​The Forever Healthy Foundation announces the public launch of the Risk-Benefit Analysis of Phospholipid Therapy, a structured review of the published evidence. It is the sixth publication of Forever Healthy's "Rejuvenation Now" initiative following the "Risk & Benefit Analysis Dasatinib and Quercetin as a Senolytic Therapy".

Forever Healthy's "Rejuvenation Now" initiative seeks to continuously identify potential rejuvenation therapies and systematically evaluates them on risks, benefits, and therapeutic protocols to create transparency regarding the current state of said therapies.

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Phospholipids - a powerful rejuvenation therapy?

Phospholipids are an important structural component of cell and organelle membranes and play a role in many cell signaling pathways. Membranes incur oxidative damage over time and in several disease conditions. Oral and/or i.v. supplementation of phospholipids (particularly phosphatidylcholine), is hypothesized to repair this damage by replacement of oxidized membrane phospholipids with "healthy" phospholipids, thus restoring or maintaining membrane integrity and function. 

Methods & Results

For this risk and benefit analysis, the team at Forever Healthy screened more than 3500 scientific papers and included the results of more than 400 clinical studies in its analysis.

The analysis shows that there is good evidence that Phospholipid Therapy is effective for short-medium term use in the treatment of many disease conditions. The benefits are mostly of small magnitude, and dependent on continuous supplementation as they diminished significantly when therapy was discontinued. There are almost no reported serious adverse drug effects, regardless of route of administration.

However, despite the widespread use of Phospholipid Therapy over the last 50 years, data on the benefits in healthy individuals is extremely limited.

On the other hand, the major long-term risks, though largely still hypothetical, are serious. Recent publications on high dietary intake of phosphatidylcholine and its correlation with increased all-cause mortality, increased risk of lethal prostate cancer, and increased risk of acute myocardial infarction warrant serious reflection on the safety of long-term supplementation with phosphatidylcholine-containing products. A possible explanatory mechanism for the damage caused by the consumption of high levels of choline-containing products has already been shown in a clinical study.

Based on the analysis of all currently available data, we find that short-term supplementation with phosphatidylcholine is a potential treatment option for cases of known liver disease, cognitive impairment, or in conjunction with NSAIDs.

Whether the benefits may also outweigh the risks in a generally healthy population is unknown. If one decides to supplement with phospholipids, risk mitigation measures such as measurement of TMAO and stool analysis should be performed regularly.

We recommend against the use of phosphatidylcholine supplementation in the case of known cardiovascular disease until the situation regarding the PC-related production of TMAO and its role in CVD has been further clarified.

More details, including an in-depth analysis of all risks & benefits, can be found here.

Mountain View, CA, U.S., September 08, 2021 – Underdog Pharmaceuticals, a key investment of Michael Greve's rejuvenation biotech VC Kizoo is one of the first companies to be awarded the Innovation Passport under the United Kingdom’s Innovative Licensing and Access Pathway (ILAP). This will enable faster patient access to its groundbreaking treatment for the prevention of heart attacks and stroke.

ILAP, introduced by the Medicines and Healthcare products Regulatory Agency (MHRA) in January, is designed to accelerate the development of and access to promising medicines of significant potential public health benefit. The ILAP program also provides the potential for significant downstream regulatory advantages, including rolling clinical reviews, accelerated assessment, and supervised early reimbursed use under adaptive authorization.

Accounting for up to 40% of deaths in Europe and the United States with annual treatment costs of over £29 billion in the UK alone, cardiovascular disease is by far the world’s most life-threatening condition, and its primary cause is atherosclerosis. Underdog is developing engineered cyclodextrins for the treatment of atherosclerosis by removing arterial plaque and clearing the non-degradable cholesterol that accumulates within cells in the arterial walls.
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"I believe the MHRA is sending a powerful message by reviewing and admitting preclinical stage programs like ours into ILAP," noted Mike Kope, Underdog Co-CEO "The advice and consultation we’ll receive will be invaluable to the success of the program and our long-term goal to deliver a simple and affordable preventive therapy for the world. The ILAP program will allow us to advance to a world without heart attacks and stroke a lot faster".

Berlin, Germany - Michael Greve, founder of the Forever Healthy Foundation and owner of Kizoo Technology Ventures, announced today that he will make available an additional €300 million to be invested in rejuvenation biotech.

The funds, to be deployed via Kizoo, will be used to create and support more startups in the rejuvenation space. They will also allow Kizoo to maintain a strong commitment to its key startups during follow-up rounds and to advance the therapies from clinical development to public availability.

With this €300 million commitment, Michael Greve and Kizoo double down on their mission to accelerate the advent of rejuvenation biotechnology by doing lighthouse investments in entirely new, repair-based approaches that treat the root causes of aging and thus overcome age-related diseases. Through the creation of successful companies, they seek to inspire scientists, investors, and the general public by demonstrating that human rejuvenation is not science fiction anymore and that the resulting therapies are affordable and uncomplicated.
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Technologies pioneered by Kizoo's startups include removal of arterial plaque, decalcification of aged tissue, breaking of protein-glucose cross-links, and delivery of new mitochondria to aged cells - all aiming to prevent and repair common age-related conditions such as myocardial infarction, stroke, high blood pressure, tissue stiffening, skin aging, and loss of muscle function.

"I am really grateful that we can use the funds we have created with our highly successful technology ventures to contribute to the quest to get aging under full medical control and to make age-related diseases a thing of the past. For me, it is a worthy cause that is exciting in a technological, commercial, and above all, a humanitarian way" says Michael Greve.

He expects that the new funds, in combination with the strong, multi-round commitment of Kizoo to its key startups, should trigger co-investments of up to 3-4 times the initial amount, resulting in a significant acceleration of the development and public availability of the therapies.

In our fifth Online Meetup, we talked about "Vascular Rejuvenation using EDTA" - how EDTA chelation therapy can be used to prevent and/or reverse vascular disease.

Our invited speaker this time was Dr. Lamas who is chair of medicine and chief of cardiology at Mount Sinai Medical Center and was the lead investigator of the TACT trial (Trial to Assess Chelation Therapy). He initiated this multi-center double-blinded clinical trial, which took 10 years to be completed, to evaluate the efficacy and safety of EDTA chelation for the treatment of coronary and peripheral artery disease. The results of the trial surprised the medical world, including Lamas, and led to further large-scale trials on chelation therapy.

The Meetup included Q&As and closed with a short networking session, in which participants had the chance to further discuss in separate breakout rooms. 
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Please find the recording of the event here.

The Forever Healthy Foundation proudly announces the third publication by its "Maximizing Health" initiative:

Lipid Monitoring for Cardiovascular Risk - A practical guide on lipid biomarkers and the best monitoring protocol

The "Maximizing Health" initiative reviews the latest medical knowledge and creates actionable guides to empower informed decisions about health and well-being.

Motivation

Numerous aspects of lipid metabolism have been implicated in the genesis of cardiovascular disease (CVD). Given the prevalence and mortality of CVD, it is essential to identify optimal biomarkers of lipid metabolism that may provide better risk prediction. Several lipid biomarkers have been proposed for monitoring, and several methods have been developed for measuring them. This Practical Guide aims to identify those markers, evaluate their relevance to CVD risk prediction, and determine the best lipid monitoring protocol available at the moment. 

Methods

A list of potential lipid parameters was compiled from medical and laboratory resources. A literature search was then conducted on PubMed for each parameter. Additionally, we reviewed the major clinical practice guidelines on lipid monitoring. 
Our search identified 21 lipid biomarkers ranging from those included in a standard lipid panel to those that are just entering clinical practice. For each biomarker, the main evidence for and against its use in CVD risk prediction was summarized. The available information on test types, standardization & error, reference values, factors affecting measurement, and frequency of testing for each parameter was analyzed.
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Results
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The following chart illustrates our results by comparing lipid biomarkers in terms of their association with CVD and the total error of the analytical technique used to measure them.

According to our analysis, only two of the markers are both closely associated with cardiovascular risk and have an acceptable level of error: apolipoprotein B (ApoB) and total cholesterol (TC). There are several other markers that have stronger associations with CVD risk and may present valuable information, however, the test results are less reliable, due in most cases, to a lack of standardization or a low level of accuracy.

The full analysis including a detailed lipid monitoring protocol based on the findings of our research can be found here.

In our fourth Online Meetup, we talked about "Skin rejuvenation using the power of light" - how low-level light therapy (LLLT) can lead to a significantly improved appearance of the skin by restoring youthful cellular functions. Our invited speaker this time was Dr. R Glen Calderhead, "the Godfather of Low-level light therapy" (The Guardian).

​Calderhead, who is currently based in South Korea as Executive Managing Director of the Lutronic Corporation, is a pioneer in the field of LLLT and an internationally recognized authority on all aspects of phototherapy, photo surgery, and energy-based medicine.

The Meetup included Q&As and closed with a short networking session, in which participants had the chance to further discuss in separate breakout rooms. The numerous questions of the participants as well as the great discussion about LLLT assured us, that we could help to raise awareness of what Calderhead called "The most underestimated therapy in the world."
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Please find the recording of the event here

​Several genome-wide association studies comparing genes of centenarians (people > 100 years) with genes of people reaching a "normal" lifespan found one gene that was associated with longevity: ApoE

This result is quite striking as it is immensely difficult to find common genetic variants in a population as heterogeneous as humans.

APOE is the gene responsible for coding Apolipoprotein E, a key player in our lipid metabolism. APOE comes in 3 significant variants: E2, E3 & E4. While the E2 variant of the gene was enriched in the centenarian population, E4 is associated with a shortened life expectancy. The E4 variant is also well known for its association with a significantly higher risk of Alzheimer's disease. There are several implications for ApoE4 carriers, particularly concerning saturated fat and heavy metal detox.

Around 20 - 25 % of the population in Europe/USA carries one or two copies of the E4 variant, meaning that a large number of people are actually carrying the "anti-longevity" gene, which is associated with a higher risk for several morbidities. While this sounds like overwhelming news, the saying “Genes load the gun, the environment pulls the trigger", also holds true for ApoE4.

In our newest publication, our team screened more than 800 scientific papers to create a practical guide focusing not only on the risks associated with the E4 variant but also proposing a risk management strategy for APOE4 carriers based on the latest scientific publications.

APOE4 - Risks and Risk Management

1E9 (Successor of Wired Germany) published an interview with our founder Michael Greve, separating science from fiction, discussing Michael's personal story, and his vision for Forever Healthy to enable people to vastly extend their healthy lifespan.  

Read the whole interview here (German)

Brief summary:

It all started with a quest for knowledge: In his times as internet-entrepreneur, Michael acquired some unhealthy habits and decided to drastically change his lifestyle. While there were some cowboy-style-marketed products available, he felt that the scientific evidence was lacking although the research in the field was actually flourishing. He decided to create the Forever Healthy Foundation to review the scientific knowledge in the field of rejuvenation, which is deeply buried in scientific journals, and make it accessible in a comprehensive way. Furthermore, he funds research and start-ups to accelerate access to healthy longevity for all of us.
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 "The entrepreneur in me is absolutely certain that this will be the greatest industry of all time."

We proudly announce the second publication by our "Maximizing Health" initiative: 

​APOE4 - Risks & Risk Management
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APOE is the gene responsible for coding Apolipoprotein E, a key player in our lipid metabolism. APOE comes in 3 significant variants: E2, E3 & E4.

The E4 variant is well known for its association with a significantly higher risk of Alzheimer's disease. Numerous other conditions have been linked to it including different forms of dementia, cardiovascular disease, and decreased longevity. There are several important implications for carriers of one or two copies of the E4 variant, particularly concerning saturated fat and heavy metal detox.
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To create this practical guide the team screened more than 800 scientific papers. We found that APOE4 was associated with significant negative effects in almost 20 categories including:

Forever Healthy Foundation and SENS Research Foundation have rescheduled Undoing Aging to May 13-15. We are looking forward to having Undoing Aging 2021 as a vibrant physical event in Berlin, which unfortunately is not possible in 2020 due to restrictions on events in Germany. We will issue ticket refunds to attendees who cannot attend the new date.

The Undoing Aging Conference in May will be focused on the cellular and molecular repair of age-related damage as the basis of therapies to bring aging under full medical control and will bring together scientists and startups from around the globe, all pioneers in their respective fields, who are leading the charge in maintaining and restoring full health in old age.

To accommodate the exciting growth of the emerging rejuvenation biotechnology industry, Undoing Aging 2021 will add a dedicated forum and exhibition space for rejuvenation biotech companies to present themselves to prospective investors and industry partners.
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Additionally, the 2021 conference will add a special "Rejuvenation Now" session highlighting the first generation of human rejuvenation therapies that are either currently in clinical trials or are available today.
Undoing Aging 2021 is not only open to the scientific community, but also welcomes startups, investors, the general media, and all interested members of the broader rejuvenation movement. The conference will feature a student poster session showing the work of innovative undergraduate and graduate students in the field of damage repair.

In our second Online Meetup, we talked about the role of senescence in aging, and about fisetin as promising natural senolytic therapy. This was the first time, we invited an external speaker and were delighted that we attracted Prof. Dr. João Pedro de Magalhães, an expert in the field of senescence and aging.

​We further developed the format of our Online Meetup by adding a short networking session, in which participants had the chance to further discuss in separate breakout rooms. The event grew profoundly since our first Meetup which assured us, that we created a promising platform for people worldwide to learn and discuss exciting new developments in the field of rejuvenation.

Please find the recording of the event here

To inspire more young scientists to join the quest to get aging under full medical control, we have created the Forever Healthy Fellowship Program. The fellowship covers support for a three-year project, to be carried out at the SENS Research Center in Mountain View, California. It includes the salary for the fellow, benefits, supplies, and space in a fully equipped research lab.

We are happy to announce, that the Forever Healthy Fellowship was awarded to Dr. Tesfahun Admasu. 

When cells age, they lose their proliferative capacity and stop dividing in a phenomenon called senescence. Cellular senescence decreases the regenerative capacity of cells and tissues and is thought to be driving age-associated pathologies. Throughout the aging process, senescent cells accumulate and secrete a characteristic set of proteins, called a senescence-associated secretory phenotype (SASP). Senescent cells can trigger healthy cells in their surrounding to become senescent, which further aggregate the effect. While primary senescent cells are fairly well characterized at this point, not much is known about secondary senescent cells and how they arise in vivo.

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Project Goals

The project of Dr. Tesfahun Admasu seeks to confirm the hypothesis that secondary senescent cells are different from primary senescent cells, and would, therefore, need a different senolytic to eradicate them. In addition, the project will study how SASP components mediate the spread of senescence. This work could provide us with the basis for a new, therapeutically viable hypothesis for stopping the spread and to rejuvenate the affected tissue.

The Forever Healthy Foundation announces the public launch of the Risk-Benefit Analysis of Dasatinib + Quercetin as a Senolytic Therapy, a structured review of the published evidence. It is the fifth publication of Forever Healthy's "Rejuvenation Now" initiative following the "Risk & Benefit Analysis of Vascular Rejuvenation using EDTA".

Forever Healthy's "Rejuvenation Now" initiative seeks to continuously identify potential rejuvenation therapies and systematically evaluates them on risks, benefits, and therapeutic protocols to create transparency regarding the current state of said therapies.


Dasatinib + Quercetin - a powerful rejuvenation therapy?

When a cell reaches the end of its life or becomes damaged beyond repair it normally either kills itself or signals the immune system to remove it. Unfortunately, every so often this mechanism fails. The cell stays around indefinitely and starts poisoning its environment. Over time, more and more of these harmful, death resistant, senescent cells accumulate. Senescent cells are thought to be one of the main drivers of aging and age-related diseases.

Senolytics are drugs that selectively remove senescent cells by disabling the mechanisms that allow them to survive. Dasatinib (D), a well-established medication used in the treatment of cancer and quercetin (Q), a flavonoid common in plants were among the first senolytics to be discovered. As they have been shown to affect different types of senescent cells, they are often employed in combination. 

Studies in rodents have shown that clearing senescent cells can prevent, delay, or alleviate multiple age-related diseases and extend the healthy lifespan by up to 35%. Based on the promising results in animal testing, it is supposed that intermittent dosing of D+Q also leads to the elimination of senescent cells in humans with the accompanying health and rejuvenation benefits.

As the first clinical trials in humans have been completed and interest in the practical application of D+Q is increasing, Forever Healthy seeks to assess the risks, benefits, and therapeutic protocols of using D+Q as a senolytic therapy.


Methods & Results

For this risk and benefit analysis, the team at Forever Healthy screened more than 3300 scientific papers and included over 150 clinical and pre-clinical studies in its analysis.

Currently, there are only results from 3 trials in humans in which D+Q was evaluated as a senolytic therapy. The majority of human studies used D or Q in cancer therapy and provided information on side effects and safety.
The benefits shown in animals were significant and were observed in many organ systems. However, several of the benefits only occurred in diseased animals (i.e. diabetic mice), while the healthy control group did not benefit from the treatment. 

The benefits reported in human studies are mainly focussed on senescent cell markers. So far, these markers are only hypothesized to translate to clinically meaningful effects. Few benefits had direct clinical relevance, and those were not really convincing. Additionally, 2 out of the 3 clinical studies were in patients with pre-existing disease so there is very limited information on the effect in healthy individuals.

The potential risks of D are extensive and well-known through its use in the treatment of cancer. While the clinical trials that used D+Q as a senolytic therapy reported only mild to moderate adverse events, it is of note that the low number of participants in these studies might not deliver a representative result.

Furthermore, the human studies all used different treatment protocols and there is no consensus on the measurement of efficacy in clinical practice. 

Therefore, until there are more studies showing benefits in humans, a clearer picture of the senolytic-use specific risk profile, and a consensus on a treatment protocol, it seems prudent to avoid the use of D+Q as a senolytic therapy.

More details, including an in-depth analysis of all risks & benefits, can be found here.

The Forever Healthy Foundation announces the public release of its Practical Guide to natural antivirals and immune boosters for COVID-19 today.

Antivirals with a broad spectrum of action and immunomodulators that improve host resilience are crucial to overcoming novel viral infections. As of yet, there aren't any evidence-based or clinically proven treatments or vaccines available for COVID-19.

However, numerous compounds, including natural antivirals and natural immunomodulators, have been suggested for both prevention and treatment. Unfortunately, the scientific evidence behind these recommendations is most often not provided, making the decision whether to use a certain compound virtually impossible.

In light of the current COVID-19 outbreak, we review the scientific, empirical, and clinical evidence of proposed natural compounds that could potentially help prevent infection or reduce the severity of symptoms.

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Method & Results

A search for recommendations of natural antivirals and immune-boosting compounds with possible relevance to COVID-19 was conducted using online resources of the leading integrative medical, naturopathic, and functional medicine associations. 

Evidence for or against each compound was then collected and in cases where supporting or refuting evidence was not found, consultations with experts and of association-specific supporting literature were carried out.

Finally, substances were categorized and a list of recommendations of compounds that have shown beneficial immunomodulatory actions, clinical efficacy, safety, and potentially specific effects on SARS-CoV-2 was created. 

The team identified 50 natural substances and mixtures recommended for preventing infection with SARS-CoV-2 or lessening the severity of symptoms of COVID-19. As there hasn't been enough time for the scientific community to conduct clinical trials on the effects of any of the compounds on SARS-CoV-2, we chose to recommend 8 substances with established safety that have shown strong antiviral or immunomodulatory effects in previously conducted clinical trials or clinical practice.

Please find the details including the final list of recommended compounds and doses here.