Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation

[Dr. B]

I can relate to that! I appreciate that Ray Peat can drink as much milk and orange juice as he does, and maybe if my personality were more geared toward getting an easy meal down so I could get back to painting i would be on board. I like variety and I cook for others so I make his recommendations my own as well :)

he does 1L orange juice and 2L milk daily?

 

[Eberhardt]

interesting. he really doesnt like rice, as he considers it even inferior to potato. hes commented potatoes protein is very high quality but theyre allergenic. btw I think allergenic doesnt simply mean a select few people who are allergic to substances and start wheezing to them or whatever. from what i have seen every allergenic substance still causes some level of inflammation even in non allergenic people... the severely allergic people are just more compromised so have a stronger reaction to the allergens whereas someone less compromised can maybe tolerate small amounts of allergens with less symptoms.
cuz Ray and Danny themselves despite all their talk of the benefits to coconut oil and hydrogenated coconut oil, those guys still prefer olive oil to hydrogenated coconut oil in their carrot salads. not just for taste but for actual digestive efficiency. according to Peat its because even HCO still has some allergens in it. these allergens whatever they are, obviously dont cause allergies for Danny/Ray yet they cause some sort digestive response

nothing about rice or potatoes but its hard to know what to think of that statement. I am afraid I cant make use of it as there is no such thing as a substance without sideeffects. True allergy is an autoimmune-reaction. Of course auto-immunity is an innflamatory state but that doesnt tell us much so using the allergy concept in that way sort of defines it out of existence as no food or substance would be of such a nature as to have 0 side effects. I think thus it is most relevant to reserve the concept for the more narrower innflamatory expression of specific auto-immune reactions. As an example peat says to use raffianted coconut oil to avoid allergenes that SOME people might react to. I understand that as saying that not all will as on the other hand he would not say avoid aluminum in the food because some people might have an allergic reaction - it is innflamatory (amongst other things proper) not allergenic in the narrow sense. Just an example to illustrate my theoretical frame for disputing the meaning of allergy

 

[Dr. B]

nothing about rice or potatoes but its hard to know what to think of that statement. I am afraid I cant make use of it as there is no such thing as a substance without sideeffects. True allergy is an autoimmune-reaction. Of course auto-immunity is an innflamatory state but that doesnt tell us much so using the allergy concept in that way sort of defines it out of existence as no food or substance would be of such a nature as to have 0 side effects. I think thus it is most relevant to reserve the concept for the more narrower innflamatory expression of specific auto-immune reactions. As an example peat says to use raffianted coconut oil to avoid allergenes that SOME people might react to. I understand that as saying that not all will as on the other hand he would not say avoid aluminum in the food because some people might have an allergic reaction - it is innflamatory (amongst other things proper) not allergenic in the narrow sense. Just an example to illustrate my theoretical frame for disputing the meaning of allergy

im not sure about Danny but Ray seems to avoid all the 'allergenic' type foods, whether they personally cause him allergies or not. apparently gluten, peanuts, corn, soy, tree nuts, cause some inflammation in everyone, its only some people who get the severe allergic responses from them. milk/eggs/shellfish probably cause allergies not due to those foods themselves but due to toxins or allergenic foods/liquids consumed by those animals.

 

[Rinse & rePeat]

interesting. he really doesnt like rice, as he considers it even inferior to potato. hes commented potatoes protein is very high quality but theyre allergenic. btw I think allergenic doesnt simply mean a select few people who are allergic to substances and start wheezing to them or whatever. from what i have seen every allergenic substance still causes some level of inflammation even in non allergenic people... the severely allergic people are just more compromised so have a stronger reaction to the allergens whereas someone less compromised can maybe tolerate small amounts of allergens with less symptoms.
cuz Ray and Danny themselves despite all their talk of the benefits to coconut oil and hydrogenated coconut oil, those guys still prefer olive oil to hydrogenated coconut oil in their carrot salads. not just for taste but for actual digestive efficiency. according to Peat its because even HCO still has some allergens in it. these allergens whatever they are, obviously dont cause allergies for Danny/Ray yet they cause some sort digestive response

Yeah i am sure in the beginning when Ray Peat was having a little rice back in the day he probably struggled like we all have trying to figure out what to eat. Just like my diet has got better his got better too. Heck I remember in the beginning of "Peating", almost 5 years ago, me taking his macadamias are safer advice and making nut butter with honey and coconut oil and eating spoonful of it all day thinking I was being "Peaty". Ray has evolved and so have I. It doesn't mean we were wrong with my nut butter and his rice, we just took it to an new and improved level.

 

[CLASH]

Fructose is fructose. I suppose that eating 100 grams of fructose per day from fruits isn't so different as eating from drink.

I suppose that lots of fats but in general lots of calories makes it a poison.

Anyway did Ray Peat said how much fructose is safe in a day?

Fructose itself is not a poison for the liver. The majority is converted to glucose, glycogen, and lactate with a marginal amount being converted to fat through DNL.

Error - Cookies Turned Off

physoc.onlinelibrary.wiley.com

Taking in fructose from a soda, or refined sucrose/ HFCS source is in fact very different from getting it from fruit juice. This has been proven directly by research.

Review of 100% Fruit Juice and Chronic Health Conditions: Implications for Sugar-Sweetened Beverage Policy

Abstract. Whether or not drinking 100% fruit juice causes poor health is controversial. Although 100% fruit juice may contain as much sugar as regular soda, it

academic.oup.com

Impact of 100% Fruit Juice Consumption on Diet and Weight Status of Children: An Evidence-based Review - PubMed

Consumption of 100% fruit juice remains controversial for its potential adverse impact on weight and displacement of essential foods in the diets of children. A systematic review of the literature published from 1995-2013 was conducted using the PubMed database to evaluate associations between...

pubmed.ncbi.nlm.nih.gov

Effect of pomegranate juice on insulin secretion and sensitivity in patients with obesity - PubMed

Pomegranate juice administration for 1 month did not modify insulin secretion and sensitivity in patients with obesity; however, the natural evolution to increased weight and adiposity was halted.

pubmed.ncbi.nlm.nih.gov

Fruit consistently proves protective against high fat, high sugar feeding studies despite the sugar content. Even mangoes do well in studies, despite having a high fructose content.

Physiological and molecular study on the anti-obesity effects of pineapple (Ananas comosus) juice in male Wistar rat - PubMed

The present study was performed to assess anti-obesity effects of raw pineapple juice in high fat diet (HFD)-induced fatness. Based on food type, rats were divided into normal diet and HFD groups. When animals of HFD group become obese, they were given pineapple juice along with either HFD or...

pubmed.ncbi.nlm.nih.gov

Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat diet | British Journal of Nutrition | Cambridge Core

Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat diet - Volume 106 Issue 10

www.cambridge.org

Corn fructose isn't safe cause is a great amount of fructose, but even with fruit you can get the same amount even with more difficult. And liver has limited capability to store it less than 100 grams.

Please supply data about what you say, otherwise this arguing is useless.

Drinking great amount of fruit juice can cause bloating and intestinal issues, so there's a limit even with these sources.

High fructose corn syrup is only 55% fructose, with 45% glucose. Sucrose is 50%/50% so not too much difference.

The liver glycogen storage is somewhat limited, but fructose isn't only turned into glycogen its turned into lactate and glucose and sent to the bodies cells and tissues.

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physoc.onlinelibrary.wiley.com

Drinking large amounts of fruit juice usually only causes issues if the juice has a high FODMAP content, a high fructose to glucose ratio leading to fructose malabsorption, and/ or you have SIBO. Fructose requires glucose to be absorbed via a co-transport mechanism in the intestine.

Error - Cookies Turned Off

physoc.onlinelibrary.wiley.com

No. if someone has an infection immune cells try to use fructose with aerobic oxidation and in this case cancer cells and bacteria ones can reduce oxygen inside micro environment and let them die whereas with glucose they can live using just anaerobic glycolisis. Read better, please.

Up regulation of inflammation is the worse thing immune system can do, cause it destroy all the tissue creating fibrosis.

You linked an in vitro study where they exposed to macrophages to fructose and LPS. In vivo this would be unlikely to occur since fructose is shuttled to the liver and converted to glucose, lactate, glycogen and fatty acids. Plus, if your fructose consumption is from fruit, the polyphenols, vitamins, and minerals would protect against any endotoxemia and modulate carbohydrate metabolism.

Your last statement is a blanket statement that mischaracterizes the immune system at best.

 

[Rinse & rePeat]

he does 1L orange juice and 2L milk daily?

I read different answers on that one Mr. Bollox, and I am sure it because, like me, what I eat in the summer is different than what i eat eat in the fall. So depending on when they asked him the question is why we might hear a different answer. Right now I am hooked on pork rinds so you wouldn't have heard me mention that in my diet lineup a month ago. Ray does say milk can be allergenic to some depending on the season and what the cows ate. So lots of variables in the "Peat" world, with not always black & white and right and wrong answers.

 

[Eberhardt]

im not sure about Danny but Ray seems to avoid all the 'allergenic' type foods, whether they personally cause him allergies or not. apparently gluten, peanuts, corn, soy, tree nuts, cause some inflammation in everyone, its only some people who get the severe allergic responses from them. milk/eggs/shellfish probably cause allergies not due to those foods themselves but due to toxins or allergenic foods/liquids consumed by those animals.

No I dont mean it that way. I am sure you are mostly right about his eating habits I was just trying to avoid confusing the subject as there seems to be no more such a thing as an allergenic substance more then there is a carcinogenic substance if we reduce it to mean inflammatory. While I agree that allergy is an inflammatory reaction it is also a specific reaction in the immunesystem. And that reaction is not a characteristic of the food/substance but better understood as a specific descrition of a certain reaction within the system. As far as I know Peat tend to say "may cause allergy in some", not "is allergenic". I agree some substances are problematic and he avoids a lot of them. I just find it better to be a bit "nitpicky" about wording. this is complex stuff and its important for the sake of not reaching the wrong conclusions not to ascibe as properties something that is a reaction. I think he is generally very adversly minded to "irritants" in the food and enviorment but this might be oversimplyfying it to. It is in according with the priniciple of keeping stressors low to maximise energetic health

 

[Dr. B]

Fructose itself is not a poison for the liver. The majority is converted to glucose, glycogen, and lactate with a marginal amount being converted to fat through DNL.

Error - Cookies Turned Off

physoc.onlinelibrary.wiley.com

Taking in fructose from a soda, or refined sucrose/ HFCS source is in fact very different from getting it from fruit juice. This has been proven directly by research.

Review of 100% Fruit Juice and Chronic Health Conditions: Implications for Sugar-Sweetened Beverage Policy

Abstract. Whether or not drinking 100% fruit juice causes poor health is controversial. Although 100% fruit juice may contain as much sugar as regular soda, it

academic.oup.com

Impact of 100% Fruit Juice Consumption on Diet and Weight Status of Children: An Evidence-based Review - PubMed

Consumption of 100% fruit juice remains controversial for its potential adverse impact on weight and displacement of essential foods in the diets of children. A systematic review of the literature published from 1995-2013 was conducted using the PubMed database to evaluate associations between...

pubmed.ncbi.nlm.nih.gov

Effect of pomegranate juice on insulin secretion and sensitivity in patients with obesity - PubMed

Pomegranate juice administration for 1 month did not modify insulin secretion and sensitivity in patients with obesity; however, the natural evolution to increased weight and adiposity was halted.

pubmed.ncbi.nlm.nih.gov

Fruit consistently proves protective against high fat, high sugar feeding studies despite the sugar content. Even mangoes do well in studies, despite having a high fructose content.

Physiological and molecular study on the anti-obesity effects of pineapple (Ananas comosus) juice in male Wistar rat - PubMed

The present study was performed to assess anti-obesity effects of raw pineapple juice in high fat diet (HFD)-induced fatness. Based on food type, rats were divided into normal diet and HFD groups. When animals of HFD group become obese, they were given pineapple juice along with either HFD or...

pubmed.ncbi.nlm.nih.gov

Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat diet | British Journal of Nutrition | Cambridge Core

Mango modulates body fat and plasma glucose and lipids in mice fed a high-fat diet - Volume 106 Issue 10

www.cambridge.org

High fructose corn syrup is only 55% fructose, with 45% glucose. Sucrose is 50%/50% so not too much difference.

The liver glycogen storage is somewhat limited, but fructose isn't only turned into glycogen its turned into lactate and glucose and sent to the bodies cells and tissues.

Error - Cookies Turned Off

physoc.onlinelibrary.wiley.com

Drinking large amounts of fruit juice usually only causes issues if the juice has a high FODMAP content, a high fructose to glucose ratio leading to fructose malabsorption, and/ or you have SIBO. Fructose requires glucose to be absorbed via a co-transport mechanism in the intestine.

Error - Cookies Turned Off

physoc.onlinelibrary.wiley.com

You linked an in vitro study where they exposed to macrophages to fructose and LPS. In vivo this would be unlikely to occur since fructose is shuttled to the liver and converted to glucose, lactate, glycogen and fatty acids. Plus, if your fructose consumption is from fruit, the polyphenols, vitamins, and minerals would protect against any endotoxemia and modulate carbohydrate metabolism.

Your last statement is a blanket statement that mischaracterizes the immune system at best.

what causes the issues with high fructose corn syrup exactly? is it the lack of the vitamins/minerals in HFCS, or is it due to the starch like materials Ray mentioned many years ago? Everything ive seen from Ray implies that he likes fructose, but prefers some sources of it more than others due to either toxins present in some sources (starch materials in HFCS) or lack of vitamins/minerals (like in table sugar) or potential allergenicity (like honey). it doesnt seem like the problem is with the type of fructose used but more so that different sources of fructose may have different advantages or disadvantages.

 

[JKX]

Abstract​

Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.

Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation - Nature Communications

Myeloid cells are able to utilize a variety of monosaccharides from our diet, including fructose. Here the authors show that when monocytes are reliant on fructose as a carbon energy source they are reprogrammed towards oxidative metabolism, glutamine anaplerosis and a pro-inflammatory phenotype...

www.nature.com

I suppose that fructose isn't so well as Ray Peat said.

The HFCS was applied to cells put into a toxic state through being injected with LPS. Each study used LPS induction of inflammation. Perhaps you should ask yourself why any study of fructose should require an LPS induced inflammatory state to be created in the first place? If you wish to determine a cells response to a substance, why not just treat it with said substance and observe the metabolic changes? Dont create a set of conditions which suit your preconceptions to steer the results in the direction you want. The studies appear illogical and immoral to me. Clearly the researchers had a preconceived result in mind they wanted to achieve and did so. Unfortunately an action which is common within present day 'science'.

 

[CLASH]

what causes the issues with high fructose corn syrup exactly? is it the lack of the vitamins/minerals in HFCS, or is it due to the starch like materials Ray mentioned many years ago? Everything ive seen from Ray implies that he likes fructose, but prefers some sources of it more than others due to either toxins present in some sources (starch materials in HFCS) or lack of vitamins/minerals (like in table sugar) or potential allergenicity (like honey). it doesnt seem like the problem is with the type of fructose used but more so that different sources of fructose may have different advantages or disadvantages.

All of the refined sugars, including sucrose are without vitamins and minerals that allow for proper processing and utilization. They also lack the polyphenols and flavonoids that fruits contain. Consistent overconsumption of refined sugar sources can lead to issues, both nutrient wise and microbiome wise. However the problem isn't inherently because of "fructose". Plain glucose, and sucrose cause issues as well.

The main difference with fructose is that it requires glucose for transport across the intestinal epithelium, and that it has a slightly different metabolism compared to glucose.

High fructose corn syrup issues are likely related to processing, and other components present within the syrup. Some studies say these components are present others, say they aren't.

Overall the safest strategy, from my opinion is to consume dried fruit, whole fruit, frozen fruit, and 100% fruit juice that has minimal FODMAPS, and a close to 1:1 glucose to fructose ratio. The vitamins, minerals, and polyphenols are extremely beneficial from the fruit, as well as the sugars.

 

[Eberhardt]

All of the refined sugars, including sucrose are without vitamins and minerals that allow for proper processing and utilization. They also lack the polyphenols and flavonoids that fruits contain. Consistent overconsumption of refined sugar sources can lead to issues, both nutrient wise and microbiome wise. However the problem isn't inherently because of "fructose". Plain glucose, and sucrose cause issues as well.

The main difference with fructose is that it requires glucose for transport across the intestinal epithelium, and that it has a slightly different metabolism compared to glucose.

High fructose corn syrup issues are likely related to processing, and other components present within the syrup. Some studies say these components are present others, say they aren't.

Overall the safest strategy, from my opinion is to consume dried fruit, whole fruit, frozen fruit, and 100% fruit juice that has minimal FODMAPS, and a close to 1:1 glucose to fructose ratio. The vitamins, minerals, and polyphenols are extremely beneficial from the fruit, as well as the sugars.

any idea how dried fruit gives me terrible sideeffects regardless of type of fruit and all else I am able to ome up with. I get blood sugar fluctations (at least it feels like it didnt measure glucose), and really dry mouth. No reaction like this to the same fruits when fresh and not to any kind of sugars I know of neither refined or in its natural context. Never figured out what happens. Is the glycemic index different??

 

[Dr. B]

All of the refined sugars, including sucrose are without vitamins and minerals that allow for proper processing and utilization. They also lack the polyphenols and flavonoids that fruits contain. Consistent overconsumption of refined sugar sources can lead to issues, both nutrient wise and microbiome wise. However the problem isn't inherently because of "fructose". Plain glucose, and sucrose cause issues as well.

The main difference with fructose is that it requires glucose for transport across the intestinal epithelium, and that it has a slightly different metabolism compared to glucose.

High fructose corn syrup issues are likely related to processing, and other components present within the syrup. Some studies say these components are present others, say they aren't.

Overall the safest strategy, from my opinion is to consume dried fruit, whole fruit, frozen fruit, and 100% fruit juice that has minimal FODMAPS, and a close to 1:1 glucose to fructose ratio. The vitamins, minerals, and polyphenols are extremely beneficial from the fruit, as well as the sugars.

where did you see that fructose requires glucose? I read something about fructose getting oxidized even in diabetics whereas glucose isnt always properly oxidized and in diabetics even less so. doesnt fructose increase the metabolism much more than glucose.
fruit, maple syrup and honey should all be fine right? and milk too?

 

[Rinse & rePeat]

Fructose series part 1: fructose depletes ATP?

Every heard that fructose might deplete ATP? That's one silly argument that I debunk here. https://men-elite.com/2021/02/18/fructose-series-part-1-fructose-depletes-atp/

raypeatforum.com

 

[schultz]

Abstract​

Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.

Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation - Nature Communications

Myeloid cells are able to utilize a variety of monosaccharides from our diet, including fructose. Here the authors show that when monocytes are reliant on fructose as a carbon energy source they are reprogrammed towards oxidative metabolism, glutamine anaplerosis and a pro-inflammatory phenotype...

www.nature.com

I suppose that fructose isn't so well as Ray Peat said.

Interesting paper. LPS challenged cells incubated with glucose had increased extracellular acidification, however fructose maintained OXPHOS which would keep carbon dioxide up. However, I'm not sure if CO2 is lost in vitro? But I suspect this effect fructose has on OXPHOS would prove to be beneficial to the organism overall compared to glucose, contrary to what the authors of this paper conclude. I'm not sure how the increased cytokines would cause things to play out in vivo.

So the takeaway is that fructose can maintain oxidative metabolism when the organism is under stress, which seems hugely important to me, especially since FFA can inhibit glucose metabolism (but not fructose). This seems to jive with Ray's article on fructose "Sugar Issues".

 

[Michael Mohn]

Interesting paper. LPS challenged cells incubated with glucose had increased extracellular acidification, however fructose maintained OXPHOS which would keep carbon dioxide up. However, I'm not sure if CO2 is lost in vitro? But I suspect this effect fructose has on OXPHOS would prove to be beneficial to the organism overall compared to glucose, contrary to what the authors of this paper conclude. I'm not sure how the increased cytokines would cause things to play out in vivo.

So the takeaway is that fructose can maintain oxidative metabolism when the organism is under stress, which seems hugely important to me, especially since FFA can inhibit glucose metabolism (but not fructose). This seems to jive with Ray's article on fructose "Sugar Issues".

If this in vitro study means anything then it means that fructose is good for stressed organisms and the immune system in particular.

 

[CLASH]

where did you see that fructose requires glucose? I read something about fructose getting oxidized even in diabetics whereas glucose isnt always properly oxidized and in diabetics even less so. doesnt fructose increase the metabolism much more than glucose.
fruit, maple syrup and honey should all be fine right? and milk too?

In the studies I posted they mention the requirement for glucose in order for larger amounts of fructose to move across the intestine. Glucose brings fructose across the intestine via co-transport through the GLUT- 2 receptor. Fructose can be brought across the intestine with GLUT-5 but in many people this is easily saturated, after which fructose is left in the intestine where bacteria turn it into endotoxins and other compounds.

Fructose malabsorption

Incomplete intestinal absorption of fructose might lead to abdominal complaints such as pain, flatulence and diarrhoea. Whether defect fructose transporters such as GLUT5 or GLUT2 are involved in the pathogenesis of fructose malabsorption is a matter ...

www.ncbi.nlm.nih.gov

•Fruit- depends on the fruit
•Maple syrup- 1:1 glucose: fructose but can contain inulin
•Honey: imbalanced towards fructose. Can cause serious fructose malabsorption
•Milk- mostly lactose which is glucose and galactose. The galactose is used for myelin production in infants, and glucose for energy. Lactose requires lactase persistence and/or a solid microbiome to be digested without issue

 

[schultz]

If this in vitro study means anything then it means that fructose is good for stressed organisms and the immune system in particular.

That was my interpretation as well. Actually, it seems quite impressive based on this paper. It appears to be robustly resistant to glycolysis even under stress. This is quite an amazing feature, although I don't know exactly how the effects of the study would play out in the body. Presumably it would be helpful in areas with higher concentrations of fructose (liver) and areas of fertility (developing fetus, sperm) and perhaps less helpful in areas where glycolysis is more expected (muscles?)

 

[Rafael Lao Wai]

That was my interpretation as well. Actually, it seems quite impressive based on this paper. It appears to be robustly resistant to glycolysis even under stress. This is quite an amazing feature, although I don't know exactly how the effects of the study would play out in the body. Presumably it would be helpful in areas with higher concentrations of fructose (liver) and areas of fertility (developing fetus, sperm) and perhaps less helpful in areas where glycolysis is more expected (muscles?)

According to the paper, the effect took a while to go away, so fructose may make the cells used to being in a configuration which promotes oxidative phosphorilation, meaning more CO2, more ATP, stronger electron flow, etc.

In one of Ray's articles, he said the placenta has a mechanism which allows glucose to go back and forth( from the intra- placental environment to the mother and vice-versa), but fructose can only go from the mother to the placenta, so the baby is effectively bathing in a fructose rich fluid. This must contribute to the low stress state that the fetus needs to be in during development.

I'm not sure if fructose can inhibit glycolysis pathologically, as in when the cells really need it. In the study in the original post, the cells still had access to oxygen, it's just that they were being posioned with LPS. LPS tend to inhibit cytochrome C oxidase, lowering the flow of electrons through the electron transport chain. In the study below, the cells were deprived of oxygen, so it makes sense that fructose couldn't maintain oxidative metabolism in this case. Even then, fructose is such a promoter of the electron flow that it continued to provide ATP to the cell even without oxygen, through the generation of lactate. Without oxygen to absorb the electrons coming from the substrate, pyruvate does that job and becomes lactate:

Fructose prevents hypoxic cell death in liver - PubMed

Perfusion of livers from fasted rats with nitrogen-saturated buffer caused hepatocellular damage within 30 min. Lactate dehydrogenase (LDH) was released at maximal rates of approximately 300 U . g-1 . h-1 under these conditions, and virtually all cells in periportal and pericentral regions of...

pubmed.ncbi.nlm.nih.gov

Pretty interesting that galactose was also very effective at maintaining metabolism under stress.

 

[dabdabdab]

but fructose causes advanced glycation end products more than glucose.

 

[dabdabdab]

what about chlorophyll as a fighting agent against endotoxins? is it true that our cousin primates fought endotoxins from fruits with eating grass and leaves?
I had a desire to occasionally taste some leaves when I was a child.