First and foremost, I want to link to the latest post in MD’s blog.  When I posted earlier about our meals in Mexico, I mentioned this great Andalusian gazpacho recipe she had.  A bunch of people asked for it, so she put it up.

Richard Feinman sent me a link to an annoying Mayo Clinic nutrition blog by a couple of ignorant dietitians.  Reading stuff like this that is written with such certainty always makes me think of a couple of lines from Shakespeare’s’ Measure for Measure:

Man, proud man!
Dress’d in a little brief authority:
Most ignorant of what he’s most assur’d.

These women are oblivious to the fact that the studies upon which they base their idiotic ramblings are worthless as proof of the nonsense they spout.  The first considers a diet with 45 percent of calories as a low-carb diet.  Oh, really?  The second is an observational study, and, as such, totally useless for proving causality.  Yet, in their words, these studies

caused a couple of “aha” moments

for them.  I suppose they could have meant, “aha, we’re really clueless.”

I read a nice little summary in the journal Hepatology of a study published in Nature Medicine.  The study looked at chaperone-mediated autophagy (CMA) and aging.  As we age, we tend to accumulate protein debris in our cells.  Over time this accumulation interfers with the proper functioning of the cell and is thought to be one of the components of aging and cellular sensescence.  Organelles within the cell called lysosomes are charged with the responsibility of basically chewing up (auto-phagy: self eating) these junk proteins to keep the cell free of garbage, allowing it to do its job.  Chaperones are proteins that bind to junk proteins and move them into the lysosomes for degradation.  Researchers developed transgenic mice that had the ability to make more of the chaperone proteins than normal mice, giving them the ability to increase the degradation of junk protein.  Their study showed that increasing the CMA in these mice resulted in lower accumulation of junk protein, better ability to deal with protein damage, and improved organ function.  The reason I like this paper so much is that it confirms what I wrote in one of my favorite posts from the past about ketosis doing the same thing.  Maybe you don’t have to be a transgenic mouse to get the benefits of cleaner cells; maybe just staying in ketosis more of the time will do the job, too.

Politics alert! POLITICS ALERT! POLITICS ALERT! For those of you who chastise me for daring to bring politics into what is at heart a nutritional blog, beware: politics to follow.  If you want to avoid reading about anything to do with politics and get back to the nutrition stuff, skip on down until the politics alert has been removed.

Here is one from the Karma-is-wonderful department.  By now everyone knows that Tom Daschle got the rug pulled out from beneath him in his attempt to become the secretary of Health and Human Services in the Obama administration because of his failure to pay over $100,000 in taxes.  And everyone knows that former Senator Daschle didn’t pay taxes on the car and driver he was provided as part of one of his lobbying efforts. (One wonders what kind of car would run up enough imputed income to result in over $100,000 in taxes.) But what many people might not know is that Mr. Daschle, in his days as a Senator from South Dakota, ran ads showing that he drove an old car while working in Washington for the folks back home.  The irony is so sweet.

Click here to view the embedded video.

While we’re at it, you might enjoy this cartoonist’s ideas on how we can afford the stimulus package being argued in Congress. Now we can add one more with Solis.  We really can begin to refill the coffers if this keeps up.

An insightful article in the Economist from a few weeks ago got me thinking.  This piece was talking about the government in the UK, but it could be applied to any government anywhere when faced with a crisis.  Governments all follow these two rules:

First, eschew all blame.
Second, do something.

I’ve never seen our own government here in the US not follow these rules.  For example, let’s look at the subprime mortgage situation that has gotten us into our current bad way.  When the house of cards began to fall, what did the government do?  Pointed fingers at everyone but itself.  It eschewed all blame.  It was the fault of all the independent mortgage lenders making shaky loans; it was greed on Wall Street; it was Bernard Madoff.  And on and on and on.

And what did our government then do, after all the finger pointing?  It did something.  It passed an emergency stimulus bill to the tune of $700 billion to keep all of these people from losing their homes and to keep the economy from cratering as a result.  As near as I can tell, I have about 5,000 people who read this blog every day.  And those 5,000 people know a lot of other people.  In fact, I would imagine that, on average, each of these 5,000 people probably knows or knows of at least 50 people, which means that all of us together know around 250,000 people.  Of all these people, some are bound to be in financial trouble and are behind on their mortgages.  So I ask you this, has anyone reading this blog learned of anyone he/she personally knows getting mortgage help from this $700 billion?  I didn’t think so.

So the government pointed fingers and did something.  We know that whatever it did, didn’t really help the individual people who were hurting during this mess.  It helped Wall Street guys get their bonuses, and it helped management of troubled banks get their health insurance premiums covered, and it redecorated a few offices, so maybe the do-something part of the equation actually helped some individuals (though not the ones it was sold to us to help).  But what about the blame?  Wasn’t it Wall Street greed and independent mortgage brokers?  As Will Rogers used to say, “All I know is what I read in the newspapers.”  I’m kind of the same way, but I like to think I’m a little bit of a critical reader.  The single best and most comprehensive piece I’ve read yet on the current financial debacle was written several months ago in The Spectator, published in London, and my favorite weekly magazine.  The author of this article musters the data to show that it is the government itself that is at fault.  And if you don’t believe the author, here is a piece written in the New York Times on September 30, 1999 when the seeds for this subprime meltdown were sown, discussing the potential problems that could come to pass.  Sadly, they did.

On the global warming front, here is part of an email I received today from an outraged friend of mine in the UK.  This friend is a famous author who hobnobs with everyone who is anyone in the UK.  Name withheld mainly because it’s too late at night there for me to be asking for permission.

Tonight I sat watching television which I don`t do a huge amount of. We have been snowed in for 4 days and tonight it is minus 8. I watched a hapless man from a council lamenting that they had run out of salt and grit so the county`s roads would be death traps. Asked why their stocks were so low, he said because they had all been led to believe we would never have winters like this again because of GW. so they spent the money on recycling and ‘Climate Change initiatives’ instead. ‘And I have to say,’ this brave man ended ‘I think we`ve all been badly conned.’   Ten minutes later the US Vice President Biden appeared on my screen – what a pleased-with-himself guy he is. In Munich, and he said to me that the USA was now wanting dialogue with Iran and Pakistan and Russian and…. and that this will be an initiative that will work … well I am glad he is so cocky about it. He then said ‘we have far more to fear from global warming than we have from international terrorism.’    What the hell planet is this guy ON?   It`ll take a 9/ll and the entire mad middle east to explode in their faces for the truth to dawn….. meanwhile, does it not occur to them that most of Western Europe has been trying to engage these countries in dialogue for the last 10 years – and that meanwhile, weekly, a terrorist plot is detected and defused by our counter-intelligence and  anti-terrorist police … He looked so smug I wanted to throw something at him.

Okay.  Politics over.  The all clear whistle has sounded.  It’s safe to go back into the water.

One of my readers sent me this great link to an article in the journal Archeology about the diet of the Roman gladiators.

It appears that far from being the cut and shredded specimens of masculinity that we see portrayed in films, the real gladiators were fat.  Why?  Because body fat protected them from injury.  It provided a kind of a built-in shield.  And how did the gladiators make themselves fat?  According to researchers on the subject, gladiators ate a lot of simple carbohydrates and not much animal protein.  I can already see Dean Ornish’s next book: The Gladiator Diet.

You’ve all read my whines and rants about the sorry press coverage of scientific studies.  Apparently I’m not the only one who feels this way.  Here is a writer from the prestigious British Medical Journal bitching about the same thing.

Says he:

Every day one of our national newspapers publishes a piece reporting on “scientific research” and nearly every day the report is misleading, inaccurate, shows poor understanding of science and scientific research methods, and irritates the hell out of many a hardworking researcher. Often the original research is crap too. Millions of innocent people are misdirected and confused as new and often harmful myths are started.

Couldn’t have said it better myself.

Last week an article appeared in the Los Angeles Times about intermittent fasting.  I’ve gone through quite an evolution myself on this subject, going from pro to not so pro back to pro with some reservations.  I’m planning a post within the next couple of weeks on the subject, specifically about one of the papers mention in this LA Times article.

A pretty good review article on the treatment of obesity appeared in Nature Clinical Practice Gastroenterology & Hepatology (free full text and pdf) last December. (See, my tabs have been up for a long time)  This article provides an overview of all the different diets available for the treatment of obesity.  And, what makes it nice, is that not only does it not ridicule or give the low-carb diet short shrift as most mainstream journals do, it actually seems to imply that the low-carb diet works the best.  Slowly but surely we’re making progress.

Last but not least, lets end with a death-defying bit of daredevilry.  Watch this guy jump this motorcycle both ways.  I like to push the envelope risk-wise sometimes, but you couldn’t get me to do this for all the money in the world.  Bravo!

Click here to view the embedded video.

Gary and me on our front porch. Photo by MD Eades 8/13/2008

A couple of days ago Gary Taubes, who was visiting family in Los Angeles, drove up to Santa Barbara, and he, MD and I got together for a long lunch. We talked about all the things we always discuss, most of which have nothing to do with nutrition or nutritional science. But, as always when we get together, talk did turn to science and the sorry state of nutritional science in the world today.

We discussed a Stanford study that was recently published in the Archives of Internal Medicine demonstrating that those who are runners live longer and have less disability. The paper proves absolutely nothing, yet an enormous number of people, many of whom should know better, profess that this study is the smoking gun that ties exercise to longevity and health.

The researchers sent questionnaires to 538 members of the 50+ Runners Association and healthy controls from the Stanford area who were 50 years old or older in 1984. By 2005, 284 runners and 156 controls had completed the 21-year follow-up. After crunching the data, the researchers found that more than double the number of controls had died as compared to the runners and that the total disability score for the controls was much higher (i.e., they had a greater degree of disability) than for the runners. The conclusion as stated by the authors:

Vigorous exercise (running) at middle and older ages is associated with reduced disability in later life and a notable survival advantage. [My italics]

The conclusion of this study, which is absolutely accurate, is that running is associated with longevity and reduced disability. The two are associated or correlated. The study does not prove that running increases longevity or decreases disability. Correlation is not causation. But you wouldn’t know that from the press coverage of this study.

If you run a Google search, you will find the study reported as proving causality. See here, here and here for just a few instances.

Let’s explore this study a little because it provides a good example of what these kinds of studies show and what they don’t. And why we should never rely on association or correlation studies as proof of anything.

First, in the USA (and in other countries as well) it is a given that exercise is good for one. We believe that exercising will make us live longer. And a lot of us believe that exercise will make us fitter and have less disability as we age. When we see a study that seems to prove this, we accept it without batting an eye. Even though the study shows no such thing. We are culturally primed to accept scanty evidence to prove what we already believe about exercise.

Let’s assume that our cultural dogma was that exercise was unhealthy and that those who did vigorous exercise were killing themselves. We used to kind of think that in this country. I’ve often heard it said that someone (who was employed in a physically demanding job) had worked himself to an early death. So let’s suppose that were our cultural default, and we are looking at the same data as presented in this study. We would ‘know’ that exercise isn’t good for us, and, in fact, is probably bad, so we would look for different differences between the two groups. We might find that the group of runners drank way more water than the non-runners. And let’s assume for argument’s sake that our culture believes that water consumption is good and healthful. This same study data could then have been presented in terms of increased water consumption negated the negative effects of running, and even allowed runners to live longer than non-runners who drank less water. What we look for in these studies is culturally driven.

Were we in France – where I’ve yet to see anyone jogging – we might get a totally different take. We might have studies showing that men who have mistresses (and keep them well occupied) live longer than men who don’t. So therefore having a mistress leads to longevity…? (Probably not in my case, especially if it were discovered.)

Studies showing associations or correlations between between activity A and result B do not mean that A causes B. Yet it is extremely easy to be beguiled into believing that A causes B, especially if it makes sense based on our belief system. It doesn’t make logical or scientific sense to jump to that conclusion, although far too many people do.

I suspect that there are a number of people reading this post right now who firmly believe – despite all I have written above – that the study in question really does prove that running improves longevity because it seems to make so much sense. But let’s explore a little further.

We don’t know and can’t possibly determine from this study whether it is the running that increases longevity or whether there is some facet of personality or physiology that drives one to run that increases longevity. Maybe people who are destined to live longer take to running or other forms or aerobic exercise. People who are depressed typically have shorter lives, and people who are depressed tend not to join groups or exercise. Perhaps a number of the people in the control group are depressed, leading to an increase in early deaths in that group. It could be that the people who have the time to join a running group and spend the time running are more financially stable and are happier. Both of those conditions are correlated with longevity. There are far too many factors separating the two groups to dissect out the one and attach the benefit to it. But our culture firmly believes that exercise promotes longevity, so this experiment seems to bear that out, and most people accept it without looking to deeply.

One of the commenters on this blog gave a good example of this in a comment today. Let’s say we have a study showing that red cars are involved in more accidents than white cars (which may be true, for all I know.) Does this prove that red cars are more dangerous? Or does it prove that drivers who have the mindset that motivates them to choose red cars are less careful drivers? Or both? Or does it prove the opposite about white cars? You can’t tell.

If what I say is true, you make ask, why even do these kinds of studies if they have no value? The answer is that they do have value. They allow scientists to derive hypotheses that can then be tested. But often the rigid testing required for proof is impossible, so people who should know better fall back on these kinds of associative studies as proof since real proof can’t be obtained. Why not? Let’s take a look.

If we wanted to firmly establish that running increased longevity, we would have to do the following study. We would have to select a large group of subjects who are all of the same age and level of health. We would then have to randomize them into two groups: one a running group and the other the sedentary group. We would have to force the people in the running group to run and force the people in the sedentary group to be sedentary. Then we would have to follow these two groups for 21 years. If the runners then substantially outlived the non-runners, we might have a case that running promotes longevity. But until we do this, we can’t state that we have proof. You can see the immense difficulty involved in performing such a study. You can’t simply randomize someone who isn’t really driven to run into the group of runners and expect that person to run daily for 21 years. Yet that’s pretty much what you have to do to establish causality.

The moral of this story is to view these studies for what they are. Interesting but not proof.

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.

LESS IS MORE…IS WORSE

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). 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.

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.

Before we get into the study, let’s take a moment and discuss AGEs so we’ll all be on the same page. When proteins are incubated with sugars, over time the sugar attaches irreversibly with the protein in a process called glycation. (There are many names for the reaction: the Maillard reaction, Schiff’s base formation, the Amadori reaction, etc. with minor differences between these different processes, but debating the differences is pointless for our purposes.) If the protein performs a specific function in the body due to its unique structural conformation, and it finds itself with a sugar attached to it that it can’t get rid of, then this protein suddenly doesn’t function so well and becomes a junk protein that the body has to dispose of.

Since most of the structures in our bodies are made of protein, and since all of these proteins are bathed in blood that contains glucose, the normal course of events is for a portion of these proteins to undergo glycation. And the longer the proteins are in contact with the sugar, the more glycated proteins will be formed. All this goes on continuously in our bodies so as we age we accumulate more and more of these substances, thus the clever name AGEs.

If we set out two beakers filled with a protein solution and add an amount of sugar to one and double that amount of sugar to the other, we will end up with many more glycated proteins in the beaker with more sugar. The same thing happens in the body. If blood sugar is chronically high, then there are more glycation products. One of these products – hemoglobin A1c – is used to measure the average blood sugar concentration over the previous couple of months.

Hemoglobin is the protein in the red blood cells that binds to and transports oxygen throughout the body. There is always sugar in the blood, some of which binds to the hemoglobin via the glycation process. If the blood sugar goes up and stays up as it does in diabetes the elevated concentrations of glucose end up producing more glycated hemoglobin, called hemoglobin A1c. (Fructose is a much more potent glycating agent (it’s actually called a fructating agent) than is glucose (blood sugar), so the inclusion of high-fructose corn syrup into almost everything isn’t doing us a lot of good glycation-wise.) And hemoglobin isn’t the only protein being glycated – it’s just the one that’s commonly measured.

More glycated proteins are not a good thing. We all want our proteins to work as nature intended and not be gummed up by having a sugar hanging off of them. These glycated proteins end up in the lysosomes, the refuse boxes of the cells, and are thought to be one of the driving forces behind the aging process. Cells with too much junk don’t function properly. And when enough of our cells don’t function properly, we don’t function properly. (Click here to read an old post about de-junking your cells)

With that background in mind, let’s take a look at the paper.

Researchers looked at a group of 19 vegetarians (lacto-ovovegetarians) and used as a comparison a group of 19 omnivorous subjects recruited from the same region (Bratislava, Slovak Republic). As you can see from the table below, the omnivores (Traditional) actually consumed a little more carb (saccharides) each day than did the vegetarians (Alternative), but not enough to reach significance. What the vegetarians ate more of in significant amounts were fruits and vegetables, giving them a significantly increased intake of fructose.

When researchers measured levels of carboxymethyllysine, an glycation product that represents

a general marker of oxidative stress and long-term damage of proteins in aging, atherosclerosis and diabetes

it was found to be significantly elevated in vegetarians as compared to omnivores. Fluorescent AGEs are basically a direct measurement of AGEs in the blood. As the authors point out fluorescent AGEs serve

as an index of advanced glycation [and] increase linearly for human serum albumin [a blood protein] incubated with glucose and exponentially when fructose [is] added to the incubation medium.

Fluorescent AGEs were also significantly higher in the vegetarians.

Another interesting aspect of this study is the finding of the authors that the vegetarians

do not use high temperature for culinary treatment. They prefer heat treatment at lower temperature for short period of time.

I find this intriguing because so many anti-meat zealots constantly harp about the dangers of overcooking meat (or cooking it on a grill) because of the AGEs that are produced in the process, which, they seem to believe end up in the bodies of those who eat grilled or overcooked meat. I don’t think it’s too much to assume that most of the omnivores eat meat, and some probably overcook it or grill it, yet they have less accumulation of AGES than the oh so fastidious vegetarians.

I’m sure I’ll get a slew of comments from surly vegetarians after this post telling me how healthy they are and how healthful the vegetarian diet is. But in this case the data show otherwise.

An annoying comment I hear all the time whenever I talk about how Ancel Keys set the country on the disastrous nutritional course it has been on for the last 40 years runs something like this: ‘I dunno. Key’s must have been doing something right because he lived to be 100.’

First, the fact that Key’s himself lived to be 100 doesn’t mean squat. Everyone has a relative somewhere that defied the odds. I would bet that just about anyone can name someone who smoked, drank and was obese who lived to a ripe old age. Winston Churchill, for one, comes to mind. Smoked, loved his booze, was obviously obese, and lived to be 90. It’s not the individuals that matter in terms of health and longevity, but populations as a whole. And since the US (and now the world, it seems) has been following the wisdom of Ancel Keys, look what has happened. Obesity and diabetes are at epidemic levels. So, while Ancel himself lived a long life, I’m not so sure a lot of his victims will.

But, since people obnoxiously continue to point out that Keys made it to triple digits by allegedly following his own recommendations, let’s look at another individual (which, again, mean nothing in scientific terms) for comparison’s sake.

A reader sent me the link to the following YouTube. It’s a few minutes long, but well worth watching. It shows diet and fitness expert Jack Lalanne having a heart to heart with viewers of his show back in the 1950s. Observe. And listen carefully to the diet he recommends. (And notice how far television production values have come in 50 years)

Click here to view the embedded video.

Now, let’s assume that Mr. LaLanne practices what he preaches. He is 93 years old now, going on 94. A photo of him taken this year is at the top of this post. Below are a couple more.

Below is a photo of Ancel Keys taken when he was 100 and was being honored by the Scripps Institute. I suppose he could have looked as good as Jack LaLanne seven years before this picture was taken, but somehow I kind of doubt it.

So, you be the judge. Who would you rather look like when you reach your golden years?

Remember these photos the next time you hear someone rabbit on about how Ancel Keys lived to be 100, therefore he must have been doing something right.

Anti-aging scientists are now pretty sure that one of the forces behind the aging and senescence process is the junk protein matter that accumulates in the cells, hampering cellular function. If the junk builds up enough, it basically crowds out the working part of the cell, killing the cell off in the process. As this inexorable process proceeds, more and more cells function less and less well until we, as a being, cease to function. There are other processes driving the aging function besides this accumulation of cellular debris, but if we can make some headway with cleaning out the junk, then we should be able to make the cells, and by extension us, function better for longer.

We have little chemically-operated waste disposal systems in our cells called lysosomes. Cellular debris that gets hauled to the lysosomes and dumped in gets degraded into individual amino acids, which are released into the circulation and used to re-synthesize other, functional, proteins. The process of transporting the junk proteins to the lysosomes is handled by enzymes designed for that purpose found within the cells. As long as the enzymes are working up to snuff, the junk doesn’t accumulate. But as the Nature paper shows, the aging process takes its toll. Random errors in protein synthesis of these enzymes due to the aging process means that some end up being functional while others aren’t. The non-functional enzymes then not only don’t help haul the junk to the lysosomes, they themselves become junk. It’s easy to see what’s going to happen as time marches on.

But how can we slow this process and de-junk our cells?

Stay in ketoses a lot of the time. How do we stay in ketosis? By following a low-carbohydrate diet.

How does ketosis help us de-junk our cells?

A paper was published in the Journal of Biological Chemistry last year that tells the story. Ketones stimulate the process of chaperone-mediated autophagy (CMA). What is CMA? It is

a cellular process that allows cells to remove proteins, organelles, and foreign bodies from the cytosol [the watery interior of the cell] and deliver them to the lysosomes for degradation.

Why would the body be designed for ketones to stimulate CMA? Simple. Ketosis is one of the signs of long term starvation. Ketones are produced throughout the day and are perfectly normal, but sustained ketosis takes place during starvation and sends a message that the body needs to conserve both glucose and protein. The body begins to conserve glucose by signaling to many of the organs and tissues to start using ketones for energy instead of glucose. The body conserves protein by decreasing its use of glucose because in the absence of dietary carbohydrate (as in starvation) the body makes glucose out of protein. Conserving glucose by switching to ketones allows the body can preserve its protein stores. The other thing the body can do is to make sure that the protein it does break down to use for glucose formation comes from non-essential sources. What more non-essential source can we have than useless junk proteins floating around in the cells?

The ketones themselves stimulate the process of CMA to salvage all the junk protein to be used for glucose conversion. Ain’t nature great?

Now, all we have to do to slow the aging process is to stay in some degree of ketosis most of the time and let nature take her course and clean all the junk out of our cellular attics. How do we do that? Easy. Keep our carbohydrate intake at (or preferably below) 100 grams or so per day. Why that particular number? Let’s figure.

It takes about 200 grams of carbohydrate per day to provide glucose for all the structures in the body that require it. After a period of low-carbohydrate intake or starvation that amount required drops to about 130 grams per day because about 70 grams are replaced by ketones. We never really get below that because certain cells can’t convert totally to ketone use and continue to require some glucose. For instance, the red blood cells must use glucose for energy as do some cells in the kidneys and the brain and central nervous system. But not to worry, the liver can easily make 200 plus grams of sugar per day to ensure that these tissues get all they need. But the liver makes most of this glucose via a process called gluconeogenesis (the generation of ‘new’ glucose) out of protein.

So, if we decrease our carbohydrate intake to below, say, 50 grams per day, the amount advised in Protein Power and other enlightened books on carb restriction, we’re in a deficit to the tune of about 150 grams per day. No problema. The liver makes up the deficit out of protein. As we start making ketones to replace the glucose, the deficit drops to about 80 grams per day, which the liver can easily provide. But here is the neat part. Most of the glucose the liver makes won’t really come from protein from our tissues; it will come from the protein we eat. We’re not starving; we’re eating a high-protein diet. So we have plenty of protein to make glucose as we need it without robbing our muscles and other protein tissues that would get pillaged were we really starving.

But, deep in the bowels of our cells this fact is unknown. All the cells know is that ketones are all over the place, which is the signal to start the CMA process to break up junk protein.

We end up losing body fat, which is both burned for energy and converted to ketones to replace glucose, while at the same time we maintain our needed protein structures because we’re eating protein, and we de-gunk our cells. All while eating steak and eggs and lambchops and ham and…

It just one more reason the low-carb diet rules.