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

Black Tea vs Green Tea: AGEs and ALEs

Theaflavins are black tea's answer to catechins in green tea. (Photo by Caro Wallis)

In previous posts, I've mentioned studies that have shown contradictory results for the effectiveness of green tea against advanced glycation end-products, or AGEs. At the time when the first post was written, I found five studies showing that green tea reduces AGE formation.

In a later post, I wrote that another in vitro study found yerba mate to inhibit AGE formation as effectively as aminoguanidine, which is one of the strongest anti-glycation drugs around. The bad news was that the same study found only a non-significant effect on AGEs from green tea. So what gives?

One possible reason for this discrepancy is dosage; perhaps low doses of green tea catechins are ineffective against glycation. Indeed, the yerba mate study used concentrations that were easily achievable in humans, whereas some of the others used stronger extracts. While a few cups of green tea may not do much in terms of AGEs, it's nonetheless promising that three of the five positive studies were in vivo. One of them was in diabetic rats and two of them were on normal rodents.

The problem with drinking copious amounts of yerba mate is that several reviews have found it to be carcinogenic. I will probably do another post on this, but based on my current knowledge, it looks like less than half a liter per day is not associated with an increased risk of esophageal cancer, while at higher levels the risk becomes clear. That means drinking enough yerba mate to inhibit AGEs may not be a smart choice.

If drinking 10 cups of green tea per day seems like a daunting task, rooibos tea is one alternative. We know that rooibos tea reduces lipid peroxidation, which causes advanced lipid peroxidation end-products, or ALEs. But there are no studies suggesting it reduces AGEs, so we're left looking for more alternatives to green tea.

Enter black tea. Most people consider green tea to be superior to black tea in all aspects, but that's not entirely true. Granted, green tea does often beat black tea because the latter contains fewer catechins, but there are also cases where black tea prevails. This is because during the longer fermentation process (which separates green tea from black tea), some of the catechins are converted to theaflavins – polyphenols unique to black tea.

AGEs in vitro: comparing black tea and green tea

Methylglyoxal (MGO) and glyoxal (GO) are highly reactive dicarbonyl compounds that modify proteins over time, forming AGEs. Although it's still unclear how harmful they are in healthy people, AGEs are known to be higher in chronic diseases such as diabetes, and levels of MGO are also 2-6 times higher in diabetics than in normal people.

In one study, epigallocatechin gallate (EGCG) – the main catechin in green tea – was found to trap both GO and especially MGO under neutral or alkaline conditions (link). Under acidic conditions (pH less than 4) this effect was not present. EGCG was as effective as aminoguanidine, which also works by trapping reactive dicarbonyl compounds.

The authors then decided to test whether other tea polyphenols might have a similar effect. And indeed they did. All of the catechins tested reduced MGO, with epigallocatechin (EGC) being the best of the four. However, they also found that black tea theaflavins outperformed all green tea catechins in reducing MGO. All theaflavins tested decreased MGO by more than 60%.

The concentration of catechin or theaflavin was the same in each test, which means that theaflavins clearly have the upper hand here. GA and PY in the above graph stand for gallic acid and pyrogallol, respectively. Interestingly, when the molar ratio of polyphenols to MGO was increased from 1:3 to 1:1 in a second experiment, some of the catechins did slightly better than theaflavins.

The difference between in vitro and in vivo

So black tea looks effective in vitro, but what about in vivo? Some studies suggest that even a few cups of green tea or black tea increases antioxidant activity in plasma, but it's not clear whether this translates directly to less AGEs and ALEs. The data on black tea and AGEs in vivo is very limited, so we'll have to focus on ALEs instead.

Green tea or black tea powder seems to protect rat livers from lipid peroxidation (link). Green tea also inhibits lipid peroxidation in their central nervous tissue – which is high in easily oxidizable polyunsaturated fatty acids. Levels of malondialdehyde (MDA), an intermediate in the formation of ALEs, were significantly reduced.

Similar findings were reported in another study, in which rats fed black tea instead of water had lower plasma MDA and protein carbonyl contents (link). Thus, black tea was effective against both ALEs and AGEs.

One study found that while black tea polyphenols strongly reduced plasma lipid peroxidation in vitro, but when human subjects were given a drink containing black tea extract, the rate of lipid peroxidation did not change (link). According to the authors, the concentrations of polyphenols in plasma would have to have been at least five times greater (5 micromoles) to see a significant effect.

Another study found that tea flavonoids reduced LDL oxidation in vitro (oxidised LDL seems to be a key player in atherosclerosis), with theaflavins being more effective than catechins (link). Then, human volunteers were given 750 mL of black tea for 4 weeks to see if the same thing happened in vivo. Although the concentration of polyphenols was now much lower, tea consumption still had a significant inhibitory effect on LDL oxidation.

Unfortunately, other studies have failed to validate this finding. Human volunteers given 900 mL (6 cups) of green tea or black tea daily for 4 weeks did not have lower levels of LDL oxidation or lipid peroxidation, even though green tea slightly increased plasma antioxidant activity (link). Since both were effective in vitro, the authors conclude that the amount of polyphenol needed is far greater than what could be achieved by drinking tea.

Another similar study found that 6 cups of green tea or black tea daily did not reduce LDL oxidation in smokers, even though they were found to be effective in vitro (link). Increasing the dose by drinking more tea does not seem feasible. Even a green tea extract equivalent to 18 cups of green tea was ineffective in the same study, and another study found that 1,000-1,250 mL of tea did not reduce markers of lipid peroxidation (link).

In one study, smokers and non-smokers were put on a diet otherwise low in flavonoids and given green tea extract with their food (link). The daily intake of catechins was 18.6 mg. No changes in markers of AGEs or ALEs was seen, although the green tea extract increased plasma antioxidant capacity, especially in smokers.

Conclusion

Black tea polyphenols are effective in inhibiting AGE and ALE formation in vitro, in some cases even more effective than green tea catechins. Green tea and black tea seem to be effective also in vivo in rodents, whereas human data is mostly disappointing.

A probable reason for the mismatch between in vitro and in vivo results is that the bioavailability of tea polyphenols is very low. Even large consumption of tea did not reduce lipid peroxidation in most human studies. Unfortunately, there are no studies looking AGEs and tea polyphenols in humans.

A closer look at the absorption of tea polyphenols and whether their bioavailability can be improved is probably in order, but we'll save that for another post. For more information on tea, AGEs and ALEs, see these posts:

Hibiscus Tea Lowers Blood Pressure
Green Tea Protects from the Psychological Effects of Stress in Rats
Carotenoids and Lipid Peroxidation: Can Vegetables & Fruit Reduce ALEs?
Fats and AGEs: PUFAs Are Even Worse than Fructose

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%