COVID-19 Treatment Strategies: Dec 2025 update

Image:  Computer Simulation of SARS-CoV-2. Reprinted with kind permission of Janet Iwasa of http://animationlab.utah.edu/cova Should I Get a COVID-19 Vaccine in December 2025 or January 2026? As we move through the winter of 2025-2026, the question of whether to get a COVID-19 vaccine is highly relevant, especially as respiratory viruses typically peak during this time. The […]

Moving Simulation of SARS-CoV-2 Delta Variant Moving Simulation of SARS-CoV-2 Delta Variant

The State of Cancer Research

And we already know how small a role the cancer gene plays in the onset of cancer: there has been an 8-fold to 17-fold increase in the incidence of cancer in the last hundred years, but not even one-millionth of 1 percent of that increase can be related to genes.

Genes evolve over hundreds of thousands (if not millions) of years, which means that the so-called cancer gene has had no impact on the huge increase we’ve seen since 1900. Virtually 90 percent of the cancer that we see today cannot possibly have anything to do with genes.

Clinical Evaluation Report (CER) Medical Writer

Perform Clinical Evaluations and write/update Clinical Evaluation Reports (CERs) and Clinical Evaluation Plans (CEPs)  in compliance with the European Union (EU) Medical Device Regulation (MDR).  Perform Literature Reviews using PubMed, Embase, Cochrane Library, and similar databases. Interpret the current, new, and changing requirements for clinical research—including heightened restrictions on product equivalency—to ensure the proper clinical […]

Combining Research, Safety, and Epidemiology

Risk Management Consulting (RMC), a health services research firm, offers Research, Safety, and Epidemiology services with experience in the healthcare consulting and biopharmaceutical industries. RMC provides the health care system, biopharmaceutical industry, academia, and the Federal Government with “real-world” data to improve the quality, safety, and affordability of healthcare. RMC’s projects range from retrospective to […]

CMS Shared Savings Program

Background The Affordable Care Act (ACA) included provisions to expand value-based purchasing; broaden quality reporting; improve the level of performance feedback available to providers; and create incentives to enhance quality, improve beneficiary outcomes, and increase the value of care. Confidential physician feedback reporting was initially implemented under Section 131 of the Medicare Improvements for Patients […]

Beyond the Nomogram: Achieving Pharmacokinetic Targets to Combat Superbugs

Posted by Michael A. S. Guth on December 13th, 2025

Antimicrobial resistance (AMR) is perhaps the most pressing global health crisis of our time. The pipeline for new antibiotics is slow, meaning that our most powerful tool in the fight against “superbugs” is optimizing the use of the drugs we already possess. The traditional approach to antibiotic dosing—relying on standard, one-size-fits-all nomograms—is increasingly inadequate because the clinical environment is highly variable. Critically ill patients, those with obesity, or individuals with impaired organ function handle medications vastly differently. This variability leads to two dangerous outcomes: underdosing, which encourages resistance development and treatment failure; and overdosing, which causes unnecessary toxicity. This is where Model-Informed Precision Dosing (MIPD) emerges as a critical, life-saving strategy.

The core principle behind MIPD is moving from a simple dosage (e.g., 1g every 12 hours) to an individualized Pharmacokinetic/Pharmacodynamic (PK/PD) target. For most antibiotics, the key to success is ensuring the patient’s drug exposure stays above a certain threshold relative to the bacteria’s susceptibility. For concentration-dependent killers like aminoglycosides, this might be achieving a high peak concentration (Cmax). But for time-dependent drugs like vancomycin and beta-lactams, the goal is often the Area Under the Curve to Minimum Inhibitory Concentration ratio (AUC24/MIC). This ratio represents the total drug exposure over 24 hours relative to the concentration required to stop bacterial growth. Achieving this precise target requires more than a standard dose—it demands a predictive model.

MIPD makes this personalized dosing possible by integrating advanced population PK models with real-time patient data. A population PK model is a mathematical framework built from thousands of patient experiences that describes how a drug is typically absorbed, distributed, metabolized, and excreted (ADME). This model accounts for common patient covariates that significantly alter drug handling, such as age, body weight, renal clearance (measured by creatinine), and disease state (e.g., sepsis). When a clinician inputs a patient’s demographics and a recent drug concentration (via Therapeutic Drug Monitoring, or TDM), the population model uses Bayesian forecasting to calculate that specific patient’s unique PK parameters.

This ability to rapidly calculate individualized PK parameters is transformative, especially in the Critical Care setting. In sepsis or burn patients, rapid fluid shifts, high fever, and inflammation can lead to augmented renal clearance—a condition where the kidneys remove antibiotics far faster than normal. Standard dosing in these patients inevitably leads to sub-therapeutic concentrations and potential treatment failure. Conversely, in elderly patients with acute kidney injury, the standard dose could quickly become toxic. MIPD allows the care team to see this real-time risk, quickly adjust the dose or frequency, and predict the next concentration to ensure the patient is on track to hit the $AUC_{24}/MIC$ target within the first 24 hours of therapy—a crucial predictor of clinical success.

The shift toward MIPD also represents a technological leap in how we use TDM. Traditional TDM required calculating a new dose using manual, often inaccurate, equations or simplified nomograms after a drug level returned. Modern MIPD is executed through sophisticated, commercially available software programs that run the Bayesian forecasting model almost instantaneously. This integration of pharmacometrics into the clinical workflow transforms TDM from a reactive check into a proactive dose-optimization tool. By reducing the time to achieve the optimal PK/PD target, MIPD not only improves individual patient outcomes but also applies selective pressure to the bacterial population, helping to slow the emergence and spread of antimicrobial resistance.

In summary, Model-Informed Precision Dosing is the necessary future of antimicrobial stewardship. It replaces generic guesswork with personalized mathematics, using powerful PK/PD models to ensure every patient receives the exact drug exposure needed to sterilize the infection. For challenging drugs like vancomycin, aminoglycosides, and beta-lactams, MIPD is not just an optimization—it is a mandatory standard of care that preserves the efficacy of our existing antibiotic arsenal. Clinicians must advocate for the implementation of these tools to ensure we stay ahead in the perpetual race against the evolution of superbugs.

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COVID-19 Treatment Strategies: Dec 2025 update

Posted by Michael A. S. Guth on December 13th, 2025
Moving Simulation of SARS-CoV-2 Delta Variant

Image:  Computer Simulation of SARS-CoV-2. Reprinted with kind permission of Janet Iwasa of http://animationlab.utah.edu/cova

Should I Get a COVID-19 Vaccine in December 2025 or January 2026?

As we move through the winter of 2025-2026, the question of whether to get a COVID-19 vaccine is highly relevant, especially as respiratory viruses typically peak during this time. The short answer, based on the latest health authority guidance, is that the updated 2025-2026 vaccine is widely recommended and remains your best defense against severe illness, hospitalization, and death from the virus. Since the peak of the respiratory season—when local COVID-19 transmission levels are highest—often spans December through February, getting the updated vaccine now, if you haven’t already, offers critical, timely protection.

Unlike the initial vaccine rollout, current guidance emphasizes individual-based decision-making for most people aged 6 months to 64 years. This means the decision should be a discussion between you and your healthcare provider, taking into account your personal risk factors. That said, the consensus among experts is clear: protection from previous vaccination and natural infection diminishes over time. The 2025-2026 vaccines are specifically updated to target the currently circulating JN.1-lineage of the Omicron variant, providing better immune matching and more robust protection against the strains most likely to cause illness this winter.

For several key groups, the recommendation to get the 2025-2026 vaccine is particularly strong. This includes adults aged 65 and older, as well as people of any age who have underlying health conditions that increase their risk for severe COVID-19 (such as chronic lung disease, heart disease, diabetes, or a weakened immune system). Individuals who are pregnant or those who have never received a COVID-19 vaccine also fall into this high-priority category. If you are in one of these groups, and you have not received the updated vaccine, December or January is an excellent time to get it to maximize protection during the high-risk winter months.

A common question is what to do if you recently had COVID-19. Health experts generally advise that you may delay getting a vaccine for about three months after your symptoms started or after testing positive without symptoms. This delay allows you to benefit from the temporary immunity boost provided by the infection while ensuring the vaccine dose is given when it can provide the most durable, long-term protection. If you have any concerns about timing, especially if you also plan to get the flu or RSV vaccine, consult your doctor or pharmacist.

Ultimately, whether you get your vaccine in December 2025 or January 2026, the important takeaway is to ensure you receive the 2025-2026 updated formulation. It is designed to offer the best possible shield against the latest viral threats this season. By getting vaccinated, you protect not only your own health but also the health of vulnerable people in your community.

To get the best advice for your personal situation, please consult your primary care physician or a licensed pharmacist.

Update September 2024

COVID-19 Treatment Strategies

  • As of 2023, a few small-molecule antiviral drugs (nirmatrelvir-ritonavir, remdesivir, and molnupiravir) and 11 monoclonal antibodies have been marketed for the treatment of COVID-19, mostly requiring administration within 10 days of symptom onset.
  • Hospitalized patients with severe or critical COVID-19 may benefit from treatment with previously approved immunomodulatory drugs, including glucocorticoids such as dexamethasone, cytokine antagonists such as Genentech’s tocilizumab, and Janus kinase inhibitors such as Lilly’s baricitinib.
  • Repurposing RNA polymerase nucleotide drugs, such as Gilead’s remdesivir and Merck’s molnupiravir, to inhibit viral RNA synthesis should have a relatively high probability of success, but it remains a trial-and-error endeavour to identify nucleotide/nucleoside analogs that escape the SARS-CoV-2 proofreading mechanism.
  • Repurposing DNA polymerase inhibitors, such as Gilead’s tenofovir, to inhibit the RNA synthesis of SARS-CoV-2 is likely to fail due to their different mechanisms of action.
  • HIV protease inhibitors, such as lopinavir, should not be repurposed for SARS-CoV-2 treatment due to the lack of similarity between the drug-binding pockets in HIV and SARS-CoV-2 proteases.
  • Except for nucleoside/nucleotide inhibitors such as tenofovir, ribavirin, and lamivudine, other virus-targeted inhibitors have not been approved by the FDA to treat more than one infectious disease. They are not good repurposing candidates because their chemical structures are often designed to target a particular drug-binding pocket with high selectivity, and thus they are unlikely to have a similar level of potency against an unrelated target.
  • Cationic amphiphilic drugs (such as hydroxychloroquine, azithromycin, and amiodarone) that induce phospholipidosis should not be repurposed, because cellular phospholipidosis is often misinterpreted as antiviral efficacy.
  • A new one-step immunoassays has been developed for rapid and sensitive detection of SARS-CoV-2 by using a single-chain variable fragment (scFv) fused to alkaline phosphatase (AP) or NanoLuc (NLuc) luciferase. First, a high-affinity scFv antibody specific to the SARS-CoV-2 nucleocapsid (N) protein was screened from hybridoma cells-derived and phage-displayed library. Next, prokaryotic expression of the scFv-AP and scFv-NLuc fusion proteins were induced, leading to excellent antibody binding properties and enzyme catalytic activities.
  • Upregulation of interleukin-6 (IL-6) has been associated with worse prognosis in COVID-19 patients. Janssen conducted a phase 2 randomized control trial to evaluate the efficacy and safety of free IL-6 sequestration by the monoclonal antibody sirukumab in severe and critical COVID-19 patients. In critical COVID-19 patients who received sirukumab, there was no statistically significant difference in time to sustained clinical improvement versus placebo despite objective sequestration of circulating IL-6, questioning IL-6 as a key therapeutic target in COVID-19.

From Dec. 1, 2021

The CDC confirmed today the first case of the Omicron variant, which is officially known as B1.1.529,  in the United States.  The most concerning aspect of this new variant is the number of mutations associated with it.  Viruses are not living organisms; they require a host to continue or survive. The more hosts that viruses can find, the more likely they are to mutate further and potentially become more harmful to the hosts. Viruses cannot replicate on their own.  Instead they capture or “hijack” the reproductive mechanism in the host cell, redirect it to copy the genetic code of the virus, and seal it in a packet called a capsid. In a single human being, there can be a billion or even a trillion copies of the SARS-CoV-2 virus. Most of the time, these mutations or mistakes involve different amino acid sequences that may give rise to different proteins but do not enhance the ability of the virus to infect or replicate any better than the original copy. Occasionally, a mutation will increase infectivity and may, or may not, code for a new protein that the immune system fails to recognize.

The spike protein on SARS-CoV-2 interacts specifically with the ACE2 receptor, which is found on the surface of our cells mainly in the GI tract, the respiratory tract, and our vasculature. When the new  viral particles are created, they may have slightly different proteins either inside or outside the viral particle.  Of particular interest, the mutation may exist on the outer tip of the spike protein, which is called the receptor binding domain (RBD).  Our immune system recognizes the SARS-CoV-2 based on the RBD. Thus any mutation that changes the proteins in areas that make it easier for the virus to bind to our cells’ receptors or evade detection by the immune system will be advantageous to virus survival.

Let’s compare Omicron to two prior variants:  Alpha and Delta.  As to the virus particle itself, Alpha had 23 mutations, Delta had 17 mutations, and Omicron has 50 mutations.  As to the spike protein, Alpha had 9 mutations, Delta had 7 mutations, and Omicron has 32 mutations. As to the RBD, Alpha had 1 mutation, Delta had 2 mutations, and Omicron has 10 mutations.  The number and variety of mutations associated with the Omicron variant deserves serious concern.

Variants

 Alpha Delta Omicron

Virus

 23 mutations 17 mutations 50 mutations
Spike 9 mutations 7 mutations

32 mutations
RBD 1 mutation 2 mutations

10 mutations

Scientists are now focused on three questions: (1) what is the transmissibility of the Omicron variant?, (2) how well does it evade our current COVID-19 vaccines?, and (3) is there a change in the virulence (the variant is more deadly)?

 

From July 24, 2021

  • The Delta variant (B.1.617.2) has proven to be more contagious than the original SARS-CoV-2 (R0 = 3.5–4.5 vs R0 ~ 2.5) perhaps through better binding or better evasion of the immune system. (The spike protein of SARS-CoV-2 is coated with sugar molecules, or glycans, that help it evade the immune system.) The REACT-1 round 12 report (Imperial College London) found the Delta variant prevalence in those aged 5–49 was 2.5 times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at 0.08% (0.06%, 0.11%). While people over age 50 may have higher vaccination rates, the Delta variant may pose a higher risk of infection for younger-aged individuals. As to hospitalization, The Lancet published correspondence (June 26, 2021) on a study in Scotland that the Delta variant had a 1.85 times higher risk of getting the person infected admitted to the hospital with severe COVID-19 [hazard ratio 1.85 (95% CI 1.39–2.47)].  The Scottish study used Reverse Transcription Polymerase Chain Reaction (RT-PCR) tests and a Cox regression analysis, which adjusts for age, sex, economic status/deprivation, temporal trend, and comorbidities.
  • As of July 2021, the Pfizer-BioNTech vaccine was shown to be effective against the Delta variant symptomatic infection at 88% (UK study), 87% (Canadian study), 64% (Israeli study), 79% (Scottish study), and effective against the Delta variant resulting in hospitalization at 96% (UK study) and 98% (Israeli study). The data for the Moderna vaccine are more limited and show the vaccine is 72% effective against symptomatic infection and 96% effective against hospitalization for the Delta variant after just the first dose of the two-dose vaccine. The Oxford-Astrazeneca vaccine was found to be effective against the Delta variant at 60% (UK study), 67% (Canadian study for single dose), 60% (Scottish study) for symptomatic infection and 93% (UK study), 88% (Canadian study) effective against Delta variant hospitalization. For the J&J vaccine, real-world evidence on effectiveness against the Delta variant is not yet available; however, J&J’s internal lab study showed it was highly effective against the South African variant, which was most prevalent at the time, and that the antibody response to the Delta variant is even better: a very good antibody response to the Delta variant based on lab testing.

From May 27, 2021

For early-onset COVID-19 cases (positive COVID-19 test and at-risk for progression of the disease but not experiencing symptoms requiring hospital-ization): “The FDA has halted the distribution of Lilly’s combination of bamlanivimab and etesevimab in Arizona, California, Florida, Indiana, Oregon and Washington––all states where coronavirus variants from Brazil and South Africa account for more than 10% of those with the disease. The antibody combo had previously been paused in Illinois and Massachusetts.

Providers in those states should use Regeneron’s antibody treatment of casirivimab and imdevimab, as per the FDA. Lab studies have shown that option is more effective against the Brazilian (P.1) and South African (B.1.351) strains, according to the agency.” [https://www.fiercepharma.com/pharma/fda-halts-use-lilly-covid-19-antibody-treatment-6-states-where-variants-are-prevalent]

Timing is important: MABS are very good at stopping the virus outside the cells. Once the SARS-CoV-2 has infected the cells, antibodies are not able to neutralize the virus. The patient then needs cytotoxic T-cells.

Two randomized clinical trials of Vitamin D, one from India (SHADE study) and one from Spain (calcifediol study), have shown that Vitamin D supplementation definitely benefitted patients with COVID-19. Emerging evidence shows Vitamin D combined with either or both Vitamin K2 and Magnesium potentiates the benefits of Vitamin D. Source for K2 synergy: https://pubmed.ncbi.nlm.nih.gov/29138634/

QUERCETIN in combination with vitamins C and D, may exert a synergistic antiviral action. Source: https://journals.sagepub.com/doi/full/10.1177/1934578X20976293

N-ACETYL-CYSTEINE (NAC) (600 mg) has known antiviral and liver protective properties. One argument for use with COVID-19 is https://pubmed.ncbi.nlm.nih.gov/32780893/ and another https://pubmed.ncbi.nlm.nih.gov/24968347/ and https://pubmed.ncbi.nlm.nih.gov/9230243/

SLEEP (7 – 9 hours): antibody and immune response after (flu) vaccination is improved if the patient has had a good night’s sleep, particularly the hours of sleep before midnight (slow wave sleep). Optimal T-cell production for disease prevention also requires optimal sleep. Melatonin may help patients get to sleep and has anti-viral properties. https://pubmed.ncbi.nlm.nih.gov/32347747/ https://pubmed.ncbi.nlm.nih.gov/32768490/

At the early stages of COVID-19 infection, the innate immune system is responsible for attacking the virus (primarily using monocytes & natural killer cells) through production of Interferon (IFN). SARS-CoV-2 delays the body’s IFN response. Patients with severe disease had less type I IFN activity in their blood compared to patients with mild to moderate disease. (The innate immune system diminishes with aging.) Any method to enhance the innate immune response in the early course of the disease could limit progression of COVID-19. Sauna baths, hot water baths, and other sources of human hyperthermia can induce a tenfold increase IFN-gamma synthesis. https://pubmed.ncbi.nlm.nih.gov/3132509/ These results suggest that raising the core body temperature akin to a mild fever may stimulate the innate immune system (particularly if followed by a cold shower or rapid cooling) and thereby attenuate COVID-19.

From APRIL 2020

“To be clear, SARS-CoV-2 is not the flu. It causes a disease with different symptoms, spreads and kills more readily, and belongs to a completely different family of viruses. This family, the coronaviruses, includes just six other members that infect humans. Four of them—OC43, HKU1, NL63, and 229E—have been gently annoying humans for more than a century, causing a third of common colds. The other two—MERS and SARS (or “SARS-classic,” as some virologists have started calling it)—both cause far more severe disease. Why was this seventh coronavirus the one to go pandemic? Suddenly, what we do know about coronaviruses becomes a matter of international concern.” Why the Coronavirus Has Been So Successful, The Atlantic

This article was inspired by the work of Jon Barron shown here: https://www.jonbarron.org/colds-flus-infectious-diseases/using-anti-pathogens. To combat the coronavirus, I have stocked my medicine cabinet with the following anti-viral pathogen natural products. In addition to providing the names and doses of the products, after each one, I provide the ten most recent citations from PubMed.gov pertaining to that substance and viruses.

  1. AHCC (Active Hexose-Correlated Compound) – 500 mg, taken on an empty stomach up to four capsules per day at outset of symptoms
  2. Olive Leaf Extract (Olea europaea) (standardized to minimum 20% oleuropein) – 500 mg, taken with food once or twice per day.
  3. Oil of Oregano (Origanum vulgare) (leaf) (10:1 extract) – 150 mg, taken up to four gelcaps per day with water
  4. Star Anise Oil – 1 fluid oz, blended and diluted with extra virgin olive oil or extra virgin coconut oil
  5. Minced Garlic — 1 tbsp added to main meal

 

AHCC (Active Hexose-Correlated Compound)

“Mushrooms have been used for various health conditions for many years by traditional medicines practiced in different regions of the world although the exact effects of mushroom extracts on the immune system are not fully understood. AHCC® is a standardized extract of cultured shiitake or Lentinula edodes mycelia (ECLM) which contains a mixture of nutrients including oligosaccharides, amino acids, and minerals obtained through liquid culture. AHCC® is reported to modulate the numbers and functions of immune cells including natural killer (NK) and T cells which play important roles in host defense, suggesting the possible implication of its supplementation in defending the host against infections and malignancies via modulating the immune system. Here, we review in vivo and in vitro effects of AHCC® on NK and T cells of humans and animals in health and disease, providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC®.” Shin MS, Park HJ, Maeda T, Nishioka H, Fujii H, Kang I. The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies. J Immunol Res. 2019;2019:3758576. Published 2019 Dec 20. doi:10.1155/2019/3758576 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942843/

Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus.

Di Pierro F, et al. Minerva Gastroenterol Dietol 2020. PMID 32162896
The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an α-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.

The prognostic factors between different viral etiologies among advanced hepatocellular carcinoma patients receiving sorafenib treatment.

Yeh ML, et al. Kaohsiung J Med Sci 2019. PMID 31254328 Free article.
Pre-treatment clinical data and viral hepatitis markers were collected and analyzed with their outcomes. The primary endpoint of the study was overall survival. …There were different prognostic factors stratified by viral etiologies in aHCC patients receiving sorafenib. Viral eradication increased survival in chronic hepatitis C patients….
Reduction of adverse effects by a mushroom product, active hexose correlated compound (AHCC) in patients with advanced cancer during chemotherapy–the significance of the levels of HHV-6 DNA in saliva as a surrogate biomarker during chemotherapy.
Ito T, et al. Nutr Cancer 2014 – Clinical Trial. PMID 24611562
The objective of this study was to evaluate the safety and effectiveness of a mushroom product, active hexose correlated compound (AHCC), on chemotherapy-induced adverse effects and quality of life (QOL) in patients with cancer. Twenty-four patients with cancer received their first cycle of chemotherapy without AHCC and then received their second cycle with AHCC. …
Roman BE, et al. Nutr Res 2013 – Clinical Trial. PMID 23351405
In this study, we hypothesized that AHCC will also improve the immune responses of healthy individuals to influenza vaccine. …Immediately post-vaccination, the AHCC group began supplementation with AHCC (3 g/d). Flow cytometric analysis of lymphocyte subpopulations revealed that AHCC supplementation increased NKT cells (P < .1), and CD8 T cells (P < .05) post-vaccination compared to controls. …
Nogusa S, et al. Nutr Res 2009. PMID 19285605
We hypothesized that AHCC supplementation would influence the immune response to influenza infection in a dose-dependent manner. …In conclusion, these data suggest that the effects of AHCC on the immune response to influenza infection are dose dependent and that low-dose AHCC supplementation improves the response to influenza infection despite no effect on total NK cell cytotoxicity….
Wang S, et al. J Nutr 2009. PMID 19141700 Free PMC article.
AHCC administration in aged mice attenuated viremia levels but led to no difference in mortality rate. Overall, our data suggests that AHCC enhances protective host immune responses against WNV infection in young and aged mice. Dietary supplementation with AHCC may be potentially immunotherapeutic for WNV-susceptible populations….
Momiyama K, et al. Cancer Chemother Pharmacol 2009. PMID 19011857
CONCLUSIONS: The percentage of Th2 cells increased in LC patients with aHCC as the efficacy of intra-arterial combination chemotherapy decreased. These results indicated that intra-arterial chemotherapy might be not useful for patients with aHCC, because it induces Th2 dominant host immunity….

Th1/Th2 balance: an important indicator of efficacy for intra-arterial chemotherapy

Nagai H, et al. Cancer Chemother Pharmacol 2008. PMID 18259753
The aim of this study was to assess the influence of intra-arterial combination chemotherapy on the Th1/Th2 balance in LC patients with aHCC. …RESULTS: Thirteen of the 21 aHCC patients (group R) showed an objective response, but the other 8 patients (group N) showed no response. …
Ritz BW, et al. J Nutr 2006. PMID 17056815
However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). …These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. …

 

OLIVE LEAF EXTRACT

“The olive tree (Olea europaea) is native to the Mediterranean region. Olive leaf extract has a long history of use against illnesses in which microorganisms play a major role. In more recent years, studies of olive leaf extracts (containing oleuropein, calcium elenolate, and/or hydroxytyrosol) were effective in eliminating a very broad range of organisms, including bacteria, viruses, parasites, yeast, mold, and fungi.25 Pio Maria Furneri, Anna Piperno, Antonella Sajia, and Giuseppe. “Antimycoplasmal Activity of Hydroxytyrosol, Antimicrob Agents.” Chemother. 2004 December; 48(12): 4892–4894. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC529223/ , 26 Harold E. Renis. “Inactivation of Myxoviruses by Calcium Elenolate.” Antimicrobial Agents and Chemotherapy Aug. 1975, p. 194-199. http://aac.asm.org/cgi/reprint/8/2/194.pdf In addition, Olive leaf has demonstrated antiviral activity against both HIV infection and replication,27 Lee-Huang S1, Zhang L, Huang PL, Chang YT, Huang PL. “Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment.” Biochem Biophys Res Commun. 2003 Aug 8;307(4):1029-37. http://www.ncbi.nlm.nih.gov/pubmed/12878215 primarily by blocking the entry of the virus into host cells in the body’s immune system.28 Bao J1, Zhang DW, Zhang JZ, Huang PL, Huang PL, Lee-Huang S. “Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41.” FEBS Lett. 2007 Jun 12;581(14):2737-42. http://www.ncbi.nlm.nih.gov/pubmed/17537437

Studies have also shown that oleuropein exhibits a significant antiviral activity against respiratory syncytial virus and para-influenza type 3 virus.29 Ma SC, He ZD, Deng XL, But PP, et al. “In vitro evaluation of secoiridoid glucosides from the fruits of Ligustrum lucidum as antiviral agents.” Chem Pharm Bull. 2001;49:1471–1473. http://www.jstage.jst.go.jp/article/cpb/49/11/49_11_1471/_pdf In addition, it has been found to be effective against viral hemorrhagic septicemia rhabdovirus, a highly deadly and infectious virus that afflicts over 50 species of both freshwater and marine water fish. 30 Micol V, Caturla N, Perenz-Fons L, Mas L, Perez L, Estepa A. “The olive leaf extract exhibits antiviral activity against viral haemorrhagic septicaemia rhabdovirus (VHSV)” Antivir Res. 2005;66:129–136. http://www.ncbi.nlm.nih.gov/pubmed/15869811 There are studies that demonstrate that olive leaf extracts augment the activity of the HIV-RT inhibitor 3TC. In fact, cell-to-cell transmission of HIV was inhibited in a dose-dependent manner, and replication was inhibited in an in vitro experiment.31 Lee-Huang S, Zhang L, Chang YY, Huang PL. “Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment.” Biochem Biophys Res Commun. 2003;307:1029–1037. http://www.ncbi.nlm.nih.gov/pubmed/12878215 One of the suspected targets for olive leaf extract action is the HIV-1 gp41 (surface glycoprotein subunit), which is responsible for HIV entry into normal cells. In order to establish HIV protein targets of olive leaf extract and its inhibitory action at the molecular level, researchers reported a joint theoretical and experimental effort has been carried out to help achieve this goal.32 Lee-Huang S, Huang PL, Zhang D, Lee JW, Bao J, et al. “Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and Hydroxytyrosol: Part I.” Integrase Inhibition Biochem Biophys Res Commun. 2007;354:872–878. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790717/ ”

Source: Jon Barron, Using Anti-Pathogens

[Comparison of Antiviral Effect of Olive Leaf Extract and Propolis with Acyclovir on Herpes Simplex Virus Type 1].

Altındiş M, et al. Mikrobiyol Bul 2020. PMID 32050880 Turkish. Free article.
In this in vitro study, olive leaf extract (OLE) and propolis alone or in combination with acyclovir were investigated for their antiviral efficacy in HSV-1.Toxic doses of OLE, propolis, and dimethyl sulfoxide, propolis diluent, for Hep-2 (ATCC, CCL-23) cells were determined by conventional cell culture. Using “endpoint” method, the viral dose infecting half of the cell culture (TCID50) was calculated, and viral quantity was determined with Spearman-Karber method. …

 

Oil of Oregano

Antifungal Activity of Selected Natural Preservatives against Aspergillus westerdijkiae and Penicillium verrucosum and the Interactions of These Preservatives with Food Components

Schlösser I and Prange A. J Food Prot 2019. PMID 31538828
The present study examined the influence of primary food components on the antifungal activity of the essential oil of Origanum vulgare, carvacrol, thymol, eugenol, and trans-cinnamaldehyde against Penicillium verrucosum and Aspergillus westerdijkiae. …The presence of oil had the strongest influence. At a concentration of 1% oil, the antifungal activity decreased significantly, and at 10% oil, almost no inhibition was observed. …

Star Anise Oil (Pimpinella Anisum)

“The Chinese star anise plant has a long history as a healing herb — for digestive problems, women’s health, and for treating colds and flu. The Swiss pharmaceutical company, Roche, focused in on the cold and flu benefit and then “subtracted out” all of the “extraneous” biochemicals in the plant until they settled on one component, shikimic acid, that they said was responsible for the star anise plant’s ability to inhibit colds and flu’s. From shikimic acid, they synthesized oseltamivir (for patent purposes), and thus was born Tamiflu. This is a subtractive process. You eliminate everything “extraneous” and get down to one single active ingredient. Of course, there are major problems with this magic bullet approach.” https://www.jonbarron.org/colds-flus-infectious-diseases/using-anti-pathogens

[Potential antiviral therapeutics for 2019 Novel Coronavirus]

Li H, et al. Zhonghua Jie He He Hu Xi Za Zhi 2020. PMID 32164080 Chinese.
Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. …

Screening for antiviral activities of isolated compounds from essential oils

Astani A, et al. Evid Based Complement Alternat Med 2011.
Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60-80% and sesquiterpenes suppressed herpes virus infection by 40-98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.

Chemical Constituents of Essential Oils Possessing Anti-Influenza A/WS/33 Virus Activity

Choi HJ. Osong Public Health Res Perspect 2018. PMID 30584499 Free PMC article.
The chemical composition detected by GC-MS analysis, differed amongst the 3 most potent anti-viral essential oils (marjoram, clary sage and anise oils) except for linalool, which was detected in all 3 essential oils. CONCLUSION: This study demonstrated anti-influenza activity in 11 essential oils tested, with marjoram, clary sage and anise essential oils being the most effective at reducing visible cytopathic effects of the A/WS/33 virus. …

Antiviral and immunostimulating effects of lignin-carbohydrate-protein complexes from Pimpinella anisum.

Lee JB, et al. Biosci Biotechnol Biochem 2011. PMID 21389629 Free article.
Three antiviral and immunostimulating substances (LC1, LC2 and LC3) were isolated from a hot water extract of seeds of Pimpinella anisum by combination of anion-exchange, gel filtration and hydrophobic interaction column chromatographies. …

Efficacy of anise oil, dwarf-pine oil and chamomile oil against thymidine-kinase-positive and thymidine-kinase-negative herpesviruses.

Koch C, et al. J Pharm Pharmacol 2008. PMID 18957177
The effect of anise oil, dwarf-pine oil and chamomile oil against different thymidine-kinase-positive (aciclovir-sensitive) and thymidine-kinase-negative (aciclovir-resistant) herpes simplex virus type 1 (HSV-1) strains was examined. …No significant effect on viral infectivity could be achieved by adding these compounds during the replication phase. These results indicate that anise oil, dwarf-pine oil and chamomile oil affected the virus by interrupting adsorption of herpesviruses and in a different manner than aciclovir, which is effective after attachment inside the infected cells. …

Inhibitory effect of essential oils against herpes simplex virus type 2

Koch C, et al. Phytomedicine 2008. PMID 17976968
In order to determine the mode of the inhibitory effect, essential oils were added at different stages during the viral infection cycle. …These results indicate that essential oils affected HSV-2 mainly before adsorption probably by interacting with the viral envelope. …

 

Garlic

Garlic for the common cold.

Lissiman E, et al. Cochrane Database Syst Rev 2014 – Review. PMID 25386977 Free PMC article.
Background Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. …The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). …

The effect of Allium sativum (Garlic) extract on infectious bronchitis virus in specific pathogen free embryonic egg.

Mohajer Shojai T, et al. Avicenna J Phytomed 2016. PMID 27516987 Free PMC article.
This study evaluated the inhibitory effects of garlic extract on IBV. MATERIALS AND METHODS: The constituents of garlic extract were detected by gas chromatography. …CONCLUSION: The garlic extract had inhibitory effects on IBV in the chickens embryo….
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𝐍𝐚𝐯𝐢𝐠𝐚𝐭𝐢𝐧𝐠 𝐀𝐈 𝐑𝐢𝐬𝐤 𝐢𝐧 𝐇𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞: 𝐈𝐭 𝐒𝐭𝐚𝐫𝐭𝐬 𝐰𝐢𝐭𝐡 𝐚 𝐅𝐫𝐚𝐦𝐞𝐰𝐨𝐫𝐤

Posted by Michael A. S. Guth on December 12th, 2025

𝐇𝐞𝐚𝐝𝐥𝐢𝐧𝐞: 𝐍𝐚𝐯𝐢𝐠𝐚𝐭𝐢𝐧𝐠 𝐀𝐈 𝐑𝐢𝐬𝐤 𝐢𝐧 𝐇𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞: 𝐈𝐭 𝐒𝐭𝐚𝐫𝐭𝐬 𝐰𝐢𝐭𝐡 𝐚 𝐅𝐫𝐚𝐦𝐞𝐰𝐨𝐫𝐤

𝐀𝐈 𝐚𝐧𝐝 𝐌𝐚𝐜𝐡𝐢𝐧𝐞 𝐋𝐞𝐚𝐫𝐧𝐢𝐧𝐠 𝐚𝐫𝐞 𝐭𝐫𝐚𝐧𝐬𝐟𝐨𝐫𝐦𝐢𝐧𝐠 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐝𝐞𝐯𝐢𝐜𝐞𝐬, 𝐨𝐟𝐟𝐞𝐫𝐢𝐧𝐠 𝐢𝐧𝐜𝐫𝐞𝐝𝐢𝐛𝐥𝐞 𝐩𝐨𝐭𝐞𝐧𝐭𝐢𝐚𝐥 𝐟𝐨𝐫 𝐝𝐢𝐚𝐠𝐧𝐨𝐬𝐢𝐬, 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭, 𝐚𝐧𝐝 𝐩𝐚𝐭𝐢𝐞𝐧𝐭 𝐜𝐚𝐫𝐞. 𝐁𝐮𝐭 𝐰𝐢𝐭𝐡 𝐭𝐡𝐢𝐬 𝐩𝐨𝐰𝐞𝐫 𝐜𝐨𝐦𝐞𝐬 𝐚 𝐜𝐫𝐢𝐭𝐢𝐜𝐚𝐥 𝐪𝐮𝐞𝐬𝐭𝐢𝐨𝐧: 𝐇𝐨𝐰 𝐝𝐨 𝐰𝐞 𝐞𝐧𝐬𝐮𝐫𝐞 𝐭𝐡𝐞𝐬𝐞 “𝐛𝐥𝐚𝐜𝐤 𝐛𝐨𝐱” 𝐬𝐲𝐬𝐭𝐞𝐦𝐬 𝐚𝐫𝐞 𝐬𝐚𝐟𝐞 𝐚𝐧𝐝 𝐞𝐟𝐟𝐞𝐜𝐭𝐢𝐯𝐞?

𝐄𝐧𝐭𝐞𝐫 𝐀𝐀𝐌𝐈 𝐓𝐈𝐑𝟑𝟒𝟗𝟕𝟏.

𝐓𝐡𝐢𝐬 𝐓𝐞𝐜𝐡𝐧𝐢𝐜𝐚𝐥 𝐈𝐧𝐟𝐨𝐫𝐦𝐚𝐭𝐢𝐨𝐧 𝐑𝐞𝐩𝐨𝐫𝐭 𝐢𝐬𝐧’𝐭 𝐚 𝐦𝐚𝐧𝐝𝐚𝐭𝐨𝐫𝐲 𝐬𝐭𝐚𝐧𝐝𝐚𝐫𝐝, 𝐛𝐮𝐭 𝐢𝐭’𝐬 𝐭𝐡𝐞 𝐞𝐬𝐬𝐞𝐧𝐭𝐢𝐚𝐥 𝐠𝐮𝐢𝐝𝐞𝐩𝐨𝐬𝐭. 𝐓𝐡𝐢𝐧𝐤 𝐨𝐟 𝐢𝐭 𝐚𝐬 𝐭𝐡𝐞 𝐢𝐧𝐝𝐮𝐬𝐭𝐫𝐲’𝐬 𝐩𝐥𝐚𝐲𝐛𝐨𝐨𝐤 𝐟𝐨𝐫 𝐚𝐩𝐩𝐥𝐲𝐢𝐧𝐠 𝐫𝐢𝐬𝐤 𝐦𝐚𝐧𝐚𝐠𝐞𝐦𝐞𝐧𝐭 𝐭𝐨 𝐀𝐈/𝐌𝐋 𝐢𝐧 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐝𝐞𝐯𝐢𝐜𝐞𝐬.

𝐈𝐭𝐬 𝐜𝐨𝐫𝐞 𝐦𝐞𝐬𝐬𝐚𝐠𝐞 𝐢𝐬 𝐜𝐥𝐞𝐚𝐫: 𝐀 𝐫𝐢𝐬𝐤 𝐦𝐚𝐧𝐚𝐠𝐞𝐦𝐞𝐧𝐭 𝐩𝐫𝐨𝐜𝐞𝐬𝐬 𝐢𝐬 𝐧𝐨𝐧-𝐧𝐞𝐠𝐨𝐭𝐢𝐚𝐛𝐥𝐞 𝐟𝐨𝐫 𝐀𝐈/𝐌𝐋. 𝐓𝐈𝐑𝟑𝟒𝟗𝟕𝟏 𝐩𝐫𝐨𝐯𝐢𝐝𝐞𝐬 𝐭𝐡𝐞 𝐜𝐫𝐮𝐜𝐢𝐚𝐥 “𝐛𝐫𝐢𝐝𝐠𝐞” 𝐛𝐞𝐭𝐰𝐞𝐞𝐧 𝐭𝐡𝐞 𝐢𝐧𝐧𝐨𝐯𝐚𝐭𝐢𝐯𝐞 𝐰𝐨𝐫𝐥𝐝 𝐨𝐟 𝐀𝐈 𝐝𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐫𝐢𝐠𝐨𝐫𝐨𝐮𝐬, 𝐩𝐫𝐨𝐯𝐞𝐧 𝐰𝐨𝐫𝐥𝐝 𝐨𝐟 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐝𝐞𝐯𝐢𝐜𝐞 𝐬𝐚𝐟𝐞𝐭𝐲 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧.

𝐈𝐭 𝐬𝐞𝐭𝐬 𝐭𝐡𝐞 𝐬𝐭𝐚𝐠𝐞 𝐟𝐨𝐫 𝐞𝐯𝐞𝐫𝐲𝐭𝐡𝐢𝐧𝐠 𝐭𝐡𝐚𝐭 𝐟𝐨𝐥𝐥𝐨𝐰𝐬 𝐛𝐲 𝐞𝐬𝐭𝐚𝐛𝐥𝐢𝐬𝐡𝐢𝐧𝐠 𝐭𝐡𝐞 𝐟𝐮𝐧𝐝𝐚𝐦𝐞𝐧𝐭𝐚𝐥 𝐩𝐫𝐢𝐧𝐜𝐢𝐩𝐥𝐞: 𝐦𝐚𝐧𝐚𝐠𝐞 𝐭𝐡𝐞 𝐫𝐢𝐬𝐤, 𝐨𝐫 𝐝𝐨𝐧’𝐭 𝐝𝐞𝐩𝐥𝐨𝐲 𝐭𝐡𝐞 𝐀𝐈.

𝐊𝐞𝐲 𝐭𝐚𝐤𝐞𝐚𝐰𝐚𝐲: 𝐓𝐈𝐑𝟑𝟒𝟗𝟕𝟏 𝐢𝐬 𝐭𝐡𝐞 “𝐰𝐡𝐲” 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐟𝐢𝐫𝐬𝐭 “𝐡𝐨𝐰” 𝐟𝐨𝐫 𝐀𝐈 𝐫𝐢𝐬𝐤 𝐢𝐧 𝐦𝐞𝐝𝐭𝐞𝐜𝐡, 𝐩𝐨𝐢𝐧𝐭𝐢𝐧𝐠 𝐟𝐢𝐫𝐦𝐥𝐲 𝐭𝐨 𝐞𝐬𝐭𝐚𝐛𝐥𝐢𝐬𝐡𝐞𝐝 𝐬𝐚𝐟𝐞𝐭𝐲 𝐩𝐫𝐨𝐜𝐞𝐬𝐬𝐞𝐬.

🔗 𝐍𝐞𝐱𝐭 𝐩𝐨𝐬𝐭, 𝐰𝐞’𝐥𝐥 𝐥𝐨𝐨𝐤 𝐚𝐭 𝐭𝐡𝐞 𝐮𝐧𝐢𝐯𝐞𝐫𝐬𝐚𝐥 𝐫𝐢𝐬𝐤 𝐦𝐚𝐧𝐚𝐠𝐞𝐦𝐞𝐧𝐭 𝐬𝐭𝐚𝐧𝐝𝐚𝐫𝐝 𝐭𝐡𝐚𝐭 𝐚𝐩𝐩𝐥𝐢𝐞𝐬 𝐭𝐨 𝐚𝐥𝐥 𝐀𝐈, 𝐛𝐞𝐲𝐨𝐧𝐝 𝐣𝐮𝐬𝐭 𝐡𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞.

#𝐀𝐈𝐑𝐢𝐬𝐤 #𝐌𝐞𝐝𝐢𝐜𝐚𝐥𝐃𝐞𝐯𝐢𝐜𝐞 #𝐌𝐞𝐝𝐓𝐞𝐜𝐡 #𝐀𝐈 #𝐑𝐞𝐠𝐮𝐥𝐚𝐭𝐨𝐫𝐲𝐀𝐟𝐟𝐚𝐢𝐫𝐬 #𝐐𝐮𝐚𝐥𝐢𝐭𝐲𝐌𝐚𝐧𝐚𝐠𝐞𝐦𝐞𝐧𝐭 #𝐀𝐀𝐌𝐈 #𝐓𝐈𝐑𝟑𝟒𝟗𝟕𝟏 #𝐃𝐢𝐠𝐢𝐭𝐚𝐥𝐇𝐞𝐚𝐥𝐭𝐡

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The Dosing Diet: PK/PD Lessons from the Incretin Revolution

Posted by Michael A. S. Guth on December 12th, 2025

The pharmaceutical landscape is being rapidly reshaped by a class of drugs known as incretin mimetics, particularly the new generation of anti-obesity medications (AOMs). While the public focuses on the dramatic weight loss achieved by agonists like semaglutide and tirzepatide, the true marvel of these therapeutics lies in their precise Pharmacokinetics (PK) and Pharmacodynamics (PD). These peptide drugs, which activate receptors for hormones like Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP), demand a delicate balance of drug exposure and receptor engagement to maximize efficacy while managing adverse effects. Understanding this PK/PD relationship is the key to unlocking the full potential of the ‘incretin revolution.’

The fundamental pharmacologic rationale for the superior efficacy of these new AOMs is rooted in optimizing the exposure-response curve. Native GLP-1 has a fleeting half-life of mere minutes due to rapid breakdown by the DPP-4 enzyme. Drug developers overcame this by creating analogs that are resistant to degradation and have prolonged clearance, allowing for sustained, therapeutic concentrations. This sustained exposure is critical, enabling chronic receptor activation that not only controls blood sugar but also drives the central and peripheral satiety signals necessary for durable weight loss. The shift to dual-agonist therapies, such as the GIP/GLP-1 combination, represents an advanced PD strategy, leveraging two complementary biological pathways to achieve a more profound metabolic and weight-loss effect than a single agonist alone.

However, the pursuit of maximum efficacy runs directly into the persistent challenge of the Nausea Conundrum. Gastrointestinal (GI) side effects—nausea, vomiting, and diarrhea—are the most common reasons for discontinuation. From a PK/PD perspective, these effects are often linked to the drug’s impact on delayed gastric emptying and central receptor stimulation. Crucially, studies suggest these adverse effects are highly correlated with peak drug exposure and the initial rate of concentration increase.

This pharmacological insight explains the necessary and rigorous dose escalation (titration) schedules used in clinical practice: a slow, gradual increase in dose helps the body adapt to the concentration-dependent side effects, allowing clinicians to manage tolerability while working toward the maximally effective dose.Achieving a sustained, once-weekly exposure is a technical triumph of drug formulation.

Since GLP-1 agonists are peptides, they are susceptible to enzymatic degradation and typically cannot be taken orally (with some notable exceptions). To achieve long-acting, weekly injections, pharmaceutical chemists utilized ingenious formulation strategies such as the addition of lipid side chains (lipidation) or chemical polymers (PEGylation). These modifications essentially camouflage the peptide, making it less susceptible to clearance by the kidneys and less prone to enzymatic breakdown, dramatically extending the half-life from minutes to an entire week.

This long PK half-life is what ensures that the effective drug concentration stays above the therapeutic threshold for seven days, maximizing patient adherence.The success of next-generation AOMs has therefore provided a powerful modern case study for applied clinical pharmacology. It showcases how a deep understanding of the native ligand’s biological limitations—its rapid clearance and short half-life—can be overcome through PK engineering to achieve unprecedented efficacy. Furthermore, it highlights the continuous, necessary struggle to balance the pharmacologic efficacy (weight loss) with receptor-mediated adverse effects (nausea), a balance dictated almost entirely by the principles of exposure and receptor saturation.

In conclusion, the ‘dosing diet’ of these incretin mimetics is far more complex than a simple schedule; it is a precisely choreographed dance between molecule and metabolism. As pharmacometricians continue to refine these models and explore combination therapies, the future of obesity management will rely on even more sophisticated PK/PD models. These models will not only predict optimal starting and maintenance doses but also guide the development of new compounds with even better therapeutic windows—maximizing long-term weight loss while minimizing the all-too-common burden of GI side effects.

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𝐌𝐞𝐝𝐢𝐜𝐚𝐥 𝐃𝐞𝐛𝐭 𝐈𝐬𝐧’𝐭 𝐉𝐮𝐬𝐭 𝐚 𝐇𝐞𝐚𝐥𝐭𝐡 𝐂𝐫𝐢𝐬𝐢𝐬. 𝐈𝐭’𝐬 𝐚 𝐒𝐲𝐬𝐭𝐞𝐦𝐢𝐜 𝐄𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐃𝐫𝐚𝐢𝐧.

Posted by Michael A. S. Guth on December 10th, 2025

𝐈𝐧 𝐓𝐞𝐧𝐧𝐞𝐬𝐬𝐞𝐞, 𝟏 𝐢𝐧 𝟒 𝐩𝐞𝐨𝐩𝐥𝐞 𝐡𝐚𝐬 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐝𝐞𝐛𝐭 𝐢𝐧 𝐜𝐨𝐥𝐥𝐞𝐜𝐭𝐢𝐨𝐧𝐬. 𝐓𝐡𝐚𝐭’𝐬 𝐧𝐨𝐭 𝐣𝐮𝐬𝐭 𝐚 𝐡𝐞𝐚𝐥𝐭𝐡 𝐬𝐭𝐚𝐭𝐢𝐬𝐭𝐢𝐜—𝐢𝐭’𝐬 𝐚 𝐩𝐨𝐰𝐞𝐫𝐟𝐮𝐥 𝐞𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐢𝐧𝐝𝐢𝐜𝐚𝐭𝐨𝐫. 𝐌𝐞𝐝𝐢𝐜𝐚𝐥 𝐝𝐞𝐛𝐭 𝐝𝐨𝐞𝐬𝐧’𝐭 𝐣𝐮𝐬𝐭 𝐫𝐞𝐟𝐥𝐞𝐜𝐭 𝐚𝐧 𝐢𝐥𝐥𝐧𝐞𝐬𝐬 𝐨𝐫 𝐢𝐧𝐣𝐮𝐫𝐲; 𝐢𝐭 𝐫𝐞𝐟𝐥𝐞𝐜𝐭𝐬 𝐚 𝐬𝐲𝐬𝐭𝐞𝐦 𝐭𝐡𝐚𝐭 𝐭𝐫𝐞𝐚𝐭𝐬 𝐡𝐮𝐦𝐚𝐧 𝐡𝐞𝐚𝐥𝐭𝐡 𝐚𝐬 𝐚 𝐬𝐨𝐮𝐫𝐜𝐞 𝐨𝐟 𝐫𝐞𝐯𝐞𝐧𝐮𝐞, 𝐥𝐞𝐚𝐯𝐢𝐧𝐠 𝐩𝐚𝐭𝐢𝐞𝐧𝐭𝐬 𝐟𝐢𝐧𝐚𝐧𝐜𝐢𝐚𝐥𝐥𝐲 𝐩𝐨𝐰𝐞𝐫𝐥𝐞𝐬𝐬.

𝐓𝐡𝐞 𝐡𝐮𝐦𝐚𝐧 𝐜𝐨𝐬𝐭 𝐢𝐬 𝐩𝐫𝐨𝐟𝐨𝐮𝐧𝐝:

𝐃𝐫𝐚𝐢𝐧𝐞𝐝 𝐬𝐚𝐯𝐢𝐧𝐠𝐬 𝐚𝐧𝐝 𝐝𝐚𝐦𝐚𝐠𝐞𝐝 𝐜𝐫𝐞𝐝𝐢𝐭

𝐇𝐨𝐮𝐬𝐢𝐧𝐠 𝐢𝐧𝐬𝐭𝐚𝐛𝐢𝐥𝐢𝐭𝐲 𝐚𝐧𝐝 𝐥𝐢𝐦𝐢𝐭𝐞𝐝 𝐞𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐦𝐨𝐛𝐢𝐥𝐢𝐭𝐲

𝐇𝐢𝐠𝐡 𝐬𝐭𝐫𝐞𝐬𝐬 𝐚𝐧𝐝 𝐝𝐞𝐥𝐚𝐲𝐞𝐝 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐜𝐚𝐫𝐞, 𝐰𝐨𝐫𝐬𝐞𝐧𝐢𝐧𝐠 𝐥𝐨𝐧𝐠-𝐭𝐞𝐫𝐦 𝐨𝐮𝐭𝐜𝐨𝐦𝐞𝐬

𝐁𝐮𝐭 𝐭𝐡𝐞𝐫𝐞’𝐬 𝐚𝐥𝐬𝐨 𝐚 𝐬𝐲𝐬𝐭𝐞𝐦𝐢𝐜 𝐜𝐨𝐬𝐭: 𝐝𝐢𝐦𝐢𝐧𝐢𝐬𝐡𝐞𝐝 𝐰𝐨𝐫𝐤𝐟𝐨𝐫𝐜𝐞 𝐩𝐫𝐨𝐝𝐮𝐜𝐭𝐢𝐯𝐢𝐭𝐲, 𝐜𝐨𝐧𝐬𝐭𝐫𝐚𝐢𝐧𝐞𝐝 𝐜𝐨𝐧𝐬𝐮𝐦𝐞𝐫 𝐬𝐩𝐞𝐧𝐝𝐢𝐧𝐠, 𝐚𝐧𝐝 𝐝𝐞𝐞𝐩𝐞𝐧𝐞𝐝 𝐢𝐧𝐞𝐪𝐮𝐚𝐥𝐢𝐭𝐲.

𝐎𝐭𝐡𝐞𝐫 𝐬𝐭𝐚𝐭𝐞𝐬 𝐚𝐫𝐞𝐧’𝐭 𝐰𝐚𝐢𝐭𝐢𝐧𝐠 𝐟𝐨𝐫 𝐟𝐞𝐝𝐞𝐫𝐚𝐥 𝐫𝐞𝐟𝐨𝐫𝐦. 𝐓𝐡𝐞𝐲’𝐫𝐞 𝐭𝐚𝐤𝐢𝐧𝐠 𝐚𝐜𝐭𝐢𝐨𝐧:

𝐌𝐢𝐜𝐡𝐢𝐠𝐚𝐧 𝐞𝐫𝐚𝐬𝐞𝐝 $𝟏𝟒𝟒𝐌 𝐢𝐧 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐝𝐞𝐛𝐭 𝐟𝐨𝐫 𝟐𝟏𝟎,𝟎𝟎𝟎 𝐫𝐞𝐬𝐢𝐝𝐞𝐧𝐭𝐬

𝐈𝐥𝐥𝐢𝐧𝐨𝐢𝐬 𝐜𝐥𝐞𝐚𝐫𝐞𝐝 $𝟒𝟑𝟎𝐌 𝐟𝐨𝐫 𝟑𝟓𝟕,𝟖𝟎𝟎 𝐩𝐞𝐨𝐩𝐥𝐞

𝐀𝐫𝐢𝐳𝐨𝐧𝐚 𝐞𝐥𝐢𝐦𝐢𝐧𝐚𝐭𝐞𝐝 $𝟒𝟎𝟎𝐌 𝐟𝐨𝐫 𝟑𝟓𝟐,𝟎𝟎𝟎 𝐢𝐧𝐝𝐢𝐯𝐢𝐝𝐮𝐚𝐥𝐬

𝐓𝐡𝐞𝐬𝐞 𝐚𝐫𝐞𝐧’𝐭 𝐣𝐮𝐬𝐭 𝐚𝐜𝐭𝐬 𝐨𝐟 𝐜𝐨𝐦𝐩𝐚𝐬𝐬𝐢𝐨𝐧—𝐭𝐡𝐞𝐲’𝐫𝐞 𝐬𝐦𝐚𝐫𝐭 𝐞𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐢𝐧𝐭𝐞𝐫𝐯𝐞𝐧𝐭𝐢𝐨𝐧𝐬. 𝐁𝐲 𝐥𝐢𝐟𝐭𝐢𝐧𝐠 𝐭𝐡𝐢𝐬 𝐝𝐞𝐛𝐭, 𝐬𝐭𝐚𝐭𝐞𝐬 𝐚𝐫𝐞 𝐟𝐫𝐞𝐞𝐢𝐧𝐠 𝐮𝐩 𝐡𝐨𝐮𝐬𝐞𝐡𝐨𝐥𝐝 𝐛𝐮𝐝𝐠𝐞𝐭𝐬, 𝐢𝐦𝐩𝐫𝐨𝐯𝐢𝐧𝐠 𝐜𝐫𝐞𝐝𝐢𝐭 𝐡𝐞𝐚𝐥𝐭𝐡, 𝐚𝐧𝐝 𝐞𝐧𝐚𝐛𝐥𝐢𝐧𝐠 𝐩𝐞𝐨𝐩𝐥𝐞 𝐭𝐨 𝐫𝐞-𝐞𝐧𝐠𝐚𝐠𝐞 𝐢𝐧 𝐭𝐡𝐞 𝐞𝐜𝐨𝐧𝐨𝐦𝐲 𝐰𝐢𝐭𝐡𝐨𝐮𝐭 𝐭𝐡𝐞 𝐰𝐞𝐢𝐠𝐡𝐭 𝐨𝐟 𝐩𝐚𝐬𝐭 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐛𝐢𝐥𝐥𝐬.

𝐖𝐢𝐭𝐡 𝐓𝐞𝐧𝐧𝐞𝐬𝐬𝐞𝐞 𝐡𝐨𝐥𝐝𝐢𝐧𝐠 𝐫𝐞𝐬𝐞𝐫𝐯𝐞𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐓𝐞𝐦𝐩𝐨𝐫𝐚𝐫𝐲 𝐀𝐬𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞 𝐟𝐨𝐫 𝐍𝐞𝐞𝐝𝐲 𝐅𝐚𝐦𝐢𝐥𝐢𝐞𝐬 (𝐓𝐀𝐍𝐅) 𝐩𝐫𝐨𝐠𝐫𝐚𝐦, 𝐰𝐞 𝐡𝐚𝐯𝐞 𝐚 𝐜𝐥𝐞𝐚𝐫 𝐩𝐚𝐭𝐡𝐰𝐚𝐲 𝐭𝐨 𝐩𝐫𝐨𝐯𝐢𝐝𝐞 𝐬𝐢𝐦𝐢𝐥𝐚𝐫 𝐫𝐞𝐥𝐢𝐞𝐟 𝐡𝐞𝐫𝐞.

𝐀𝐝𝐝𝐫𝐞𝐬𝐬𝐢𝐧𝐠 𝐦𝐞𝐝𝐢𝐜𝐚𝐥 𝐝𝐞𝐛𝐭 𝐢𝐬𝐧’𝐭 𝐨𝐧𝐥𝐲 𝐚𝐛𝐨𝐮𝐭 𝐡𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞—𝐢𝐭’𝐬 𝐚𝐛𝐨𝐮𝐭 𝐞𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐫𝐞𝐬𝐢𝐥𝐢𝐞𝐧𝐜𝐞, 𝐡𝐨𝐮𝐬𝐞𝐡𝐨𝐥𝐝 𝐬𝐭𝐚𝐛𝐢𝐥𝐢𝐭𝐲, 𝐚𝐧𝐝 𝐫𝐞𝐬𝐭𝐨𝐫𝐢𝐧𝐠 𝐟𝐢𝐧𝐚𝐧𝐜𝐢𝐚𝐥 𝐚𝐠𝐞𝐧𝐜𝐲 𝐭𝐨 𝐭𝐡𝐨𝐮𝐬𝐚𝐧𝐝𝐬 𝐨𝐟 𝐓𝐞𝐧𝐧𝐞𝐬𝐬𝐞𝐞 𝐟𝐚𝐦𝐢𝐥𝐢𝐞𝐬.

𝐖𝐡𝐚𝐭 𝐞𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐢𝐧𝐭𝐞𝐫𝐯𝐞𝐧𝐭𝐢𝐨𝐧𝐬 𝐡𝐚𝐯𝐞 𝐲𝐨𝐮 𝐬𝐞𝐞𝐧 𝐞𝐟𝐟𝐞𝐜𝐭𝐢𝐯𝐞𝐥𝐲 𝐚𝐝𝐝𝐫𝐞𝐬𝐬 𝐡𝐨𝐮𝐬𝐞𝐡𝐨𝐥𝐝 𝐝𝐞𝐛𝐭 𝐚𝐧𝐝 𝐬𝐭𝐢𝐦𝐮𝐥𝐚𝐭𝐞 𝐥𝐨𝐜𝐚𝐥 𝐫𝐞𝐜𝐨𝐯𝐞𝐫𝐲?

#𝐄𝐜𝐨𝐧𝐨𝐦𝐢𝐜𝐏𝐨𝐥𝐢𝐜𝐲 #𝐌𝐞𝐝𝐢𝐜𝐚𝐥𝐃𝐞𝐛𝐭 #𝐏𝐮𝐛𝐥𝐢𝐜𝐇𝐞𝐚𝐥𝐭𝐡 #𝐅𝐢𝐧𝐚𝐧𝐜𝐢𝐚𝐥𝐇𝐞𝐚𝐥𝐭𝐡 #𝐄𝐜𝐨𝐧𝐨𝐦𝐢𝐜𝐌𝐨𝐛𝐢𝐥𝐢𝐭𝐲 #𝐓𝐞𝐧𝐧𝐞𝐬𝐬𝐞𝐞 #𝐇𝐞𝐚𝐥𝐭𝐡𝐄𝐪𝐮𝐢𝐭𝐲 #𝐏𝐨𝐥𝐢𝐜𝐲𝐒𝐨𝐥𝐮𝐭𝐢𝐨𝐧𝐬 #𝐂𝐨𝐧𝐬𝐮𝐦𝐞𝐫𝐅𝐢𝐧𝐚𝐧𝐜𝐞 #𝐄𝐜𝐨𝐧𝐨𝐦𝐢𝐜𝐑𝐞𝐜𝐨𝐯𝐞𝐫𝐲

 

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𝐅𝐃𝐀 𝐂𝐥𝐞𝐚𝐫𝐬 𝐀𝐥𝐳𝐡𝐞𝐢𝐦𝐞𝐫’𝐬 𝐁𝐥𝐨𝐨𝐝 𝐓𝐞𝐬𝐭𝐬: 𝐀 𝐊𝐞𝐲 𝐌𝐨𝐦𝐞𝐧𝐭 𝐟𝐨𝐫 𝐃𝐢𝐚𝐠𝐧𝐨𝐬𝐭𝐢𝐜𝐬 & 𝐏𝐫𝐢𝐦𝐚𝐫𝐲 𝐂𝐚𝐫𝐞

Posted by Michael A. S. Guth on December 10th, 2025

A new era in Alzheimer’s diagnosis began this year. The FDA granted clearance to two blood biomarker tests for Alzheimer’s disease, moving them from the category of Laboratory Developed Tests (LDTs) to In Vitro Diagnostic (IVD) devices.

This transition isn’t just regulatory paperwork; it’s a critical evolution in making advanced diagnostics more accessible and standardized for primary care providers.

So, what’s the practical difference for clinicians?

LDTs: Developed and performed within a single laboratory. They are essential for rapid innovation, allowing labs like Quest Diagnostics or Labcorp to bring crucial tests to market quickly to meet urgent, unmet clinical needs where no FDA-cleared option exists.

IVDs: Undergo formal FDA review and clearance. This process ensures standardized performance and accuracy across all labs that run the test, enabling broader adoption and integration into healthcare systems nationwide.

Why does this matter for your practice?

Both pathways play a vital, complementary role:

LDTs offer flexibility and speed to address emerging diagnostic gaps.

IVDs provide consistency and scalability, building confidence for wider clinical use.

The clearance of these Alzheimer’s blood tests means primary care teams can now access more standardized, less invasive tools to aid in the diagnostic pathway. It represents progress toward earlier, more accessible detection.

Understanding the evolving diagnostic landscape is key to modern patient care.

To explore the roles of LDTs and IVDs—and their specific impact on neurology and primary care—read the first post in our new blog series.

#Alzheimers #Diagnostics #PrimaryCare #Neurology #FDA #IVD #LDT #LabMedicine #HealthcareInnovation #PrecisionMedicine

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The Case for Looking It Up (After a Brief Struggle)

Posted by Michael A. S. Guth on December 9th, 2025

𝐈 𝐜𝐚𝐧𝐧𝐨𝐭 𝐫𝐞𝐦𝐞𝐦𝐛𝐞𝐫 𝐭𝐡𝐞 𝐧𝐚𝐦𝐞 𝐨𝐟 𝐚 𝐬𝐮𝐩𝐩𝐥𝐞𝐦𝐞𝐧𝐭 𝐭𝐡𝐚𝐭 𝐈 𝐭𝐚𝐤𝐞 𝐦𝐨𝐬𝐭 𝐰𝐞𝐞𝐤𝐬, 𝐛𝐮𝐭 𝐧𝐨𝐭 𝐝𝐚𝐢𝐥𝐲. 𝐈 𝐫𝐞𝐜𝐚𝐥𝐥 𝐞𝐱𝐚𝐜𝐭𝐥𝐲 𝐰𝐡𝐚𝐭 𝐢𝐭 𝐥𝐨𝐨𝐤𝐬 𝐥𝐢𝐤𝐞 𝐚𝐧𝐝 𝐜𝐚𝐧 𝐬𝐞𝐞 𝐢𝐭 𝐢𝐧 𝐦𝐲 𝐫𝐞𝐟𝐫𝐢𝐠𝐞𝐫𝐚𝐭𝐨𝐫, 𝐛𝐮𝐭 𝐈 𝐜𝐚𝐧’𝐭 𝐫𝐞𝐦𝐞𝐦𝐛𝐞𝐫 𝐢𝐭𝐬 𝐧𝐚𝐦𝐞. 𝐈𝐬 𝐢𝐭 𝐛𝐞𝐭𝐭𝐞𝐫 𝐟𝐨𝐫 𝐦𝐞 𝐭𝐨 𝐤𝐞𝐞𝐩 𝐞𝐱𝐞𝐫𝐜𝐢𝐬𝐢𝐧𝐠 𝐦𝐲 𝐦𝐞𝐦𝐨𝐫𝐲 𝐚𝐧𝐝 𝐭𝐫𝐲𝐢𝐧𝐠 𝐝𝐚𝐲 𝐚𝐟𝐭𝐞𝐫 𝐝𝐚𝐲 𝐭𝐨 𝐫𝐞𝐦𝐞𝐦𝐛𝐞𝐫 𝐭𝐡𝐞 𝐧𝐚𝐦𝐞? 𝐎𝐫 𝐬𝐢𝐦𝐩𝐥𝐲 𝐭𝐨 𝐥𝐨𝐨𝐤 𝐢𝐭 𝐮𝐩 𝐛𝐚𝐬𝐞𝐝 𝐨𝐧 𝐢𝐭𝐬 𝐩𝐫𝐨𝐩𝐞𝐫𝐭𝐢𝐞𝐬 𝐚𝐧𝐝 𝐟𝐢𝐧𝐝 𝐢𝐭𝐬 𝐧𝐚𝐦𝐞 𝐢𝐧 𝟏𝟎 𝐬𝐞𝐜𝐨𝐧𝐝𝐬? 𝐖𝐡𝐢𝐜𝐡 𝐢𝐬 𝐛𝐞𝐭𝐭𝐞𝐫 𝐟𝐨𝐫 𝐩𝐫𝐞𝐯𝐞𝐧𝐭𝐢𝐧𝐠 𝐝𝐞𝐦𝐞𝐧𝐭𝐢𝐚: 𝐣𝐨𝐠𝐠𝐢𝐧𝐠 𝐦𝐲 𝐦𝐞𝐦𝐨𝐫𝐲 𝐝𝐚𝐢𝐥𝐲 𝐢𝐧 𝐚𝐧 𝐚𝐭𝐭𝐞𝐦𝐩𝐭 𝐭𝐨 𝐜𝐨𝐦𝐞 𝐮𝐩 𝐰𝐢𝐭𝐡 𝐭𝐡𝐞 𝐜𝐨𝐫𝐫𝐞𝐜𝐭 𝐧𝐚𝐦𝐞 𝐨𝐫 𝐜𝐫𝐞𝐚𝐭𝐢𝐧𝐠 𝐚 𝐧𝐞𝐰 𝐬𝐲𝐧𝐚𝐩𝐬𝐞 𝐨𝐯𝐞𝐫 𝐝𝐢𝐬𝐜𝐨𝐯𝐞𝐫𝐲 𝐨𝐟 𝐭𝐡𝐞 𝐧𝐚𝐦𝐞 𝐭𝐡𝐚𝐭 𝐈 𝐡𝐚𝐯𝐞 𝐛𝐞𝐞𝐧 𝐬𝐞𝐞𝐤𝐢𝐧𝐠 𝐟𝐨𝐫 𝐬𝐞𝐯𝐞𝐫𝐚𝐥 𝐝𝐚𝐲𝐬?

This is an excellent and practical question that gets to the heart of cognitive health strategies. Based on current neuroscience, the best approach is a nuanced combination of both, but with a strong leaning toward looking it up after a genuine, brief attempt.

Here’s a breakdown of why, and how to optimize it for brain health:

The Case for Looking It Up (After a Brief Struggle)

  1. The “Tip-of-the-Tongue” State is the Exercise, Not the Recall: The valuable cognitive work happens during the attempt to retrieve the memory—when you’re activating related neural networks (e.g., what it’s for, its color, shape, where you bought it). This mental “jogging” strengthens those associative pathways. Prolonged frustration and daily failure, however, can be stressful and counterproductive.

  2. Accurate Reinforcement is Crucial: Once you’ve struggled, providing the correct answer (looking it up) reinforces the right memory trace. Letting an error or a gap persist doesn’t help the brain learn the correct information. Synapses are strengthened when retrieval is successful.

  3. Efficiency and Reduction of Stress: Chronic stress from frustration can elevate cortisol, which is harmful to the hippocampus, a key memory center. Efficiently resolving the search reduces this stress.

  4. You’re Still Creating/Strengthening Synapses: The moment you see the name and think, “Yes! That’s it!” you experience a strong “Aha!” moment. This reconsolidates the memory, now linking your sustained effort (the search) with the correct label, potentially making the memory stronger and more accessible next time.

The Case Against Day-After-Day Attempts Without Resolution

  • Potential for Error: You might inadvertently reinforce the wrong name or the feeling of “not knowing.”

  • Negative Association: The supplement and the act of remembering could become associated with frustration, making you less likely to engage in the healthy behavior of taking it.

  • Wasted Opportunity: The time spent in repeated failed retrieval could be used for other, more varied brain-health activities (learning something new, physical exercise, social interaction).

The Optimal Strategy for Brain Health & Dementia Prevention

Think of this as a “Struggle, then Solve” protocol:

  1. Engage in a Focused, 1-2 Minute Retrieval Attempt: When you first notice you’ve forgotten the name, don’t immediately reach for your phone. Mentally walk through the associations: “It’s the green bottle in the fridge door, for joint health, with the dropper…” Actively try to retrieve it.

  2. If It Doesn’t Come, Look It Up: After a short, earnest struggle, resolve the uncertainty. Use a search engine: “green liquid supplement joint health dropper bottle.” You’ll likely find it in seconds.

  3. Practice Elaborative Rehearsal Upon Discovery: When you see the name (e.g., “Glucosamine Chondroitin MSM Liquid”), don’t just note it and move on.

    • Say it out loud.

    • Spell it in your mind.

    • Connect it vividly: “Right, GLUCOSAMINE—that’s the ‘G’ word I was missing. It’s the thick, sweet-tart green liquid.”

    • Imagine the label. This deep, multi-sensory processing builds a richer, more resilient memory engram.

The Bigger Picture for Dementia Prevention

Preventing cognitive decline relies less on memorizing isolated facts and more on overall brain resilience and health.

  • Neuroplasticity is Key: The brain’s ability to form new connections is vital. Learning truly novel things (a language, instrument, skill) is even more potent than retrieving old facts.

  • Variety is Critical: “Jogging your memory” for one word daily is a small, specific exercise. A holistic approach includes:

    • Cardiovascular Exercise: Increases blood flow and BDNF (brain-derived neurotrophic factor), the “fertilizer” for the brain.

    • Social Engagement: Complex, interactive conversation is a full-brain workout.

    • Healthy Diet: Mediterranean or MIND diets are strongly associated with lower dementia risk.

    • Sleep: Essential for memory consolidation.

Conclusion

For your specific supplement question: Briefly struggle, then look it up and reinforce the memory deeply. The synaptic benefit comes from the active retrieval attempt followed by successful re-encoding, not from prolonged failure.

The single best thing you can do for dementia prevention is to lead a brain-healthy lifestyle overall. Using efficient strategies to manage daily memory lapses (like this one) reduces stress and frees up time and energy for those broader, more impactful activities—like actual physical jogging, which is one of the most evidence-supported ways to protect your brain.

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𝗙𝗿𝗼𝗺 𝗥𝗲𝗳𝗲𝗿𝗲𝗲 𝘁𝗼 𝗕𝘂𝗶𝗹𝗱𝗲𝗿: 𝗥𝗲𝗶𝗺𝗮𝗴𝗶𝗻𝗶𝗻𝗴 𝗘𝗰𝗼𝗻𝗼𝗺𝗶𝗰 𝗦𝘁𝗿𝗮𝘁𝗲𝗴𝘆

Posted by Michael A. S. Guth on December 7th, 2025

𝗡𝗼 𝘀𝘂𝗿𝗽𝗿𝗶𝘀𝗲: 𝗜 𝘀𝘂𝗽𝗽𝗼𝗿𝘁 𝗨𝗻𝗶𝘃𝗲𝗿𝘀𝗮𝗹 𝗛𝗲𝗮𝗹𝘁𝗵𝗰𝗮𝗿𝗲 𝗮𝘀 𝗮𝗹𝗹 𝘁𝗵𝗲 𝗺𝗼𝗱𝗲𝗿𝗻 𝗶𝗻𝗱𝘂𝘀𝘁𝗿𝗶𝗮𝗹𝗶𝘇𝗲𝗱 𝗰𝗼𝘂𝗻𝘁𝗿𝗶𝗲𝘀 𝗼𝗳 𝘁𝗵𝗲 𝘄𝗼𝗿𝗹𝗱 𝗵𝗮𝘀, 𝗘𝗫𝗖𝗘𝗣𝗧 𝘁𝗵𝗲 𝗨𝗦𝗔. 𝗜 𝗸𝗻𝗼𝘄 𝗽𝗲𝗼𝗽𝗹𝗲 𝘄𝗵𝗼 𝗱𝗶𝗲𝗱 𝗶𝗻 𝘁𝗵𝗲 𝗽𝗮𝘀𝘁 𝗳𝗿𝗼𝗺 𝗹𝗮𝗰𝗸 𝗼𝗳 𝗵𝗲𝗮𝗹𝘁𝗵 𝗶𝗻𝘀𝘂𝗿𝗮𝗻𝗰𝗲, 𝗮𝗻𝗱 𝗜 𝘄𝗶𝗹𝗹 𝗸𝗻𝗼𝘄 𝗺𝗼𝗿𝗲 𝗶𝗻 𝘁𝗵𝗲 𝗳𝘂𝘁𝘂𝗿𝗲. 𝗙𝗿𝗼𝗺 𝗥𝗲𝗳𝗲𝗿𝗲𝗲 𝘁𝗼 𝗕𝘂𝗶𝗹𝗱𝗲𝗿: 𝗥𝗲𝗶𝗺𝗮𝗴𝗶𝗻𝗶𝗻𝗴 𝗘𝗰𝗼𝗻𝗼𝗺𝗶𝗰 𝗦𝘁𝗿𝗮𝘁𝗲𝗴𝘆 𝗧𝗵𝗲𝗿𝗲’𝘀 𝗮 𝗽𝗿𝗲𝘃𝗮𝗶𝗹𝗶𝗻𝗴 𝗺𝗼𝗱𝗲𝗹 𝗼𝗳 𝗴𝗼𝘃𝗲𝗿𝗻𝗺𝗲𝗻𝘁 𝗮𝘀 𝗮 𝗿𝗲𝗳𝗲𝗿𝗲𝗲 𝗶𝗻 𝘁𝗵𝗲 𝗲𝗰𝗼𝗻𝗼𝗺𝘆—𝘀𝗲𝘁𝘁𝗶𝗻𝗴 𝗿𝘂𝗹𝗲𝘀 𝗯𝘂𝘁 𝗻𝗼𝘁 𝗽𝗹𝗮𝘆𝗶𝗻𝗴 𝘁𝗵𝗲 𝗴𝗮𝗺𝗲. 𝗧𝗵𝗶𝘀 𝗮𝗹𝗶𝗴𝗻𝘀 𝘄𝗶𝘁𝗵 𝗮 𝗺𝗮𝗿𝗸𝗲𝘁-𝗽𝘂𝗿𝗶𝘀𝘁 𝘃𝗶𝗲𝘄. 𝗕𝘂𝘁 𝘁𝗵𝗶𝘀 𝗰𝗼𝗺𝗺𝗲𝗻𝘁𝗮𝗿𝘆 𝗮𝗿𝗴𝘂𝗲𝘀 𝘄𝗲’𝘃𝗲 𝘁𝗿𝗮𝗻𝘀𝗶𝘁𝗶𝗼𝗻𝗲𝗱 𝗳𝗿𝗼𝗺 𝗮 𝗺𝗶𝗱-𝗰𝗲𝗻𝘁𝘂𝗿𝘆 “𝗯𝘂𝗶𝗹𝗱𝗲𝗿” 𝘀𝘁𝗮𝘁𝗲 𝘁𝗼 𝗮 “𝗯𝗹𝗶𝗻𝗱𝗳𝗼𝗹𝗱𝗲𝗱 𝗿𝗲𝗳𝗲𝗿𝗲𝗲,” 𝗮𝗻𝗱 𝗼𝘂𝗿 𝗮𝗳𝗳𝗼𝗿𝗱𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗰𝗿𝗶𝘀𝗶𝘀 𝗶𝘀 𝘁𝗵𝗲 𝗿𝗲𝘀𝘂𝗹𝘁.

𝗪𝗵𝗲𝗻 𝘁𝗵𝗲 𝘀𝘁𝗮𝘁𝗲 𝗮𝗰𝘁𝘀 𝗼𝗻𝗹𝘆 𝗮𝘀 𝗮 𝗿𝗲𝗳𝗲𝗿𝗲𝗲, 𝗶𝘁𝘀 𝗺𝗮𝗶𝗻 𝗮𝗳𝗳𝗼𝗿𝗱𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝘁𝗼𝗼𝗹𝘀 𝗮𝗿𝗲 𝗽𝗲𝗻𝗮𝗹𝘁𝗶𝗲𝘀, 𝗶𝗻𝗰𝗲𝗻𝘁𝗶𝘃𝗲𝘀, 𝗮𝗻𝗱 𝘀𝘂𝗯𝘀𝗶𝗱𝗶𝗲𝘀. 𝗜𝘁 𝘁𝗿𝗶𝗲𝘀 𝘁𝗼 𝗴𝘂𝗶𝗱𝗲 𝗽𝗿𝗶𝘃𝗮𝘁𝗲 𝗮𝗰𝘁𝗼𝗿𝘀. 𝗕𝘂𝘁 𝗶𝗻 𝘀𝗲𝗰𝘁𝗼𝗿𝘀 𝘄𝗶𝘁𝗵 𝗶𝗻𝗲𝗹𝗮𝘀𝘁𝗶𝗰 𝗱𝗲𝗺𝗮𝗻𝗱 𝗮𝗻𝗱 𝗵𝗶𝗴𝗵 𝗯𝗮𝗿𝗿𝗶𝗲𝗿𝘀 𝘁𝗼 𝗲𝗻𝘁𝗿𝘆 (𝗵𝗼𝘂𝘀𝗶𝗻𝗴, 𝗵𝗲𝗮𝗹𝘁𝗵𝗰𝗮𝗿𝗲, 𝘂𝘁𝗶𝗹𝗶𝘁𝗶𝗲𝘀), 𝘁𝗵𝗶𝘀 𝗼𝗳𝘁𝗲𝗻 𝗳𝗮𝗶𝗹𝘀 𝘁𝗼 𝗰𝗼𝗻𝘁𝗿𝗼𝗹 𝗰𝗼𝘀𝘁𝘀. 𝗧𝗵𝗲 “𝗯𝘂𝗶𝗹𝗱𝗲𝗿” 𝗺𝗼𝗱𝗲𝗹 𝗶𝘀 𝗱𝗶𝗳𝗳𝗲𝗿𝗲𝗻𝘁. 𝗜𝘁 𝗶𝗻𝘃𝗼𝗹𝘃𝗲𝘀 𝗰𝗿𝗲𝗮𝘁𝗶𝗻𝗴 𝗽𝘂𝗯𝗹𝗶𝗰 𝗼𝗽𝘁𝗶𝗼𝗻 𝘀𝘂𝗽𝗽𝗹𝘆: 𝗽𝘂𝗯𝗹𝗶𝗰 𝗵𝗼𝘀𝗽𝗶𝘁𝗮𝗹𝘀, 𝗽𝘂𝗯𝗹𝗶𝗰 𝗯𝗿𝗼𝗮𝗱𝗯𝗮𝗻𝗱, 𝗽𝘂𝗯𝗹𝗶𝗰 𝗵𝗼𝘂𝘀𝗶𝗻𝗴 𝗱𝗲𝘃𝗲𝗹𝗼𝗽𝗺𝗲𝗻𝘁.

𝗧𝗵𝗶𝘀 𝗶𝘀𝗻’𝘁 𝗮𝗯𝗼𝘂𝘁 𝗿𝗲𝗽𝗹𝗮𝗰𝗶𝗻𝗴 𝗽𝗿𝗶𝘃𝗮𝘁𝗲 𝗲𝗻𝘁𝗲𝗿𝗽𝗿𝗶𝘀𝗲 𝗯𝘂𝘁 𝗮𝗯𝗼𝘂𝘁 𝗰𝗼𝗺𝗽𝗲𝘁𝗶𝗻𝗴 𝘄𝗶𝘁𝗵 𝗶𝘁. 𝗔 𝗽𝘂𝗯𝗹𝗶𝗰 𝗼𝗽𝘁𝗶𝗼𝗻 𝗶𝗻 𝗵𝗲𝗮𝗹𝘁𝗵𝗰𝗮𝗿𝗲 𝗺𝗲𝗮𝗻𝘀 𝗽𝘂𝗯𝗹𝗶𝗰 𝗵𝗼𝘀𝗽𝗶𝘁𝗮𝗹𝘀 𝗮𝗻𝗱 𝗰𝗹𝗶𝗻𝗶𝗰𝘀, 𝗻𝗼𝘁 𝗷𝘂𝘀𝘁 𝗶𝗻𝘀𝘂𝗿𝗮𝗻𝗰𝗲. 𝗧𝗵𝗲 𝗴𝗼𝗮𝗹 𝗶𝘀 𝘁𝗼 𝗽𝗿𝗼𝘃𝗶𝗱𝗲 𝗮 𝘀𝗲𝗿𝘃𝗶𝗰𝗲-𝗮𝘁-𝗰𝗼𝘀𝘁 𝗯𝗲𝗻𝗰𝗵𝗺𝗮𝗿𝗸 𝘁𝗵𝗮𝘁 𝗱𝗶𝘀𝗰𝗶𝗽𝗹𝗶𝗻𝗲𝘀 𝘁𝗵𝗲 𝗲𝗻𝘁𝗶𝗿𝗲 𝗺𝗮𝗿𝗸𝗲𝘁, 𝗽𝗿𝗲𝘃𝗲𝗻𝘁𝗶𝗻𝗴 𝗲𝗻𝗱𝗹𝗲𝘀𝘀 𝗲𝘅𝘁𝗿𝗮𝗰𝘁𝗶𝗼𝗻.

𝗘𝗰𝗼𝗻𝗼𝗺𝗶𝗰𝗮𝗹𝗹𝘆, 𝘁𝗵𝗶𝘀 𝗶𝘀 𝗮𝗯𝗼𝘂𝘁 𝗹𝗲𝘃𝗲𝗿𝗮𝗴𝗶𝗻𝗴 𝗽𝘂𝗯𝗹𝗶𝗰 𝗯𝗮𝗹𝗮𝗻𝗰𝗲 𝘀𝗵𝗲𝗲𝘁𝘀 𝗳𝗼𝗿 𝗱𝗶𝗿𝗲𝗰𝘁 𝗶𝗻𝘃𝗲𝘀𝘁𝗺𝗲𝗻𝘁 𝘁𝗼 𝗶𝗻𝗰𝗿𝗲𝗮𝘀𝗲 𝘁𝗼𝘁𝗮𝗹 𝘀𝘂𝗽𝗽𝗹𝘆 𝗮𝗻𝗱 𝗶𝗻𝘁𝗿𝗼𝗱𝘂𝗰𝗲 𝗿𝗲𝗮𝗹 𝗽𝗿𝗶𝗰𝗲 𝗰𝗼𝗺𝗽𝗲𝘁𝗶𝘁𝗶𝗼𝗻. 𝗜𝘁’𝘀 𝗮 𝘀𝗵𝗶𝗳𝘁 𝗳𝗿𝗼𝗺 𝗺𝗮𝗻𝗮𝗴𝗶𝗻𝗴 𝗱𝗲𝗺𝗮𝗻𝗱 𝘁𝗼 𝗮𝗰𝘁𝗶𝘃𝗲𝗹𝘆 𝘀𝗵𝗮𝗽𝗶𝗻𝗴 𝘀𝘂𝗽𝗽𝗹𝘆. 𝗧𝗵𝗲 𝗰𝗼𝗻𝘃𝗲𝗿𝘀𝗮𝘁𝗶𝗼𝗻 𝗶𝘀 𝗺𝗼𝘃𝗶𝗻𝗴 𝗳𝗿𝗼𝗺 “𝗛𝗼𝘄 𝗱𝗼 𝘄𝗲 𝗵𝗲𝗹𝗽 𝗽𝗲𝗼𝗽𝗹𝗲 𝗽𝗮𝘆?” 𝘁𝗼 “𝗪𝗵𝗼 𝘄𝗶𝗹𝗹 𝗯𝘂𝗶𝗹𝗱 𝘄𝗵𝗮𝘁 𝘄𝗲 𝗻𝗲𝗲𝗱, 𝗮𝗻𝗱 𝘂𝗻𝗱𝗲𝗿 𝘄𝗵𝗮𝘁 𝘁𝗲𝗿𝗺𝘀?”

𝗜𝘀 𝘁𝗵𝗲 𝗺𝗼𝘀𝘁 𝘃𝗶𝗮𝗯𝗹𝗲 𝗽𝗮𝘁𝗵 𝘁𝗼 𝗮𝗳𝗳𝗼𝗿𝗱𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗮 𝗿𝗲𝘁𝘂𝗿𝗻 𝘁𝗼 𝘁𝗵𝗲 𝘀𝘁𝗮𝘁𝗲 𝗵𝗮𝘃𝗶𝗻𝗴 𝗮 𝗱𝗶𝗿𝗲𝗰𝘁 𝗰𝗮𝗽𝗮𝗰𝗶𝘁𝘆 𝘁𝗼 𝗯𝘂𝗶𝗹𝗱?

#𝗘𝗰𝗼𝗻𝗼𝗺𝗶𝗰𝗗𝗲𝘃𝗲𝗹𝗼𝗽𝗺𝗲𝗻𝘁 #𝗣𝘂𝗯𝗹𝗶𝗰𝗦𝗲𝗰𝘁𝗼𝗿 #𝗛𝗲𝗮𝗹𝘁𝗵𝗰𝗮𝗿𝗲 #𝗛𝗼𝘂𝘀𝗶𝗻𝗴𝗖𝗿𝗶𝘀𝗶𝘀 #𝗜𝗻𝘃𝗲𝘀𝘁𝗶𝗻𝗴 #𝗙𝘂𝘁𝘂𝗿𝗲𝗢𝗳𝗪𝗼𝗿𝗸

 

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𝐀 𝐇𝐢𝐬𝐭𝐨𝐫𝐲 𝐋𝐞𝐬𝐬𝐨𝐧 𝐢𝐧 𝐄𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐁𝐮𝐢𝐥𝐝𝐢𝐧𝐠: 𝐓𝐡𝐞 𝐓𝐕𝐀 𝐌𝐨𝐝𝐞𝐥

Posted by Michael A. S. Guth on December 7th, 2025

𝐈 𝐥𝐢𝐯𝐞 𝐢𝐧 𝐓𝐞𝐧𝐧𝐞𝐬𝐬𝐞𝐞 𝐚𝐧𝐝 𝐡𝐚𝐯𝐞 𝐫𝐞𝐜𝐞𝐢𝐯𝐞𝐝 𝐞𝐥𝐞𝐜𝐭𝐫𝐢𝐜𝐢𝐭𝐲 𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐞𝐝 𝐛𝐲 𝐓𝐕𝐀 𝐦𝐨𝐬𝐭 𝐨𝐟 𝐦𝐲 𝐥𝐢𝐟𝐞. 𝐀𝐦 𝐈 𝐰𝐨𝐫𝐫𝐢𝐞𝐝 𝐭𝐡𝐚𝐭 𝐬𝐨𝐦𝐞 𝐢𝐠𝐧𝐨𝐫𝐚𝐧𝐭 𝐩𝐞𝐨𝐩𝐥𝐞 𝐭𝐡𝐢𝐧𝐤 𝐓𝐕𝐀 𝐢𝐬 𝐬𝐨𝐜𝐢𝐚𝐥𝐢𝐬𝐦? 𝐍𝐨! 𝐍𝐨𝐭 𝐚𝐭 𝐚𝐥𝐥! It is a fantastic example of socialism for the benefit of all.  𝐀 𝐇𝐢𝐬𝐭𝐨𝐫𝐲 𝐋𝐞𝐬𝐬𝐨𝐧 𝐢𝐧 𝐄𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐁𝐮𝐢𝐥𝐝𝐢𝐧𝐠: 𝐓𝐡𝐞 𝐓𝐕𝐀 𝐌𝐨𝐝𝐞𝐥 𝐃𝐢𝐬𝐜𝐮𝐬𝐬𝐢𝐨𝐧𝐬 𝐚𝐛𝐨𝐮𝐭 𝐚𝐟𝐟𝐨𝐫𝐝𝐚𝐛𝐢𝐥𝐢𝐭𝐲 𝐨𝐟𝐭𝐞𝐧 𝐡𝐢𝐭 𝐚 𝐰𝐚𝐥𝐥: “𝐈𝐭’𝐬 𝐭𝐨𝐨 𝐞𝐱𝐩𝐞𝐧𝐬𝐢𝐯𝐞” 𝐨𝐫 “𝐓𝐡𝐞 𝐠𝐨𝐯𝐞𝐫𝐧𝐦𝐞𝐧𝐭 𝐜𝐚𝐧’𝐭 𝐛𝐮𝐢𝐥𝐝 𝐞𝐟𝐟𝐢𝐜𝐢𝐞𝐧𝐭𝐥𝐲.” 𝐇𝐢𝐬𝐭𝐨𝐫𝐲 𝐩𝐫𝐨𝐯𝐢𝐝𝐞𝐬 𝐚 𝐩𝐨𝐰𝐞𝐫𝐟𝐮𝐥 𝐜𝐨𝐮𝐧𝐭𝐞𝐫𝐩𝐨𝐢𝐧𝐭: 𝐭𝐡𝐞 𝐓𝐞𝐧𝐧𝐞𝐬𝐬𝐞𝐞 𝐕𝐚𝐥𝐥𝐞𝐲 𝐀𝐮𝐭𝐡𝐨𝐫𝐢𝐭𝐲 (𝐓𝐕𝐀).

𝐓𝐡𝐞 𝐓𝐕𝐀 𝐰𝐚𝐬𝐧’𝐭 𝐚 𝐬𝐮𝐛𝐬𝐢𝐝𝐲 𝐨𝐫 𝐚 𝐥𝐢𝐠𝐡𝐭-𝐭𝐨𝐮𝐜𝐡 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐢𝐨𝐧. 𝐈𝐭 𝐰𝐚𝐬 𝐭𝐡𝐞 𝐟𝐞𝐝𝐞𝐫𝐚𝐥 𝐠𝐨𝐯𝐞𝐫𝐧𝐦𝐞𝐧𝐭 𝐞𝐧𝐭𝐞𝐫𝐢𝐧𝐠 𝐭𝐡𝐞 𝐞𝐧𝐞𝐫𝐠𝐲 𝐦𝐚𝐫𝐤𝐞𝐭 𝐚𝐬 𝐚 𝐝𝐢𝐫𝐞𝐜𝐭, 𝐩𝐮𝐛𝐥𝐢𝐜 𝐜𝐨𝐦𝐩𝐞𝐭𝐢𝐭𝐨𝐫. 𝐈𝐭 𝐬𝐞𝐢𝐳𝐞𝐝 𝐥𝐚𝐧𝐝, 𝐝𝐚𝐦𝐦𝐞𝐝 𝐫𝐢𝐯𝐞𝐫𝐬, 𝐛𝐮𝐢𝐥𝐭 𝐢𝐧𝐟𝐫𝐚𝐬𝐭𝐫𝐮𝐜𝐭𝐮𝐫𝐞, 𝐚𝐧𝐝 𝐬𝐨𝐥𝐝 𝐩𝐨𝐰𝐞𝐫 𝐚𝐭 𝐜𝐨𝐬𝐭 𝐭𝐨 𝐦𝐨𝐝𝐞𝐫𝐧𝐢𝐳𝐞 𝐚 𝐫𝐞𝐠𝐢𝐨𝐧 𝐩𝐫𝐢𝐯𝐚𝐭𝐞 𝐜𝐚𝐩𝐢𝐭𝐚𝐥 𝐡𝐚𝐝 𝐚𝐛𝐚𝐧𝐝𝐨𝐧𝐞𝐝. 𝐓𝐡𝐢𝐬 𝐝𝐢𝐝𝐧’𝐭 𝐝𝐞𝐬𝐭𝐫𝐨𝐲 𝐭𝐡𝐞 𝐦𝐚𝐫𝐤𝐞𝐭; 𝐢𝐭 𝐜𝐫𝐞𝐚𝐭𝐞𝐝 𝐨𝐧𝐞 𝐰𝐡𝐞𝐫𝐞 𝐧𝐨𝐧𝐞 𝐩𝐫𝐨𝐟𝐢𝐭𝐚𝐛𝐥𝐲 𝐞𝐱𝐢𝐬𝐭𝐞𝐝 𝐚𝐧𝐝 𝐟𝐨𝐫𝐜𝐞𝐝 𝐞𝐱𝐢𝐬𝐭𝐢𝐧𝐠 𝐮𝐭𝐢𝐥𝐢𝐭𝐢𝐞𝐬 𝐭𝐨 𝐚𝐝𝐚𝐩𝐭.

𝐓𝐡𝐢𝐬 𝐫𝐞𝐟𝐥𝐞𝐜𝐭𝐬 𝐚 𝐛𝐫𝐨𝐚𝐝𝐞𝐫 𝐦𝐢𝐝-𝐜𝐞𝐧𝐭𝐮𝐫𝐲 𝐞𝐜𝐨𝐧𝐨𝐦𝐢𝐜 𝐩𝐫𝐢𝐧𝐜𝐢𝐩𝐥𝐞: 𝐨𝐮𝐭𝐜𝐨𝐦𝐞𝐬 𝐦𝐚𝐭𝐭𝐞𝐫𝐢𝐧𝐠 𝐦𝐨𝐫𝐞 𝐭𝐡𝐚𝐧 𝐦𝐚𝐫𝐤𝐞𝐭 𝐩𝐮𝐫𝐢𝐭𝐲. 𝐅𝐫𝐨𝐦 𝐭𝐡𝐞 𝐃𝐞𝐟𝐞𝐧𝐬𝐞 𝐏𝐥𝐚𝐧𝐭 𝐂𝐨𝐫𝐩𝐨𝐫𝐚𝐭𝐢𝐨𝐧 𝐛𝐮𝐢𝐥𝐝𝐢𝐧𝐠 𝐟𝐚𝐜𝐭𝐨𝐫𝐢𝐞𝐬 𝐭𝐨 𝐭𝐡𝐞 𝐬𝐭𝐚𝐭𝐞 𝐦𝐚𝐧𝐝𝐚𝐭𝐢𝐧𝐠 𝐩𝐚𝐭𝐞𝐧𝐭 𝐬𝐡𝐚𝐫𝐢𝐧𝐠 (𝐥𝐢𝐤𝐞 𝐭𝐡𝐞 𝐭𝐫𝐚𝐧𝐬𝐢𝐬𝐭𝐨𝐫), 𝐭𝐡𝐞 𝐚𝐩𝐩𝐫𝐨𝐚𝐜𝐡 𝐰𝐚𝐬 “𝐭𝐚𝐱 𝐚𝐧𝐝 𝐛𝐮𝐢𝐥𝐝,” 𝐧𝐨𝐭 𝐣𝐮𝐬𝐭 “𝐭𝐚𝐱 𝐚𝐧𝐝 𝐬𝐩𝐞𝐧𝐝.” 𝐓𝐡𝐞 𝐠𝐨𝐚𝐥 𝐰𝐚𝐬 𝐛𝐮𝐢𝐥𝐝𝐢𝐧𝐠 𝐦𝐢𝐝𝐝𝐥𝐞-𝐜𝐥𝐚𝐬𝐬 𝐬𝐭𝐚𝐛𝐢𝐥𝐢𝐭𝐲 𝐭𝐡𝐫𝐨𝐮𝐠𝐡 𝐝𝐢𝐫𝐞𝐜𝐭 𝐩𝐮𝐛𝐥𝐢𝐜 𝐢𝐧𝐯𝐞𝐬𝐭𝐦𝐞𝐧𝐭 𝐚𝐧𝐝 𝐜𝐨𝐦𝐩𝐞𝐭𝐢𝐭𝐢𝐨𝐧.

𝐅𝐨𝐫 𝐛𝐮𝐬𝐢𝐧𝐞𝐬𝐬 𝐥𝐞𝐚𝐝𝐞𝐫𝐬, 𝐭𝐡𝐞 𝐥𝐞𝐬𝐬𝐨𝐧 𝐢𝐬𝐧’𝐭 𝐚𝐛𝐨𝐮𝐭 𝐢𝐝𝐞𝐨𝐥𝐨𝐠𝐲 𝐛𝐮𝐭 𝐚𝐛𝐨𝐮𝐭 𝐦𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦. 𝐖𝐡𝐞𝐧 𝐰𝐞 𝐬𝐚𝐲 “𝐛𝐮𝐢𝐥𝐝 𝐦𝐨𝐫𝐞 𝐡𝐨𝐮𝐬𝐢𝐧𝐠” 𝐨𝐫 “𝐥𝐨𝐰𝐞𝐫 𝐡𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞 𝐜𝐨𝐬𝐭𝐬,” 𝐰𝐡𝐚𝐭 𝐢𝐬 𝐭𝐡𝐞 𝐚𝐜𝐭𝐮𝐚𝐥 𝐛𝐮𝐢𝐥𝐝𝐢𝐧𝐠 𝐦𝐞𝐜𝐡𝐚𝐧𝐢𝐬𝐦? 𝐓𝐡𝐞 𝐓𝐕𝐀 𝐫𝐞𝐦𝐢𝐧𝐝𝐬 𝐮𝐬 𝐭𝐡𝐚𝐭 𝐩𝐮𝐛𝐥𝐢𝐜 𝐜𝐚𝐩𝐚𝐜𝐢𝐭𝐲 𝐭𝐨 𝐛𝐮𝐢𝐥𝐝 𝐚𝐧𝐝 𝐜𝐨𝐦𝐩𝐞𝐭𝐞 𝐜𝐚𝐧 𝐫𝐞𝐬𝐡𝐚𝐩𝐞 𝐦𝐚𝐫𝐤𝐞𝐭𝐬 𝐚𝐧𝐝 𝐞𝐧𝐟𝐨𝐫𝐜𝐞 𝐩𝐫𝐢𝐜𝐞 𝐝𝐢𝐬𝐜𝐢𝐩𝐥𝐢𝐧𝐞 𝐢𝐧 𝐰𝐚𝐲𝐬 𝐬𝐮𝐛𝐬𝐢𝐝𝐢𝐞𝐬 𝐚𝐧𝐝 𝐢𝐧𝐜𝐞𝐧𝐭𝐢𝐯𝐞𝐬 𝐚𝐥𝐨𝐧𝐞 𝐜𝐚𝐧𝐧𝐨𝐭.

#𝐄𝐜𝐨𝐧𝐨𝐦𝐢𝐜𝐇𝐢𝐬𝐭𝐨𝐫𝐲 #𝐈𝐧𝐟𝐫𝐚𝐬𝐭𝐫𝐮𝐜𝐭𝐮𝐫𝐞 #𝐄𝐧𝐞𝐫𝐠𝐲 #𝐂𝐨𝐦𝐩𝐞𝐭𝐢𝐭𝐢𝐨𝐧 #𝐏𝐮𝐛𝐥𝐢𝐜𝐏𝐫𝐢𝐯𝐚𝐭𝐞𝐏𝐚𝐫𝐭𝐧𝐞𝐫𝐬𝐡𝐢𝐩 #𝐈𝐧𝐧𝐨𝐯𝐚𝐭𝐢𝐨𝐧

 

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 New Interventional Cardiology Trial Alert: PROCTOR Study Results

Posted by Michael A. S. Guth on December 5th, 2025

🚨 New Interventional Cardiology Trial Alert: PROCTOR Study Results

In patients with prior CABG and failing saphenous vein grafts (SVGs), the choice of which vessel to re-intervene on is a common dilemma. The just-published PROCTOR trial provides compelling evidence.

➡ The Study: Randomized 220 post-CABG patients with SVG failure to receive PCI either on the native coronary artery (108 pts) or on the saphenous vein graft itself (112 pts).

➡ Key Finding at 1 Year: PCI on the native artery was associated with worse outcomes than PCI on the SVG.

Major Adverse Cardiac Events: 34% (native) vs. 19% (SVG) | HR 2.14

Nonfatal MI: Significantly higher with native PCI | HR 2.12

Repeat Revascularization: Higher with native PCI | HR 2.19

PCI-Related MI: 13% (native) vs. 1% (SVG) | HR 14.85

Mortality: No significant difference.

Conclusion: In this population, SVG PCI produced significantly better one-year clinical outcomes than attempting native vessel PCI.

This challenges some conventional wisdom and underscores the complexity of managing post-CABG patients. It highlights that technical success in a native vessel does not always translate to better patient outcomes, possibly due to vessel quality, complexity, and collateral flow.

#Cardiology #InterventionalCardiology #CABG #PCI #ClinicalTrials #PROCTORTrial #CardioTwitter #MedEd

Acronym Definitions:

PCI: Percutaneous Coronary Intervention. A minimally invasive procedure to open blocked coronary arteries, typically using a balloon and stent.

SVG: Saphenous Vein Graft. A segment of the leg vein used during CABG surgery to bypass a blocked coronary artery.

CABG: Coronary Artery Bypass Grafting. Open-heart surgery to restore blood flow by grafting vessels to bypass coronary blockages.

MI: Myocardial Infarction. A heart attack, caused by a blockage of blood flow to the heart muscle.

HR: Hazard Ratio. A measure of how often an event happens in one group compared to another over time in a study. An HR >1.0 indicates a higher risk.

PROCTOR: (Trial Name) Likely an acronym related to the trial’s focus (e.g., PCI of Restenotic Occluded Coronary naTive arteries versus bypass grafts), though the full expansion is not standardized in the summary provided.

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