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Type Name Latest commit message Commit time README.md feat: add harvard study Feb 19, 2022 View code [ ] Theory of winter-fasting and the cure for cancer Abstract Credentials Background theory Statistics Cancer and ketogenesis Hormone seasonality Fasting during spring Autophagy Cancer and fasting Cancer and caloric restriction Discussion My logic The Paleolithic diet The carnivore diet Other diseases Resistance training and permanent mitochondrial adaptation Everything is cumulative The "Metabolic Winter" Hypothesis Long term ketosis Fasting in rats and humans Fat fueled mutations Summary Sources README.md Theory of winter-fasting and the cure for cancer This repository explores the theory of winter-fasting and its correlation with cancer prevention. Please submit a Pull Request if you want to add to the paper, we strive for readability and simplicity. This paper has been reviewed by: * Kjell Asplund, professor in Medicine at Umea University * Charlotte Hoybye, professor in Neuroendocrinology at Karolinska Institute * Miriam Kalamian, MS in Human Nutrition, specializing in therapeutic ketogenic diets for cancer * Kerstin Brismar, professor in Diabetes and Metabolism at Karolinska Institute Abstract The theory is that the majority of people on earth, especially those of descendants from a cold environment, are getting cancer and diseases because they are missing a long term period of fasting, caloric restriction and a ketogenic diet during winter and spring, which was prevalent in their ancestors' lives. The purpose of this paper is to explore the evidence of fasting, caloric restriction and the ketogenic diet and it's correlation to cancer. As well as exploring the advent of agriculture as the cause of cancer. The arguments are analyzed from a logical standpoint using the first principles approach. Credentials I graduated from Uppsala University in 2018 where I majored in Information Systems which can be concluded as the study and analysis of different systems, be it systems in nature, information technology or psychology. I minored in Software Engineering. Since Yoshinori Ohsumi won the Nobel Prize in 2016 on autophagy, I started doing intermittent fasting and advancing to eating one meal a day since 2020-01-01 (with a few breaks here and there). Also I incorporated some longer fasting intervals sporadically. I also find it interesting to speculate about evolution and how different genetics affect our day-to-day lives. However, I'm not educated in this subject, I'm only a reader and have tried to speculate a conclusion based on information around the topic. Background theory Statistics Cancer is the second highest cause of deaths, where cardiovascular diseases take first place, according to data collected from 2017 (Roser and Ritchie 2015). The techniques used in this theory would probably eliminate cardiovascular disease but I'm only focused on cancer for the topic of this paper. My speculation is that cancer started to significantly develop alongside the constant consumption of carbohydrates, probably caused by agriculture and the availability of carbohydrates. We can base some assumption that the current society is suffering from cancer, however there is little to no evidence that pre-agriculture society was suffering from cancer. Johnson (2010) found the oldest remains of cancer to date back to 2700 years ago. The specimen was found to have a form of prostate cancer, and according to Kaiser et al. (2020), prostate cancer has a direct association with insulin resistance. They found that a low carbohydrate/ketogenic diet should be favored for their superior impact on metabolic parameters. This does support the theory based on that the advent of agriculture started getting traction around 7000 to 10000 years ago, where carbohydrate consumption rose, alongside with insulin resistance. Meaning that no statistically significant evidence has been found for cancer deaths, pre-agriculture. Li (2014) shows some statistics in his Ted talk, where he explains that 40% of women in their 40s and 50s actually have microscopic breast cancers, 50% of men in their 50s and 60s have microscopic prostate cancers, and viritually 100% of us when we reach our 70s will have microscopic thyroid cancers. These will however not develop further because they lack a angiogenisis (blood supply). Bray et al. (2018) investigated some statistics about cancer rates in developed countries. They found that, on average, every type of cancer in both sexes was 2.5 times more prevalent in society with a high Human Development Index. Cancer and ketogenesis DeLauer (2019) simplifies the complex cancer growth processes in a video, highlighting that most cancer cells differ from regular cells in how they are converting energy to proliferate. He references a recent study by Hsieh et al. (2019) where they conclude that cell glycolysis is the main cause for cancer growth, but also not a very efficient one, meaning that most cancers respond to high insulin and blood-glucose levels to grow and that cancer use high amounts of glucose to grow a very small amount. Lowering the blood-glucose level was shown to inhibit cancer growth and switching to a ketogenic diet was shown to completely starve the cancer. It was concluded that (most) cancer cells can't convert ketones for growth. Poff et al. (2014) writes in their paper on the survival rate in mice with metastatic cancer, and they mention that cancer cells express an abnormal metabolism characterized by increased glucose consumption, and that, just supplementing ketones, resulted in a greater survival rate. This notion is also supported by Gannett (2016) where she explains that she has stopped the growth of a malignant brain cancer, as well as curing polycystic ovarian disease, Hashimoto's thyroiditis and pre-stage breast fibroids cancers, using the ketogenic diet. Berg (2020) explains in his talk that a human body running on ketones is much healthier compared to one that uses glucose as fuel. His main points are that tumors can't grow on ketones and that a ketogenic diet doesn't increase insulin as much as a regular glucose diet would. D'Agostino (2013) explains in his ted talk that he researched the effect on ketones as a cure for oxygen and pressure based seizures in navy seal divers. He explains multiple examples of people that have used the ketogenic diet as a cure for epilepsy and they are using ketone supplements as a cure for the navy seal divers. He later points out that cancer cells can only use large amounts of glucose as energy and are unable to proliferate on ketones. He quotes professor Thomas Seyfried, the author of Cancer is a metabolic disease. Lunt (2016) also talks about how cancer is extremely dependent on sugar, and she also speaks of how some cancer cells can rewire their own glucose metabolism based on the availability of oxygen. D'Agostino (2013) also did some research on cancer cells and oxygen where he found evidence that a high oxygen environment was highly effective at destroying cancer cells. Harper (2020) presents a few interesting findings on the ketogenic diet. He explains a graph called the axis of illness, where the base cause is carbohydrates which leads to insulin resistance which leads to obesity which leads to inflammation. He notes that, just simply switching to a ketogenic diet would eliminate approximately 70% of chronic diseases. He also goes on about cancer and confirms that cancer cells are dependent on glucose for fuel, and he shows an interesting theory where his hypothesis is that glucose and insulin are very strong growth factors in the body and by lowering them, using the ketogenic diet, allows the immune system to catch cancer cells before it spreads. His latest study on ketogenic adaptation explored the effects on women with terminal breast cancer at stage four, where they supplied them with a ketogenic diet alongside chemotherapy. This resulted in extreme cancer regression after six weeks. Li (2014) explains that all cancers are dependent on mutated angiogenesis for growth. He also demonstrates that cancer cells can be efficiently removed by anti-angiogenesis compounds. Woolf et al. (2015) explores the effect a ketogenic diet has on angiogenesis in mice, they noted that angiogenesis is significantly reduced on a ketogenic diet. Woolf et al. also summerizes the ketogenic diet: "The mechanisms underlying the anti-tumor benefits of the ketogenic diet, caloric restriction (and intermittent fasting) and other potential metabolic therapies have not yet been fully elucidated; however, preclinical data strongly suggests that metabolic alteration may be a highly effective therapy and may in fact enhance the current standard of care for malignant gliomas." Hormone seasonality A recent study from Tendler et al. (2021) measures the change in hormones based on the different seasons. They concluded that, like all other animals, humans also have different winter-spring peaks in hormones for reproduction, growth, metabolism and stress adaptation. The study suggested that humans have a circannual clock that can keep track of the seasons, regulating hormones based on the seasons. The observed changes were in the hormones, cortisol, ACTH, T3, T4, TSH, estradiol, testosterone, LH, FSH, GH, IGF-1 and prolactin. Fasting during spring Dr Francoise Wilhelmi de Toledo mentions in an interview with Buchinger Wilhelmi fasting institute, about the effect that fasting has on spring allergies. She uses fasting to resolve an allergy to birch pollen during April (Wilhelmi 2021). There is also fasting incorporated in the major religions. Both Christianity and Islam have their major fasts usually between March and May. Judaism uses fasting more spread out throughout the year (Wikipedia 2021). Autophagy Autophagy was first measured by Yoshinori Ohsumi, who won the Nobel Prize in Physiology and Medicine in 2016, where the processes is the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components. Autophagy is present in different states of life, but most notably after aerobic exercise or fasting (Wikipedia 2021). Berg (2020) mentions in his talk that he recommends patients to follow a consistent aerobic exercise regime for the benefits of autophagy and health. According to Tramazzo (2019) autophagy will trigger about 10 hours faster if the person is already in nutritional ketosis/fat adapted, amplifying its effects. One common misconception is that one has to be in a fasted state for autophagy to start, however, Chung and Chung (2019) explored the changes of the primary autophagy-related genes using caloric restriction. They found that autophagy-related genes in humans were significantly increased in response to a reduction in calories by 30 percent. Cancer and fasting In his presentation about therapeutic fasting, Fung (2016) goes into detail about the benefits of fasting and that the modern human is built to withstand repeated episodes where there is no food. He goes over that in a fasted state, the body increases it's energy expenditure and cell oxygen availability over four days of fasting, peaking at day three. He explains fasting as the way the body cleans out all the junk that accumilates. Longo (2016) speaks about fasting and how it affects aging and diseases. He did some research with the IGF-1 receptor and genetically created mice with 50% of their normal size. He found that they would live almost 50% longer compared to normal mice alongside with the finding that they also would never develop any diseases, compared to 10% of the normal mice. He also shows his research from UCLA where they would starve worms, bacteria and yeast, and the outcome was that if you switch them from a lot of nutrients to only water, they would live much longer. Another reference of this is from Cheng et al. (2014) where they found that prolonged fasting reduces IGF-1 and promotes hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Brandhorst (2015) did a study on a periodic fasting diet and found that mice on this diet would have an almost halved cancer rate, and they would experience cancer only in their later stages of life and the majority of tumors was benignant, compared to the control group where they would have it from early stages in life and majority was malignant. Sinclair (2019) speaks of his research in anti-aging at Google. His techniques goes around the topic of epigenome manipulation and the prevention of aging, this will in turn prevent every disease that could be age related, including risk for developing cancer. He later mentions that a natural way to manipulate your epigenome is to eat less frequently, and he is currently following an intermittent fasting regime. He also answers a question from the audience on insulin and aging where he concludes that aging is a direct correlator with high insulin and blood-glucose levels. Also there is an important epigenome pathway-chemical called nicotinamide mononucleotide (NMN) which is correlated with nerve health and epigenome repairing. Mills et al. (2017) writes in a paper that NMN occurs naturally in different types of food such as: edamame, broccoli, cucumber seed, cucumber peel, cabbage, avocado, tomato, mushroom, raw beef and shrimp. All of which are low in carbohydrates. Mokhtari et al. (2017) found that some plant foods contain sulforaphane, a compound that is able to specifically target cancer cells to induce apoptosis (programmed cell death). The plant foods include: broccoli sprouts, broccoli, cauliflower, kale, brussels sprouts, cabbage and bok choy. All of which are low in carbohydrates. Li (2014) has a list of anti-angiogenic foods. Some of them are: green tea, strawberries, blackberries, raspberries, oranges, bok choy, kale, ginseng, maitake mushroom, licorice, turmeric, artichokes, lavender, pumpkin, tuna, parsley, garlic, tomato, olive oil and dark chocolate. All of which are low in carbohydrates. Cancer and caloric restriction Caloric restriction has long been used as a measure for people to lose weight, but there are also appliances against disease. O'Flanagan et al. (2017) explored the effects that calorie restriction has on cancer patients. Their specification was to lower the patients' caloric intake by 30 percent, without the incurrence of malnutrition. Their data suggest that caloric restriction acts against inflammation, angiogenesis, insulin and IGF-1. They also mention that a 30 percent reduction in calories in mice, displayed an overall 75.5 percent reduction in tumor incidence. They speculated that caloric restriction combined with a ketogenic diet, would probably increase that number. Discussion My logic What got me starting on this theory was a documentary about how the Greenland vikings came to be, and how they lived. It's described that they lived on an extremely restrictive diet since nothing grew on Greenland. Most of their diet consisted of fish and seal. I got curious about that and came to the conclusion that people would probably have to adapt to their environment, that would then define their diet. The Paleolithic diet The Paleolithic diet is well known in the literature to be a clear replicate of our ancestors' diet. The diet consists of fresh lean meats, fish, shellfish, eggs, nuts, seeds, fruits, berries, vegetables and small amounts of honey. This diet breakdown would be low in carbohydrates except for some sparse times of the year, probably in summer when certain fruits and honey was available. Following this diet, paired with regular exercise and fasting, would leave any individual in ketosis for more or less their entire life. The Paleolithic era lasted from 2.5 million years ago until 9000 years ago, when we switched to an insulin spiking, carbohydrate based diet (Wikipedia 2022). Sebastian et al. (2002) explains that natural selection has had < 1% of evolutionary time to adapt to our new modern diet from the advent of agriculture. They also measured the difference in acid net load of the Paleolithic diet compared to the western diet and found a mismatch between the nutrient composition of the diets and genetically determined nutritional requirements. The carnivore diet My idea here was that people who lived in the north, where winters were harsh, would probably not eat any vegetables during the long winters, because nothing grew. We know that people stocked up on food, but what would they do if the food would perish, they then would have to find food local to the environment. What is interesting about this is that carbohydrates are only prevalent in certain vegetables, and a purely carnivore diet contains almost no carbohydrates. Saladino (2020) talks about the carnivore diet and how skeletal analysis of early humans showed that they were almost exclusively carnivores. He also confirms that humans would eat based on their environment, and that the vegetables today looked nothing like they did for the early humans. He mentions that the domestication of popular vegetables have resulted in favoring the least toxic, the highest yielding and highest caloric version of that plant. And that the availability of plants was nowhere near as they are today. My thoughts on this is that humans probably lived mainly on a carnivore based diet, with a small amount of plants and carbohydrates, consumed in a supplementary way. That would explain the quick energy reaction the body has to carbohydrates. A recent study from Lennerz (2021) shows self reported evidence from people following the carnivore diet for at least 6 months. They concluded that adults consuming a carnivore diet experienced few adverse effects and instead reported health benefits and high satisfaction. As the basis of my theory is that you should enter a ketogenic diet during winter and also do sessions of fasting, Saladino (2020) brings up a few studies where they observed an decrease in oxidative stress when people entered a carnivore diet. This could be connected to either the benefits of the ketogenic or the carnivore diet, however, I think that they are very similar. Other diseases While researching ketosis, I found that it can cure a lot of diseases. Harper (2020) confirms this with his presumed, axis of illness. He explains the axis of illness as a connected model where eating a high frequent and high carbohydrate diet increases insulin resistance which then promotes inflammation and obesity, which then leads to more insulin resistance. This is a bad spiral and it will eventually lead to chronic disease. Harper estimates that 70% of chronic disease, but most notably, cardiovascular disease, cancer, diabetes and alzheimers, could be cured by just breaking this cycle. Now the question at hand, how long should you break the cycle to gain the benefits? Well in Harper's research they see a change in cancer growth and a metabolic change in just six weeks, so if you do this up to six months every winter I would assume that it has some effect. The literature also supports this, Byrne et al. (2017) found that periodic diet breaks work extremely well in a scenario of weight loss without muscle loss and metabolic slowdown. Bosworth (2019) talks about how ketones are a superior fuel for the brain and how a small supplementation of Medium-Chain Triglyceride (MCT) oil in a non-ketogenic diet, would increase the levels of ketones in the blood and in term lead to a larger brain engagement of all cells. This was most noted in older patients with lower brain function, lower memory function or alzheimers. She also speaks of diseases like, ADHD, parkinssons, epilepsy, depression as a result of chronic brain swelling and inflammation, we can probably assume that this is the axis of illness portrayed in the brain. I also remember seeing some sources that newborns have a 70 times higher blood-ketone level compared to those in grown humans, maybe meaning that it's used for brain development in early stage in life. Why we see cancer in children could be that bad cell-components are inherited from the mother. Since the immune systems t-cells have a form of register to remember diseases, that would result in a sort of a learning period for the immune system to slowly adapt. And since it takes seven to ten years to replace every cell in one's body, we could assume that the cancer caused in children is probably inherited from the mother. Mikhaila Peterson (2022) explains how she had lived with severe arthritis, skin rashes and depression for years. But all diseases went away after a few months following a carnivore diet. Resistance training and permanent mitochondrial adaptation Groennebaek and Vissing (2017) writes in their paper on the function of permanent adaptation of mitochondria in the skeletal musculature as a response to resistance training. They found that resistance training could result in a permanent increase in muscle mitochondria, what is interesting about this is the function it could have had on ancient humans. What we know today is that a person with more mitochondria in their skeletal musculature will respond faster to resistance training and hypertrophy, rather than a person with less mitochondria. And if one can permanently adapt to an increase of mitochondria, and then stop training and losing lean muscle mass, one can then regain lean muscle mass faster at a later stage of life. What evolutionary routine would have caused this adaptation? Could it be that ancient humans would fast during the winter and lose muscle mass, that then would be regained during summer when food was more abundant? I think so. Everything is cumulative Longo (2016) says that most people can live without food for six months, without major preparation. This does incite the theory in that humans had to live with less food for a length of a winter. Longo also says that the current western diet, with a high amount of carbohydrates, allows damaged cells and cell-components to accumulate. Ekberg (2021) talks in his video that insulin resistance builds up and eventually becomes "chronic storage" that leads to diabetes and disease. My stance here is that the winter was used as the body's cleaning process for a build up of bad cell-components, and going back to that way of living would tick all the boxes of what has been stated above. One argument against the point I make, that the advent of agriculture is the cause of cancer of the dietary increase of carbohydrates, is the early deaths of ancient humans. Since cancer is cumulative, early deaths could be an explanation for its lack of appearance. However, the discovery of the Shanidar Cave shows four specimens of ancient Neanderthals, which were aged between 30-50. They are dated from around 65000-35000 years ago, well before the advent of agriculture. This gives some idea that ancient humans managed to reach an older age, child mortality might be a cause for the low average age (Wikipedia 2021). The "Metabolic Winter" Hypothesis Cronise et al. (2014) has an interesting hypothesis that food scarcity, longer sleep and cold exposure during winter is a way to remove obesity and cardiometabolic disease. They mention that caloric restriction triggers a network of genes that evolved to protect organisms during times of food scarcity. These genes are shown to down regulate insulin and IGF-1 and release cellular energetics and defense enzymes. These enzymes play a big part in obesity, metabolic syndrome, diabetes, cancer, inflammation, and cardiovascular disease. Moreover, some of these enzymes also promote nonshivering thermogenesis, which would increase internal heat production. Cronise et al. also talk about how increased sleep in cool environments and long nights of winter may work synergistically to promote the conservation of valuable calories. Long term ketosis A common misconception about the ketogenic diet is that the elevated ketones produced will eventually lead to ketoacidosis, which is a state where the body can't regulate the blood-ketone level, resulting in the acidification of the blood and death. Ekberg (2019) explains that this is only prevelent in people without the ability to create insulin, specifically in diabetics. And that nutritional ketosis won't lead to ketoacidosis. Vitamin C is also an interesting observation. Lennerz et al. (2021) found that even with people consuming <10 percent daily recommended intake, no deficiency was ever reported. This could be because of the low antioxidant and vitamin C need during ketosis, compared to a carbohydrate metabolism. Fasting in rats and humans Many of the studies mentioned in this theory are using mice as subjects for fasting trials. In his paper, Demetrius (2005) found that mice and humans have a strong metabolic homogeneity, even in specialized cells and molecular mechanisms that regulate growth, replication, differentiation and death. Demetrius also measured the difference in basal metabolic rate per gram of body weight, they were on average seven times faster in mice compared to humans. Knowing this, we can base some assumption in the different lengths of fasting intervals to apply to humans, based on the studies on rats. Fat fueled mutations According to Xia et al. (2017), there exists a mutation that equips the cancer with the ability to proliferate using fat as fuel. The mutation is found occurring in over 50 percent of melanomas, 10 percent of colorectal cancer, 5 percent of multiple myeloma and 2 percent of leukemia. Also noted by Grabacka, Plonka and Reiss' (2020) paper, ketones do not directly inhibit the proliferation of melanoma and glioblastoma cells. The method that Xia et al. (2017) used was to feed mice a high fat diet and inject acetoacetate to provide a more acidic environment to enhance cancer proliferation potential. This will, however eliminate the biological function of autophagy, which might work against the cancer. Xia et al. also discussed that their tests were isolated and that other bodily functions might have an impact on a whole-organism level. This is supported by Antunes et al. (2016), where they found that fasting increases the sensitivity of human melanoma cells, to cisplatin, which is a type of chemotherapy. Grabacka, Plonka and Reiss (2020) also mention how melanoma cells take advantage of local inflammation for growth. This could be attributed to the reduction of inflammation in the body during fasting. Mokhtari et al. (2017) also writes that sulforaphane reduces inflamation, which can possibly assist in melanoma prevention. Woolf et al. (2015) also noted a reduction in inflammation signaling pathways in glioma tumors, in rats that were fed a ketogenic diet. O'Flanagan et al. (2017) found that caloric restriction reduces systemic inflammation as well. Summary The current lifestyle and diet of modern humans are not sustainable, given the brought up sources, we could probably benefit greatly as a society if we were to follow a regime of a ketogenic diet with caloric restriction and fasting sessions, for six months of the year, probably during winter and spring. The key part about the ketogenic diet, fasting and caloric restriction is that they all work in conjunction and amplifying the benefits. From all I've gathered, there should not be any problems for a person to start following this technique, however, humanity's strongest trait is the ability to adapt, but that adaptation must come slowly. So if you try to follow this, do so slowly and do consult someone with knowledge if you have diabetes or an eating disorder. Otherwise, happy fasting. 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Arbiser, Jun Fan, Qun-Ying Lei and Jing Chen About Theory of winter-fasting and the cure for cancer Resources Readme Stars 17 stars Watchers 1 watching Forks 0 forks Releases No releases published Packages 0 No packages published * (c) 2022 GitHub, Inc. * Terms * Privacy * Security * Status * Docs * Contact GitHub * Pricing * API * Training * Blog * About You can't perform that action at this time. You signed in with another tab or window. Reload to refresh your session. You signed out in another tab or window. Reload to refresh your session.