Benfotiamine & AD

Pat & Dennis Bender Early Dementia Diagnosis & Prognosis Fund

 

J. Dennis Bender

Office, Home & Cell Phone: 859-391-5226

5726 La Jolla Blvd. – Suite 311

La Jolla, CA 92037-7345

&

Office - 100 Riverside Pl. - Suite 303

Covington, KY 41011-5711

 

We support the development of improved diagnostic methods for the early detection and diagnosis of MCI, Alzheimer’s, vascular and other dementias, their likely prognosis, and best treatment options. We focus on the development of Bayesian-based, medical-decision-support systems, comparative-effectiveness research, and the better utilization of these for the above. (After incorporating in KY as a 501(c)3 in 2002, we dissolved that entity in favor of a simplified form of two entirely self-financed, private philanthropies utilizing a Vanguard Charitable Trust for making annual-research-grants for early-dementia-detection and its correct differential-diagnosis and likely-prognosis. They will continue on, after I am long gone, either mentally or physically, with annual grants. Scripps Foundation, Profs. Randall Bateman, James Brewer and others will be our fund’s future research grant advisors. KMK Law is our legal advisor and my estate executor is Elizabeth Dunn.

 (See: https://www.alz.org/alzheimers-dementia/research_progress/earlier-diagnosis)

 

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www.JDBender.com – EMS/eVTOL & Educational Experimental Aviation Fund (Vanguard Charitable Trust)

www.JDBender.org – Dementia Diagnosis Fund (Vanguard Charitable Trust)

 

October 2, 2024

 

 

“With the improved biomarkers that have been developed since the pilot, this next phase will provide a deeper understanding of how benfotiamine works in the brain. Novel approaches that target the many biological factors which contribute to Alzheimer’s, like metabolic-dysfunction, are essential to finding effective treatments for this disease.”

In one study, 5 people with AD took 300 milligrams (mg) of benfotiamine daily for 18-months. They all had some cognitive improvement.⁶ A small-sample-size limited that trial. Also, there was no placebo control to compare to the benfotiamine treatment. Another study of 70 patients with either mild-cognitive-impairment or mild-AD showed that 300 mg. of benfotiamine twice a day for 12-months increased thiamin-levels and improved cognitive-function, as measured by several tests.⁷ These results suggest benfotiamine may be helpful for mild-AD, but more research is needed. I’ve increased my own dosage from 100-mg. to 500-mg. daily. Here is an update on this promising on-going research as I investigate joining the trial as soon as I return to La Jolla.

Gary Gibson and The Burke Neurological Inst. at Weill Cornell Medicine in NYCity has been working on benfotiamine for 50+years and completed a pilot-study on it. Partnering with UCSD and Columbia U. Irving Medical Center they are now working on a $45-million grant for a larger study at 50 US medical centers, as well as at our local UCSD, which I am hoping to be able to join when I return to La Jolla.

 

Early symptoms of thiamine-deficiency and AD include memory-loss, irritability and sleep disorders. AD patients have adequate blood-levels but their ability to move thiamine from the blood to the brain is reduced. The theory is that if one raises the thiamine-blood-level to very-high-levels, the brain returns to somewhat normal levels. Gibson has developed a special formulation for this purpose, but one can try a 500-mg. OTC supplement, as I am now starting, until it becomes commercially available.

 

Benfotiamine is a “prodrug” of thiamine and comes with an excellent safety-profile. The study drug is taken by mouth as a capsule. A “prodrug” is an inactive compound that turns into an active form once it enters the body. Benfotiamine absorbs better than thiamine, raising thiamine in the blood. You can get the details at: www.benfoteam.org.

 

Dietary Supplements

The Link Between Benfotiamine, Thiamine, and Your Health

By Megan Nunn, PharmD - September 17, 2024 - Medically reviewed by Suzanne Fisher, RD

Top of Form

Benfotiamine is a dietary-supplement that is converted in the body to thiamine (vitamin-B1). Thiamine helps your body turn nutrients into energy and is essential for brain function.¹ Some people use benfotiamine to raise thiamine levels because it is considered highly bioavailable.² This means it reaches the bloodstream quickly and produces high levels of thiamine in the body.³

Because it has antioxidant and anti-inflammatory properties, benfotiamine may also be helpful for diabetic neuropathy (nerve pain) and Alzheimer’s-disease.³ However, more research is needed to confirm these benefits.

In the United States, the Food and Drug Administration (FDA) does not regulate supplements the way it regulates prescription drugs. That means some supplement products may not contain what the label says. When choosing a supplement, look for third-party tested products and consult a healthcare provider, registered dietitian nutritionist (RD or RDN), or pharmacist.

Benfotiamine and Thiamine: What's the Link? Benfotiamine is a dietary supplement that converts to thiamine in the body. Recommended daily levels of thiamine are 1.2 milligrams (mg) for adult males, 1.1 milligrams for adult females, and 1.4 mg during pregnancy and breastfeeding.¹

Some people may develop a thiamine deficiency when:

• Intake is lower over time than recommended levels.
• They have a specific risk factor for lower-than-normal levels.
• They are unable to digest or absorb thiamine.

Thiamine deficiency is rare in the United States, but it is more likely in older adults and people with the following conditions:⁴

• Alcohol dependence
• Human immunodeficiency virus (HIV) or AIDS
• Diabetes
• After bariatric surgery¹

Thiamine deficiency can lead to nerve, heart, and brain conditions. Initial symptoms include weight loss, memory loss, confusion, and muscle weakness. More severe forms are beriberi (characterized by peripheral neuropathy or nerve pain) and the life-threatening Wernicke-Korsakoff syndrome, which involves peripheral neuropathy and psychosis.

Benfotiamine can boost thiamine levels and help prevent these effects.

Other Health Uses Some research supports the use of benfotiamine for Alzheimer’s-disease (AD) and diabetic neuropathy as well. Here's the latest evidence supporting these claims.

Alzheimer’s-Disease AD is a degenerative brain disease. Symptoms include:⁵

• Progressive memory loss
• Poor judgment
• Misplacing things
• Getting lost
• Mood and personality changes

AD symptoms are believed to involve abnormal clumps of proteins in the brain called amyloid plaques. Those features may be linked to processes in the body that rely on thiamine. However, thiamine supplements have been found ineffective for slowing disease progression or reducing symptoms, even at high doses of 3 grams (g) per day for a year.³ It's thought this is because thiamine is poorly bioavailable or unable to be used by the body efficiently.

In one study, 5 people with AD took 300 milligrams (mg) of benfotiamine daily for 18 months. They all had some cognitive improvement.⁶ A small sample size limited this trial. Also, there was no placebo (sugar pill) control to compare to the benfotiamine treatment.

Another study of 70 patients with either mild cognitive impairment or mild AD showed that 300 mg of benfotiamine twice a day for 12 months increased thiamin levels and improved cognitive function, as measured by several tests.⁷ These results suggest benfotiamine may be helpful for mild AD, but more research is needed.

Diabetic Neuropathy Diabetes involves high blood sugar levels, which can damage blood vessels and cause diabetic neuropathy.

Symptoms of neuropathy include:⁸

• Pain or diminished sensation in the feet
• Burning or shooting pains in the lower legs
• Balance and coordination problems

Benfotiamine inhibits what are known as advanced glycation end-products (AGEs), which are markers for diabetic complications.⁹ Because thiamine deficiency is also known to cause nerve pain, in theory, supplementing with benfotiamine could alleviate some symptoms of neuropathy.¹⁰

However, clinical data is minimal. A review of six trials that studied the effect of benfotiamine on diabetic nerve pain was inconclusive.¹⁰ Overall, there was not enough evidence to support the use of benfotiamine for people with this condition.

The recent BENDIP study found neuropathy symptoms improved after taking 300 mg of benfotiamine twice a day for six weeks, but symptoms didn't improve when taken only once per day.¹¹

Natural Remedies for Type-2 Diabetes

Additional Uses In addition to the potential health benefits listed above, some people use benfotiamine to support:

• Alcohol use disorder¹²
• Diabetic kidney disease¹³

There is currently not enough evidence to recommend benfotiamine for these uses.

Recap Benfotiamine supplements help increase thiamine (vitamin B1) levels.² Thiamine is key to a healthy nervous system. Some research suggests it helps with diabetes-related nerve damage and the cognitive declines of Alzheimer's.

What Are the Side-Effects of Benfotiamine? Your provider may recommend you take benfotiamine for nerve pain or Alzheimer’s-disease, or another reason. However, consuming a supplement like benfotiamine may have potential side effects. These side effects may be common or severe.

While few side effects have been reported, extremely high doses aren't advised. Little is known about the long-term safety of benfotiamine.

A safety and tolerability study reported that the rate of adverse effects for short-term benfotiamine use in young, healthy volunteers was similar to that for placebo.¹⁴ The maximum doses studied were 1,200 mg daily for up to ten days. Side effects reported with benfotiamine included:

• Increased liver enzymes
• Increased blood pressure
• Sinus bradycardia, or slow heart rate
• Increased pulse rate
• Increased white blood cell (WBC) count
• Proteinuria

Severe Side-Effects There are no documented severe side effects of benfotiamine. However, most studies have been short-term, and safety data are limited.

Precautions The safety of supplements hasn't been established for: 

• Pregnant people
• Nursing people
• Children
• Those with specific medical conditions
• Those taking medications

Benfotiamine contains sulfur. Don't take it if you have a sulfur sensitivity.

Dosage: How Much Benfotiamine Should I Take? Always speak with a healthcare provider before taking a   to ensure that the supplement and dosage are appropriate for your individual needs.

No safe or effective dosage recommendations have been established for benfotiamine as a treatment for any condition.

Most studies in people with diabetes have used dosages of 300 mg twice a day. Other trials have used doses as high as 900 mg per day without significant problems.⁷

Benfotiamine does not appear to cause toxicity.³

If you want to try benfotiamine supplements, talk to your healthcare provider. They can advise whether it's safe for you and help determine an appropriate dosage.

Supplement Facts

• Active ingredient: S-benzoylthiamine O-monophosphate
• Alternate name: Benphothiamine, betivina, benzoylthiamine monophosphate, benfotiamina, benfotiaminum¹⁵
• Legal status: Over-the-counter (OTC) supplement in the United States
• Suggested dose: 300 milligrams twice a day⁷
• Safety considerations: Safety unknown during pregnancy, lactation, and in children

Interactions Little is known about benfotiamine's potential drug or food interactions.

Prescription medications furosemide (Lasix) and fluorouracil (Adrucil) lower the levels of thiamin in the body, so those medicines might also make benfotiamine less effective.¹

Similar Supplements Commonly used supplements for thiamin deficiency include:

• Thiamine mononitrate
• Thiamine hydrochloride
• Combination B-vitamin products¹

National Institutes of Health Office of Dietary Supplements. Thiamin.

Other supplements that may benefit patients with diabetic neuropathy include:

• Alpha-lipoic acid¹¹
• Capsaicin¹⁶
• Ginger¹⁷
• Raspberry¹⁸

Supplements of interest in Alzheimer’s-disease include:

• Turmeric¹⁹
• Omega-3 fatty acids²⁰
• Vitamin B12²¹
• Vitamin E²²
• Ginkgo biloba²³
• Creatine²⁴

Sources of Benfotiamine and What to Look For Several sources of benfotiamine are available, including foods and dietary supplements.

Food Sources of Benfotiamine Benfotiamine is found in roasted garlic and other herbs from the Allium family, such as chives, shallots, and leeks.²⁵

Benfotiamine Supplements Benfotiamine supplements are widely available online and in stores specializing in supplements. They may be purchased in capsule or powder form.

When choosing one, review the Supplement Facts label. It will tell you how much of the active ingredient it contains and list any fillers, binders, or flavorings.

Summary Benfotiamine is a supplement that can increase the level of the essential vitamin, thiamine, in the body. It may help with diabetic neuropathy and Alzheimer’s-disease. More research is needed, though.

Side-effects are possible, but they've been rare in studies. Official dosages aren't yet established. Check with your healthcare provider before taking benfotiamine.

25 Sources

By Megan Nunn, PharmD
Nunn is a community pharmacist in Tennessee with 12 years of experience in medication counseling and immunization.

Burke Neurological Institute Receives a $45-Million NIH Grant to Study a Vitamin-B1 Precursor for Treatment of Alzheimer’s-Disease in Multi-center Clinical Trial

July 7, 2022 - White Plains, N.Y. (Business Wire)

The Burke Neurological Institute (BNI) has received a 5-year award expected to total $45-million from the National Institutes of Health (NIH) to launch a large-scale, multi-center clinical-trial to evaluate benfotiamine, a synthetic-precursor of thiamine (vitamin-B1), as a potentially effective therapy for mild-Alzheimer’s-disease (AD) or mild-cognitive-impairment (MCI). This follow-up-trial will expand on previous work completed at BNI, suggesting that high levels of benfotiamine significantly slowed the rate of functional decline in participants with mild-cognitive-impairment or early-AD.

“With the improved biomarkers that have been developed since the pilot, this next phase will provide a deeper understanding of how benfotiamine works in the brain. Novel approaches that target the many biological factors which contribute to Alzheimer’s, like metabolic dysfunction, are essential to finding effective treatments for this disease.”

“It is gratifying to see research which the Alzheimer’s Drug Discovery Foundation initially identified as promising and supported in a pilot study continue to be pushed forward with funding from the NIH’s National Institute on Aging,” said Dr. Howard Fillit, Co-Founder and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF). “With the improved biomarkers that have been developed since the pilot, this next phase will provide a deeper understanding of how benfotiamine works in the brain. Novel approaches that target the many biological factors which contribute to Alzheimer’s, like metabolic dysfunction, are essential to finding effective treatments for this disease.”

Dysfunction in the brain’s ability to metabolize glucose is a known marker of AD and other dementias and can begin decades before a person has clinical symptoms or memory loss. Previous work by Burke Neurological Institute/Weill Cornell Medicine researcher Dr. Gary E. Gibson, who will also be a leader of the upcoming clinical trial, suggested that reduction in glucose metabolism is due to a decline in thiamine-dependent processes. Using multiple experimental models, he and others have shown that increasing thiamine to very high levels via benfotiamine was protective against Alzheimer’s-like symptoms. Dr. Gibson noted, “I am particularly excited about this trial because it will determine how relevant these decades of research are to the treatment of Alzheimer’s disease. If our hypothesis is correct, we will advance an exciting investigative clinical treatment pathway relevant for millions of patients, and with potential advantages in safety and value.”

These foundational experiments led to a recent pilot study, published in the Journal of Alzheimer’s Disease in 2020 and carried out by Dr. Gibson along with research partners at Weill Cornell Medicine, Burke Rehabilitation Institute, and Columbia University Irving Medical Center. The study suggested a slowed rate of cognitive decline in 35 participants with mild-MCI or early-AD who took 300-mg benfotiamine pills twice daily, and the treatment was completely safe.

The larger upcoming clinical trial will be carried out in collaboration with leading researchers in AD and related dementias; Dr. Howard Feldman, Director of the Alzheimer’s Disease Cooperative Study (ADCS) at the University of California, San Diego and Dr. Jose Luchsinger, investigator at Columbia University Irving Medical Center. “We are excited to receive this funding which will enable the further testing of benfotiamine through to its clinical proof of concept, including adaptively testing for the optimal dose and treatment response across clinical and biomarker measures,” said Dr Feldman. Dr. Luchsinger stated “I have been conducting research to understand the metabolic contributions to AD for 20 years and believes that understanding the role of thiamine in AD is an important step in this field.”

Enrolling roughly 400 patients in up to 50 US-based clinical-trial-sites, with study coordination by the ADCS, will support the new study to be among the first to select patients and follow progression over 18-months, using several measures, including cognitive-tests and blood-markers that signal AD and MCI status and progression. The trial will provide a larger and more-robust evaluation of benfotiamine’s potential use in treating AD by following cognitive measures as well as a number of blood-markers that reflect the brain’s glucose-use, neuron-loss, inflammation, and even aspects of brain-pathology. These promising blood-markers to track AD-progression have themselves been under investigation for many years and represent the cumulative work of researchers across the globe.

Additional academic institutions partnering with BNI to support this trial include the University of Gothenberg (Gothenberg, Sweden), the University of Cambridge (Cambridge, United Kingdom) and Georgetown University (Washington, DC). BNI is also pleased to collaborate with C₂N Diagnostics (St. Louis, MO), a company focused on advanced brain-health diagnostics.

There is enormous unmet need regarding both treatment and prevention of AD in the growing and aging population. More than 6-million Americans are living with AD, which is forecasted to rise to nearly 13 million by 2050. Globally, the prevalence of AD is projected to rise from 57 million to 153 million in 2050. There is no true cure for the disease and no effective treatments exist. Clinical trials over the last decade have frequently failed, and the most recently approved therapy has been met with controversy regarding efficacy, safety, value and pricing. Treatments for AD and MCI that are effective, safe, and affordable are critically needed across the globe.

Enrollment of trial participants is expected to begin in the first quarter of 2023.

The Phase-II randomized-controlled-trial of benfotiamine in early-Alzheimer's-Disease is funded by NIH grant R01AG076634.

The content of this press-release is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About Alzheimer’s Disease Cooperative Study: The Alzheimer’s Disease Cooperative Study (ADCS) is an academic research organization located at UC San Diego which is dedicated to developing treatments for those at risk or affected by Alzheimer’s-disease. For upwards of 30-years, with funding including the National Institute on Aging, it has been a field leader in progressing potential new treatments through innovation in clinical trials with design, methods, and analytics. It has a trials coordinating center in San Diego and a network of participating sites across the United States.

About Alzheimer’s Drug Discovery Foundation Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer's Drug Discovery Foundation (ADDF) is dedicated to rapidly accelerating the discovery of drugs to prevent, treat and cure Alzheimer's disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer's, employing a venture philanthropy model to support research in academia and the biotech industry. Through the generosity of its donors, the ADDF has awarded more than $209 million to fund over 690 Alzheimer's drug discovery programs, biomarker programs and clinical trials in 19 countries. To learn more, please visit: http://www.alzdiscovery.org/.

About Burke Neurological Institute The Burke Neurological Institute is based in White Plains, NY, and was established in 1978 by Dr. Fletcher McDowell as a research institute dedicated to finding cures for chronic neurological disabilities. The Institute transforms groundbreaking research into clinical treatments so that people can see, talk, and walk again. Their goal is to combine the most rigorous, contemporary brain science with heartfelt compassionate care to innovate and develop novel cures for stable disability in those afflicted with neurological conditions such as stroke, traumatic brain injury or spinal cord injury. Burke Neurological Institute is an academic affiliate of Weill Cornell Medicine.

Contacts

David Gould, M.D., Chief Operating Officer
Phone: 914.368.3172
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Website: burke.weill.cornell.edu

Gary E. Gibson, Ph.D.
Phone: 914.597.2291
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Website: burke.weill.cornell.edu

 

10/2/2024 10:03 PM

 

{Benfotiamine & AD}