Over the long term, regular exercise is correlated with improved cognitive function in later life, a slower decline of that function with aging. This is well established. The work here is interesting for showing that even in the very short term, exercise produces improvements in specific aspects of cognitive function, such as memory. One might add these results to the very long list of good reasons to avoid a sedentary lifestyle. Exercise cannot add a large number of years to life span, and indeed in mice it has no effect on overall life span, but given that it is essentially free and produces highly reliable benefits to health and resilience, slowing and postponing age-related disease, it would be foolish to ignore it.
How quickly do we experience the benefits of exercise? A new study of healthy older adults shows that just one session of exercise increased activation in the brain circuits associated with memory – including the hippocampus – which shrinks with age and is the brain region attacked first in Alzheimer’s disease. “While it has been shown that regular exercise can increase the volume of the hippocampus, our study provides new information that acute exercise has the ability to impact this important brain region.”
The research team measured the brain activity (using fMRI) of healthy participants ages 55-85 who were asked to perform a memory task that involves identifying famous names and non famous ones. The action of remembering famous names activates a neural network related to semantic memory, which is known to deteriorate over time with memory loss.
This test was conducted 30 minutes after a session of moderately intense exercise (70% of max effort) on an exercise bike and on a separate day after a period of rest. Participants’ brain activation while correctly remembering names was significantly greater in four brain cortical regions (including the middle frontal gyrus, inferior temporal gryus, middle temporal gyrus, and fusiform gyrus) after exercise compared to after rest. The increased activation of the hippocampus was also seen on both sides of the brain. “Just like a muscle adapts to repeated use, single sessions of exercise may flex cognitive neural networks in ways that promote adaptations over time and lend to increased network integrity and function and allow more efficient access to memories.”
Advanced glycation end-products (AGEs) form in tissues as a side-effect of the normal operation of cellular metabolism where it touches on the processing of sugars. There are many types of AGEs, most short-lived, but some persistent and challenging for our biochemistry to break down. These persistent AGEs lead to cross-links, binding together molecules in the extracellular matrix and thereby altering the structural properties of tissues. This is perhaps most harmful where it reduces tissue elasticity, and is thus an important contributing cause of skin and vascular aging.
While sugars are involved, it is much debated as to whether the contents of diet, either fully formed AGEs from certain cooked and processed foods, or precursors in the form of excessive amounts of sugar, has much influence at all over the generation of the types of AGE involved in aging. As mentioned, there are many types of AGE. One of the big questions in the small research community focused on AGEs is whether or not glucosepane AGEs are the only target worthy of attention in the matter of aging. There is certainly good evidence for cross-links in humans to be overwhelmingly made of glucosepane, but equally there is a faction who argue that the research community does not yet have sufficiently robust data to be able to ignore AGEs such as carboxymethyl-lysine (CML).
The challenge inherent to all work on AGEs, and why this part of the larger field has been a comparative backwater for decades despite its great importance to aging, is that the usual tools for cell, tissue, and molecular biochemistry work just don’t exist. AGEs are hard to work with. The usual recipes for making the molecule of interest, the standardized tests for assessing its presence, and so forth, just don’t exist or didn’t exist until comparatively recently. Most research groups take a look at this desert of tooling and move on to something easier – it is a self-reinforcing problem. This was the case until the SENS Research Foundation and allied philanthropists turned up to try to solve the missing tools problem. Those efforts have led to significant progress in the past five years or so, but there is still a fair way to go yet. Today’s paper is of interest for showing progress towards tooling for CML, rather than for glucosepane. It is not open access, but sufficiently interesting to note nonetheless.
Elevated levels of AGEs are linked to the pathology of many metabolic and degenerative diseases of aging, such as diabetic complications, atherosclerosis, and Alzheimer’s disease. This association is manifested by age-dependent increases in cross-linking, browning, fluorescence, and AGE content in long-lived proteins such as collagens and lens crystallins. Structural characterization and synthesis of some of the more prevalent AGEs (e.g., glucosepane) have allowed more focused investigations into their individual chemical properties and formation. Indeed, chemical studies have shown strong correlations between specific AGEs and the development of age-related illnesses; however, it has been difficult to unequivocally demonstrate that any AGEs are direct causal factors largely due to the lack of tools for investigating the reversal of mature AGE modifications at the molecular level.
Here, we show that MnmC, an enzyme involved in a bacterial tRNA-modification pathway, is capable of reversing the AGEs carboxyethyl-lysine (CEL) and carboxymethyl-lysine (CML) back to their native lysine structure. Combining structural homology analysis, site-directed mutagenesis, and protein domain dissection studies, we generated a variant of MnmC with improved catalytic properties against CEL in free amino acid form. We show that this enzyme variant is also active on a CEL-modified peptidomimetic and an AGE-containing peptide that has been established as an authentic ligand of the receptor for AGEs (RAGE).
To the best of our knowledge, this is the first biochemical demonstration of an enzyme that can reverse a mature AGE-functionalized peptide. While the kinetic parameters, which are similar to known Amadoriases, could be substantially improved, C-MnmC variants represent lead catalysts for further directed evolution and development. As MnmC natively acts on nucleic acids, glycated DNA (e.g., carboxyethyl/carboxymethyl-deoxyguanosine) may also be suitable substrates to test in future studies. Such improved AGE-reversal tools could in principle enable a better understanding of the biology of AGEs at the molecular level, elucidate their direct roles in the pathogenesis of age-related diseases, and serve as leads for recombinant enzyme therapies.
The U.S. has asked China to lift a ban on U.S. pork fed the additive ractopamine, but so far China has rejected the request. China has seen huge losses in the pork industry due to African swine fever, which may lead to the deaths of up to 200 million pigs.1
Still, even while facing protein deficits as a result, the country has been resistant to importing ractopamine-treated meat. In fact, ractopamine, a beta agonist used to increase weight gain, feed efficiency and leanness in pigs, cattle and turkeys, is banned in most other countries, including China, Russia, Taiwan and the European Union.2
Only 26 major meat-producing countries allow ractopamine use,3 while at least 160 have banned it.4 The growth drug, marketed as Paylean for pigs, Optaflexx for cattle and Topmax for turkeys, is controversial not only because it’s linked to adverse effects in animals but also because of human health concerns.
The continued use of the drug in U.S. meat is causing tensions during talks aimed at ending the U.S.-China trade war. According to Reuters:5
“China would likely lift a ban on U.S. poultry as part of a trade deal and may buy more pork to meet a growing supply deficit, but it is not willing to allow a prohibited growth drug used in roughly half the U.S. hog herd, two sources with knowledge of the negotiations said.”
Ractopamine Mimics Stress Hormones, Leads to Health Problems in Pigs
The U.S. Food and Drug Administration (FDA) approved the use of ractopamine in feed for pigs in 1999, later adding in approval for cattle and turkeys. The approval was based largely on studies conducted by the drug’s maker, Elanco, which focused not on safety for the animals or humans, but rather on economics, including what dosage to administer to raise bigger animals, faster.6
According to the Center for Food Safety (CFS), “The drug mimics stress hormones and increases the rate at which the animals convert feed to muscle.”7 In so doing, however, a number of adverse effects have been reported in pigs, including high stress levels, lameness, hyperactivity, broken limbs and death.
Problems with behavior and cardiovascular, musculoskeletal, reproductive and endocrine systems have also been reported.
“Fed to an estimated 60 to 80 percent of pigs in the U.S. meat industry, ractopamine use has resulted in more reports of sickened or dead pigs than any other livestock drug on the market,” CFS noted. “According to FDA’s own calculations, more pigs have been adversely affected by ractopamine than by any other animal drug — more than 160,000.”8
One study of ractopamine in monkeys showed the animals developed rapid heartbeat, whereas rats developed a host of birth defects ranging from cleft palate and short limbs to open eyelids and enlarged heart.9,10
Further, a study published in Translational Animal Science reported that the use of ractopamine has been associated with increased risks of nonambulatory and injured pigs, increased cattle mortality on feedlots and abnormal cases of hoof sloughing at beef packing plants.11 In short, hoof problems appear common in cattle taking the drug and related beta agonist drugs such as zilpateral (Zilmax), including the outer shell of the hoof falling off.
Pigs taking the drug are more likely to lose the ability to walk and become more difficult to handle and transport, succumbing more easily to stress as well.12 Ractopamine-treated pigs may become more aggressive and are more likely to be handled roughly by their handlers.
Due to their stimulated aggressive behavior, pigs taking the drug are also more likely to be injured during transport.13 In a review of the evidence, the researchers found additional adverse effects depending on the dose:14
“The evidence presented in the current review demonstrates that RAC [ractopamine] fed pigs may be more difficult to handle at doses above 5 mg/kg and physiological responses and rates of non-ambulatory pigs may increase when RAC fed pigs are subjected to aggressive handling, especially at the 20 mg/kg dose.”
Health Risks of Ractopamine to Humans
The Codex Alimentarius Commission approved a maximum residue level of ractopamine of 10 parts per billion (ppb) in pork and beef, 40 ppb in liver and 90 ppb in kidneys.15 Only one human study was reviewed in the setting of this international standard — a study that involved six men, one of whom dropped out of the study due to adverse effects.16 Further, according to CFS:17
“Data from the European Food Safety Authority indicates that ractopamine causes elevated heart rates and heart-pounding sensations in humans. Other examples of health problems include information from the Sichuan Pork Trade Chamber of Commerce in China, which estimates that between 1998 and 2010, 1,700 people were poisoned from eating pork containing ractopamine.”
Further, two drugs similar to ractopamine — zilpaterol and clenbuterol — are banned by the Olypmics because they affect adrenalin. In 2010, a cycler in the Tour de France failed an antidoping test for clenbuterol, which he blamed on residues from eating meat.18
A study in the journal Talanta further explained, “The use of highly active beta-agonists as growth promoters is not appropriate because of the potential hazard for human and animal health.”19 There’s even data showing human intoxication after consuming liver or meat from cattle treated with beta-agonists.20
Warning labels on the drug also state the risks outright, the Cornucopia Institute reported, including telling handlers to wear gloves and protective gear when handling it:21
“‘WARNING: The active ingredient in Topmax, ractopamine hydrochloride, is a beta-adrenergic agonist. Individuals with cardiovascular disease should exercise special caution to avoid exposure,’ says the label for the turkey feed. “Not for use in humans. Keep out of the reach of children.
The Topmax 9 formulation (Type A Medicated Article) poses a low dust potential under usual conditions of handling and mixing. When mixing and handling Topmax, use protective clothing, impervious gloves, protective eye wear, and a NIOSH-approved dust mask.
Operators should wash thoroughly with soap and water after handling. If accidental eye contact occurs, immediately rinse eyes thoroughly with water. If irritation persists, seek medical attention.”
Ractopamine Is Administered Right Before Slaughter
Part of what makes ractopamine so controversial is the timing of its use. While some other livestock drugs are stopped in the weeks leading up to slaughter, giving some time for them to dissipate from the animal’s system, ractopamine is administered in the weeks before slaughter.
When the U.S. Agricultural Research Service tested more than 1,000 pork kidney samples for four veterinary drugs, including ractopamine, the drug was detected in 22 percent.22 A Consumer Reports investigation also found detectable levels of ractopamine in about one-fifth of 240 pork products tested. The drug was also said to negatively affect the taste and tenderness of the meat.23
“While levels we found were below U.S. and international limits, Consumers Union, the policy and action arm of Consumer Reports, calls for a ban on the drug, citing insufficient evidence that it is safe,” Consumer Reports noted.24 There is also evidence that the drug is present in manure, which is applied as fertilizer to soil, making it likely that it is also entering waterways, with unknown effects.25
However, research suggests the drugs may have endocrine-disrupting effects on marine species, including Japanese rice fish, or medaka.26 At least one study also showed ractopamine may be taken up by alfalfa and wheat from contaminated soil, at varying quantities depending on the concentration in soil.27
‘Natural’ Meat May Come From Ractopamine-Treated Animals
In a survey of more than 1,700 adults who said they try to eat healthy at least some of the time, 45% said they are likely to look for options that are all natural.28 When it comes to meat, however, the U.S. Department of Agriculture (USDA) allows the claim to be made for products that contain no artificial ingredients and minimal processing.
This means the meat may contain drugs, including antibiotics, hormones and preservatives, and still legally claim it’s natural on the label, misleading consumers. The Animal League Defense Fund (ALDF) filed a lawsuit against meat giant Hormel for this very reason, alleging that the company engaged in potentially misleading advertising by using a Natural Choice label.
It turns out that the pigs used for Hormel Natural Choice products are the same as those used to create their spam, lunchmeat and bacon products, most of which consumers would not regard as natural. Further, most of the pigs have no access to the outdoors, and some products labeled Natural Choice came from pigs that received antibiotics and ractopamine.
The Superior Court of the District of Columbia dismissed ALDF’s lawsuit, however, because the labeling is legal under the USDA definition of natural. “There’s a difference between what’s legal and what’s ethical,” Nikolas Contis, a senior partner at brand consultant PS212, told Farm Progress. “I think it’s unethical. They know the words are misleading.”29
ALDF attorney David Muraskin added, “It’s a massive attempt to manipulate and dupe the consumer to purchase something they have no intention to purchase.”30
Where to Find Truly Natural Pork
At one time, all pigs raised on U.S. family farms were heritage pigs, accustomed to roaming on pasture and in forests. The pigs don’t take well to confinement conditions, however, and were soon replaced by commercial pigs bred to grow fast and tolerate crowding.
Whereas commercial pigs reach market weight in about six months, heritage pigs take about a year to do so. They’re raised by a number of small farms, which typically sell the meat through farmers markets, food co-ops and occasionally to restaurants or niche markets.
The USDA doesn’t define heritage breeds of pork, but the Livestock Conservancy defines them as heritage breeds if they have a long history in the U.S., are of noncommercial stock, thrive outdoors and on pasture and are purebred animals of their breed, according to Civil Eats.31
If you choose to eat pork, I encourage you to avoid CAFO meats and instead either buy your meat direct from a trusted grass fed farm raising heritage breeds or look for the American Grassfed Association (AGA) logo, a much-needed grass fed standards and certification for American-grown grass fed meat and dairy.32
The AGA standard allows for greater transparency and conformity33 and is intended to ensure the humane treatment of animals and meet consumer expectations about grass fed meat and dairy, while being feasible for small farmers to achieve.
The AGA pastured pork standards include a forage-based diet derived from pasture, animal health and welfare, no antibiotics and no added growth hormones. Because of the atrocious state of the CAFO pig industry, grass fed heritage pork is the only pork you should eat. At the very least, if you can’t find grass fed heritage pork, choose organic pork products, as ractopamine is not allowed in organic foods.
In the podcast above, Chris Kresser — an acupuncturist, licensed integrative medicine clinician and co-director of the California Center for Functional Medicine — and I talk about KetoFasting, the program I developed and detail in my latest book, “KetoFast: A Step-By-Step Guide to Timing Your Ketogenic Meals,” which launches today. Within a week or two the accompanying KetoFast cookbook will also be released.
My previous book, “Fat for Fuel,” released May 16, 2017, became an instant nationwide No. 1 best seller, beating out the No. 2 best-selling book by a significant margin.1
However, while The Washington Post and some others accurately listed “Fat for Fuel” as No. 1 based on Nielsen ratings for that first week,2 The New York Times (NYT) — considered the pre-eminent list of best-selling books in the U.S. since 1931 — didn’t even include it in their top 15.3
Such a blatant omission is highly unusual, so Hay House, my publisher for that book, reached out to find out why the NYT censored it. The NYT replied the book was “disqualified” because too many of the sales went through Amazon. This in and of itself is unusual, considering Amazon is a primary outlet for all books.
Based on what happened with “Fat for Fuel,” I expect more of the same with “KetoFast.” Still, the NYT was unable to prevent “Fat for Fuel” from becoming a best-seller and fueling a keto revolution that is now the hottest lifestyle trend around, and I doubt the NYT will be able to quell the success of KetoFasting either, even if they decide to repeat their censorship.
From ‘Fat for Fuel’ to ‘KetoFast’
There’s no doubt conventional, government-approved advice has utterly failed to help people manage their weight and prevent disease. We’re facing overwhelming rates of obesity, heart disease, cancer and Alzheimer’s, with future projections heralding more of the same. We need a radical U-turn, and the foundations for how to accomplish that are clearly spelled out in “Fat for Fuel.”
This is why I recommend you read that book first, and implement the nutritional basics of a cyclical ketogenic diet and intermittent fasting before you move on to “KetoFast.” You could look at the two books as two parts of a complete lifestyle program, with “KetoFast” picking up where “Fat for Fuel” left off.
The key to weight management and optimal health is to optimize your mitochondrial function — hence, the term metabolic mitochondrial therapy (MMT) used in “Fat for Fuel.” In short, if your mitochondria are not functioning properly, none of your bodily systems will function properly, and in order for your mitochondria to work, having the metabolic flexibility to burn fat is essential.
“Fat for Fuel” explains the many metabolic advantages you gain once your body regains the ability to burn fat for fuel, and details how to do it. The initial phase of the MMT program — which ends once your body is able to effectively burn fat for fuel — can take anywhere from weeks to months or longer, depending on how metabolically damaged you are.
While much of the book centers around diet (raising the amount of healthy fat and decreasing net carbs is what pushes your body into burning fat for fuel), it also reviews a variety of other strategies to improve your mitochondrial function, such as cold thermogenesis, photobiology, detox, exercise, the dangers of iron overload and the pernicious influence of electromagnetic fields (EMF).
“KetoFast” is the next phase once you’ve successfully implemented the MMT program, as it now combines a cyclical ketogenic diet and intermittent fasting with cyclical partial fasting.
KetoFasting Will Amplify Benefits of My Basic MMT Program
The impetus behind “KetoFast” was two major realizations: First, that water-only fasting is a tremendously beneficial health intervention; and second, that while water-only fasting used to be an ideal strategy, the fact that in the 21st century we have increased toxic exposure that makes it potentially dangerous to do extended water fasts.
We’re now surrounded by and exposed to some 80,000 chemicals in our environment, most of which are fat soluble, meaning they accumulate in your fat cells. Meanwhile, fasting effectively drives toxins out of fat cells, which can have devastating results if you’re severely toxic.
What’s more, since you’re not eating, you’re also not providing your body with the nutrients it needs to effectively neutralize and eliminate those released toxins. My answer to make fasting safer was to devise — based on the best scientific evidence I could find — a fasting program that mimics multiday water-only fasting, while supporting your detox pathways and minimizing the risks associated with toxicity.
The KetoFast protocol is also easier to comply with than multiday water fasting, and provides greater benefits because you’re able to do it far more frequently than you could do multiday water fasting.
The caveat, again, is that you need to have done at least a month of daily intermittent fasting and achieved nutritional ketosis as laid out in “Fat for Fuel” before you move on to KetoFasting. Once you’re metabolically flexible and can burn fat for fuel, the combination of cyclical nutritional ketosis and partial fasting can further amplify your weight loss and overall health and longevity.
As mentioned in the featured interview, fasting has a wide range of health benefits, including radically improved sleep, which in turn is a crucial component of good health and longevity. When you’re fasting, you’ll often find you’re sleeping much better, and your cognition typically improves thanks to the biological cleansing and regeneration that occurs throughout your body, including your brain.
In my view, one of the primary reasons for why you would want to fast is to accelerate autophagy. This is your body’s innate cleanout process, in which damaged mitochondria, proteins and cellular components are digested and then recycled during the regeneration phase, which occurs during refeeding.
It’s important to realize that many of the benefits of fasting actually occur when you start eating again, and this is why cycling in and out of fasting and feasting is so imperative. Half of the process occurs in the absence of food, while the other half occurs when food is reintroduced.
This is yet another reason why I don’t recommend longer fasts, as this will prevent you from fasting often, hence limiting the number of cycles of regeneration you get.
Fasting also boosts your readiness score, which means following a fast, you’re able to work out really hard. I do KetoFasting twice a week, and on the days following my KetoFast, that’s when I do my strength training and load up on protein and carbs. I’ve found it’s a really fabulous and nearly pain-free way to radically improve your metabolic health.
Other Benefits of Fasting
Fasting is also known to provide many other health benefits, including:4,5,6,7,8
Stem cell activation — Stem cells play an important role in health and longevity as they are instrumental in repairing and rejuvenating your cells and tissues. By upregulating autophagy and mitophagy (autophagy in your mitochondria) 9 and boosting stem cells you will lower your risk of most diseases, including cancer10 and neurodegeneration.11
Nutrient composition is important here, and in “KetoFast” I provide details on how to optimize autophagy and stem cell activation processes by eating certain foods (and avoiding others) at the right time.
Releasing ketones into your bloodstream, which help preserve brain function and protect against epileptic seizures, cognitive impairment12 and other neurodegenerative diseases.
Boosting brain-derived neurotrophic factor, which stimulates creation of new brain cells and triggers brain chemicals that protect against brain changes associated with Alzheimer’s and Parkinson’s disease.13,14
Increasing growth hormone by as much as 1,300 percent in women and 2,000 percent in men,15 thereby promoting muscle development and vitality.
Lowering insulin and improving your insulin sensitivity; studies have shown intermittent fasting can both prevent and reverse Type 2 diabetes, which is rooted in insulin resistance.16,17,18,19
Increasing levels of the neurotransmitter norepinephrine, which helps your body break down fat to be used as fuel and benefits your metabolism.20,21,22
Boosting mitochondrial energy efficiency and biosynthesis.
Lowering oxidative stress and inflammation.23
Improving circulating glucose24 and lipid levels.
Reducing blood pressure.
Improving metabolic efficiency and body composition, modulating levels of dangerous visceral fat and significantly reducing body weight in obese individuals.
Reproducing some of the cardiovascular benefits associated with exercise.
Regenerating the pancreas25 and improve pancreatic function, reversing diabetes.
Improving gut health — While the exact mechanisms are still unclear, I believe fasting helps jump-start microbiome health by increasing bacterial diversity and repairing leaky gut. Overall, fasting facilitates healing of your gastrointestinal tract and enhances the integrity of your gut lining.
Protecting against cardiovascular disease.
Reducing low-density lipoprotein and total cholesterol.
Improving immune function.26
Synchronizing your body’s biological clocks.27
Eliminating sugar cravings as your body adapts to burning fat instead of sugar.
Increasing longevity — There are a number of mechanisms contributing to this effect. Normalizing insulin sensitivity is a major one, but fasting also inhibits the mTOR pathway, which plays an important part in driving the aging process.
Safety and Contraindications
For all its benefits, fasting — especially multiday water-only fasting — is not for everyone. As with other types of extended fasting, you should not do KetoFasting if you are:
Have an eating disorder
This is a small minority of people, and for pregnant and breastfeeding women it’s a temporary contraindication. For most others, fasting is likely to provide significant health benefits, and my KetoFast protocol raises not only your chances of fasting successfully but also improves safety, as it’s designed to support detoxification.
Why I Don’t Recommend Continuous Nutritional Ketosis
“Fat for Fuel” and “KetoFast” both stress the importance of a cyclical ketogenic diet. A common misconception is that because nutritional ketosis is so beneficial, it stands to reason that remaining in ketosis for the rest of your life would be the way to go. I disagree with this approach, having experienced the drawbacks of it firsthand.
For starters, continuous keto can start wreaking havoc with your hormonal system, specifically your thyroid. It’s important to realize that nutritional ketosis is a catabolic process, meaning you’re breaking things down. This is a good and necessary process, but you also need to build your body back up!
Many advertise the ketogenic diet as something you stay on forever, and I quickly learned that was a bad idea. After some months, you begin to lose muscle mass, for example, which is the complete opposite of what you’re looking for, especially if you’re older, since you will automatically lose muscle mass with age anyway.
Hence, I strongly recommend cycling in and out of ketosis once you’ve regained your metabolic flexibility and are able to effectively burn fat for fuel. In other words, you stay in ketosis only long enough to make sure you’re burning fat, and then you move into a more balanced approach where you’re adding in higher amounts of healthy carbs once or twice a week.
The Dark Side of Water-Only Fasting
I also do not recommend strict multiday water-only fasting, even though historically this has been a very successful and beneficial approach. The reason for my change in view is because our toxic exposures have dramatically increased, which makes fasting riskier now than it ever was historically.
As mentioned, fat-soluble toxins are stored in your fat cells, and when you fast and rapidly lose weight, those toxins are released, with potentially devastating effects.
Matters are made worse by the fact that many people have poorly functioning detoxification systems and simply aren’t metabolically healthy enough to metabolize all those toxins. Phase 2 detox pathways in particular tend to be dysfunctional or impaired in many. Toxicity is typically the reason why people feel horrible when fasting. It’s not an artifact of the fasting process in and of itself.
Another reason why I don’t recommend multiday water fasting is because compliance is so poor. Naturally, if you cannot comply with the program, you cannot reap the benefits. Many would rather lose a foot than go without food for five to seven days straight. My KetoFasting protocol is a pragmatic approach designed to optimize compliance.
Lastly, when you’re doing multiday water fasting, you’re really limited in how many times a year you can do it. If you did it once a month, which would be rare, you’d still only cycle through the regeneration process just 12 times in a year. If you fast once a quarter, you’re down to four times a year. You also have to refeed more cautiously after going without food for several days.
With KetoFasting you can cycle through the regeneration process anywhere from 52 to 104 times a year, and you can jump right into feasting, eating lots of protein and carbs the day you break your fast.
I do not think it is wise to jump into KetoFasting without doing the preliminary work detailed in “Fat for Fuel.” You really need to be metabolically flexible and able to burn fat for fuel before you start KetoFasting. At bare minimum, you should not skip step No. 1 (below). That said, the following is a three-step summary of my KetoFast protocol.
1. Introduction — The first step is to compress your daily eating window to six to eight hours for at least four weeks, meaning you eat all of your calories for the day during those six to eight hours, and for the remaining 16 to 18 hours, you’re fasting. Also, be sure to eat your last meal at least three hours before bedtime to avoid creating unnecessary free radicals.
I recommend testing your ketones to confirm that you are in ketosis (which means your body is burning fat), especially if you are heavy to start with, or diabetic, as it might take you longer to shift. Ketocoachx.com is the best blood ketone meter out there and only costs 70 cents per strip. It is a brand-new meter that became available at the end of April 2019.
2. KetoFast days — Once you’ve restored your metabolic flexibility to burn fat for fuel you can move into the second phase, which involves having a single 300 to 500-calorie meal, ideally breakfast, followed by a 24-hour, water-only fast, once or twice a week.
To determine how many calories you should have at this meal, first calculate your lean body mass by subtracting your percent body fat from 100. (So, if you have 20% body fat, you have 80% lean body mass.)
Multiply that percentage (in this case, 0.8) by your current total body weight to get your lean body mass in pounds. Next, multiply your lean body mass in pounds by 3.5. This is the number of calories you’ll want to eat for that meal. The following is a general guide for the nutrient ratios you’re looking for in this meal:
Carbs — Less than 10 grams of net carbohydrates (total carbs minus fiber) so as not to replete your glycogen stores. Primarily, your carbs would then be nonstarchy vegetables, seeds or nuts.
Protein — Half of your personalized daily protein requirement, with a focus on plant based protein, not animal protein. If you’re younger than 60, a general recommendation for your daily protein requirement would be 0.8 grams of protein per kilogram of lean body mass, or 0.5 grams of protein per pound of lean body mass.
Let’s say your daily protein requirement is 80 grams. For this meal, you’d cut that in half to 40 grams. The key here is not just lowering your overall protein intake, though; rather, it’s restricting branched-chain amino acids (such as leucine, for example), found primarily in meat and dairy products.
The reason you want to restrict branched-chain amino acids at this meal is because they inhibit autophagy — essentially blocking the very cleanout process you’re trying to activate through fasting. Aside from plant-based protein, an ideal form of protein to include in this meal is collagen and/or bone broth, which provide great support for your connective tissue without inhibiting autophagy. Chlorella is another excellent protein you can include.
Fat — The remainder of your calories comes from healthy fats such as coconut oil, avocado, MCT oil, butter, olive oil and raw nuts.
By eating just that one 300- to 500-calorie meal and then fasting for 24 hours, you essentially end up having eaten once in 42 hours. This will effectively allow your body to deplete the glycogen stores in your liver, which sends autophagy soaring.
On your KetoFast days, you also need to avoid any supplements you might normally take that will inhibit autophagy. Commonly used supplements that should be avoided for this reason include methylfolate, vitamin B12, exogenous ketones, colostrum and glutamine.
Supplements that support autophagy that you can take during your KetoFast include berberine, ECGC, pomegranate peel extract or powder and organic chamomile tea, as these activate autophagy and will support the process.
3. Refeed day — After completing your 42-hour KetoFast, it’s time to feast. This is also the perfect time to do hardcore strength training and load up on animal protein such as grass fed organic steak and/or whey protein, as now you’re in rebuilding mode, which includes muscle building.
You can also kick your carbs up to 100 or 150 grams. An ideal sequence for this day is to do your strength training in a fasted state, then have a big meal afterward. Now’s also the best time to use your sauna (see below).
As for the number of meals on refeed day, I keep it consistent with my normal intermittent fasting schedule. I simply eat more at each meal. So, for example, instead of having two eggs on my salad, I’ll have three on refeed day; instead of having vegan protein in my smoothie, I’ll switch over to organic grass fed whey concentrate.
Tips and Tricks
In the featured interview, I also discuss tips and tricks to get you through some of the more common issues people complain about when fasting or going on a cyclical ketogenic diet. Here’s a quick summary of some of the key points:
• Cravings — Many struggle with hunger when fasting, but one of the beautiful benefits of intermittent fasting is that once you’re able to burn fat for fuel, hunger and carb cravings vanish, since at that point your body is able to access your fat stores and create energy out of your body fat.
This is one of the reasons why you’ll want to do intermittent fasting for at least a month and make sure you’re in nutritional ketosis before you start KetoFasting. When you are insulin resistant, your body is not able to access and convert body fat to energy in an efficient manner, hence carb cravings and hunger pangs are the norm among sugar-burners.
• Sauna — Aside from a cyclical ketogenic diet, intermittent fasting and cyclical partial fasting (KetoFasting), another key strategy that can help optimize your health span are sauna bathing and thermogenesis, or the cycling between hot and cold exposures.
I specifically recommend using an EMF-free near-infrared sauna for general health optimization but especially when KetoFasting to help with detoxification.
I recommend using your sauna daily but especially the morning after your KetoFast, as at this time your body will be releasing a significant amount of toxins. If you’re strength training, consider taking a sauna directly after, and then break your fast with a high-protein meal that has plenty of branched chain amino acids and fresh fruit to stimulate mTOR.
In atherosclerosis, fatty deposits form in blood vessel walls, narrowing and eventually rupturing or blocking them. It is one of the largest causes of death. The majority of efforts to treat atherosclerosis are focused on reducing the input of LDL cholesterol. This means statins and other, more recent approaches to lower levels of LDL cholesterol in the bloodstream, such as PCSK9 inhibitors. It is possible to reduce blood cholesterol to very low levels indeed, far below normal, and this actually has comparatively little effect on existing atherosclerotic lesions. Patients still die. The disease still progresses, just more slowly.
Atherosclerosis isn’t a condition of cholesterol, for all that this is how it largely discussed in the medical profession, but rather a condition in which the macrophages responsible for clearing cholesterol from blood vessel walls become dysfunctional. The focus should be on the macrophages. Nonetheless, the research community remains largely focused on LDL. The work here is illustrative of attempts to find yet more ways to reduce LDL cholesterol in blood vessel walls, this time somewhat more specifically than by simply lowering levels everywhere. Still, I suspect it will be unlikely to produce benefits significantly greater than those of PCSK9 inhibitors and their general reduction in LDL cholesterol in the bloodstream.
Since low-density lipoprotein, or LDL, cholesterol entry into the artery wall drives the development of atherosclerosis, or hardening of the arteries, and atherosclerosis leads to heart attacks and strokes, future treatments preventing the process may help decrease the occurrence of these life-threatening conditions. A new study reveals for the first time how a protein called SR-B1 (short for scavenger receptor class B, type 1) ferries LDL particles into and then across the endothelial cells that line arteries. The study also found that a second protein called dedicator of cytokinesis 4, or DOCK4, partners with SR-B1 and is necessary for the process.
In the early stages of atherosclerosis, LDL that has entered the artery wall attracts and is engulfed by important immune system cells called macrophages that ingest, or “eat,” LDL particles. LDL-laden macrophages become foam cells that promote inflammation and further the development of atherosclerotic plaques. The plaques narrow the artery and can become unstable. Plaques that rupture can activate blood clotting and block blood flow to the brain or heart, resulting in a stroke or heart attack. In studies of mice with elevated cholesterol, the investigators determined that deleting SR-B1 from the endothelial cells lining blood vessels resulted in far less LDL entering the artery wall, fewer foam cells formed, and atherosclerotic plaques that were considerably smaller.
In their studies, the researchers compared SR-B1 and DOCK4 abundance in areas of the mouse aorta that are prone to plaque formation compared with regions less likely to become atherosclerotic. They found higher levels of SR-B1 and DOCK4 in the disease-prone regions long before atherosclerotic plaques formed. This finding suggests that atherosclerotic lesions may be more common in particular artery sites because of more SR-B1 and DOCK4 present there. To determine if these findings might apply to people, the researchers reviewed data on atherosclerotic and normal arteries from humans in three independent databases maintained by the National Institutes of Health (NIH). In all three databases, SR-B1 and DOCK4 were more abundant in atherosclerotic arteries compared with normal arteries. The researchers are now exploring the possibility of using gene therapy to turn off or reduce the function of SR-B1 or DOCK4 in the endothelial cells that line arteries in order to prevent atherosclerosis.
This popular science article discusses at length the chronic inflammation that is characteristic of the old, and its role as a proximate cause of age-related disease. Inflammation is a necessary part of the immune response to injury and pathogens, and when present in the short term it is vital to the proper operation of bodily systems. But when the immune system runs awry in later life, and inflammatory processes are constantly running, then this inflammation corrodes metabolism, tissue function, and health.
In 2007, researchers already knew that exercise reduces the risk of cardiovascular disease as much as cholesterol-lowering statin drugs do. By analyzing biomarkers in the blood of 27,055 women participating in a long-term study, and other objective measures, they hoped to tease out how much of the benefit was attributable to improved blood pressure, to lower body weight, or to something else. “We were actually surprised that reduced inflammation was the biggest explainer, the biggest contributor to the benefit of activity, because we hadn’t hypothesized that. We knew that regular exercise does reduce inflammation over the long term, but we also knew that acute exercise transiently increases inflammatory biomarkers during and immediately after exertion.” About a third of the benefit of regular exercise, they found, is attributable to reduced inflammation. The anti-inflammatory effect of exercise was much greater than most people had expected. That raised another question: whether inflammation might also play a dominant role in other lifestyle illnesses that have been linked to cardiovascular disease, such as diabetes and dementia.
In 2017, two cardiologists, who suspected such a link, published the results of a human clinical trial which involved more than 10,000 patients in 39 countries, and was primarily designed to determine whether an anti-inflammatory drug, by itself, could lower rates of cardiovascular disease in a large population, without simultaneously lowering levels of cholesterol, as statin drugs do. The answer was yes. But the researchers went a step further, building into the trial additional tests seeking to clarify what effect the same anti-inflammatory drug, canakinumab, might have on illnesses seemingly unrelated to cardiovascular disease: arthritis, gout, and cancer. Only the researchers themselves, and their scientific colleagues, were unsurprised by the outcome. Lung cancer mortality dropped by as much as 77 percent. Reports of arthritis and gout also fell significantly.
In medicine, believing something is true is not the same as being able to prove it. Because the idea that inflammation – constant, low-level, immune-system activation – could be at the root of many noncommunicable diseases is a startling claim, it requires extraordinary proof. Can seemingly unconnected illnesses of the brain, the vasculature, lungs, liver, and joints really share a deep biological link? Evidence has been mounting that these common chronic conditions – including Alzheimer’s, cancer, arthritis, asthma, gout, psoriasis, anemia, Parkinson’s disease, multiple sclerosis, diabetes, and depression among them – are indeed triggered by low-grade, long-term inflammation. But it took that large-scale human clinical trial to dispel any lingering doubt: the immune system’s inflammatory response is killing people by degrees.
Now the pertinent question is why, and what can be done about it. The pharmaceutical industry is deeply interested in finding ways to stop inflammation with medicines like canakinumab, an orphan drug that blocks a specific pro-inflammatory pathway called IL-1beta. But some researchers suggest that the inflammatory process – a normal and necessary part of the natural immune response – has itself has been misunderstood. Scientists know that the process can be turned on and off, but have only recently understood that this doesn’t mean normal physiology will resume once the inflammation caused by infection, injury, or irritant has been shut down. Instead, the restoration of health is an active phase of the inflammatory process itself, facilitated by a little-known class of molecules called pro-resolving mediators – the protectins, resolvins, maresins, and lipoxins – brimming with marvelous, untapped, regenerative capacities.
Do you find yourself making excuses for not exercising? If so, you’re not alone. However, you may not realize that failure to exercise is part of a vicious cycle that, if not reversed, could set you up for muscle loss, frailty and a loss of independence.
The human body was built to move. Anthropological evidence provides clues that running after prey was essential to our survival. But if the fitness of humans in developed countries is any indication, we’ve forgotten our birthright. The majority of waking life for many of the world’s people is spent seated in front of a flickering screen.
Learn more about exercise below and listen to the Live Foreverish Podcast with Life Extension’s own Michael A. Smith, MD, as he discusses “Getting Your Workout to Work.”
Why is exercise so hard?
Inertia is a common experience among humans, particularly as we get older. In psychological terms, inertia describes indisposition to change that occurs among those who know they need to accomplish a task but have trouble finding the motivation to get started.
In our culture of instant gratification, the long-term benefits of exercise don’t always appear real or worth the continual investment of time and energy.
There’s a vicious cycle involved in failing to exercise: Without it, muscle mass diminishes, and with weakened muscles—or even frailty—people are less likely to exercise.
Although some people have injuries or illnesses that prevent them from exercising the way they’d like to, others do not. Sometimes all that’s needed is a sobering re-examination of priorities in light of what we know concerning the essentiality of regular physical activity to our health.
Does exercise really matter?
When it comes to health and well-being, exercise is one of the most important factors.
According to the World Health Organization, the determinants of health are:
· the social and economic environment · the physical environment · the person’s individual characteristics and behaviors
These behaviors include keeping active, as well as balanced eating, not smoking, moderation in drinking, and being able to cope with stress.1
A study published in the British Journal of Sports Medicine reported more than double the percentage of individuals who experienced healthy aging (defined as not developing chronic disease, depressive symptoms, or physical or cognitive impairment over eight years of follow-up), among men and women who engaged in moderate activity in comparison with inactive subjects.2 For those who reported vigorous activity at least once per week, there was an even greater increase. Furthermore, becoming active over the course of the study was associated with more than three times the chance of experiencing healthy aging, and for those who remained active, the increase was over seven times greater in comparison with remaining inactive during follow-up.
If the prospect of healthy aging isn’t enough to motivate you, consider the results of a study published in the BMJ, which analyzed 16 meta-analyses (including 305 randomized controlled trials with a total of 339,274 participants) of the effects of exercise and pharmaceutical trials on mortality.3 Husyein Naci and John P.A. Ioannidis found that physical activity interventions were more effective than drugs at preventing death in men and women recovering from stroke. It was also observed that “no statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes.” And in another study, researchers from Australia found that men and women who engaged in a high amount of recreational physical activity had an 84% lower risk of mortality from cardiovascular disease than those with a low activity level, and an 88% lower risk of mortality from coronary heart disease.4
Immediate health benefits of exercise
While it may be hard to think about the effects of exercise that you’ll experience eight years from now, or even in a month when your clothes fit better, some benefits are immediately noticeable. Despite the possibility of temporary muscle fatigue, mental fatigue may vanish, mood may lift and “inertia” may lessen in a short period of time. People who exercise may feel more energetic, think more clearly, sleep better and remember more. Exercise can sometimes help banish a blue mood, worry or grief in a very short time.
Importance of exercise
Exercise is important in the prevention of aging-associated diseases such as cardiovascular disease and Alzheimer’s disease, as well as a condition known as sarcopenia. 5,6Sarcopenia is defined as a loss of muscle mass and function. The condition, which occurs in 5% to 10% of those over the age of 65, can lead to loss of mobility and function, falls and premature mortality. The condition can be the result of several causes, and lack of regular exercise can be a contributing factor. Exercise, particularly resistance exercise, is one of the treatments for sarcopenia, along with vitamin D and protein supplementation.7
Older individuals who exercise may find it more challenging to build muscle compared with when they were younger. As people age, they become more susceptible to a slowdown in the body’s ability to rebuild muscle.8
Fortunately, a supplement known as HMB (beta-hydroxy-beta-methylbutyrate), a metabolite of the amino acid leucine, helps support muscle growth in response to exercise, which could be a boon to older individuals who find it difficult to maintain muscle mass.9,10 In a study involving older individuals, supplementation with HMB improved strength and muscle quality even in the absence of resistance exercise.11
Long ago, the philosopher Lao Tzu remarked that “a journey of a thousand miles begins with a single step.” One might add that the step that is the most difficult is the first one. Humans are creatures of habit. By literally taking the first step in any exercise routine, you are beginning a journey that is much more certain to approach the elusive Fountain of Youth than any of the travels of Ponce de Leon.
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Life expectancy, mortality, and risk of age-related disease are well known to correlate with a complicated web of socioeconomic factors. Educational attainment correlates with life expectancy, but so does intelligence. The relationship with intelligence might have underlying genetic causes, in that more intelligent people may be more physically robust. Or it may be that intelligence and education are inextricably linked – smarter people are better educated or better educated people do well on tests of intelligence – and the effect on life expectancy has little to do with genetics.
Further, educational attainment correlates with wealth, both of the region, and of the individual. Is it thus a proxy for greater access to medical technology purely due to greater wealth? What about the education and intelligence needed to use that access well? Or perhaps it has little to do with medical technology for most of the life span, and education and intelligence tend to lead to better lifestyle choices? Trying to peel apart these relationships is a complex task, and one that has not yet succeeded in any meaningful way, I would say.
The various epigenetic clocks are measures of age based on an algorithmic weighting of patterns of DNA methylation on the genome that appear to be a characteristic reaction to the damage and dysfunction of aging, occurring in very similar ways in every individual. The underlying molecular damage that causes aging is, after all, the same for everyone. It is as yet unknown as to exactly which underlying processes correspond to which DNA methylation sites on the genome, but the correlation is quite good overall. People in groups with higher risk of mortality or exhibiting age-related diseases tend to have higher assessed DNA methylation age than their healthier peers, which provides a way to determine pace of aging to some degree. Can this be useful as a tool to start dissecting the complicated relationships between aging, lifestyle, and socioeconomic status in populations? Perhaps.
Aging is characterized by a gradual and constant increase in health inequalities across socioeconomic groups, an association based on strong epidemiological evidence known as the social gradient in health. On average, individuals with lower socioeconomic position (SEP) have lower life expectancy, higher risk of age-related diseases, and poorer quality of life at older ages compared with less disadvantaged groups. Although lifestyles differ by SEP, unhealthy habits only partially explain this association.
The role of epigenetic mechanisms in response to trauma, and evidence for their involvement in intergenerational transmission of biological impacts of traumatic stress have been proposed to explain how social adversity gets biologically embedded, leading to differences in biological functionalities among individuals in different social conditions, especially at older ages. Epigenetics, specifically DNA methylation (DNAm) has been proposed as one of the most powerful biomarkers of biological aging and as one of the plausible biological mechanisms by which social adversities get ‘under the skin’ and affect physiological and cellular pathways leading to disease susceptibility.
Two measures of epigenetic clocks have gained considerable popularity, and the concept of epigenetic aging acceleration (EAA) has been introduced as the difference between predicted DNAm age and chronological age. EAA has been associated with all-cause mortality, cancer incidence and neurodegenerative disorders, as well as non-communicable disease risk factors such as obesity, poor physical activity, unhealthy diet, cumulative lifetime stress and infections.
Given the above, it can be assumed that the various epigenetic clocks describe different aspects of the biological (epigenetic) aging process. We previously showed a dose-response relationship between SEP and EAA. Further, our results suggest that the effect could be partially reversible by improving social conditions during life. In addition, ours and two more recent studies indicate that childhood SEP might have a stronger effect on EAA than adulthood SEP.
Despite extensive research in the field, to date no studies have compared the effect of SEP on epigenetic aging biomarkers with those of other lifestyle-related risk factors for age-related diseases. We aimed to systematically investigate the association of education level, as a proxy for SEP, with the total number of SEMs and ‘accelerated aging’ as assessed using the three epigenetic clocks, and to compare the independent effect of low education with those of the main modifiable risk factors for premature aging: smoking, obesity, alcohol intake, and physical inactivity, by conducting a meta-analysis including data for more than 16,000 individuals belonging to 18 cohort studies from 12 different countries worldwide.
Epigenetic aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.