This is a lengthy, complicated comment. The Basic idea is that excessive arachidonic acid intake over-activates the endocannabinoid system deranging appetite and causing insulin resistance. The modern weight loss drugs are molecules that unblock receptor sites thus reversing the action of endocannabinoids derived from arachidonic acid molecules residing in cell membranes.
That said, a great big yes for number 2. Biomedical research consistently emphasizes developing treatments over discovering underlying causes. That is why the global obesity/diabetes epidemic exists and persists.
Arachidonic acid research. (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/
AI (artificial Intelligence) Overview: "Arachidonic acid (AA) is a crucial fatty acid that plays a pivotal role in various physiological processes within the body, primarily acting as a precursor for the synthesis of bioactive molecules called eicosanoids, which are involved in inflammation, immune response, blood clotting, and pain perception; however, due to its potential to promote inflammation when present in excess, maintaining a balanced level of arachidonic acid is critical for optimal health."
Animal science research perspectives: (2010) "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." https://pmc.ncbi.nlm.nih.gov/articles/PMC2875212/
In a 2011 article entitled 'Animal products, diseases and drugs: a plea for better integration between agricultural sciences, human nutrition and human pharmacology' the authors wrote, " Even though the underlying biochemical mechanisms have been thoroughly studied for more than 30 years, neither the agricultural sector nor medical practitioners have shown much interest in making practical use of the abundant high-quality research data now available." https://pmc.ncbi.nlm.nih.gov/articles/PMC3031257/
This 2013 narrative contains two mistakes. Can you spot them? "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. Similarly, oleoyl ethanolamide, a product of oleic acid, induces satiety, decreases circulating fatty acid concentrations, increases the capacity for β -oxidation, and is capable of inhibiting the action of AEA and 2-AG in adipose tissue. Thus, understanding how dietary fats alter endocannabinoid system activity is a pertinent area of research due to public health messages promoting a shift towards plant-derived fats, which are rich sources of AEA and 2-AG precursor fatty acids, possibly encouraging excessive energy intake and weight gain." https://pmc.ncbi.nlm.nih.gov/articles/PMC3677644/
The first mistake is in this sentence: "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." Removing 'based endocannabinoids' corrects the sentence. Only unsaturated fatty acids, not endocannabinoids, can displace arachidonic acid from cell membranes.
The other mistake is in this sentence: "Thus, understanding how dietary fats alter endocannabinoid system activity is a pertinent area of research due to public health messages promoting a shift towards plant-derived fats, which are rich sources of AEA and 2-AG precursor fatty acids, possibly encouraging excessive energy intake and weight gain." Plants contain linoleic acid, the precursor to arachidonic acid which is the only fatty acid precursor for AEA and 2-AG endocannabinoids.
In a 2018 article these same researchers wrote, "Linoleic acid (LA) is the precursor of the two main endocannabinoids, anandamide (AEA) and 2-arachidonyl glycerol (2-AG), both of which promote hedonic food intake and adipose tissue energy storage. Additionally, the endocannabinoid system is upregulated in obesity, which may further perpetuate excessive energy intake. The importance of LA in the postprandial state is not only due to its potential to modulate hunger and satiety, it is also the precursor of arachidonic acid, which can be converted to several different inflammatory mediators." https://pmc.ncbi.nlm.nih.gov/articles/PMC6213143/
As previously noted, linoleic acid is not a precursor for AEA and 2-AG endocannabinoids. That would be arachidonic acid. Linoleic acid does have potential to "modulate hunger and satiety" by displacing arachidonic acid from cell membranes. "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/
Note that prostanoids are endocannabinoids synthesized from arachidonic acid. Thus, AEA and 2-AG are prostanoids.
I think these suggestions point in the right direction.
What I would like to see is a mandate that the results of NIH-funded research be made freely available to the public who paid for them, which would send a heck of a shock through the sclerotic science journal industry.
And the fence around the main NIH campus should be taken down. Openness should be the new norm. The fence was put up after 9/11 due to concerns about some research having bioterrorism concerns (as this was explained to me by someone who worked there), but I think any research that really requires that level of protection should probably be done elsewhere in the first place.
Thank you for your piece. Would add that the review process for proposals needs to be faster and more transparent, with summary statements sent to investigators in time for them to resubmit in a timely manner.
Many good proposals. Unfortunately, attempts to reform government agencies have a zero success rate. Bureaucracies and bureaucrats are hard to get at and they have built many self-protective mechanisms into the system. Policy changes can be undone in an instant with the next election. The only real solution is to abolish the entire agency or department. "Public health" is a collectivist fiction and should be eliminated at all levels---federal, state, and local.
Agree completely. Here's more on point 8. "Bar all institute directors from participation in public health policy creation or advocacy.".
There are no elected positions in any of the PH agencies. Hence, accountability is only an indirect path through the president. The result was that Fauci, Collins, CDC Directors, etal, can make unjust pronouncements of enormous impact on our lives, arbitrarily and with impunity. To start a long list, think school and business closures, the six-foot distancing rule, masking and vaccine mandates.
Technically, these pronouncements mostly don't have a statutory basis. This falls to state public health agencies who have actual authority on most PH rules and enforcement. And in some cases, the president issued executive orders.
Hence, Fauci can later claim "I never closed any schools". https://fee.org/articles/fauci-claims-he-had-nothing-to-do-with-school-closures-his-own-statements-suggest-otherwise/ And he admitted that the six foot rule "sort of just appeared". (Unfortunately, based on the commerce clause of the constitution, the CDC has authority to regulate interstate and international travel. However, they still can enforce arbitrary rules based on flimsy science while maintaining impunity.)
Even so, Fauci knows full and well that nearly every state health agency feels obligated to follow his pronouncements. Cautious state health agency bureaucrats readily fall in line to avoid the perceived threat of being sued (e.g. by the teacher's union) or the butt of bad publicity, etc. De Santis was an outlier who understood that Fauci's pronouncements could be defied, because the states are the ones who create actual PH policy. He and the Florida Surgeon General Joseph Ladapo maintained common sense policies during covid to the benefit of Florida's schoolchildren and many others.
Fauci's and the CDC's activities during covid are a convincing argument of the evils of authoritarian deep state bureaucrats. Like venomous serpents, they need to be defanged.
This is a lengthy, complicated comment. The Basic idea is that excessive arachidonic acid intake over-activates the endocannabinoid system deranging appetite and causing insulin resistance. The modern weight loss drugs are molecules that unblock receptor sites thus reversing the action of endocannabinoids derived from arachidonic acid molecules residing in cell membranes.
That said, a great big yes for number 2. Biomedical research consistently emphasizes developing treatments over discovering underlying causes. That is why the global obesity/diabetes epidemic exists and persists.
Cannabis researchers: (2023) "With obesity and metabolic-related diseases on the rise, the endocannabinoid system may be a therapeutic target." https://www.endocannabinoidmedicine.com/features/an-integrative-approach-to-treating-obesity-metabolic-dysfunction-and-eating-disorders-via-the-endocannabinoid-system/
Arachidonic acid research. (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/
AI (artificial Intelligence) Overview: "Arachidonic acid (AA) is a crucial fatty acid that plays a pivotal role in various physiological processes within the body, primarily acting as a precursor for the synthesis of bioactive molecules called eicosanoids, which are involved in inflammation, immune response, blood clotting, and pain perception; however, due to its potential to promote inflammation when present in excess, maintaining a balanced level of arachidonic acid is critical for optimal health."
Animal science research perspectives: (2010) "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." https://pmc.ncbi.nlm.nih.gov/articles/PMC2875212/
In a 2011 article entitled 'Animal products, diseases and drugs: a plea for better integration between agricultural sciences, human nutrition and human pharmacology' the authors wrote, " Even though the underlying biochemical mechanisms have been thoroughly studied for more than 30 years, neither the agricultural sector nor medical practitioners have shown much interest in making practical use of the abundant high-quality research data now available." https://pmc.ncbi.nlm.nih.gov/articles/PMC3031257/
This 2013 narrative contains two mistakes. Can you spot them? "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. Similarly, oleoyl ethanolamide, a product of oleic acid, induces satiety, decreases circulating fatty acid concentrations, increases the capacity for β -oxidation, and is capable of inhibiting the action of AEA and 2-AG in adipose tissue. Thus, understanding how dietary fats alter endocannabinoid system activity is a pertinent area of research due to public health messages promoting a shift towards plant-derived fats, which are rich sources of AEA and 2-AG precursor fatty acids, possibly encouraging excessive energy intake and weight gain." https://pmc.ncbi.nlm.nih.gov/articles/PMC3677644/
The first mistake is in this sentence: "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." Removing 'based endocannabinoids' corrects the sentence. Only unsaturated fatty acids, not endocannabinoids, can displace arachidonic acid from cell membranes.
The other mistake is in this sentence: "Thus, understanding how dietary fats alter endocannabinoid system activity is a pertinent area of research due to public health messages promoting a shift towards plant-derived fats, which are rich sources of AEA and 2-AG precursor fatty acids, possibly encouraging excessive energy intake and weight gain." Plants contain linoleic acid, the precursor to arachidonic acid which is the only fatty acid precursor for AEA and 2-AG endocannabinoids.
In a 2018 article these same researchers wrote, "Linoleic acid (LA) is the precursor of the two main endocannabinoids, anandamide (AEA) and 2-arachidonyl glycerol (2-AG), both of which promote hedonic food intake and adipose tissue energy storage. Additionally, the endocannabinoid system is upregulated in obesity, which may further perpetuate excessive energy intake. The importance of LA in the postprandial state is not only due to its potential to modulate hunger and satiety, it is also the precursor of arachidonic acid, which can be converted to several different inflammatory mediators." https://pmc.ncbi.nlm.nih.gov/articles/PMC6213143/
As previously noted, linoleic acid is not a precursor for AEA and 2-AG endocannabinoids. That would be arachidonic acid. Linoleic acid does have potential to "modulate hunger and satiety" by displacing arachidonic acid from cell membranes. "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/
Note that prostanoids are endocannabinoids synthesized from arachidonic acid. Thus, AEA and 2-AG are prostanoids.
I think these suggestions point in the right direction.
What I would like to see is a mandate that the results of NIH-funded research be made freely available to the public who paid for them, which would send a heck of a shock through the sclerotic science journal industry.
And the fence around the main NIH campus should be taken down. Openness should be the new norm. The fence was put up after 9/11 due to concerns about some research having bioterrorism concerns (as this was explained to me by someone who worked there), but I think any research that really requires that level of protection should probably be done elsewhere in the first place.
All data and information used and/or developed by the NIH should be posted online daily. It's the public's money so it's the public's information.
Thank you for your piece. Would add that the review process for proposals needs to be faster and more transparent, with summary statements sent to investigators in time for them to resubmit in a timely manner.
You forgot step 0. Fire 10,000 of them. As you were....carry on!
Excellent! Agree with all of this. Thank you for such well thought-out analysis and suggestions.
Many good proposals. Unfortunately, attempts to reform government agencies have a zero success rate. Bureaucracies and bureaucrats are hard to get at and they have built many self-protective mechanisms into the system. Policy changes can be undone in an instant with the next election. The only real solution is to abolish the entire agency or department. "Public health" is a collectivist fiction and should be eliminated at all levels---federal, state, and local.
Great piece. Keep them coming.
I think this is a great, common sense start.
Well thought out and concise. It’ll never work in the current gov’t climate though, will it?
We can hope! Committed reformers are coming into government and the public wants more accountability.
Agree completely. Here's more on point 8. "Bar all institute directors from participation in public health policy creation or advocacy.".
There are no elected positions in any of the PH agencies. Hence, accountability is only an indirect path through the president. The result was that Fauci, Collins, CDC Directors, etal, can make unjust pronouncements of enormous impact on our lives, arbitrarily and with impunity. To start a long list, think school and business closures, the six-foot distancing rule, masking and vaccine mandates.
Technically, these pronouncements mostly don't have a statutory basis. This falls to state public health agencies who have actual authority on most PH rules and enforcement. And in some cases, the president issued executive orders.
Hence, Fauci can later claim "I never closed any schools". https://fee.org/articles/fauci-claims-he-had-nothing-to-do-with-school-closures-his-own-statements-suggest-otherwise/ And he admitted that the six foot rule "sort of just appeared". (Unfortunately, based on the commerce clause of the constitution, the CDC has authority to regulate interstate and international travel. However, they still can enforce arbitrary rules based on flimsy science while maintaining impunity.)
Even so, Fauci knows full and well that nearly every state health agency feels obligated to follow his pronouncements. Cautious state health agency bureaucrats readily fall in line to avoid the perceived threat of being sued (e.g. by the teacher's union) or the butt of bad publicity, etc. De Santis was an outlier who understood that Fauci's pronouncements could be defied, because the states are the ones who create actual PH policy. He and the Florida Surgeon General Joseph Ladapo maintained common sense policies during covid to the benefit of Florida's schoolchildren and many others.
Fauci's and the CDC's activities during covid are a convincing argument of the evils of authoritarian deep state bureaucrats. Like venomous serpents, they need to be defanged.
I vote for 1,2 and 8
Yes please!
With the exception of #7 (quibbles here), these are excellent suggestions. I also agree that Dr Bhattacharya would be an excellent choice.
YES!!!!!!
1. Yes 2. Yes 3. Ye$$$$ 4. Yes 5. Yes 6. Yes 7. Yes 8. Yes 9. Yes 10. Yes
And Yes! to Dr. Jay Bhattacharya!