I am curious to learn whether you doctors are familiar with endocannabinoid system in general and arachidonic acid research in particular. An 'Adam Cifu arachidonic acid' web search which brought up a comment I posted on this site on May 22, 2024. Exploring further, I found a 2024 article entitled "Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases". The article says, "In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes."
In medicine the objective is to develop drugs to control some aspect of endocannabinoid system function. It is far less risky and expensive to reduce arachidonic acid and linoleic acid intake as recommended by these Norwegian animal science researchers. "Chicken meat with reduced concentration of arachidonic acid (AA) and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet...Combining reduction of the intake of AA with enhancement of the intake of oleic acid will, moreover, also be a better strategy for reducing the total extent of in vivo lipid peroxidation, rather than adding more EPA (with 5 double bonds) and DHA (with 6 double bonds) to a diet already over-abundant in arachidonic acid and linoleic acid." (web search - Anna Haug Individual Variation)
A 'John Mandrola arachidonic acid' web search brings up a comment I posted on this site on May 6, 2024.
A 'Vinay Prasad arachidonic acid' web search brought up an article entitled 'Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome'.
I urge you doctors to read 'Omega Balance' by Anthony Hulbert. A 2021 paper he wrote ends with this comment: "... I note that we are only beginning to understand the implications of the balance between omega-3 and omega-6 fats in the human diet. Although most animals have a relatively constant diet, we humans are especially diverse (both between individuals and over time) in the types of food we consume. Over the last half-century, the modern human food chain has emphasised omega-6 and diminished omega-3 intake, largely because of: (i) a shift from animal fats to vegetable oils, (ii) an increase in grain-fed meat and dairy, and (iii) a decline in full-fat dairy products from grass-fed livestock (an important source of omega-3). In the opinion of the current author and others, these diet trends are likely to be responsible for the increased incidence of obesity and other modern epidemics of chronic disease, but that is a story for another time." (web search - Anthony Hulbert The under-appreciated fats of life)
Thank you for sharing your knowledge, inspiring critical appraisal and now giving us subscribers the opportunity to ask you anything!! Questions will come. So great to have this forum for intellectual exchanges, mentoring and CME.
Thank you, Doctors Cifu, Mandrola, and Prasad, for your generosity in sharing your wisdom and insights with us. I particularly love Friday Reflections, more so now that my college senior is intent on going forward with an MD/PhD - I share many of your writings with her in the hopes that it exposes her to the quality and compassion that may be scattershot at best in formal training.
Do you think there is any chance that the medical community will drop its Covid mRNA vaccine booster requirements in the near future? She would rather complete her training without being exposed to the dangers inherent in this vaccine.
I enjoy your thorough evaluations of topics especially your critical evaluations of studies. I would like to know your opinion about Covid vaccines for older healthy individuals who have had Covid and previous vaccines. There is a lot of information about people under 60 and those with co-morbidities. And obviously Covid vaccines for children are a travesty. I am assuming from Dr. Prasad's assessment that Paxlovid is a waste for vaccinated people of all ages . Thank you for your attention. Cecille
I really love your thoughts and also your discussion. I fully accept, that you three and most of the readers and listeners are from the US. But please: consider, that you also have international readers (in my case: Germany): there is not much use for us, if you (Vinay :-)) keep on batteling one of your US Senators thoughts or FDA opinions for the 100th time. It would be much more interesting if you integrate or debate different ways of dealing with health problems as other health systems/countries do it.
Philosophical questions for my three heroes: is it the doctor's job to ration tests and treatments, or to serve the individual patient in front of him or her? Are you more like the patient's attorney or the hospital's? How concerned should you be with "correctly" using your hospital's resources? Should you lean on population statistics in individual cases, rather than the patient's cost-benefit analysis?
I am a Hospitalist and would love to hear you guys deep dive into the issue of anticoagulation with atrial fibrillation. I have maintained that the net benefits are much oversold and god knows there is a lot of money at stake in this area. It’s such a common matter in my workday and no doubt also in the outpatient world. I am confident that there would be a lot of interest if you took this subject on.
I just had to take this opportunity to thank you ALL for ALL that you do!! You three are the DREAM TEAM of doctors, doctors that we all wish we had as our personal doctors. My family and I live in So Cal, and it has been so hard to find doctors who are willing to have conversations about "controversial" topics and choose still to follow the guidelines set by the CDC and the FDA and other three letter organizations. So I thank you all for giving us non-doctors (I'm a physical therapist) insights into your world and for being willing to take the time out of your super busy schedules to share your priceless expertise and wisdom with us. It is a privilege that I truly cherish, and I just wanted to thank you and wish you all the best!
Thank YOU all for all of your informative, entertaining, and relevant insights and observations. I have a question for Vinay. As a retired drug rep, I appreciate you making me uncomfortable. I recommend that all my friends still in the business subscribe and read what you say; they will become better reps if they learn from you.
Your criticisms about lack of OS in oncology trials is noted (has always bugged me). How do you design a trial that gets at clinically meaningful benefit when patients can and do just switch to another drug/trial?
I only had meds for adult acute leukemia, and I think a disease that is so terribly swift lends itself more to an OS trial, but I wonder about solid tumors or slower-moving hematologic malignancies. How do we get OS in MM when the patients have so many options?
And I have given thought to your point about quality of life. My sister has a glio, and I can see there will be a time when no therapy is worth the degraded QoL. I also have a friend who has survived metastatic BC, but she says when it comes back, she will not undergo any treatment--the pain is too great. As a healthy person, I selfishly want to hold on to those I love. You have helped me see things differently. So thank you.
I've been "invited" to participate in a Phase 3 double blind trial of a drug being developed by a major pharma co that is supposed to lower levels of Lipoprotein(a). My Lp(a) is elevated and I qualify for the study. After reading all the posts on here by John and Adam about use and abuse of clinical trials by Big Pharma (esp in oncology!), I'm kind of hesitant. Just wondered what you thought.
I know Dr. Prasad never sees a primary care doctor, let alone a dentist…But for us non-doctors, any advice on how to look for a primary care doc and/or specialist that is a practitioner of EBM? I’m tired of looking through insurance portals and hospital websites looking for a Dr. Cifu.
Medicine has attracted a variety of personalities that are supposed to share common values and traits that lead to being an effective clinician. When I see public discourse and private discourse in my clinical rotations, I see that the more analytic-oriented folk make up the majority of the people interested EBM. People not cut from the same cloth try to avoid it at all costs. The consequence of this is that the people who are most susceptible to not doing skillful EBM are the ones who are also least attracted to learning more about it.
My question is two-fold.
1) Is this a problem worth resolving? Why or why not?
Dr.’s Mandrola, Prasad and Cifu—I enjoy reading your sensible medicine and appreciate this opportunity to present a question. Approximately 25 years ago I had a gastrointestinal reaction to the fish-Sea Bass. It presented with terrible vomiting and diarrhea about 3 hours after eating, lasting 4 hours then I felt fine. I thought it was bad fish but when i again ate Sea Bass the very same thing happened. Also , over the years I had a similar reaction , although not as dramatic, to anything with anchovy paste specifically caesar and green goddess dressing. Fast forward to 2023 I began taking Krill Oil because the statin I was taking was causing my blood sugar to rise. I am a 77 year old , healthy , active, 125 pound female so I blamed the slight rise in blood sugar on the statin. After about 4 months of taking the Krill Oil I developed Atrial fibrillation, I stopped taking it immediately. I only had 3 episodes of A.fibrillation and have not had another one in over a year. I’m curious about the sensitivities to these different fishes and if they might have caused the Afib. I have read studies that Omega 3’s might be causing afib. Thank you so much for considering an answer.
Have you been tested for haemochromatosis? I have recently found out that I have it. I have been informed not to eat sea food as a particular bacteria present in such can have the effect you describe. It may be worth checking your ferritin levels.
I am curious to learn whether you doctors are familiar with endocannabinoid system in general and arachidonic acid research in particular. An 'Adam Cifu arachidonic acid' web search which brought up a comment I posted on this site on May 22, 2024. Exploring further, I found a 2024 article entitled "Transcriptomic Analysis of Arachidonic Acid Pathway Genes Provides Mechanistic Insight into Multi-Organ Inflammatory and Vascular Diseases". The article says, "In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes."
In medicine the objective is to develop drugs to control some aspect of endocannabinoid system function. It is far less risky and expensive to reduce arachidonic acid and linoleic acid intake as recommended by these Norwegian animal science researchers. "Chicken meat with reduced concentration of arachidonic acid (AA) and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet...Combining reduction of the intake of AA with enhancement of the intake of oleic acid will, moreover, also be a better strategy for reducing the total extent of in vivo lipid peroxidation, rather than adding more EPA (with 5 double bonds) and DHA (with 6 double bonds) to a diet already over-abundant in arachidonic acid and linoleic acid." (web search - Anna Haug Individual Variation)
A 'John Mandrola arachidonic acid' web search brings up a comment I posted on this site on May 6, 2024.
A 'Vinay Prasad arachidonic acid' web search brought up an article entitled 'Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome'.
I urge you doctors to read 'Omega Balance' by Anthony Hulbert. A 2021 paper he wrote ends with this comment: "... I note that we are only beginning to understand the implications of the balance between omega-3 and omega-6 fats in the human diet. Although most animals have a relatively constant diet, we humans are especially diverse (both between individuals and over time) in the types of food we consume. Over the last half-century, the modern human food chain has emphasised omega-6 and diminished omega-3 intake, largely because of: (i) a shift from animal fats to vegetable oils, (ii) an increase in grain-fed meat and dairy, and (iii) a decline in full-fat dairy products from grass-fed livestock (an important source of omega-3). In the opinion of the current author and others, these diet trends are likely to be responsible for the increased incidence of obesity and other modern epidemics of chronic disease, but that is a story for another time." (web search - Anthony Hulbert The under-appreciated fats of life)
Thank you for sharing your knowledge, inspiring critical appraisal and now giving us subscribers the opportunity to ask you anything!! Questions will come. So great to have this forum for intellectual exchanges, mentoring and CME.
Thank you, Doctors Cifu, Mandrola, and Prasad, for your generosity in sharing your wisdom and insights with us. I particularly love Friday Reflections, more so now that my college senior is intent on going forward with an MD/PhD - I share many of your writings with her in the hopes that it exposes her to the quality and compassion that may be scattershot at best in formal training.
Do you think there is any chance that the medical community will drop its Covid mRNA vaccine booster requirements in the near future? She would rather complete her training without being exposed to the dangers inherent in this vaccine.
I enjoy your thorough evaluations of topics especially your critical evaluations of studies. I would like to know your opinion about Covid vaccines for older healthy individuals who have had Covid and previous vaccines. There is a lot of information about people under 60 and those with co-morbidities. And obviously Covid vaccines for children are a travesty. I am assuming from Dr. Prasad's assessment that Paxlovid is a waste for vaccinated people of all ages . Thank you for your attention. Cecille
I really love your thoughts and also your discussion. I fully accept, that you three and most of the readers and listeners are from the US. But please: consider, that you also have international readers (in my case: Germany): there is not much use for us, if you (Vinay :-)) keep on batteling one of your US Senators thoughts or FDA opinions for the 100th time. It would be much more interesting if you integrate or debate different ways of dealing with health problems as other health systems/countries do it.
Any thoughts on Direct to Consumer drugs? Do we trust doctors that are associated with the drug companies?
Philosophical questions for my three heroes: is it the doctor's job to ration tests and treatments, or to serve the individual patient in front of him or her? Are you more like the patient's attorney or the hospital's? How concerned should you be with "correctly" using your hospital's resources? Should you lean on population statistics in individual cases, rather than the patient's cost-benefit analysis?
I am a Hospitalist and would love to hear you guys deep dive into the issue of anticoagulation with atrial fibrillation. I have maintained that the net benefits are much oversold and god knows there is a lot of money at stake in this area. It’s such a common matter in my workday and no doubt also in the outpatient world. I am confident that there would be a lot of interest if you took this subject on.
I would be very interested in this one too!
I love SM so much- one of my favorite Substacks. Thanks for your hard work and commitment to critical thinking.
Thanks so much Leslie.
Adam
I just had to take this opportunity to thank you ALL for ALL that you do!! You three are the DREAM TEAM of doctors, doctors that we all wish we had as our personal doctors. My family and I live in So Cal, and it has been so hard to find doctors who are willing to have conversations about "controversial" topics and choose still to follow the guidelines set by the CDC and the FDA and other three letter organizations. So I thank you all for giving us non-doctors (I'm a physical therapist) insights into your world and for being willing to take the time out of your super busy schedules to share your priceless expertise and wisdom with us. It is a privilege that I truly cherish, and I just wanted to thank you and wish you all the best!
Thanks so much for you kind words.
Adam
Thank YOU all for all of your informative, entertaining, and relevant insights and observations. I have a question for Vinay. As a retired drug rep, I appreciate you making me uncomfortable. I recommend that all my friends still in the business subscribe and read what you say; they will become better reps if they learn from you.
Your criticisms about lack of OS in oncology trials is noted (has always bugged me). How do you design a trial that gets at clinically meaningful benefit when patients can and do just switch to another drug/trial?
I only had meds for adult acute leukemia, and I think a disease that is so terribly swift lends itself more to an OS trial, but I wonder about solid tumors or slower-moving hematologic malignancies. How do we get OS in MM when the patients have so many options?
And I have given thought to your point about quality of life. My sister has a glio, and I can see there will be a time when no therapy is worth the degraded QoL. I also have a friend who has survived metastatic BC, but she says when it comes back, she will not undergo any treatment--the pain is too great. As a healthy person, I selfishly want to hold on to those I love. You have helped me see things differently. So thank you.
I've been "invited" to participate in a Phase 3 double blind trial of a drug being developed by a major pharma co that is supposed to lower levels of Lipoprotein(a). My Lp(a) is elevated and I qualify for the study. After reading all the posts on here by John and Adam about use and abuse of clinical trials by Big Pharma (esp in oncology!), I'm kind of hesitant. Just wondered what you thought.
I know Dr. Prasad never sees a primary care doctor, let alone a dentist…But for us non-doctors, any advice on how to look for a primary care doc and/or specialist that is a practitioner of EBM? I’m tired of looking through insurance portals and hospital websites looking for a Dr. Cifu.
Two questions actually.
1. Was Fauci the “right guy?”
2. How might you have handled the opiate epidemic?
To all,
Medicine has attracted a variety of personalities that are supposed to share common values and traits that lead to being an effective clinician. When I see public discourse and private discourse in my clinical rotations, I see that the more analytic-oriented folk make up the majority of the people interested EBM. People not cut from the same cloth try to avoid it at all costs. The consequence of this is that the people who are most susceptible to not doing skillful EBM are the ones who are also least attracted to learning more about it.
My question is two-fold.
1) Is this a problem worth resolving? Why or why not?
2) If it is worth resolving, how would you do it?
Dr.’s Mandrola, Prasad and Cifu—I enjoy reading your sensible medicine and appreciate this opportunity to present a question. Approximately 25 years ago I had a gastrointestinal reaction to the fish-Sea Bass. It presented with terrible vomiting and diarrhea about 3 hours after eating, lasting 4 hours then I felt fine. I thought it was bad fish but when i again ate Sea Bass the very same thing happened. Also , over the years I had a similar reaction , although not as dramatic, to anything with anchovy paste specifically caesar and green goddess dressing. Fast forward to 2023 I began taking Krill Oil because the statin I was taking was causing my blood sugar to rise. I am a 77 year old , healthy , active, 125 pound female so I blamed the slight rise in blood sugar on the statin. After about 4 months of taking the Krill Oil I developed Atrial fibrillation, I stopped taking it immediately. I only had 3 episodes of A.fibrillation and have not had another one in over a year. I’m curious about the sensitivities to these different fishes and if they might have caused the Afib. I have read studies that Omega 3’s might be causing afib. Thank you so much for considering an answer.
Hello.
Have you been tested for haemochromatosis? I have recently found out that I have it. I have been informed not to eat sea food as a particular bacteria present in such can have the effect you describe. It may be worth checking your ferritin levels.
I can eat all other sea food except these particular ones.