1. What are the best bets in the supplement field for delaying the onset of dementia, a.k.a. vascular disease or Alzheimers?

    Supplements which boost vascular production of the protective hormone nitric oxide, which quell oxidative stress, and which suppress the activity of brain inflammatory cells should be useful for slowing age-related cognitive decline and preventing Alzheimers or stroke-induced dementia.  These can include: phytochemical polyphenols such as quercetin, cocoa flavanols, and (possibly) resveratrol; potassium nitrate (or natural sources thereof, such as green leafy vegetables and beet juice); antioxidants such as spirulina, lipoic acid, melatonin, astaxanthin; and agents which have anti-inflammatory effects on the brain, such as vitamin D, soy isoflavones, caffeine, and fish oil.  These measures should be complementary to lifestyle strategies which prevent/control metabolic syndrome and hypertension, and which exert protective hormetic stresses on the brain: calorie restriction or caloric hormesis, as achieved practically with carb-concentrated dieting; exercise training; and regular mental exercise.  More scientific detail →

  2. I’ve heard that apple cider vinegar may aid weight loss; is there any validity to this, or is it just one of those “old wives’ tales”?

    Believe it or not, a recent double-blind clinical study in Japan found that overweight people ingesting 2 tablespoons of apple cider vinegar daily (a drink of equal calorie content featuring lactic acid was used as a control) lost an average of 5 pounds of weight over the course of 12 weeks, which was significantly different than the small weight gain seen in the placebo group.  Vinegar should also be of interest to carb concentrated dieters because it slows the absorption of dietary carbohydrate (and blunts the associated rise in insulin) when administered prior to meals.  Don’t drink apple cider vinegar straight, though, because its acidity could traumatize your esophagus.  A good way to take it is to add 1 tablespoon (15 ml) of apple cider vinegar to 1 cup of water or juice, and then add a packet of non-caloric sweetener to offset the acidic flavor; you should find that this is remarkably palatable.  Drink this before your carb-containing meals and you will reduce the effective glycemic index of the meal, and blunt the post-meal rise in insulin too.  More scientific detail →

  3. What is insulin resistance, why does it occur, and why is it typically associated with high insulin levels?

    Insulin has a prominent hormonal effect on skeletal muscle fibers, liver cells, and fat cells; in these tissues, it encourages uptake and discourages the release of blood sugar (glucose) and fats.  In other words, insulin promotes fuel storage. Insulin resistance refers to a condition in which these tissues respond inefficiently to the insulin signal, so that higher levels of insulin are required to get its metabolic job done properly.  Insulin resistance is usually compensated by increased insulin release by the pancreas, which leads to elevated blood levels of insulin all day long; that’s why combating insulin resistance is crucial to a low-insulin lifestyle.  Insulin resistance of muscle, liver and fat cells is typically seen in a common metabolic disorder known as “metabolic syndrome”, which is usually associated with and caused by an excessive accumulation of fat in the body’s abdominal regions.  People with metabolic syndrome are at increased risk for heart disease, stroke, dementia, diabetes, and many types of cancer. More scientific detail →

  4. How does low IGF-I bioactivity decrease cancer risk?

    . IGF-I (insulin-like growth factor-I) is often referred to as “the universal cancer promoter”.  This reflects the fact that a high proportion of the tissues most likely to give rise to cancer are sensitive to its growth factor activity.   In the many body tissues that are responsive to it, high IGF-I activity can accelerate the onset of cancer by increasing the rate at which mutations occur in DNA, and also by blocking a protective process whereby pre-cancerous cells commit suicide to protect the body from cancer.  Conversely, relatively low IGF-I bioactivity is protective in these respects.  More scientific detail →

  5. What is the Appropriate Glycemic Load of Accessory Meals?

    In order to determine which food portions have a glycemic load equal to 10 or less, one can consult GlycemicIndex.com for a very large number of foods. An alternative source listing 100 foods can be found at Harvard Health Publications.

    More scientific detail →

  6. Is the CC diet approach just a reissuing of the Heller’s Carbohydrate Addict’s Diet?

    The Carbohydrate Addicts Diet of the Hellers, and their approach to the diet, differ from the (non-profit) Carbohydrate Concentration Diet approach in a number of ways. The Hellers focused on helping Carbohydrate “addicts” rather than on the entire population. And the Carbohydrate Concentration Diet is more general in not requiring that carbohydrates be eaten at one meal, or within one hour, as the Hellers’ diet requires. Thus the CC diet can incorporate, for example, the Herring Fast-5 diet which urges that all carbs be eaten within a fixed five hours.

    Of special importance, the Carbohydrate Addicts Diet of the Heller’s originated through their perception that they themselves were carbohydrate addicts and their conviction that other addicts like themselves would benefit from the diet. The Carbohydrate Concentration approach, by contrast, originated through the perception of Jeremy J. Stone that a successful weight-loss diet he had fallen into of eating one large meal a day (plus a snack) had close links to the very positive scientific results of eight decades on caloric restriction and intermittent fasting of mammals and the more recent scientific investigations into autophagy.

    Accordingly, the Catalytic Longevity website, incorporating the important work of Mark McCarty, explores and documents the effects of this diet on cancer, heart disease, diabetes, Alzheimer’s and the like, through a mining of relevant scientific research.

    But the Addict’s diet has been cited repeatedly and positively in this work. And readers are encouraged to visit www.carbohydrateaddicts.com, to learn from it, and to purchase and learn from the Hellers’ books.

  7. Is there anything I can take with my meals that could blunt the increases in blood sugar and insulin provoked by the meal?

    Nutrition researcher Dr. David Jenkins and his colleagues at the University of Toronto have discovered that almonds may have remarkable potential in this regard. They had their volunteers consume diets on two different days that were virtually identical, differing only in that one day’s diet contained 36 grams of almonds (a little over an ounce) and the other day’s diet contained a high-carb muffin providing exactly the same number of calories as the almonds. Remarkably, total daily insulin secretion was found to be one-third lower when the volunteers ate the diet containing almonds! This benefit was at least partially attributable to a reduction in post-meal glucose rises, as shown in other studies. The fact that the almond diet was slightly lower in total carbs could only account for a small proportion of the large reduction of insulin secretion observed.

    Why almonds have this remarkable effect remains mysterious, although the plant protein and monounsaturated fat provided by almonds might play a role. Almonds are very low in saturated fat, and are a good source of plant protein, fiber, minerals, and phytochemicals; studies show that almond-enriched diets have favorable effects on blood fat profiles, and are unlikely to provoke weight gain. So including a small handful of almonds in your meals may be a winning strategy. More scientific detail →

  8. If a human achieves the same caloric restriction as a mouse, e.g. 20%, would be we expect the human to have the same health benefits as a mouse? And what about primates?

    There is no clear answer to this at this time — that why scientists at the Wisconsin Primate Center are currently studying lifelong calorie restriction (30%) in rhesus macaque monkeys — presumably more pertinent to humans than rats. So far, the monkeys in this study have attained the median lifespan of (unrestricted) monkeys, and the death rate from age-related disorders has only been one-third as high in the restricted monkeys as in the restricted ones. It’s not yet clear how this will equate to increased longevity, but there is already clear evidence that calorie restriction can be tremendously protective in primates.

    However, perhaps our best current way to address this problem is to look at Okinawans, a contemporary human experiment in calorie restriction. Studies show that, prior to 1970, Okinawans consumed about 11% fewer calories than would have been considered “weight maintenance” for their lean physiques (averaging BMI 21). By the “BMI 22 reference man” standard, their “true” calorie restriction may have been closer to 12%. But after 1970, the Okinawans were no longer calorie restricted. Yet aging Okinawans now have an average and maximal life expectancy that is about 4-5 years longer than that of current Americans. In rodents, life extension achieved by calorie restriction appears to be more or less proportional to the extent of calorie restriction and the portion of one’s total life spent in calorie restriction. Elderly Okinawans achieved about a 12% calorie restriction for perhaps about half their lives — and now enjoy a 4-5 year advantage in life expectancy. This suggests that humans who managed to achieve a 20% restriction for most of their lives could enjoy a quite substantial increase in life expectancy — provided that this benefit is proportionate in humans as it is in rodents.

  9. How can I estimate my degree of caloric restriction — as understood in Caloric Restriction Experiments — from my measurement of the reduction in caloric consumption that I am experiencing?

    By estimating your average daily calorie intake at baseline, and then once again after your weight has equilibrated after a year or so of CC dieting, you can calculate the percent reduction in daily calorie intake made possible by your new lifestyle.  But many people who embark on CC dieting do so not just to get leaner and improve their risk factors, but also in the hope of achieving some of the aging-retardant benefits observed in rodents and rhesus monkeys who are chronically fed less than their ad-libitum calorie intake.

    How can you estimate how much calorie restriction benefit you are achieving with your CC regimen? This is not as straightforward as it might sound.   Consider two people:  Person A was quite heavy, but has managed to reduce his average daily calorie intake by 30% and lose significant weight with CC dieting.  Yet his daily calorie intake may now be little different than that of a moderately lean person with a comparable height and activity level — because his metabolic rate had been pushed upwards during his years of overeating.  Contrast him with Person B, who may have been quite lean when he embarked on CC dieting — say, a BMI of 20 — and achieves an average daily calorie reduction of 10%.  It is quite conceivable that person B is enjoying a greater calorie restriction metabolic benefit than person A — even though his calorie consumption has fallen by a lesser percentage.

    If you would like to estimate the true degree of calorie restriction you have achieved with CC dieting — so that you can compare your experience with that of other people who are consciously engaged in calorie restriction protocols (or underfed mice or rhesus monkeys!) — we suggest that you visit this website.

    The Calorie Restriction Calculator on this website estimates the daily calories burned by a person who has a moderately lean BMI of 22, but who has a height, activity level, age, and sex similar to your own.  The extent to which your current calorie intake is below this estimated calorie intake can be considered your “true” calorie restriction.  In other words, if your current calorie intake is about 1900 kcals daily, whereas your “twin” with a BMI of 22 is estimated to burn 2200 kcals daily, then the calorie restriction you have achieved would be 300 kcals daily, or 300/2200 = 13.6%.

    To get reasonably accurate results with this Calorie Restriction Calculator, be careful not to overestimate your daily activity level.  The great majority of Americans would fall into the “sedentary” or “lightly active” categories, even those who go to a gym several times weekly.  Only people who are exercise fanatics — substantial exercise most days of the week – or who have physically demanding occupations would fall into the higher activity categories.

  10. I’ve lost a lot of weight with carb concentrated dieting, and now that my weight has equilibrated, I calculate that my daily calorie intake is lower than that of my “reference man” with a BMI of 22 — but my own BMI is still higher than that. In other words, I’m achieving true calorie restriction, but I’m not as lean as I would expect to be. What’s the problem?

    Studies show that, when people lose a lot of weight, their daily energy expenditure tends to decline.   In fact, when their weight equilibrates, their daily energy expenditure tends to be lower than that of people of comparable size and body composition who haven’t lost weight.  Only a small portion of this difference is attributable to a lower resting metabolic rate – most of the reduction is in so-called “non-resting energy expenditure” associated with physical activity.  And it’s not because people who have lost weight are lazier.  Apparently, an adaptation occurs whereby it takes less food energy (ATP) to fuel a given amount of muscular effort; in other words, your body becomes more “energy efficient”.  This may account for the fact that you may not get as lean as other people with comparable activity levels who eat more calories than you do.  More scientific detail →

  11. Mice experiments on caloric restriction compare caloric restricted mice with mice eating as they wish (ad libitum). By contrast, in human dieting, humans eat less calories than they were doing previously at their higher weight. How can the reduction in calories of the human, e.g. a reduction of 20%, be compared and calibrated with the forced reduction of the mice? What role does the reference-man calculation comparing caloric consumption with a same-BMI person of BMI 22 mean here?

    Here is no truly objective way to calculate the degree of calorie restriction you are achieving on a CC diet regimen or other calorie restriction protocols. Obviously, you can calculate your percent reduction of calorie intake from baseline when you go on a CC regimen; this calculation will be most meaningful once your weight has equilibrated at a new lower set point, and you thus are on a sustainable regimen. However, if you had been substantially overweight and were really stoking in the calories, a 20% reduction from baseline in calorie intake — while no doubt beneficial for your body weight and your long-term health prospects — cannot be presumed to provide the same degree of calorie-restriction health benefit that a relatively lean and abstemious person would achieve if he likewise reduced his calorie intake 20% from baseline. That’s why some experts on calorie restriction suggest that we calculate our “true” level of calorie restriction by comparing our calorie intake to that of a person of comparable height who has a relatively lean, healthy BMI of 22 and is taking in sufficient calorie to maintain his weight. Choosing a BMI of 22 was rather arbitrary — 21 or 23 might have served as well. But by employing this standard, we can then seek to correlate one’s “true calorie” restrictions with health outcomes, and perhaps use the results of studies in rats or rhesus monkeys to estimate the life expectancy benefits we might hope to enjoy.

  12. What role does autophagy play in improving the health of cells outside the nervous system and what do we know about its role with regard to the brain?

    Studies show that stimulation of autophagy is plays a vital role in the life prolongation achieved by calorie restriction in lower organisms such as yeast and worms. Many scientists suspect that a key mediator of the health benefits of prolonged calorie restriction in mammals is a preservation of the capacity for autophagy, at least outside the brain. Although fasting induces an acute increase in autophagy in most tissues, the more intriguing effect of long-term calorie restriction is to prevent an age-dependent reduction in basal or stimulated autophagy. No one seems to have a clue as to why this happens. It is clear that properly regulated autophagy (i.e. balanced by new synthesis of proteins and organelles such as mitochondria) helps to keep the interior of our cells “clean” and optimally functional by getting rid of proteins, aggregates of proteins, and organelles that have been damaged by oxidative stress or other mechanisms. By keeping our mitochondria in optimal working order, autophagy may help to control oxidative stress that contributes to mutagenesis and cancer. Theoretically, this could be valuable for preserving the functional status of our vital organs, particularly those with long-lived cells like our heart or skeletal muscles. Could shorter-term calorie restriction or fasting regimens have a “rejuvenative” effect on our organs via increased autophagy? This is an intriguing prospect, but so far little research in rodents or humans has addressed this possibility. Water fasting regimens of ten days or so appear to have some intriguing health benefits, but the extent to which these are mediated by autophagy is not clear.

    It is however very clear that an adequate basal level of autophagy in brain neurons is required to prevent neurodegenerative disorders — many of which are associated with and mediated by undue accumulation of toxic protein aggregates in neurons. Indeed, drugs which accelerate autophagy in the brain have been shown to be useful in rodent models of Alzheimer’s and Parkinson’s disease. Unfortunately, however, there is no consensus that calorie restriction or fasting is capable of activating brain autophagy; many scientists doubt this. One report indicates that a 48 hour fast activates brain autophagy in mice, but a similar study fails to support this; and no studies have examined the impact of calorie restriction protocols on brain autophagy. The good news is that, regardless of the impact of calorie restriction on brain autophagy, restriction exerts hermetic effects on the brain that boost the activity of neuronal growth factors and other proteins that can protect the brain from a wide range of stressors, and very likely provide some protection from our most common neurodegenerative disorders.

  13. What can I take with a carb-rich meal that could decrease the post-meal elevations in both glucose and insulin?

    A more uniformly beneficial strategy that CC dieters can use to minimize the effective glycemic index of carb-rich meals is to include factors such as soluble fiber, vinegar, or almonds. These have the potential to suppress meal-induced increases in both glucose and insulin. How these work to achieve this benefit is still not entirely clear, but the current scientific literature offers some clues. Soluble fiber forms a dense meshwork that slows the interaction between starch and the key digestive enzyme which degrades it, amylase. The acetic acid in vinegar appears to decrease the activity of enzymes (disaccharidases) in the intestinal lining required for full digestion and absorption of starch and sucrose. Substituting modest amounts of almonds for carbohydrate intake of equal caloric value is associated with a large reduction in daily insulin secretion — up to a third — that is clearly disproportionate to the reduction in carb intake; why almonds are so effective in this regard remains mysterious.

    More scientific detail →

  14. Does combining my carbohydrates with protein or fat dilute the glycemic index of the carbohydrates and lower the effective blood sugar rise?

    Ingestion of protein and of fat (especially monounsaturated fat) along with carb-rich foods often does indeed blunt the post-meal rise in blood glucose, effectively lowering the glycemic index of the meal. This appears to reflect increased production of certain hormones, produced by cells in the intestinal tract, that act on the pancreatic beta cells to boost the insulin response to absorbed glucose. These hormones can also slow the emptying of the stomach into the upper intestine, possibly decreasing the effective glycemic index of food still remaining in the stomach. These hormones also promote satiety — which helps to explain why meals containing protein or fat tend to be more satisfying than meals of pure carbohydrate. The downside of this mechanism is that, whereas it helps to restrain the post-meal rise in glucose, it accomplishes this mainly by boosting insulin secretion — which rather misses the point if your goal in CC dieting is to minimize your daily insulin levels. Nonetheless, moderating postmeal rises in glucose is inherently beneficial for diabetics, and may also aid in diabetes prevention. More scientific detail →

  15. When I eat carbohydrates to excess in a day and develop higher insulin and glucose levels, does this produce a short-term increase in weight — and what is the nature and permanence of this weight gain?

    If you gain a couple of pounds because of a day of indulgence, it’s not primarily fat weight you have gained, but rather water weight. Increases in blood insulin levels act on the kidneys to boost the retention of sodium and chloride; if you are eating a salted diet, as most of us do, this will be associated with some temporary fluid retention. Once you get back on your CC regimen, and your insulin goes down, you will readily get rid of that sodium and water, and your weight will be back down. Don’t become too distressed or elated about temporary small variations in your weight — just try to stick with the program as best you can. If you succeed most of the time, you should do well.

  16. Is this a brittle diet that I must follow carefully; what harm will result if, for example, I drop off the diet for a weekend or a week?

    Aside from a trivial weight gain if you “fall off the wagon” for a number of consecutive days, there should be no meaningful long-term adverse consequences to your weight or your health from occasional short-term lapses. In fact, even if your standard practice is to do a CC diet only several days a week, this likely will aid your weight control and improve your risk factors, even if you won’t gain the calorie-restriction and lifespan extension benefits achieved by more dedicated adherents. Realistically, because of travel or social commitments, most people will depart from their dietary ideals now and then — don’t be too hard on yourself. Lapsing for a few days or even weeks won’t reverse the health benefits earned by previous months or years of dedication. Bear in mind that elderly Okinawans are still enjoying significant lifespan extension, even though most of them haven’t been calorie restricted since the 1970s.

  17. Besides a Carb Concentrated Diet, what else do you recommend if it is not contraindicated by your condition or contradicted by your doctor?

    A baby aspirin a day; medium chain triglycerides, supplements (discussed below), stress reduction and low salt.

  18. Why haven’t I heard more about Carb Concentration diets?

    This formulation has just begun to be circulated. But millions of people bought the Hellers’ books, so a lot of people have heard about a special case of them. Unfortunately, the Hellers have never published their clinical experience in formal scientific papers, so the medical profession knows little about this strategy. They did do a comparison study that looked at how people did when carbs were split over 3 meals or eaten in one meal; the CC dieter were much more successful at achieving weight loss. But for whatever reason this isn’t in the medical literature. Other than that, the Hellers have years of experience in helping overweight people get leaner and healthier, but the medical authorities tend to deride this as “anecdotal experience”. If CC diets are ever to gain greater respect from “the powers that be”, doctors need to be encouraged to try CC diets with their patients, and to publish their clinical experience in medical journals. We hope to encourage this. And scientists investigating practical life extension strategies ought to take a serious look at CC diets too. But especially important in the CC approach is the link deduced in the above paper between CC diets and caloric restriction dieting experiments. This plus links to autophagy and hormesis suggest that diets with long windows of low insulin should be very promising.

  19. I’m a vegetarian because I love animals and I’m worried about global warming. Could a CC diet work for me?

    Sure, because a CC diet does not need to be a low-carb diet. You can eat all your favorite foods in your major daily meal. For your subsidiary meal, you can have low-carb plant foods like green salads, nuts, and soy products.

  20. The Hellers say that eating carbs with three meals daily is bad for weight control. Then why did the Japanese stay so lean on their traditional diet that is about 80% carbs — mostly high-glycemic-index white rice?

    If all your life your diet has been extremely low in fat, you’re not likely to ever get fat. That’s because almost all of the fatty acids in our bodies come from the fat in our diet. But that isn’t very relevant to what most Americans face — they’ve already gotten fat by eating diets rich in both fat and in high-glycemic index carbs, which have prevented that fat from being burned. Clinical studies show that moderately reducing dietary fat while keeping carb intake high just isn’t very effective for achieving meaningful weight loss. Diets very severely restricted in fat — like the Pritikin diet — work somewhat better, if accompanied by exercise — but most people find them unappealing and won’t stick with them. Diets that promote fat burning either by keeping total carb intake low, or by restricting significant carb intake to a single meal, seem to work better for most people.

  21. Just what is it about low insulin that is so protective?

    Many things. Low insulin decreases the effective bioactivity of cancer-promotional hormones like IGF-I and estrogen by increasing the liver’s production of proteins that block their action. These hormones increase cancer risk by stimulating cell multiplication and thereby boosting the rate at which mutations occur in tissues sensitive to their action; these hormones also suppress a process called apoptosis that kills off many pre-cancerous cells before they can become cancers. Low levels of insulin and of IGF-I bioactivity also enable the protective process of autophagy, which is sort of like vacuuming out the old and damaged cell constituents so that they can be replaced with shiny new ones. And maintaining low insulin for most of the day enables your body to burn your stored fat so you have a chance to get leaner. Insulin is the primary hormonal signal that causes fat cells to store and retain fat, and it also blocks fat burning in other tissues. This probably explains why the Heller’s patients often lose a lot of weight. And getting lean or staying lean greatly reduces your risk for vascular disease, diabetes, and many cancers.

  22. Will you have enough energy to do effective exercise on a CC diet? I tried an Atkins diet once, but I just didn’t feel much like exercising when I was on it.

    That’s not uncommon. Studies show that people on low-carb diets tend to be less motivated to do aerobic exercise, probably because their liver glycogen stores are very low. (When runners run out of glycogen, they “hit the wall”.) But a CC diet is not necessarily low carb — in fact, you can eat a lot of carbs with your daily “reward meal” — enough to fill your liver glycogen stores. So if you want to do lots of aerobics with a CC diet, just make sure you eat a lot of carbs when permitted to. Note that the Hellers strongly recommend exercise with their regimen. This helps to burn more fat, and also promotes muscle insulin sensitivity, so that your daily insulin secretion will be even lower.

  23. How can you know that CC diets will increase healthspan?

    Most important is the literature on caloric restriction and intermittent fasting. But the clinical experience of the Hellers is that overweight people tend to get a lot leaner on CC diets, and metabolic parameters associated with metabolic syndrome (blood pressure, triglycerides, HDL) as well as LDL tend to improve markedly. All of these changes point to decidedly lower risk for diabetes, heart disease, and cancer — and these are some of the key disorders that decrease healthspan.

  24. You say that the number of consecutive hours of low insulin is what might matter. But on alternate-day fasting regimens, insulin levels are low for up to 36 hours consecutively. In rodents, we know that this is long enough to get an extension in longevity. Why do you think that 20 hours of low insulin with a CC diet is long enough to get the same effect?

    The main reason we are advocating a CC diet rather than an alternate day diet is that we judge it as much more feasible for large numbers of humans to maintain indefinitely. Moreover, we are emphasizing healthy aging rather than longevity and we believe this will work based on much work related to low insulin diets (see next question). Of course, we don’t know for sure how well it will work and no one will have a definitive answer on this for some time. But one way we might evaluate this experimentally is to look at the impact of blood serum derived from people engaged in specific diets on certain longevity markers in cultured human cells incubated with that serum. This is a strategy pioneered by researchers at the National Institute of Aging (NIH), and there is no reason why we couldn’t compare the effects of serum from people on CC diets with those of serum from people who are doing calorie restriction or intermittent fasting.

  25. If a person eats three meals a day and no snacks, his insulin will be at or near fasting levels for about 18 hours a day. Why is a few less hours a day of elevated insulin with CC diets so important?

    Two points here. It’s not just the total number of hours, but the number of consecutive hours of low insulin that may be the key factor. The physiological adaptations that protect animals that are calorically restricted probably don’t happen instantly as soon as insulin goes down. It may take a number of hours for them to rev up. With a CC diet, if your subsidiary meals release only a little insulin, your insulin will be low or relatively low for about 20 hours consecutively. That gives low insulin a lot of time to act on your system.

    Another point is that when people scatter meals rich in high-glycemic index carbs throughout the day, this can cause wild swings in blood sugar that trigger hunger and cravings in some people, making it hard for them to control their food intake and keep their weight down. That’s probably why the Heller’s diet works well for people whom they describe as “carb addicted”.

  26. I’ve read that reduced IGF-I activity is the real reason why calorie-restricted diets increase longevity and prevent or postpone cancer. Yet you say little about IGF-I. Will a CC diet reduce IGF-I levels?

    Not necessarily. But what is important is IGF-I bioactivity. Because CC diets keep insulin low most of the day, the liver makes more of a protein called IGFBP-1 that binds to the IGF-I in the blood and prevents it from interacting with its receptor. So IGF-I activity should go down even if the IGF-I level doesn’t . And it seems likely that even the level of IGF-I will go down on a CC diet if it is vegan (plant-based and moderate in protein content).

  27. Are there supplements that you specially recommend for enhancing the effect of the CC diet or otherwise strengthening healthy aging?

    Yes. We recommend consideration of the following supplements:

    • Acetyl-l-Carnitine and Alpha Lipoic Acid which can be best purchased through www.Juvenon.com where a discussion of their health benefits can be found.
    • COQ-10 of the newer form called ubiquinol (rather than ubiquinone); this can be purchased and is discussed at the website www.lef.org or Life Extension Foundation.

  28. In what way might a CC diet slow the aging process?

    Low insulin levels, maintained by the CC diet, decreases the effective bioactivity of a hormone IGF-I that, in rodent studies has emerged as a key driver of the aging process. More scientific detail →

  29. I am well along in age, is it too late for me to benefit from a CC diet?

    No. Calorie restriction and maintenance of low insulin levels can have a rapid impact on inflammation, oxidative stress, pain perception, growth factor activities, and the process of autophagy which helps to keep the interiors of our cells in optimal working order. Hence – particularly to the extent that a CC diet achieves a measure of calorie restriction – a CC diet initiated even late in life can be expected to have a rapid beneficial impact on: risk of heart attacks, aches and pains, inflammatory disorders, cancer, cognitive function and exercise capacity. More scientific detail →

  30. Besides concentrating my carbs in a single daily meal, are there special food choices that will enhance the effects of the CC diet?

    Try not to binge on carbohydrates in this main meal and to eat the carbs with a balanced meal. The foods you choose, besides carbs, and in the other meals, can be chosen to be low in glycemic index. More scientific detail →

  31. How important is exercise in this dietary regime and how best should exercise be adjoined to this diet to maximize its effect?

    Exercise while insulin is low is much more effective in cutting fat than exercise after a meal when insulin is higher. And, besides its effect on body weight, exercise training can have a direct insulin sensitizing effect on the muscles employed in the exercise which can translate into a further reduction in daily insulin secretion. Exercise will have good effects on the arteries, on the bones and on a healthy brain. More scientific detail →

  32. Will Carb Concentrated Diets Help Me Reduce the Risk of Insulin Resistance Syndrome, a.k.a. metabolic syndrome, which includes the risk of heart attack, stroke, type 2 diabetes, heart failure, hypertension, fatty liver disease, many common types of cancer, and aging-related cognitive decline and dementia?

    We believe it will. This syndrome is a type of “fat poisoning” and chronically elevated insulin levels. Maintaining leanness with this diet and keeping insulin levels low, as this diet does, should be important. More scientific detail →

  33. Will Carb Concentrated Diets Help Me Reduce the Risk of, or Delay the Onset of, Neurological Diseases such as Alzheimer’s and Parkinsons?

    Recent research on Caloric Restriction–and on the effects of Alternate-Day Fasting which is a related low-insulin diet–suggest that they produce neuroprotective benefits in rodents; better preservation of cognitive function against diseases like Alzheimers; less loss of functional capacity following stroke; and a retardation of age-related deficits in learning.  Long-term calorie restriction in rhesus monkeys has been associated with greater preservation of gray matter in some part of the brain.  For more scientific detail see Neuroprotective Potential of Calorie Restriction, Alternate-Day Fasting, and Carb-Concentrated Diets.

  34. Neuroprotective Potential of Calorie Restriction, Alternate-Day Fasting, and Carb-Concentrated Diets

    A considerable amount of recent research has focused on the neuroprotective properties of intermittent fasting and chronic calorie restriction; the impacts of calorie restriction and alternate-day fasting appear to be quite parallel in this regard, although the effects of alternate-day fasting have been more dramatic in some studies, possibly because it is associated with higher levels of ketones bodies, which are themselves neuroprotective in various respects.  In rodents, these strategies increase brain levels of an array of protective factors, including Sirt1, “neurotrophic” hormones such as BDNF, and heat shock proteins (that help to prevent or correct protein mis-folding, a common cause of cellular distress.)  In aggregate, these effects are thought to be largely responsible for the wide range of neuroprotective benefits observed in rodents subjected to chronic calorie restriction or intermittent fasting: improved neuronal survival and better preservation of cognitive function in rodent models of Alzheimer’s, Parkinson’s, and Huntington’s disease; better neuronal survival and decreased loss of functional capacity following induced stroke or exposure to various neurotoxins; a retardation of the age-related deficits in learning and motor coordination, associated with relative preservation of the “long-term potentiation” mechanism that underlies learning.  As mentioned above, long-term calorie restriction in rhesus monkeys is associated with greater preservation of gray matter in some parts of the brain.  And, although relatively few epidemiological studies to date have examined the impact of total daily calorie intake on health outcomes, studies in New York City have concluded that people who keep their calorie intake relatively low are at reduced risk for both Alzheimer’s and Parkinson’s diseases.

    A remarkable aspect of this neuroprotective effect is that, whereas calorie restriction or intermittent fasting tend to reduce growth factor activities (insulin/IGF-I) throughout much of the body – an effect which appears to be crucial to the anti-aging and cancer-preventive impacts of these strategies – they actually appear to increase effective growth factor activity in the brain!  Thus, calorie restriction in mice has been found to increase both the expression level and activation state of insulin receptors in the brain – even though blood levels of insulin are of course notably reduced.  This may reflect, in part, a compensatory increase in the efficiency with which insulin is transported into the brain via the blood-brain barrier.  Moreover, as noted, these food deprivation strategies also boost the expression of other growth factors that target neurons, most notably brain-derived neurotrophic factor (BDNF).  This increase in brain growth factor activity promotes reparative neurogenesis, helps neurons to survive a range of toxic insults, and aids the efficiency of learning.

    An area of ongoing controversy is the impact of calorie restriction on autophagy in the brain.  As we have noted elsewhere, autophagy (or more properly, macroautophagy) is a carefully regulated process which sweeps proteins and membranes – including sub-cellular structures (organelles) such as mitochondria – residing in the cell’s cytoplasm into special vacuoles, where they are degraded to yield their constituent amino acids and fatty acids.  When this process is properly balanced with the biosynthesis of new proteins, membranes, and mitochondria (using the amino acids and fatty acids derived from autophagy as building blocks), the net effect is to insure that the proteins and organelles inside our cells are “shiny and new”, so that they function optimally.  The proteins and membranes inside our cells are under constant attack by oxidative stress, and can also spontaneously lose their proper conformation; autophagy compensates for this by clearing out the damaged cellular constituents, which can then be replaced.  Autophagy is of particular importance to the proper functions of organs such as the brain and heart whose cells are long-lived and difficult to replace.

    When properly regulated, autophagy aids the proper function and survival of neurons, by disposing of toxic protein aggregates and insuring that mitochondria are structurally and functionally sound.  Indeed, a steady low level of neuronal autophagy is crucial to brain health; mice in whom the process of autophagy is genetically defective develop fatal neurodegenerative disorders.  Moreover, activation of brain autophagy by certain drugs (e.g. rapamycin) has been found to be protective in rodent models of Alzheimer’s and Parkinson’s disease; pharmaceutical companies are scrambling to develop other, safer drugs that could be used to treat neurodegenerative disorders by stimulating brain autophagy.  However, whereas the reduction in growth factor activities associated with calorie restriction tends to boost protective autophagy in most tissues, the few studies that have examined brain autophagy in short-term fasted mice (none so far have looked at this in calorie-restricted mice) have yielded conflicting conclusions.  The increase of brain growth factor activity seen during fasting or calorie restriction would be expected to inhibit autophagy; on the other hand, certain enzymes which can be activated in the brain by fasting or calorie restriction, such as sirt1 or AMPK, have the potential to boost autophagy.  Clearly, further studies are required to clarify whether calorie restriction has the potential to protect the brain via autophagy induction.  But even if such studies ultimately have a negative outcome, it is clear that the net impact of calorie restriction on the brain is neuroprotective.

    As noted, the somewhat greater neuroprotection seen with intermittent fasting than with daily calorie restriction may be attributable in part to increased production of ketone bodies.  Ketogenic diets, in which the liver converts large amounts of fat to ketone bodies that can be utilized by the brain as fuel when glucose availability is reduced, have long been known to be an effective treatment for epilepsy.  Such diets have also shown neuroprotective properties in rodent studies.  This may stem, in part, from the value of ketones as alternative fuel for brain neurons when energy production from glucose is suboptimal; however, it is clear that additional factors are involved.  In particular, there are theoretical grounds for suspecting that neuronal metabolism of ketone bodies might promote activation of AMPK, an enzyme which has the potential to activate neuronal autophagy, and exert other neuroprotective effects.  As we discuss elsewhere on this website, the liver’s production of ketone bodies can be increased not only by fasting, but by ingestion of a type of oil known as medium-chain triglycerides; it would be interesting to know whether these can boost autophagy in the brain.

    Evidently, CC dieting, to the extent that it can mimic the metabolic effects of intermittent fasting, and can achieve a genuine moderate reduction in daily calorie intake, has real potential for slowing the inroads of the aging process on optimal cognitive function, and for providing some measure of protection from age-related neurodegenerative disorders such as Alzheimer’s and Parkinson’s which can have such a devastating impact not only on their victims, but their loved ones as well.

← Back to Frequently Asked Questions