For heaven’s sake, if you want to,lose weight stop eating crap. And if you need to control your blood sugar/glucose levels try berberine and milk thistle. Works better than metformin with fewer side effects.
May 5, 2023·edited May 5, 2023Liked by Modern Discontent
I would give these a hard pass. There is a consequence to throwing anything out of balance.
They promote systemic upregulation of proinflammatory and oncogenic & autoimmune related interleukin 6 (il-6).
Il-1 is also oncogenic.
It's also one of the reasons why cancer patients waste away. Yeah.
***
Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6
(2013)
...Glucagon-like peptide 1 (GLP-1), produced in the intestine and the brain, can stimulate insulin secretion from the pancreas and alleviate type 2 diabetes. The cytokine interleukin-6 (IL-6) may enhance insulin secretion from β-cells by stimulating peripheral GLP-1 production. GLP-1 and its analogs also reduce food intake and body weight, clinically beneficial actions that are likely exerted at the level of the CNS, but otherwise are poorly understood. The cytokines IL-6 and interleukin 1β (IL-1β) may exert an anti-obesity effect in the CNS during health. Here we found that central injection of a clinically used GLP-1 receptor agonist, exendin-4, potently increased the expression of IL-6 in the hypothalamus (11-fold) and the hindbrain (4-fold) and of IL-1β in the hypothalamus, without changing the expression of other inflammation-associated genes.
Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
...IL6 appears to act in a paracrine fashion to promote angiogenesis and tumor growth. Inhibiting IL6 may therefore have therapeutic utility for treatment of cancers characterized by oncogenic Ras mutations.
Plasma concentration of interleukin-6 was upregulated in cancer cachexia patients and was positively correlated with plasma free fatty acid in female patients
Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats.
...Interleukin-1 (IL-1), a cytokine produced by bone marrow cells and bone cells, has been implicated in the pathogenesis of postmenopausal osteoporosis because of its potent stimulatory effects on bone resorption in vitro and in vivo.
A lot of interesting links Carp! If I have the time I'll look through them. As to the relationship to interleukins that makes sense. Inflammation is heavily associated with cardiometabolic disease and so this isn't too much of a surprise. I'd have to look into what goes on with respect to these drugs and whether they incur some sort of inflammatory response. As of now the possibility of resistance is one area I'd be more interested in.
you are providing excellent content - please add PayPal to your Kofi - shouldn't cost you anything and you won't get rich but it will allow some of us to show our appreciation in a small way for the efforts you make.
Thank you chico! I certainly will consider it in the very near future. I'm figuring which direction I would like to take monetization. As of now I haven't considered PayPal as I didn't want to juggle two payment processors. Both Substack and ko-fi use Stripe so that allowed me to just synch both without having to worry about another processor. However, it does allow for greater flexibility for readers and so it would be better in the long-run. If I do consider it I will make sure to make readers aware!
Super article! I "shouted it out. " Unfortunately I couldn't get that @ thing to work, no matter the spaces, no spaces, and hyphens, and underscores I tried, so that's why I'm notifying you. :-D
It's gonna be super hot summer with all the diarrhea and nausea caused by these drugs.
So crazy that these super expensive drugs have similar problems as the old Alli, orlistat weight loss drug that made people crap their pants. :-D :-D
Thank you weedom! I...haven't figured out Notes as well if that's what you're referring to. It makes me feel out of touch!
The drug is really fascinating. A lot of the symptoms are likely related to the nervous system providing a feedback of satiety while also having an empty stomach? Not quite sure but it would be interesting to explore. What's interesting is that there was a Reddit post that I came across (which I unfortunately lost) where someone was commenting that they had a lot of side effects but lost weight while on Ozempic. However, as soon as the side effects subsided the weight came back on.
Of course, one may argue that feelings of nausea likely will stop people from eating, but I'm curious if people may have become desensitized to the drug as well. We don't have a lot of data there.
As far as I can recall, Alli stopped your body from absorbing fat. By all accounts it should have served as a way of disincentivizing a high fat diet, but instead I guess people would rather wear diapers. 🤷♂️
I don’t have the use of Notes optimized, but some is better than none. I help bring some subscriptions to people, and they do the same for me, just by talking to each other about anything. Just dive in.
That Reddit post describes what we see. A fair amount of patients are too nauseated to eat much. The Alli was interesting. A lot of people tried it and dropped it, due to intolerable steatorrhea which is tooo nasty. Changing eating habits is hard for people. That “wet and hot incretin summer” was extremely evocative of the pitfalls of incontinence in a population which has extra struggles with personal hygiene.
I salute the nurses and the PCAs, as well as the environmental staff.
Probiotics for the Treatment of Overweight and Obesity in Humans—A Review of Clinical Trials
(also related to short chain fatty acids)
Makes me wonder if taking SCFA directly and absorbing in the small intestine has the same effect. I've seen one formulation said to carry it down through the bowels, so simulating more of the effects of probiotics digesting prebiotics. What I also found interesting is that polyphenols have probiotic boosting effects. I have not read about the mechanisms though. I do know that whenever I take inulin and fibers I get gassy, but not so with polyphenol food sources and supplements
see section: Metabolic disorders and A. muciniphila
but it's a little out of date with regards to:
"Currently, there are no published open clinical trials of A. muciniphila for humans and therefore resulting in a lack of strong evidence on the safety of A. muciniphila in humans. This could explain why A. muciniphila has not been involved in food production or drug use. However, some preliminary studies have indicated this bacterium should be safe for interventions in human."
Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation
... which includes Akkermansia muciniphila in the formulation, and whose strain has been available for food, OTC supplement use for I believe 2+ years now
For heaven’s sake, if you want to,lose weight stop eating crap. And if you need to control your blood sugar/glucose levels try berberine and milk thistle. Works better than metformin with fewer side effects.
But it's almost beach season! I'm worried marine biologists may mistake me for a washed up whale!
I would give these a hard pass. There is a consequence to throwing anything out of balance.
They promote systemic upregulation of proinflammatory and oncogenic & autoimmune related interleukin 6 (il-6).
Il-1 is also oncogenic.
It's also one of the reasons why cancer patients waste away. Yeah.
***
Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6
(2013)
...Glucagon-like peptide 1 (GLP-1), produced in the intestine and the brain, can stimulate insulin secretion from the pancreas and alleviate type 2 diabetes. The cytokine interleukin-6 (IL-6) may enhance insulin secretion from β-cells by stimulating peripheral GLP-1 production. GLP-1 and its analogs also reduce food intake and body weight, clinically beneficial actions that are likely exerted at the level of the CNS, but otherwise are poorly understood. The cytokines IL-6 and interleukin 1β (IL-1β) may exert an anti-obesity effect in the CNS during health. Here we found that central injection of a clinically used GLP-1 receptor agonist, exendin-4, potently increased the expression of IL-6 in the hypothalamus (11-fold) and the hindbrain (4-fold) and of IL-1β in the hypothalamus, without changing the expression of other inflammation-associated genes.
https://pubmed.ncbi.nlm.nih.gov/24048027/
***
Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis
...IL6 appears to act in a paracrine fashion to promote angiogenesis and tumor growth. Inhibiting IL6 may therefore have therapeutic utility for treatment of cancers characterized by oncogenic Ras mutations.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920165/
***
Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503335/
***
You know how you lose your appetite when you are ill? You really don't want to recreate these illness factors:
Inflammatory cytokines, appetite‑regulating hormones, and energy metabolism in patients with gastrointestinal cancer
https://www.spandidos-publications.com/10.3892/ol.2020.11662
***
Plasma concentration of interleukin-6 was upregulated in cancer cachexia patients and was positively correlated with plasma free fatty acid in female patients
https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-019-0409-9
***
Weight loss via your bones is not good:
Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats.
...Interleukin-1 (IL-1), a cytokine produced by bone marrow cells and bone cells, has been implicated in the pathogenesis of postmenopausal osteoporosis because of its potent stimulatory effects on bone resorption in vitro and in vivo.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC294303/
A lot of interesting links Carp! If I have the time I'll look through them. As to the relationship to interleukins that makes sense. Inflammation is heavily associated with cardiometabolic disease and so this isn't too much of a surprise. I'd have to look into what goes on with respect to these drugs and whether they incur some sort of inflammatory response. As of now the possibility of resistance is one area I'd be more interested in.
Resistance would be the ideal protective outcome.
Without it you won't know you have been overexposed to il-1 or il-6 that can lead to cardiovascular disease, autoimmune disorders and cancer.
You will lose weight that way.
Alex Azar:. Eli Lily exec and formerly of the US Health and Human Services.
Interesting. Didn't know that!
you are providing excellent content - please add PayPal to your Kofi - shouldn't cost you anything and you won't get rich but it will allow some of us to show our appreciation in a small way for the efforts you make.
Thank you chico! I certainly will consider it in the very near future. I'm figuring which direction I would like to take monetization. As of now I haven't considered PayPal as I didn't want to juggle two payment processors. Both Substack and ko-fi use Stripe so that allowed me to just synch both without having to worry about another processor. However, it does allow for greater flexibility for readers and so it would be better in the long-run. If I do consider it I will make sure to make readers aware!
So sexy, wet, hot incretin in summer! 😄🏖️🌊
Another way to sell drugs as our food supply becomes less nutritious.
Can you just imagine everyone shooting up on the beachfront? We'll have to be careful of a different type of needle in the sands now! 😅
Super article! I "shouted it out. " Unfortunately I couldn't get that @ thing to work, no matter the spaces, no spaces, and hyphens, and underscores I tried, so that's why I'm notifying you. :-D
It's gonna be super hot summer with all the diarrhea and nausea caused by these drugs.
So crazy that these super expensive drugs have similar problems as the old Alli, orlistat weight loss drug that made people crap their pants. :-D :-D
Thank you weedom! I...haven't figured out Notes as well if that's what you're referring to. It makes me feel out of touch!
The drug is really fascinating. A lot of the symptoms are likely related to the nervous system providing a feedback of satiety while also having an empty stomach? Not quite sure but it would be interesting to explore. What's interesting is that there was a Reddit post that I came across (which I unfortunately lost) where someone was commenting that they had a lot of side effects but lost weight while on Ozempic. However, as soon as the side effects subsided the weight came back on.
Of course, one may argue that feelings of nausea likely will stop people from eating, but I'm curious if people may have become desensitized to the drug as well. We don't have a lot of data there.
As far as I can recall, Alli stopped your body from absorbing fat. By all accounts it should have served as a way of disincentivizing a high fat diet, but instead I guess people would rather wear diapers. 🤷♂️
I don’t have the use of Notes optimized, but some is better than none. I help bring some subscriptions to people, and they do the same for me, just by talking to each other about anything. Just dive in.
That Reddit post describes what we see. A fair amount of patients are too nauseated to eat much. The Alli was interesting. A lot of people tried it and dropped it, due to intolerable steatorrhea which is tooo nasty. Changing eating habits is hard for people. That “wet and hot incretin summer” was extremely evocative of the pitfalls of incontinence in a population which has extra struggles with personal hygiene.
I salute the nurses and the PCAs, as well as the environmental staff.
Have you looked into probiotics and GLP-1? https://pubmed.ncbi.nlm.nih.gov/23836895/
Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465252/
Probiotics for the Treatment of Overweight and Obesity in Humans—A Review of Clinical Trials
(also related to short chain fatty acids)
Makes me wonder if taking SCFA directly and absorbing in the small intestine has the same effect. I've seen one formulation said to carry it down through the bowels, so simulating more of the effects of probiotics digesting prebiotics. What I also found interesting is that polyphenols have probiotic boosting effects. I have not read about the mechanisms though. I do know that whenever I take inulin and fibers I get gassy, but not so with polyphenol food sources and supplements
https://pubmed.ncbi.nlm.nih.gov/20927337/
Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein (ANGPTL4)
Also Akkermansia muciniphila: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801136/
see section: Metabolic disorders and A. muciniphila
but it's a little out of date with regards to:
"Currently, there are no published open clinical trials of A. muciniphila for humans and therefore resulting in a lack of strong evidence on the safety of A. muciniphila in humans. This could explain why A. muciniphila has not been involved in food production or drug use. However, some preliminary studies have indicated this bacterium should be safe for interventions in human."
See: https://drc.bmj.com/content/8/1/e001319.full
Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation
... which includes Akkermansia muciniphila in the formulation, and whose strain has been available for food, OTC supplement use for I believe 2+ years now