I would argue that a skeptical cardiologist also should be skeptical on the premises of more drugs = less CVR!
First, a skeptical should be skeptical of the "LDL hypothesis". To read some who wrote and study the issue, see the work of the canadians James McCormack and colleagues and Therapeutics Initiative. Moreover, LDL less than 80 is already pretty good. Double moreover, IMPROVE-IT (ezetimibe plus statin) wasn't very impressive. The trials on PCSK9i also not.
Second, we should be skeptical on anti-inflammatory drugs for coronary disease. Just in time, the recent (presented 2 weeks ago) new and biggest trial on colchicine until present was negative. JMM appraised it on last TWIC. The other drugs weren't positive on trials. I also don't know convincing date on thr advantage of lowering hs-CRP (again: read/listen to James McCormack, Mike Allan and etc)
I am not disregarding the argument that semaglutide is not a cardiovascular preventive drug by nature, but I just find the arguments presented here very convincing.
PS - I would try to focus on the population, percentage of weight loss and comparison with the same weight loss by other means
"However, I can’t help but view the SELECT trial as cynically engineered to achieve an indication for preventing CV disease in a population that was not being appropriately treated with currently available and much more accessible therapy."
Why would you think that? After all, the pharmaceutical companies don't have a history of manipulating clinical trial designs, regulatory capture of the FDA, and putting profits over people, do they? /s
Insightful interpretation of the data and outline of a strategy to reduce CV events without the GLP-1 RA. I am a firm believer that semaglutide is not the answer for weight loss or reducing CV risk. It’s a quick fix without long term results. It’s already known that compliance on GLPs is poor and the patient will rebound once the drug is discontinued. All that money down the drain and the patient is no better off. Lets stop over-medicalizing patients and let’s provide patients with better access to Primary Care through DPC, nutrition education and counseling, access to free exercise programs and education and find a way to incentivize them to take control of their health.
Dear skeptical cardiologist, your analysis is correct under the classical model of biomedical thinking, which focuses on controlling (to target) signs and symptoms and the idea that syndromes are established diseases.
However, from an alternative perspective, “vascular disease” (macro and microvascular) can be seen as an intermediate pathogenic variable resulting from the metabolic disruption of biological rhythms and artificial exposures on our ancestrally evolved genome—a consequence of the advances of modernity. Recent evidence shows that 9 out of 10 American adults do not have “metabolic health.”
In this context, what Reaven, in 1988, referred to as Syndrome X, is now understood as a set of compensatory homeostatic reactions to counteract the metabolic and inflammatory damage caused by a diet rich (75%) in simple and complex carbohydrates from fruits and plants, along with polyunsaturated fatty acids (PUFAs) from seed oils, with a shortage of vital animal (saturated) fats. Additionally, a sedentary lifestyle, lack of sun exposure, and disruptions in circadian rhythms of sleep, rest, and study compound this situation.
All this metabolic stress on our genome has strained the series of adaptive adjustments and mutations in our biology, among others, the evolutionary achievement since the Paleolithic of insulin resistance and uricase deficiency, which enabled survival during the last glaciation.
This irregular exposure of our genome is exacerbated by an evolutionary congenital deficiency of the enzyme coded in the GULU gene, gulonolactone oxidase, which completes the synthesis of ascorbate. Thus, a humanity in a state of permanent hyperglycemia combined with hypoascorbemia (in the absence of sufficient supplementation) is responsible for collagen disease, the origin of 90% of the modern disease and mortality burden, and of all cardiovascular disease.
In fact, the atheromatous plaque is the body’s response to seal gaps and tears in the endothelial layer due to the loss of subendothelial collagen, preventing the risk posed by systolic pressure on the large blood vessels.
There is credible experimental evidence showing that systolic hypertension and the shortening of apnea time are two sensitive diagnostic tests for mitochondrial dysfunction in cells and tissues subjected to hypoxia and chronic ischemia during the initial histopathological phases of this “pathology” (Syndrome X).
From this perspective, if valid, it would be at the very least illogical to lower levels of blood pressure, glycemia, cholesterol, triglycerides, uric acid, CRP, to “normal” levels with antagonists when these are merely epiphenomena, signals calling for correction of the underlying disease. This explains why GLP-1 receptor agonists are effective, though in the SELECT study they showed an NNT of 66 for the primary outcome.
Dear skeptical cardiologist, if you examine the SELECT study, you will see that all participants had metabolic disease, and the study did not control for the proportion of carbohydrates in the standard diet of these individuals, which was never systematically modified as a target or outcome variable.
In the following essay (Link below), a critical analysis of the evidence and the “unifying” causal theory of Syndrome X, in the context of the “worldwide” standard diet
I agree that the ARR in SELECT is quite small, and vis-a-vis the cost of this agent, the cost-QALY/ICER type cost-effectiveness analyzes (if they ever get done) likely will not be that compelling. It is also unfortunate that, while the result for the composite primary endpoint was positive, the hierarchical analysis failed at the first secondary endpoint, so we have no clear info on what drove the benefit (it isn’t CV death, although it appears to show a trend for reduction in non-fatal MI).
However, I am less bearish than you on these results, insofar as it potentially represents a new pathway for secondary prevention that is separate from LDL and “inflammation”. Admittedly, we don’t yet know the mechanism of benefit of GLP-1 RA’s for reducing ASCVD outcomes, but there is hope it goes beyond simple weight loss (which seems to be the only mechanism for its benefit shown in HFpEF).
I agree, at the bedside, a decision would need to be made on whether “residual risk” would be better addressed with ezetimibe (although as another commenter noted, a very small effect that took 7 years to be demonstrated; benefit driven by non-fatal MI and stroke); PCSK-9 inhibitors (also not cheap; the landmark trials showed benefit in composite primary endpoint likely driven by CV revasc events…in Fourier….while Odyssey Outcomes hierarchical secondary endpoints also failed at first outcome); or colchicine, which failed to show a benefit in CLEAR SYNERGY OASIS 9 presented at TCT, in contradistinction to its prior results in trials like Lodoco 2 or COLCOT. For the reasons you stated, I don’t think Semaglutide should be the default add-on agent by any means. However, I think there is enough there to warrant its consideration in an appropriate subset of patients, particularly among the cohort will significantly increased BMI.
I started to read this article because I had hope to LEARN something more about Ozempic, detailed FACTS about its BIOCHEMISTRY action on the human body. But this post does NOT INFORM ON ANYTHING in that direction, instead it jumps between drugs trials and apparent patients outcomes, without a SINGLE MENTION about what these patients actually eat!!! MD's are until these days a MIDDLEMAN between corrupt DRUGS- AND FOOD INDUSTRIES!!!! Are you guys realize that??? Can you finally start learning more and look really DEEPER into the HUMAN BODY as a self healing WONDER and NOT AS A COLLECTION BAG of your prescriptions???? Few writers banned me here on this wonderful buS-Kcats platform, so please go ahead and cancel me for these remarks;)
It doesn't require a great deal of skepticism to question the significance of differences of a few percentage points in absolute risk reduction of composite end points in ASCVD trials. The same statement can be applied to statin therapy or any other manipulation of lipoprotein levels, anti-inflammatory meds, or any other "risk factor". The blind alley that is the risk factor paradigm for ASCVD has gotten us nowhere over the past 70 years.
Drugs are NEVER the answer. Healthier living always is as the body is eager to repair the damage done to it. How the heck do you think humanity survived for thousands of years without big pharma drugs living in conditions often more horrendous than we see today?
While I often agree with ACP, I disagree with almost this entire piece. I don't have the time to go through all the issues in detail, but I want to highlight just one: the claim that we would get "more bang for our buck" with giving these patients ezetimibe. I wonder what evidence ACP has to justify this claim.
The absolute benefit at three years in SELECT on MACE was 1.5% and on all-cause mortality was 0.9%. Ezetimibe added to inadequate statin therapy in an acute ACS population (IMPROVE-IT) decreased MACE by 2% at seven years and had no effect on mortality.
So, semaglutide in a shorter time period in a much healthier population (acute ACS as in IMPROVE-IT is the easiest place to show intervention benefits) had far more impressive benefits. I know of no evidence that adding ezetimibe to appropriate statin therapy improves mortality in any population, or even that it improves MACE.
Don’t underestimate the value of weight loss in people. Period. You could do all those things you could suggest and semaglutide — even from these data — would still reduce risk even further. You haven’t given a compelling argument for why it shouldn’t be used. One point good point: it should be cheaper for Americans.
Cost utility analysis would also take into account number of pills taken per day (versus one shot), and the ADEs associated with polypharmacy--and those that go along with pushing lower BP. In addition, patients value lower BMI (with improved metabolic parameters) versus improved metabolic parameters with pills alone. Cost of GLPs is the rate limiter, as you point out. We can only speculate without the RCTs, but the calculous is not as straightforward as relay.
Here's a thought. Though not widely publicized, there is a dietary approach that can dramatically reduce risk of heart attack if adopted early enough. Steve Blechman explains why it works. "The Mediterranean diet is low in arachidonic acid and rich in healthy fats such as monounsaturated fats found in extra-virgin olive oil (EVOO), nuts and omega-3 fatty acids from fish, which has been shown to lower the risk of inflammation, heart disease, cancer, diabetes and obesity, and other degenerative diseases." https://advancedmolecularlabs.com/blogs/news/new-red-meat-study-controversy
Researchers have known about the arachidonic acid problem for a long time. (1996) "Excessive signaling of arachidonic acid (AA) metabolites has been associated with various chronic degenerative or autoimmune diseases, and intervention with the metabolism of AA is widely employed therapeutically in these afflictions. In essence, AA is the most biologically active unsaturated fatty acid in higher animals. Its concentration in membranes and its magnitude of effects depend on its amount, or that of its precursors and analogues, in the diet. The tendency of the field of nutrition to ignore the role of dietary AA will optimistically be reversed in the future." The article also said, "The underlying rationale for this symposium is that dietary AA is perhaps the single most important nutritional determinant in regulating AA levels in Americans. This may ultimately account in part for the striking differences in chronic diseases between strict vegetarians and the bulk of the omnivorous population." https://pubmed.ncbi.nlm.nih.gov/8642436/
Purdue University researchers have noted that “Poultry meats, in particular chicken, have high rates of consumption globally. Poultry is the most consumed type of meat in the United States (US), with chicken being the most common type of poultry consumed. The amounts of chicken and total poultry consumed in the US have more than tripled over the last six decades… Limited evidence from randomized controlled trials indicates the consumption of lean unprocessed chicken as a primary dietary protein source has either beneficial or neutral effects on body weight and body composition and risk factors for CVD and T2DM. Apparently, zero randomized controlled feeding trials have specifically assessed the effects of consuming processed chicken/poultry on these health outcomes.” https://pmc.ncbi.nlm.nih.gov/articles/PMC10459134/
That article was published in 2023. In 2010 Norwegian animal science researchers wrote, "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.” It was also noted that “The degree of fatty acid unsaturation of mitochondrial membrane lipids has been found to be one of those biochemical parameters that are most strongly correlated with longevity, when different species of mammals and birds are compared, with a low degree of fatty unsaturation being correlated with less lipid peroxidation and a longer normal life-span." https://pmc.ncbi.nlm.nih.gov/articles/PMC2875212/
What I find strange is that in articles about the new weight loss and diabetes drugs there is no mention of the endocannabinoid system. Excessive arachidonic acid intake coupled with omega-3 deficiency is what puts the endocannabinoid system out of balance. For example, "Endocannabinoids and their G-protein coupled receptors (GPCR) are a current research focus in the area of obesity due to the system's role in food intake and glucose and lipid metabolism. Importantly, overweight and obese individuals often have higher circulating levels of the arachidonic acid-derived endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) and an altered pattern of receptor expression. Consequently, this leads to an increase in orexigenic stimuli, changes in fatty acid synthesis, insulin sensitivity, and glucose utilisation, with preferential energy storage in adipose tissue. As endocannabinoids are products of dietary fats, modification of dietary intake may modulate their levels, with eicosapentaenoic and docosahexaenoic acid based endocannabinoids being able to displace arachidonic acid from cell membranes, reducing AEA and 2-AG production." https://pubmed.ncbi.nlm.nih.gov/23762050/
The authors of the above 2013 article made a mistake. They should have said this: "Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation. Thus, the best strategy for dampening prostanoid overproduction in disease situations would be to reduce the intake of AA, or reduce the intake of AA at the same time as the total intake of competing fatty acids (including oleic acid) is enhanced, rather than enhancing intakes of EPA and DHA only. Enhancement of membrane concentrations of EPA and DHA will not be as efficient as a similar decrease in the AA concentration for avoiding prostanoid overproduction." https://pmc.ncbi.nlm.nih.gov/articles/PMC2875212/
Clearly, it is much less expensive to reduce arachidonic acid (meat) intake to improve insulin sensitivity and fix a deranged appetite than to take GLP-1 agonists.
Yes but many patients would rather eat ribeyes and cake and take a pill/ shot so…….. we work with what people are willing to do to get them as healthy as we can
What these people need is another pill for their LDL-cholesterol, colchicine for their elevated hs-CRP, another pill or two to bring down their systolic bp, and screening tests for elevated apo-b and Lp(a). Then follow-up blood tests and office visits for the rest of their lives. Very good for the preventive cardiologist, but really how good for the patient? Do you really “eliminate the residual risk” with this assault? Skeptical, I’m worried that you’ve drunk the Kool-aid.
Interesting that all the talk of “significant “ event reduction translates into a small ARR irrespective of the intervention ( reducing LDL/other lipoprotein fragments/ adding more cholesterol modifying meds). We need better approaches that don’t just touch on marginal benefit.
I would argue that a skeptical cardiologist also should be skeptical on the premises of more drugs = less CVR!
First, a skeptical should be skeptical of the "LDL hypothesis". To read some who wrote and study the issue, see the work of the canadians James McCormack and colleagues and Therapeutics Initiative. Moreover, LDL less than 80 is already pretty good. Double moreover, IMPROVE-IT (ezetimibe plus statin) wasn't very impressive. The trials on PCSK9i also not.
Second, we should be skeptical on anti-inflammatory drugs for coronary disease. Just in time, the recent (presented 2 weeks ago) new and biggest trial on colchicine until present was negative. JMM appraised it on last TWIC. The other drugs weren't positive on trials. I also don't know convincing date on thr advantage of lowering hs-CRP (again: read/listen to James McCormack, Mike Allan and etc)
I am not disregarding the argument that semaglutide is not a cardiovascular preventive drug by nature, but I just find the arguments presented here very convincing.
PS - I would try to focus on the population, percentage of weight loss and comparison with the same weight loss by other means
"However, I can’t help but view the SELECT trial as cynically engineered to achieve an indication for preventing CV disease in a population that was not being appropriately treated with currently available and much more accessible therapy."
Why would you think that? After all, the pharmaceutical companies don't have a history of manipulating clinical trial designs, regulatory capture of the FDA, and putting profits over people, do they? /s
Insightful interpretation of the data and outline of a strategy to reduce CV events without the GLP-1 RA. I am a firm believer that semaglutide is not the answer for weight loss or reducing CV risk. It’s a quick fix without long term results. It’s already known that compliance on GLPs is poor and the patient will rebound once the drug is discontinued. All that money down the drain and the patient is no better off. Lets stop over-medicalizing patients and let’s provide patients with better access to Primary Care through DPC, nutrition education and counseling, access to free exercise programs and education and find a way to incentivize them to take control of their health.
Dear skeptical cardiologist, your analysis is correct under the classical model of biomedical thinking, which focuses on controlling (to target) signs and symptoms and the idea that syndromes are established diseases.
However, from an alternative perspective, “vascular disease” (macro and microvascular) can be seen as an intermediate pathogenic variable resulting from the metabolic disruption of biological rhythms and artificial exposures on our ancestrally evolved genome—a consequence of the advances of modernity. Recent evidence shows that 9 out of 10 American adults do not have “metabolic health.”
In this context, what Reaven, in 1988, referred to as Syndrome X, is now understood as a set of compensatory homeostatic reactions to counteract the metabolic and inflammatory damage caused by a diet rich (75%) in simple and complex carbohydrates from fruits and plants, along with polyunsaturated fatty acids (PUFAs) from seed oils, with a shortage of vital animal (saturated) fats. Additionally, a sedentary lifestyle, lack of sun exposure, and disruptions in circadian rhythms of sleep, rest, and study compound this situation.
All this metabolic stress on our genome has strained the series of adaptive adjustments and mutations in our biology, among others, the evolutionary achievement since the Paleolithic of insulin resistance and uricase deficiency, which enabled survival during the last glaciation.
This irregular exposure of our genome is exacerbated by an evolutionary congenital deficiency of the enzyme coded in the GULU gene, gulonolactone oxidase, which completes the synthesis of ascorbate. Thus, a humanity in a state of permanent hyperglycemia combined with hypoascorbemia (in the absence of sufficient supplementation) is responsible for collagen disease, the origin of 90% of the modern disease and mortality burden, and of all cardiovascular disease.
In fact, the atheromatous plaque is the body’s response to seal gaps and tears in the endothelial layer due to the loss of subendothelial collagen, preventing the risk posed by systolic pressure on the large blood vessels.
There is credible experimental evidence showing that systolic hypertension and the shortening of apnea time are two sensitive diagnostic tests for mitochondrial dysfunction in cells and tissues subjected to hypoxia and chronic ischemia during the initial histopathological phases of this “pathology” (Syndrome X).
From this perspective, if valid, it would be at the very least illogical to lower levels of blood pressure, glycemia, cholesterol, triglycerides, uric acid, CRP, to “normal” levels with antagonists when these are merely epiphenomena, signals calling for correction of the underlying disease. This explains why GLP-1 receptor agonists are effective, though in the SELECT study they showed an NNT of 66 for the primary outcome.
Dear skeptical cardiologist, if you examine the SELECT study, you will see that all participants had metabolic disease, and the study did not control for the proportion of carbohydrates in the standard diet of these individuals, which was never systematically modified as a target or outcome variable.
In the following essay (Link below), a critical analysis of the evidence and the “unifying” causal theory of Syndrome X, in the context of the “worldwide” standard diet
https://bit.ly/EcheverryJ_2024_Falsehod_origin_diabesity_pandemic
Best regards
JAIRO ECHEVERRY-RAAD MD
Very interesting and thought provoking piece.
I agree that the ARR in SELECT is quite small, and vis-a-vis the cost of this agent, the cost-QALY/ICER type cost-effectiveness analyzes (if they ever get done) likely will not be that compelling. It is also unfortunate that, while the result for the composite primary endpoint was positive, the hierarchical analysis failed at the first secondary endpoint, so we have no clear info on what drove the benefit (it isn’t CV death, although it appears to show a trend for reduction in non-fatal MI).
However, I am less bearish than you on these results, insofar as it potentially represents a new pathway for secondary prevention that is separate from LDL and “inflammation”. Admittedly, we don’t yet know the mechanism of benefit of GLP-1 RA’s for reducing ASCVD outcomes, but there is hope it goes beyond simple weight loss (which seems to be the only mechanism for its benefit shown in HFpEF).
I agree, at the bedside, a decision would need to be made on whether “residual risk” would be better addressed with ezetimibe (although as another commenter noted, a very small effect that took 7 years to be demonstrated; benefit driven by non-fatal MI and stroke); PCSK-9 inhibitors (also not cheap; the landmark trials showed benefit in composite primary endpoint likely driven by CV revasc events…in Fourier….while Odyssey Outcomes hierarchical secondary endpoints also failed at first outcome); or colchicine, which failed to show a benefit in CLEAR SYNERGY OASIS 9 presented at TCT, in contradistinction to its prior results in trials like Lodoco 2 or COLCOT. For the reasons you stated, I don’t think Semaglutide should be the default add-on agent by any means. However, I think there is enough there to warrant its consideration in an appropriate subset of patients, particularly among the cohort will significantly increased BMI.
Not nearly skeptical enough , cardiologist
FAERS Deaths from Semaglutide, Wegovy. Tirzepatide and the like are rising.
https://geoffpain.substack.com/p/semaglutide-vs-tirzepatide-for-weight
I started to read this article because I had hope to LEARN something more about Ozempic, detailed FACTS about its BIOCHEMISTRY action on the human body. But this post does NOT INFORM ON ANYTHING in that direction, instead it jumps between drugs trials and apparent patients outcomes, without a SINGLE MENTION about what these patients actually eat!!! MD's are until these days a MIDDLEMAN between corrupt DRUGS- AND FOOD INDUSTRIES!!!! Are you guys realize that??? Can you finally start learning more and look really DEEPER into the HUMAN BODY as a self healing WONDER and NOT AS A COLLECTION BAG of your prescriptions???? Few writers banned me here on this wonderful buS-Kcats platform, so please go ahead and cancel me for these remarks;)
It doesn't require a great deal of skepticism to question the significance of differences of a few percentage points in absolute risk reduction of composite end points in ASCVD trials. The same statement can be applied to statin therapy or any other manipulation of lipoprotein levels, anti-inflammatory meds, or any other "risk factor". The blind alley that is the risk factor paradigm for ASCVD has gotten us nowhere over the past 70 years.
Drugs are NEVER the answer. Healthier living always is as the body is eager to repair the damage done to it. How the heck do you think humanity survived for thousands of years without big pharma drugs living in conditions often more horrendous than we see today?
While I often agree with ACP, I disagree with almost this entire piece. I don't have the time to go through all the issues in detail, but I want to highlight just one: the claim that we would get "more bang for our buck" with giving these patients ezetimibe. I wonder what evidence ACP has to justify this claim.
The absolute benefit at three years in SELECT on MACE was 1.5% and on all-cause mortality was 0.9%. Ezetimibe added to inadequate statin therapy in an acute ACS population (IMPROVE-IT) decreased MACE by 2% at seven years and had no effect on mortality.
So, semaglutide in a shorter time period in a much healthier population (acute ACS as in IMPROVE-IT is the easiest place to show intervention benefits) had far more impressive benefits. I know of no evidence that adding ezetimibe to appropriate statin therapy improves mortality in any population, or even that it improves MACE.
Thoughts?
Don’t underestimate the value of weight loss in people. Period. You could do all those things you could suggest and semaglutide — even from these data — would still reduce risk even further. You haven’t given a compelling argument for why it shouldn’t be used. One point good point: it should be cheaper for Americans.
Cost utility analysis would also take into account number of pills taken per day (versus one shot), and the ADEs associated with polypharmacy--and those that go along with pushing lower BP. In addition, patients value lower BMI (with improved metabolic parameters) versus improved metabolic parameters with pills alone. Cost of GLPs is the rate limiter, as you point out. We can only speculate without the RCTs, but the calculous is not as straightforward as relay.
Here's a thought. Though not widely publicized, there is a dietary approach that can dramatically reduce risk of heart attack if adopted early enough. Steve Blechman explains why it works. "The Mediterranean diet is low in arachidonic acid and rich in healthy fats such as monounsaturated fats found in extra-virgin olive oil (EVOO), nuts and omega-3 fatty acids from fish, which has been shown to lower the risk of inflammation, heart disease, cancer, diabetes and obesity, and other degenerative diseases." https://advancedmolecularlabs.com/blogs/news/new-red-meat-study-controversy
Researchers have known about the arachidonic acid problem for a long time. (1996) "Excessive signaling of arachidonic acid (AA) metabolites has been associated with various chronic degenerative or autoimmune diseases, and intervention with the metabolism of AA is widely employed therapeutically in these afflictions. In essence, AA is the most biologically active unsaturated fatty acid in higher animals. Its concentration in membranes and its magnitude of effects depend on its amount, or that of its precursors and analogues, in the diet. The tendency of the field of nutrition to ignore the role of dietary AA will optimistically be reversed in the future." The article also said, "The underlying rationale for this symposium is that dietary AA is perhaps the single most important nutritional determinant in regulating AA levels in Americans. This may ultimately account in part for the striking differences in chronic diseases between strict vegetarians and the bulk of the omnivorous population." https://pubmed.ncbi.nlm.nih.gov/8642436/
Purdue University researchers have noted that “Poultry meats, in particular chicken, have high rates of consumption globally. Poultry is the most consumed type of meat in the United States (US), with chicken being the most common type of poultry consumed. The amounts of chicken and total poultry consumed in the US have more than tripled over the last six decades… Limited evidence from randomized controlled trials indicates the consumption of lean unprocessed chicken as a primary dietary protein source has either beneficial or neutral effects on body weight and body composition and risk factors for CVD and T2DM. Apparently, zero randomized controlled feeding trials have specifically assessed the effects of consuming processed chicken/poultry on these health outcomes.” https://pmc.ncbi.nlm.nih.gov/articles/PMC10459134/
That article was published in 2023. In 2010 Norwegian animal science researchers wrote, "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.” It was also noted that “The degree of fatty acid unsaturation of mitochondrial membrane lipids has been found to be one of those biochemical parameters that are most strongly correlated with longevity, when different species of mammals and birds are compared, with a low degree of fatty unsaturation being correlated with less lipid peroxidation and a longer normal life-span." https://pmc.ncbi.nlm.nih.gov/articles/PMC2875212/
What I find strange is that in articles about the new weight loss and diabetes drugs there is no mention of the endocannabinoid system. Excessive arachidonic acid intake coupled with omega-3 deficiency is what puts the endocannabinoid system out of balance. For example, "Endocannabinoids and their G-protein coupled receptors (GPCR) are a current research focus in the area of obesity due to the system's role in food intake and glucose and lipid metabolism. Importantly, overweight and obese individuals often have higher circulating levels of the arachidonic acid-derived endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) and an altered pattern of receptor expression. Consequently, this leads to an increase in orexigenic stimuli, changes in fatty acid synthesis, insulin sensitivity, and glucose utilisation, with preferential energy storage in adipose tissue. As endocannabinoids are products of dietary fats, modification of dietary intake may modulate their levels, with eicosapentaenoic and docosahexaenoic acid based endocannabinoids being able to displace arachidonic acid from cell membranes, reducing AEA and 2-AG production." https://pubmed.ncbi.nlm.nih.gov/23762050/
The authors of the above 2013 article made a mistake. They should have said this: "Because arachidonic acid (AA) competes with EPA and DHA as well as with LA, ALA and oleic acid for incorporation in membrane lipids at the same positions, all these fatty acids are important for controlling the AA concentration in membrane lipids, which in turn determines how much AA can be liberated and become available for prostaglandin biosynthesis following phospholipase activation. Thus, the best strategy for dampening prostanoid overproduction in disease situations would be to reduce the intake of AA, or reduce the intake of AA at the same time as the total intake of competing fatty acids (including oleic acid) is enhanced, rather than enhancing intakes of EPA and DHA only. Enhancement of membrane concentrations of EPA and DHA will not be as efficient as a similar decrease in the AA concentration for avoiding prostanoid overproduction." https://pmc.ncbi.nlm.nih.gov/articles/PMC2875212/
Clearly, it is much less expensive to reduce arachidonic acid (meat) intake to improve insulin sensitivity and fix a deranged appetite than to take GLP-1 agonists.
Yes but many patients would rather eat ribeyes and cake and take a pill/ shot so…….. we work with what people are willing to do to get them as healthy as we can
What these people need is another pill for their LDL-cholesterol, colchicine for their elevated hs-CRP, another pill or two to bring down their systolic bp, and screening tests for elevated apo-b and Lp(a). Then follow-up blood tests and office visits for the rest of their lives. Very good for the preventive cardiologist, but really how good for the patient? Do you really “eliminate the residual risk” with this assault? Skeptical, I’m worried that you’ve drunk the Kool-aid.
Interesting that all the talk of “significant “ event reduction translates into a small ARR irrespective of the intervention ( reducing LDL/other lipoprotein fragments/ adding more cholesterol modifying meds). We need better approaches that don’t just touch on marginal benefit.