizing cellular structures and scavenging free radicals.

Trehalose isn’t just a simple sugar; it’s the multitasking overachiever of the carbohydrate world. Like a microscopic repair technician, trehalose fortifies cells against oxidative stress, tidies up the intracellular mess through autophagy, and whispers calming words to overactive immune responses. Its knack for stabilizing proteins and membranes makes it a cellular bodyguard, protecting against inflammation’s fiery wrath.

In your gut, trehalose plays host to a microbial symphony, nurturing beneficial bacteria while keeping the bad actors in check. Beyond digestive harmony, it steps into the metabolic world as a blood sugar whisperer, supporting insulin sensitivity and mitigating inflammation tied to obesity and diabetes.

Trehalose doesn’t stop there—it dons a neuroscientist’s hat, soothing neuroinflammation in conditions like Alzheimer’s and Parkinson’s, and even moonlight as a gut healer for those battling IBD. All this while safeguarding mitochondrial powerhouses to keep your cells energized and efficient.

Is trehalose too good to be true? It could be consumed recklessly in environments teeming with misbehaving bacteria like C. difficile. But for most, this “miracle sugar” offers a sweet blend of protection, healing, and metabolic finesse—a modern-day panacea in the guise of a humble carbohydrate.

*Take waypoints: Throw out your processed sugar and start using Trehalose. I used to drink coffee with one teaspoon of sugar; now, I use trehalose, and because it is not as sweet, I need two teaspoons. You can cook, bake, or add Trehalose to your water. It has no side effects but offers tremendous benefits, including Anti-aging, Metabolic Syndrome, and Autoimmune disease. It is beneficial for fighting cancer or being in remission from cancer ( Cancer cells love glucose).

This brings me back to the corruption of the food industry. In the 1990s, two food flavorings were introduced: MSG and Trehalose. One was terrible (MSG), and one was good. Of course, MSG was promoted over Trehalose. When RFK Jr. is officially in charge, I hope he will bring up Trehalose.

Anthony Phan MD

References:

1. Trehalose Reduced Glycemic and Insulinemic ResponsesLink: Cambridge Journal

• Findings: Trehalose ingestion significantly attenuated rises in plasma glucose and insulin levels post-meal in overweight subjects.

• Implications: Offers an alternative carbohydrate source for improving postprandial substrate utilization.

2. Effects on Glucose-Intolerant Subjects

Link: Cambridge Journal

• Findings: Reduced postprandial plasma glucose and insulin spikes in glucose-intolerant individuals when trehalose was ingested, compared to glucose or sucrose.

3. Trehalose and Incretin Hormones

Link: Springer

• Findings: In healthy subjects, trehalose reduced insulin release and lowered blood glucose levels without causing hyperglycemia. It also influenced incretin hormone responses favorably.

4. Daily Consumption Study

Link: Springer

• Findings: One teaspoon of trehalose daily improved glucose tolerance and maintained glucose homeostasis in a controlled trial.

5. Comparative Sweetener StudyLink: Taylor & Francis Link: MDPI Link: NCBI Link: Elsevier

6. Insulin Resistance and Endothelial Dysfunction

• Findings: Highlights the role of hyperinsulinemia in impairing endothelial function, a key driver of atherosclerosis and hypertension, which are significant contributors to cardiovascular diseases.Link: Read on Academic Journals

7. Role of Hyperinsulinemia in Hypertension

• Findings: Demonstrates how hyperinsulinemia activates the sympathetic nervous system, contributing to vasoconstriction and increased blood pressure, a leading risk factor for CVD.Link: Full Article on NIH

8. Trehalose in Increasing Intracellular Hydration

Study Title: Synergic Effects of Glucose and Trehalose on Hydrated Lipid Bilayer Properties

Authors: S. Maity, M. Jana

Publication: National Institute of Technology Repository, 2024

Link: Read Full Text

9. Trehalose as a Stabilizer of Proteins and Membranes

• Study: Key Amino Acid Residues of the Agt1 Transporter for Trehalose Transport by Saccharomyces cerevisiae • Link: Read Full Study on MDPI

10. Trehalose as a Neuroprotective and Membrane-Stabilizing Role

• Study: Trehalose: Neuroprotective Effects and Mechanisms• Link: Read Full Text on MDPI

11. Trehalose Neuroprotection Through Autophagy Induction

• Study: Trehalose Attenuates In Vitro Neurotoxicity of 6-Hydroxydopamine by Reducing Oxidative Stress and Activation of MAPK/AMPK Signaling Pathways Link: Read on MDPI

12. Trehalose in Fermented Beverages and Gut Health

• Study: Exploring the Diversity of Fermented Plant-Based Beverages with an Emphasis on the Therapeutic Role of Probiotics• Link: Access Full Text (PDF)

13. Trehalose Biological Properties of Boletus edulis Extract on Caco-2 Cells

• Study: Antioxidant, Anticancer, and Anti-Inflammatory Effects of Boletus edulis Extract• Link: Read on MDPI