Re: Ketogenic Diet - Path To Transformation?
Since I spend a few hours every day commuting to work in the countryside, I have spent many hours listening to various podcasts. There are several researchers talking about very good stuff out there, but the two that caught my attention due to their clarity was any podcast ever done to Dominic D'Agostino and Ronda Patrick. The latter also has her own podcast where she has interviewed a dozen or so key longevity researchers. I'll try to summarize below what I have learned. Dominic D'Agostino talks about the ketogenic diet research and Ronda Patrick talks about fasting, saunas and longevity research.
Dominic D'Agostino's research is funded by the Department of Defense (U.S.). In short, he is funded to make military people more effective in battle. Unfortunately that is where the money is though he admits that people with various chronic diseases would benefit the most out of the keto research. He also researches the ketogenic diet for cancer.
One thing that has been around for some time are exogenous ketones (ketone esters). These are ketones in the form of supplements. I've always been against it, even refusing free samples when a company contacted me way back then. Now I'm keeping an open mind on those after listening to D'Agostino's research and results. Specially within the context of brain cancer and epilepsy where research has revealed some clear benefits. I heard D'Agostino go through other people's arguments against exogenous ketones and he does a very convincing job explaining why one shouldn't throw the baby with the bathwater. Exogenous ketones are pricey, though for a specific debilitating disease, it might be worth it.
It seems that there are some people who can sustain healthy levels of ketosis by using exogenous ketones alone and a semi-restricted carbohydrate diet.
According to D'Agostino's experience, some people can take 6 months up to a year to achieve ketoadaptation... Not very practical. Others just get their bodies way too stressed. He also says that if your blood tryglicerides increase after a few months on the ketogenic diet, then the diet is not indicated or beneficial for an individual. In these cases, it is better to drop the ketogenic diet.
According to his research, if you are older than 35-40 years old, it might be worth to do a ketogenic diet (or a 1-3 week fasting under medical supervision) some two to three times per year to "reset" all the cancerous or pre-malignant cells in the body. This is more doable if you can achieve ketoadaptation within a couple of weeks or so though.
Ronda Patrick suggests a good alternative: Do time-restricted eating. That is, eat within a span of 9 hours per day, beginning like at 8 am and having your last meal by 5pm. This allows for the process of autophagy to clear your body from debris. She clarifies that anything other than water already counts as breaking the fast (coffee, supplements, etc. ) Apparently you can put muscle mass by doing only this time restricting eating and nothing else. People have experimented and agree that it can make the whole difference in your health and performance. I've been doing it for a week or so and am also suprised on how better my energy levels are and how my food cravings subsided. She says that you can take a break two days per week and still benefit.
She also recommends that anybody doing a ketogenic diet should check their thyroid function after 6 months.
D'Agostino's protocol for cancer treatment includes
DCA (dichloroacetate sodium) which acts like a mild chemotherapeutic drug for cancerous cells, exogenous ketones mentioned previously, titrating doses of metformin (a drug which sensitizes insulin levels) and a ketogenic diet. He also uses hyperbaric chamber as an oxygen treatment for cancer cells.
I was surprised to learned that he uses metformin to sensitize his insulin levels. Since I'm at risk for insulin resistance due to shift work, I decided to experiment with metformin, but the lowest dose gives me diarrhea. I'll insist for a few more days to see if the diarrhea subsides and to see if this is worth it. Many people are against it, opting for the natural supplement equivalent. Still, metform is something used in functional medicine since the days of Mark Hyman and his book "Ultra Mind Solution".
D'Agostino says that glucose uptake by the brain decreases as we age, so a good solution would be a ketogenic diet and/or exogenous ketones. Apparently, the good results seen in Alzheimer's disease is related to this. Since Alzheimer's is considered a type 3 diabetes where there is impaired glucose uptake in the brain, people get better when they use ketones bodies as a source of brain nourishment instead.
He also gets onboard with the Omega 3 research: It induces oxidative stress at long-term.
From D'Agostino, I learned the concept of the ketogenic diet acting as HDACs inhibitors:
https://en.wikipedia.org/wiki/Histone_deacetylase_inhibitor
Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylase.
HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are being investigated as possible treatments for cancers,[1][2] parasitic[3] and inflammatory diseases.[4]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176946/
Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. Here, we review the regulation and functions of ketone bodies, the relationship between ketone bodies and calorie restriction, and the implications of HDAC inhibition by the ketone body βOHB in the modulation of metabolism, and diseases of aging...
Ketone bodies are emerging as crucial regulators of metabolic health and longevity, via their ability to regulate HDAC activity and thereby epigenetic gene regulation
I also learned that the ketogenic diet inhibits deleterious inflammasomes which have a key role in chronic inflammation.
http://www.nature.com/nm/journal/v21/n7/full/nm.3893.html
The inflammasomes are innate immune system receptors and sensors that regulate the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules derived from host proteins. They have been implicated in a host of inflammatory disorders. Recent developments have greatly enhanced our understanding of the molecular mechanisms by which different inflammasomes are activated. Additionally, increasing evidence in mouse models, supported by human data, strongly implicates an involvement of the inflammasome in the initiation or progression of diseases with a high impact on public health, such as metabolic disorders and neurodegenerative diseases. Finally, recent developments pointing toward promising therapeutics that target inflammasome activity in inflammatory diseases have been reported. This review will focus on these three areas of inflammasome research.
http://ketolifestyle.diet/feature-article/ketogenic-diet-inflammation/
On one hand, inflammasomes can be beneficial to fight against numerous types of pathogens. However, on the other hand, inflammasome activation can be linked to an excess of inflammation involved in the development of several diseases, mainly autoinflammatory and autoimmune diseases. As such, activation of NLRP3 inflammasome in our body in response to diverse DAMPs has been linked to several diseases such as some types of cancer (reviewed in [17]), atherosclerosis (corresponding to a hardening of the arteries leading to heart attack and stroke) [18], multiple sclerosis [19], Alzheimer’s disease [20], Parkinson’s disease [21], type 2 diabetes [22, 23], age-related functional decline [24], gout [13], obesity [22], and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease [25-27]. Notably, NLRP3 inflammasome has also been linked to neuroinflammation involved in chronic mild stress-induced depression [28]. In order to treat or alleviate the symptoms related to many diseases associated with uncontrolled inflammation, the scientific community and drug companies have been researching pharmacological inhibitors targeting constituents of the NLRP3 inflammasomes and its related activated cytokines, such as IL-1β and IL-18 (reviewed in [29]). For instance, the inhibition of IL-1β using antibodies or receptor antagonists is currently used to treat multiple diseases (reviewed in [30]). However, this type of drug is associated with multiple adverse side effects, mainly related to the increase susceptibility to infections, as the drug targets an essential component of the immune system...
This leads us to a review of the following study examining an alternative inhibitor of the NLRP3 inflammasome that can be triggered by a ketogenic diet.
The Study
Prolonged fasting, high-intensity exercise and a ketogenic diet (KD) are known to increase the concentration of β-hydroxybutyrate (BHB), the first ketone produced from acetoacetate in the liver in order to serve as an alternative source of energy instead of glucose when the body is in a fasting state [32]. This phenomenon has been linked to the reduction of oxidative stress [33], to an increase in the AMPK activity [34], an enzyme involved in cellular energy homeostasis, and to autophagy [35], a process involved in the degradation and recycling of altered cellular components. It is interesting to note that these three mechanisms are involved in the regulation of NLRP3 inflammasome [1], meaning that BHB plays at least an indirect role in this process. Furthermore, it has been suggested that BHB may act as a signaling molecule through the binding of the G protein coupled receptor GPR109a [36] or by inhibiting the histone deacetylase (HDAC) molecule [33].
Recently, Youm et al. (2015) [37] reported that BHB suppresses the activation of NLRP3 inflammasome in response to several different NLRP3 activators, with no impact on the activation of other types of inflammasomes. This finding suggests that an elevation in the circulating BHB level, such as the one obtained with a KD, might be beneficial against NLRP3-mediated proinflammatory diseases. The following sections will summarize the main results obtained in this article by Youm et al. (2015) [37].
D'Agostino recommends plenty of soluble fiber in the ketogenic diet which will feed gut bacteria which in turn will produce short chain fatty acids from the fiber. Short chain fatty acids are very good for our health. He claims that a ketogenic diet increases a microbiome based on fat that is not detrimental. He also says that eating less than 100 grams of fat in the ketogenic diet will lead to less testosterone in men and less T3 (thyroid hormone) in women. It also leads to amenorrhea (lack of menstruation), hypothyroidism and lowered function of the hypophysis (pineal gland).
He suggests 1-1.5 grams of protein per kilo of body weight. He covers several research books on cancer and dietary measures in a very clear and down to earth way. When he doesn't, usually the host of the podcast will ask questions for clarifications. He also did one podcast where he covers dozens of questions of lay people regarding cancer protocols and other frequently asked questions. He covers specific brands used in certain studies and what he is currently using.
You can check D'Agostino's website here:
https://www.ketonutrition.org/resources
Ronda Patrick's podcasts can be found at https://www.foundmyfitness.com/ She has been interviewed by several people on the benefits of fasting. She summarizes very complicated research in a clear way. For instance, she talks about heat shock proteins and why cold adaptation and saunas are important. She prefers high temperature saunas as opposed to low temperature FIR saunas just because of its potential to activate heat shock proteins with a higher temperature. I just listened to a couple of interviews done to her. In the next several weeks, I'll catch up with the podcasts she has done and report if there is anything relevant. Here is more background on heat shock proteins:
Healthy brown fat can improve your metabolic health and keep you slim
https://www.sott.net/article/362338-Healthy-brown-fat-can-improve-your-metabolic-health-and-keep-you-slim
"Heat-shock proteins (HSPs) are used by your cells to counteract potentially harmful stimulus. Whenever a cell is exposed to an unfriendly environment, the DNA separates in certain regions and begins to read the genetic code to produce these stress proteins. HSPs are actually beneficial, helping to both prevent and repair damaged proteins. Heat-shock proteins are induced by heat, and this is one reason why sauna use is so beneficial."
I also listened to an interview with Volek (one of authors of The Art and Science of Low Carbohydrate Living) which explains quite clearly the difference with a bad saturated fat and a good saturated fat in terms of cardiovascular risk. De novo lipogenesis ("endogenous saturated fat") is any new fat your body will manufacture from carbohydrates (anything higher than the personal carbohydrate tolerance) and it is correlated with metabolic and chronic disease. De novo lipogenesis creates atherogenic dyslipidemia (cholesterol that induces atherosclerosis). There are lab markers for this endogenous saturated fat.
Exogenous saturated fat (animal fat) has a non-atherogenic effect, regardless of the value of LDL cholesterol which in some people can get very high on a low carb diet.
Well, maybe the explanation is not that clear for some people, but the vocabulary he used is best for the medical community and their difficulty in understanding how a saturated fat can be sometimes good and sometimes bad.
I have settled to eat between 6:30 am and 5pm at the latest at least 5 days per week. I will try to postpone breakfast until 8am to stick to the protocol in the next few weeks. I also will consider doing a short fasting or a strict ketogenic diet (few weeks) at least twice per year. Very easy to do, BTW, if you are only eating before 5pm. I do notice from the past that a mild ketosis is very beneficial for me in terms of energy levels.
I have listened to other podcasts with people speaking against a ketogenic diet as a long-term approach. D'Agostino is hard-core and he says it is worth giving it a try, at least temporarily. He gives tricks to spare muscle mass by using branched amino acids. Still, it is clear that some individuals do need plenty of carbs to thrive.
I wouldn't say there is anything terribly new in the research I listened in the podcasts, except for D'Agostino's cancer research protocols which might be of interest to some forum members. The ketogenic diet has more application in certain cancers, not all of them. The greatest benefit seems to be for those with very malignant gliomas.
FWIW!
