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?

My Current Health Regimen v2.0

One of the changes has been an increased intake of fruit and vegetables. (Photo by YimHafiz)

This is my updated health regimen, aimed at adding a significant number of healthy years to my expected lifespan. As it's subject to change, I will keep this post updated accordingly. Major revisions (such as v2.0) will appear once a year or so; minor changes (such as v2.1) will be made as needed. With every major revision, I will move the post from the archives to the front page.

Since a long, healthy life is preferable to a short life by most people, following the regimen would make sense even without considering technological innovations. The true goal of my regimen, however, is to stay alive long enough to see rejuvenation therapies become a reality. In the long run, each year that I'm able to add to my expected lifespan now through things like dietary changes, exercise, and supplements, may grant me several extra years in the future.

Therefore, even those lifestyle changes that require considerable effort and resources while offering a seemingly limited benefit, make sense if one looks at the big picture. For a chance to see the world in 2090, I'm willing to skip the cheeseburger today.

My health regimen consists of four categories: diet, supplements, physical exercise, and brain health. All of the items under each category have some kind of scientific basis, and in contrast to my ongoing experiments, will remain a part of the regimen for the time being. Therefore, my current experiments are not a part of my long-term health regimen – unless they prove to be beneficial, in which case they'll be moved from ongoing experiments to the regimen.

Main changes from v1.0: none.

Avoiding harmful foods

The most important part of my diet is avoiding unhealthy things; increasing the intake of healthy things only comes in second. This is because preventing damage from happening in the first place is easier than repairing it later on.

I consider the worst culprit of modern diets to be an emphasis on grain products, fructose, and polyunsaturated fatty acids. There's considerable evidence to suggest that most people would do much better without them. Hence, things like pasta, rice, bread, candy, fruit juices, and most vegetable oils are off the daily menu. I only eat them rarely, and then simply because they taste good. For the past few months, I've allowed myself to eat whatever I want once a week (usually foods like pizza or fresh bread), which seems to be working well.

I originally cut back on my fruit intake, which used to be quite high some years ago, because I learned that fructose increases triglycerides especially in men, and fructose is not handled very well by the body in general. I later learned that fructose also forms AGEs much more rapidly than glucose, which kept me from reintroducing most fruits to my diet and eat berries instead, since they contain more nutrients per fructose calorie. However, I've now increased even my fruit intake a little, having read more about the AGE-inhibiting effects of phytonutrients found in fruit. I will expand on this later, but for an example of what I'm talking about, see my post about carotenoids inhibiting lipid peroxidation.

While much of this fits well with paleo dieting, I also diverge from the paleo diet these days. You may or may not remember that I used to be a potato hater back in the day, both because they could not be eaten raw (making them anti-paleolithic) and because of their high carb content. Basically, potatoes are just empty calories. But once you have your insulin sensitivity and blood glucose under control, I don't think a few potatoes now and then is much of a concern. At least they're low in fructose.

As you may recall, I followed a low-carb diet for the past year with an emphasis on paleo foods. I got on the low-carb, high-fat wagon in the first place to prove that eating a diet high in fat does not make you fat – and it didn't. However, this diet combined with my year-long intermittent fasting experiment resulted in a moderate-to-high intake of protein, the longevity effect of which I'm now questioning. To lower my protein intake slightly means eating either more fat or more carbohydrates, and since my fat intake is already very high, I've reintroduced some carbs into my diet. That is, I now occasionally eat potatoes not because I think they are necessary for health, but because they are low in protein. More on protein and longevity in future posts.

I still don't make nuts a dietary staple, because of their poor omega-3/omega-6 ratio and because I like to keep my PUFA intake low. That is, I aim not only for a good ratio of omega-3 and omega-6 fatty acids, I try not to eat too much of them in general. Omega-3 is particularly prone to undergo lipid peroxidation, and while nuts probably have micronutrients that protect them from oxidation to some degree, I'm playing it safe until I learn more.

Main changes from v1.0: slightly increased carb intake, slightly decreased protein intake, slightly decreased polyunsaturated fatty acid intake.

Eating healthy foods

Despite eating some more carbs these days, my diet is still fairly low in carbohydrates. My daily intake used to be around 100 grams; I have not measured my current intake, but I suspect it's around 100-150 grams these days. My main protein sources used to be meat, fish and eggs, but during the past year I've cut back on eating eggs because of their high methionine content. I'm still figuring out whether methionine restriction makes sense in humans, but in the meantime I limit my egg intake to 3-4 eggs a week.

Sources of fat, in the order of importance, are olive oil, palm oil, butter, cocoa butter, coconut milk, ghee, coconut oil, and sesame oil. Olive oil tops the list because I love the taste and because it's high in MUFAs but low in PUFAs and consistently does well in just about every health study. There may not be anything magical about MUFAs per se, but even if it's the polyphenols in olive oil that are behind all the positive health effects, olive oil still seems like a good choice. Palm oil is there because it's rich in tocotrienols (at least compared to other natural foods), low in PUFAs and high in SAs (making it suitable for heating), and because I've grown to like the taste.

Lard is off the menu for now because I ran out. Heavy cream has been replaced by coconut milk, partly because of dairy products increasing IGF-1, which may be bad for longevity (more on that in future posts). I don't eat cocoa butter raw (although I could, it's delicious), but I get plenty from all the dark chocolate I eat. Somebody asked me in the comment section why I eat sesame oil since it contains quite a bit of PUFAs, and noticing this was indeed so, I was going to remove it from my diet altogether. However, doing some reading I found that sesame oil seems to reduce markers of lipid peroxidation, so I kept it on the menu. I just use it for taste, however, so my intake of sesame oil is very low anyway.

Depending on my daily menu, anywhere between 50 to 70% of my total calorie intake is from fat. My daily menu has changed a bit, but percentage of fat is still the same. Most of this is saturated fat, which has been given a bad rep for reasons I believe are incorrect. I began reducing grain products and increasing my saturated fat intake years ago, and it hasn't killed me yet. In fact, my HDL has increased and my LDL has decreased on this diet. Triglycerides are not bad but could be better – a testament to my main vices, beer and wine.

There is one cereal grain I regularly eat, however: rolled oats. They're a convenient source of beta-glucan, which appears to be good for cholesterol and avoiding heart disease, and they don't contain gluten. Oats also contain quite a bit of quality protein. I used to eat them with milk and berries, but then switched to a combination of heavy cream and water to reduce my consumption of lactose and galactose (which easily form advanced glycation endproducts, AGEs). Now, I've stopped adding even heavy cream, because milk protein seems to interfact with the polyphenols in berries. So it's a mixture of coconut milk and water nowadays – not as good as cold milk, but still pretty good.

As for red meat, despite how it's portrayed in the media these days, I'm not convinced that meat consumption is harmful. Indeed, a recent review supports the hypothesis that processed meat, not meat in itself, may be harmful. The biggest problem I used to see with meat is the generation of AGEs. Though there is disagreement just how harmful consuming AGEs with food are, I tried to minimize the potential damage by avoiding overcooking and taking supplements. I no longer think AGEs in meat are a huge problem, however – more on this later. The reason I don't eat huge portions of meat like I used to is because of the high protein content.

And finally, the beverage department. I still love my daily coffee, which I drink 1-2 cups per day. Coffee has some nice health benefits too. Green tea is obviously staying on the menu; the studies showing positive health effects just keep on piling up. All in all, beer doesn't really belong to the "eating healthy foods" category, but even beer does contain some good stuff.

As you may recall, I used to drink yerba mate with meals to reduce the formation of AGEs. It's since come to my attention that yerba mate is carcinogenic at higher doses, so I now drink it only rarely. Green tea or black tea are safer bets, despite somewhat contradictory results in reducing AGEs and ALEs.

Main changes from v1.0: decreased egg intake, changes in the use of fats and oils, reduced yerba mate consumption, avoidance of lipid peroxidation.

A note on diet tweaking

It's much easier to point out things that are wrong in various foods than it is to prove something is healthy. These days, I'm more wary of advertising my diet as the best choice for everyone than I was before. Part of the reason is that the more I read and learn about nutrition, the more complicated everything becomes.

Case in point: I used to tell people vegetables are bad because, as an evolutionary strategy, they produce toxins to protect them from being eaten (which is true). Now, having learned of the importance of hormesis, I think vegetables are good because of those same toxins! I was also a huge fan of eating fruit (especially organic fruit) at one point, because it seemed to make sense from an evolutionary point of view. The, I got a little skeptical towards them because of their fructose content. Now, I think the benefits may outweigh the negatives.

All this, however, doesn't stop me from wanting to find the optimal diet for longevity. On the contrary, it's a healthy reminder not to get too emotionally attached to my health regimen, and to be ready to admit mistakes and make alterations as I learn more.

Going without food

The third key component of my diet used to be intermittent fasting. I stated in the first version of this post that "I may change my mind in the future, but for now I expect periodic food deprivation to remain in the regimen." That is still true to some degree: I no longer do a 24/24 hour cycle of fasting and eating, but I don't make it a point to eat three meals with snacks a day either. I often skip breakfast and lunch and eat only dinner.

The thing that lured me to try intermittent fasting was that there are studies suggesting that all or most of the benefits of chronic calorie reduction can be had by alternating zero calories with double the normal calories every 24 hours. While I no longer believe that IF is equivalent to CR, I do think that fasting in general is beneficial. An improved insulin sensitivity is a known result of intermittent fasting. Insulin sensitivity is associated with longevity, and among supercentenarians, insulin sensitivity is common.

Perhaps a more interesting thing about fasting is that it increases autophagy, a process in which the cell consumes a part of itself for energy. This can happen during ordinary cell maintenance, or when the body is deprived of nutrients. Since improved autophagy is at least in part why caloric restriction works, this makes other, less demanding forms of nutrient deprivation attractive options.

The reason I stopped doing strict IF is because I don't think there is much evidence that fasting for 24 hours and then eating for 24 hours is somehow optimal in itself. Most importantly, IF does not extend lifespan in most studies. Why IF is not equivalent to CR is not clear, but recent studies suggest protein may have a lot to do with it. My intermittent fasting diet resulted in huge meals with lots of protein, and I now suspect that this may have diminished much of the potential benefits.

Main changes from v1.0: no more 24/24 intermittent fasting, no more huge protein-heavy meals.

Supplements

The most important supplement in my regimen is vitamin D3. Most people are deficient in vitamin D, and the health benefits are so overwhelming that if there's one supplement I would recommend spending money on, it's vitamin D3. I usually take 5,000 IU of vitamin D3 daily, and at last check, my levels were at 45 ng/mL, which is in the optimal range. Now that it's summer, I'm taking 2,500 IU daily. I know some people take the same amount all year round, but since I do spend some time in the sun, I don't want to overdo it.

One of the supplements that has remained in the regimen since last time is vitamin K2, which is sort of a newcomer in the supplement scene but nonetheless has some impressive studies behind it. I'll write more about it in the future, but here's one study of interest for men: dietary vitamin K2 may reduce prostate cancer. Since fermented dairy products, which I'm not sure are the best choice for health otherwise, are the best dietary source of vitamin K2, I'm taking supplements instead. At the moment, I take 90 mcg of MK-7 (Jarrow MK-7) and 5 mg of MK-4 (Carlson Labs Vitamin K2) every third day in an attempt to find a balance between affordability and the long serum half-life of vitamin K2.

I used to take a tablespoon of fish liver oil daily, because it has lots of omega-3 fatty acids in bioavailable form (EPA and DHA) and almost no omega-6 fatty acids. A higher dietary ratio of omega-3 to omega-6 seems to be very beneficial in general, and fish oil has been shown to decrease inflammation. A commonly quoted optimal ratio is between 1:1 and 1:4, which seems to be close to how our paleolithic ancestors ate. As part of my plan to avoid excess PUFAs, I've dropped fish liver oil from the menu. I'm currently in the process of weighing the pros and the cons; it may be that a tablespoon per day will prove to be worth it in the end.

I also used to take resveratrol with quercetin during fasts to increase autophagy. I would still continue to take them, but unfortunately I can't afford all the supplements I might like to take (including AOR Ortho-Core, which is off the list for the time being), so I take resveratrol only occasionally. Meanwhile, I'm on the lookout for other things that increase autophagy. Curcumin is a cheap alternative, and it has other health benefits too, which is why I add turmeric to most of my foods.

Since my damn blender keeps leaking from the bottom, I'm no longer making smoothies every day like I used to. So these days I just add some ground flax seeds to my rolled oats for the flax lignans. Flax lignans may prevent hair loss, among other health benefits. Some people prefer to take them in supplement form, but flaxmeal is a cheaper and equally effective way to consume flax lignans. For best effects, they should be consumed twice a day with ~12 hours in between. Other things I do to prevent hair loss is use shampoos with ketoconazole and piroctone olamine.

Main changes from v1.0: no more fish liver oil, some supplement cutbacks due to costs, increased curcumin intake.

Exercise

My exercise routine is probably the weakest part of my regimen, compared to how much effort I put into diet and supplements. In the summer, I run for 30-45 minutes once a week to get some aerobic exercise (I should start again, since summer is here!) The goal is to keep the heart and lungs healthy, reduce blood pressure, and improve mood. In the winter, when it gets too cold for running outside, I go to the gym for strength training instead. Strength training reduces the risk of injury, prevents osteoporosis, supports joint health, and prevents muscle loss resulting from aging.

I also practice martial arts, which combines aerobic and strength training, to a degree. The main reason for me, however, is that it provides me with a basic set of self-defense skills and improves coordination. With aging, there is usually an increased fear of falling and hurting oneself – something children naturally don't have. Getting thrown around every week is a way to maintain a healthier attitude towards my body and prevent an irrational fear of getting hurt. I want my mind to rule over my body, not the other way around.

Main changes from v1.0: none.

Brain training

Any anti-aging regime should also take into account the importance of maintaining mental health. It doesn't take a genius to see that people who use their brains actively retain their cognitive abilities far longer than those who are passive.

One of the ways I keep the rational side of my brain fit is reading scientific papers and writing about them on this blog. I like logical problems in general, and I think practicing problem-solving skills are important for everyone, whether it's through work or hobbies. To train the creative side, I do things like play instruments, compose music, and read and write fiction.

My biggest problem is and always has been rather poor short-term memory. I don't know whether it's because my mind is always occupied with a zillion things, but it's more than once that I've gone to the grocery store to buy something I need and come back with something else entirely. This kind of absent-mindedness seems to run in the family. I believe it can be improved through training, however. The memory game experiment intends to increase IQ, but it improves short-term memory as well (I've pretty much forgotten about this experiment lately, by the way – I'll have to start playing again!)

Main changes from v1.0: none.

Quick summary of the health regimen

As a part of my diet, I regularly eat the following foods:

- Meat, fish
- Olive oil, palm oil
- Butter
- Vegetables, berries, fruit, oats, dark chocolate, coconut milk
- Coffee, tea, wine, beer

I limit or avoid eating the following foods:

- Grain products like pasta, bread, and rice
- Fruit juices, candy
- Vegetable oils high in PUFAs

In general, my diet is high in fat and lowish in carbohydrates. I consume saturated fat and monounsaturated fat liberally but limit polyunsaturated fats.

My supplement regime consists of the following:

- Vitamin D3: 2,500-5,000 IU daily
- Vitamin K2: 90 mcg of MK-7 and 5 mg of MK-4 every third day
- Varying amounts of green tea daily
- Flax lignans: 1-2 tablespoons of ground flax seeds daily

My physical health regime consists of martial arts, running (in the summer), and strength training (in the winter). For mental health, I do things that train the creative and logical sides of the brain.

For more information on anti-aging methods and living longer, see these posts:

Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol
How to Live Forever: My 5 Steps to Immortality
L-Carnitine, Acetyl-L-Carnitine and Cognitive Function in Humans
Caloric Restriction Improves Memory in the Elderly

60 Minutes on Boosting Brain Power

Drugs like Adderrall and Ritalin are becoming more and more popular as brain boosters.

Yesterday, 60 minutes ran a segment titled "Boosting Brain Power" (link). It's about students taking drugs such as Adderrall and Ritalin to enhance their cognitive performance.

Adderrall is a prescription drug used to treat ADHD. It's a combination of amphetamines, which is why it decreases fatique and increases alertness, concentration and even libido. By boosting dopamine, amphetamine also tends to make people more motivated and interested in what they're doing. No surprise it's popular among students these days.

So popular, in fact, that according to 60 minutes, more than half of juniors and seniors at the university have tried attention deficit drugs for neuroenhancement. Only about 4% of the students actually have a prescription for them, but since doctors tend to prescribe more pills than the patients are taking, they're left with extra pills that then get distributed around campuses. For Adderrall, the market price is up to $5 per pill.

Although that might seem expensive, the students using smart drugs think it's an acceptable price to pay for better grades. The consensus seems to be that the drug is effective even in people without ADD or ADHD, and that there's nothing wrong in taking a drug to boost cognitive performance.

I find the generally positive attitude of the students a very good thing. I think nootropics and brain enhancement will become more and more mainstream as people begin to realize how much they can increase their own productivity. Sure, there will be skeptics, and once the bureaucrats get a clue of what's going on in colleges and universities, there will probably be more attempts at regulating nootropic use.

Together with potential long-term harm such as addiction, the general objection to smart drugs seems to be that it makes things less fair (see the comment section of the article for examples). As one student comments:

I feel that it is an unfair advantage. If the person next to me that has the exact same schedule takes an Adderall they can stay up the entire night knowing the material and come in and make a grade better than me.

This attitude is usually based on the idea that we should make people equal in all aspects of life. Since you can simply pop a pill to get a better grade, everyone who wants to compete would have to take one, so why not ban them to prevent unfairness?

The fallacy here is that people are not created equal in the first place – some are born smarter than others, some are willing to work harder than others, some have skills others don't, etc. There is no way to truly make people equal. We're not making it illegal for hard-working students to study more than their peers, nor are we forcing intelligent people to take stupid pills. So why should we ban nootropics?

Some people say that there's a difference to studying hard and taking a smart drug, because the former requires honest work and the latter is somehow "cheating". It is true that those taking Adderrall or some other drug may have an advantage compared to those not taking it, but so what? Surely increasing people's cognitive function is a good thing, even if there are those who don't want to do so. Is it cheating to get a good night's sleep before an exam or to eat healthily?

Once smart drugs become the norm – and in some campuses, they already are – people will still have to work hard to get good grades, because the general level of competition will go up. The end result, however, is that people will be smarter and more productive.

For those who wish to cling to some strange ideal of accepting nature as it is, I have only one question: What is more admirable, to be lucky enough to be born with good genes or to do everything in your power to be as good as you can be?

Besides, the world is already full of things that boost brain performance. Caffeine is probably the most famous one. Are those who are opposed to using Adderrall also against drinking a cup of coffee or a Red Bull before an exam? And, even though smoking is banned in many places, you can slap a nicotine patch on your arm and gain a similar "unfair advantage" without anyone raising an eyebrow. But for some reason, people accept old things as given and view new things with irrational suspicion.

The nootropic meme is spreading so fast that it's not just the students who view nootropics in a positive light – even the professors and lecturers are now admitting to taking stimulants to enhance their brains.

If you're still skeptical about nootropics, try to think of the good side. Yes, some of them are indeed addictive (like caffeine) and have side effects, and you shouldn't start popping pills randomly without reading about them first. But not everything that gives you an edge is harmful; some smart drugs are even neuroprotective against things like Alzheimer's disease.

Who knows, maybe they could even help you finish that book you always wanted to write, like the economics teacher at Harvard interviewed in the video.

For more information on nootropics and brain function, see these posts:

The Many Health Benefits of Rooibos Tea
Ashwagandha as a Nootropic – Experiment Begins
Nootropic Battle Conclusion: Acetyl-L-Carnitine vs. Ginkgo Biloba vs. Taurine
Green Tea Protects from the Psychological Effects of Stress in Rats

The Many Health Benefits of Rooibos Tea

Oxidation gives rooibos its familiar reddish colour. (Photo by Smaku)

The herbal tea made from rooibos has been a popular drink in Southern Africa for generations. The plant, Aspalathus linearis, is grown only in a small area in the Western Cape province of South Africa, but during recent years rooibos has become popular in other parts of the world as well.

Though not technically a tea, the infusion made from oxidised rooibos leaves is commonly referred to as rooibos tea. Traditionally, it is enjoyed hot with a slice of lemon and sugar or honey, but iced tea versions and even a rooibos espresso made from concentrated rooibos are apparently gaining popularity.

While many people have acquired a taste for rooibos and know that it is considered something of a health drink, most of us are clueless as to what exactly the health benefits of rooibos are. In this post, we'll review what the studies say on rooibos tea.

The antioxidant activity of rooibos tea

Like regular tea, rooibos tea contains flavonoids which act as antioxidants. While the most beneficial flavonoids of green tea are catechins such as epigallocatechin gallate (EGCG), the main flavonoids in rooibos tea are aspalathin and nothofagin. One in vitro study found that aspalathin is even more effective at scavenging free radicals than EGCG (link) – a rather surprising result, given that just about everyone knows about antioxidants in green tea but not in rooibos tea. All in all, green tea still seems to beat rooibos tea in antioxidant activity, however (link).

The second flavonoid tested, nothofagin, was not as effective as quercetin but still potent. Oddly enough, an older study found that aspalathin and nothofagin can also act as pro-oxidants under certain in vitro conditions (link). The authors comment:

Fermentation (i.e., oxidation) of rooibos decreased the pro-oxidant activity of aqueous extracts, which was contributed to a decrease in their dihydrochalcone content. The in vitro pro-oxidant activity displayed by flavonoid-enriched fractions of rooibos demonstrates that one must be aware of the potential adverse biological properties of potent antioxidant extracts utilized as dietary supplements.

This is not a unique case, however. Vitamin C, probably the most famous antioxidant, has also been said to act as a pro-oxidant in some conditions in vitro; there is much less evidence to suggest it does so in vivo, however (link).

Feeding normal, healthy rats given rooibos tea instead of water had significantly higher serum superoxide dismutase (SOD) levels than the control rats (link). They also had less DNA damage, a result that confirms the findings of an earlier study (link). Futhermore, when the rats were given dextran sodium sulfate to induce colitis, the rooibos group had higher SOD levels, and the drop in hemoglobin levels seen in the control group was prevented. Thus, rooibos tea seems to be anti-inflammatory and have the potential to prevent DNA damage.

The cardiovascular benefits of rooibos tea

Due to their effects on vasodilation and vasoconstriction, angiotensin I-converting enzyme (ACE) inhibitors and nitric oxide (NO) are used to treat conditions such as high blood pressure and heart failure. In one study, the effect of green tea, black tea and rooibos tea on ACE and NO was compared in healthy human volunteers (link). None of the three had a marked effect on NO concentration, but both green tea and rooibos tea inhibited ACE activity, suggesting that they have cardiovascular benefits. This is in contrast to an earlier in vitro study which found that only green tea and black tea inhibited ACE (link).

Closely related to cardiovascular disease is diabetes. The good news is that that rooibos tea may help with this as well. In a mouse model of type 2 diabetes, aslapathin suppresses the increase in fasting blood glucose levels. It also improves glucose tolerance, apparently through stimulating glucose uptake in muscle tissues and insulin secretion from the pancreas (link). Drinking rooibos tea during a meal may not be a bad idea.

Rooibos tea for liver disease and respiratory problems

In rats, rooibos tea aids in liver tissue regeneration after prolonged intoxication. Compared to the rats receiving water during the regeneration period, the rooibos group had less fibrotic tissue in their livers and lower tissue malondialdehyde levels. The authors conclude that rooibos tea "can be recommended not only for the prevention but also as a co-adjuvant for the therapy of liver diseases."

Rooibos tea also has therapeutic potential for respiratory ailments. According to a study on rats, in addition to lowering blood pressure, rooibos tea is both a bronchodilator and an antispasmodic (link, link). This helps explain why rooibos tea is commonly used for gastrointestinal and respiratory problems. The flavonoid chrysoeriol seems to be mainly responsible for the bronchodilator and antispasmodic effect.

Rooibos extract fights HIV

Rooibos tea extract seems to be helpful in antigen-specific antibody production by increasing interleukin-2 (IL-2) production in vitro and in vivo (link). According to the authors, rooibos tea intake "may be of value in prophylaxis of the diseases involving a severe defect in Th1 immune response such as cancer, allergy, AIDS, and other infections."

Another study found that an alkaline extract of rooibos tea leaves suppressed HIV-induced cytopathicity (link). Green tea extract, on the other hand, was ineffective. The authors conclude that HIV infection may be suppressed by the daily intake of the alkaline extract of rooibos tea. Note that the extraction mechanism is important here, because regular rooibos tea does not have anti-HIV activity (link). See the abstracts for details.

Rooibos tea, lipid peroxidation and brain aging

The uncontrolled oxidation of lipids, which can happen during cooking or inside the body, leads to the formation of advanced lipid peroxidation end-products (ALEs). The accumulation of such products is one of the types of damage that occurs with aging.

Lipid peroxides also accumulate in the brain. Rooibos tea may help prevent this damage, however. Rats given rooibos tea instead of water accumulate significantly less aging damage in the brain than rats given water (link). In fact, the 24-month old rats given rooibos tea for most of their lives had brains similar to young 5-week-old rats. This is quite a remarkable result.

One study found that out of the flavonoids tested, quercetin and EGCG (found in green tea) were the best inhibitors of lipid peroxidation, while aspalathin had a similar potency as catechin (link). Nothofagin was of no use here, however. Since polyunsaturated fats or PUFAs are especially prone to form ALEs, it seems like a cup of green tea or rooibos tea with a meal containing polyunsaturated fats might be useful.

The difference between red and green rooibos tea

Typically, rooibos leaves are oxidised before they are used to make rooibos tea. This process, which is not exactly the same as the fermentation process used in making black tea, gives them the familiar reddish-brown color and the slightly sweet taste. However, unoxidised rooibos tea is also available, if you know where to look. The color and taste are quite different; I personally prefer the red version, but green rooibos tea is not bad either.

Like in the case of regular tea, the oxidation process also affects the flavonoid content of the tea. Unoxidised rooibos tea contains more about twice as much total flavonoids as oxidised tea and 10-fold higher levels of aspalathin and nothofagin (link, link). In the studies that have directly compared the two, the unoxidised version seems to generally come out on top. For example, unoxidised rooibos tea seems to protect rats from liver cancer more effectively than oxidised tea (link). The antimutagenic activity of the two depends on the mutagen in question, however (link).

Summary

The health benefits of rooibos tea seem to be mostly due to the flavonoids aspalathin and nothofagin, although other compounds in rooibos may also play a part. Here's a summary of the benefits:

• Acts as an antioxidant and increases SOD levels
• Prevents DNA damage
• Cardiovascular protection through ACE inhibition
• Suppresses fasting glucose levels
• Improves glucose uptake and insulin secretion after a meal
• Aids in liver tissue regeneration
• Lowers blood pressure
• Acts as a bronchodilator and antispasmodic
• Inhibits lipid peroxidation and brain aging
• Rooibos extract improves immune defects such as HIV

Since nothofagin and especially aspalathin are not really found in any other plant, rooibos tea looks like a valuable addition to one's health regimen. Even people who are not fans of green tea usually like the taste of rooibos tea. Since rooibos contains no caffeine, it can be also enjoyed in the evening.

For more information on various teas and health, see these posts:

Hibiscus Tea Lowers Blood Pressure
Tea, Coffee and Cocoa: All Good for Your Teeth
Yerba Mate Inhibits AGE Formation
Drinking 3 Cups of Green Tea Increases Plasma Antioxidant Activity in Humans by 12%

Dietary Supplement Increases Lifespan by 11% in Healthy Mice

When will they start serving anti-aging cocktails in bars? (Photo by fanfan2145)

Declining physical activity with aging is seen in almost all species – just think of how much more active kids are than elderly people. This decline contributes to things like metabolic syndrome and frailty in old age. More importantly, life is less enjoyable in general when you're physically unable to do the things you could when you were younger.

To some degree, this process can be slowed down by physical activity itself. People who exercise tend to be more physically fit than people who don't. Nevertheless, no matter how active you are, the decline can only be postponed, not completely prevented. To retain our youthful vigor indefinitely, scientific breakthroughs in regenerative medicine are needed.

And yet, anything that is postponing the inevitable at this point might just prove to have been postponing what is evitable in the future. Stay healthy and stick around long enough and you might just see those breakthroughs happen in your lifetime. That's why anything that gives us even a few extra years of healthspan should be warmly welcomed.

Many people who are proponents of exercise are skeptical of using dietary supplements to increase healthspan, and rightly so: there is little if any evidence to show that popping a generic multivitamin will do any good. But what about a supplement that has a more scientific basis to it? A new study shows that a dietary supplement containing readily available ingredients ameliorates locomotor, neurotransmitter and mitochondrial aging in mice (link). It also modestly extends their lifespan.

Study design

The dietary supplement was developed with five factors related to aging in mind: oxidative stress, inflammation, mitochondrial function, insulin resistance and membrane integrity. A slurry of the supplement was soaked onto pieces of bagel and then given to normal mice and transgenic growth hormone mice (which show accelerated aging compared to normal mice). Here's the ingredient list:

Ingredient	Mg
Bioflavonoids	7.93
Vitamin A (beta-carotene)	0.22
Vitamin B1	0.31
Vitamin B3	0.31
Vitamin B6	0.61
Vitamin B9	0.006
Vitamin B12	0.02
Vitamin C	3.51
Vitamin D	.0002
Vitamin E	3.27
Rutin	3.05
Chromium picolinate	0.003
Magnesium	0.46
Manganese	0.19
Potassium	0.18
Selenium	0.0005
Acetyl L-carnitine	1.47
Alpha-lipoic acid	1.83
Aspirin	1.32
Coenzyme Q10	0.61
Cod liver oil	12.20
Flax seed oil	12.20
Garlic	0.04
Ginger root extract	6.00
Ginkgo biloba	0.18
Ginseng	6.31
Green tea extract	4.88
L-Glutathione	0.31
Melatonin	0.007
N-acetyl cysteine	3.05

The amounts of ingredients in the original data are given in "mg/day/100 mice"; presumably all the treated mice were allowed to eat from the same food lot, which would mean that the amount of ingredients eaten varied between mice. I've divided the numbers by a 100 here to show the average amount for each mouse. You can get the original data from the link to the study if you need it.

Effect on activity levels

According to the authors, when the untreated normal mice reached 24 months of age, their physical activity levels had dropped by more than half. The untreated normal mice are represented by the second line from the top (and I may be missing something here, but it doesn't seem like the decrease is over 50% in the graph – still, a significant drop). Normal mice given the supplement, on the other hand, were almost as active in old age as in young ages.


As you can see, the transgenic mice (represented by the two bottom lines) showed much lower activity in general than the normal mice, which is to be expected. In the untreated transgenic mouse group (the first line from the bottom), activity was pretty uniformly low with not much further decline from aging. In younger transgenic mice (the second line from the bottom), the supplement clearly increased activity, but by the time they reached 13 months, they were as inactive as the untreated group.

According to the authors, exercise duration generally declined with age, but remained higher in supplemented normal mice across all ages. Bouts of intense activity decreased with age even in these mice, but this was offset by increases in moderate activity.

Effect on protein carbonyls

Protein carbonyls, a marker of oxidative damage, correlate negatively with cognitive skills and activity levels. Protein carbonyl levels were lower in the brains of supplemented mice than in untreated mice. Although this kind of damage tends to correlate well with aging (link), the number of protein carbonyls in the brain did not increase with age in either group of normal mice. In transgenic mice, supplementation resulted in a non-significant trend for reduced carbonylation.

Mitochondrial protein carbonyls increased with aging in normal mice. Young normal mice had only 34% of the mitochondrial carbonyls seen in old normal mice, and supplemented normal mice had only 64% of the carbonyls seen in untreated normal mice. In untreated transgenic mice, protein carbonyl levels were the highest, while in supplemented transgenic mice they were the lowest of all four groups. For some reason there appears to be U-curve in the level of protein carbonyls in transgenic mice, with young and old mice showing higher levels than middle-aged mice.

The fact that the dietary supplement reduced protein carbonyls in the brain and mitochondria means that it was able to cross the blood-brain barrier and mitochondria. These are considered key goals of aging interventions. Indeed, supplemented normal mice had an 11% increase in lifespan. The authors think of this as a modest increase and suggest that the increases in physical and mitochondrial activity are the reason the mice didn't live even longer. I'm not sure the "higher metabolic rate = pro-aging" theory they hint at is correct, but nevermind: the fact that normal, healthy mice showed increased maximum lifespan is what's important.

Conclusion

A dietary supplement containing non-prescription ingredients ameliorated the age-related decline in physical activity in both normal and senescence-accelerated mice. The supplemented mice retained their physical activity more than non-supplemented mice and had lower levels of protein carbonyls, an age-related marker of oxidative damage. Importantly, an lifespan increase of 11% was seen in normal mice, showing that an "anti-aging cocktail" based on dietary supplements is feasible at least in mice.

For more information on aging and lifespan extension, see these posts:

Aubrey de Grey in Helsinki, Finland
Giving Heat Shocks to Roundworms Extends Lifespan by Almost 40%
How to Live Forever: My 5 Steps to Immortality
Drinking 10 Cups of Green Tea Daily and Not Smoking Could Add 12 Years to Your Life

Ashwagandha as a Nootropic – Experiment Begins

Ashwagandha, the 'Indian ginseng', shares some of the properties of Korean ginseng. (Photo by bartpogoda)

Ashwagandha is one of the plants used in Ayurvedic medicine. Also known as Indian ginseng, the scientific name of this nightshade family member is Withania somnifera. The latter part of the name means "sleep-inducing" in Latin, suggesting that the plant is used for its relaxing properties.

Ashwagandha is also said to be an adaptogen – a herb that increases the body's resistance to stress, anxiety and fatique by "normalizing" its functions. Before you dismiss the whole thing as new age garbage, let me point out that unlike some other Ayurvedic herbs, this one has been studied quite extensively. A pubmed search on 'ashwagandha' gives about 360 results.

Having browsed through the entire list, it appears that ashwagandha has a variety of effects on health. In this post, however, I will concentrate on the nootropic aspect of the herb. Bear in mind that I'm using the term in a very broad sense here: any paper examining the effect of the herb on cognition, mood, stress-relief, or motivation will be included. We'll save the studies on topics such as immune function for later.

The effect of ashwagandha on mood and libido

GABA, which is short for gamma-Aminobutyric acid, is the chief inhibitory neurotransmitter in mammals. GABA agonists – drugs that stimulate or increase the action at the GABA receptor – usually have a relaxing and stress-relieving effect. Alcohol is one such agonist. At least one paper has shown that ashwagandha contains an ingredient that activates the GABA receptor in a dose-dependent manner (link). Thus, the GABAergic activity may explain why many people report feeling more relaxed after taking ashwagandha.

GABA agonists are sometimes also used to treat psychostimulant addiction. Indeed, in animal models of drug addiction, ashwagandha apparently reduces alcohol intake and morphine tolerance (link). Ashwagandha itself appears to be well-tolerated: a review concluded that it has little or no risk of toxicity (link).

In a study that examined the role of stress in male infertility, 5 grams of ashwagandha root powder was given daily for 3 months to infertile men suffering from psychological stress (link). The treatment resulted in a decrease in stress levels and an increase in the level of antioxidants. At the same time, semen quality improved, which led to pregnancy in 14% of the subjects' partners.

Another study showed similar results, with reduced oxidative stress and improved sperm count and motility in infertile men (link). Testosterone levels increased significantly, while prolactin decreased. This is interesting, because prolactin counteracts the effect of dopamine. Dopamine is responsible for sexual arousal and motivation, while prolactin is thought to cause the sexual refractory period after an orgasm. High levels of prolactin cause impotence and loss of libido. The increase in testosterone and decrease in prolactin may therefore explain some of the claimed positive effects of ashwagandha on motivation and libido.

Some of the evidence on ashwagandha and libido is contradictory, however. When male rats were given 3,000 mg/kg of the root extract for 7 days, a marked impairment in libido, sexual performance, sexual vigour and penile function was seen (link). The authors state that since no change in testosterone levels was seen, the negative effects may be due to an increase in prolactin levels or the activity of GABA and serotonin. The increase in prolactin is interesting because it's opposite to what was seen in the study on humans. Note, however, that the dose used here was much higher than in the other rodent studies – perhaps the dose-response curve is U-shaped and more is not necessarily better.

Ashwagandha, stress and memory function

In mice, ashwagandha improves retention of a passive avoidance task (link). In this task, the mouse learns to refrain from stepping through a door to an apparently safer but previously punished compartment, which allows their memory to be assessed. The dosages used were 50, 100 and 200 mg/kg orally. The treatment also reversed the negative effects of scopolamine and electroconvulsive shocks on memory. Furthermore, mice and rats seem to do better on a forced swimming test when treated with ashwagandha (link, link).

Korean red ginseng, also known as Panax ginseng, is also called an adaptogen and shown to be helpful in treating stress. In a study comparing the two, both Panax ginseng and ashwagandha alleviated stress-related conditions such as sexual dysfunction, cognitive deficits and depression in mice subjected to footshocks (link). Ashwagandha was given orally in a dose of 25 or 50 mg/kg and was apparently more effective than Panax ginseng.

Acetylcholinesterase (AChE) is an enzyme that degrades the neurotransmitter acetylcholine, which is a facilitator of memory formation. AChE inhibitors increase the availability of acetylcholine, presumably leading to an improvement in memory. They can be extremely harmful in high doses: AChE inhibitors occur in natural venoms and poisons and are also used in nerve gases. However, AChE inhibitors are also used for medicinal purposes, for example to treat Alzheimer's disease. Huperzine A and galantamine, which are used for memory support and as nootropics, inhibit acetylcholinesterase. Ashwagandha appears to be an AChE inhibitor as well, with methanol extracts being more potent than water extracts (link).

In memory-deficient mice with neuronal atrophy and synaptic loss in the brain, withanolide A – an extract of ashwagandha – induced significant regeneration of nerve fibers and dendrites, as well as a reconstruction of pre- and postsynapses in the neurons (link). Treatment with the extract resulted in a reversal of the memory deficit. Two other extracts, withanoside IV and withanoside VI, appear to have similar effects (link). Ashwagandha or its extracts could thus be used to reconstruct neuronal networks.

Methanol extracts and withanolides are not the only useful part of ashwagandha, however. One study showed that even a withanolide-free water extract of ashwagandha roots had significant antistress activity (link).

Conclusion & my self-experiment

The evidence supports the claims that ashwagandha is an adaptogen and a nootropic. While there are no studies showing that ashwagandha improves mood per se, it does have a range of benefits.

The relaxing and anti-stress effect can be at least partly attributed to the fact that ashwagandha acts as a GABA agonist. It also improves stress-related memory problems by acting as a AChE inhibitor, and has the ability to prevent cognitive degeneration and even reconstruct neuronal networks.

Ashwagandha also seems to correct hormonal imbalances and reduced libido in men by increasing testosterone and decreasing prolactin. Very high doses may have the opposite effect, however.

For the purposes of my own human experiment, I have a bottle of NOW Foods' Ashwagandha extract. The bottle contains 90 capsules with 450 mg of root extract standardized to a minimum of 4.5% total withanolides. Once again, the measuring stick will be my own subjective evaluation of my mood, stress level and libido. Stay tuned for a conclusion of the experiment once I've finished the bottle.

Meanwhile, if you've tried ashwagandha, feel free to drop a comment about your experience. For more information on cognition, stress, mood and libido, see these posts:

Nootropic Battle Conclusion: Acetyl-L-Carnitine vs. Ginkgo Biloba vs. Taurine
Green Tea Protects from the Psychological Effects of Stress in Rats
The Effect of Maca Root on Energy and Libido – Experiment Conclusion
Caloric Restriction Improves Memory in the Elderly

10 Human Experiments of 2009 – Year in Review

One of this year's big themes among bloggers was vitamin D deficiency. (Photo by Gail S)

Only a few days left until the end of the year, which means it's time to take a look at the inhuman experiments of 2009. For a summary of the experiments of 2008, click here.

1. Maca root experiment

The purpose of this experiment was to see whether taking maca powder increased energy and sex drive. While those who sell the stuff claim that maca is the ancient Incan remedy for just about every problem you can imagine, the scientific evidence behind it is more modest. That said, a couple of studies have indeed shown improved libido and increased sperm count from maca, so the claims are not entirely baseless.

Personally, I didn't notice anything different on the days I took maca, even in large doses. I speculated in the experiment conclusion that perhaps maca is only effective in those whose sex drive and energy levels are low to begin with. Another possible reason suggested by one of the studies is that only red maca is effective while yellow and black maca are not. The maca powder I purchased was yellow.

2. Retinol cream experiment

The retinol cream experiment was quite unique in the sense that it's one of the very few experiments that actually gave a positive result. The goal was to see whether retinol, the animal form of vitamin A, would improve skin quality. Since retinol is less harsh on the skin than retinoids, I thought it would be useful to try a retinol cream before moving on to the stronger stuff.

While the appearance of my skin didn't change visibly during the experiment, there was an unexpected growth of new hair on my left temple. I even took a few pictures to show I wasn't making it up. I'm not sure whether the effect was simply due to increased collagen production and skin cell proliferation or something else, but if you're suffering from hair loss, I would recommend giving retinol a go. As another experiment, I'm currently applying tretinoin on my face to see if retinoids are even more effective.

3. Tocotrienol experiment

Like tocopherols, tocotrienols are a form vitamin E. Most multivitamins contain only alpha-tocopherol, but it's the tocotrienols that seem to have all the interesting health benefits. Well, at least potential health benefits. One study reported an increase in hair growth in all subjects taking the tocotrienol supplement. Such a result seemed so unbelievable that I had to try it out for myself.

One major problem with this experiment was that tocotrienol supplements are not cheap, which meant that the duration of the experiment was only two months. As I wrote in the conclusion, I didn't see a visible increase in hair growth, but there appeared to be a reduction in the number of hairs lost daily. If I get my hands on an affordable tocotrienol supplement, I look forward to repeating the experiment to see if the reduction was due to tocotrienols or something else.

4. Topical vitamin C, vitamin E & ferulic acid experiment

In this experiment, I applied a topical consisting of ascorbid acid, vitamin E and ferulic acid on my face. All three compounds have some evidence behind them showing that they increase collagen production and improve skin quality. The product I was testing was called SkinCeuticals CE Ferulic acid, which is really expensive if you buy it the usual way; I purchased several smaller sampler bottles online, which was cheaper. Another way to save cash is to make a similar product yourself.

In the experiment conclusion I reported that I didn't see any improvement in my skin quality. A possible reason is that some of the liquid in the sampler bottles was apparently oxidised, which would render it useless. I concluded that it was not worth the price to keep using the product. However, some months later I read a book on skin aging that made me reconsider the whole thing, and so I decided to re-visit the experiment and order another set of sampler bottles. The experiment is still going on, and so far, none of the samplers have contained oxidised liquid.

5. Vitamin D3 experiment

As I'm sure you've noticed, vitamin D3 was really big in the health blogosphere this year. After reviewing the data I concluded that I've very likely been deficient in vitamin D3 for most of my life and decided to start supplementation. I know standing naked in the sun to get the required dosage is a big thing in the paleo circles, but at these latitudes it's not very feasible. Besides, sun damage seems to be a major cuplrit in skin aging.

For a few months, I took 2,000 IU per day and then increased to 5,000 IU. This got my serum 25-hydroxyvitamin D levels up to 113 nmol/L (45 ng/mL), which is in the optimal range. I'm still taking 5,000 IU daily, and while it hasn't given me complete immunity against all infections, this is the first experiment that has resulted in a reduction of colds. Not even intermittent fasting or the paleo diet did that.

6. Hyaluronic acid experiment

In a sort of continuation to my experiment with MSM, chondroitin and glucosamine, I decided to try oral supplementation with hyaluronic acid. Despite the high price, hyaluronic acid seems to be quite popular and is said to improve skin quality and promote hair growth. The evidence for oral supplements is shaky, however, except maybe for joint problems.

Because hyaluronic acid is so damn expensive, the experiment lasted for only a month, which is probably the shortest duration of any experiment on this blog. I didn't see any difference in skin quality or hair growth, but feel free the take the results with a grain of salt. I think hyaluronic acid may actually be quite useful, but next time I'd rather try applying it topically.

7. Tea tree oil vs. Korean red ginseng experiment

Now here was an experiment that seemed to go on forever. In this "classic" hair growth battle, Korean red ginseng and tea tree oil fought it out on my legs. Since Korean red ginseng (also known as Panax ginseng) has been shown to promote hair growth, and tea tree oil is supposed to be anti-androgenic, I was expecting ginseng to increase and tea tree oil to suppress hair growth on my legs.

After meticulous experimentation with various carrier oils and different parts of the body, I got sick of the whole thing and called it quits without ever seeing any results. You can read the "exciting" conclusion if you're interested in the details. All in all, I would think twice before adding these two to a hair loss regimen.

8. Intermittent fasting experiment

A couple of months ago I wrote on the blog that a year had passed since I began my intermittent fasting experiment. While I've occasionally experimented with different variations of the same thing, I have mostly followed the 24/24 hour cycle of feasting and fasting. That is, for most of the year I stopped eating at about 6 PM and then started eating again the next day at 6 PM.

After the last post describing my year on the diet, I've slowly returned towards a more "normal" way of eating again. Compared to other people, I still have lengthy periods of not eating, but I'm no longer on the strict 24-hour cycle. The main reason for the change is that intermittent fasting does not appear to increase lifespan like caloric restriction does, and life extension is my main interest, after all. For losing weight and improving insulin sensitivity it still appears to be beneficial, provided you do it the right way.

Beyond weight loss, however, I'm thinking there are better ways to incorporate fasting into my health regimen than the 24-hour cycle. Perhaps longer fasts done less frequently, perhaps periodical protein restriction. I'll write more about the subject once I do some more reading. Anyway, I feel pretty good about being able to follow my intermittent fasting routine so strictly for an entire year. Life extension or not, it surely taught me to think of hunger in a new, more positive way. The looks and comments I got from family members, friends, and strangers alike were pretty entertaining, too.

9. Emu oil vs. Hair Again experiment

This experiment was another battle between two hair growth products. This time the competitors were emu oil and a topical gel called Hair Again. Emu oil comes up every year in hair loss forums, but the fact is that the evidence behind it is very limited, to say the least. The commercial product, on the other hand, contained many ingredients that looked quite useful.

After eight months, I concluded that the battle had no clear winner, since there was no change on either side of my face. Yes, the hairs I grew with the retinol were still there, but no further improvement was seen. I still have some of the emu oil left, but I haven't found much use for it ever since I ran out of the topical gel. Sadly, even if I wanted to continue the experiment I couldn't, because the company that makes the gel refuses to ship to Finland any longer.

10. Nootropic experiment

The purpose of this three-way battle between taurine, acetyl-L-carnitine and ginkgo biloba was to see if any of them were effective as nootropics, either taken alone or in combinations. My subjective evaluation of my energy levels, mood, and ability concentrate would serve as the indicators. As an objective measurement, I compared my scores in a memory game meant to improve IQ.

For all the money I spent on these supplements, it's a bit of a disappointment that none of them seemed to do anything for me. As I wrote in the experiment conclusion, one possible reason why ginkgo didn't work is that the plant extracts may differ significantly among brands. Acetyl-L-carnitine and taurine, on the other hand, should be pretty much the same stuff regardless of the manufacturer. In the future, I may try another brand of ginkgo, and I'm thinking of using taurine to prevent glycation and hangovers. Further experiments may follow.

Conclusion

So there you have, the ten inhuman experiments of 2009. Once again, not many positive results, but hey, at least we've learned something, right? As you can see in the top-right corner of the blog under "Current Experiments", many of the experiments that started this year will continue into 2010, so stick around and see how they end.

Finally, I'd like to thank all the readers for your encouraging comments and questions during the past year – and for pointing out the mistakes, of course! You've been very helpful in making this blog better, and I hope the improvement continues the next year. Until then, happy holidays and take care!

Nootropic Battle Conclusion: Acetyl-L-Carnitine vs. Ginkgo Biloba vs. Taurine

The search for ways to improve cognition and mood continues. (Photo by mtungate)

For the past several months, I've been experimenting with these three supplements to see if they have an effect on cognitition and mood. Many people report good effects, and there is some scientific evidence to support these claims.

However, because of the nature of the medicine business, most of the studies have been done either on animals or on people suffering from a disease such as Alzheimer's. The use of these supplements as nootropics in healthy people is therefore something of a grey area.

The idea of the experiment was to find out if they might increase mood, energy or cognitive performance using myself as the test subject. Below is a description of my experiences with each of the supplements along with a quick summary of the science behind their use.

Taurine

Taurine is added into many energy drinks, but the evidence behind its effectiveness is very limited. In mice, fairly low doses of taurine have been shown to either increase or decrease social interaction and anxiety, whereas in humans data is virtually non-existent except as a treatment for alcoholism.

In my own experiments, I did not see any effect from taking taurine. The recommended amount on the label is 675 mg between meals or at bedtime; my own intake varied between about 200 and 2400 mg. I tried taking it before meals, with meals, and after meals. The only time I thought I noticed something was when I took it before going to bed and had more vivid dreams than usual, but I was unable to reproduce the effect later on.

The potential benefit for preventing hangovers still intrigues me, so I may continue to take taurine in the future. However, I actually did take some taurine once after drinking, and unlike I usually do, did not drink much water before going to sleep. I woke up with a headache, so if it is effective, it's not a miracle drug.

Acetyl-L-carnitine

Carnitine in its various forms has quite a bit of scientific evidence behind it for use as a nootropic. Both L-carnitine and acetyl-L-carnitine help rodents perform better in maze tests and protect them from age-related cognitive decline. Elderly people seem to benefit from carnitine too, especially with higher doses. One study reported a nootropic effect even in young, healthy people.

This was the supplement I was expecting the best results from, but alas, it didn't have any effect on me. The doses used in human studies usually range from 1 to 3 grams; my own intake varied between 500 mg and 3,000 mg. Like in the case of taurine, I tried it during various times of the day. Most people suggest it should be taken away from meals, which is what I did towards the end of the experiment.

There was one time when it seemed that a higher dose resulted in suppression of hunger, but as I was unable to reproduce the effect, I concluded that it was due to something else. Indeed, one of the potential side effects of carnitine is an increase, not a decrease in appetite.

Another time when I thought I noticed an effect was when I took about a half an hour before going for a run. This was towards the end of a fast, and I felt more energetic than usual while running. There is some evidence that L-carnitine may increase aerobic performance, but since later attempts didn't produce similar results, I assume that the increased energy I felt was simply due to variations in the hunger cycle of intermittent fasting.

Although I feel that carnitine may have some long-term benefits for preventing cognitive decline, I find the price too high for me to keep supplementing with it. If I were to take it, however, I would go for bulk powder instead of capsules to save some cash.

Ginkgo biloba

Even though ginkgo biloba has been studied quite a bit, the results are inconclusive. It seems that gingko biloba does have a neuroprotective effect. In addition, it may reduce anxiety and prevent cognitive decline in elderly people.

The standard dose used in many studies is 120 mg, but doses two or three times as large are not unheard of. Comparing doses and ginkgo biloba supplements is difficult, because the extracts can be standardized differently. In my own experiments, I took between 60 mg and 360 mg at various times of the day.

This was perhaps the one supplement that had me wondering the most whether I was experiencing placebo or an actual effect from the pills. I often took 2-4 capsules (with 60 mg each) of ginkgo before going out, and sometimes it seemed like it gave me an energy boost. On the other hand, it may well have been due to other things, such as the caffeine from coffee or yerba mate. Indeed, taking only ginkgo biloba produced very inconsistent results: sometimes I thought I felt more energetic, other times I definitely didn't notice anything.

Anecdotal evidence suggests that some brands of ginkgo may be more effective than others, probably because of differences in the extraction methods. The price of ginkgo biloba is generally not terribly high, so I may experiment with other brands in the future.

Conclusion

In my own experience, none of the three supplements mentioned above produced significant and consistent results in terms of mood, energy or cognitive enhancement. As I mentioned at the beginning of the experiment, I also tried various combinations of the three, but this did not change the fact that for me, they were ineffective. This is based on both my own subjective evaluation and my scores in a memory game that I use to rate my concentration.

For the record, the supplements used in the nootropic battle were: Nu Health Ginkgo Biloba, Source Naturals Taurine, and Doctor's Best Acetyl-L-Carnitine.

Based on these results, I'm beginning to think that my susceptability to the placebo effect is fairly low. I don't necessarily mean that's a good thing, either – an imagined increase in mood or energy levels is just as good as an objectively measured increase, right? On the other hand, it probably does help me weed out the things that have a measurable effect on most people. Caffeine taken on an empty stomach still remains the unbeatable nootropic in my books.

If you have tried taurine, carnitine or ginkgo biloba (or any other nootropic), feel free to drop a comment and share your experience. Meanwhile, for more information on cognition, see these posts:

Green Tea Protects from the Psychological Effects of Stress in Rats
Caloric Restriction Improves Memory in the Elderly
Moderate and Severe Caloric Restriction Alter Behavior Differently in Rats
Anti-Aging in the Media: Rolling Stone on Ray Kurzweil

Green Tea Protects from the Psychological Effects of Stress in Rats

Feeling stressed? Enjoying a cup of green tea with your lunch may help. (Photo by chotda)

It's no secret that a cup or two of green tea can make you relaxed, but now scientists have shown that green tea can reduce the effects of psychological stress in rats.

In a paper yet to be published, rats were put under stress and given either their usual diet or a diet enriched with green tea polyphenols (link). To see how psychological stress and green tea were related, experiments measuring cognitive performance and serum levels of stress hormones were done.

Study method

The rats were divided into five groups: control group (CT), stress group (ST), and three stress groups given low, medium and high doses of green tea polyphenols (LG, MG and HG). The green tea polyphenol (GTP) content of the three diets were 0.1%, 0.5% and 1%, respectively.

Psychological stress was induced by keeping the rats restrained and inhibiting their movements six hours every day for three weeks. Their cognitive performance was then evaluated using an open-field test, a step-through test and a water maze. These tests measure both the activity level and memory ability of rats.

Green tea polyphenols and cognitive performance

In the open-field test, which measures how actively rats explore the arena, the stressed rats were much less active than the control rats. No significant improvement was seen in the rats fed the low dose of green tea polyphenols, while the rats given the medium or high dose were almost as active as the control rats.

The memory of the rats was also affected by stress during the step-through test and water maze test. These tests measure spatial memory and the ability to remember adverse stimuli. Again, only the medium and high doses of GTPs significantly reduced the harmful effects of stress on the rats' memory.

Green tea polyphenols and stress hormones

Stress activates the symphatetic nervous system, which results in a release of catecholamines. Catecholamines are "fight-or-flight" hormones that consist of epinephrine, norepinephrine and dopamine. They are involved in the modulation of cognition, awareness, attention, and emotional state, helping the body to cope with a stressful situation. According to the authors, when the stress level is too high for the body to cope with, cognitive impairments appear and the levels of these hormones begin to decline.

Plasma levels of norepinephrine (another stress hormone, also known as noradrenaline) and dopamine were remarkably reduced in the ST and LG rats. In the MG and HG groups norepinephrine and dopamine levels were lower than in the control group, but much higher than in the LG group. In other words, medium and higher levels of green tea polyphenols partially inhibited the stress-induced decrease in the levels of these hormones.

All four stress groups had higher levels of plasma cortisol than the control group. Cortisol is often referred to as the "stress hormone", since its levels increase in the presence of stress and anxiety. Cortisol also causes blood pressure to rise and immune responses to be reduced. Feeding the stressed rats green tea polyphenols lowered their cortisol levels, but the reduction was statistically significant only in the MG group.

The levels of reactive oxidative species (ROS) were increased in the brain tissue of stressed rats, but again, medium and high doses of GTPs partially inhibited this increase. Similarly, the total antioxidative capacity in brain tissue was reduced by stress but to a smaller extent in the MG and HG groups. The levels of superoxide dismutase showed a similar trend, but the differences were not statistically significant.

A different effect was seen in the levels of interleukin-6 and interleukin-2. While stress increased IL-6 and IL-2, feeding the rats GTPs did not inhibit this increase. In fact, green tea polyphenols increased IL-6 even further. This may be because increased levels of IL-6 can enhance the body's adaptability to stress. Similar effects have been reported in other studies on green tea.

Conclusion

Psychological stress negatively affected the behavior and memory of rats. This adverse effect was associated with higher levels of cortisol, reactive oxygen species, IL-2, and IL-6, and lower levels of norepinephrine, dopamine, and total antioxidative capacity.

These changes were partially inhibited by diets containing 0.5% and 1% green tea polyphenols, except for IL-6, which was further increased by GTPs. A diet containing only 0.1% GTPs did not show significant results.

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