Reversing the Inhibition of Metabolic Pathways in the Aluminum Age

 

Reversing the Inhibition of Metabolic Pathways in the Aluminum Age

Dennis N. Crouse 8-16-26

Hypometabolism is a biomarker of Alzheimer’s Disease and is measured as the degree of inhibition of the first step in glycolysis. Glycolysis is the primary pathway that metabolizes carbohydrates. Aluminum inhibits the first step in glycolysis and other metabolic pathways resulting in lower energy production from the food we eat. The metabolic pathways in our bodies that produce energy from carbohydrates and fatty acids are facilitated by several different enzymatic sequences:

·       Glycolysis of carbohydrates to pyruvate from which acetyl-CoA is produced

·       Beta-oxidation of fatty acids to acetyl-CoA

·       Krebs cycle converting acetyl-CoA to carbon dioxide

Remarkedly, the human body’s biochemistry can switch from 100% carbohydrate diet to a 100% fatty acid diet. This dietary switch-over is called the “Schwatka Imperative”.  This is named after Lieutenant Frederick Schwatka who volunteered for a single-handed 19-month 3,000-mile Arctic mission looking for information on why the men of the Franklin Expedition perished in the Arctic¹. Schwatka intentionally took with him only enough carbohydrate to last the first 10 months.  On June 15th of 1879 he ate his last hard bread and then it became imperative that his body switch to a diet (a.k.a. keto diet) of primarily fresh-killed reindeer meat with occasional fish. For the first two or three weeks on the ketogenic diet he felt “… an apparent weakness and inability to perform severe exertive, fatiguing journeys.”  Then miraculously after two to three weeks on the ketogenic diet his strength and stamina returned to normal. For example, during the last two days of the expedition he hiked 75 miles.

Sixteen years later Dr. Fridjof Nansen and Lieutenant Fredrik Hjalmar Johansen made a dash for the North Pole from their ship the “Fram” with the intention of eating a ketogenic diet of freshly shot polar bear meat when their supplies ran out after the first month². Unable to find the “Fram” on the shifting arctic ice they hiked hundreds of miles and after fifteen months they accidentally encountered the Jackson Expedition on June 17th of 1896 on Cape Flora in Franz Joseph Land³.  Remarkably at the time of this encounter both men were in excellent health.  Dr. Nansen, who stood 6 feet 2 inches tall, was 21 pounds over his normal weight of 184 pounds and Lieutenant Johansen was “a sturdy muscular little chap ... the picture of health” according to Jackson³. These dietary experiments proved that a ketogenic diet does provide strength and stamina.    

Schwatka was lucky he traveled ten years before the Bayer Process for aluminum purification from bauxite was developed in 1888. Nansen and Johansen were also lucky as by 1890’s aluminum had not yet entered the food supply on the scale seen during aluminum age that began in 1900. Since 1900 people living in the aluminum age have been dosed with ever increasing levels of aluminum that negatively impact the three metabolic pathways resulting in energy deprivation. This is called hypometabolism and is a biomarker of Alzheimer’s disease (AD). The prevalence of AD has increased exponentially as has the worldwide production of aluminum in the aluminum age (shown in figure 1).

     Figure 1. Exponential growth of AD prevalence and worldwide aluminum production in the aluminum age⁴

Glycolysis, beta-oxidation, and the Krebs cycle comprise the primary biochemical pathways for energy production in living organisms on earth. Aluminum at physiological concentrations (i.e., 36 – 75mcMolar in the brains of those with AD) inhibits these pathways. causing energy deprivation and hypometabolism⁴.

Glycolysis starts with the enzyme hexokinase converting glucose to glucose-6-phosphate and ends with two pyruvic acid molecules, two ATP molecules and two NADH molecules. The concentration of aluminum required to drop an enzyme’s activity to 50% is called IC50.  Aluminum inhibits hexokinase at an IC50 of 4-9mcMolar⁵.

The link between glycolysis and the Krebs cycle is pyruvate dehydrogenase (PDH) and required cofactors thiamine pyrophosphate (a.k.a. vitamin B1) and lipoic acid. Pyruvic acid is oxidized to acetyl-CoA and a molecule of NADH. In addition, the enzyme pyruvate carboxylase (PC), with required cofactor biotin, adds carbonic acid to pyruvic acid making oxaloacetate. Beta-oxidation of fatty acids also produces acetyl-CoA in the body (see below).

This link between glycolysis and the Krebs cycle is inhibited by low levels of thiamine in the plasma of those with AD but not Parkinson’s disease⁶. Low levels of thiamine is caused by oxidation of thiamine. Aluminum generates reactive oxygen species (ROS such as hydrogen peroxide) in human neuronal glial cells⁷. Hydrogen peroxide is converted in the body to hypochlorous acid by the enzyme myeloperoxidase⁸. Hypochlorous acid oxidizes thiamine to three metabolites (shown in figure 2)⁸. Aluminum generated hydrogen peroxide causes thiamine loss by oxidation in the brains of those with MCI and AD.

Note that benfotiamine, a thiamine derivative, when taken as a supplement boosts blood and brain thiamine levels and helps to restore brain glucose metabolism. Benfotiamine at a daily dosage of 25mg or more per day is 2-3-fold more readily absorbed by the intestine than thiamine¹⁵. Benfotiamine does not remove aluminum and is not an FDA-approved medication for AD.  

Krebs cycle starts with citrate synthetase combining acetyl-CoA with oxalacetate making citric acid. The citric acid is then converted to isocitric acid with the enzyme aconitase. Aluminum inhibits aconitase at an IC50 of 25mcMolar⁹. The Krebs cycle is also fed by glutamate being converted to alpha-ketoglutarate by the enzyme glutamate dehydrogenase (GDH).  Aluminum inhibits glutamate dehydrogenase at an IC50 of 25mcMolar^9,10.  

For every molecule of glucose entering glycolysis two molecules of NADH and two molecules of pyruvate are produced. The two pyruvate molecules are oxidized to make 2 more molecules of NADH. Also, the Krebs cycle turns twice producing two ATP (or GTP) molecules, six molecules of NADH and two molecules of FADH₂. Therefore, each molecule of glucose entering glycolysis and Krebs cycles produce an NADH to FADH₂ ratio of 10/2 = 5.   

 

                             Figure 2. Oxidation of thiamine by hydrogen peroxide and myeloperoxidase⁸

Beta-oxidation requires the prior conversion of long-chain fatty acids to acylcarnitine for importation into the mitochondria by the carnitine shuttle. The enzyme carnitine palmitoyltransferase 1 (CPT1) catalyzes the rate-limiting step of transferring the acyl group of acyl-CoA to L-carnitine. A translocase shuttles the acylcarnitine from the cytosol across the inner mitochondrial membrane where it is converted back to acyl-CoA and L-carnitine. Fatty acids other than 16-carbon palmitic acid can be substrates for CPT1. The number of beta-oxidation cycles equals the number of carbons in the fatty acid divided by 2 and then subtract 1. For example, palmitic acid requires 7 cycles for complete beta-oxidation.

Each beta-oxidation cycle produces one molecule of NADH, one molecule of FADH₂ and one molecule of acetyl-CoA. Each cycle of the Krebs cycle requires one molecule of acetyl-CoA and produces one ATP (or GTP) molecule, three molecules of NADH and one molecule of FADH₂. Therefore, each cycle of the beta-oxidation and Krebs cycles produce an NADH to FADH₂ ratio of 4/2 = 2.   

Aluminum (10-100mcMolar) and hydrogen peroxide (40mcMolar) lowers L-carnitine levels by inhibiting the activity of two enzymes involved in the biosynthesis of L-carnitine: gama-butyrobetainealdehyde dehydrogenase (BADH) and butyrobetaine dioxygenase (BBDOX) and lowering expression of BBDOX¹¹.

Aluminum impairs the body’s ability to use stored fatty acids as an energy source by lowering L-carnitine levels in the blood, decreasing beta-oxidation, and causing cellular lipid accumulation. Also since fatty acids are a component of triglycerides, it is not surprising that occupational aluminum accumulation results in both low L-carnitine and high triglyceride levels in the blood¹². In women with amnestic mild cognitive impairment (aMCI) and early-AD  free-carnitine levels are significantly lower than controls¹³. In men and women with AD there are significantly decreased levels of acylcarnitine compared with controls¹³.  

Note that daily dietary carnitine intake for an omnivororus adult provides insufficient carnitine to compensate for urinary losses¹⁶. Therefore, carnitine biosynthesis does contribute to overall carnitine supply. Also, the bioavailability of carnitine supplements is low¹⁶.     

Reversing Aluminum Inhibition of Metabolic Pathways with OSA

Regularly drinking water rich in orthosilicic acid (3-4 cups a day with OSA greater than 48ppm) lowers aluminum levels in the body and restores energy production in the brain. My mother was diagnosed first with aMCI due to declining cognition/memory and then Alzheimer’s due to her accelerated brain atrophy. At age 86 she started regularly drinking OSA (Fiji water 146ppm). Within a year her cognition including memory  improved. My mother was APOE 3,4. My mother lived to 97 and did not die of end-stage AD. 

I am APOE-2,4 age 80 and have been drinking OSA rich water (Silicade 146ppm) for over a decade. I have lowered my aluminum body burden to a level considered safe by the Mayo Clinic (less than 0.48mcMoles/24hr.) as tested by periodic 24-hour urine tests provoked by regularly drinking 3-4 cups of OSA 146ppm daily. I do not have aMCI, MCI, or AD

Palliative Therapy for AD

Lieutenant Schwatka completely switched from carbohydrates to a keto diet with only “… an apparent weakness and inability to perform severe exertive, fatiguing journeys.” He performed the Schwatka imperative in 1879 before the aluminum age that began with aluminum purification from bauxite in the 1890’s. Because we now all have an aluminum body burden, it has become more difficult to completely switch, but the body will still try to adapt.

Adaptation involves reconfiguring the amount of three respiratory complexes (CI, CII, and CIII) in the mitochondrial electron transport chain (mETC) from NADH to FADH₂ dependent enzymes by using ROS to degrade CI to CIII. The NADH to FADH₂ ratio switches from 5 to 2 during the Schwatka imperative. This requires using the redox status of coenzyme CoQ10 as a metabolic sensor of ROS generated by reversed electron transport (RET) of the mETC (see figure 3)¹⁴. The Schwatka imperative does work to provide some palliative relief from AD but does result in added ROS generation due to RET and aluminum accumulation.

Figure 3. During the Schwatka imperative the mETC is optimized to better handle the different fuel using CoQ10 (Q) as a metabolic sensor and ROS generated by RET to degrade CI to CIII¹⁴.

A curative therapy for AD is available that involves lowering the body burden of aluminum to recover normal operation of glycolysis, beta-oxidation, and the Krebs cycle. This therapy does not involve a dietary change and reconfiguration of the mETC as it only requires removing aluminum by daily drinking an OSA rich mineral water.

  

References

1.    1. Schwatka, F.; The long arctic search – The narrative of Lieutenant Frederick Schwatka, U.S.A. 1878-1880; Marine Historical Association; Mystic Connecticut (1965) 

2. 2. Nansen, F.; Farthest north; Vol. 1 -2; Harper and Brothers: NY and London (1898)  

3. 3. Jackson, F.G.; A thousand days in the arctic; Harper and Brothers: NY and London (1899) 

4. 4.   Crouse, D.N.; Finding a cause and potential cures for Alzheimer’s disease; Climbing the ladder of causation; Etiological Publishing (2022) 

5. 5.     Lai, J.C., and Blass, J.P.; Inhibition of brain glycolysis by aluminum; J. Neurochem.; Feb.; 42(2):438-46 (1984) 

6. 6. Gold, M., et al.; Plasma thiamine deficiency associated with Alzheimer’s disease but not Parkinson’s disease; Metab. Brain Dis.; Mar.; 13(1):43-53 (1998) 

7. 7.  Pogue, A.I., et al.; Metal-sulfate induced generation of ROS in human brain cells; Detection using an isomeric mixture of 5- and 6-carboxy-2’,7’-dichlorofluorexcein diacetate (carboxy-DCFDA) as a cell permeant tracer; Int. J. Mol. Sci.; 13:9615-26  (2012) 

108.  Sasatsuka, H., et al.; Quantitative analysis of oxidized vitamin B1 metabolites generated by hypochlorous acid; Free Radical Biol. Med.; May; 152:197-206 (2020)  

9. 9.   Zatta, P., et al.; Effects of aluminum on activity of Krebs cycle enzymes and glutamate dehydrogenase in rat brain homogenate; Eur. J. Biochem.; 267:3049-55 (2000) 

1010.  Yang, S.-J., et al.; Inactivation of human glutamate dehydrogenase by aluminum; Cell. Mol. Life Sci.; 60:2538-46 (2003) 

1111.  Lemire, J., et al.; The disruption of L-carnitine metabolism by aluminum toxicity and oxidative stress promotes dyslipidemia in human astrocyte and hepatic cells; Toxicol. Lett.; June; 203(3):219-26 figures 6,7 and 8 (2011)  

1212.  Gaballa, I.F., et al.; Dyslipidemia and disruption of L-carnitine in aluminum exposed workers; Egyptian J. Occupat. Med.; 37(1):33-46 (2013) 

1313.  Bigio, B., et al.; Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer’s disease in two independent study cohorts; Mol. Psych.;  30:2573-83 (2025)  

1414.  Guaras, A., et al.; The CoQH2/CoQ ratio serves as a sensor of respiratory chain efficiency; Cell Reports; 15:197-209 (2016)  

1515.  Fujiwara, M., et al.; Review of the Japanese literature on beriberi and thiamine; Chapter VIII. Absorption, excretion, and fate of thiamine; Table 55; p205; Vitamin B Research Committee of Japan; Editors: Shimazono, N. and Katsura, E. (1965)  

1616.  Krims-Davis, K., et al.; Low bioavailability and high TMAO production: Novel insights into acetylcarnitine and carnitine metabolism; Mol. Nutr. Food Res.; 69:e70316 (2025)

  

Book Release: 'Discovering the Magic in Water" Available on Amazon

Discovering the Magic in Water – Dennis N. Crouse – Release date March 2026

People living in some regions of the world are healthier and live longer than people living in neighboring regions. It is a long-held belief, now known to be true, that this is due to a magical molecule in their drinking water. 

In my new book “Discovering Magic in Drinking Water that Makes Life Possible on Earth” it is shown that this same magical molecule was in the paleolithic drinking water our ancestors drank during our 2-million-year evolution. Humans evolved to use this molecule to protect themselves from a neurotoxin that is the third most abundant element in the earth’s crust, aluminum. 

My new book describes how new cultural practices adopted over the last 100-years have exposed humans to exponentially more neurotoxin than our adaptive advantage can handle. This has resulted in exponentially increasing prevalence of five human diseases that can be prevented and treated by drinking water containing the magic molecule. These diseases are: Alzheimer’s, autism, cardiovascular disease, childhood epilepsy, and male infertility. Find the local sources of this drinking water and instructions on making paleolithic drinking water in my new book. 

order book    

    

Introduction to book titled: Discovering the Magic in Water that Makes Life on Earth Possible (publication date January 2026)

 

Introduction to: 

Discovering the Magic in Water that Makes Life Possible on Earth

Preventing & Treating Mismatch Diseases: Alzheimer’s, Autism,

Arterial Hardening, Colorectal Cancer, Childhood Epilepsy,

and Male Infertility

 

 

Author:  Dr. Dennis N. Crouse, BSc Biochemistry, - Harvard College, Ph.D. Organic Chemistry - Harvard University - Chemistry Department, Post-graduate courses:  Understanding Dementia - Wicking Faculty of Health, University of Tasmania, Fundamentals of Neuroscience - Harvard.

Introduction

I became interested in human evolution in high school with my study of local artesian spring waters and the ability of some to magically support life while others were relatively sterile. The question I posed years ago as a scientific inquiry was “Is there magic in the water that makes life on earth possible and could this magic prevent and treat certain human diseases?” This book focuses on answering this question by first discussing how humans evolved to protect themselves from an environmental toxin that is a causal (i.e. etiological) factor of the following diseases:

·       Autism

·       Childhood Epilepsy

·       Alzheimer’s Disease

·       Coronary Heart Disease

·       Colorectal Cancer

·       Male Infertility 

In 2013 I read a book that changed the way I viewed these idiopathic diseases titled “The Story of The Human Body” by Daniel E. Liberman an evolutionary biologist at Harvard⁶. In his book Professor Liberman points out that over thousands of years humans have evolved protection against toxins in our environment. This protection has worked well until recently when the amount of some toxins have risen, due to dysevolutionary cultural practices, to levels that exceed our evolved protection mechanisms. This mismatch between levels of toxins versus levels of evolved protection results in the above list of idiopathic diseases called “Mismatch Diseases”.

The rising prevalence during the last 100 years of these mismatch diseases with no evolutionary advantage can’t be explained by genetic mutations. Only genetic mutations with an evolutionary advantage can upset the evolutionary equilibrium. Therefore, mismatch diseases are caused by increasing human exposure to noninfectious environmental xenobiotic toxins.

My inquiry into mismatch diseases and dysevolutionary cultural practices began when my 85-year-old mother was diagnosed with two health issues:

·       Cardiovascular disease (CVD) that required several stents

·       Cognitive impairment that was progressing to Alzheimer’s disease (AD)

As a son I wanted to help my mother by both avoiding end-stage AD and prolonging her life. I was successful in this regard as she lived to 97 without having end-stage AD. As a scientist I became interested in finding what caused these diseases in my mother. Without knowing the cause of a disease, it is almost impossible to prevent or cure the disease. My mother’s health issues made me wonder if these two diseases had a common cause.    

Arteriosclerosis (hardening of the arteries) and atherosclerosis (plaque on arterial inner walls) are associated with Alzheimer’s disease^1-3. In fact, in autopsied brains of 84% of aged subjects, morphology is seen as a characteristic of both AD and CVD⁴. Deaths from cardiovascular disease (CVD) surged 60% globally over the last 30 years. In 2023 it was reported by the World Heart Association that deaths from CVD jumped globally from 12.1million in 1990 to 20.5million in 2021 making CVD the leading cause of death⁵. This rapid growth in CVD deaths points to an environmental factor, that is exponentially increasing with time, as being a causal factor of CVD. This book presents data that shows the environmental factor aluminum is a causal factor of CVD. In 2022 I published a book titled “Finding a Cause and Potential Cures for Alzheimer’s Disease” in which aluminum is shown to be a causal factor of AD³⁵.  

CVD, and AD are mismatch diseases where increasing exposure to aluminum exceeds the body’s evolved protection mechanisms⁶. Humans have slowly evolved over millions of years to protect themselves from aluminum, the third most abundant element in the earth’s crust. This evolution resulted in unique human evolutionary advantages that are described in this book. Dysevolutionary cultural practices are those practices that impair our ability to use our evolutionary advantages. The dysevolutionary cultural practices discussed in this book are:

·       Accepting Worldwide Declining Male Fertility

·       Adding Aluminum to Drinking Water

·       Vaccinating Children with Aluminum Containing Vaccines

·       Drinking From an Aluminum Can, Cup, or Bottle

·       Cooking in Aluminum Cookware

·       Baking with an Aluminum Containing Baking Powder

·       Avoiding a Good Sweat

Treating CVD with Fiji Water is an example of a cultural evolution fueled by social media moving much quicker through a population than genetic mutations. This anecdotal information was posted on March 17^th 2025 at my wife’s (Laurie Adamson’s) Facebook group - Alzheimer’s: Late and Early Onset, APOE-4:

“We are winning too! My husband who is 75 had hypoxia issues, … out of control C-reactive protein, homocysteine, and blood pressure. My husband has the APOE4 gene and the MTHFR gene. He has never taken a statin. We decided never on that as the brain needs cholesterol.

 

We’ve been on this Journey 4 plus years. Prior to January of 2024 we used the Bredesen Protocol, along with Bredesen trained ND (Doctor of Naturopathic Medicine). We added drinking Fiji water almost a year ago in late January of 2024, because I trusted the science behind heavy metals and inflammation, and really there is no risk in trying this. 

 

His August 2024 blood work and tests of his carotid artery showed a reduction to about 9-12 percent blockage from 78 percent blockage in 2021 and 2023. For the first time in 4 years his CRP and homocysteine levels were in the normal range. His blood pressure, previously considered uncontrollable, is now in the 117/80 range.

   

His tests were performed by Lifeline screening, who we have used since 2010, and Labcorp for blood work. These were done August 29th and 30th of 2024 and are the latest results. His carotid artery is now showing mild risk down from significant risk in 2021 to 2023.

 

His vascular surgeon, Dr. Hirchfeld in Las Vegas, had been monitoring him since late 2021 when his carotid artery was just under 80 percent occluded. Also, Labcorp results in August of 2024 for C-reactive protein were 1.05mg/L. Thats down from the 3.5 to 3.9mg/L we were seeing up to and including 2023 testing. This was part of our NDs full range of tests begun in the fall of 2021 in response to my husband’s declining cognition.

 

Was lucky to find your group and your husband's book which is helping to take us the rest of the way. Drinking 1 liter of Fiji water a day was the only change we made from January of 2024 to December of 2024 and then 0.5 liter a day in 2025. Read the book. Do tests for metal detox, food sensitivity, and blood work. Knowledge of what issues can be addressed is important”.

 

Treating AD with Fiji Water is another example of how cultural evolution works. This anecdotal information was posted on October 10^th 2025 at my wife’s (Laurie Adamson’s) Facebook group - Alzheimer’s: Late and Early Onset, APOE-4:

This may be too short a time period to attribute my husband's improvements to the Fiji water. But here's what happened:

He is currently 89 and was diagnosed with Alzheimer's almost two years ago. He has had numerous neurological evaluations plus an MRI and a Pet scan. His last evaluation, he achieved a score of 19 (Mini-Mental Status Exam) .

In June of this year, he started drinking 32 ounces of Fiji water a day. Two months later, he had another neurological evaluation and his score was 25. His doctor said she had never seen this happen and that he has almost tested out of Alzheimer's. We were there to possibly start him on the infusions, but now we are taking a wait and see attitude.

His short-term memory is still not good, but it is a lot better than it was. While, he still has some problems with sundowners that's getting a lot better as well. I'm very hopeful! Oct. 2025

These two anecdotal descriptions of treating CVD and AD with Fiji Water are examples of many more reported in this book that describe reversal of the above listed human mismatch diseases with waters rich in orthosilicic acid (OSA) the magic in water. 

 Table of Contents

About the Author and Two Artesian Springs. 6

Introduction. 9

Chapter 1. Finding the Magic in Paleolithic Drinking Water 13

Chapter 2. Discovering OSA’s Magic. 17

Chapter 3. Human Evolutionary Advantages of OSA’s Magic. 24

Chapter 4. Dysevolution is Not Taking Advantage of OSA’s Magic. 35

Chapter 5. Aluminum Induced Mismatch Diseases. 53

Chapter 6. Biomarkers for Aluminum Accumulation. 55

Chapter 7. Discovering How to Make the Magic. 61

Chapter 8. Preventing and Treating the Mismatch Disease Autism.. 70

Chapter 9. Preventing and Treating Childhood Epilepsy. 88

Chapter 10. Preventing and Treating Alzheimer’s Disease. 92

Chapter 11. Preventing and Treating Cardiovascular Disease. 95

Chapter 12. Preventing and Treating Colorectal Cancer 108

Conclusion. 109

References. 110