Dark Chocolate Reduces Blood Pressure and Improves Insulin Sensitivity in Just Two Weeks

Not all things that are good for you taste bad. (Photo by CC Chapman)

Everyone knows that dark chocolate is healthy, but how many of us really know why exactly it's healthy? It's the same as with red wine: it's common knowledge that it's healthy – it contains those magical polyphenols, after all – but the actual effects are mentioned less frequently.

Most things that are labeled healthy by mainstream media are things that reduce the risk of cardiovascular disease. The same is true of red wine and dark chocolate, although I'm sure there's more to them than just heart health. Resveratrol, found in red wine, for example has a multitude of effects. What I found interesting, however, is how quickly dark chocolate can have a beneficial effect on two common health problems: blood pressure and glucose intolerance (link).

Study design

To study how dark chocolate affects glucose tolerance, insulin sensitivity and blood pressure, 19 subjects with hypertension and impaired glucose tolerance were chosen for the experiment. Smokers and those with significant overweight (BMI > 30) or diabetes were excluded.

The subjects were then randomized and given either 100 grams of flavonol-rich dark chocolate or flavonol-free white chocolate for 15 days. They were told to eat the chocolate in two 50 gram doses, one for breakfast and one for lunch. After a washout period of one week the two treatments were switched, so that those who had been eating dark chocolate got white chocolate instead and vice versa.

Results

Two weeks of dark chocolate consumption decreased insulin resistance significantly compared to baseline and white chocolate. The graphs below show the results from various measurements.

The graph on the left show the results from the homeostasis model asssessment of insulin resistance (HOMA-IR) for baseline, flavonoid-rich dark chocolate (FRDC) and flavonoid-free white chocolate (FFWC). The three other graphs show the differences in insulin sensitivity. White chocolate had no effect on any of the tests, while dark chocolate improved glucose and insulin responses to the oral glucose tolerance test.

Compared to baseline, blood pressure decreased after dark chocolate consumption. White chocolate had no effect on 24-h, daytime or nighttime blood pressure. The graphs below show the changes in systolic and diastolic blood pressure.

Dark chocolate also increased flow-mediated dilation, which measures endothelial function. Again, white chocolate had no effect compared to baseline. Interestingly, dark chocolate also reduced LDL cholesterol compared to baseline and white chocolate but had no effect on triglycerides and HDL.

Conclusion

In people with hypertension and impaired insulin sensitivity, dark chocolate (but not white chocolate) reduced blood pressure and improved glucose tolerance and insulin sensitivity. Endothelial function was also improved.

What's interesting about this study is that the duration was so short: the participants saw improvements in just two weeks. And, unlike in many studies, they weren't given cocoa powder or a small dose of dark chocolate, but an entire 100 gram chocolate bar for each day. Also, the subjects were not diabetic, and they only had stage 1 hypertension (systolic 140-159 mmHg, diastolic 90-99 mmHg), which suggests that dark chocolate is helpful even before things get really bad.

I try to keep my intake at around 50 grams per day on average, but at least this study shows that higher amounts are not bad for cholesterol, blood pressure or insulin sensitivity. The reasons I try to stay below 100 grams are the high iron and copper contents and possible lead contamination in cocoa powder.

Still, if you're eating milk chocolate with a low cocoa content (typically around 30%), consider upping the ante and slowly progressing towards darker chocolates. It's the better choice in at least five different ways.

For more information on blood pressure, insulin and cholesterol, see these posts:

Hibiscus Tea Increases HDL, Lowers LDL and Triglycerides
The Many Health Benefits of Rooibos Tea
Intermittent Fasting Improves Insulin Sensitivity Even without Weight Loss
Intermittent Fasting with a Condensed Eating Window – Part III: Fasting Blood Glucose, Cortisol & Conclusion

What a "Heart-Healthy" Diet Does to Your Cholesterol Levels

It's the butter that is bad for you, not the bread... right? (Photo from flickr.com)

What happens when you follow the American Heart Association's dietary recommendations? You know, a diet high in whole grain, vegetables, fruit and berries, but low in animal protein and fat, especially that nasty artery-clogging saturated fat.

According to conventional wisdom, you will be healthier in general. In particular, your cholesterol levels are supposed to improve – though it's never quite clear what "improvement" here means. Is it lower total cholesterol? Or perhaps lower LDL and higher HDL? And what about triglycerides and oxidized LDL?

Fortunately, a few years ago the Journal of the American Heart Association published a study that looked at what happens to cholesterol levels while on the officially heart-healthy diet (link). In contrast to many other studies, the participants in this one were healthy and had normal cholesterol levels to begin with. The idea was to see whether adopting an optimal diet would make them even healthier.

Study design and composition of diets

The study included 37 healthy women and consisted of two phases. During the first phase, the women followed a low-fat, low-vegetable diet for five weeks. After that, there was a three week washout period, followed by the second experimental diet. This second diet was the "optimal" diet, which was also low-fat but this time included lots of vegetables, fruit and berries. To make sure that the dietary guidelines were followed, the meals were supervised.

Both diets included 8 portions of grain products, 3-4 portions of low-fat or fat-free dairy products, and 2 portions of lean meat, chicken or fish. In the first phase, the subjects were given 2 portions of fruit and vegetables per day. In the second phase, the amount of fruit and vegetables was increased to 4-5 and 5-6 portions, respectively.

Dietary fats were replaced vegetable oils and spreads which contained minimal amounts of trans fats. The amount of total fat and saturated fat decreased, whereas the amount of polyunsaturated fats increased. To replace the lost calories, the subjects ate more carbohydrates and protein. Fiber intake also increased; in the second phase, it was nearly twice as much as at baseline.

Thus, both diets were very close to official recommendations: they included only moderate amounts of fat and animal protein, the fat was mostly from vegetable oils high in polyunsaturated fatty acids, dairy products were low in fat or fat-free, and grain products high in fiber were included. In addition, the second phase was high in veggies, fruits and berries.

HDL, LDL and triglycerides

After the low-fat, low-vegetable phase, total cholesterol was unchanged. On the other hand, triglycerides and HDL decreased, while LDL levels increased. The increase in LDL was apparently not statistically significant, which is probably due to the small sample size.

When the amount of vegetables, fruit and berries was increased, total cholesterol decreased. Triglycerides remained the same, but both HDL and LDL decreased:

Thus, reducing the amount of fat in the diet and replacing animal fats with vegetable oils did not change total cholesterol but did change the cholesterol profile: HDL and triglycerides decreased, while LDL increased. From the "good cholesterol, bad cholesterol" standpoint, adopting a low-fat diet actually changed things for the worse.

Things were not much better when vegetables, fruit and berries were added to the low-fat diet. Total cholesterol was clearly reduced, which by some standards is admittedly a positive change. Importantly, however, this change was not achieved through a decrease in "harmful" LDL but in "healthy" HDL.

The amount of triglycerides did decrease compared to baseline, but the reason is unclear. Generally, replacing fats with carbohydrates seems to increase triglycerides. Also, triglycerides decreased after the first phase, when the diet was low in vegetables, and did not decrease further after the second phase, so dietary antioxidants don't seem to be the explanation either. One thing that comes to mind is alcohol intake, which is not reported in the study. Perhaps the subjects reduced their alcohol intake while on the experimental diets? That would show up as a lower triglyceride score, but we can't know for sure.

Oxidized LDL and lipoprotein (a)

Both oxidized LDL and lipoprotein (a) are independently associated with a higher risk of atherosclerosis – more so than total cholesterol or LDL. In fact, oxidized LDL (ox-LDL) is believed to cause clogging of arteries and inflammation. Lipoprotein (a), also called Lp(a), is a known risk factor in many cardiovascular diseases, although its function is not entirely understood.

The most interesting result of the study is that the number of oxidized LDL particles and Lp(a) increased significantly as a result of following the low-fat diets. Oxidized LDL increased by a whopping 27% in the first phase. Even after vegetables, fruits and berries were added to the diet, ox-LDL levels were still 19% higher than at baseline. Similarly, Lipoprotein (a) was 7% higher after the first phase and 9% higher after the second phase compared to baseline.

What this means is that two important risk factors of atherosclerosis worsened markedly after following the very dietary recommendations that are supposed to reduce risk of atherosclerosis. Although plasma antioxidant capacity correlated with the intake of fruit, vegetables and berries, the antioxidants in them were clearly not enough to protect from these harmful changes.

The changes in total cholesterol, HDL, LDL and triglycerides were relatively small, which may be partly due to the short duration of the study. However, the 27% increase in ox-LDL demonstrates that diet can have a dramatic even in a short period of time.

Conclusion

The authors describe the results as "unexpected". According to them, a decreased intake of fat – especially saturated fat – should have led to a decrease in risk factors. They quote a number of studies where replacing saturated fatty acids with polyunsaturated fatty acids led to a "beneficial" decrease in total cholesterol. So why did the risk factors of atherosclerosis not see a similar "beneficial" change?

It is true that fats and oils high in polyunsaturated fatty acids generally tend to lower cholesterol (although the relationship between different fatty acids and cholesterol is more complicated than that). A completely different question is whether total cholesterol even matters, however. Even official recommendations acknowledge that the ratio of LDL to HDL is a better predictor of CVD than total cholesterol.

As was to be expected, the low-fat diets in this study did reduce total cholesterol. But if that decrease happens by reducing HDL and not changing or even increasing LDL, is the change really for the better? Most importantly, if the drop in total cholesterol comes with a marked increase in Lp(a) and oxidized LDL, can the results really be seen as beneficial?

Since the results of the study are incompatible with the cholesterol hypothesis and dietary recommendations, the authors came up with an alternative explanation. According to their hypothesis, high Lp(a) and ox-LDL may in fact be a sign of existing artherial damage being fixed and therefore a positive thing – but of course only in the case of low-fat diets. Right.

For anybody who has been keeping up with the gradual destruction of the cholesterol hypothesis, these results are not all that surprising. For example, we already know that polyunsaturated fatty acids oxidize much more easily than monounsaturated or saturated fats. It seems logical that LDL would be oxidized also.

What is somewhat surprising, however, is that the study was published in a journal that promotes the official dietary recommendations as heart-healthy.

For more information on cholesterol and diets, see these posts:

Which Oils and Fats Are Best for Cooking?
Carotenoids and Lipid Peroxidation: Can Vegetables & Fruit Reduce ALEs?
Sugar and AGEs: Fructose Is 10 Times Worse than Glucose
Anthocyanins from Berries Increase HDL and Lower LDL

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 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

Fish Oil Decreases Inflammatory and Atherogenic Gene Expression

Salmon contains more than 2 grams of omega-3 fatty acids per 100 grams. (Photo by Marco Veringa)

While the argument over polyunsaturated fats in general continues, most people consider omega-3 fatty acids to be very beneficial.

The most important omega-3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA and DHA are often marketed as good for heart health, and indeed there is a lot of evidence to support this claim. ALA, on the other hand, is much less effective, because it first needs to be converted to EPA and DHA by the body to be usable, and only a very small amount gets converted (link).

One of the best and easiest sources of EPA and DHA is fatty fish such as salmon. Another good option is fish oil or fish liver oil, which contain high amounts of EPA and DHA. While several studies have shown beneficial effects from consuming these omega-3 fatty acids, the mechanism of action has not been clear.

To shed light what EPA and DHA actually do in the human body, a new study looked at changes in gene expression after consuming fish oil (link). In healthy subjects, daily ingestion of fish oil changed the gene expression profile to a more anti-inflammatory and antiatherogenic status.

Study method

The study included 111 healthy elderly subjects (at least 65 years old) who did not take fish oil supplements and ate fish no more than four times a week. They were randomized to receive either fish oil with a low or high omega-3 content or sunflower oil.

The high-dose fish oil contained on average 1,093 mg of EPA and 847 mg of DHA, while the low-dose fish oil provided 226 mg of EPA and 176 mg of DHA. The total amounts omega-3 polyunsaturated fatty acids were 1.94 grams and 0.4 grams, respectively. According to the authors, the higher dose is about the same as eating 10 portions of fatty fish weekly, and the lower dose equals 2 portions weekly.

Results

Consuming the high-dose fish oil resulted in gene expression changes of 1040 genes, whereas sunflower oil changed the expression of 298 genes. Out of these, 140 genes were overlapping, meaning that the combination of EPA+DHA uniquely changed 900 genes. Except for one gene, the direction of change was the same in both groups.

Supplementation with a high dose of EPA+DHA for six months significantly decreased the expression of genes involved in the inflammatory pathways, including eicosanoid synthesis, interleukin signaling, and MAP kinase signaling.

Moreover, a similar effect was seen in processes involved in the formation of atherosclerosis. Decreased gene expression was observed in pathways related to cell adhesion, scavenger receptor activity, and adipogenesis. Participants taking the high-dose fish oil also showed a reduction in oxidative stress. You can find the full figures from the paper here and here.

In the low-dose fish oil group, only a small sample of the genes were measured for changes in expression. The results showed that the lower dose of EPA+DHA also resulted in a down-regulation of genes and that this change was somewhere in between those seen from high dose EPA+DHA and sunflower oil.

Conclusion

Supplementing with 1.9 grams of EPA and DHA (~1.1 g EPA and ~0.8 g DHA) daily resulted in favourable changes in gene expression related to inflammation and atherosclerosis in elderly subjects. Among the genes whose expression was decreased were NF-kappa-beta targets, proinflammatory cytokines, and genes involved eicosanoid synthesis.

These results are in agreement with earlier ex vivo studies and support the idea that EPA and DHA, two omega-3 polyunsaturated fatty acids found in fish, are beneficial in reducing inflammation and preventing atherosclerosis.

For more information on inflammation and fish oil, see these posts:

Swine Flu and Avoiding the Cytokine Storm: What to Eat and What Not to Eat?
Examining Possible Causes for Slower Wound Healing
Green Tea Protects from Arthritis in Rats
Intermittent Fasting with a Condensed Eating Window – Part III: Fasting Blood Glucose, Cortisol & Conclusion

Blood Test Analysis: The Cholesterol and Saturated Fat Issue Revisited

Alcohol and triglycerides don't go well together. (Photo by paulaloe)

I just got my yearly blood test results back last week. I would've liked to have had a much larger blood panel done, but healthcare being what it is, I had to settle for two tests: a vitamin D test and a cholesterol test.

This post is a report on my cholesterol levels and how they differ from the results of the previous blood test. Possible explanations for the changes are also discussed.

My old cholesterol levels

If you're a long-time follower of this blog, you may remember my high-fat diet experiment from a year and a half ago. Part of the idea behind the experiment was to see whether eating a diet high in fat (especially saturated fat) is bad for cholesterol. My cholesterol levels after the experiment were as follows:

LDL: 3 mmol/l (117 mg/dl)
HDL: 2.24 mmol/l (87.36 mg/dl)
Total: 5.7 mmol/l (222.3 mg/dl)
Triglycerides: 0.92 mmol/l (81.88 mg/dl)

For a more thorough summary of the experiment and its results, see this post. In any case, I was quite pleased with my cholesterol levels, despite the fact that official recommendations consider my total cholesterol to be a bit too high.

My current cholesterol levels

So how do the old levels compare with the new ones? Here's the data from the most recent blood test:

LDL: 2.4 mmol/l (93.6 mg/dl)
HDL: 2.67 mmol/l (104 mg/dl)
Total: 5.7 mmol/l (222.3 mg/dl)
Triglycerides: 1.5 mmol/l (133.5 mg/dl)

As you can see, total cholesterol has remained the same, but the ratio of LDL to HDL (which is much more important for health than total cholesterol) has improved from 1.34 to 0.9 – that is, HDL is actually higher than LDL.

Triglycerides have increased, which is bad of course, but I suspect this is due to a two-week drinking binge right before the measurement. Low-carb diets lead to lower triglyceride levels, and since my cholesterol levels in general had improved, this is the only explanation I can think of. Apparently even moderate alcohol consumption can lead to large changes in triglyceride levels (link). I probably should've had the blood test before my holiday instead of after it.

Dietary changes I've made

So what is the explanation behind this improved LDL/HDL ratio? Compared to my diet during the high-fat experiment, I've made the following changes:

- Less cream
- Less butter
- Less yoghurt
- Less cheese
+ More dark chocolate
+ More coconut milk
+ More red palm oil
+ More green tea

Even though I ended the experiment, my fat intake on a typical day is still very high. I also get a lot of saturated fat from chocolate, coconut milk, red palm oil and meat – so much that according to official standards I should probably be dead by now from all the "artery-clogging harmful fats". Thus, while I have gotten rid of much of the dairy I was consuming before, most of the fat I eat is still saturated, and fat is still the main constituent of my diet.

Other changes in lifestyle

In addition to these dietary changes, I've started taking vitamin D3 (2,000 IU daily for a few months, then 5,000 IU) and a multivitamin (2 capsules of Ortho-Core daily) regularly. I've also tried various other supplements, but most of the experiments have likely been too short to have had any effect on cholesterol. In addition, my exercise routine has shifted somewhat from resistance training to aerobic training (i.e. less gym and more running), but I doubt this would have much effect either.

And then there's of course intermittent fasting, which is one of the longest-running experiments on this blog. For the past few weeks I've been skipping breakfast and lunch, but before that, I was eating for 24 hours and then fasting for 24 hours. There is one study that suggested eating only one large meal instead of three smaller ones could be bad for cholesterol, but as I wrote in the post, there were some problems with this study. My hunch is that periods of fasting are either neutral or good for cholesterol.

Conclusion

Continuing to eat a diet high in fat, especially saturated fat, has improved my ratio of LDL to HDL. Though I don't believe the matter is as simple as labeling one "good cholesterol" and the other "bad cholesterol", I do think the ratio is a much better indicator of health risk than total cholesterol. In particular, high HDL appears to be very good, while the potential unhealthiness of LDL depends on the size of the LDL particles.

My diet is in stark contrast to official recommendations, which promote polyunsaturated fats and discourage the consumption of saturated fats and meat. As I've written before, the science does not appear to support the hopelessly outdated official position on fats and cholesterol. The pamphlet I got with my results actually warns never to eat coconut or organ meats but to eat as much candy as you want!

At least in my case, going against the grain has not resulted in any health problems – on the contrary, a higher HDL than LDL is a very good sign. Until I see clinical studies that show saturated fats are harmful, I'm not planning on making huge changes to my diet.

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

Coconut Lowers LDL, VLDL and Triglycerides, Raises HDL
How Does Fructose Affect Triglyceride and Cholesterol Levels?
Niacin Raises HDL, Lowers LDL, VLDL & Triglycerides
Low-Carb vs. Low-Fat: Effects on Weight Loss and Cholesterol in Overweight Men