Aubrey de Grey (here, here and here) is an iconoclastic anti-aging researcher living in Cambridge, UK who approaches the science of anti-aging medicine from an engineering perspective (requires free registration). He lectures extensively and constantly pushes the boundaries of anti-aging research. He isn’t trained in biology or medicine, but as an engineer. His extensive knowledge of medicine and the biological sciences is pretty much self taught. He doesn’t subscribe to any particular medical or scientific ideology, i.e., alternative medicine verses mainstream medicine, or any specific dietary practices other than the idea that caloric restriction has been shown in animal studies to prolong life. But Dr. de Grey isn’t interested in the mere 20-30 percent increase in lifespan brought about by caloric restriction; he’s more interested in increasing lifespan 100 to 200 years or more. Which he believes can be done if we look at forestalling aging from an engineering point of view.
He has written (co-written, actually) a book titled, appropriately enough, Ending Aging, describing his theories of aging and discussing the problems that must be overcome to undo the forces of our own biochemistry and physiology that grind us down over time. I read the book when it first came out and found it fascinating. I wouldn’t think it’s a particularly an easy read for one not scientifically inclined. If you thought Gary Taubes’ book was difficult, I wouldn’t recommend this one. If you do get it and are prepared to spend some time really digging in, you will come away rewarded, if not in understanding (which you will certainly get), at least in the knowledge that there are many extremely clever people working to keep us living longer. If you just want to read a little of the book, I recommend Chapter 5, Meltdown of the Cellular Power Plants, which is a virtuoso piece of scientific reasoning. Dr. de Grey published his theory of mitochondrial survival of the slowest, the subject of this chapter, a few years back, and I thought it a brilliant piece of scientific detective work.
As I was reading this book last year I got to the chapter about advanced glycation end-products (AGEs) I came across something troubling. Dr. de Gray was describing the AGEing process, which, as most readers of this blog probably know, is the process whereby sugar irreversibly binds to proteins, causing the proteins to lose their functionality. The proteins so bound up by sugar also cross link with other such proteins, making them even less functional. One of the prime examples of this phenomenon that we have all witnessed is the formation of cataracts in the eyes of some elderly people. AGE cross-links accumulate on the clear crystalline proteins in the lenses of the eyes, making them opaque. These opaque lenses, cataracts, impair vision and require surgical removal for vision to be restored.
Another place this AGEing reaction is seen is in hemoglobin, the oxygen carrying molecule in blood. Glucose, fructose and other sugars bind to the hemoglobin protein giving us the hemoglobin A1c that is a measure of long-term elevated blood glucose in those with diabetics. But there is measurable Hgb A1c in all of us, which is an indicator that this process operates even at normal blood glucose levels. Granted, it’s significantly higher in diabetics, but it’s performing its evil handiwork on those of us without the disease.
The same goes for fats in the blood. One of the reasons that meats brown is the conversion of the fat to AGEs. So elevated triglycerides along with elevated blood sugar are a set up for the formation of AGEs, which is probably one of the reasons that those with diabetes tend to have accelerated aging and an increased incidence of the diseases of aging (high blood pressure, cardiovascular disease, etc.) as compared to those without diabetes. So, you would think that a low-carb diet, which reliably reduces blood sugar and triglycerides significantly, would be a good thing. Right?
Not according to Dr. de Grey who writes

…not all AGEs are even derived from glucose. Blood fats (triglycerides) can also cause the cross-linking of proteins, particularly if there’s a high level of oxidative stress: this is the chemistry that underlies the browning of a turkey skin as it roasts, even without a sweet, syrupy slather on its surface. As with blood sugar, diabetics usually have high triglyceride levels, and even many nondiabetic people would benefit from having their triglyceride levels brought down; but triglycerides also resemble blood sugar in being indispensable to normal function, so there’s only so far that such a strategy can be safely pursued.
And that’s not all: attempts to control levels of both these early precursors of AGEs, even by nonpharmacological means, can have perverse metabolic consequences.
For instance, one established effect of very low-carbohydrate diets of the Atkins type is to bring down both triglyceride levels and the body’s total exposure to carbohydrates, so some advocates have hypothesized that these diets would reduce a person’s AGE burden. Unfortunately, it turns out that the metabolic state that these diets induce (the notorious “ketosis”) has the unfortunate side effect of causing a jump in the production of the oxoaldehyde methylglycoxal, a major precursor of AGE’s that is also, ironically, produced within the cells of diabetic patients when they are forced to take in more glucose than they can immediately process. A recent study tested the size of this effect in healthy people who successfully followed the first two phases of the Atkins diet for a month, and who had the ketones in their urine to prove that they were sticking to the diet. These previously healthy people suffered a doubling of their methylglycoxal levels, leading to concentrations even worse than those seen in poorly controlled diabetics. Like other oxoaldehydes, methylglycoxal is far more chemically reactive than blood sugar (up to 40,000 times more reactive, in fact), and is known to cause wide-ranging damage in th body, of which AGE cross-links are but one example. This potentially makes the Atkins diet a recipe for accelerated AGEing, not a reprieve from it.

The study Dr. de Grey refers to was published a few years ago in a paper in the Annals of the New York Academy of Science. Aside from the fact that this is the only such paper in the literature showing this phenomenon, you must realize that the papers published in this journal are the print versions of talks given at NY Academy of Science meetings. These meetings are organized around specific topics and dozens of researchers present their work. These presentations are then written up and published in the Annals. As such, they really don’t go through the peer-review process that other such studies must before they appear in print in standard scientific journals. In fact, most papers that appear in the Annals of the NY Academy have been published elsewhere first because the published papers are what led the organizers of the particular meeting to seek out these researchers and ask them to speak. The fact that this paper has never been published elsewhere either before or after the publication in this journal makes me suspect that the work couldn’t pass the peer-review process. If you think about how slight the evidence needs to be in the mainstream medical press to publish negative data about low-carb diets, especially the Atkins version, it makes you wonder why this wasn’t published elsewhere if the data were even semi-worthwhile.
Virtually all of the other papers I’ve seen point to elevated glucose as the driving force behind the elevated levels of methylglyoxal in patients with diabetes. And the glucose levels are in such greater quantity wreaking their havoc than even a doubling (the increase implied by the Ann NY Acad article) of methygloxal would cause. It’s kind of the same situation we find with melanoma and colon, breast and prostate cancers. It has been shown that vitamin D is protective against colon, breast and prostate cancers so going out in the sun and getting vitamin D helps you avoid a host of common cancers. But, supposedly (I don’t believe it, but let’s accept it for this argument’s sake) sunlight causes melanoma. What no one ever tells you is that there is one melanoma for every 200 of these other cancers, so by avoiding the sun you increase your risk for common cancers to prevent an extremely uncommon one. Same goes for the glucose/methylglyoxal situation. If you worry about methylglyoxal, but let your glucose and triglycerides go up as a consequence, you’ll suffer much more damage than if you keep glucose and triglycerides down and let methylgloxal double simply because there is so vastly much more glucose and triglyceride. And that’s even if the methlygloxal levels double, which I seriously doubt. (If you want to read a little more on my thoughts on this subject, go to this post and scroll down to the comments (there are several) by Tim Lundeen and my responses.)
But, as it turns out, we probably don’t need to worry about the situation.
As part of his continuing quest to move the science of anti-aging medicine forward, Dr. de Grey took over as editor of the major journal of anti-aging medicine and renamed it Rejuvenation Research. Most of the articles this journal publishes are fairly technical and esoteric, of interest to only those in the biz of hardcore anti-aging research. But as I was going through a few back issues catching up on my journal reading, my eyes lit on an article titled Effect of Short-Term Ketogenic Diet on Redox Status of Human Blood. Hmmm, thought I, I’ll bet this is another article in the same vein as the one from the Ann NY Acad. In fact, I couldn’t remember the names of the authors of said article and thought it might be the original article finding the light of day in a strict peer-reviewed journal. When I downloaded the full text, however, I was delightfully surprised.
The authors of this paper had also seen the article in the Ann NY Acad and wanted to take a look for themselves. They wanted to see just what a low-carbohydrate, ketogenic diet would do to the oxidative stress levels and the anti-oxidant capacity of healthy subjects. Recall that in the lengthy quote above from de Grey’s book he states that

…blood fats (triglycerides) can also cause the cross-linking of proteins, particularly if there’s a high level of oxidative stress…

These researchers wanted to see if there really was an increase in oxidative stress as the other paper (and de Grey’s book) intimated.
They put 20 healthy normal weight females on a low-carbohydrate (55 g carb per day), high-fat (138 g per day) diets for two weeks.

The diet was based on animal products enriched in fat including pork, beef, butter, lard, cheese, eggs, and up to 100 g/d of vegetables and fruits.

After only two weeks on this diet significant changes came about in numerous parameters.

3HB TAS, UA, and SH content were significantly increased. MDA content was not altered. Activities of CAT and SOD remained unchanged.

What does all this mean? 3HB is 3-β-hydroxy-butyrate, a ketone body, which would be expected to be elevated since the subjects were following a ketogenic diet. It’s important to know that 3HB levels are elevated, however, because it lets us know that the subjects were following the diet. TAS is total antioxidant status, which is a measure of the ability of fresh plasma to inhibit oxidation. If TAS is up, then the body has more antioxidant capacity. UA is uric acid, which scavenges oxidative free radicals and protects against oxidative stress. SH is sulfhydryl group content, which is a measure of glutathione, a major home-grown antioxidant. Increased SH means the body is increasing its level of its own self-made antioxidants in the mitochondria where all the bad free radical activity takes place.
But what if all this increased antioxidant activity is because the diet is so inflammatory (as the section in de Grey’s book would have us believe is the case with low-carb diets)? That’s where the CAT and SOD measurements come into the picture. CAT and SOD are catalase and super oxide dismutase, both enzymes involved in the body’s defense against increased oxidation. If CAT and SOD are not elevated, that indicates that the body isn’t threatened with increased oxidative stress. MDA is the malondialdehyde levels, which were unchanged. MDA is another marker for oxidative stress. The fact that it’s unchanged also is just another indicator that the diet didn’t increase oxidative stress.
The dietary changes brought about an increase in antioxidant capacity without an increase in oxidative stress. In other words, the body isn’t simply producing more antioxidants because the diet is inflammatory. As the authors put it

Elevated antioxidative capacity was not an adaptive response to increased oxidative stress because no evidence was obtained indicating increased oxidative stress. Increased antioxidative capacity was also not due to inactivation of antioxidant enzymes because SOD and CAT activities were not decreased.

And all this in only 14 days in healthy, young subjects, who, one assumes, were in pretty good shape to begin with. Just imagine the improvement we might see in overweight middle-aged diabetics (or even non-diabetics) who have inflammation out the yang. Were I in that condition, I would gladly trade the results seen in these subjects for a doubling of methylgloxal, assuming such a change would actually occur.
Oh, and speaking of ketones and antioxidant capacity, when I was going through the medical literature looking for other papers on the subject, I came across a paper waiting to be published in the Journal of Neurochemistry showing that a ketogenic diet increases the levels of glutathione inside the mitochondria. For decades scientists have known that mitochondria throw off free radicals as they do their work of converting food energy to ATP, the energy currency of the body. And scientists have known that these free radicals damage the mitochondria. Long ago the assumption was made that taking antioxidants in the form of supplements should squelch the free radicals generated within the mitochondria and result in a prolongation of life. Problem is that it doesn’t work, apparently because antioxidants taken orally don’t penetrate into the mitochondria where the free radicals are. A zillion studies have shown that taking antioxidants doesn’t increase lifespan.
The only thing that reliably does increase lifespan is caloric restriction (CR) in lab animals, at least. CR is thought to work in great measure by decreasing the number of free radicals fired off in the mitochondria as a consequence of the mitochondria having less food that they have to process. The mitochondria make their own antioxidants – one of which is glutathione – to help protect themselves from the free radicals they generate. Anything that increases the glutathione within the mitochondria is going to help increase longevity and decrease many of the ravages of disease, many of which stem from excess mitochondrial free radical production. This study indicates that a ketogenic diet significantly increases the production of glutathione within the mitochondria, which is right where you want it, especially to protect the mitochondrial DNA.
Granted, this study was a rat study, and I’m not a big fan of extrapolating rat studies to human studies. But, rat mitochondria aren’t that different from ours so it’s a little easier to make the leap of faith. So, I would recommend for a long and healthy life that you ketonate as much as possible. Let those ketones do the job of blood sugar, keeping your blood sugar low. Lower sugar, lower AGEs, Lower AGEs, longer life.


  1. “One of the reasons that meats brown is the conversion of the fat to AGEs.”
    Here’s a study I found showing that there are vastly more AGEs in cooked fats and meats than there are in carbohydrates. The implication I would make is that it’s best to avoid eating meat and fat cooked at high temperatures – or for long durations. Most of the studies on AGEs use cooked food. It seems obvious that raw foods wouldn’t contain much if any AGEs. There have been many beneficial substances identified in unheated honey, some of which are destroyed even at modest heat (like 104F). Many doctors used unheatd honey to cure diseases, such as diabetes, in the past. Nowadays, most use toxic drugs and supplements rather than giving the body a natural food that has not been processed to death..
    Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc. 2004 Aug;104(8):1287-91.
    “RESULTS: Foods of the fat group showed the highest amount of AGE content with a mean of 100+/-19 kU/g. High values were also observed for the meat and meat-substitute group, 43+/-7 kU/g. The carbohydrate group contained the lowest values of AGEs, 3.4+/-1.8 kU/g. The amount of AGEs present in all food categories was related to cooking temperature, length of cooking time, and presence of moisture. Broiling (225 degrees C) and frying (177 degrees C) resulted in the highest levels of AGEs, followed by roasting (177 degrees C) and boiling (100 degrees C).”
    I agree that there are vastly more AGEs in cooked foods, especially meats. What I’m not so sure about is whether or not the AGEs we eat end up as AGEs in us. The transit through the extreme acidity of the stomach would, I imagine, reduce the AGEs to their components, which we would absorb. The healthy human GI tract doesn’t have the ability to absorb large molecules. Even diglycerides (sugars composed of two other sugars, sucrose, for example) must be broken down to monoglycerides before being absorbed, so I seriously doubt that complex molecules such as AGEs could be absorbed in there native state. As a consequence, I’m not particularly worried about the AGEs I eat – I much more worried about the AGEs I create within.

  2. Dr. Mike,
    Thanks for another great post.
    “UA is uric acid, which scavenges oxidative free radicals and protects against oxidative stress.”
    Wow, I did not know Uric Acid was an antioxidant. I have kept my gout at bay by staying in ketosis as much as possible, except Sundays when I pig out on carbs. When I do get one of those twinges that indicate an oncoming gout attack I increase my purines instead of following the conventional medical literature that suggest you reduce high purine foods. Literature from most major health sites recommends avoiding fats and meats and other high purine foods. I do just the opposite and increase my protein and fat sky high and avoid all plant foods and include several whey protein powder drinks. By increasing my protein I know it increased my Uric Acid output but my kidneys will kick into double duty and excrete it faster than I produce it, thus I lower my overall Uric Acid level and avoid the attack. I thought Uric Acid was just a by product of cellular activity now I feel better knowing it’s doing more than causing a pain in the foot.
    Yep, it’s a good antioxidant. I find that it almost always increases in my patients after they start following low-carb diets.

  3. Hi Mike,
    Thanks again for another wonderful blog post. A few questions if I may…
    1. You said “But, supposedly (I don’t believe it, but let’s accept it for this argument’s sake) sunlight causes melanoma”. Coming from Australia, we are brainwashed on mass to always wear sunscreen to avoid skin cancer. Would you be so kind as to someday do a blog post on this please? I would love to know what the real research says, rather than the anti-cancer council’s propaganda. Thanks.
    2. I’ve been experimenting with your low-carb diet for a while now, and enjoying the results. I do a lot of exercise and high-intensity weight training. Tim Ferris, who I know is a friend of yours, recommends having a “off-day” once a week where you can pig out on anything you want (Tim calls it a “Dieters Gone Wild” day, he states “to excess”). Here’s what he says:
    “I recommend Saturdays as your “Dieters Gone Wild” day. I am allowed to eat whatever I want on Saturdays, and I go out of my way to eat ice cream, Snickers, Take 5, and all of my other vices in excess. I make myself a little sick and don’t want to look at any of it for the rest of the week. Paradoxically, dramatically spiking caloric intake in this way once per week increases fat loss by ensuring that your metabolic rate (thyroid function, etc.) doesn’t downregulate from extended caloric restriction. That’s right: eating pure crap can help you lose fat. Welcome to Utopia.”
    I’ve also read elsewhere that a low carb diet should have one or two off-days a week with a lot of carbs if you’re a body-builder, needing to replenish glycogen.
    Is this advice accurate in your opinion? And, is a day with a lot of carbs as Tim Ferris states (with chocolates, ice-cream etc to excess) useful for overall weight-loss… or slows it down… worse… or otherwise?
    Thanks so much. I check your blog first thing everyday since your content is so exceptional.
    P.S. I’ve recently read some of Dr. Perricone’s books on skin-care. Very interesting that he largely agrees on everything you say, but in the context of skin. He promotes a low-carb, high-fish protein diet for great skin. The more I read his stuff the more it fits with what you say — if he is right then a low-carb diet may be the best for great looking skin too!
    I will do a post on the melanoma and sunlight issue in the near future.
    Tim Ferriss is a young (years old), healthy, muscular fit male who works out regularly. What works for him won’t necessarily work for a 55 year old out of shape abdominally obese male with hyperinsulinemia. I wouldn’t prescribe that treatment to any of my patients.

  4. One issue that arises with all such research is that it looks only at averages and does not take into account the diversity of genetic flaws which cause abnormal glucose metabolism.
    For example, few of us people with diabetes have the same genetic flaw that causes high blood sugar in the Wistar Rat. We have any one of dozens of different unrelated flaws. And each of these flawed genes also affects hundreds of other metabolic processes–most of which are completely unknown to science.
    So all conclusions about the effect of diet–positive and negative–apply only to groups of diverse individuals with very different underlying metabolisms.
    That is why each individual has to test any proposed diet on themselves and see how it works for them. This is just as true for very low carb diets as any other diet.
    This lack of understanding of the diversity of causes leading to blood sugar dysregulation and hence the need for individualized treatments is the single biggest blind spot I see in the academic community studying the subject.
    I agree. Biological variability makes us all who we are. Some respond someways, others in other ways. But the only way we have to study is by evaluating populations. Otherwise it’s all anecdotal.

  5. Who wants to live forever?
    I mean, yes, If I stay youngish for another 30-40 years, into my mid 70’s, I will be young and free from debt, with a high income (or a nice retirement) and the ability to do whatever. But, how do I pay for this whatever? And how does the next generation (which so many people seem to care about, me not included) find jobs if I’m staying young and working for 140+ years. I feel a Malthusian thought coming on.
    Say 50% of the current population lives to the ripe old age of 250. They will consume roughly 3 times the current number of resources. They will have kids, and each generation will have 50% living for 250 years, or 300% of some arbitrary average lifespan I picked out. Within a few normal breeding generations, you’ve increased population large. Very large. Now, tech may save you (as it mostly has for the last 200 years), but where will the jobs come from? The food (I guess they’re eating less, even though CRON longevity hasn’t been shown in people)? The fuel? One must wonder.
    And, if you’re SciFi inclined, what does living 3* the normal lifespan do to the value you put on life? Is life more precious because you have more of it, or less precious, because you have too much of it. Is there reason to Carpe Diem in a world where you’re going to see a third century?
    All sci fi stuff. Personally, I think I’ll take my 80-105 (probably 115 by the time I get there) and cash checks and explore what’s next. Course, when I get there, I may get a DNR order like my grandma’s: “Resuscitate only once, then we’ll see how we feel.”
    Thanks for the post, Dr. Mike.
    If you read much of de Grey’s work, you’ll find that he discusses all these issues about the stress on resources if everyone lived to be 250.
    As for me, I wouldn’t mind being 250 as long as I still had my golf swing.

  6. Nice post Mike. What would you suggest a person’s doctor test for specifically upon a routine physical exam to determine that your AGEs are sufficiently low? Obviously triglyceride levels want to be low but, what other blood markers should be measured?
    One readily available measure is hgbA1c. Most of the other measures of AGEs are used primarily in research settings.

  7. Michael,
    My new best friend Joseph Kanner has done some work to suggest that red wine consumed with cooked meat might mitigate some of the oxidative damage. His earlier works suggest that high antioxidant (and low carb) veggies and fruit might have a similar effect in “real time” in the bioreactor that is the stomach.,j
    On another note, with all the work done on CR, I don’t see much mention of the idea that maybe it’s not the calorie restriction that’s so important but specifically the insulin restriction. We know from numerous animal studies that those animals (of any species) that secrete less insulin over a lifetime live longer than higher secreters. I would think that the appeal of a low carb, higher fat, moderate protein diet and its relative ease and lack of perceived sacrifice would be a much easier sell than the late Roy Walford’s spartan (dare I say miserable) basic CR programs. I did a post on this last week in which I discussed what I call the “context of calories”
    Hey Mark–
    You’re on the money on the caloric-restriction issue. When calories are restricted in lab animals, the macronutrient that is restricted the most is carbohydrate. Protein stays pretty much the same and there is a little reduction in fat, but the carbs really bear the brunt of the cutting. So calorically restricted diets are really low-carb, low-calorie diets. And the free-living low-carb studies show that when people go on self-selected low-carb diets, they markedly restrict calories, yet aren’t hungry. All interesting stuff.

  8. I have read that the ATP level inside Mitochondria may be raised by means of bio-electric stimulation therapy that applies low-level current pulses. I’m currently testing that effect, and for me it does appear to confer more energy and muscle stamina. Is “topping up” the mitochondria ATP in this way likely to be good news or bad news as regards aging? Im almost 79 so I need to find out soon.
    Thank you,
    I think the amount of ATP made by a mitochondrion is whatever it is. It’s a function of the amount of high-energy electrons from the breakdown of food entering the mitochondrial factory that more or less determines what comes out the other end. It really isn’t that simple because there are other factors as well. But if you want to increase the ability to produce ATP, the best thing you can do is increase the number of mitochondria in the cells. Which can be done with exercise and, interestingly enough, with a higher fat diet.

  9. Since people with arthritis have elevated CRP do they have a higher risk of heart attack?
    People with rheumatoid arthritis and other such autoimmune diseases in which inflammation is high do indeed have much greater risk for heart disease.

  10. Off-topic (with apologies) but I’d like to hear your response to this article I was just reading…
    “Glucose Levels Trigger Compensation For Type 2 Diabetics” at
    One paragraph caught my eye:
    “In a study appearing in the January issue of the Journal of Clinical Investigation, Takashi Kadowaki and colleagues from the University of Tokyo, Japan, show that in mice with high-fat diet–induced insulin resistance, changes in glucose concentration are likely to be the main trigger of increased beta-cell mass.”
    They mentioned this “high-fat diet-induced insulin resistance” a couple of times. Is this more media presumption of those evil fats, or does such a mechanism really exist?
    High-fat diets do induce insulin resistance in mice because mice don’t normally eat a high-fat diet. But, mice aren’t humans, and the same diet doesn’t make humans insulin resistant.

  11. ..i saw an interview with the fella.
    Firstly his Doctorate was gotten by some old Cambridge as i recall rule whereby the holder of a degree from said gaff can do his Doctorate fantastically more easily than if they were at another school.
    Also and the main point he was talking of how much ale he drinks and what he eats….lots of mars bars and sweets.He also has the gaiut of a low insulin secreter.
    Also anecdotally the pitch and tone of his voice……..i’d say he ‘spends’ a disproportionate amount of time ‘in his head’ versus connecting to what might be called ‘physical reality’.
    I hope you can the book back ?!
    His theories don’t involve dietary changes – they are more along the line of high-tech pharmaceutical intervention. If he eats as you say, I guess he’s counting on his own research to save his bacon in the years to come.

  12. Hi Dr. Mike.
    Thanks for an extremely interesting post. I was wondering if you have tried to contact Dr. de Grey to see if his opinion has changed regarding ketogenic diets and the AGEing process. I recall reading the transcript of an interview with him and thinking just how unusual it is to find a reasearcher in the medical field to be so open minded and able to change assumptions based on new information. I attribute his flexible thinking to his engineering background. Incidentally, I consider you to fall into this same catagory. But then, my being an engineer tends to bias me. 🙂
    Take care,
    Since he is the editor of Rejuvenation Research I would assume that he reviewed the article prior to its publication. And I would assume that he must have agreed with the data otherwise it probably wouldn’t have seen the light of day.

  13. Dr Eades you’re right about exogenously produced versus endogenously produced AGE’s. I did a lot of research into this about 2 years ago when switching to the low carb protocol. It turns out that we absorb about 10% of the AGE’s we ingest which in certain populations can exacerbate insulin resistance, inflammation, etc. Ive been consuming a low AGE diet in conjunction with your plan for about the same time period for Type 1 Diabetes. I steam and Crockpot most of my protein which dramatically reduces AGE formation and supplement with AGE blockers like carnosine, benfotiamine, turmeric, quercetin, lipoic acid and a few other supplements in rotation for good measure. Probably overkill since my last 3 Hemoglobin A1cs have been 4.3% but I dig the science.
    Hi Neal–
    Thanks for the feedback. Glad you’re doing so well.

  14. Dr. Mike and Dan Harrington: Thank you. I developed gout three years ago and July 4th I developed the worst attack I have ever experienced. No novice with pain (I have had 8 abdominal repairs for bowel obstruction/incarcerated hernia, broken bones, wipeouts with bikes, skis, trampoline, boats), this was the worst pain I have ever experienced. I had to resort to using a wheeled walker just to go from bed to bathroom and back (10 minute trip the pain was so excruciating). Today, 10 days later, I still am sore in toes, sole of foot, side of foot, and ankle but can walk without assistance. I get to the bathroom now in 30 seconds. This was definitely brought on by eating pizza and pasta (one time only will not hurt, right?) because I just did not want to cook or turn down what others were eating. Live and learn.
    Can you please post your thoughts on gout. Googling for information gets me to a state of confusion. Sites for and against: High-purine protein versus low-purine; high intake of B-complex versus claims it promotes attacks; promoters of vitamin C increase and those that claim it makes it worse; sites that claim wheat causes attacks and sites that claim whole grain is what one has to do; the do-not-take vitamin D and the ones who promote it (I am currently on 12,000 IU Carlson’s softgel daily and using Dr. Dowd’s D calculator for exposure as my 25(OH) test was 7 with normal range 35 to 100 and doing the Carlson’s fish oil); sites that swear by increase in fruit (especially) and others that state fructose causes and aggravates gout attacks. Yikes! Oh yeah and the sites about apple cider vinegar and baking soda abound. Not all that effective, if at all.
    The comments about higher uric acid levels helping to pump out the extra is something I have not heard before. What is best for me to do? So glad not to be doing a body-builder grunt or shout even time I step on my leg again. I do know these episodes pass in about 10 days, but they are getting worse and more of my anatomy is affected. They are debilitating. Sure I know the smart answer is don’t eat that again, but I have eaten that before and had no attack. What is the best way to approach this condition? I see posts on your membership site and the site with lots of members who suffered from this problem. No more pizza or pasta for me.
    I am really sorry I am so late in getting to your comment. You got caught up in my spam filter (and I don’t know why because you don’t have a hypertext link in your post, which is what usually catches people in the filter), and I just found your comment.
    First off, you really should work to get your vitamin D levels up to at least the normal range. The best way to do that is to take vitamin D3 supplements (5000 IU) until your levels come up. Also, it’s been my experience that a low-carb diet is a wonderful treatment for gout, at least in terms of a preventative. You probably wouldn’t want to go on one until the acute attack as resolved, but once it has, a low-carb diet should prevent future attacks. I’ve taken care of numerous patients who have had gout attacks, and all of them have been gout free on the low-carb diet. A high-carb splurge, however, can bring an attack on, as you have discovered.

  15. Ahh.. I found the article that links insulin resistance to high fat diets, as I mentioned earlier.
    1. Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats. Journal of Clinical Investigation, July 10, 2008
    At least that’s the way this article interprets the research outcome…
    Help. “I’m conflicted.”

  16. Dr. Mike,
    I know how much you love questions, especially off topic ones, but I have one for you. Sorry if it’s ignorant.
    You often refer to looking back into “the medical literature” when you want to make sure something is valid and whatnot. Where are the studies being published?
    It’s not an ignorant question at all. Going back through the literature typically involves first searching PubMed, a government maintained site providing references and abstracts to virtually all the medical and scientific literature published. Go to this link and enter a search term, hyperinsulinemia, for example, or low-carb diet, and hit the search button. You will be provided with hundreds, sometimes even thousands, of papers. Once you find a paper that you think is what you’re looking for based on the abstracts presented, you have to go to a medical library or an online source to find the entire paper. PubMed is a great resource and is absolutely free.

  17. Fabulous post and referencing to several great papers. I agree about self created AGE’s being more serious than the potential ingested AGEs. This assumes perfect dissolution and time spent in the stomach. I’ve seen my quota of carrots, occasionally, in stools.
    Is it possible to compare the structure of AGE molecules with other similar shaped molecules that may pass through the GI wall, eg, is coQ10 etc similar in shape and size. Does mad cow’s disease factors move through the GI wall, for example.
    It does not matter much. I will do a diet experiment on myself starting with the thoughts behind these papers!
    many thanks
    AGEs are typically large protein structures. Stomach acid denatures protein, which means that it changes its configuration and sometimes breaks it down. Plus the acid in the stomach activates an enzyme called pepsin that further degrades proteins into smaller peptide units. Once in the small intestine, other enzymes continue the process. Proteins can’t really make it through the GI tract intact, therefore AGEs, since they are primarily protein, can’t either. Other molecules can make it through relatively unscathed, just not proteins.

  18. I have seen some interviews with Dr. de Grey, as well as conversed with him via email. He certainly is very sagacious. And, Dr. Eades is right, is approach to “ending aging” is not dietary in nature, but in treating the body as a machine, so to speak. He suggests that just as a machine can be repaired by replacing worn-out parts, so, too, can the body.
    By the way, it’s true. He consumes plenty of ale and junkfood. In fact, if i remember correctly, he is able to drink pints of alcohol in the morning on an empty stomach without any ill effects, that is, no intoxication.

  19. You’ve previously discussed ‘futile cycling’ and other processes by which excess dietary calories are spent when carbs (and, therefor, insulin) are kept low, keeping people who overeat but stay low-carb from gaining weight as would be expected. How would these processes affect AGEs and/or other oxidative stress factors? I’m guessing the act of ‘burning off’ those extra calories would still be unhealthy, even if you were spared the weight gain.
    Also, I think I read in one of Jonny Bowden’s books a recommendation for eating blueberries (or other high-ORAC fruits or veggies) after a meal to help reduce free-radical activity from eating, as well. Sounds like a good justification of having fresh fruit for ‘dessert’ after each meal! (He mentions one of his favorites is to toss some frozen blueberries or cherries in some sugar-free, live active culture yogurt and stir it up until the yogurt semi-freezes. I’ll have to give that a try!) Any thoughts?
    Actually the futile cycling and especially the proton leak and uncoupling proteins in the mitochondria reduce the free radical load. I’ll explain how when I do the post on this subject, which is planned for the sort of near future.
    Foods that have a high ORAC content (we wrote about this in the PPLP) do tend to reduce free radical activity. Much more so, in fact, than supplements containing the same levels of known anti-oxidants. There’s just something about getting it from food that makes it better.

  20. Raymond Francis mentions the AGE topic halfway through his radio show and then again in more detail at the end of his July 13th radio program: Apparently 30% of the AGEs from cooked food are absorbed and of that 30% nearly 10% are accumulated in our tissues. Ive seen this 10% in a few research papers as well. The Dietary Glycotoxin and Potential Renal Acid Load issues are the only possible drawbacks I see to the the higher protein intake. The myriad benefits of high protein intake more than trump these two concerns when one considers the other choices.

  21. Dr. Eades
    Do you know what Dr. de Grey’s views on exercise are as far as slowing or at least not speeding up aging?
    No, I don’t. But the consensus seems to be that moderate exercise improves longevity whereas long-term, indurance exercise – marathon running, for example – reduces longevity by increasing the inflammatory load.

  22. Hi doc, sorry for the off-topic post, but a thought occurred to me the other day when I saw an overweight person with one of those enormous sugar-free soft drinks: do artificial sweeteners affect insulin at all? I would assume the answer is “No”, but has anybody ever done a study to find out?
    There are a handful of studies showing a minimal insulin response to artificial sweeteners and others that show no change. I would bet that artificial sweeteners provoke a slight first phase insulin response, but I have no data showing that.

  23. Many people are deficient in stomach acid and large molecules can be absorbed even if they aren’t. Ray Peat has pointed out that starches in grains and beans can be absorbed intact to the blood. He suggests eliminating grains and beans, but thinks potatoes and root vegetables are safe in modest amounts. I think your body will produce less AGEs if you eat a diet high in saturated fat and mono-unsaturated, but very low in poly-unsaturated. Not cooking meats at high temperature or “browning” them also seems like a good idea. I would like to see the “in vivo” effects long-term of various foods prepared in different ways.

  24. “High-fat diets do induce insulin resistance in mice because mice don’t normally eat a high-fat diet. But, mice aren’t humans, and the same diet doesn’t make humans insulin resistant.”
    Also, when they say “high-fat diet”, it’s usually high in carbs too, typically refined ones. So it’s about like the Standard American Diet (SAD) – 35% fat, 50% carbs, 15% protein. This is dishonest because the diet is high-fat AND high-carb, not JUST high-fat. This is something people should remember, when seeing claims about “high-fat” diet. What were the actual percentages of fat and carbohydrate? Also, what type of fat and carbohydrates were used? Just because corn oil causes some effect doesn’t mean that coconut oil or butter or beef fat does the same. Colin Campbell fed mice refined sugar, corn starch, corn oil, and casein in hit studies claiming that “animal protein” causes cancer. The question can and should be asked whether saturated fats and whole foods would have done the same thing. Any study feeding animals protein powder (like casein) is suspect, IMO, unless it’s duplicated with whole foods, pref minimally processed foods like raw milk, raw cheese, etc.

  25. Dr De Grey i will arrogantly wager is kinda daft as a brush.
    I mean a hypothesis can be anything and can be given some/any creedance as 1. it hooks into human hard wired wants (living longer in our ancestral past which was dodgy it seems at best and now transposed into our contemp life and its style) and 2. throw a bunch of science and rhetoric and it seems plausible.
    We might be an evolved primate who can go to le moon but we are made of the same stuff as other animals and for me, and i might be wrong and woefully so here , it’s another example of someone who thinks (and ironically in doing so forgets the biology that allows that (absurd) thinking) anything is possible..which it isn’t and only an idiot thinks like that.
    The difference between reality and what pings around within our brains….wallop !

  26. Hey
    You said above in a reply to a different comment “…so I seriously doubt that complex molecules such as AGEs could be absorbed in there native state. As a consequence, I’m not particularly worried about the AGEs I eat – I much more worried about the AGEs I create within…”
    However on the internet there are lots of articles saying how in studies, people had higher levels of C-reactive proteins and higher inflammation after consuming more AGES. What do you make of this?
    There are all kinds of studies on the internet saying all kinds of things. But that doesn’t mean they are valid. I would have to look at a specific study to comment intelligently. I made my comment based on a pretty sound knowledge of how the GI tract works, and given how it works, it would be difficult for these large proteins to pass through unchanged. The fact that the GI tract breaks down protein is the reason diabetics can’t take insulin orally. Insulin is a protein, and it would never make it through the GI tract intact.

  27. “I?m not particularly worried about the AGEs I eat – I much more worried about the AGEs I create within.”
    I’m sorry, but this seems like an ad-hoc hypothesis. If Neal’s figures are correct that a person absorbs 10% of the AGEs in their diet, they would still absorb more from cooked proteins and cooked fats. Raw foods would have little or no AGEs, by comparison. Also, AGE is a misnomer, since proteins and fats are 13 – 29 times more vulnerable to this damage than carbohydrates. Many low-carb proponents make a big deal about AGEs in (cooked) carbohydrates, then they ignore the vastly higher levels of AGEs in cooked fats and proteins. It’s good that you pointed out the truth here, but it seems like you’re moving the goal-posts.
    Also, I have seen much higher figures than the 10% absorption rate listed by Neal. The figures I’ve seen are 70-90% absorption, with diabetics and unhealthy people absorbing more of them than normal people. So, if I were in Neal’s shoes, I would eliminate the AGEs in my diet, using raw or rare meat, boiled food not baked or fried, low PUFA intake, and other strategies that would cut my levels of oxidative stress and glycation/lipoxidation.
    It may be an ad hoc hypothesis, but it’s one based on a sound knowledge of GI physiology. And until I see a well-controlled study that refutes it, I’m sticking with my hypothesis.

    1. The following paper published in 1997 showed a dose-dependent relationship between oral consumption of AGE and serum levels of AGE in people. It indicates that the consumed AGE are getting through the digestive system or that they are modulating endogenous AGE production (or both).
      From the paper:
      “The increases in AGE concentration in serum and urine of
      normal individuals after ingesting the AGE-rich protein meal
      confirmed that AGE moieties present in foods survive the
      digestive process and are transported, as small molecular
      weight particles into the bloodstream, along with short peptides and amino acids present in the digest, in a manner directly proportional to the amount ingested. Although not more than 10% of ingested AGEs was accounted for in the intravascular space, an additional portion is likely to be distributed to the extravascular space along with endogenously formed AGEs.”
      The full text is available for free at PNAS.
      Proc. Natl. Acad. Sci. USA
      Vol. 94, pp. 6474–6479, June 1997
      Medical Sciences
      Theodore Koschinsky
      Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic?nephropathy

  28. Dr Eades,
    You wrote,
    ” the work couldn’t pass the peer-review process.”
    I found on their website, confusing information.
    At the top of the page they say-
    “Each Annals volume contains edited, [b]reviewed[/b] papers based on presentations made at symposia, conferences, and workshops held around the world. ”
    I noticed that they did not say “peer-reviewed” in this overall description of what the annals are.
    However, down at the bottom, they say
    “If the topic of the meeting and the proposal materials are deemed appropriate for possible publication in the Annals, the proposal will be sent out for peer review. ”
    So are they “Peer Reviewed” in the full meaning of “Peer Review”
    I think this is kind of hogwash. I’ve been to a number of these meetings put on by the NY Acad, and I can tell you that every talk from every meeting gets published. I don’t know what the peer-review process consists of (if it really even exists), but pretty much everything makes it through.

  29. While I think an engineering approach can shed some useful light on a subject, I’m always cautious when applying engineering solutions to biological problems. IMHO, that’s what leads to ‘factory farm’ style cattle raising and processing, extensive mono-cropping using lots of artificial fertilizers and pesticides, and one-size-fits-all medicine such as the mass prescription of statin drugs.
    Variety and diversity, which seem to be so key to biological systems, are the bane of efficiency and engineering.

  30. Dear Dr. Mike,
    My question is a bit off-topic, but does relate to aging and brain health. This article, which includes citations, reports an increase of brain lesions accompany higher levels of Vitamin D and calcium supplementation:
    Some of the confounding variables are that a major source of the increased supplementation was milk (presumably supplemented by D-2) and the higher concentrations of Chlamydia pneumoniae and Mycoplasma pneumoniae, labeled as “L form bacteria” and leading to the hypothesis that the Vitamin D supplementation may have been immunosuppressive.
    Any light you can shed on this subject would be much appreciated!
    I homed in on the following sentence in the article:

    The team found that vitamin D intake, (mean 341 IU and maximum intake 1014 IU), was the only variable that retained a significant correlation with the brain lesions when analyzed by a multivariate analysis.

    This means that vitamin D intake was the only variable out of all the variables the researchers chose to analyze. There are literally an almost infinite number of variables that could cause the findings, and the researchers chose to analyze only a handful. And out of that handful, they fingered vitamin D as the culprit.
    I would have to see many, many more studies evaluating a lot more variables replicating this finding before I will believe it.

  31. I know of a situation where large proteins can get into the system: leaky gut syndrome. PPLP talks about this in Chapter 6: The Leaky Gut: Diet and the Autoimmune Response. If people have a hard time breaking down dietary proteins, for whatever reason, and they have inflamed bowels, proteins and anything else that is in the bowel, can leak into the system.
    I agree. But in Leaky Gut Syndrome, partial protein breakdown products make it across the barrier, not large intact protein structures.

  32. Hi Dr. Eades, and all,
    I’m Dr. de Grey’s research assistant, Michael, who cowrote Ending Aging; one of your readers passed the link to this post on to Dr. de Grey, and I thought I’d take a moment to say that I’m pleased and flattered that you found the book so useful, and address this particular matter.
    I don’t actually see the two studies as contradictory. One of the central points of the AGE chapter is that AGE chemistry is extremely complex and multifarious, so that while one might expect that lowering at least some markers of oxidative stress (as shown in the Rejuvenation Research paper) might well be expected to reduce the formation of AGE, there is no guarantee that AGE of other metabolic origin (such as the methylglyoxal in the Annals paper) may yet be unaffected or even increase. You might recall another pair of papers summarized in the book (Diabetes 54(2):517-26; Int J Vitam Nutr Res 73(6):453-6):
    Diabetic rodents were given diets fortified with different antioxidant supplements (vitamins or green tea extracts), and the impact on the animals’ AGE burden was assessed …
    Antioxidant supplements had no effect on the levels of those AGEs whose formation doesn’t require free radicals, of course – but the intervention actually increased levels of the two glycoxidation-derived AGEs , so that diabetic animals receiving green tea extracts actually wound up with more total crosslinking than those who simply suffered the “natural” course of the disease.

    Also, while the degree of editorial rigor imposed in Annals papers varies and (I agree) can sometimes be quite cursory, it can also in some cases be rigorous; it really depends on the editor(s) of the volume and the hosting organization. One thing that gives me confience about the Annals paper is the principal investigator, Paul Beisswenger, who has a great deal of experience in evaluating the in vivo effects of methylglyoxal on the organism and of interventions on MG levels. See
    Diabetes 54(11):3274-81; Biochem Soc Trans 31(Pt 6):1358-63; Diabetes Care 28(10):2465-71; BBA 1637(1):98-106; Diabetes Care 24(4):726-32;
    Diabetes 48(1):198-202.
    Overall, I think that the Annals report merits being taken quite seriously — though I certainly wouldn’t suggest leaping to the other extreme of an Ornish-esque, ultra-high-carb diet. As we indicated in the book this is all very difficult to sort out, and trying to outguess the horrific complexity of metabolism is a mug’s game. At the end of the day, we’re all going to need biotechnological solutions if we’re to escape the terrible age-related slide into disease, disability, dependence, dementia, and death. The good news that forms the core of the book is that such tech is foreseeable, and can be developed with sufficient investment of intellectual and financial capital.
    Live long — live young!
    Hi Michael–
    It is a pleasure to hear from you. I want to tell you that I think you did a bang up job writing the book. You made extremely complex subjects both easy to understand and enjoyable to read about, which is difficult to do. I’m a real fan of the book and your work. In fact, schedule permitting, I would love to attend the SENS4 conference, which I assume will be in September 2009.
    My argument with the methylglyoxal paper in terms of how it was presented in your book is as follows: Lowering triglycerides is a good thing in terms of AGE production. Lowering blood sugar is a wonderful thing in terms of AGE production. Both of these changes occur without exception when people go on low-carbohydrate diets. Perhaps these low-carbohydrate diets do produce a little more methylglyoxal (which idea I haven’t totally accepted, but let’s say it does happen just for argument’s sake), but at what concentrations? And do the consequent AGEs increase in amounts that exceed the lowering brought about by the low-carb diet? I don’t think so. If, indeed, there is an increase of methylglyoxal along with an attendant increase in AGEs I would view it as two steps forward and one step back. If we avoid a low-carb diet in an effort to reduce production of methylglyoxal, then I would say we would be taking one step forward and two steps back.
    I do agree that trying to sort out all the intricacies of metabolism is kind of a mug’s game, but I believe we have to at least give it a whirl. I can tell you that I have treated somewhere in the neighborhood of 10,000 patients with low-carb diets and have found a reduction in triglycerides and blood sugar (not to mention an increase in HDL-C) in virtually all of them. And they lost weight. And they improved their health – at least by all the ways we docs measure it.
    Thanks again for writing. I look forward to meeting in the future.

  33. “Long ago the assumption was made that taking antioxidants in the form of supplements should squelch the free radicals generated within the mitochondria and result in a prolongation of life. Problem is that it doesn’t work, apparently because antioxidants taken orally don’t penetrate into the mitochondria where the free radicals are. A zillion studies have shown that taking antioxidants doesn’t increase lifespan”.
    So, would you say that consuming those expensive acai berry drinks doesn’t do any good? Is there much benefit? The main reason I would buy them was for the antioxidants. Is it worth the carbs?
    I don’t know if it’s worth the carbs or not. Antioxidant supplements don’t seem to penetrate the mitochondria and do much good, but foods, on the other hand, do. Know one knows why. Maybe there are substances in foods we haven’t discovered yet or maybe the form of the antioxidants in foods works better. Who knows? But this is the reason I like to get most of my antioxidants in good whole-food form. I still do take them orally, but just as insurance, I guess.

  34. Dr. Eades: Very late comment, but I hope that you’ll see it. The study you reported on raised glutathione levels and lowered oxidative stress. As you may know, oxidative (or nitrosative) stress is now thought to underlie chronic fatigue syndrome, as set out by Martin Pall. I’m a longtime sufferer of CFS, and have recently switched from a low-fat vegetarian diet to Paleo eating (and it seems that I already feel somewhat better after 2 weeks of it). My own lab work shows low levels of glutathione, much of it oxidized, also methylation defects.
    My specific question is this: is a low carb approach – lower than Paleo – the way to go? Are my low levels of glutathione due to lack of dietary protein and/or oxidative stress brought on by it?
    Thanks for your blog. I was a staunch opponent of everything you stand for until very recently, but I’ve become a convert, mainly thanks to Cordain’s Paleo book, which convinced me that that it what we’re designed to eat.
    I guess the short answer is that I’m not sure. You could try a lower carb diet for a while to see what happens. If your symptoms improve even more, then you’ve got your answer.
    I’m not so sure I would rely on a lab test for glutathione, because the glutathione that counts is that found within the mitochondria, which is difficult, if not impossible, to test for. Either that or someone has devised a test that I don’t know about.

  35. As I slowly make my way through older posts, I have to say I’m more and more impressed. You’ve completely risen about the vast majority of your peers, in my opinion, by having an open-mind to all available research, and continually seeking the Truth.
    This blog entry is an excellent example of digging deep and assembling a more complete picture.
    BTW, I read de Grey’s book, found it excellent overall, but have a few quibbles of my own with it. I’m a long-time member of (nickname: DukeNukem), and I contribute to the MPrize (a member of “The 300”). I’m a firm believer that our lives can be extended indefinitely, given enough brain-power behind the effort.
    Curious, have you read Breakthrough, the newest book by Suzanne Somers? At 47, I supplement with several hormones (since age 41), including hGH and testosterone, and believe strong in the benefits of doing so. Have you considered HRT, or perhaps you already do?
    Thanks for the kind words. I’m impressed that someone is actually digging through the archives.
    My wife does HRT because she is perimenopausal and her saliva tests show she needs the replacement. My last saliva test (about 6 months ago) indicated that my levels were where they should be. If they do start to fall – which I’m certain they will at some point – I will strongly consider it.

  36. >>> My last saliva test (about 6 months ago) indicated that my levels were where they should be. <<<
    Dr. Eades, perhaps *your* doctor is making the age-old mistake when it comes to measuring your hormones: s/he is comparing them against the average of your age group. The idea behind HRT is not to adjust your hormones relative to your current age, but to keep them at youthful levels, generally about where they would be at 30 years of age.
    If you are over 40, then almost assuredly your hormones have declined, and you would benefit tremedously from HRT. I follow the research on this like a hawk, and testostorone, especially, has been absolutely validated as a highly beneficial hormone that is correlated with heart disease and other negative conditions as it declines. Additionally, in the last year it has finally been put to rest that testosterone supplementation will increase chances of prostate cancer, or aggrevate/worsen existing cancer.
    Anyway, I assume you have Tivo, and now that you have it, you can hardly imagine life before Tivo. This is what most Tivo/DVR users think, anyway. Well, if you’re above 40, HRT is the same. Until you start, you don’t realize just how amazing it is. After you start, you realize you can never go back.
    BTW, I hope your wide is using bio-identical hormones. Otherwise, likely she placing herself at a significant cancer risk using Big Pharma’s non-bio-identical versions (Big Pharma cannot patent the bio-identical versions, so they create synthetic, non-identical versions, that come loaded with negative side effects.)
    Finally, while here, have you heard about Pycnogenol? It’s a propriatary supplement, the inner bark of a specific French grown pine tree, and heavily researched (easily googled). I bring this up because a study by the maker of Pycnogenol appeared last year showing that taking Pycnogenol before a meal greatly delays the absorbtion of glucose within meals, for up to 8 hours after it’s taken. I take 100mg of Pycnogenol prior to any meal now, in which I will have more that 10 grams of carbs. I also take Phase2 (a white bean extract) for the same purpose (easily googled, too). Pycnogenol, though, seems to be a powerhouse supplement for numerous benefits, and blocking carbs is definitely one you might want to look into.
    In this case, I am my doctor. And I didn’t make the age-old mistake. I’m a little cleverer than that. My testosterone isn’t at the 30 year-old level, but it’s not far off. It’s close enough that I don’t feel the need to boost it. Not at this time, anyway. Who knows what I’ll find on my next test?
    My wife is taking bio-identical hormones. She wouldn’t take any other kind.
    I’m familiar with both pycnogenol and the while bean extract (which goes by a number of names). I like the former, although I’m not sure I believe the part about how it delays the absorption of glucose. I don’t like the latter because it sends undigested carbs to the colon, which is not where they belong. I has also been shown to cause some pancreatic enlargement, and I’m not sure of the long-term consequences of that. It’s much easier for me to not eat the carbs so that I don’t have to worry about blocking them or delaying their absorption.

  37. Dr mike,
    I found an article with the following title:
    “Mitochondrial recycling of ascorbic acid as a mechanism for regenerating cellular ascorbate” (DOI :10.1002/biof.5520300105).
    Now I am not a biochemical expert, but reading the abstract I got the impression that ascorbate actually enters the mitochondria. Apparently the mitochondria recycle the AA from dehydroascorbate back to ascorbate. How can you be sure that this strong anti-oxidant doesn’t have a protecting value inside the mitochondria? And we know that supplementing with ascorbate will increase ascorbate levels in bloodserum, even if it didn’t come from an orange or lime.
    Besides, if we can boost the number of mitochondria through exercise, who cares some of them die?
    Last point : I read an article that stated that research had shown that supplementing with testosteron makes your prostate grow. Carnitine on the other hand had the same hoped for result (libido) without the effect on the prostate. So I tend to stay away from testosteron as a supplement.
    This blog really gives a lot to think about. A whole new world has opened to me. Thanks to you!

  38. And how about this one?
    “Consequences of Aging on Mitochondrial Respiratory Chain Enzymes in Cultured Human Fibroblasts Treated with Ascorbate”. The report states:
    This study demonstrates an age-related decline in mitochondrial respiratory chain activity as well as a protective role for ascorbate in aging.
    So, again, supplementing with vitamin C – in adequate doses- doesn’t seem so silly.

  39. And this one?
    “Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury” .
    This was the last one I will submit. But I’m sure you get my point.

  40. Your comments about lowering your intake of carbohydrates to deal with the problem of oxidative stress are interesting.
    I made this same comment at some other blog but it might also be helpful here:
    I understand that breathing Activated Air helps improve protein function which helps stop or even fix damage caused by oxidative stress. I have not seen a lot on protein function, does anyone know of other companies doing this besides Eng3, the activated air people? They have a post at their blog on this

  41. Dr Mike,
    This morning I recieved the lab work results and all are good. Only the Uric acid has increased from ~5.5 to 8.0. I am a Type II Diabetic, Male, 38 years old.
    The Dr was asking me to be cautious on the uric acid levels else I will have Kidney/heart problems later. I am not sure what to do? Do I need to control my uric acid by cutting on Protein intake?
    I consume ~40g net carbs everyday. Other than this one, everything else works perfectly.

  42. Dr Eades,
    I’m sorry to post a little off-topic, but I wished to point out an article in the New York Times to you – It outlines an argument against taking antioxidant supplements when using exercise to improve insulin response. I wonder if you could treat us all to a brief excursus on the processes and relationships that they are describing here?
    With thanks from a very regular reader – Alison

  43. Dr. Eades, I just stumbled onto some research stating that the possible culprit behind graying hair is a build up of hydrogen peroxide which bleaches the hair from the inside out.
    The build up of hydrogen peroxide is cause by the inactivity of catalase according to this study. So if I understand correctly, hydrogen peroxide is an oxidant that should raise catalase levels. So my guess is that somehow, high levels of blood glucose can inhibit catalase production allowing hydrogen peroxide levels to rise, in some people. Sooo,by relying on a ketogenic diet to reduce glucose levels could in turn cause the reduction of hydrogen peroxide levels regardless of the presence of CAT, since glucose is.
    The reason I am just babbling on about this is I have noticed a good reduction of gray hair.I have always thought that my low carb lifestyle had something to do with it and I believe that I made a comment about this somewhere deep in your archives. I also recently sprouted a gray hair in my eye brow. I just checked in the mirror and now it is gone. This is making me insane doctor…What does it all mean??? 😉
    I’ve never heard this theory, but if it works, great.

  44. Hi again Dr. Eades,
    Following up on our previous discussion: the below is an in vitro study, but it does provide a mechanism that might explain the finding of higher methylglyoxal in Atkins dieters, despite lower levels of “usual-suspect” AGE precursors. Note that (a) as they say, it was already known that high glucose levels could form methylglyoxal, through overloading the glycolytic machinery and generating triosephosphates, and (b) they did specifically monitor ketosis in the Atkins dieters in the study. This of course wouldn’t apply to a less strict low-carb regime, probably even including Atkins’ own “Ongoing Weight Loss” (OWL) plan.
    Metabolism. 2008 Sep;57(9):1211-20.Click here to read Links
    Methylglyoxal production in vascular smooth muscle cells from different metabolic precursors.
    Dhar A, Desai K, Kazachmov M, Yu P, Wu L.
    Methylglyoxal (MG), a metabolic by-product, reacts with certain proteins to yield irreversible advanced glycation end products (AGEs) and increases oxidative stress that causes the pathophysiological changes in diabetes, hypertension, and aging. Although MG production from glucose has been well documented, the contribution of other intermediates of different metabolic pathways to MG formation is far less known. …
    There was a concentration-dependent increase in MG levels in [in cultured rat aortic vascular smooth muscle cells (VSMCs)] after 3-hour incubation with 5, 15, and 25 mmol/L of D-glucose, fructose, or aminoacetone. Aminoacetone produced a 7-fold increase in MG levels above the basal value followed by fructose (3.9-fold), D-glucose (3.5-fold), acetol (2.8-fold), and sucrose (2.3-fold) after a 3-hour incubation with 25 mmol/L of each precursor. …
    In conclusion, aminoacetone is the most potent precursor of MG production in VSMCs, followed by fructose and d-glucose. This could have important implications in relation to high dietary fructose and protein intake.
    PMID: 18702946

    “High protein intake,” of course, wouldn’t be the issue, but very low carb intake.
    Maybe, but I seriously doubt it. I’ll wait for the in vivo studies instead of the in vitro ones. I read this study when it came out, and I wondered at the time how fructose could have a 3.9 fold increase and glucose a 3.5 fold increase in MG production when sucrose, which is half fructose and half glucose had only a 2.3 fold increase.

  45. Hi again Dr. Eades,
    I’m trying to post a study that I’ve just discovered that updates and informs the issues we discussed here. I posted last night, and nothing happened; I came back this morning, tried to post again (I’d saved a draft in an email), and was told “Duplicate comment detected; it looks as though you’ve already said that!”
    Do you have some sort of blocking or hold-for-approval system? Any tricks I can try or snares into which I may’ve fallen?
    No, I’m just chronically woefully behind on moderating comments.

  46. Hi Dr. Eades:
    Re the double comment: it’s more than just the moderating queue: when I posted the second comment above, it appeared on the screen, with the note that it was awaiting moderation; the original post didn’t appear at all …
    Re the study, you wrote:
    I’ll wait for the in vivo studies instead of the in vitro ones. . Well, of course, there was an in vivo study: that’s how this thread got started 😉 . I agree, however, that it would be good to see it repeated, and perhaps with more subjects (although 10 is a fairly common study size for metabolic studies of this kind) and without the accursed ITT analysis 😉 .
    I wondered at the time how fructose could have a 3.9 fold increase and glucose a 3.5 fold increase in MG production when sucrose, which is half fructose and half glucose had only a 2.3 fold increase.
    Being in vitro, the acidity and digestive enzymes of the mouth and GI aren’t available to hydrolyze it, and I’m guessing that it just wasn’t metabolized by the cells into methylglyoxal or much of anything else.
    In vivo, of course, this is rather a moot point: with the possible exception of in the upper jejunum, cells would very rarely be exposed to unhydrolyzed sucrose as such, and even their constituent fructose would not reach many cells in that chemical form, having first been metabolized into glucose in the liver (although I certainly don’t have to tell you or most of your readers that this process is itself metabolically deleterious). By contrast, cells routinely encounter and metabolize glucose, fructose (plasma concentration 35 µmol/L, formed endogenously from glucose through the aldose reductase pathway, vs ~5 mmol/L for glucose), and ketone bodies. Very low-carb diets substantially increase ketone body formation, shifting the substrate mix for cellular fuel and metabolic byproducts, as the Beisswenger study suggests.

  47. I came across a rather troubling study that seems to indicate that high-fat diets cause insulin resistance and an increase in free radicals. I hope someone can find a way to refute this. The details are at
    Here is a link to the actual study:
    I dealt with this in a previous comment. I wrote:

    I don’t think the study is relevant at all. The very first line of the abstract is a lie. It says: “High dietary fat intake leads to insulin resistance in skeletal muscle,…” I would love to see the proof of this. It doesn’t exist. I didn’t have time to read this study critically, but my quick overview tells me that most of the data is from rat studies, and rats aren’t just furry little humans. The didn’t evolve to eat a high-fat diet, so they don’t react the same as we do. The one study they did in humans, was a muscle biopsy study after a single high-fat meat (and we don’t know what the rest of the meal was – it could have been sugar), which causes a different reaction than would be the case in someone who was low-carb, high-fat adapted.

  48. Look at the meal content:
    “After muscle samples were obtained, subjects consumed a single high-fat meal (35% daily kcal intake; >60% kcal from fat), and a second muscle biopsy was taken 4 hours later. Subjects then consumed a high-fat diet (isocaloric; >60% kcal from fat) for 5 days and returned 12-hour fasted on the morning of the sixth day, when a final muscle biopsy was obtained.”
    60% fat. Not 100%. Big difference. Why blame the fat?
    Because fat is the whipping boy for most academicians.

  49. This is very interesting. Anecodotally, I can say that I have seen obvious visible improvements in aging after I stopped eating carbs. My face and skin lost that puffy, inflamed look that I thought was due to a dust allergy. The dark skin around my eyes got lighter and lines decreased. My eyes look clearer and brighter. My skin’s usually chronic dryness/eczema improved dramatically and my skin glows, which I attribute to the increased animal fat that I now eat. Generally I think I peeled about 5 years off my appearance but that could be because carbs were making me fat and sick and it may have nothing to do with AGE’s.
    As an aside- a picture of Mr. de Grey on wikipedia suggest that he is not aging well (

  50. Speaking of Aubrey de Grey, a lot of people in the life-extension/calorie-restriction community have adopted very-low-fat/low-calorie diets since those seem to be effective for rats (studies by Roy Walford et al). Last I checked the primate studies were not as promising.
    In my experience, such a diet does not lead to a “healthy” appearance or high quality of life.
    It would be tragically ironic if these folks were actually shortening their lifespans.

  51. Great article. I read a study about the neuroprotective effect of ketones and the prevention of glutamate excitotoxicity by reducing ROS in neurons. Basically the study indicates that ketones decrease the production of reactive oxygen species as opposed to ketones increasing glutathione.
    Either way it is a great argument for adopting a low carb or ketogenic diet.

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