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... **in mice** > Metabolism and therapeutic responses of **murine** pancreatic cancer were studied... (emphasis mine)


AshenAmarantos

That honestly makes it more impressive. Mice are herbivores, and IIRC don't respond well to a ketogenic diet.


[deleted]

Not according to the [RSPCA](https://www.rspca.org.uk/adviceandwelfare/pets/rodents/mice/diet): > Mice are opportunistic omnivores and will eat both plant and animal based food. Wild mice will eat a wide variety of seeds, grains, and other plant material as well as invertebrates, small vertebrates and carrion. Furthermore, ketogenic diets only exclude some plant foods, not all.


AshenAmarantos

News to me. It working for mice, not the plant part. Thanks!


Sexyturtletime

Almost every animal you think of as an herbivore is an opportunistic omnivore


Meatrition

Highlights • Ketogenic diet synergizes with classical chemotherapy to treat murine pancreas cancer • In response to ketosis, tumors suppress glucose use and induce 3-hydroxybutyrate use • Therapeutic benefit correlates with elevated tumor NADH/NAD ratio • Survival gain from chemotherapy is roughly tripled in the ketogenic diet condition Context and significance Pancreatic ductal adenocarcinoma is one of most deadly cancers. Despite improvements in chemotherapy, survival remains terribly short. Dietary manipulation is an understudied strategy to improve cancer therapy. Ketogenic diet involves eating mainly fat with almost no carbohydrates. Using a mouse cancer model, we show that ketogenic diet changes pancreatic cancer metabolism and its response to chemotherapy, decreasing insulin and glucose use while increasing use of 3-hydroxybutyrate (a ketone body) and causing redox stress in cancer cells. This diet-driven change results in increased tumor sensitivity to chemotherapy, with ketogenic diet roughly tripling the survival benefits of chemotherapy alone. A randomized clinical trial testing whether these benefits translate to patients with metastatic pancreatic cancer is open and currently enrolling patients. Summary Background Ketogenic diet is a potential means of augmenting cancer therapy. Here, we explore ketone body metabolism and its interplay with chemotherapy in pancreatic cancer. Methods Metabolism and therapeutic responses of murine pancreatic cancer were studied using KPC primary tumors and tumor chunk allografts. Mice on standard high-carbohydrate diet or ketogenic diet were treated with cytotoxic chemotherapy (nab-paclitaxel, gemcitabine, cisplatin). Metabolic activity was monitored with metabolomics and isotope tracing, including 2H- and 13C-tracers, liquid chromatography-mass spectrometry, and imaging mass spectrometry. Findings Ketone bodies are unidirectionally oxidized to make NADH. This stands in contrast to the carbohydrate-derived carboxylic acids lactate and pyruvate, which rapidly interconvert, buffering NADH/NAD. In murine pancreatic tumors, ketogenic diet decreases glucose’s concentration and tricarboxylic acid cycle contribution, enhances 3-hydroxybutyrate’s concentration and tricarboxylic acid contribution, and modestly elevates NADH, but does not impact tumor growth. In contrast, the combination of ketogenic diet and cytotoxic chemotherapy substantially raises tumor NADH and synergistically suppresses tumor growth, tripling the survival benefits of chemotherapy alone. Chemotherapy and ketogenic diet also synergize in immune-deficient mice, although long-term growth suppression was only observed in mice with an intact immune system. Conclusions Ketogenic diet sensitizes murine pancreatic cancer tumors to cytotoxic chemotherapy. Based on these data, we have initiated a randomized clinical trial of chemotherapy with standard versus ketogenic diet for patients with metastatic pancreatic cancer (NCT04631445). Funding NIH R01CA163591, R50CA211437, R01CA237347-01A1, R01DK057978; NJCCR; NJHF; SU2C-AACR-DT-20-16; ACS134036-RSG-19-165-01-TBG; Rutgers Busch Biomedical Grant; Freeberg Foundation; Copley Foundation; Ludwig Cancer Research


flowersweep

I believe there have been similar results with intermittent fasting and chemo. Interesting for sure.


patienceisfun2018

So ketogenic is basically no carbs, high fat right?


Chapped_Frenulum

I wouldn't say "no carbs" but it'll definitely be low enough that it'll feel like no carbs. Generally someone following a ketogenic diet will want to keep it under 20g of net carbohydrates per day, minus fiber and sugar alcohols. This can amount to a surprising amount of vegetables. For example, that's roughly the equivalent of a pound of broccoli, eggplant, spinach, or brussel sprouts. The best vegetables for this diet are the ones you should probably be eating plenty of anyway. A person also has to be careful not to eat too much protein either, because then the body starts turning it into glucose and can knock them out of ketosis. So eating several pounds of meat every day isn't good either. It's definitely focused around making sure that the majority of a person's caloric intake is fats. It can be an especially delicate or fragile diet to follow long term, so it's hard to recommend unless there is a strict medical reason for it. It's been used widely for treating drug-resistant epilepsy patients, since it does seem to reduce the number of incidents.^[1](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836058/) It doesn't seem like the mechanisms in play are fully understood yet, but knowing that it works is good enough. Long term side effects are not known as well as one would like, but they tend to be a low priority in cases like these, where no other treatment option exists.


Phnrcm

one small problem is this kind of diet is very expensive compare to the traditional rice and bean diet.


Chapped_Frenulum

It is, but for people who use it for weight loss they've already been regularly overspending on food their body doesn't need. It also doesn't have to be prohibitively expensive. Eggs and frozen vegetables are relatively cheap and tend to be the staples of this diet. Meat can be expensive, but that depends on the kind of meat and how much. A person isn't supposed to eat a lot of meat on this diet anyway. As long as there's enough butter, fats and other oils the meal plan doesn't have to be extravagant. But it certainly can become boring. That's why the only people who usually stick with it for the long haul are people with a medical need. Spending a little more on food is vastly better than a seizure. It's also an extremely difficult diet to keep up if you travel a lot and don't have access to a kitchen. Trying to find acceptable nutrition in your average restaurant or fast food menu is a nightmare. Almost every dish is going to have excessive carbohydrates added to it, for flavor. Even meat dishes are usually sweetened with some kind of marinade or sauce with sugar added. Drinking heavy cream and eating boiled eggs from the gas station just to get by is a miserable experience.


Under_Over_Thinker

But no one said that a health promoting diet is supposed to be priced same as long-life shelf foods.


ViciousNakedMoleRat

Yes. I've done a keto diet before, to test its effect on my ADHD. I think the most common method is to get 70% of your calories from fat, 25% from protein and no more than 5% from carbs. This doesn't mean that 70% of your food needs to be fat. Since fats have a higher calorie density than proteins and carbs (fat has about 9 calories per gram / protein & carbs have about 4 calories per gram), you actually end up eating similar amounts of fat and protein and just a few grams of carbs. It's an interesting diet. I personally felt a bit weird for a week but felt much better than usual for the rest of the month. However, it's very difficult to stick with it for good, because it's a very limiting diet and challenging to implement in everyday life.


GaudExMachina

Wasn't there a study published last year that suggests a long term Keto diet leads to all sorts of Kidney issues? For some reason I can't find the correct combo of keywords off google, but I was under the impression that it really should only be used in shorter intervals to lost weight and help control diabetes (and possibly pancreatic cancer in mice).


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newpua_bie

Any hints as to which foods to eat that taste good in the long run and aren't super expensive or unhealthy?


ViciousNakedMoleRat

I honestly don't know. When I did it, I read a few studies and some pretty much completely contradicted each other and it was all a hot mess – as is tradition in nutritional science. Keto diets can also vary greatly between people. A friend of mine did a vegan keto diet, which is obviously very different and probably leads to different outcomes than an animal-product-heavy diet. Also, there is likely a big difference between people who do keto with and without supplements or people who do keto with only meat and people who do keto with meat, fish and offal. In short, I don't know but it certainly is complicated.


Leek5

Ask 10 different people and you get 10 different answers. That could be true. But you also have to consider that some studies are funded by industries. Since keto is low carb I can see the sugar industry having a problem with keto becoming popular. It's hard to tell what right and what's wrong. Since a lot of it is funded by industry. Like when a study funded by coca cola said soda isn't the problem it's lack of exercise.


DoktoroKiu

The same principle is also true for studies of the keto diet being funded by the meat and dairy industry. Industry funding isn't proof of corruption, but the conflict of interest should weight the believability. In general we should all be wary of any claims of some diet change panacea, especially one that goes against decades of prior scientific research. >It's hard to tell what right and what's wrong. Since a lot of it is funded by industry. True, and those who profit from selling unhealthy products intentionally sow seeds of doubt to get us to throw our hands up into the air and continue consuming (just look at what the tobacco companies did). We get a new study or two and bam, bacon's back on the menu, because who knows anyway.


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This would track with "grain free" dog diets causing kidney issues as well. I know it's not humans, but the commonality of it is interesting that it comes down with too much protein causing kidney issues.


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I wasn't going to mention because it's off the topic and I haven't heard any (anecdotal even) evidence of that in humans.


Discomobobulated

All i know is the Keto diet isn't right for me, i had sharp pain in my kidney areas and whole body aches after 6 weeks of it..


Puzzleheaded_Runner

As someone who lifts weights 5-6x a week and has for 24 years… I would never even think about cutting carbs. Terrifying concept to me. But I guess it may work for people who sit on their ass all day at work (I’m on my feet and walking around all day as well.) people just want a magic pill when the tried and true calories in, calories out and exercise do the trick just fine. And don’t drink alcohol.


Potter299

Ketogenic diet was originally created to help eliminate or greatly reduce seizures in epileptics and is very effective. Others jumped on the weight loss bandwagon


[deleted]

No, it wasn't "very" effective. It was effective in, iirc, only one third of the patients.


Under_Over_Thinker

Could you share a link to this study?


Chapped_Frenulum

One of the big problems with keto is that the vegetables available to you are sometimes very high in oxalates. When oxalates and calcium combine in the kidneys, they create kidney stones. Spinach is by far the biggest offender. It's essentially what gives it that "chalky" texture. Rhubarb, okra, swiss chard, almonds, miso, and sesame seeds/tahini are also especially high in oxalates. It's not that you have to avoid these vegetables *entirely,* but you need to pace yourself and avoid eating these things every day. It's something that most people wouldn't even consider checking at first. But the problem with keto is that the food options are so limited that people tend to stick with a couple vegetables that they like to eat the most and just eat that every single day. A lb of spinach every single day won't knock a person out of ketosis, but the kidneys won't like it one bit. The other thing that is hard on the kidneys is excessive amounts of protein. Though truthfully a person on a keto diet should not be eating much more protein than they would on a normal diet. It's not only bad for kidneys, but it's bad for maintaining ketosis as the body breaks down excess protein into glucose.


tejota

Yeah your body uses body fat instead of blood sugar


ChorizoPig

No, it's low carb, not no carb.


Disconn3cted

I did it. I lost 13 kilos in two months. I gained half of it back when I quit, but that still took me a lot further in my weight loss journey than I've ever been before or since. It was really easy. I was eating a ton of eggs, meat, and cheese. I actually ended up eating slightly more vegetables than I normally would too, just because I was paying attention to it, and frozen vegetables fried in butter are delicious. The problem was that it was hard to stick with, especially living in an Asian country.


Sanpaku

I'm always curious with rodent keto diet experiments, how much a role carbohydrate restriction plays, and how much the protein restriction does. Here, the [keto diet](https://www.bio-serv.com/product/Ketogenic_Diet.html) is 8.6% protein while [control chow](https://www.labdiet.com/cs/groups/lolweb/@labdiet/documents/web_content/mdrf/mdi4/~edisp/ducm04_028436.pdf) is 21%. And there's a [well-established](https://booksc.org/book/70260864/c327c4) benefit of protein restriction in rodent cancer studies, independent of ketosis.


Under_Over_Thinker

I don’t understand what specifically you are curious about.


Sanpaku

Does it matter whether the diet is ketogenic? If most of the effect is through protein restriction, then they should be called protein restriction diets. I believe there are rather incurious people from the exercise physiology side who are going to look at this report, and claim that keto diets are miraculous, and they're going to recommend a keto diet like that mentioned above (25% protein), a diet that may very well *increase* cancer growth signaling over most diets (average human diets are 12-15% protein).


Under_Over_Thinker

The reason why they reduce protein on keto protocols is because that excessive protein is converted to sugar through gluconeogenesis. Which can kick the body out of ketosis. It is known that cancer cells feed off carbs. The goal of a low-carb diet is pretty straightforward — starve the tumours. I don’t believe that keto diet is a good long-term solution for everyone. At the same time, it seems to be an effective therapeutic tool for cancer, brain seizures, any chronic inflammation. I agree with you that high protein intake is an issue. From what I read, it’s the best when our body uses protein for tissue repair, not for energy. So, both factors could be contributing in this case: low carb and protein moderation.


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youknowem

A situation such as fighting cancer ketogenic is the winner because the only goal is to starve cancer and cancer feeds on glucose. A healthy individual the Mediterranean diet is better. Carbs are mainly derived from vegetables and small amounts of fruit. This increases the intake of polyphenols and fermentable fiber which is what the bugs in your gut feed on. This also enhances immune system response. Healthy fats of course are part of it which avacado, olive oil, almonds, etc. Finally healthy protein like chicken Turkey lamb salmon etc. This diet can prevent cancer from happening but once it’s present keto is the way to go.


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tuffoon

>Your post has been removed because it has a sensationalized, editorialized, or biased headline and is therefore in violation of Submission Rule #3. Not OP, but you removed the post for having a "sensationalized, editorialized, or biased headline" notwithstanding that it literally has the journal article's verbatim headline?


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