Jumping Head First into the Fountain of Youth

Go on, it'll knock 50 years right off your age. (Photo by JB London)

I don't know if you noticed, but yesterday a study on telomeres and aging hit the news big time. Various media bought into the hype, claiming that aging had been reversed in mice. Daily Mail, for example, published a story that begins as follows (link):

Have they found the elixir of eternal youth? Scientists reverse the ageing process in landmark trial

The secret of eternal youth has been unlocked by scientists in remarkable research that paves the way for a ‘forever young’ drug. Lives could be longer and healthier, free from illnesses such as Alzheimer’s and heart disease, with skin and hair retaining its youthful lustre. Such a drug might allow men and women to have children naturally until they are a ripe old age.

The secret of eternal youth, huh? And just in case you missed what that would be like, the writer states:

The experiments mirror the plot of the film The Curious Case of Benjamin Button, where the lead character played by Brad Pitt ages in reverse.

Except, of course, that Brad Pitt was born as an old man and eventually turned into a fetus and died, which is not exactly the kind of eternal youth I'm looking for. As you might guess, the paper and its authors are slightly less modest about the results – but only slightly. Professor Ronald DePinho, who did the mouse experiments, says:

In human terms, it would be like having a 40-year-old person who looked 80-plus and reversing the effects to the levels of a 50-year-old.

Reporters obviously love statements like this, but the truth behind the hype is somewhat different. First, mice are not humans, so drawing conclusions about what results from mice would mean "in human terms" without actually replicating the experiments in humans can be misleading.

Second, and more importantly, the mice were not normal mice: they were genetically modified to have no telomerase – which, in simple terms, lengthens telomeres – resulting in prematurely short telomeres and thus premature aging. The authors then gave the mice a drug that kickstarted telomerase, and lo and behold, many of the signs of premature aging began to reverse.

Thus, this is very far from giving the same drug to a healthy person and making them live forever. The rejuvenation in this case applies to the damage caused by having artificially short telomeres, not to all the other kinds of damage that comes with aging. This is precisely why the mice given the drug "become normal", so to speak, but were not rejuvenated in the sense that the whole "fountain of youth" metaphor might suggest.

If this were truly a fountain of youth, the mouse would have lived exceptionally long – but they didn't. They lived as long as normal mice.

While I'm glad that the attitude of the media towards life extension seems to be positive and even optimistic these days, the people writing these articles don't seem to have much grasp of reality when it comes to anti-aging science. I don't claim to be an expert, but even a quick glance at the abstract of the paper (link) would have shown that this is not only "ten years away from being available for sale", it's simply not directly applicable to healthy people.

What I found encouraging, however, was that the mice given the drug not only stopped accumulating more damage, but that their organs did indeed begin to rejuvenate. I say encouraging because it shows that aging damage can be repaired and not only slowed down – which is a crucial difference, because for most of us alive today to make it past 120, it will have to be repaired and not just halted.

Another positive thing about the study is that the mice whose telomerase was reactivated did not get cancer. Since one of the purposes of telomere shortening is said to prevent harmful mutations from spreading, many people worry that boosting telomerase may increase the risk of cancer. It would be interesting to see what the same drug does to normal mice.

For more information on anti-aging and rejuvenation, see these posts:

Aubrey de Grey Interview in Wired.com
Russian Scientist Claims to Have Found Cure for Aging
How Do People Feel about Life Extension?
Anti-Aging in the Media: The Independent on Immortality

Ashwagandha as a Nootropic – Experiment Update

The search for nootropic herbs continues. (Photo by Jim Brekke)

It's time for an update on my self-experiment with Ashwagandha, which began earlier this year in February. The herb in question, also known as Withania somnifera, is one of the many used in Ayurvedic medicine. Since many people use it as a nootropic, being a fan of cognitive boosting I figured I had to try it myself.

While Ashwagandha is commonly used for its relaxing properties, a review of the literature shows that it has a range of benefits. I've gone through the nootropic effects of Ashwagandha in detail in my previous post, so I'll only list them briefly here:

• Activates the GABA receptor
• Inhibits acetylcholinesterase (AChE)
• Reduces alcohol and morphine addiction
• Decreases stress
• Improves sperm count and motility
• Increases testosterone and reduces prolactin levels
• Improves memory function in mice
• Regenerates nerve fibers and dendrites
• Little or no risk of toxicity
• Negative effects on libido at very high doses

An impressive list, as you can see – but note that some of the results are from rodent studies or studies on humans suffering from high stress. The fact that Ashwagandha has been shown to bring things back to normal, so to speak, doesn't necessarily mean that it'll improve things beyond baseline in healthy people. Indeed, Ashwagandha is considered an adaptogen, which refers to herbs that supposedly normalize the body's functions.

For the purposes of my experiment, I bought a bottle of NOW Foods' Ashwagandha extract, which contains 450 mg of the root extract (standardized to a minimum of 4.5 mg withanolides) per capsule. My evaluation was based on subjective effects on mood, libido and stress.

The bottle is now finished, and I'm somewhat disappointed to conclude that I didn't notice much effects from the product. I tried various approaches: taking a capsule in the morning, during the day, or in the evening, but none of them resulted in anything clearly noticeable. The only possible effect I saw was more vivid dreams when I took Ashwagandha before going to sleep, but even then the results were inconsistent. All I can say is that the combination of magnesium and Ashwagandha before bed seemed to give me a good night's sleep.

As for boosts in mood or cognition, I didn't see any. Neither did I notice a difference in my libido or stress levels. I did try taking two or three capsules at once to see if a larger dose would help, but as far as I can tell, it made no difference. At least there were no negative effects either.

To be clear, I'm not saying that Ashwagandha is useless, just that this particular product at these doses didn't do anything for me. NOW Foods has very reasonably priced products, but there are probably several ways of making a herbal extract and a wide range of effectiveness between brands, so I'm tempted to try a couple of different brands before concluding the experiment.

The active ingredients in Ashwagandha are supposedly the withanolides, so in theory, any product that contains a sufficient amount of them should give similar results. Nonetheless, based on other people's experiences, some brands may be more effective than others. If you have personal experiences (positive or negative) with Ashwagandha, please share them in the comment section. Specifically, if you can recommend a brand that worked for you – preferably one that is available at iHerb – I will consider trying that product next.

For more information on nootropics and cognition, see these posts:

60 Minutes on Boosting Brain Power
Nootropic Battle Conclusion: Acetyl-L-Carnitine vs. Ginkgo Biloba vs. Taurine
Green Tea Protects from the Psychological Effects of Stress in Rats
Does Ginkgo Biloba Improve Cognitive Performance?

The Twinkie Diet: Thoughts on Weight Loss and Cholesterol

You can lose weight on any diet, but is it healthy? (Photo by OkayCityNate)

A few days ago, CNN reported on a nutrition professor who lost 27 pounds in ten weeks eating mostly Twinkies (link). Not only that, but health markers improved too – LDL went down and HDL went up.

Some people seem to think the results resolve the old question of whether calories are all that matter in weight loss. After all, if you can lose weight by eating Twinkies, Doritos and Oreos, what else could it be than calories? Surely that's just about the worse diet you can have.

While I'm obviously a big fan of self-experimentation, I think the results have been misrepresented in some cases. What do I mean by that? Let's look at the experiment and the results a bit more closely. Here's a quote from the article:

For a class project, Haub limited himself to less than 1,800 calories a day. A man of Haub's pre-dieting size usually consumes about 2,600 calories daily. So he followed a basic principle of weight loss: He consumed significantly fewer calories than he burned.

If we take the 2,600 calories daily as the correct figure, then for the ten weeks, Haub was running an 800 calorie deficit. It's hardly surprising that he lost weight. When you cut back enough on your energy intake, you start losing weight – in this sense, a calorie is a calorie.

But since this is an experiment with only one participant, it's impossible to say whether more or less weight would have been lost if the diet had been different. Did all the sugar he was eating prevent him from losing the maximum amount of body fat? There's no way to tell.

There are some hints, however, that it's not all about calories. The amount of calories consumed may be the primary factor in how much weight or fat is lost, but that doesn't rule out other factors. In rats, for example, green tea increases weight loss during calorie restriction. The rats consuming green tea burned more of their body fat and absorbed less fat from the diet, despite eating the same amount of calories.

In real life settings, the argument that a calorie is a calorie is difficult to examine, because the number of calories we burn is not constant – it depends on many variables. We now know, for instance, that genetics play a role. Some people have a hard time putting on weight, because the more they eat, the more calories they burn. They may get an urge to exercise more, for example. And anyone who's tried different diets knows that some foods make you more energetic than others, despite having a similar number of calories.

But that's not all. Some people don't put on weight even when exercise is forbidden. Their bodies just start using all that excess energy in other ways: increasing metabolic rate, heat production, etc. Is a calorie really a calorie in this case?

Then there's the question of how to count the absorption of calories from different macronutrients. If you divide people into two groups and feed both the same amount of calories, but have one group eating more protein and the other group eating more carbohydrates, their weights will be different. In general, high-protein diets result in more weight loss than high-carbohydrate diets.

As you can see, the question is hardly as simple as some people make it out to be. And there are more similar things that complicate the issue. Stephan from Whole Health Source has a good post on the Twinkie diet and how it relates to hormones and fat mass regulation, and I'm sure there are other health bloggers who have picked up on the same article.

Putting the calorie issue aside, perhaps the thing that aroused the most interest was the part about improved biomarkers. Sure, you can lose weight eating a terrible diet, as long as your eating very little, but shouldn't that wreck your health in other ways? Apparently not:

Haub's "bad" cholesterol, or LDL, dropped 20 percent and his "good" cholesterol, or HDL, increased by 20 percent. He reduced the level of triglycerides, which are a form of fat, by 39 percent.

But that's not really big news. You see similar things happening in many studies where the participants are put on weight loss diets, regardless of what the diets are like. Even in the studies where overweight people are put on the conventional low-fat, high-carb diet – which is not really a good approach for improving cholesterol levels, glucose and insulin – these health markers improve while they're losing weight. As a spokeswoman for the American Dietetic Association says in the article:

"When you lose weight, regardless of how you're doing it -- even if it's with packaged foods, generally you will see these markers improve when weight loss has improved," she said. 

However, as in the case of the amount of weight lost, there's really no way to tell based on this experiment whether his health markers would have changed differently on another diet with the same calories. Low-carb and low-fat diets have very different effects on cholesterol during a calorie deficit, for example (note also how the subjects lost more weight during the low-carb diet despite eating more).

Since the study only lasted for ten weeks, the fact that his LDL and triglycerides decreased while HDL increased doesn't say much about the long-term effects. I wonder what his cholesterol levels would have been after a year of following the Twinkie diet.

Also, there's more to cholesterol than just LDL, HDL and triglycerides. In the case of lipoprotein particles, size matters. A diet consisting mostly of sugary snacks is probably not going to do a whole lot of good for LDL particle sizes in the long run. And even when HDL and LDL levels look good on the surface, there's oxidized LDL and lipoprotein (a) to worry about.

What we can say with some certainty is that regardless of how you do it, returning to a normal weight seems healthier than being obese. In the maintenance phase, which lasts much longer, more things should probably be taken into consideration. Haub himself seems to have mixed feelings about his experiment:

"I wish I could say the outcomes are unhealthy. I wish I could say it's healthy. I'm not confident enough in doing that. That frustrates a lot of people. One side says it's irresponsible. It is unhealthy, but the data doesn't say that."

While the health markers are interesting, it would have been interesting to hear more about his experience in general. How did he feel before, during and after the diet? Was he feeling energetic or tired? How was his mood? Did he have any problems, digestion, bad skin, etc?

Before you kickstart your own Twinkie diet, note that professor Haub also had a multivitamin and a protein shake daily, which may have influenced the results somewhat. And if you've already tried a strange diet and managed to lose weight, drop a comment and tell us how it went.

For more information on diets and weight loss, see these posts:

Alternate-Day Feeding and Weight Loss: Is It the Calories Or the Fasting?
A Year of Intermittent Fasting: ADF, Condensed Eating Window, Weight Loss, And More
Green Tea and Capsaicin Reduce Hunger and Calorie Intake
Green Tea Extract Increases Insulin Sensitivity & Fat Burning during Exercise

Tretinoin Results After a Year – Experiment Update

Retinoids – one of the better ways of looking young. (Photo by eisenbahner)

Some of you have been asking for an update on my experiment with retinoids. Now that I've gone through my first tube of tretinoin, it's time to review the results.

As I mentioned in my review of the anti-aging benefits of retinoids, I have both tretinoin cream (0.05%) and tretinoin gel (0.05%). I decided to go with the cream first, applying it only on the left side of my face. The right side has therefore acted as the control side.

Looking back at the first post on this experiment, it seems it's been over a year since my order arrived. Given that I've used the cream regularly and actually stuck with the experiment more strictly than with some other experiments of mine, it strikes me as odd that I only finished the 20 gram tube a few weeks ago. Granted, I have applied only a small amount and only on one half of the face, and I've had some breaks, but still, a little really seems to go a long way in this case.

I use the cream either nightly or every other night after washing my face and before going to bed. This seems to be the most common way to use retinoids. However, contrary to what is recommended, I often apply the tretinoin after a shower. The reason why this is not recommended is because after a hot shower, the pores of the skin will be open, and the peeling and redness that sometimes result from retinoids may be worse.

For me, this is a positive thing and a good a reason to use retinoids after a shower, since the absorption of the retinoids will be increased. I don't get much redness or peeling with the 0.05% strength anyway, unless I apply it to very sensitive areas. For example, I've tried it below the eyebrows, close to the eyelids, where the skin is very thin, and it was a rather painful experience. Applying tretinoin under the eyes is not problematic, though.

In my first post on retinoids I included a list of benefits that I'd seen mentioned in the literature. Here's the list again, along with a comment on whether the claim has been true so far in my case:

• Increased skin thickness and firmness – YES
• Increased skin hydration – NO
• Increased skin tolerance to external factors – NOT SURE
• Reduced visible signs of sun damage – NOT APPLICABLE
• Reduced fine wrinkles – NOT SURE
• Restoration of even skin tone and reduced hyperpigmentation – YES
• Reduction in dark circles under the eyes – NOT APPLICABLE
• Reduced skin roughness – YES
• Reduced irritation from shaving – NOT APPLICABLE
• Less risk of skin cancer – NOT APPLICABLE
• Reduced stretch marks – NOT APPLICABLE
• A healthy, 'rosy glow' – NOT SURE

As for skin thickness, I can't really be sure, as it would have to be measured with professional equipment. Skin firmness is one of those things that I notice after applying tretinoin and even in the morning. My face just feels kind of tighter on the side where I've applied it. The feeling tends to go away after a few days of not using the cream, though.

Skin hydration is another thing I don't really know how to estimate properly. One thing I do notice is that the left side of my face is quite often dry the next morning, which is a result of the peeling effect. It's not painful, however, and putting on some moisturizer gets rid of the problem.

I assume that by "external factors", things such as pollution and maybe UV rays are meant. Since I haven't burnt in the sun lately, and there's not much pollution here, I can't really say whether there has been an effect or not. I also don't have visible signs of sun damage (although I'm sure some internal, non-visible damage does exist), so I can't comment on that. I would expect this to be one of the areas where tretinoin is most effective, however.

The reduction of fine wrinkles is a tricky one. I've been trying to observe changes in three things during the experiment: fine forehead wrinkles, crow's feet (the wrinkles next to the eyes), and nasolabial folds. The fine lines on my forehead have not changed either way. I have to look pretty close to see them, but they are the same on both sides of the face.

The crow's feet, on the other hand, have gone through various changes. They too are visible only if I look very closely, but on the left side of the face they've gone from good to worse to better. At first, it seemed like they got deeper with the peeling, but now the skin looks somehow different compared to the other side, and I'm inclined to say the fine lines are less visible. A similar thing is happening with a few fine lines on my lower eyelid, very close to the eye, where I've applied the cream only randomly. It does indeed seem worse now than the right side. I think this is consistent with how retinoids work – they thin the dry outermost layer of the skin but eventually thicken the dermis and epidermis. This, along with the exfoliation, can make things look worse in the beginning.

As for nasolabial folds, they are not very deep but nonetheless visible. I haven't seen much change there, unfortunately, and sometimes I feel like the left side looks better, while other times I see no difference. I know there are many people who wonder whether retinoids can help with nasolabial folds (and many who believe they can't), but more time will have to pass before I can make a proper evaluation.

I don't have skin cancer, stretch marks or even irritation from shaving, so I can't really comment on those. The dark circles under my eyes have changed more drastically as a result of other lifestyle changes such as diet, so it's hard to see much difference there either.

The biggest difference for me has been in skin tone and skin roughness. It may not be visible to other people without me pointing it out, but I immediately see the difference in the mirror. I never even thought about skin tone and hyperpigmentation before, but I see now that the left side of my face has a much more even tone and looks smoother than the right side. There is indeed a slight "rosy glow" on the skin over the cheek bone, but otherwise there is no redness – unlike on the right side, where the tone is less even and slightly red. The pores of the skin also seem smaller on the left side, including the nose. In general, it just looks healthier and better.

So there you have it, my experience with retinoids so far. I've tried a lot of different stuff and written about it here, but this is the clear winner. For once, the results are actually visible. I'm now going to start applying tretinoin on both sides of the face, probably trying the gel version next. Since my left side already has a head start, it'll be interesting to see how fast the right side can "catch up".

Oh, and for the Scandinavians out there looking for where to buy retinoids: I can't help you there. I ordered six tubes from alldaychemist.com over a year ago, but due to repeated problems with customs, they no longer ship to any Scandinavian countries. The same is true for other online drugstores I've tried. No luck.

That's a real shame, because their stuff was dirt cheap and of a high quality. What can I say, this is a perfect example of the long-term effects of the Scandinavian socialist mindset – no one is responsible of their own actions, the government takes care of everyone, the bureacurat knows better than you.

EDIT: I almost forgot; I've also applied tretinoin to my left temple, and it looks like there are a couple of new hairs growing. This is the same temple that had some new hair growth with retinol, the milder version of retinoids. Those hairs are still there, but they don't grow very long – not exactly like vellus hairs but not terminal either. And I think my left eyebrow has some more hairs than the right one, although the difference is slight.

For more information on skin care, see these posts:

Topical Retinoids Increase Hair Growth in Most People
BioSil, JarroSil & Beer – Silicon Experiment Conclusion
Topical Vitamin C for Skin: Re-examining the Case
Lutein for Skin Elasticity, Hydration and Photo-Protection – Experiment Begins