The Deep End

I decided to create a “Deep End” resource to serve as a repository of information that tends to go a bit deeper into various subject matter. Jump in if you feel inclined. I highly recommend it.

Added: 10/15/2017 12:00 PM

Fat: Storing(insulin) vs. Burning/Wasting(ketones)

You can always count on Dr. Rhonda Patrick to go next-level with the people she interviews, which typically results in a more profound Q&A.

Dr. Rhonda Patrick’s podcast interview with Dr. Dominic D’Agostino on Modified Atkins Diet, Keto-Adaptation, Ketosis & More:

Dr. Rhonda Patrick’s podcast interview with Dr. Guido Kroemer on Autophagy, Caloric Restriction Mimetics, Fasting & Protein Acetylation:

Dr. Rhonda Patrick’s podcast interview with Dr. Valter Longo on Fasting-Mimicking Diet & Fasting for Longevity, Cancer & Multiple Sclerosis:

Dr. Rhonda Patrick’s podcast interview with Dr. Ruth Patterson, Ph.D. on Time-Restricted Eating in Humans & Breast Cancer Prevention (video added 9/7/2017 1:45 PM):

Discussed in this podcast:
•The importance of time-restricted eating as a practical public health intervention, mostly for it’s ease of implementation, that may have a widespread impact on disease risk.
•Why you should probably make sure your time-restricted eating window occurs earlier in the day, rather than later.
•How the first 5% drop in weight loss can have disproportionately large effects on the metabolic factors associated with breast cancer risk when compared with subsequent weight loss.
•The association of longer fasting durations beginning earlier in the evening and improved sleep in humans, as well as spontaneous physical activity in their day-to-day lives.
•The relationship between metabolism and breast cancer risk.
•The effect of lifestyle factors, such as obesity, physical activity, what and even when you eat, whether or not you smoke tobacco… and how even modest changes, such as consuming food earlier in the day and only during an 11-hour window, can decrease breast cancer risk and recurrence by as much as 36%.
•The importance of starting your fast earlier in the evening, and how an earlier eating window has been shown to correlate to reductions in inflammatory markers.
•The association of higher circulating insulin levels with breast cancer risk, and how insulin itself has an important relationship with estrogen by affecting the levels of sex-hormone binding globulin.
•The dangers of having a cellular environment that is inflamed, as the case is with the obese, and simultaneously having elevated cellular growth signals, which is also characteristic of the hormonal milieu of the obese.
•The surprisingly small role heredity plays in determining overall risk of breast cancer when compared to lifestyle factors.
•How healthful lifestyle habits, like choosing to eat during the right window, ultimately helps us trend our risk for many of the diseases of old age in the correct direction instead of influencing only one or another.

Ray Cronise on Cold Thermogenesis, Intermittent Fasting, Weight Loss & Healthspan:

Dr. Rhonda Patrick speaks with Ray Cronise, a former NASA material scientist and co-founder of zero gravity, a company that offers weightless parabolic flights to consumers and researchers. In this episode, coming at the tail end of a rather extreme 23-day water fast for Ray, we discuss, perhaps unsurprisingly, some of the benefits that are associated with fasting! Ray talks about shifting one’s perspective from looking at nutrition only through the lens of meeting day-to-day nutritional needs, and instead, also considering optimizing metabolism for longer-term effects as well, the importance of thinking about longevity in the context of functional healthspan, some of the similarities between the body’s physiological response to heat stress, cold stress, and exercise and so much more.

Added 12/18/2017 12:30 PM

Dr. Eric Verdin on Ketogenic Diet Longevity, Beta-Hydroxybutyrate, HDAC Inhibitors & NAD+:

“The most remarkable thing we saw is that these older mice on the ketogenic diet showed actually better memory than younger mice, and we did not see the loss of memory function that one would normally see associated with the aging process.” – EricVerdin

Some of the key topics discussed in the episode include…
•The effects of a low protein cyclic ketogenic diet beginning in midlife (12 months of age) in male mice. The result? Increased healthspan and improved memory. Dr. Verdin explains how the cyclic ketogenic diet decreased insulin, IGF-1, and mTOR signaling and decreased fatty acid synthesis, and increased PPAR-alpha (which promotes beta-oxidation and mitochondrial biogenesis in muscle).
•How this diet is somewhat qualitatively similar to fasting.
•Some of the possible reasons why the cyclic ketogenic diet created such a striking improvement in memory even when compared to younger mice.
•How beta-hydroxybutyrate, which is the major circulating ketone body during fasting and nutritional ketosis, may, in addition to being an energy source, regulate inflammation and gene expression by acting as a signaling molecule by inhibiting what are known as class 1 histone deacetylases (HDACs).
•How this inhibition of class 1 HDACs leads to the increased expression of notorious longevity gene Foxo3, which may help explain why mice given an exogenous beta-hydroxybutyrate ester had lower markers of inflammation and oxidative damage, which are physiological contributors to the aging process.
•The role of the nicotinamide adenine dinucleotide (NAD+) in the aging process and how replacing declining levels (or preventing them from declining in the first place) may prove to be an important anti-aging strategy.
•Some of the reasons why NAD+ might be declining with age, its role in DNA damage repair via an enzyme known as PARP, and what the literature says about the NAD+ precursor nicotinamide riboside.
•How a special class of enzymes called sirtuins, also known to be activated by caloric restriction and caloric restriction mimetic resveratrol, is tightly correlated with the level of NAD+ and how this “energetic currency” rises in response to fasting.
•The role of the sirtuin enzymes in regulating mitochondrial function, neuronal functions, stem cell rejuvenation and why they may be important in delaying the aging process.

Eric M. Verdin, M.D. is the fifth president and chief executive officer of the Buck Institute for Research on Aging and is a professor of Medicine at UCSF. Dr. Verdin’s laboratory focuses on the role of epigenetic regulators in the aging process, the role of metabolism and diet in aging and on the chronic diseases of aging, including Alzheimer’s, proteins that play a central role in linking caloric restriction to increased healthspan, and more recently a topic near and dear to many of you, ketogenesis. He’s held faculty positions at the University of Brussels, the NIH and the Picower Institute for Medical Research.

Dr. Rhonda Patrick has such great interviews and more. She is brilliant, questioning. independent, well researched, and crowd funded by her community of supporters (about $15,000/mo.). She isn’t institutionalized, she is not selling a book(s), offers no supplements or product lines; she is my type of unbiased, next-level intellectual on a path to help people increase helthspan. Her site:

Sugars & Alcohol (same): The Biochemistry (video added 8/24/2017 1:00 PM)

The video above is excerpted from Sugar: The Bitter Truth, which I highly recommend.

In-depth interviews with Dom D’Agostino (videos added 9/6/2017 5:00 PM)

Dom D’Agostino Q&A Part 1 -The Power of the Ketogenic Diet (8/14/2016):

•Why is there so much resistance among dieticians and researchers toward ketosis despite evidence in its favor? [07:12]
•Can you gain muscle size and strength on a ketogenic diet? [15:20]
•How much protein should you take in with a ketogenic diet? [16:21]
•What is the impact of the ketogenic diet on Type 1 diabetes? [19:16]
•Is it better to analyze ketone production by breath or blood? [27:42]
•How does ketosis affect performance at altitude? [30:53]
•Are there any differences females need to be aware of when considering a ketogenic diet? [35:53]
•Can a female obtain a sub-10 percent body fat with a ketogenic diet? [40:43]
•How does ketosis affect the microbiota? [44:53]
•Is counting calories just as important as tracking fat intake and carb restriction if you want to avoid weight gain? [52:00]
•What are Dom’s nutritional tricks to surviving scientific conferences where the food is often less than healthy? [55:36]
•What stimulants aid in ketosis? [58:53]
•Can a vegetarian or vegan follow a ketogenic diet? [1:05:01]
•Should you be concerned if a ketogenic diet increases your LDL or LDL-P (bad cholesterol)? [1:08:55]
•Elevated triglycerides? A ketogenic diet isn’t for everyone. [1:14:17]
•Is it dangerous to use ketone salts? [1:15:29]
•What’s Dom’s advice for people suffering from fatty acid oxidation disorders? [1:24:39]
•Does Dom really support Kegenix? [1:29:40]
•What are Dom’s go-to products? [1:37:21]
•Are exogenous ketones only useful in a state of ketosis, or would they benefit someone who is not keto-adapted? [1:45:28]
•Can exogenous ketones combined with a low-carb diet (but not a ketogenic diet) still give some or all of the benefits of a strict ketogenic diet? [1:48:38]

Dom D’Agostino Q&A Part 2 – Disease Prevention, Cancer, and Living Longer (10/20/2016):

•Does the ketogenic diet “beat” chemotherapy for cancer? [06:45]
•Dom elaborates on the detoxifying effects of ketosis on precancerous cells in healthy individuals. [15:07]
•How does one jump start a daily ketogenic cycle without supplements? [16:25]
•How can lean muscle mass be maintained when fasting? [17:56]
•What types of cancers are most affected by ketosis? [21:34]
•What process is most effective for targeting cancer? [23:25]
•The ketogenic diet as a do no harm therapy. [26:14]
•Nutritional ketosis and hyperbaric oxygen therapy: how, why, and when? [27:51]
•How long would an amateur endurance athlete need to be in ketosis to get the full benefit of being fat adapted for a marathon, and what supplement stack would Dom recommend? [33:47]
•Should an APOE4 (Apolipoprotein E) carrier — someone at genetic risk for Alzheimer’s disease — be careful with a ketogenic diet? [36:35]
•Are there any downsides to shifting out of ketosis for an occasional cheat meal? [41:06]
•What does Dom have to say about the study that found ketogenic diets have no metabolic advantage? [46:19]
•If your body doesn’t do well with dairy or nuts, what would be good fat source alternatives on a modified ketogenic diet? [48:58]
•Dom talks about Metformin, methylene blue, and other non-food substances meant to increase longevity. [50:24]
•Can the ketogenic diet be used while glycolytic training? [58:06]
•What is it like for Dom to be an academic who makes serious weight training a big part of his life, and how do these two pursuits complement (or complicate) each other? [1:01:06]
•Dom’s thoughts on John Kiefer’s carb backloading. [1:07:26]
•Are ketone salt products on the market safe — specifically the DL beta-Hydroxybutyric salts? [1:12:27]

Dom D’Agostino on Fasting, Ketosis, and the End of Cancer (11/20/2015):

•How Dom D’Agostino responds when someone asks him, “what do you do?” [5:28]
•Describing the Institutional Review Board (IRB) [9:53]
•Research on advanced lifters in a state of ketosis [12:13]
•Thoughts on getting big (hypertrophy) and strong while in a state of ketosis [15:53]
•Defining ketones and ketosis [20:48]
•The implications of fasting, nutritional ketosis and/or exogenous ketones for preventing/mitigating the onset of neurodegenerative diseases [28:23]
•Defining cachexia, sarcopenia, anabolism, and catabolism [30:48]
•Thoughts on the use of anabolic agents in cancer patients [34:48]
•The advantage of SARMS instead of pre-existing low androgenic anabolic therapies [38:53]
•To what extent is it possible to mimic the benefits of pre-chemo therapy fasting with exogenous ketones? [43:23]
•How to accelerate the induction of ketone projection through use of exogenous ketones[49:18]
•Ketone esters [56:13]
•The benefits of eating exogenous ketones while in a carbohydrate attractive environment (for example, when traveling in Italy) [1:16:08]
•What a traveling ketogenic breakfast looks like [1:20:43]
•Reasons for using glutamine [1:25:08]
•Thoughts on being considered a “nutritionist” [1:32:18]
•The impact of Metformin on the survival rates of animals that have metastatic cancer [1:41:38]
•If Dom D’Agostino learned that he had advanced cancer, what tools would he use to fight it? [1:46:18]
•Thoughts on therapeutic fasting [2:03:03]
•Observations of people who experiment with fasting [2:08:23]
•Describing the risks and toxicities of consuming a cocktail of exogenous ketones [2:14:33]
•Unusual foods or beverages that spike ketone levels [2:22:45]
•Top resources for those seeking to learn about a ketogenic diet [2:41:33]
•Most gifted books [2:43:13]
•How to approach fighting Lyme Disease with the ketogenic diet [2:50:18]
•The effect of ketosis on mitochondria [2:53:18]
•Healing from use of antibiotics [2:55:53]