James Cain

Hi Dean and others. I got a few messages from Dean about this but have had the fantastic opportunity to travel abroad and am just now having regular (or non-firewalled) access to the Internet. I love the idea of the FoL trip, or really even just a meetup somewhere domestic. I've been to Costa Rica before and it was fantastic. Do pack whatever packaged food you need because options are limited and otherwise quite expensive. Local fruits and veggies are abundant though, and the food options at FoL sound awesome. I'm really not interested in a packaged retreat that costs $2000 for many of the reasons already provided by others. My major limitations are that I teach and have the typical academic breaks, so winter and summer breaks would work best. Even a long weekend isn't very convenient for international travel. James

Thanks, Dean. It looks like those same authors published a similar paper a few months earlier, but autopsied brains to assess Alzheimer's pathology vs. testing cognitive tests in the more recent study. http://www.ncbi.nlm.nih.gov/pubmed/26836731 Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults. I wish they tested the tissue levels of omega-3. Other studies have shown no benefit from omega-3 supplements in ApoE4 carriers, so either there's something unique about fish oil omega-3 bioavailabilty (there is, but I'm not sure it matters based on other evidence) or it's a lifestyle issue or similar confounder. On a lighter note, am I the only one wondering about the accuracy of annual food frequency questionnaires in demented patients? :-) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518784/ Dietary omega 3 polyunsaturated fatty acids and Alzheimer's disease: interaction with apolipoprotein E genotype This is an excellent review, and the section "4. Putative mechanisms underlying this interaction" explains a lot of why I doubt the results of the most recent study you posted, Dean, at least for a direct effect of omega-3 fatty acids.

Thanks for this, Dean. Being E4/E4, I've found tremendous benefit to my lipids and some other health parameters by avoiding dietary cholesterol (vegan diet), and less so by reducing saturated fat, and no additional benefit from reducing total dietary fat. I've decided to consume a low-fat diet because this aids in ALA conversion to EPA, but only with quite low intakes of n-6 PUFA. It's also just easier for me to plan my diet. I've decided to avoid EPA/DHA supplements for various reasons, but none so convincing that I'd avoid taking one if ALA alone wasn't adequate. It's nice to see another study showing ALA alone without EPA/DHA supplements shows some benefit. Sadly, as far as ApoE4 goes, almost no intervention seems to work in this population, including n-3 supplements--and if anything does show benefit it's usually less than for ApoE3.

Thanks for sharing, Dean! I've found myself progressively shifting towards a more overall frugal lifestyle, diet included. I've never been materialistic, but you could say I'm trending towards minimalism--nothing extreme, but definitely more conscientious about material goods, natural resources, and food waste. Potentially because of my upbringing and my past days in athletics and bodybuilding, I have a tendency to clean my plate regardless of what's on it. This paired with my developing frugality has required some consideration of my dietary habits to keep myself from over-consumption. I assume you tend to wake up early anyway, but you also seem like the kind of person who likes to keep things consistent by setting an alarm slightly earlier than usual. Do you set an alarm? I've woken up without an alarm for quite a few years, usually waking between 3:30-4:30am (5:30am is a lucky day of sleeping in for me!). I'm also usually unable to keep myself awake after 8:30pm. I think I've asked before, but are you (semi)retired? You are certainly prolific when you set yourself to a task, and I'd imagine you have a lot of free time, and the content you generate on this forum is evidence of that (and many thanks for that!). We share many of the same principles and motivations. I usually find what you post here, and also stuff form the old mailing lists, to be very similar to my own thoughts and interpretations. What do you consider early waking, assuming you were to have a restless night and not be able to get back to sleep? For me it's around 2:30-3:00am. I try to stay in bed on those nights, but often once 4:00am rolls around my body is awake enough that it's too late to get back to sleep. Any idea why you think you're sleeping better recently?

100 g/d protein is not excessively high, especially considering it is 100% plant-based and Dean is very active. Similarly, Dean's intake of sugar and total carbohydrates are high, but research and Dean's personal results show that healthy glycemic control can be maintained in some individuals. Generally being lean, being active, being habituated to a high-carb/lower-fat diet, consuming low saturated fats, and consuming carbohydrates earlier in the day all help here, and Dean has these pretty well covered. As an example, I consume a very similar carbohydrate and protein intake but much less fat, also whole-food vegan, and my fasting glucose, post-prandial glucose, HbA1c, IGF-1, and inflammatory markers are all low-normal in line with a CR practitioner. I'm also quite lean and try to be somewhat active with light bodyweight workouts and a treadmill desk. I'm not sure why you say 50g of PUFA from whole-foods with a good n-3/n-6 balance is "stupid high." Most research I'm familiar with showing high PUFA intake to be unhealthy included purified oils, a high free-sugar or processed food intake, n-3/n-6 or other fatty acid imbalance, or obese subjects. Dean doesn't qualify for any of these and seems to be doing quite well otherwise. Perhaps he could get his tissue fatty acid composition, oxidative markers, or advanced lipid testing done but I'd bet any potentially negative effect of 50g whole-food PUFA would be hidden by his otherwise beneficial lifestyle and diet. Ultimately, I support (and personally follow) Dean's approach to first measure biomarkers and subjective well-being, and second measure BMI and body composition, as markers of CR. There is some evidence that it is total calorie intake which matters, and that consuming more calories and exercising more to obtain the same calorie restriction as a sedentary CR subject abolishes the CR phenotype, but Dean has shown he's able to maintain a CR phenotype demonstrated through blood tests, anthropometry, biometrics, and subjective observations. It is indeed an unusual approach to CR, but what is the goal of CR except obtaining a set of biomarkers that are associated with health and longevity outcomes? Research and many practitioners' experiences suggest "classic CR" with low calorie intake and just enough activity to maintain physical health is the most reliable way to obtain the associated biomarkers, but the approach is only a means to an end rather than the goal itself (the biomarkers). For example, research clearly demonstrates that extreme weight and fat loss are a consequence of a CR diet but are not required to obtain the benefits of CR. Conversely, stimulating weight and fat loss without CR usually does not fully replicate the biomarkers associated with classic CR benefits. I'll repeat that Dean (and me, and a few others I know) are able to obtain the markers of classic CR while being somewhat outside of the norm for dietary intake, physical activity, and/or anthropometry typically associated with classic CR. Most practitioners must follow classic CR to fully obtain these biomarkers. The real question that can't be answered is related my my question #5. That is, despite biomarkers, Dean and other outliers may be losing out on the some CR benefits despite having good biomarkers. I'd reason that the biomarkers are in place so he's probably going to get the classic CR benefits, but my primary concern is with cardiovascular changes associated with extreme levels of physical activity, but these are usually associated with prolonged high-intensity activity. For example: Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise We don't know all the pieces of the puzzle, so maybe there's something we aren't measuring or that can't be observed which is negating the health-span and (especially) lifespan prolonging effects seen later in life in experimental models. We can speculate and made educated guesses, but that's the gamble with CR. I side with Dean that he gets immediate benefit and pleasure from his CR approach, and he can reasonably expect late-life benefits similar to classic CR based on what we know of the mechanisms, and if future research or well-reasoned arguments are presented in the future then Dean would probably change his practice to maximize the potential life-long benefit. As a last random comment I think your eating a single meal at the same time every morning would have a very profound positive impact for entraining your circadian rhythms. Breakfast would be better than evening-only as it would better synchronize the central and peripheral clocks. However, I vaguely recall a study showing strengthened circadian entrainment by eating twice each day as breakfast + second meal, but that breakfast-only showed no benefit. I'll have to dig it up. I tend towards a large breakfast, moderate lunch, and light dinner (45%, 35%, 20% daily calorie intake) partly for the entrainment and metabolic benefits. Circadian rhythms seem to play a massive role in regulating health and potentially aging, and CR seems to be the most profound non-light circadian modifier, with restricted meal times (modified fasting) coming in a close second. For example [both free full-text]: Impact of the Circadian Clock on the Aging Process. Circadian rhythms, aging, and life span in mammals. (This is a fantastic paper!)

Dean, thanks for sharing! I'm familiar with how your diet has changed over time from reading your website and following your posts in the mailing lists. I think I know the answer to some of these, and I'm not suggesting I disagree with your approach, but rather it always helps to have more info and I'm a curious person. Why have you changed from two meals to a single meal, and why in the morning? Why have you settled on your current ratio of food choices/categories? In another thread you mentioned not (always, or ever?) tracking calories. How do you regulate your intake? You do a lot of physical activity. What is the level of exertion during your typical 8-9 hours of physical activity each day? I know most is walking or biking while at a desk. Is this truly "physical activity" or could it be considered "exercise," and how/why did you settle on that volume each day? You seem to base CRON success on BMI, perceived well-being, and blood tests. Are you concerned that you are consuming too many calories to balance the high physical activity, such that you may be at least partially negating some of the primary anti-aging effects of CR? Are you still gardening? What do you feel is the greatest benefit of your current dietary approach (either in general or compared to previous approaches)? What do you feel is the most difficult aspect of your current dietary approach (either in general or compared to previous approaches)? What is your average caffeine consumption? I assume alcohol is zero? Do you add fiber supplements for textural improvement of your dressings and/or are you specifically including them for functional purposes (even considering your otherwise high fiber intake)? What would you say is the average daily food volume (or weight, as roughly 1ml = 1g)? As an extension of #11, and most important for giving anything other than general feedback, do you have a sample day in CRON-O-Meter you could share?

I read this and thought it might be conjecture as I considered the various possible mechanisms for why this could be the case. I thought it more likely that the mucus would degrade for other reasons, which while very likely in itself turns out not to be the only contributor. In 2013 some researchers finally got direct proof of mucous-eating bacteria! Science Daily: On the trail of mucus-eaters in the gut. http://www.sciencedaily.com/releases/2013/03/130305131036.htm Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing. http://www.pnas.org/content/110/12/4720

Cloud, I'll hop in and agree with the advice already given. Correcting B12 deficiency and ensuring maintenance often takes 500 mcg supplementation, which is what I've been taking for years to maintain a good mid-level B12 level. Irregardless of plasma B12, you should also be tested for methylmalonic acid (MMA) (and about the MMA test here) and possibly homocysteine as these require B12 to be metabolized, so elevated levels indicate ineffective B12 activity. This is most often the case with B12 deficiency, but some people need higher B12 levels to properly regulate these metabolic pathways.

I compose in an editor with frequent saves, and paste into the browser only to preview and post. I imagine a lot of brilliance is forever lost when the post is vaporized. Dean found a way to recover autosaved text, as he explained here. Thanks! I used this to recovery my almost-lost post in the coffee thread this morning. I usually copy and paste partially done posts into Word as a sort of "save" but it'd help to have a text editor with coding functions built in. The "Stir-fry vegetables, frozen, unprepared" is a custom recipe entered from weighing the individual components averaged from a few bags of standard frozen stir-fry vegetables. By creating a recipe with the whole foods I get an entry with the micronutrient values included. Most custom foods and packaged foods in the databases only include the information from the nutrition label, so lacks the more detailed breakdown of foods in the USDA database. Here's the "Chili1" recipe: 2 cans (520 g) - Black beans, canned, drained, low sodium 200 g - Lentils, pink or red, raw 2 x 1 lb bags (900 g) - Brussels sprouts, frozen, unprepared 900 g - Mushrooms, portabella, raw 450 g - Kale, raw 2 cans (820 g) - Tomato, canned, low sodium 3 cups - Tap water The Cronometer report for 1/7 of the Chili 1 recipe, which was included in my sample day, is attached. My typical chili recipe is more along the following lines: Standard ingredients: 2 cans various beans, drained and rinsed, low sodium if possible (most often black, pinto, and kidney) 100-200 g red lentils (I prefer red over brown lentils for flavor and easier digestibility) 2 small cans (170g) tomato paste 2 cans (411 g) diced tomatoes, low sodium 2 x 1 lb bags (900 g) Brussels sprouts, frozen 3-4 cups water Various spices The most common additional ingredients to fill the 8-quart pot, varies depending on the week: Frozen pearl onions, peas, and corn Fresh carrots, cauliflower, and mushrooms 1/7 of the various chili recipes ranges from 540-620 g and 290-370 kcal, is pretty high in protein, fiber, and micronutrients. Chili 1 (0.14 of total recipe).pdf

I wrote up a long response to this and then lost it before posting, demoralizing a second attempt for a while, but here's round two: I did see Dean's post, as well as Michael's extensive post on supplements for vegetarians. I take daily 500 mcg B-12, 2000 IU D3 (I don't get out much, and when I do I usually wear UV-blocking clothing or sunscreen), 250 mg calcium citrate (with 175 IU D3), 1/2 tab of a general multivitamin, 3 mg melatonin, and 2.5 g creatine. The melatonin isn't necessary but it noticeably enhances my sleep, and I think the antioxidant value of melatonin (especially for neurons) is motivation enough for me to take it. The multivitamin is mainly for iron, iodine (I usually don't use much salt), and to generally fill in a few potential gaps depending on a day's intake (like zine, vitamin E, selenium). I know some research shows multivitamins may be unhelpful or harmful overall, but I think taking the modest 1/2 tab per day is safe. I started it a while back because my digestion was, and sometime still is, wonky enough that I was concerned with getting adequate micronutrient absorption. I could probably ditch my calcium and maybe even the D3 and B12 since these are covered in the multi at probably adequate levels. The B12 is inexpensive, effective (blood work confirms), and safe, so I'd rather keep the dedicated B12 supplement just to be sure. I also currently include vitamin K1 and K2 complex (1 capsule per week), CoQ10 with vitamin E spectrum (3-7 capsules per week), and zinc methionine (very infrequently, perhaps every 6-8 weeks, to enhance my sleep when I have insomnia). I think the research on vitamin K2 (from animal products) is promising, showing benefit regardless of adequate K1 (from plant products) levels. I doubt it's at all necessary or beneficial on top of everything else, but for the moment I have a few bottles left over and it lasts a long time taking one capsule each week. The CoQ10 has a noticeable effect on increasing my stress resistance to increased exercise, less sleep, and general stress. I don't always take it but do when I feel I'd like the extra boost. The vitamin E is full-spectrum and is probably accounting for the perceived benefits, and I'm less concerned about this supplement than I would be of overusing a pure dl-alpha tocopherol supplement. The potatoes provide a lot of nutrients that fill in the gaps of an otherwise vegetable and fruit heavy diet. Cooked potatoes of various varieties are somewhere around .9-1 calorie/gram, and are satiating for me, and are relatively nutrient dense, so they are a staple in my diet. Observations of various cultures like the Andean and Irish people have shown a long-term potato-based diet supports healthy disease-free growth and development, and research trials show a practically potato-only diet (especially when supplemented with a few vegetables) is capable of healthily supporting an adult. The CR community often maligns the potato, but for me I seem to do well with it both subjectively and metabolically. They are also extremely inexpensive. I'm pretty lazy as a cook and spend a few hours on Sunday baking about 15 points of potatoes and making a big batch of chili. I put these in the fridge to portion out throughout the week. I use canned beans, and often eat just raw veggies or put frozen veggies in the microwave using a glass steamer. As there is no reliable source of plant-based B12, I consume tempeh mostly because I enjoy it and as a source of probiotics, fiber, protein, and fat. Vitamin D - I get from supplements. I changed a few of the nutrients ranges in Cronometer, and removed them completely for some items for which the data is somewhat meaningless of just serves as noise when looking at the overall report. For me the fatty acid breakdown falls into this category. I've seen the recommended ratio range from 1:1 to 4:1 n-6:n-3, and sometimes a bit higher, depending on which specific tissue or population is being studied. My ratio is 1.042 (6.2 g n-3, 6.5 g n-6), which meets the minimum PUFA requirement and seems to fall within that range. I enjoy the foods that allow me to keep my overall fat intake low and don't feel the need to specifically add more fat unless its out of gastronomic preference. I also consume all of my n-3 as ALA so don't worry when it is sometimes higher than my n-6 intake, and keeping overall PUFA intake quite low enhances ALA conversion into EPA and DHA, evidenced here and here.

This is how I feel about most of their posts as well. I'm sure in person I'd make some comments and generally praise the effort and quality of information, but I'm otherwise left feeling mostly content and in agreement. Thanks for saying this so I could simultaneously express my gratitude and that I do read through almost every post here.

I've been following this conversation with interest because I follow a similar diet. I did get an NMR LipoProfile done a few months ago that confirms that a very high-carb low-fat diet, and a relatively high whole-food sugar intake, isn't a problem for me. General diet 70C/14F/11P, 2350kcal (sometimes up to 3000kcal on very active days), whole-food vegan, 80-100g fiber per day; no alcohol; weight stable I've attached a CRON-O-Meter report (actually for the day just prior to the blood draw) to show typical foods, though this is a bit lower in calories than I usually eat, and the high Fitbit activity data is from walking around campus and on my treadmill desk. The amount of fruit and starch (mostly potatoes) may vary but the macro ratios are pretty consistent. I actually have oats in this sample day but that's most often replaced with more fruit. My typical food choices include potatoes (all kinds), fruit (apples, bananas, berries), veggies (lettuce, tomatoes, cauliflower, and carrots raw, otherwise cooked frozen stir fry, broccoli, brussels sprouts and kale), beans or tempeh, flax (rarely other nuts/seeds), pea protein powder, and most of my lunches are a homemade chili with canned tomato paste and tomatoes, brussels sprouts, carrots, beans, lentils, and whatever produce leftovers from the prior week. Body temp--97.0-97.5 F Blood pressure--105/65 Lipids--Chol (134), HDL-C (38) LDL-C (81), TAG (76), LDL-P (867) Fasting glucose--77 mg/dL Fasting insulin--2.9 (range 2.6-24.9 uUI/mL) HbA1c--5.0 IFG-1--126 (range 98-282 ng/mL) CRON-O-Meter - 150727.pdf

Dean, good analysis and I'd agree. This same phenomenon seems to exist for many biomarkers including insulin, thyroid hormones, and as you've said IGF-1 and T, and others. You're focus on why these are lowered rather than just analyzing the lowering itself is important in assessing the physiological impact and health, and this is often difficult when parsing epidemiological data.

I'm very interested to hear how you like it! The major issue with most inexpensive stationary bikes is that they don't have weighted (or adequately weighted) flywheels, which makes the movement less smooth and puts extra stress on the knees. I currently have a treadmill workstation and this adjustable standing desk from IKEA. Both are amazing. I'd like to get a bike to switch up the movements though, and possibly just slide it under my adjustable desk.

Thanks for following up! This is fantastic news. Perhaps if promote this in some way like putting a big label on their products advertising a low-cadmium product it will bring more public attention to environmental contamination of foods. If the cadmium contamination is mostly (entirely?) from the soil, I'd expect the nibs be just as much of a problem as the powder, as you similarly speculated. Some post-harvest/processing contamination (like lead!) comes from the fuel and pollution in those countries, so perhaps cadmium and others fall into this category as well. Rather than testing a handful of packages I think we'd need more thorough testing to get a better idea of what the average contamination of products is, and to better speculate as to why some are worse than others.