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%

The Long-Term Effects of Antibiotics on Health and Immunity

Garlic is the famous natural antibiotic. (Photo by stijn)

This is the third and last installment in a series of posts on immune function and gastrointestinal health. Given that the swine flu is still making rounds around the world, learning more about how beneficial bacteria can ward off viral infections has been very useful at least for me.

So far, we've seen that foods and supplements containing probiotics can reduce the occurrence and severity of the common cold. Probiotics also have other benefits, such as protection from cancer and increased resistance to cancer. We've also seen that another way to increase beneficial bacteria in the gut are prebiotics, which are a form of fiber found in foods such as Jerusalem artichoke and chicory root. The combinations of prebiotics and probiotics are known as synbiotics and may be superior to either one alone.

Antibiotics and resistant bacterial strains

The one group of biotics that's left to tackle is antibiotics. Most people have probably gotten a prescription of antibiotics at least once in their life. Most people are probably also aware that antibiotics are prescribed way too frequently these days by many doctors, even for health issues that antibiotics can't relieve. As antibiotics only work against bacterial infections, not viruses, taking them for flu symptoms is useless.

The commonly known problem is that as the use of antibiotics becomes more and more widespread, the bacteria become more and more resistant. This is especially common when people quit their antibiotics prescription halfway through because they "feel fine"; some of the surviving bacteria then mutate into more resistant strains and spread into other people.

In a way, there is an evolutionary war going on between medicine and bacteria, and while antibiotics are a fantastic discovery and have many applications, their overuse is a serious problem. That's why taking antibiotics "just in case" is not a great idea long-term.

Other health problems from antibiotics

If the well-being of the rest of humanity doesn't bother you all that much, there are also other, less known reasons to stay away from antibiotics unless you actually need them. Let's look at some of the evidence showing the harmful effects of antibiotics.

Most of the negatives stem from the positive fact that antibiotics are so effective. The problem is that antibiotics are not as specific as we'd like: while they do destroy harmful bacteria, they also destroy beneficial bacteria. That's why it's never recommended to take probiotics at the same time with antibiotics, because the probiotics are just rendered useless.

Since one of the functions of intestinal bacteria is to aid in food digestion, it's no surprise that antibiotics can cause digestive problems. Diarrhea occurs in about 25% of patients receiving antibiotics (link). Probiotics, on the other hand, can counter some of this effect. At least Lactobacillus GG and Saccharomyces boulardii appear to be effective. As mentioned before, leave about 3 hours between taking antibiotics and probiotics to avoid killing the beneficial bacteria right away.

The effect of antibiotics may be especially pronounced in babies, whose bacterial colonies have not yet matured. In one study, rats who were given an antibiotic for 10-17 days saw a near complete eradication of Lactobacillus in the intestine along with a drastic reduction in other bacteria (link). This would obviously have a negative effect on immunity in general.

Another group to whom antibiotics may pose a real danger are the critically ill. One study showed that not only did the microflorarl biodiversity of patients in the intensive care unit significantly decrease with antibiotics, but there were also more organ failures and deaths in patients given antibiotics (link).

Antibiotics also seem to have a negative effect on phytoestrogens. The levels of the lignan enterolactone, a type of phytoestrogen, were significantly lower in men and women who had taken oral antibiotics up to 16 months before measurement (link). The reduction was associated with the number of treatments and time from last treatment. Although not life-threatening, this reduction should be of some concern to those who are taking for example flax lignans for hair growth or other health benefits.

Long-term impairment of immunity from antibiotics

If the above reasons didn't put you off antibiotics for good, here comes the worst part: the previously unknown long-term effects of antibiotics.

Until recently, the effect of antibiotics was thought to be temporary. As long as you took your prebiotics at least 3 hours after your antibiotics, you'd be fine. Any long-term changes in intestinal microflora were considered to last only a few months, after which everything would return to normal.

Unfortunately, some new studies have begun to show that this is not necessarily the case. A study funded by the Finnish Academy found that the earlier estimates were too conservative, and that the effects of antibiotics on intestinal bacteria were visible even after a year (link). Surprisingly, they also discovered that using one type of antibiotic (such as penicillin or tetracycline) increases the resistance of bacteria to other types of antibiotics as well. The old idea of switching to a different antibiotic to avoid resistance doesn't seem so good after all.

A study from last year confirms these findings. Using a novel method of observing the human gut microbiota, the authors found that antibiotic treatment "influenced the abundance of about a third of the bacterial taxa in the gut, decreasing the taxonomic richness, diversity, and evenness of the community" (link). While the conditions partly returned to normal after four weeks, several bacterial taxa failed to recover even after six months.

Conclusion

While antibiotics certainly have their uses, taking them when unnecessary can be harmful in many ways. Here's a summary of the negatives:

• Increased resistance to antibiotics
• Diarrhea and digestive problems
• Reduction in beneficial phytoestrogens
• Impaired immunity, especially in children and the critically ill
• Long-term changes in gut microflora

Since antibiotics, by definition, are substances or compounds that kill or inhibit the growth of bacteria, it's good to keep two things in mind. First, antibiotics destroy not only bad bacteria but also good ones. Second, antibiotics are only effective against bacteria, not viruses. So before getting antibiotics for an infection, make sure it really is a bacterial and not a viral infection (the common cold, for example, is a viral infection).

For more information on health and immunity, see these posts:

Prebiotics, Synbiotics and the Immune System
The 7 Types of Aging Damage That End up Killing You
Intermittent Fasting Reduces Mitochondrial Damage and Lymphoma Incidence in Aged Mice
Swine Flu and Avoiding the Cytokine Storm: What to Eat and What Not to Eat?

Prebiotics, Synbiotics and the Immune System

Bananas contain a small amount of prebiotics. (Photo by clairity)

Last week I wrote about the effectiveness of probiotics for improving gut health and immunity. While not all studies agreed they could ward off the flu, pretty much all of them found at least some positive effects on the immune system from taking probiotics.

As mentioned, probiotics are available as supplements and in some foods such as dairy products. But there's also another way of promoting healthy bacteria in the gastrointestinal tract: prebiotics. Prebiotics are non-digestible ingredients in food that stimulate the growth and activity of healthy bacteria inside the body. In a sense, prebiotics cause the body to produce its own probiotics.

What are prebiotics?

There is some disagreement in the scientific community over which substances are probiotics, but at the minimum this category includes oligofructose and inulin. Oligofructose is a fructooligosaccharide, which refers to a short chain of sugar (in this case fructose) molecules. Inulins are a group of polysaccharides, which means a long chain of sugar molecules.

Since these prebiotics are composed of sugars, they are carbohydrates, and since they are indigestable, they are fibers. Further, inulin and oligofructose are soluble fibers, meaning that they're able to dissolve in water. Though they can't be digested, they do undergo fermentation as the bacteria get their hands on them. At the same time, the microflora of the gut is affected.

As the bacteria metabolise prebiotics in the colon, significant quantities of carbon dioxide, hydrogen and methane are released, which means that eating foods with prebiotics can cause gas. With long-term consumption, as the body grows accustomed to inulin and oligofructose, this unpleasant side effect is reduced.

Food sources of prebiotics

Inulin and oligofructose are naturally present in many plant foods, but their quantities differ significantly. Here's a list of foods in decreasing order of their average prebiotic content (values per 100 g [link]):

• Chicory root: 41.6 g inulin, 22.9 g oligofructose
• Jerusalem artichoke: 18.0 g inulin, 13.5 g oligofructose
• Dandelion greens: 13.5 g inulin, 10.8 g oligofructose
• Garlic: 12.5 g inulin, 5.0 g oligofructose
• Leek: 6.5 g inulin, 5.2 g oligofructose
• Asparagus: 2.5 g inulin, 2.5 g oligofructose
• Wheat bran: 2.5 g inulin, 2.5 g oligofructose
• Wheat flour, baked: 2.4 g inulin, 2.4 g oligofructose
• Banana: 0.5 g inulin, 0.5 oligofructose

Note that unless stated otherwise, these figures apply to raw foods. Cooking in general seems to reduce content of prebiotics by 25-75%. Chicory root and Jerusalem artichoke (not to be confused with the globe artichoke, which is green in color) clearly take the cake. Even when cooked, these two plants still contain plenty of inulin and oligofructose.

Prebiotics and the immune system

Since probiotics have been shown to benefit the immune system, and prebiotics promote probiotic bacteria in the gastrointestinal tract, it makes sense that the consumption of prebiotics would have similar effects. Unfortunately, for those interested in preventing the common cold and other viral infections, not many studies have actually looked at whether prebiotics are effective. With that in mind, let's take a look at the evidence behind prebiotics and their effect on immune health in general.

There are some studies on humans showing that the consumption of prebiotics does modify the immune system (link, link). Specifically, prebiotics may reduce intestinal infections and intenstinal inflammation. On the other hand, inulin and oligofructose can also activate immune cells and increase the cytotoxicity of natural killer cells and the production of cytokines (link). In rats, prebiotics increase the number of T cells, interleukin-2 and interleukin-4, which indicates that prebiotics enhance the immune system (link).

One study found that a prebiotic galacto-oligosaccharide mixture was helpful in reducing travellers' diarrhoea (link). Those who got the prebiotic instead of the placebo had fewer incidences and less symptoms of diarrhoea when travelling to foreign countires. In infants, human milk protects from morbidity and mortality due to diarrhoea compared to formula milk, most likely because of the presence of prebiotic oligosaccharides in human milk (link). Some studies have also shown that prebiotics may help with irritable bowel syndrome (link), but the evidence is inconclusive. And, even though prebiotics may cause gas, they can also help with lactose intolerance (link).

A commonly cited example of the health effects of probiotic-containing foods is their anticarcinogenic activity. This is at least in part due to the stimulation of lactic acid producing bacteria in the colon, since lactic acid producing bacteria reduce the ability of microflora to produce carcinogens. Prebiotics seem to have a similar effect (link), possibly being even more effective than probiotics (link).

As for influenza, one study found that gamma-inulin, the active component of inulin preparations, improved the response to a variety of antigens in mice (link). When given a lethal dose of the influenza virus, all of the mice died, but when gamma-inulin was administered at the same time, half of them survived.

Synbiotics: even better than prebiotics and probiotics?

Synbiotics is the fancy name given to combinations of probiotics and prebiotics. The idea is that these two would work synergistically to produce even better results than either one would alone. Indeed, there is some evidence that synbiotics are superior to prebiotics and probiotics (link). In any case, the effect of synbiotics is different from that of pre- or probiotics (link).

Not all the studies are quite as promising, however One study found that rats fed prebiotics actually had a poorer resistance to salmonella than controls (link). This impairment was partially but not entirely prevented by calcium phosphate. It's not clear whether the same applies to humans, but it does emphasize the fact that we don't entirely understand how synbiotics affect the immune system.

Conclusion

While almost all studies have shown at least some benefit from probiotics, less is known about the effect of probiotics and synbiotics on the immune system. Prebiotics appear to increase the number and activity of probiotic bacteria in the body, but studies in humans and animals have yielded inconclusive results.

Sources of prebiotics, namely inulin and fructooligosaccharide, include nutritional supplements and plant foods. Compared to most commonly consumed foods with prebiotics, such as wheat and banana, supplements are often a better source. However, Jerusalem artichoke and chicory root are the best sources of inulin and fructooligosaccharide, containing much more than any supplement.

For more information on immunity and supplements, see these posts:

Enhancing Immunity with Probiotics: Can They Ward Off the Flu?
Swine Flu and Avoiding the Cytokine Storm: What to Eat and What Not to Eat?
Examining Possible Causes for Slower Wound Healing
How to Choose Between Different Forms of Coenzyme Q10: Ubiquinone vs. Ubiquinol

The 7 Types of Aging Damage That End up Killing You

The longer you live, the more time you have to explore the world. (Photo by iko)

If aging merely meant the passage of time, there'd be nothing wrong with it.

In fact, it'd be a good thing. The older you got, the more things you would know, the more skills you would've acquired, the more experiences you would've had, and the more people you would've met. All this while retaining the strength and vigour of youth. Doesn't sound too bad.

The problem is that what aging really means is the passage of time accompanied by a set of degenerative biological processes that harm the abilitity of our bodies to function and eventually cause us to die. What good is all that knowledge and all those experiences if you can't remember any of it? What good are all those skills when you're no longer able to use them?

We don't really know why we age. That's an interesting question in its own right, but it's beyond the scope of this post. The point of this post is to take a closer look at the biological processes that accompany the passage of time and together form the seven classes of aging damage.

It is because of this process of biological decay that we grow old. Not old the way vampires are "old" yet still magically look the same, but the way people and animals are old – fragile, weak and sick. To be clear, despite what most people tell themselves, there is nothing good about growing old, because all it really means is a cumulative and irreversible increase in fragility, weakness and sickness.

The good news is that despite decades of studying aging, we have identified only seven types of primary damage to our bodies from aging. The rest are secondary consequences of primary damage. If you prevent the primary damage from occurring, you will prevent the secondary consequences as a result, but not vice versa.

And why is it a good thing that there are seven causes of aging? Because it means that the aging process is not a complete mystery anymore. Or rather, the consequences of the aging process are not a complete mystery to us. Even though we don't have a clear explanation for why these seven types of damage occur in the first place (i.e. why are we not born biologically immortal?) we have a pretty good understanding of how they work.

And if we know all the things that are going wrong with our bodies as we age, we can begin to fix them.

The three approaches to the sinking boat problem

Imagine that the human body is a boat. For many years, the boat sails without a problem. But then, somewhere in the middle of the ocean, there's a problem: a hole has appeared in the bottom, and the boat is going to sink.

Now imagine that on that boat, there are three people: an architect, a mechanic, and a museum keeper. You go to them and ask each one in turn what could be done to fix the situation.

The architect has no experience in repairing boats. He is interested in understanding the nature of boats. He has heaps of drawings of boats and calculations for which kind of materials are suitable for a specific type of boat, but he doesn't actually build the boats. His suggestion is to study the boat carefully to understand the exact reasons that caused the hole to appear. If we understand the causes, he figures, we are better equipped to fix the problem.

You know there's no time for all that because the boat is sinking fast, so you go to the museum keeper. He runs a museum with old boats on display and has some experience on renovating worn down boats for museum use. He's not really interested in making them actually usable at sea; all they need to do is look good. His suggestion is to just let the boat sink, because sink it will, and then come back later to drag it from the bottom of the ocean and put it on display.

That doesn't feel like such a great idea either, so you turn to the mechanic. He has no idea where the hole came from, isn't familiar with the exact type of boat, and is in no hurry to visit the ocean floor. But he does have a plan: have two of you scoop the water back into the sea as fast as possible, while the other two find something to fill the hole with. There's no guarantee that another hole won't appear later on, but at the very least, his plan is going to buy you extra time.

At this point, extra time sounds pretty damn good, so you go with the mechanist's suggestion and grab the nearest bucket to start scooping.

Gerontology, engineering and geriatrics

There are three approaches to the study of aging: gerontology, engineering and geriatrics. In the boat metaphor above, the architect is the gerontologist, the mechanic is the engineer, and the museum keeper is the geriatricist.

Broadly defined, gerontology is the study of aging. It encompasses a wide range of subfields, but for the purposes of this post, biogerontology is the subcategory of interest. Biogerontologists seek to understand the biological processes that cause aging. A fascinating field of study, for sure, but as the boat example illustrates, when you're the one actively falling apart, perhaps a bit too theoretical.

Geriatrics, on the other hand, is a branch of medicine focused on the health care of the elderly. The emphasis is on treatment rather than prevention. One could even say it's about alleviating the symptoms rather than reversing the damage, much less fixing the cause. The problem is that the geriatricist has no interest in helping you unless your boat is already beyond repair.

The engineering approach to aging is to fix the damage as it occurs. The purpose is not to fully understand all the reasons that the damage happens in the first place, interesting as it may be; it's enough to know that it's there. Rather, the emphasis is on periodic repair and maintenance, so that even after years of use, the boat still looks, feels and sails like new. And if during those extra years of use maintenance buys us we learn something new about how to make boats more resistant to damage, all the better.

To me, the engineering approach is a matter of priorities. Yes, it would be fascinating to understand the complete workings of the human body, but it's much less fascinating to die trying now than it is to live significantly longer and find out later. Besides, the more years you have left, the more time you have for things like research and thus the more chance of succeeding in mapping out every possible metabolic pathway. Life should be our first priority in everything, because death cuts everything else short.

The seven deadly sins of aging

Without further ado, let's take a look at what the seven types of aging damage are and what we think can be done about them. Again, while identifying the different ways in which aging manifestates itself doesn't really explain why the damage happens, or even why there are exactly seven types of damage, it does provide us with clear goals for an engineering approach to life extension.

This approach of focusing on rejuvenation rather than slowing down aging itself is referred to as SENS, or Strategies for Engineered Negligible Senescence, a term originally coined by Aubrey de Grey in his book The Mitochondrial Free Radical Theory of Aging. Each of the SENS strategies targets one of the seven types of damage, listed below.

1. Cell loss and shrinking tissue

Worn out cells in the body are usually replaced by cell division. However, as we age, some of the cells we lose can no longer be replaced or they are replaced very slowly, which means that cells are being lost faster than they are produced.

In skeletal muscle, cell loss means shrinking tissue and weaker muscles. In the heart muscle, it means a more fragile heart. In the brain, it means a loss of neurons and causes a host of mental problems. Currently, one of the best approaches to cell loss is exercise, but its effects are nevertheless very limited.

The solution: stimulating cell division or introducing new cells (repleniSENS)

2. Mutations in the cell nucleus

Two types of changes in our chromosomes occur as we age: mutations and epimutations. The former are changes to the DNA itself, while the latter are changes to the propensity of the DNA to be decoded into proteins.

In some cases, changes to the DNA can lead to the formation of cancer. Non-cancerous mutations and epimutations do not in most cases contribute to the aging process, and in the rare cases that they do pose a problem, they are taken care of by other strategies (repleniSENS and apoptoSENS), so we don't have to worry about them at this point. Cancer, however, is definitely a problem, as anyone who's looked at mortality statistics in the Western world can testify .

The solution: removing the genes needed for telomerase (OncoSENS)

3. Mutations in the mitochondria

Mitochondria are known as the "power plants" of cells, because they play a key role in energy production. They also control cell growth and the cell cycle. Mitochondria contain their own mitochrondrial DNA (mtDNA), which encodes a small but important part of the proteins in the mitochondrion.

The problem is that the mitochrondrial environment is highly oxidative, and the repair mechanisms are much less sophisticated than those in the cell nucleus, which contains most of the DNA. The result is that mitochondria are very vulnerable to the accumulation of mutations, which is thought to accelerate aging. Therefore, preventing the accumulation of mitochondrial mutations requires a strategy of its own.

The solution: moving the DNA into the cell nucleus for better protection (MitoSENS)

4. Cells that refuse to die

Sometimes cells can acquire a state in which they are no longer able to divide but refuse to die, causing damage to neighboring cells. There are three classes of cells that can go into this harmful state: visceral fat cells, senescent cells and immune system cells. The problems that the accumulation of these cells cause are insulin resistance, tissue degradation, and vulnerability to infection.

Normally, the body is able to get rid of such harmful cells through apoptosis, a signal for the cell to kill itself. When the cells stop responding to these signals, other methods are needed to destroy them. While surgery can be used to remove visceral fat, the main alternatives to destroying senescent and immune system cells are injecting something to force apoptosis or stimulating the immune system to kill the cells.

The solution: forcing cell suicide or using the immune system to kill target cells (ApoptoSENS)

5. Tissue stiffening from crosslinks

The body is much better at keeping the insides of cells clean than it is maintaining proper functioning outside the cells. Inside the cells, proteins are regularly destroyed and rebuilt to keep things running smoothly, but outside, some proteins are recycled very slowly or never. With time, these long-lived proteins can run into problems.

Chemical reactions can sometimes cause two proteins to form a chemical bond known as a crosslink, which hinders their ability to slide across or along each other. Advanced glycation endproducts (AGEs) are probably the most famous example of crosslinks. When too many crosslinks occur, tissues lose their elasticity and problems arise. In artery walls, for example, tissue stiffening causes an increase in blood pressure. Breaking these crosslinks is needed to maintain a youthful state.

The solution: using specific enzymes or proteins to break crosslinks (GlycoSENS)

6. Junk outside the cells

This is another form of junk outside the cells that accumulates with aging, but it differs from crosslinks in that it has no useful function whatsoever. This junk should be cleared out of the body, but as in the case of death-resistant cells, the body is not able to digest or remove the material.

An example of junk outside the cells are the amyloid plaques in the brains of Alzheimer's patients. This web-like material accumulates in everyone's brains with age, but problems become visible only after a certain threshold has been reached. In supercentenarians, extracellular junk is one of the biggest killers.

The solution: stimulating the immune system to clear out the junk (AmyloSENS)

7. Junk inside the cells

As mentioned earlier, the body is fairly good at breaking break down proteins and other molecules in the cell which are no longer useful. However, sometimes these molecules have gone through chemical changes that makes the cell unable to digest them any longer. They then end up in the lysosome, which is the most powerful place to degrade molecules. If the lysosome is unable to get rid of them, they end up as intracellular junk and stay there practically forever.

In dividing cells this is not too big of a problem, because each division dilutes the junk, and the threshold where problems occur is not reached. But in non-dividing cells, the accumulation of this junk eventually causes the cells to stop functioning correctly. The result is problems such as atherosclerosis, blindness, liver spots, and a host of neurogenerative diseases.

The solution: making the lysosome more powerful to degrade the junk (LysoSENS)

Summary

There you have it, the seven types of aging damage that need to be fixed in order for true rejuvenation engineering to happen. And how do we know the list ends here? Isn't it possible there are other causes we just don't know of yet? Theoretically, yes, but it seems highly unlikely. Here's an explanation taken from the SENS Foundation website:

We can be confident that this list is complete, first and foremost because of the fact that scientists have not discovered any new kinds of aging damage in nearly a generation, despite the facts that research into aging has been slowly accelerating and that we have had ever-increasingly powerful tools with which to investigate the aging body.

Challenging as fixing this damage may be, the fact that we know what we need to do should still leave you with a fairly optimistic view of things. As I've said before, solving these problems is really a question of "when", not "if". And the sooner it is, the better – for all of us.

Even if you're not studying or working in the field, there are a couple of very practical ways to help make these rejuvenation therapies come true in your lifetime. The SENS website has a pretty good list of things with something for everyone, but I'll mention two important ones here.

Money is always needed, so one good option is to donate to the Methuselah Foundation or to the SENS Foundation to support research (and if you're sceptical of donations actually doing anything, here's some good news: a recent target of $16,000 was succesfully reached and exceeded earlier this month for research on using lasers to remove intracellular junk).

Another important thing is to talk to people and spread the word: many people don't have any idea that life extension is not just science fiction anymore. Significantly longer and healthier lifespans are the future, and just how far away this future is depends entirely on us.

For more information on preventing aging, see these posts:

How to Live Forever: My 5 Steps to Immortality
Slowing Down Aging with Intermittent Protein Restriction
Who Wants to Live Forever? Results from a Global Survey
Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol

Dietary Vitamin K2 May Reduce Prostate Cancer

Edam cheese has more vitamin K2 than other cheeses. (Photo by Sifu Renka)

Vitamin K2 hasn't really made it into the mainstream yet, but a lot health blogs have caught up on its importance.

One explanation is that vitamin K2 fits poorly into the conventional view of what is healthy, and everything that the conventional view disapproves of, contrarian health bloggers embrace. The irony of vitamin K is that contrary to what one might expect, vitamin K1 just doesn't seem to have the same punch as vitamin K2.

And the interesting difference between the two? The main dietary source of vitamin K1 (phylloquinone) in the Western world is green leafy vegetables, while the main sources of vitamin K2 (menaquinones) are meat and cheese.

For some people, advocating meat and cheese over green leafy vegetables is pure blasphemy, but when it comes to prostate cancer, it may not be such a bad idea. In this post, we'll take a look at a large study that found a reduced risk of prostate cancer in men who ate more vitamin K2 in their diet.

The EPIC study and dietary vitamin K intake

The European Prospective Investigation into Cancer and Nutrition (EPIC) is the largest study of diet and disease to be undertaken. It has more than half a million participants, most of whom are 35-70 years old. The study begun many years ago and is still ongoing, with results being published every now and then.

One of the papers from last years looked at the incidence of prostate cancer in the Heidelberg cohort of the EPIC study (link). The Heidelberg cohort included almost 12,000 men aged 40-65 years from Heidelberg, Germany. Their dietary intake of phylloquinone and menaquinones was assessed by using a food-frequency questionnaire and a list of the vitamin K content of ~2000 commonly consumed foods.

The median daily intakes of phylloquinone and menaquinones were 93.6 micrograms and 34.7 micrograms, respectively. Menaquinone-4 (MK-4) accounted for 14.4 mcg of total menaquinones, while menaquinone-7 (MK-7) accounted for only 0.8 mcg. The main dietary menaquinones in terms of quantity appear to be MK-4 and MK-9.

Vegetables, especially green leafy vegetables, were the main source of vitamin K1. In the case of vitamin K2, meat products were the main source of MK-4 and dairy products the main source of higher menaquinones. Since fermented dairy products contain only a very small amount of MK-7, and the only food that has a lot of it is natto, it's not surprising MK-7 intake was so low among participants. Nonetheless, even small amounts may be enough to see benefits.

Perhaps unsurprisingly, those who consumed more vitamin K appeared to be healthier in general:

Subjects in the upper quartiles of phylloquinone and menaquinones had a lower body mass index, were more likely to have a university degree, and were more likely to practice vigorous physical activity >2 h/wk than were subjects in the lower intake quartiles.

This was despite the fact that as the intake of vitamin K increased, so did energy intake. Smoking status, however, was not significantly different between quartiles of vitamin K intake. These factors, along with things like calcium intake and family history of prostate cancer were adjusted for in the multivariate analysis.

Dietary intake of vitamin K1 & K2 and prostate cancer

The analysis showed that dietary intake of phylloquinone was not associated with the incidence of prostate cancer. In other words, those who ate more vitamin K1 had just as much prostate cancer as the ones who ate less vitamin K1.

Menaquinone intake, on the other hand, was inversely related to the risk of prostate cancer after excluding cases who were diagnosed within the first two years of follow-up. When the authors looked at only advanced cases of prostate cancer, the inverse relationship was even clearer. Thus, in contrast to vitamin K1, those who ate more vitamin K2 had less incidences of advanced prostate cancer.

The food source of vitamin K2 was also important. Only menaquinones from dairy products were associated with a significantly lower risk of advanced prostate cancer, while those from meat products were not. Accordingly, the risk of advanced prostate cancer was lower in those who consumed more MK-5–9 but not in those who consumed more MK-4. In contrast, menaquinone intake from meat products were associated with a lower risk of all cases of prostate cancer, but this difference was not statistically significant.

If one were to interpret these numbers literally, then, it would seem that an increased intake of MK-4 (from meat sources) may reduce the risk of prostate cancer in general, while an increased intake of higher menaquinones (from dairy sources) reduces the risk of advanced prostate cancer.

So why would vitamin K2 reduce advanced prostate cancer but not total prostate cancer? The authors offers a possible explanation:

Our findings of stronger associations of vitamin K intake with advanced than with total prostate cancer could be a hint that menaquinones play a role in tumor promotion and progression rather than in tumor initiation.

In other words, vitamin K2 may not decrease your odds of getting prostate cancer, but if you do get it, menaquinones decrease the odds of the cancer reaching an advanced stage. This makes sense, given that menaquinones have been shown to have an antiproliferative effect on several cancer lines in vitro.

Conclusion

An increased intake of menaquinones (vitamin K2) but not phylloquinone (vitamin K1) is associated with a reduced risk of advanced prostate cancer. Based on this study, the main sources of vitamin K2 in the Western diet are meat and dairy products.

When comparing different food sources of vitamin K2, dairy products were more strongly associated with a reduced risk of advanced prostate cancer than meat products. Accordingly, higher menaquinones (MK-5–9), which are found mostly in dairy products, were more strongly inversely associated with prostate cancer than MK-4, which is found mainly in meat.

For more information on diet and cancer, see these posts:

Red Meat and Mortality: A Closer Look at the Evidence
Green Tea Catechin Reverses the Effect of DHT in Prostate Cancer Cells
Intermittent Fasting Reduces Mitochondrial Damage and Lymphoma Incidence in Aged Mice
Slowing Down Aging with Intermittent Protein Restriction