The layman’s version: Veterans Ketogenic Diet trial 2016

March 25, 2022

Dear Dr. Tan,

I found your abstract , but can you please send me a link to a layman's version that I can understand? Thanks in advance.

Canadian follower

 

Results of the ketogenic diet in cancer trial

http://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-016-0113-y

Abstract- Veteran Affairs ketogenic diet trial

 

Goals :

To see whether veteran cancer patients can tolerate the low carbohydrate/Atkins/modified ketogenic diet .

To observe how much weight loss will happen as a result of this ketogenic diet trial and whether this weight loss is healthy or dangerous for cancer patients.

To see whether cholesterol and blood glucose levels will be affected by the diet.

To examine the emotional health of cancer patients while on the modified Atkins/ketogenic diet.

To examine whether the energy levels of cancer patients increase or decrease while on the modified Atkins/ketogenic diet.

How long will it take to develop ketosis while on the diet?

To observe the tolerance of elderly cancer patients while on the modified Atkins/ketogenic diet. There was no age limit other than having a minimum age of 18.

 

Background :

Both cancer cells and normal cells have the ability to use glucose , starch and sugar for growth and energy. Cancer cells however are quite primitive and lack the sophistication to fully use fats and proteins. Within the cancer cell, there is an important portion of it that we call the "mitochondria", in other words, it functions as the battery pack/energy supplier of the cell. Cancerous "mitochondria" develop internal defects making them unable to produce as much energy as a normal cell. When we fast or starve, the body can survive for many days and stay alive because our normal cells will start to use our stored fats and muscle protein to survive. Normal cells can use this energy from the hidden stores within our muscles and fat until we can find food again. On the other hand, cancer cells, are too simple in structure and too primitive to extract energy from the fat and protein, therefore will starve. They also have a defective "mitochondria" within their cells so they naturally will not have enough energy to power themselves in times of stress or starvation. The ketogenic diet is specially formulated to imitate the effects of starvation or fasting. When we use this diet, we are in effect trying to stress our bodies and starve the tumor. When we fast, the body also produces energy packed substances called "ketones". Cancer cells cannot use these ketones for food while normal cells can. Aside from supplying energy, these ketones have another additional advantage. They can be directly toxic to cancer cells and stop tumor signaling proteins found in the blood to slow down the growth of cancer.

Methods:

We recruited patients from the Pittsburgh VA Medical Center. All of the qualified candidates must have a diagnosis of advanced solid cancer and other wise be in good physical shape. They enrolled in this veterans ketogenic diet trial and were taught to limit their starch, sugar and sweets intake to a total of 20 grams of less a day. That's probably the equivalent of a half of a bagel! Their blood cholesterol levels , kidney and liver tests were monitored closely while they were on the diet. Blood pressure and weights were closely recorded. Full body scans were done at the beginning of the trial and repeated approximately every 2 months. We gave them a questionnaire /survey during their visits and asked them to comment on their symptoms. There were questions on whether they had worsening or improvement of fatigue, poor appetite, breathing problems, financial problems, mood disorders , constipation, diarrhea, or sleep disturbances. To each of these questions they had to give a score. Their weight and blood pressure, heart rates and breathing rates were also recorded at each visit. We wanted to see if their quality of life remained stable while on the diet. In addition, we also drew blood at every visit , to monitor their ketone levels. You will recall that ketones are produced by the body as a defense mechanism when food is lacking. We also measured the ketones in their blood as a way to ensure that they were following the diet correctly. We used statistical tests to analyze the collected data in order to measure the effectiveness and safety of the diet.

The Menu:

Sweets, starchy food and fruits were not allowed. Soda was banned and so was wine. Hard liquor however was allowed but in small amounts. Coffee and tea were allowed , and so was unflavored soda and low calorie drinks. Water intake was encouraged because the diet made one urinate often and may put one at danger of dehydration. Full fats like butter, coconut oil and ghee, full cream dairy , eggs, meat, fish and green vegetables were encouraged. Non fat dairy (milk or low fat yogurt) had a lot of hidden carbohydrates to make up for the loss of fat, therefore these were prohibited. Patients were encouraged to snack only if hungry but we suggested they replace high carbohydrate foods with green vegetables, nuts and cheese or meat jerky. Multivitamin supplements were also added. Artificial sweeteners were used often as long as there were not sugar alcohols. You will recognize sugar alcohols because they end in "ol", like sorbitol, xylitol, etc.

Results:

Many prospective candidates applied for this ketogenic diet trial. Many were not veterans and were therefore immediately disqualified. Out of approximately 300 candidates, 17 male Caucasian veterans were accepted and qualified to join the trial. All of them had advanced stages of their solid cancers. Most had 2 or more treatments in the past which failed to control their tumors. They all had about 6 months or less to live because of the advanced stage of their disease. All of them were in good physical shape other than their cancers. When they began the diet, they were not allowed to have chemotherapy. Most of the patients were in their mid 60s but some were in their early forties and a few were in their late 80s. There was one patient with prostate cancer, another had cancer of the liver and one had cancer of the bile ducts. Two had brain cancer, one patient had colon cancer , two had cancers of the head and neck, and two had pancreatic cancer. There was one patient with kidney and another had thyroid cancer. Three had melanoma, two had lung cancer. One of them had diabetes which was poorly controlled. When he started the diet, he found that his blood sugars went down and he no longer needed his insulin. The diet made them all lose at least 10% of their weight. Some veterans lost as much as 25% of their starting weight. Their blood tests however remained stable and the average cholesterol levels did not rise.  They did not have any worsening of their symptoms. A few of the patients reported some improvement in their breathing while others reported a slight improvement of their nausea and vomiting. The scores showed that the quality of life did not change and in some instances did improve with the diet. Dieting did not make their blood sugars drop, nor did they go up.


When the PET/CT scans were performed, they showed that some patients had worsening of their cancers despite the diet and therefore had to quit before 8 weeks were up. Some patients felt well and their tumors did not grow therefore they continued to diet until 16 weeks. Overall, half of the patients had no growth in their tumors after 4 weeks. After 8 weeks, slightly less than half ( 45%) of the patients had no tumor growth, and after 16 weeks, about one third of the total number of patients still had good control of their tumors. The rest had worsening tumors or they decided that the diet was too difficult to follow therefore they quit. Some patients signed the consent but were not able to start the diet because their tumors grew too quickly. One patient had a brain tumor that did not light up on a PET scan, and was disqualified because his tumor was not actively seeking glucose. Only four patients were able to continue the diet for more than 16 weeks. All of these four patients underwent PET scans which showed that their tumors remained unchanged or became smaller at 16 weeks. Three of them had melanoma, a deadly form of skin cancer. The fourth patient had stage 4 lung cancer. This lung cancer patient however, decided to return to a regular diet and died after 40 weeks. The other three with melanoma continued to stay on this diet and lived almost two years or more. The 88 year old's melanoma eventually spread to his brain but he continued on the diet nevertheless and stayed active until he died at 80 weeks , The 62 year old also had his melanoma spread to the brain but he did try some chemotherapy and radiation after that and survived a total of 116 weeks while on the diet. The 42 year old had some tumor remaining in his left arm and had it surgically removed. He then went on the diet for two more years and stopped. He is now on a low carbohydrate but no longer a strict ketogenic diet. He currently has no tumor visible at his 131 week PET/CT scans and remains alive and well at 138 weeks.

 

Discussion and Conclusions- Veterans ketogenic diet trial:

This ketogenic diet trial was not easy to perform. It requires planning, motivation and perseverance. A family member could be very helpful in menu planning and can keep one motivated. Out of 17 patients, only 3 did very well. Dropout rates were high. The diet appears safe even when one has lost weight. As long as one feels well and energetic, the weight loss becomes less of an issue. It appears that cancer patients who had high levels of ketones in their blood but did not lose much weight, lived a shorter time than those who did lose a lot of weight but had only mediocre ketone levels. Why was this the case? Before we began this trial we predicted  that high ketone levels would be better than low. It could have been because the timing of the blood tests were not always uniform, or the patient may have eaten something shortly before the test, the results were therefore affected.

There is a formula that we use to calculate for the target levels of blood glucose and blood ketones. According to this formula (GKI Glucose ketone index), when someone diets, the blood glucose goes down, while the blood ketones rise to compensate for the loss of energy /loss of glucose. This ratio divides the glucose by the ketone values with the target number as 1.0 or something around that range. Only a few of our trial patients achieved this target number. Was it the weight loss that made the difference in the superior survival of the three patients in this trial? It appears to be so. Was the presence of tumor promoting hormones that lurk in the body's fat deposits, causing cancer to fail treatment? Possibly. Some scientists speculate that a stricter form of this diet, the ketogenic diet instead of the modified Atkins diet, could possibly produce better results in the future. The ketogenic diet has a larger proportion of fats compared to the Atkins diet. We chose the Atkins diet because we felt it would be an easier diet to perform.


This veterans ketogenic diet trial was a short one and we can't make any conclusions about it being a cancer cure, but it appears that for the time being a low carbohydrate ketogenic diet is safe for cancer patients and may possibly help make chemotherapy treatment better tolerated and maybe even more effective. More studies are desperately needed.

Exploring the Link Between Cancer and Weight Loss:

March 14, 2024
Breaking Down the Fear  Ketogenic diets often result in weight loss. Cancer patients frequently lose weight. Does this mean that keto diets are harmful to use in cancer patients? Cancer and weight loss are two topics that often come hand in hand, yet the relationship between them can be complex and sometimes frightening. Weight loss, particularly unexplained or rapid, can evoke fear in many individuals, often signaling underlying severe health concerns. However, when it comes to cancer, weight loss can sometimes be one of the earliest signs of the disease. In today's blog, we delve into the connection between cancer and weight loss, unraveling why the latter often instills fear and how understanding this relationship can lead to better health outcomes. Understanding Cancer and Weight Loss: Cancer involves uncontrolled cell growth and abnormal spread of cells throughout the body. These invading cells affect various organs and systems and disrupt their normal function. Weight loss can be very subtle or profound depending on the type of organ invaded. As cancer takes root and establishes itself, it also spews out cytokines (unique inflammatory proteins) that also serve as signal messengers, signaling muscles to lose volume, resulting in a weight loss phenomenon known as cachexia. Cachexia is a complex syndrome. Inflammation is often at the root of this problem, of profound muscle wasting, generalized fatigue, and poor appetite, Why Are We Afraid of Weight Loss? Weight loss, in general, is often perceived negatively in society. There's a prevailing notion that thinness equates to health, beauty, and success, while weight loss may imply illness or a lack of control. However, when weight loss occurs without intentional dieting or exercise, it can be a red flag for underlying health issues, including cancer. In cancer, especially, the presence of weight loss is disturbing because we traditionally associate it with illness. Association with Illness: Unexplained weight loss is commonly associated with illness, particularly severe conditions like cancer. The fear of the unknown and the potential implications of such weight loss can be daunting for individuals. To be of "normal" weight is equated with health. Loss of Control: Weight loss, especially rapid or involuntary, can make individuals feel like they've lost control over their bodies. This loss of power can be unsettling and exacerbate feelings of anxiety or fear. Uncertainty: Weight loss without a clear cause can be perplexing and raise questions about what might happen within the body. The uncertainty surrounding the underlying cause can contribute to fear and anxiety. During chemotherapy, however, weight loss is inevitable because we are in a catabolic state. The active cancer is making us lose weight. The key is to control or snuff out the underlying cancer. Once you weaken the tumor, less cytokine release and less inflammation will follow. As this occurs, the "source" of the cytokine release will die, and weight gain should naturally recover. Therefore, loading up on carbohydrates to make us appear to be of "normal weight" is incorrect. Loading up on sugary treats will only strengthen the cancer and will only be counterproductive! Conclusion: The fear of weight loss, particularly in the context of cancer, is understandable, given the potential implications for health and well-being. However, by understanding the complex relationship between cancer and weight loss and challenging societal stigmas, we can accept some form of healthy weight loss during chemotherapy. We can learn to recognize unhealthy weight loss (loss of muscle mass) and differentiate it from healthy weight loss during a ketogenic diet (most of which is weight loss from fat and excess water). As long as one feels energetic, with normal blood parameters and no indication of significant liver or kidney failure, anemia, or marrow failure, then some healthy weight loss during chemotherapy or implementation of a ketogenic diet CAN be acceptable.

GINGER ALE DURING CHEMOTHERAPY

March 4, 2024
Are you still drinking "ginger ale" during your chemotherapy sessions? You know, those gleaming, chilled cans of sparkly soda that your cheerful chemotherapy nurse hands out along with your anti nausea pills?  The scent and the taste of ginger help nausea stay away. But did you know that your "ginger ale" contains no ginger? Worse, the HFCS high fructose corn syrup, a highly processed sugar, can do you more harm than good. And making your cancer cells really happy. Next time you go for your chemo session, ask for water instead. Or better yet, bring your own ginger-infused drink from home. Here is some background about ginger. For centuries, ginger has been used as a remedy for nausea and digestive issues, and some scientific evidence supports its effectiveness. Here are some examples. Morning Sickness: Pregnant women often experience morning sickness, and ginger has been traditionally used to alleviate these symptoms. Several studies have shown that ginger can reduce nausea and vomiting during pregnancy. For example, a meta-analysis published in the Journal of Obstetrics and Gynaecology Research in 2014 concluded that ginger supplementation significantly reduced the severity of nausea and vomiting in pregnant women without any significant side effects. Motion Sickness: Ginger is effective in reducing motion sickness. A study published in Aviation, Space, and Environmental Medicine 1986 found that ginger was more effective than a placebo in reducing symptoms of motion sickness. Subsequent studies have supported these findings, suggesting ginger can alleviate symptoms like nausea, vomiting, and cold sweating associated with motion sickness. Chemotherapy-Induced Nausea: Cancer patients undergoing chemotherapy experience nausea and vomiting. The Journal of Alternative and Complementary Medicine 2009 published a review that analyzed several randomized controlled trials and found that ginger supplementation could reduce the severity of chemotherapy-induced nausea. Postoperative Nausea: Nausea and vomiting are common after surgery. A meta-analysis published in the journal Integrative Cancer Therapies in 2012 found that ginger effectively reduced postoperative nausea and vomiting compared to a placebo. However, we need more research to fully understand its mechanisms and best dosage. Everyone responds differently, but ginger, in its natural form, is usually safe to take during chemotherapy. Just make sure its the real thing! Photo credit Dan Sorum @ unsplash

Welcome to all our new members

January 30, 2023
Welcome to all our new members

Getting Started On A Keto Diet

May 17, 2022
Getting started on the keto diet usually sounds like someone is trying to lose weight? When you add cancer to that recipe, it becomes a whole new ball game. Do any of these thoughts sound familiar? “ I want to fight my cancer , and I heard that this diet can help me heal “ “ I’m confused because the keto diet will make me lose weight” “I’m afraid to lose more weight.” “I can’t afford to lose weight! “ “When is weight loss just right, and when is it too much? “ Is there real hope for me? Over the past two decades, I’ve seen my share of cancer patients. Yup, the whole package - diagnosis, anxiety, chemo, radiation, hair loss, weight loss, and, failures. But, I also saw many patients who achieve clean CT scans, remission, happy news, hair growth, and of course, the coveted weight gain. I have my own collection of patients with stage four cancers, a few have actually reached their ten to twelve year anniversary with me. Most of them have made it past five years and some are in complete remission. Yes, stage four to stage zero! How did they do it? You may have come to this website, searching for answers. I wish that I could tell you all that I know, in one sentence, but I can’t. It usually takes me several office visits to educate my patients. For now, you can stick around, and try to absorb the knowledge from current posts. Take time to read through my past blogs. Signup for a keto conference. There is one coming up very soon. The MHS 2022 in Santa Barbara California. May 5 to 8. Read books, and more books. You might be surprised. Not all books are the same. Some are full of dense material, while some are mostly fluff. But eventually, you will find the right book for you. Join me in one of my subgroups. But you need to fit the profile and be past the beginners stage when you join. Or you might get bored! I do show up there from time to time, to break the ice. And by the way, when you are stuck and can’t find the answers you are looking for...you need to make your voice heard and post your questions. What if my cancer doctor doesn’t approve? If your cancer doctor doesn’t know much about the keto lifestyle, or about metabolic approaches to cancer, don’t lose hope. Try to educate them, Share your knowledge. Even if they are at first resistant, with time, some will marvel at your progress and will notice that you are doing better than their average patients. Finally... the number one question that shows up on my blog.... What diet is best for me? I’m so CONFUSED! “ Dr. XXX on YouTube said that a keto diet and weight loss is good for cancer, but another doctor YYY said the opposite, that I should eat, healthy carbs, more plants, fruit , avoid fat and protein, try to gain weight. “ Dr. WWW advocates a vegan diet, but Dr ZZZ said do a carnivore diet.... , help!!!! Let me know your thoughts in the comments below!

New drug for relapsed Glioblastoma, a deadly form of brain cancer

March 30, 2022
There is exciting news on the horizon for glioblastoma, which is a deadly form of brain cancer. Have you heard of activated T cell therapy? It is similar to the car-T cell therapies that you often hear about for blood cancers. Well, this form of therapy is now available for patients with brain cancers. The catch is, you must enroll in a clinical trial. It is not yet available to the public. To qualify, one must have glioblastoma, a form of brain cancer , and cancer must have relapsed after the first diagnosis. Patients who are interested are now able to ask for information about enrolment at the Cedars Sinai Medical Centre in Los Angeles. This trial will be classified under a Phase one type of clinical trial. The drug company, Kairos pharma is the sponsor. This exciting new therapy, otherwise known as KROS 201, is a form of activated T cell therapy. The patient’s white blood cells are first harvested. Blood is removed by a simple intravenous blood draw, and then sent off to the lab to be processed in a cell culture. In the lab, the white blood cells are primed by exposing them to small protein substances called cytokines. This process will in turn activate the white blood cells, specifically the killer T cells. Once activated, these cells can now fight cancer by inactivating cancer stem cells. The T cells are returned to the patient’s body by intravenous infusion. The link for enrolment is not yet available but do keep checking on www.clinicaltrials.gov

Mistletoe plus chemotherapy in non small cell lung cancer

March 25, 2022
Iscador, a type of mistletoe preparation was tested by a medical team in Israel alongside conventional chemotherapy in the treatment of patients with advanced non small cell lung cancer. Although no improvement in survival or quality of life was noted,non hematological side effects from the chemotherapy and hospitalizations were less in the group which received the mistle toe preparation. Possible yet unproven mechanisms of action include improvement of immune function via increasing the number of NK natural killer cells as well as improve the function of Tumor Necrosis Factor Alpha. Fever which is also a noted side effect of this preparation has been described prior to spontaneous regression of certain cancers such as melanoma implying a possible role of immunotherapy in the fight against cancer. No randomized trials on cancer patients have yet been published. 

Brain cancer – Challenges with the ketogenic diet

March 25, 2022
We made little progress in the way of survival in the treatment of malignant brain tumors, specifically the deadly glioblastoma multiform. Despite aggressive surgery followed by radiation therapy and precautionary chemotherapy, they relapse early and survival is measured in months. Patients rarely survive beyond a year. Alternative therapies abound with few successes. Some patients attempt to enroll in clinical trials in search of new drugs that might make a difference in their survival.  There is a biologic treatment available. It is the monoclonal antibody called Bevacizumab. It supposedly controls the growth of blood vessels that supply nutrition to the brain tumor. Shrinking the blood supply supposedly starves the tumor. Very exciting, but nonetheless isn't a cure. Long term survivors still remain a rarity. There is mounting interest in metabolic basis of cancer development. In this respect, I do feel that ketogenic diets have potential benefit in brain cancer patients. The role of sugar and carbohydrates in the progression of brain tumors is interesting. Since most patients also are on steroids to improve brain swelling. It is also bad for them because this also increases their blood glucose. I wonder, if we are indeed adding fuel to the fire. A few case reports of brain tumor patients who were offered the ketogenic diet showed that some tumors stopped growing while others improved their survival. Notably, upon discontinuation of the diet, the tumor was noted to again progress, only to regain control upon reinitiation. Currently there are 4 clinical trials ongoing in the United States involving the ketogenic diet in the treatment of various forms of cancer. Another is ongoing in Germany. More clinical trial participation is desperately needed if we are going to move ahead and forge any progress with this deadly cancer. =

Lonsurf, newly approved colon cancer drug

March 25, 2022
Three weeks ago I got word that another new chemotherapy drug has been approved for the treatment of colorectal cancer. Ideal candidates for this drug are patients who failed previous chemotherapy involving one of the following drugs: 5-Fluorouracil, Oxaliplatin, Irinotecan, Cetuximab (also known as Erbitux) and Avastin ( also known as Bevacizumab).This new drug has two active components, trifluridine and tipiracil. Trifluridine is a new nucleoside analog. In other words, a nucleoside is a nitrogen containing biologic compound linked to a sugar, which when phosphorylated, turns into a nucleotide, which is a vital part of the DNA backbone. Trifluridine therefore is a nucleoside analog, meaning it isn't but acts like a nucleoside. It incorporates itself into the DNA structure and interferes with cell growth and proliferation. Tipiracil inhibits the enzyme thymidine phosphorylase, which catalyzes the degradation of Trifluridine, thus allowing it to last longer. Thymidine phosphorylase by itself has pro-angiogenic properties, meaning it promotes blood vessel formation and encourages better blood supply of tumors, so Tipiracil directly stops this advantage. Furthermore, Tipiracil by stopping thymidine phosphorylase, prevents the formation of thymine and 2-deoxy-alpha-D-ribose 1-phosphate. 2DARP is a strong reducing sugar product of thymidine catabolism and causes increased oxidative stress within tumors, promotes release of more tumor blood vessel promoting factors ( angiogenic growth factors) such as interleukin-8, vascular endothelial growth factors VEGF, and matrix metalloproteinase-1 an enzyme which breaks down collagen and extracelular matrix, which is key in promoting tumor metastases. This three mode action of tipiracil ( inhibits thymine production, thymidine phosphorylase VEGF activity, stops ROS and MMP-1 , VEGF and cytokine production)- makes it more attractive since it can potentiate the action of the common colorectal chemotherapy drug 5- fluorouracil whose main action is to inhibit formation of thymine. The RECOURSE trial, a —international, randomized, double-blind, placebo-controlled study conducted in patients with previously treated metastatic colorectal cancer apparently resulted in statistically significant improvement in overall survival and progression free survival . The drug is given orally, twice a day, for two straight weeks, minus weekends, followed by a two week break. Side effects are listed as anemia, neutropenia, asthenia/fatigue, nausea, —thrombocytopenia, decreased appetite, diarrhea,vomiting, abdominal pain,—pyrexia. Since it is barely a month since FDA approval ( Sept. 24, 2015) it still has not hit our pharmacy shelves. I am however eager to try this. Will update you again in a few months. 

Getting into ketosis

March 25, 2022
How long does it take to get into a state of clinical ketosis? By ketosis, I mean the levels of beta-hydroxybutyric acid reaching to above normal levels yet not high enough to bring you into a medical emergency such as ketoacidosis. As little as a day is all it takes. You an achieve this in different ways. The most common and sure fire method is to simply stop eating. If you fast and only limit your intake to water or sugarless herbal , which technically has ZERO calories, you will achieve a state of ketosis in no time. Another way is to try fasting for 15 hours a day, or roughly, just eat one full meal daily. this should bring you into ketosis too, though not all 24 hours are involved. If you try a ketogenic diet, that means, you will be limiting your carbohydrate intake to approximately 20% of your total daily intake, and take the rest in the form of fats ( 70-75%) and proteins (5 to 10%).  Monitoring your progress will be helpful. A simple glucometer will suffice. Individual serum Ketone sticks, readily available from Amazon.com or special order through your pharmacy can be used to check your ketone levels throughout the week.

Update on clinical trials of the ketogenic diet in cancer

March 25, 2022
Several clinical trials are ongoing throughout the United States at the moment.  The University of Iowa Department of Radiation Oncology is running a couple of Phase I trials on the use of the ketogenic diet plus radiation and chemotherapy in head and neck cancers, and they also have another which studies the ketogenic diet plus chemoradiation in non-small cell lung cancers and pancreatic cancer. Michigan State University has one which recruited brain cancers, also known as glioblastomas, a very deadly type of brain cancer. Duke University recently began a randomized trial studying the ketogenic diet plus androgen deprivation therapy in prostate cancer , using the ketogenic diet versus a control standard diet. Unfortunately per recent info posted on the clinicaltrials.gov website, the trial was terminated as of December 2015, due to lack of funding, and due to the principal investigator leaving . Closer to home, the Veterans Affairs Medical Center in Pittsburgh has their own trial which recently concluded in 2015. This trial recruited patients with advanced solid tumors across broad tumor types and patients dieted up to 16 weeks or until tolerated. The results have not yet been publicly released as it is currently under manuscript review.
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