Alzheimer’s Disease: The Story of Ketones

By Mary Newport – Unbekoming Book Summary - 20 Questions & Answers

In my interview with Dr Christopher Exley, Alzheimer’s came up several times. The main points related to Alzheimer's were:

Interview with Dr Christopher Exley - Lies are Unbekoming

• Aluminium as a Primary Cause of Alzheimer's: Research spanning over 30 years led Dr. Exley to conclude that aluminium in brain tissue is the primary cause of Alzheimer’s disease. He asserts that individuals without aluminium in their brain tissue would not develop Alzheimer’s within a normal lifespan.

• Aluminium Exposure and Disease Prevention: Exley believes that Alzheimer’s is entirely preventable by minimizing aluminium exposure. He recommends reducing exposure in daily life, which includes regular consumption of silicon-rich mineral water to aid in aluminium excretion.

• Effectiveness of Silicon-Rich Water: Clinical trials indicate that drinking silicon-rich mineral water can promote aluminium excretion through urine. In a trial involving individuals with Alzheimer’s, 20% showed clinically significant cognitive improvement, a success rate that exceeds any mainstream Alzheimer’s treatment.

• Fluoride and Aluminium Absorption: Exley warns that fluoride in drinking water enhances aluminium absorption in the gut, contributing to cognitive decline and linking it to Alzheimer's disease. He advocates for reducing fluoride exposure as a precautionary measure.

• Copper vs. Aluminium in Alzheimer’s: Dr. Exley suggests that copper might be more beneficial than harmful in Alzheimer’s due to its antioxidant properties. In contrast, iron, particularly when interacting with aluminium, contributes to neuronal death in Alzheimer’s patients.

A takeaway for me from that interview was that Alzheimer’s can be both prevented and reversed.

To that end here is the Alzheimer’s Series of stacks so far:

• Alzheimer's

• Interview with Dennis N Crouse PhD

• The End of Alzheimer’s

This book by Mary Newport is the latest addition to the series. I think it’s worth reviewing books that I don’t entirely agree with, like this one, to find the babies in the bathwater. The book barely touches the subject of aluminium, and overall is very positive towards vaccines including flu vaccines for older people. It’s a mainstream book after all.

But I still think there is enough here to be useful and helpful.

Alzheimer's Disease: What If There Was a Cure (3rd Edition): The Story of Ketones: Newport, Mary T.: 9781684429240: Amazon.com: Books

Let’s start with an analogy of the primary ideas in the book.

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Analogy

Imagine a vast, bustling metropolis powered entirely by an intricate electrical grid system (the brain). This city has millions of buildings (neurons) connected by complex networks of power lines (neural pathways). The main power plant runs primarily on coal (glucose), which requires special transport trucks (insulin) to deliver it to each building's furnace.

Over time, these transport trucks begin to malfunction or disappear (insulin resistance/deficiency). Some buildings can no longer receive their coal deliveries, causing their lights to dim and their operations to slow (cognitive decline). Eventually, without fuel, entire blocks of the city go dark (brain cell death), and vital services begin to fail (loss of memory and function).

However, this city was built with a remarkable backup system: every building has a secondary power generator that can run on solar energy (ketones). While the coal delivery system is failing, these solar panels remain fully functional. The remarkable thing about these solar panels is that they don't need the special transport trucks – they can absorb and use energy directly from the sun.

When city planners (doctors/researchers) discover this alternate power source, they find that by installing more solar panels (providing ketones through diet or supplements), they can restore power to many of the dimmed buildings. While this doesn't repair the damaged coal delivery system, it bypasses the problem entirely. Some buildings that appeared abandoned spring back to life (improved cognitive function), and the city regains much of its former vitality.

Just as a solar-powered building needs consistent sunlight to maintain operations, the brain needs a steady supply of ketones to maintain its improved function. This isn't a one-time fix but rather an ongoing alternative energy solution. While it doesn't rebuild the original power infrastructure (cure the disease), it provides a crucial "workaround" that allows many parts of the city to function again, giving the metropolis precious additional time of productive operation.

This alternative power source won't work perfectly for every building, and some areas of the city may still struggle, but for many districts, it provides a vital lifeline that keeps the lights on and the city running when the primary power system fails.

Alzheimer's Disease: What If There Was a Cure (3rd Edition): The Story of Ketones

20 Questions & Answers

1. What inspired Mary Newport to write this book and what are its main objectives?

Mary Newport was compelled to write this book after discovering that ketones could potentially treat Alzheimer's disease, which led to a dramatic improvement in her husband Steve's condition. As both a physician and the wife of an Alzheimer's patient, she felt a deep responsibility to share their personal journey and the scientific breakthrough that provided them with nearly four additional years of improved quality of life together.

The book's primary objectives are twofold: to raise awareness about ketones as an alternative fuel source for the brain and to support Dr. Veech's research on ketone esters. Newport specifically aimed to draw attention to the existence of ketone esters and help secure funding for mass production and clinical trials that would expedite FDA recognition for Alzheimer's treatment.

2. What is the background story of Steve and Mary Newport?

Steve and Mary's story began in 1968 in the parking lot of Good Samaritan Hospital in Cincinnati, when Steve was eighteen and Mary was sixteen. Steve was working full-time in the hospital's housekeeping department while attending Xavier University, becoming the first person in his family to graduate college with a BSBA in accounting. His choice of accounting was influenced by a simple interaction during his high school career day, where a counselor suggested it based on his ability to count to ten.

Mary came from a middle-class family where her father worked as a machinist and roundhouse foreman for the Baltimore and Ohio Railroad. Her path to medicine began at age ten after spending a night in Good Samaritan Hospital with a broken arm, and Steve supported her dream of becoming a doctor while working to provide for their family. Her medical training, particularly her work with premature infants, would later prove crucial in her ability to understand and research treatments for Steve's condition.

3. How did Steve's Alzheimer's disease manifest and progress?

The first noticeable signs appeared when Steve was 51, manifesting as difficulty completing accounting tasks at work and struggling with routine reports that he had done for years. He began having trouble balancing the checkbook and making basic mathematical calculations, which was particularly concerning given his background in accounting. These cognitive challenges led to him leaving his job prematurely.

The symptoms gradually progressed from forgetting trivial things like misplacing items to more significant impairments. The disease progressively affected his brain cells, causing short-term memory loss, difficulty finding words, and problems with daily tasks. He would forget conversations that had just taken place, struggle to follow recipes he had previously mastered, and show increasing confusion with time and place. The most heartbreaking aspect was the eventual failure to recognize loved ones who cared for him.

4. How did ketone treatment impact Steve's condition?

After beginning coconut oil supplementation, Steve showed remarkable improvement within just 37 days. His cognitive function, memory, and ability to perform daily tasks significantly increased. He became more alert, his personality re-emerged, and he could engage in conversations and activities that had become impossible before the intervention.

The improvement continued as the treatment evolved to include MCT oil¹ and eventually ketone esters². Steve regained his ability to read and comprehend, his sense of humor returned, and he could once again perform many daily activities independently. These positive changes lasted for nearly four years, providing precious additional time with better quality of life for both Steve and his family.

5. What is the role of ketones in treating Alzheimer's disease?

Ketones serve as tiny molecules of organic fuel that have been present since the beginning of life on Earth and act as an alternative energy source when glucose metabolism is impaired, which is a key feature of Alzheimer's disease. Unlike glucose, which requires insulin to enter brain cells, ketones can freely cross the blood-brain barrier and provide energy to neurons even when insulin resistance is present, making them particularly valuable in treating Alzheimer's, which some researchers now refer to as "Type 3 diabetes."

The brain's ability to use ketones remains intact even in advanced Alzheimer's disease, with ketones capable of providing up to 60% of the brain's energy needs. The human body naturally produces ketones during fasting, starvation, vigorous exercise, or when following a high-fat, low-carbohydrate diet. Additionally, medium-chain triglycerides found in coconut oil and palm kernel oil can be converted by the liver into ketones, providing an accessible alternative fuel source for the brain.

“Type 3 diabetes” also comes up in Bredesen’s book.

The End of Alzheimer’s - Lies are Unbekoming

Question 9: What is the connection between insulin resistance and Alzheimer's disease?

Insulin resistance is so closely linked to Alzheimer's disease that some researchers have dubbed Alzheimer's "type 3 diabetes." When cells become resistant to insulin, it affects their ability to use glucose for energy. This is particularly problematic for brain cells, which have high energy demands. Insulin resistance also interferes with insulin's important role in supporting synapses and neural connections.

Furthermore, chronically high insulin levels have another detrimental effect. The enzyme that degrades insulin, insulin-degrading enzyme (IDE), also degrades amyloid-beta. When IDE is constantly occupied with breaking down excess insulin, it can't effectively clear amyloid-beta from the brain. This leads to an accumulation of amyloid and contributes to the development of Alzheimer's. Addressing insulin resistance through diet, exercise, and other interventions is therefore a crucial part of preventing and treating cognitive decline.

6. What was Dr. Richard L. Veech's contribution to Alzheimer's research?

Dr. Richard L. Veech was a pioneering researcher who spent decades studying ketone bodies and their potential therapeutic applications for various neurological conditions. He developed the ketone ester at the National Institutes of Health and chose Steve Newport as the first person with Alzheimer's to test it in a pilot study, which led to significant improvements in Steve's condition.

His groundbreaking work continues to influence current research even after his death in 2020 at age 84, including an ongoing NIH National Institute on Aging clinical trial studying the effects of ketone esters on cognition and brain metabolism in people with metabolic syndrome. His research laid the groundwork for understanding how ketones could potentially treat various neurodegenerative diseases, including Alzheimer's, Parkinson's, and other conditions.

7. How do current Alzheimer's statistics compare to other major diseases?

While deaths from stroke, heart disease, and certain cancers declined between 2000 and 2019, Alzheimer's disease deaths increased by 145 percent. As of 2021, Alzheimer's was the seventh leading cause of death in the United States.

The disease affects more than 6.5 million Americans, with one in nine older Americans diagnosed. The impact extends beyond mortality rates, as another five million people have mild cognitive impairment, with 10 to 15 percent of these cases potentially progressing to Alzheimer's. Additionally, at least 30 percent of people with Alzheimer's die of other causes, suggesting the actual number of affected individuals may be significantly underestimated.

8. What is the economic impact of Alzheimer's care in the United States?

The financial burden of Alzheimer's has reached unprecedented levels, with annual costs of $321 billion to Medicare, Medicaid, and U.S. businesses. This figure represents only direct medical and care costs, while the hidden economic impact extends much further through lost wages and premature job departures of both patients and caregivers who often must leave their jobs early.

The economic burden is further magnified by the $271.6 billion worth of unpaid caregiving provided by 11.3 million people, of whom 83 percent are family members and predominantly women. This creates a devastating ripple effect through families, forcing many caregivers to sacrifice their own financial security and careers to provide care for their loved ones, affecting entire family structures and future plans.

9. What is the projected growth of Alzheimer's cases and its implications?

By 2050, the number of Alzheimer's cases is predicted to double in the United States, with global cases expected to reach over 130 million. This dramatic increase reflects both the aging population and improved diagnosis capabilities, creating unprecedented demands on healthcare systems, caregivers, and economic resources.

The impact of this growth extends far beyond patient numbers, affecting healthcare infrastructure, family dynamics, and societal resources. This projection has led to increased urgency in finding effective treatments and preventive measures, as the current healthcare system is not equipped to handle such a dramatic increase in cases.

10. How does early-onset Alzheimer's differ from late-onset?

Early-onset Alzheimer's occurs before age 65, affecting approximately 200,000 people in the U.S. It often progresses more rapidly than late-onset cases and can be linked to specific genetic mutations that can be passed from parent to child with a 50% probability. These cases can appear as early as in a person's thirties or forties.

Late-onset Alzheimer's, which is more common, typically occurs after age 65. The risk doubles every five years past age 65, with one-third of people over 85 affected. Late-onset cases generally progress more slowly and may have multiple contributing factors beyond genetics, making treatment approaches more varied and complex.

11. What is the relationship between insulin resistance and brain function in Alzheimer's?

Insulin resistance in the brain is a fundamental feature of Alzheimer's disease, leading to the term "type 3 diabetes" coined by Dr. Suzanne de la Monte in 2005. When brain cells become insulin resistant, they struggle to utilize glucose effectively, leading to cellular malfunction and death, as insulin plays a crucial role in allowing glucose to enter cells either directly or indirectly.

This insulin resistance and compromised glucose metabolism appears years or even decades before obvious symptoms emerge, creating an energy crisis in brain cells that contributes to the progressive cognitive decline characteristic of Alzheimer's disease. This understanding has led to the exploration of alternative fuel sources, particularly ketones, which can bypass the glucose-insulin pathway and provide energy to brain cells.

Unbekoming: I’m happy to stand corrected but I’m going to call out this insulin resistance narrative, that is implied to be causal. I don’t doubt that a “feature” of Alzheimer’s is insulin resistance, and I’m sure it doesn’t help, but…

Toxins in the brain, cause chronic inflammation, that cause Alzheimer’s, and autism for that matter.

But chronic inflammation can also cause insulin resistance. When the body experiences persistent inflammation, immune cells release inflammatory cytokines—chemical messengers that can interfere with insulin signaling pathways. This interference hampers the ability of insulin to facilitate glucose uptake into cells, leading to insulin resistance.

In the context of Alzheimer's disease, chronic inflammation in the brain may exacerbate insulin resistance of neural cells. This insulin resistance impairs glucose metabolism in brain cells, contributing to the energy deficits and cognitive decline characteristic of Alzheimer's.

Talking about insulin resistance means you don’t need to talk about inflammation causing aluminium and mercury (from flu shots) in the brain.

12. What are the current treatment options and how have they evolved?

Current FDA-approved medications aim to slow the progression of the disease, typically providing about six to twelve months of delayed progression in approximately half of the patients who take them. The newest treatment, Aduhelm®, approved in 2021 after a 15-year gap in new drug approvals, is administered intravenously and costs approximately $37,000 annually, though Medicare will only cover it for patients participating in clinical trials.

Beyond traditional medications, treatment approaches have expanded to include lifestyle modifications such as dietary changes, exercise, blood pressure control, smoking cessation, and addressing sleep apnea. Alternative approaches, particularly ketogenic strategies including coconut oil, MCT oil, and ketone supplements, have gained increasing recognition for their potential in providing alternative fuel for brain cells when glucose metabolism is impaired.

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Unbekoming: Here is a better take on Aduhelm

Alzheimer's - Lies are Unbekoming

The Aduhelm story

This story highlights significant controversies and concerns surrounding the drug's development, approval, and efficacy:

Aduhelm (generic name: aducanumab) is an Alzheimer's drug developed to target and remove amyloid plaques in the brain, based on the long-standing amyloid hypothesis of Alzheimer's disease. However, its approval and use have been highly controversial:

1. Clinical trial results: The drug showed minimal effectiveness in improving cognitive function. It demonstrated some ability to reduce amyloid plaques, but its impact on patients' cognitive abilities was limited and controversial.

2. FDA approval process: Despite the drug's limited efficacy, the FDA approved Aduhelm. This decision was made against the strong recommendation of the FDA's own advisory panel, where 10 out of 11 members voted against approval.

3. Safety concerns: In clinical trials, 41% of patients experienced significant side effects, including brain swelling or bleeding. This high rate of adverse effects raised serious safety concerns.

4. Cost: The annual cost for Aduhelm treatment was set at $56,000, making it an extremely expensive option with questionable benefits.

5. Criticism: The approval and promotion of Aduhelm have been criticized as an example of the pharmaceutical industry profiting from ineffective treatments. It's seen as a continuation of a trend where drugs with minimal benefits are heavily marketed despite lack of clear evidence of efficacy.

6. Broader implications: The Aduhelm story is presented as part of a larger narrative about the potential misdirection of Alzheimer's research, the influence of pharmaceutical companies on treatment approaches, and the persistence of the amyloid hypothesis despite repeated failures in clinical trials.

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13. What is the historical significance of Auguste Deter's case?

Auguste Deter was the first documented case of Alzheimer's disease, presenting at age 51 with symptoms of impaired memory, difficulty speaking, disorientation, and psychosocial incompetence. Her case allowed Dr. Alois Alzheimer to identify and document the hallmark characteristics of the disease through autopsy, where he found nearly one-third of her cerebral cortex cells had died.

During her autopsy in 1907, Dr. Alzheimer discovered large numbers of what are now called amyloid plaques and neurofibrillary tangles, along with abnormal lipid deposits in the brain. This groundbreaking case established the foundation for understanding early-onset Alzheimer's and led to the disease being named after him, setting the stage for future research into the condition.

14. How has the medical community's view of ketone treatment evolved?

Initially, the medical establishment was skeptical of ketogenic approaches to treating Alzheimer's, with the Alzheimer's Association showing resistance to these alternative treatments. However, by 2022, the organization had begun funding ketone research, and the Alzheimer's Association International Conference included multiple sessions on ketones.

The evolution of acceptance has been marked by increased clinical trials, including an NIH National Institute on Aging study of 150 participants examining the effects of ketone esters on cognition and brain metabolism. This shift represents a growing recognition of the potential role of ketones in treating neurodegenerative diseases, supported by emerging research and clinical evidence.

15. What is Dr. Suzanne de la Monte's contribution to Alzheimer's understanding?

In 2005, Dr. de la Monte coined the term "type 3 diabetes" to describe Alzheimer's disease, marking a pivotal shift in understanding the condition's relationship to insulin resistance in the brain. This terminology helped establish a crucial connection between metabolic dysfunction and cognitive decline, opening new avenues for research and treatment approaches.

Her work highlighted how insulin deficiency and insulin resistance in the brain are prominent features of Alzheimer's disease, leading to cell malfunction and death. This understanding has fundamentally changed how researchers approach the disease, suggesting that metabolic interventions might be as important as traditional approaches targeting amyloid plaques.

16. What is the significance of the book's third edition and its message of hope?

The third edition, published in 2023, completes Steve's story and provides updated information about Alzheimer's disease and treatments, including the most current statistics and research developments. It covers recent developments such as the controversial approval of Aduhelm® in 2021 and provides comprehensive updates on the state of Alzheimer's research and treatment options.

The author challenges the common narrative that Alzheimer's "has no survivors" or that a cure is always "within five years." Instead, she advocates for immediate action through alternative approaches like ketogenic strategies, emphasizing that while these messages might promote research contributions, families need practical solutions in the present moment. She stresses that there are steps that can be taken to potentially improve outcomes, rather than waiting for a cure.

17. How has Alzheimer's research evolved over recent decades?

Despite billions spent on intense worldwide research since the early 1970s, the exact cause or causes of Alzheimer's disease remain unknown as of 2022. The research landscape has shifted from focusing primarily on amyloid plaques to considering other factors, including insulin resistance and brain metabolism, leading to more diverse treatment approaches.

Recent advances in imaging technologies have made it possible to detect subtle changes in the brain a decade or more before obvious symptoms develop, providing opportunities for early intervention. This has led to a growing emphasis on preventive measures and alternative treatment approaches, with researchers increasingly recognizing the complex, multifaceted nature of the disease.

18. What specific role did Steve play in ketone research?

Steve became the first person with Alzheimer's to test Dr. Veech's ketone ester in a pilot study at the National Institutes of Health, making his case particularly significant in demonstrating the potential effectiveness of ketone treatment. His experience became a catalyst for further research and investigation into ketone treatments for Alzheimer's disease.

His case report, co-authored with Mary Newport, was later published in Alzheimer's & Dementia, contributing to the scientific literature on alternative treatments for the disease. The nearly four years of improved quality of life that Steve experienced helped establish the potential of ketone-based interventions and inspired further research in this area.

19. What are the key mortality trends in Alzheimer's disease?

Between 2000 and 2019, while deaths from stroke, heart disease, and certain cancers declined, Alzheimer's disease deaths increased by 145 percent. By 2021, it had become the seventh leading cause of death in the United States.

The true mortality rate may be even higher, as at least 30 percent of people with Alzheimer's die of other causes, suggesting that the actual number of people affected by the disease might be significantly underestimated. This trend highlights the growing impact of Alzheimer's as a major public health concern.

20. How does the author describe the path forward for Alzheimer's treatment?

The author emphasizes a shift from solely focusing on finding a cure to implementing practical interventions that can help patients and families in the present. This includes exploring alternative approaches like ketogenic strategies, while also supporting traditional research and medical interventions that might lead to more effective treatments in the future.

The path forward involves a multi-faceted approach, combining medical treatments with lifestyle modifications and alternative therapies. The author stresses the importance of remaining hopeful while taking practical steps to improve quality of life, advocating for a balance between pursuing future cures and implementing helpful interventions that are available now.

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1. MCT oil stands for Medium-Chain Triglycerides oil. Here are some key points about it:

Composition:

• MCTs are types of fatty acids that have a chain length of 6-12 carbon atoms. The most common MCTs found in MCT oil are:

  • Caproic acid (C6)

  • Caprylic acid (C8)

  • Capric acid (C10)

  • Lauric acid (C12), although some sources debate its classification as an MCT due to its longer chain length.

Sources:

• MCT oil is typically derived from coconut oil or palm kernel oil, where these medium-chain fatty acids are naturally more abundant.

Benefits:

• Quick Energy Source: MCTs are metabolized differently than longer-chain fatty acids. They're absorbed more quickly and go directly to the liver where they can be used as an immediate source of energy or converted into ketones.

• Ketogenic Diet: MCT oil is popular among those following a ketogenic diet because it can help increase ketone levels, promoting ketosis.

• Appetite Control: Some studies suggest MCTs might help reduce hunger, thereby aiding in weight management.

• Easier Digestion: They can be easier to digest than other fats, beneficial for those with digestive issues.

Uses:

• Often used as an additive in coffee (known as "Bulletproof Coffee"), smoothies, or other foods to provide an energy boost.

• Incorporated into cooking, though it has a low smoke point, making it less suitable for high-heat cooking.

Note:

• Not all MCT oils are the same; some contain just C8 and C10, while others might include C12 or even longer chains. The effects can differ based on the composition.

2. Ketone esters are dietary supplements containing a concentrated form of ketones, specifically beta-hydroxybutyrate (BHB), which is one of the three ketone bodies produced during ketogenesis. Here's a breakdown of ketone esters:

What They Are:

• Ketone esters are created by chemically bonding BHB with an alcohol or another compound to form an ester, which can then be ingested.

• The most common ketone ester used is (R)-3-hydroxybutyl (R)-3-hydroxybutyrate.

Purpose and Use:

1. Induction of Ketosis:

   • They provide a direct source of ketones, which can increase blood ketone levels rapidly, inducing ketosis without the need for a ketogenic diet or fasting.

2. Athletic Performance:

   • Some research suggests that ketone esters might improve endurance by providing an alternative energy source for muscles, sparing glycogen stores.

3. Cognitive Enhancement:

   • Ketones are an efficient fuel for the brain, and there's interest in ketone esters for potentially enhancing cognitive function, especially under conditions of stress or energy deficit.

4. Medical Applications:

   • There's investigation into their use for conditions like epilepsy, Alzheimer's disease, Parkinson's disease, and other neurological disorders where alternative energy substrates could be beneficial.

Mechanism:

• When ingested, the ester is hydrolyzed in the gut or liver, releasing BHB into the bloodstream. This BHB can then be used as fuel by various tissues, particularly the brain and muscles.

Effects:

• Metabolic: They can lead to an increase in blood ketone levels, potentially leading to a state of ketosis where the body preferentially uses fat for fuel, sparing glucose.

• Appetite: Some users report reduced appetite, which might aid in weight management.

• Energy: Users often note a different kind of energy or focus, sometimes referred to as "mental clarity."