Day 2, Part 1 (Ketosis, Clinical Applications for Cancer)
I was excited heading into Day 2. . . the first five speakers were all going to speak towards ketosis as a potential cancer treatment.
Also, in case I don't get back around to mentioning it. . . the food at this conference was phenomenal, and all keto-friendly. Eggs and bacon for breakfast one day (and some kind of dairy/berry combo), eggs and sausage the next day. Salads with protein and dressing options for lunch. Delicious. Many people at my table agreed that it was the best conference food they'd ever been served. Also, I wasn't even the only one at my table who brought their own salt! (I brought Redmond Real Salt, someone elese brought pink himalayan salt.)
Other note: I was surprised that a couple people at the conference still balked at mentions of the carnivore diet. I thought the keto crowd would be all on board for it! Most people I talked to were on board, but a couple people seemed thrown off by the idea.
Colin Champ, MD: Dietary Recommendations for Cancer
He didn't call this out, but if you want to read more from Dr. Champ on cancer, check out his website. Specifically, on keto and cancer.
Champ is a clinician and researcher at the University of Pittsburgh. He founded and runs the Cancer Prevention Project. Warburg metabolism was discovered 70 years ago-- this is where cancer cells rely on sugar. This is why ketogenic seem promising for (some) cancer treatments (no sugar for the cancer cells to feed on). This has something to do with faulty mitochondria.
With increased glucose, there is increased cancer cell growth, and with that there is increased fatality.
In a pancreatic cancer study, people who showed blood glucose levels > 200 had low survival. As blood glucose goes up, survival at 2 years decreases.
A 2014 study of ketogenic diets on glioblastoma showed that the ketogenic diet brought blood glucose down.
Exercise, fasting, carb restriction, ketosis are all ways to activate AMPK which decreases cancer growth.
Champ discussed a study where women who formerly had cancer had higher recurrence when eating a high-carb diet when compared to a low-carb diet. This may have something to do with IGF-1 stimulation.
Champ referenced a 1913 (yes, 1913!!!) study published in the Journal of Medical Research that showed a lack of carbohydrates leading to resistance to tumor growth in animals.
Champ said the ketogenic diet is not a miracle cure. He said it is often effective before cancer. And that it can be effective during treatment-- the ketogenic diet works synergystically with radioactive treatment, not by itself.
Interestingly, Champ mentioned a study about statins improving survival in pancreatic cancer patients. (Interesting because low-carbers often are anti-statins for other conditions)
Excess adipose tissue has been shown to be associated with increased cancer recurrence.
Champ, from Pittsburgh, took some pot shots at Cleveland and Cincinnati sports teams. Then he related that to the competition between low-carb and low-fat diets. Out of 57 studies, he found 29 ties, Low Carb won 28, Low Fat won 0.
Champ mentioned that hospital vending machines are a big problem. Lots of people talked about this at the conference-- it isn't something that was on my radar previously. But hearing from these doctors dealing with patients in the real world. . . that is be a huge problem!!
Eugene Fine, MD: Ketogenic Diet and Cancer Treatment
Dr. Eugene Fine was presenting to talk about glucose-avid metastases.
He talked about a 10-patient study he was part of called RECHARGE, where all ten patients had advanced PET+ cancer, and they treated those patients with a very low carbohydrate ketogenic diet (VLCKD), where carbs make up <= 5% of total energy intake. In that study, the patients whose cancers stabilized had 3x higher ketosis. (I have a photo of the chart and the Y-axis shows Dietary BHB / Baseline BHB. I don't have a full understanding, so I am going off of the description of said chart: "Ketosis is 3-fold higher among stabilizers"). Links to information about this study are here, here, and here. The ten patients in this study completed without adverse side effects (note: the patients were specifically chosen because they had glucose-dependent tumors).
For new work, he is working on a 65-patient human randomized controlled trial on patients with breast cancer. A previous study showed that the drug Metformin dropped Ki-67 protein (a prognostic marker for breast cancer, marker of cellular proliferation) in three weeks. The ketogenic diet is usually better than Metformin at controlling glucose and insulin levels, so with that knowledge and the RECHARGE trial vouching for its potential, the keto diet was cleared to be attempted in this 65-patient trial.
They only have data back from their first patient.The patient's Ki-67 (and therefore the patient's health) got worse. That patient was randomized to. . . the ketogenic diet. So the keto diet did not stop this patient's cancer from progressing. Dr. Fine was straightforward about this, and admitted that he was surprised. This was unexpected. He did say that from looking at the patient's tracked BHB levels, the patient was not in nutritional ketosis (BHB too low). He said he, the other researchers, and the doctors take the blame for that. It was interesting. And though obviously sad and painful for the anonymous patient, it was refreshing to see Dr. Fine own up to being surprised by the results. He did not try to sugar-coat things.
Fine went on to talk about how researchers in mouse imaging now think they can trace BHB circulating in the body. He also mentioned ongoing research of rapamycin as a potential anti-cancer drug, as it down-regulates mTOR (but does it cause counter-regulatory effects?).
Angela Poff, PhD: Non-Toxic Methods of Exploiting Cancer Metabolism
Dr. Poff is a PhD working out of the University of South Florida. She mentioned that in many cancers, there is a direct correlation between blood glucose and tumor growth. She showed a chart from this study (study led by Thomas Seyfriend, author of Cancer as a Metabolic Disease) to show this correlation.
Poff said ketones may have an anti-cancer effect in some cancers. Goes back to work done by Magee in 1979.
The idea is that ketones lead to better oxidative metabolism, lower inflammation, lower HDAC, lower blood glucose.
She said exogenous ketones can inhibit some tumor growth.
Cancer cells have increased free radicals.
Hyperbaric chambers can restore oxygen to tumors. In an animal study, animals with cancer did best with a combination of ketogenic diet, ketone esters, and hyperbaric oxygen chamber treatment.
She then discussed press-pulse metabolic therapy. Where press = a chronic environmental stressor and pulse = an acute event with high mortality. She hypothesized that ketosis could be a press stressor for cancer, while hyperbaric oxygen could be a pulse (acute) distressor for cancer. So I think of it like: jab the cancer with sustained ketosis to keep it on the ropes, then go for the knockout punch with the hyperbaric oxygen chamber.
She also talked briefly about the danger of cancer cachexia (loss of skeletal muscle) and how there is no current standard of care to treat cachexia.
From slide: "Cancer will likely require a multifaceted approach", "Effects will be cell, cancer, and model-type dependent", and "Metabolic therapies often work best as adjuvant and investigated as such, including with standard of care". Poff used very cautious language, but she clearly sees lots of potential for ketosis in certain cancer treatments.
Adrienne Scheck, PhD: Tumor Metabolism and the Ketogenic Diet
In vitro, BCNU (a cancer drug) + ketones are effective against cancer.
A 2017 study by Scheck and others showed glowing tumors in mice. I wasn't sure what the takeaway was here honestly, but I'm also kind of dense sometimes :)
She mentioned an increase in survival for mice fed KetoCal vs. standard diet. Study abstract here-- 9 of 11 mice treated with radiation and fed KetoCal were cured
Ketogenic diet reduces Reactive Oxygen Species
Scheck initially thought the ketogenic diet was snake oil; no longer believes so. (Does she think it's extra-virgin olive oil now?)
In vitro, ketones have great effects separate from glucose restriction. BHB increases histone acetylation, increases DNA damage following radiation, is an inhibitor of HDAC, and BHB + radiation leads to enhanced treatment of glioma cells.
Promising keto/cancer research.
Parker Hyde, PhD candidate: Nutritional Ketosis and Advanced Stage Breast Cancer
While all the speakers were excellent, Parker really stood out. He made all of this research hit home as he told the story of his mother being diagnosed (on her 40th birthday) with breast cancer. He made all the high-level scientific discussion reach a personal level. He has spent the last 20 years trying to figure out how to cure breast cancer. (1/6 or 1/8 women will get breast cancer diagnosis in their life. And median survival for metastatic breast cancer [AKA stage 4 breast cancer] is just 26.9 months)
90-95% of occurrence of metastatic breast cancer (MBC) is due to non-heritable traits.
Over 40% of metastases have PIK3CA mutations, and there are reasons to believe ketosis can help against such mutations.
Hyde took care to say not all breast cancers are the same.
Women with post-menopausal obesity have twofold increase in being diagnosed with breast cancer.
Insulin resistance and obesity are correlated (with one another, and with breast cancer diagnoses, if I recall correctly)
Hyde referenced work by Phinney and Volek, and he stated the hypothesis that nutritional ketosis could help breast cancer outcomes. Because metabolism is important, it would decrease inflammation, mTOR would be inhibited, sleep quality would be improved, and emotional functioning would be improved.
He mentioned ketosis being a hammer and everything else being nails.
Then he dug into his work-- the KETO-CARE study (Keto & Chemo for Breast Cancer). 6 months, non-randomized controlled study. Standard care (20 patients, AKA n=20), keto (n=20). For the first three months, the study would feed the patients everything to tightly control what they ate (test biological effect). Then the next three months would be free living (test feasibility-- can the patients maintain the diet on their own?).
Hyde had some very interesting imaging; it showed that the heart even begins using ketones!
It also showed improvements for the patients who were getting the ketosis treatment.
(Blurry photo below, sorry for poor cell phone image quality. Still interesting. I forget what the imaging specifically highlights, but it was certainly a good thing that less of it was showing up in the 3-month image than the baseline image. The patient was treated with the ketogenic diet.)
Powerfully, here is one of the KETO-CARE ketosis-treated patient's quotes. Important to remember this impacts real people. A real person:
"I am so glad I participated in this clinical trial. The study team have taught me a new way of eating that is healthier for me in many ways aside from any effects it may have on my cancer treatment. My most recent scans showed that my liver mets have regressed and are almost undetectable! I have lost 20 pounds without trying and am off sugar without any cravings. I never thought that would happen!"
Q&A Session, Cancer Speakers
A nutritionist from Costa Rica asked about something he'd seen: advisees who got hyperglycemia after taking Vitamin C injections. Dr. Poff responded that many blood glucose meters actually measure Vitamin C on accident, so their hyperglycemia may not be real; it may just be a defect showing hyperglycemia when the true cause of the meter's spike is Vitamin C.
Is cancer a metabolic disease? Answered: Yes, and a genetic disease, and an epigenetic disease.
A Virta doctor asked if there are concerns about chronically inhibited HDAC from ketosis. Champ's answer included something about ketones potentially protecting against radiation. Poff answered that inhibited HDAC could actually increase the antioxidant response.
An infectious disease doctor asked about wound care. He speculated that carbohydrates are exacerbating wound problems but that administrative restrictions (e.g. national dietary guidelines as standard of care) keep him from being able to prescribe low carb as a treatment. He asked if micro-RNA could play a role in wound care. They responded that it would make a good clinical trial. Poff cited some work done by Lisa Gould, Shannon Lynn Kesl in a mouse model where exogenous ketones quickened wound healing. She said it is not published yet, but told the doctor he could email Poff for more research. (Here is Poff's Facebook page if you are interested)
Someone from Vancouver asked a question about T-cells, B-cells, immune cells that require glucose, and essentially asked if it is a concern that ketosis could inhibit the work of these glucose-dependent cells. Dr Scheck said she was not convinced glucose would go too low. Champ said glucose lowering does not across-the-board help on its own.
An area physician asked about treating patients with insulin to treat cachexia (to lower blood glucose). Champ cited work from the 1960s and/or 1970s: case reports of two patients whose tumors were reported to have gone away using such a strategy. However, he said after that a clinic opened in Mexico for that kind of treatment and it did not go well.
How do ketogenic diets affect PET scan imaging? Do the ketones affect the imaging itself and that's why colors stop showing up after adopting keto? Champ said the scans are trustworthy. Hyde added in measured language about how the Warburg effect (e.g. starve cancer by starving cancer cells of glucose) is complex.
A researcher from the NIH asked about efficacy of treatment vs. toxicity of treatment and asked about lean body mass of patients. Hyde said they are tracking lean body mass with DEXA scans. Mentioned that gaining weight is typically a contraindication for health. He said they are collecting health information on toxicity. Dr. Fine said most patients lost weight, which was positive since most were overweight (so the weight loss was indication of health improvement). Champ said weight loss is not encouraged by the mainstream (due to conflation with cachexia), so that is a barrier in a lot of people's treatment. (General idea: fat loss = good, skeletal muscle loss [cachexia] or lean body mass loss = bad). Champ says we now see heavier patients doing worse. Dr. Maryam Lustberg (panel moderator) jumped in and said social lives complicate nutritional ketosis adherence. Hyde brought it back to the personal again and said patients face discrimination. Several patients, upon cancer diagnoses, end up losing jobs. Then they drop out of studies (which shows in the dropout rate as if they could not do the ketogenic diet).
An OSU nurse asked about how the panel's dream for how their work could be applied to real time. Hyde said they need more funding so they could get more data. Dr. Fine said cancer is more complex than many people originally thought. Keto diet doesn't always work on its own. Also, the reverse Warburg effect exists (some cancer cells are actually fueled by ketones). Scheck said patients think of diet as "just food". Said dieticians need keto training and cancer training. She also said funding is tough because most comes from pharmaceutical companies (so keto makes no $$ for them). Scheck also talked about the need for biomarkers and the need to find out which cancers keto helps vs. the ones that keto makes worse. Finally, practically, all clinicians would need to be fully bought-in to support patients in this approach (think, hospital food, etc).
An oncologist from Uruguay asked about the importance of keeping the glucose/ketone index (G/Ki) between 0.7 and 1.0 (based on Seyfried's animal study recommendations. Hyde said they have seen promising results with relatively low ketones (0.5-0.6 BHB levels). Said you can get that low of a glucose/ketone index in vitro or in mice but not in reality. Dr. Fine said you can't extrapolate from mouse models for the G/Ki. Scheck talked about one patient she know of with a G/Ki =/= 1 who is doing well. She talked about the concern of telling a patient to "hit this number" which can in turn increase stress and cortisol levels, which is counterproductive. She said they don't even know the ideal G/Ki for epilepsy treatment which has used ketosis for decades.
Someone from a medical college in Georgia asked about ketosis for blood-based cancers. No one knew anything about keto for blood-based cancers.
Dr. Kushner asked what it is going to take to help ketosis become accepted by the mainstream. He said something about there being little communication between scientists and SROs (scientific research organizations??).
Someone referenced Cantley's article in Nature. I'm not sure for what, but here's a page showing Nature's results for Lewis Cantley Panelists talked about increasing dialogue with NCI, talked about RFAs. Scheck said they need nutrition to be one of the three legs of the stool of cancer care. Champ talked about the difficulty fighting with institutional review boards (IRBs). Scheck said she got into ketosis studying via a high school student group (but I didn't get the name written down, unfortunately). Grassroots. Hyde said they haven't sought traditional grant money-- they need more collaboration. Dr. Fine talked up experiment.com (like kickstarter but for science)-- raised $75K from it, and then 2 weeks after campaign, an anonymous donor gave big $$ to fund their research.
The Uruguay nutritionist asked about BCAA supplementation for cancer patients on the ketogenic diet. Poff said a mouse study did not show a benefit (anything would be speculation at this point)
Someone from Penn who specializes in microbiome asked what the pivotal studies are that need done. Poff said mechanism is important for traditional funding (perfect for drug companies). The ketogenic diet has too many mechanisms so it makes traditional funding hard to come by. Scheck said that whatever study you are doing, you need to collect as much data as you can, whether you know what you need it for or not. The questioner said we need to collaborate and break down silos. Lustberg biopsies taken over time will lead to greater acceptance.
And with that, those are my notes from the first part of Day 2 of the keto conference. . . this doesn't even get us to Day 2 lunch yet! So I'm ending this post for now. More about Day 2 later-- Day 2 would go on to look at the research of ketosis in relation to neurology and performance (with a keynote speech by Gary Taubes in the middle).
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