Maximizing ketosis – Examining the old research

March 25, 2022

Maximizing ketosis. Aside from being on a ketogenic diet, what else can one do in order to be as "ketogenic" as possible?

 

SOME BASIC SCIENCE BACKGROUND

The body normally produces ketones in the liver. What are ketones? ketones

 

When the body produces more ketones than it can excrete, we begin to see high levels in the blood or urine. This is ketosis.

 

EXPLAINING THE LINGO

 

IS IT IN THE BLOOD OR IS IT IN THE URINE?

(Emia vs uria)

Hyperketonuria –“Hyper (too much), keto (acid that is produced during fasting), uria (in urine)- in other words, amount of ketones ketones found in urine.

Hyperketonemia- hyperketone (many ketones) + emia (in blood) – from the word “heme or hemoglobin which is what makes blood red- in other words, hyperketonemia stands for “amount of ketones found within blood”.

THERE ARE THREE MAIN TYPES OF KETONES

The ketones are of three main types and are formed inside the liver. They have special names that set them apart and are called acetoacetate, acetone, and beta-hydroxybutyrate.

These ketones all come from Acetoacetate, which is also found in the liver. Of the three, beta-hydroxybutyrate would be the most abundant measurable ketone seen in human ketosis.

 

TRACKING YOUR KETONE LEVELS

At the beginning of ketosis, the first substance to appear is acetoacetate. As ketosis increases, you begin to see beta-hydroxybutyrate. When I monitor for ketosis during a ketogenic diet, I like to measure the serum for beta-hydroxybutyrate, or BHB for short. Urine tests measure acetone and not BHB. I prefer to measure blood ketones , not urine. Blood tests measure BHB, which is a better indicator of a higher level of ketosis. We can measure BHB ketones by drawing blood in the clinic and sending it off to a special lab, or a more convenient way would be via finger prick blood testing using a home ketone monitor which you can buy online. Urine tests for ketones measure acetone and not BHB. You might detect acetone but a better test would be for BHB.

 

DIABETIC KETOACIDOSIS -

NOT THE SAME AS NUTRITIONAL KETOSIS

DIETARY ketosis is different from DIABETIC ketoacidosis (DKA) that is seen in uncontrolled diabetes, which can be a dangerous thing. Fortunately with dietary/therapeutic ketosis, the levels do not get high enough to be life threatening. Diabetics who go on a ketogenic diet, find that not only do they lose weight , their glucose levels may become more controlled. Caution must be taken though if you are diabetic, and already on anti diabetic medications like insulin or glipizide. The resulting lower glucose levels might mean greater risk of very low glucose levels and might result in lightheadedness and dangerously low glucose levels in diabetics on medication. Always consult a doctor when trying the ketogenic diet for the first time! This is a medical diet, not a fad diet, and should be monitored medically to be safe and successful.

NUTRITIONAL KETOSIS

 ACHIEVING KETOSIS VIA FASTING or a HIGH FAT DIET

 

FASTING OR STARVATION

The quickest way to becoming ketotic is via fasting , starvation or in other words, by not eating! One could fast from solid food for 14 to 18 hours and quickly reach ketotic levels but must keep up with their hydration and drink water or low calorie broth.

 

HYDRATION IS IMPORTANT TOO- DRINK!!!

Drink plenty of water. If you find yourself drinking less than a liter a day you can quickly LOWER ketosis, (antiketogenic) therefore it is important to take enough water to keep well hydrated during periods of fasting. Fasting also has a "diuretic" effect , meaning it makes you want to urinate or “pee” more. Too much urine output will lead to dehydrations and lower ketosis.

 

KETOGENIC DIETS

Another way to ketosis is by taking in more fat compared to protein or carbohydrates. This is generally what we call a ketogenic diet.   In the 1950s and 1960s, experimental studies on human subjects used diets that consisted only of oleomargarine and saltine crackers which provided 1000 to 2000 kilocalories a day, out of which 900 came from fat, which would be roughly equivalent to 20% of carbohydrates, 2-5 % protein, and 75-78% from fat . Sounds a bit extreme to me!

 

SOME PEOPLE ARE BETTER KETONE PRODUCERS THAN OTHERS

The scientists also found out something interesting. After consuming this type of diet, not all of the young men in their studies had ketosis. Inspite of the fact that they all ate the same diet, some were not ketotic at all while others achieved high levels of ketosis. It appears that other hidden factors came into play, and diet was not the only driving force. After 7 days of starvation some of the men measured ketone levels as high as 7 mM/L while others only made 1 mM/L.

 

MEAT EATERS

Another ketogenic diet regimen used during the late 1950s/1960s contained only dried meat and lard, which meant that 70 % was fat and 30% was protein, with zero carbohydrates! You can clearly see however that with a diet like this, ketosis will be achieved easily, but the overall nutritional content might need more attention .

 

TYPES OF MODERN KETOGENIC DIETS (1990s-2017)

I wrote about this previously, (diets )but will go over them again. Nowadays, the ketogenic diets are used in children with uncontrollable  seizures. Nutritionists made these diets more pleasing and use more ingredients other than just saltines and margarine. You can probably find a lot of these online. These diets still contain an overwhelmingly high amount of fats (70-75%), and lower amount of carbohydrates ( 5-10%). The rest of the diet contains the protein (~20%). When using a ketogenic menu, all ingredients are weighed, and not simply measured with a spoon or cup.

In the 1980s and 1990s, the Atkins diet became popular, this means limiting the daily amount of carbohydrates to 20-40 grams daily, while allowing more proportions to fats and protein. While ketosis can be achieved, the levels may or may not be as high as with a strict ketogenic diet.

This is the same as the Atkins diet. Fats are 60% and Carbs are 10% of the diet. Contrary to belief, Atkins does not have to be high in protein.

Strict ketogenic diet. Notice the large proportion allocated to fats. 70-75%

 

POST EXERCISE KETOSIS, WEIGHT AND KETOSIS

 

WEIGHT DOES MATTER- Less is more

Weight and exercise also can affect ketosis. When starting the ketogenic diet, most if not all people will lose weight immediately, but because of differences in body weight, not all will become ketotic. Scientists noticed that heavier subjects produced less ketosis compared to normal weight people despite being on the same diet. More fatty tissue appears to be less conducive to achieving ketosis, despite adherence to a strict ketogenic diet. Newer evidence regarding the presence of the hormone leptin, which is found in fat, show a link between higher leptin levels and cancer risk.

 

EXERCISE CAN INCREASE KETOSIS, BUT REST IS IMPORTANT TOO

Moderate prolonged exercise followed by a prolonged rest period, can also quickly produce ketosis. During moderate exercise, the liver produces ketones while the muscles are busy destroying (oxidizing) them. Due to this balanced process, we don't see elevated blood ketones during exercise.  However, once exercise stops, the ketone destruction stops, but the liver keeps producing ketones, therefore the levels now begin to rise. Therefore one has to have a period of rest right after the exercise, in order to see the higher levels of ketones in the blood.

 

COLD EXPOSURE AND KETOSIS

 

Cold Temperature appears to increase ketosis.

Patients measured higher levels of blood ketones during winter and they produced less ketones during summer Subjects who were exposed to extreme cold (8-14 C) also produced more ketones than those who were exposed to warm (21-25 C) temperatures.

 

Winter ketosis versus lower ketones in summer

 

The cold exposure appears to trigger the pituitary gland ( pea sized gland in the brain to increase catabolism (opposite of anabolism). Catabolism is a breakdown of energy. 

Increased catabolism will lower overall blood glucose while at the same time, increase blood and urine levels of ketones

 

SUMMARY - MAXIMIZING KETOSIS -

HOW TO?

 

See your doctor first, then get a good menu plan

Seems like the key to success is to get together a decent menu plan or diet plan, monitor one's weight, and see a health professional first before embarking on any diet, especially if it is a ketogenic diet.

Diabetics , take some precautions

Diabetics should be especially aware that this low carb approach might lead to dangerously low blood glucose / sugar levels. We can avoid this by cutting back on some of the glucose lowering medications. It is probably a good idea to have a doctor supervise you while you try to do this.

 

OTHER THINGS THAT CAN HELP BESIDES DIET

Losing some weight will help in maximizing ketosis. A target goal of BMI (Body Mass index) 29 or below . We calculate BMI using body height and weight. If the weight is too much for the height, the BMI rises.

Obese people will have larger BMIs. There are many online BMI calculators that one can use to estimate the correct weight for one's height.

Here is a handy BMI calculator:(BMI calculator)

 

Exposure to cold climates can increase ketosis. There is some decent research behind it. See this  interesting  JAMA paper. I thought this was pretty much " Vintage  research" , but this is understandable because very little research was done on ketosis between the 1960's-1990s!

 

Daily moderate exercise followed by rest is another achievable goal. A daily half mile or mile walk followed by a few hours of rest should be decent exercise for most people. People with heart disease or high blood pressure should see a doctor before trying  any strenuous exercise regimen.

Keep well hydrated. Drink at least 2 liters of water daily. Anything less than a liter a day is antiketogenic. Take into account the body weight. More weight means you need to drink more in order to keep hydrated.

 

SUMMARY

A brisk early morning walk gives you the benefits of the previous night's fast (assuming it is 7-8 hrs minimum). Eat dinner early (~before 6 pm). Take a nice long walk in the cold (winter preferred) air. This will keep the heart pumping !

Don't forget to take a long rest after the exercise.

During the exercise, we produce no ketones. It is only after the exercise ends that we see ketones rising during the rest period!. This exercise + fast strategy will quickly help the " get-into-ketosis-quick" plan. Add to that, drinking at least a liter of water will improve hydration and boost ketosis!

 

BLUE LIGHT CAN BE BAD

Lastly, a good night's quality sleep and shutting down your iPads and iPhones early in the night should help top off your day


March 14, 2024
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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
January 30, 2023
Welcome to all our new members
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!
March 30, 2022
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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. 
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. =
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. 
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.
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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