Dr. Adrienne Scheck – Tumor Metabolism and the Ketogenic Diet
healthy diets October 22nd. 2019, 4:34amFilmed at the Emerging Science of Carbohydrate Restriction and Nutritional Ketosis, Scientific Sessions at The Ohio State University
Learn more at https://blog.virtahealth.com/category/science-research/
An impressive body of scientific evidence over the last 15 years documents long term benefits of carbohydrate-restricted, especially ketogenic, diets. We now understand molecular mechanisms and why they work. Popular books and articles now challenge the advice ‘carbohydrates are good and fats are bad.’ Circa mid-19th century urinary ketones were identified in diabetics sealing their toxic label for the next 150 years. Despite work four decades ago showing ketones were highly functional metabolites, they are still misidentified as toxic byproducts of fat metabolism. The vilification of fat by regulatory and popular dogma perpetuates this myth. But the nutrition-metabolic landscape is improving dramatically.
A growing number of researchers have contributed to what is now a critical mass of science that provides compelling clinical evidence that ketogenic diets uniquely benefit weight loss, pre-diabetes, and type-2 diabetes. In the last five years, basic scientists have discovered that b-hydroxybutyrate (BHB), the primary circulating ketone, is a potent signaling molecule that decreases inflammation and oxidative stress. BHB has been suggested to be a longevity metabolite, with strong support from recently published mouse studies showing decreased midlife mortality and extended longevity and healthspan. Although type-2 diabetes is often described as a chronic progressive disease, emerging evidence indicates that sustained nutritional ketosis can reverses the disease. There is growing interest in studying potential therapeutic effects of ketosis on cardiovascular diseases, cancer, and neurodegenerative diseases including Alzheimer’s and Parkinson’s. There are even reasons certain athletes may benefit from nutritional ketosis and ketone supplements ─ debunking the long-standing dogma that high carbohydrate intake is required to perform optimally.
With the support of the well-established Ohio State Food Innovation Center, this conference will bring together the top experts in these fields to share what has been achieved and what remains to be done to advance this exciting field of scientific discovery.
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Filmed at the Emerging Science of Carbohydrate Restriction and Nutritional Ketosis, Scientific Sessions at The Ohio State University
Learn more at https://blog.virtahealth.com/category/science-research/
An impressive body of scientific evidence over the last 15 years documents long term benefits of carbohydrate-restricted, especially ketogenic, diets. We now understand molecular mechanisms and why they work. Popular books and articles now challenge the advice ‘carbohydrates are good and fats are bad.’ Circa mid-19th century urinary ketones were identified in diabetics sealing their toxic label for the next 150 years. Despite work four decades ago showing ketones were highly functional metabolites, they are still misidentified as toxic byproducts of fat metabolism. The vilification of fat by regulatory and popular dogma perpetuates this myth. But the nutrition-metabolic landscape is improving dramatically.
A growing number of researchers have contributed to what is now a critical mass of science that provides compelling clinical evidence that ketogenic diets uniquely benefit weight loss, pre-diabetes, and type-2 diabetes. In the last five years, basic scientists have discovered that b-hydroxybutyrate (BHB), the primary circulating ketone, is a potent signaling molecule that decreases inflammation and oxidative stress. BHB has been suggested to be a longevity metabolite, with strong support from recently published mouse studies showing decreased midlife mortality and extended longevity and healthspan. Although type-2 diabetes is often described as a chronic progressive disease, emerging evidence indicates that sustained nutritional ketosis can reverses the disease. There is growing interest in studying potential therapeutic effects of ketosis on cardiovascular diseases, cancer, and neurodegenerative diseases including Alzheimer’s and Parkinson’s. There are even reasons certain athletes may benefit from nutritional ketosis and ketone supplements ─ debunking the long-standing dogma that high carbohydrate intake is required to perform optimally.
With the support of the well-established Ohio State Food Innovation Center, this conference will bring together the top experts in these fields to share what has been achieved and what remains to be done to advance this exciting field of scientific discovery.
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October 22nd, 2019 at 4:46 am
It’s frustrating just TRYING to get someone to try a keto diet even when they have a brain tumor. And the people around them too- they won’t try any of this. There’s nothing to lose! It’s maddening
October 22nd, 2019 at 5:16 am
My 31 month old grandson was diagnosed with DIPG and is almost done with radiation. I have mentioned ketogenic diet several times but parents want to follow just what the doctor says. I feel frustrated,
October 22nd, 2019 at 5:30 am
ROS (Reactive Oxygen Species) ???
October 22nd, 2019 at 5:57 am
Cancer cells can use glucose, fructose, ketones, lactate, fatty acids and some amino acids as fuel sources.
Ketones and lactate “fuel” tumor growth and metastasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047616/
"Ketones are a “super-fuel” for mitochondria, producing more energy than lactate and simultaneously decreasing oxygen consumption.15–17" "So, just as ketones are a “super-fuel” under conditions of ischemia in the heart and in the brain, they could fulfill a similar function during tumorigenesis, as the hypoxic tumor exceeds its blood supply. Stromal ketone production could obviate the need for tumor angiogenesis. Once ketones are produced and released from stromal cells, they could then be re-utilized by epithelial cancer cells, where they could directly enter the TCA cycle, just like lactate. In this sense, ketones are a more powerful mitochondrial fuel, as compared with lactate." "Similarly, acute fasting in rodent animal models is also sufficient to dramatically increase tumor growth.22 Both of these experimental conditions (diabetes and fasting/starvation) are known to be highly ketogenic and, thus, are consistent with our current hypothesis that ketone production fuels tumor growth. Finally, given our current findings that ketones increase tumor growth, cancer patients and their dieticians may want to re-consider the use of a “ketogenic diet” as a form of anti-cancer therapy."
Ketone body utilization drives tumor growth and metastasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507492/
"Thus, the tumor stroma may serve as a reservoir for ketone body production, while cancer cells upregulate the enzymes required for ketone body re-utilization, driving oxidative mitochondrial metabolism (OXPHOS) in epithelial cancer cells (Fig. 9). To prevent this form of “two-compartment tumor metabolism,” ketone inhibitors should be designed to halt ketone body production in cancer-associated fibroblasts and ketone body re-utilization in epithelial cancer cells. This simple strategy could effectively starve cancer cells to death by “cutting off their fuel supply.” Finally, it is worth noting that ketogenic fibroblasts were more prone to a loss of stromal Cav-1 expression. In breast cancer patients, a loss of stromal Cav-1 expression is associated with increased tumor recurrence, metastasis, drug resistance and overall poor clinical outcome.10-13 Thus, stromal Cav-1 could be used as a biomarker to select patients that would be more likely to benefit from therapy with ketone inhibitors, allowing biomarker-based treatment stratification and personalized cancer therapy."
Ketone bodies and two-compartment tumor metabolism
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507491/
"We have previously suggested that ketone body metabolism is critical for tumor progression and metastasis. Here, using a co-culture system employing human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts, we provide new evidence to directly support this hypothesis. More specifically, we show that the enzymes required for ketone body production are highly upregulated within cancer-associated fibroblasts. This appears to be mechanistically controlled by the stromal expression of caveolin-1 (Cav-1) and/or serum starvation. In addition, treatment with ketone bodies (such as 3-hydroxy-butyrate, and/or butanediol) is sufficient to drive mitochondrial biogenesis in human breast cancer cells. This observation was also validated by unbiased proteomic analysis. Interestingly, an MCT1 inhibitor was sufficient to block the onset of mitochondrial biogenesis in human breast cancer cells, suggesting a possible avenue for anticancer therapy. Finally, using human breast cancer tumor samples, we directly confirmed that the enzymes associated with ketone body production (HMGCS2, HMGCL and BDH1) were preferentially expressed in the tumor stroma. Conversely, enzymes associated with ketone re-utilization (ACAT1) and mitochondrial biogenesis (HSP60) were selectively associated with the epithelial tumor cell compartment. Our current findings are consistent with the "two-compartment tumor metabolism" model. Furthermore, they suggest that we should target ketone body metabolism as a new area for drug discovery, for the prevention and treatment of human cancers."
October 22nd, 2019 at 6:52 am
My mother in law was diagnosed with TNBC. After reading Dr. Seyfried's case study regarding a patient with stage 4 TNBC, I came searching. This is so encouraging. I'm nearly crying. How wonderful. Thank you for posting. I hope people will listen.
October 22nd, 2019 at 7:18 am
Absolutely fascinating
October 22nd, 2019 at 7:37 am
I didnt understand a damn thhing she said lmao
October 22nd, 2019 at 8:25 am
BTW, I think an important message that shouldn't be lost here is…
while the ketogenic diet may not be as "effective" in treating cancer as radiation and keto combined, this should not be interpreted that a ketogenic diet would be ineffective in PREVENTING cancer in the first place.
(Excellent and insightful talk)
October 22nd, 2019 at 8:59 am
What happens in establishment medical training that would cause someone as smart as this woman to think a ketogenic diet "snake oil." Particularly given the great research work done in the 1960s and 1970s?
October 22nd, 2019 at 9:48 am
Awesome. Great results.
October 22nd, 2019 at 10:38 am
Very informative. Thanks.
So brains love ketones. And ketones stop the brain cells from dying and thus prevent alzhimers ?
Why does glucose to the brain reduce as we grow older ????
October 22nd, 2019 at 10:51 am
Amazing. I think ketones are our normal and original source of energy. We’ve been forced to consume glucose these past 70 years through big food & pharma companies. Sad that we think sugar is the primary source. Crazy…
our ancestors 500 years ago didn’t have refined processed sugar & carbohydrates. And they survived…
I’ll never understand how it’s BAD to NOT eat carbohydrates. Lol. So stupid. Can’t stand the health & food industry.
October 22nd, 2019 at 10:52 am
On his disclosures he shows receiving money from Nestlé. Nestlé is one of the world's largest promoters and sellers of sugar laden products. I wish he would explain his disclosures. I had to stop watching. I am not a troll and I welcome any educational advice. I love Virta Health.
October 22nd, 2019 at 10:56 am
But on keto diet you have little glucose so maybe that is the reason why the brain “prefer” ketones, because then it is more stable choice of energy
October 22nd, 2019 at 11:12 am
The people doing these expirments are incredible! Thank you Dr. Stephen and your team for such insightful research.
October 22nd, 2019 at 11:14 am
Do you support keto diet?
October 22nd, 2019 at 11:16 am
Thank you for your research
I l try the best i can to practice ketone diet .
October 22nd, 2019 at 12:11 pm
Hello, I have a question about sugar on keto, can I have it in small amounts as they are in some products? For example sausage that have 3 grams of carbs but 1.5 grams in it are sugar. What is the safe limit of sugar in that form per meal and per day?
October 22nd, 2019 at 12:48 pm
ketones seem to be well advertised but who and where can get product?
October 22nd, 2019 at 1:34 pm
Wow!
October 22nd, 2019 at 2:21 pm
Just think if these people were fat adapted compared to 60 yrs on glucose these stats would be way more in favor of ketones
October 22nd, 2019 at 3:04 pm
Hey, look! Christopher Walken is presenting metabolic science!
October 22nd, 2019 at 3:36 pm
The more reason I've to stay in this keto-if lifestyle diet..thx for the presentation Dr Sthephe..
October 22nd, 2019 at 4:27 pm
Thank you for your research. Such encouraging findings and so much more to learn.
October 22nd, 2019 at 5:01 pm
Such an incredibly interesting lecture and very well presented. Thank you.
October 22nd, 2019 at 5:04 pm
I'm still thinking that the cause of alzheimer's is tissue damage due to excessive glucose levels, so then it's reasonable to expect that energy deficit would be a side effect, not a cause. The fact that ketone metabolism is preserved is consistent with either model. The exercise cohort backs this up too. Exercise lowers average glucose/insulin levels. Lower glucose/insulin should result in additional energy deficit in cells with impaired glucose metabolism. However, if it is shown, that low carb/ketogenic not only improves energy balance – but also slows progression of the disease then either the ketones are protective OR lower glucose levels are sparing the remaining undamaged tissues…..
October 22nd, 2019 at 5:38 pm
It's fascinating to hear that human milk is said to be the food that puts / keeps human infants (babies) in ketosis. After all, human milk has a higher lactose content – milk sugar – than cows' milk. Of course, human milk is usually served raw.
Some people cannot make good use of the milk from cattle. However, many who think they cannot find that they can enjoy milk from cows, IF it is consumed unprocessed. 'Raw' milk is a very different thing from the highly processed stuff sold in supermarkets:
– It contains enzymes which aid digestion, including lactase which digests the lactose, so people don't need to 'have the adaptive gene' to produce lactose.
– Unprocessed milk contains beneficial bacteria, also known as 'probiotics'.
– Unprocessed milk also contains all the vitamins we need, including those destroyed by the heat treatment, like Vit C.
– The cooking process alters the proteins in milk, making them more allergenic.
– In processing, the butterfat is separated from the rest of the milk. The fat globules are artificially reduced in size, allowing them to be absorrbed across the gut wall without being digested, especially those with 'leaky gut'.
– The butterfat is then added back to a level of 3.25% in 'whole' milk. Unprocessed milk from well managed Holstein cows averages nearly 4%. Cattle from many breeds on high forage or all 'grassfed' diets averages as high as 5-6% butterrfat, or more.
– The processing steps expose the milk to air which can oxidize the fats. And to surfaces that can collect bacteria.
– Supermarket milk almost always comes from CAFOs – not ecologically sustainable. Instead of allowing the cows to harvest much of their own feed themselves from perennial pastures, which they naturally fertilize. Properly managed, livestock grazing pasture asequesters carbon, reduces or eliminates soil erosion, increases the diversity of the soil life below the surface and the plant community above, provides habitat and food for a range of wildlife, including pollinators, birds, etc, increases rain infiltration which mitigates the effects of drought and reduces flooding, while replenishing springs, ponds & lakes, streams, rivers, and aquifers…
Cows in CAFO operations are confined, then fed a TMR (total mixed ration) that does not allow each cow to select what she needs that day. The feedstuffs in the TMR are farmed mechanically, using petroleum, synthetic fertilizers, and an array of toxic chemical 'cides'.
– CAFO milk is usually from cows given GMO hormones, rGBH.
– In the North and East, CAFO cows are increasingly being kept indoors 24/7 with little or no access to pasture or sunlight.
– Processed milk is almost always from cows fed a high grain ration, dropping levels of the beneficial Omega 3 fatty acids to nearly nothing.
– Many raw milk producers bottle their milk in glass. The plastic lined cartons and plastic jugs transfer synthetic chemicals to the milk, which some people can even taste and smell.
Most raw milk is produced on pasture-based farms, and some is 100% 'grassfed' with levels as much as 7+ times higher than grass + grain fed milk. The farms producing this milk generally avoid synthetic hormones, antibiotics (except in emergencies, which are rare in pasture-based cows), The profits from milk sold in supernarkets go mostly to the processor, and to the stores. Dairy farmers are often paid little over the cost of production, sometimes less than the cost to produce the milk.
Whenever we make a purchase we are voting with our dollars – the vote that counts most. Seeking high quality milk, meat, eggs, etc from small farms and buying DIRECTLY from those farms is a vote for sustainable, ethical, regenerative farming.
Best of all – the flavor is fantastic!
October 22nd, 2019 at 6:32 pm
I am sold on the ketone being the preferred brain fuel but how can you answer the question "If it is the preferred fuel, why do the brain still need 25% glucose with 75% ketone to function?"
October 22nd, 2019 at 7:15 pm
October 22nd, 2019 at 7:30 pm
Also thanks for this insightful research.