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

Enhancing Immunity with Probiotics: Can They Ward Off the Flu?

Kefir is a natural source of probiotics. (Photo by uncle andrey)

I don't know if it's the swine flu or a normal influenza virus going around, but seems like everybody's been getting sick during the past few months. This particular virus is particulary resilient, with people being ill for weeks at a time.

I succesfully managed to avoid the flu for about a month, while just about everyone else was complaining about the cold that just won't go away. Feeling very pleased with myself, I put my exceptional immunity down to the optimal vitamin D levels I've achieved after supplementing with 5,000 IU per day. This really has reduced the frequency of colds, but it wasn't enough to save me from catching the same thing as everyone else.

So, having nothing better do to than to lie in bed feeling crappy, I thought I'd educate myself on the subject of curing and preventing viral infections such as the common cold. Given that a prescription for antibiotics (to treat an ear infection) oddly coincided with my falling ill, I was interested in whether probiotics might be of use. In this post, we'll take a look at the evidence behind probiotics and immunity.

What are probiotics?

Our bodies are host to trillions of microorganisms, most of which are good and some of which are harmful. Probiotics is the name given to some strains of bacteria (a type of microorganism) that are thought to promote overall health.

These bacteria either naturally exist in foods, or are used to fortify foods, or sold as supplements. Yoghurt, for example, may naturally contain live strains or bacteria, but there are also lots of yoghurts with added bacteria. The idea is that by consuming these bacteria, their proportion in the gastrointestinal tract is increased, which in turn will have benefits for health.

Probiotic bacteria play several roles in maintaining overall health. We probably don't know all the ways probiotics effect health, but here's a list of functions commonly cited in the literature:

• Boosting the immune system
• Limiting the growth of pathogenic organisms
• Food digestion
• Nutrient absorption
• Protection from cancer
• Allergy resistance

The function we're interested here is immune enhancement. Probiotic bacteria play a key part in immune function through a variety of mechanisms (link). For example, they increase the number of circulating white blood cells or leukocytes, which defend the body against infectious disease. They also increase levels of antibodies or immunoglobulins, which are used to identify and neutralize foreign objects like viruses and bacteria.

Can probiotics prevent the flu?

While the bacteria in the gastrointestinal tract clearly play an important role in immune function, it's far less clear whether probiotics consumed with foods or as supplements have any effect. Some product reviews have revealed that up to a half of the probiotic products studied may contain significantly less live bacteria than advertised. And even if they do contain the bacteria, will eating them enhance the immune function?

Well, at least pharmaceutical grade probiotic products seem to do the trick. In one study, healthy Swedish workers were randomised to receive either Lactobacillus reuteri or placebo for 80 days (link). In the placebo group, 26.4% reported being sick during this period, compared with only 10.6% in the probiotic group. These figures included only illnesses related to the respiratory and/or gastrointestinal tracts, so the probiotic treatment clearly improved their immune system. It was especially effective in those participants who worked the night shift.

In a 6-month study on children, probiotic consumption reduced both the duration and incidence of fever and cough compared to placebo (link). The probiotic strains used were Lactobacillus acidophilus and Bifidobacterium animalis. The combination of the two was better than L. acidophilus alone, reducing fever incidence by 72.7%.

Another study found that the cellular immunity of the elderly improved when the probiotic Bifidobacterium lactis HN019 was added into their milk (link). The authors note that the improvements were greatest in those participants who had poor immune systems before the treatment. Instead of measuring how often they got sick, however, the authors measured the proportions of T lymphocytes and natural killer cells, so it's not clear how this translated into overall health.

Indeed, not all studies have shown that probiotics can prevent you from catching a cold. One large study found that supplementing healthy adults with probiotic lactobacilli and bifidobacteria had no effect on the incidence of the common cold (link). It did, however, reduce the severity of symptoms and shorten their duration by almost 2 days.

Conclusion

Probiotic bacteria are known to play an important role in immune function. Less is known, however, about whether taking probiotic supplements can enhance the immune system and reduce the incidence of viral infections such as the common cold.

Based on the few studies that have actually looked into this, it seems that at the very least, long-term supplementation with probiotics reduces the duration and severity of the symptoms flu. Some of the studies also found that probiotics dramatically reduced the incidence of flu. Thus, there is a basis for the claim that probiotics can help prevent you from getting sick.

There's no evidence that taking probiotic supplements after you've gotten sick will do anything, however. It also appears that the effect of probiotic is greatest in those people whose immune systems are not working properly or are under a lot of stress.

Keep in mind that some of the foods with added probiotics may not actually contain any live bacteria, despite what it says on the label, since the bacteria die quickly unless the product is kept refridgerated. The same is true of supplements in capsule form, unless it specifically states that the product is stable in room temperatures. With powdered supplements, moisture is a potential problem.

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

L-Carnitine, Exercise Performance & Oxidative Stress
The Role of Coenzyme Q10 in Oral Health
Swine Flu and Avoiding the Cytokine Storm: What to Eat and What Not to Eat?
Examining Possible Causes for Slower Wound Healing

5 Reasons Why Dark Chocolate Is Better than Milk Chocolate

Look good? Forget it, there's way too much sugar. (Photo by .craig)

You may have thought of chocolate as a guilty pleasure, but the ancient Maya considered it the food of gods.

Granted, the Maya also thought cutting out someone's heart in a ritual ceremony was a good fun, but they did get one thing right: chocolate really is a health food. That is, as long as you buy the dark kind. In fact, the darker the chocolate the healthier it is. As good as that sugar-laden milk chocolate bar may taste, it wouldn't have made its way into any self-respecting Maya feast.

If you don't believe me, read further for three good reasons to choose dark chocolate instead of milk chocolate.

1. Dark chocolate is better for weight loss.

Even though the amount of calories in milk chocolate and dark chocolate are pretty similar (and in fact milk chocolate sometimes contains fewer calories), dark chocolate contains significantly less carbohydrates. Milk chocolate usually has about 50 grams of carbs per 100 g, while the amount of carbs in dark chocolate ranges from 8 to 35 carbs, depending on how dark it is. A chocolate with 70% cocoa has ~30 grams; a 85% chocolate has ~20 grams.

If weight loss or maintenance is your goal, the combination of large amounts of carbohydrates and fat is something to avoid. A high carbohydrate load will increase insulin secretion, which is a signal for the body to store energy as fat. The reason why low-carb diets are so effective for weight loss is their effect on insulin: even if you eat lots of fat, if there are no carbs present to drive insulin up, the energy from dietary fat won't be stored into fat cells.

Unless you consume only a small quantity or restrict other carb sources to a minimum, combining milk chocolate with a low-carb diet is going to be difficult. If your goal is to stay under 50 grams per day, 100 grams of milk chocolate fills up your entire quota. But 100 grams of 85% dark chocolate still leaves you with 30 grams to spend on other carb sources, making dark chocolate a viable option even for low-carb dieters.

2. Dark chocolate causes less aging.

Okay, so perhaps a bit of an exaggeration there, since we don't know exactly how big a role advanced glycation end-products play in the aging process. We do know, however, that the accumulation of AGEs is one of the seven biomarkers of aging, which makes avoiding them a sensible goal.

As it happens, weight gain is not the only problem with the carbs in milk chocolate. Almost all of the carbohydrate in chocolate is sucrose, which is half glucose and half fructose. Even though the word 'glycation' in 'AGE' implies that glucose is the culprit, the fact is that fructose is much more prone to cause AGEs in the body. Since the main ingredient in milk chocolate is sugar, a 100 grams of milk chocolate will also give you a hefty dose of fructose.

Dark chocolate, on the other hand, is mostly composed of fat – cocoa butter, to be specific. The fatty acid composition is 61% saturated fat, 36% monounsaturated and only 3% polyunsaturated fat, making cocoa butter very resistant to oxidation. And if you're worried about cholesterol, here's something to ease your mind: almost all of the saturated fat in cocoa butter is cholesterol-neutral stearic acid. Fructose, however, may increase triglycerides levels.

Unlike dark chocolate, milk chocolate also contains some lactose. In addition to making milk chocolate an impossible treat for some lactose intolerants, lactose also causes glycation. Lactose breaks down to glucose and galactose, and like fructose, galactose appears to form AGEs more rapidly than glucose.

3. Dark chocolate has more cocoa polyphenols.

The health benefits of chocolate are almost entirely due to the polyphenols found in cocoa. As a rule of thumb, whenever you read something good about chocolate, what they're really talking about is cocoa. Therefore, as the cocoa content of chocolate increases, so do its positive effects on health. A standard milk chocolate will contain about 30% cocoa, while premium dark chocolates usually have more than 70%.

Another thing that reduces the polyphenol content of chocolate (by 60-90%) is alkalization (link), also known as Dutch processing or simply Dutching. Alkalization was invented in the 19th century to get rid of some of the bitterness of cocoa powder and to make it more palatable. Non-alkalized cocoa powder is a more light brown in color and tastes less sweet than alkalized cocoa powder.

Nowadays Dutch processing is very common among industrial chocolate makers (link), which suggests that there's a good chance the average high-sugar milk chocolate will contain alkalized cocoa. Many dark chocolates seem to use non-alkalized cocoa, however, probably because the bitterness is perceived as preferable among chocolate enthusiasts.

4. The cocoa polyphenols in dark chocolate are more bioavailable.

Even if your dark chocolate happens to be made from alkalized cocoa, you'll still get more bang for your buck in terms of polyphenols, because the polyphenols will be more bioavailable. This is again related to differences in the macronutrient composition of chocolates.

First, the bioavailability of cocoa polyphenols depends partly on the fat content of chocolate. One in vitro study showed that cocoa liquor (which is about 50% fat) retained more polyphenols than cocoa powder (about 15% fat) when submitted to a digestion model (link). The reason appears to be that the higher fat content increases the stability of cocoa polyphenols during digestion. Second, sucrose and milk protein may affect the absorption of polyphenols negatively (link).

Dark chocolate contains no milk protein, less sucrose and much more cocoa liquor than milk chocolate. The actual content varies, since different countries have different regulations on what kind of chocolates can be called "dark chocolate". The FDA, for example, states that dark chocolate must contain at least 35% chocolate liquor, while milk chocolate only needs to have more than 10%.

Also, chocolates with 40-70% cocoa are also sometimes sold as "dark chocolate", so be sure to check the ingredient list before purchase. The words "cocoa mass", "cocoa liquor", "cocoa powder", "cocoa paste", "cocoa solids", or something to that effect should be first on the list – if "sugar" is mentioned first, it's definitely not real dark chocolate.

5. Dark chocolate is more filling.

Anyone who has tried both milk chocolate and dark chocolate must have noticed that it takes much less to satisfy chocolate cravings with the latter than the former. I can personally eat 200 grams of milk chocolate (more than 1,000 kcal) in one go without having my craving satisfied. With 99% dark chocolate, a few pieces is enough. A similar effect was shown in a study from last year (link).

This, as mentioned before, is not related to energy content, because milk chocolate and dark chocolate have virtually the same amount of calories. Rather, the reason why a smaller quantity of dark chocolate is enough is probably a combination of less sugar and more nutrients. Humans generally have a preference for sweet foods, which is why we love candy when we're kids. But part of the reason why we can't stop eating candy until we feel sick is that there are no nutrients in candy, only calories. This lack of nutrients causes our body to send the satiety signal way too late.

Since dark chocolate is higher in cocoa powder, it's also higher in many nutrients, such as iron, magnesium, phosphorus, copper and manganese. Combined with the lower amount of sugar and high amount of fat, it's no surprise you get your daily chocolate fix quicker with dark chocolate than milk chocolate.

Summary

Dark chocolate contains less sugar, more cholesterol-neutral fat, and more cocoa polyphenols in a more bioavailable form than milk chocolate. Dark chocolate is also more filling, which means it takes less calories to satisfy your chocolate cravings.

Keep in mind, however, that excess consumption of dark chocolate has its downsides too. Cocoa powder is high in iron and oxalates, which are harmful in high quantities. We'll return to the subject of optimal intakes in future posts, but for now, I limit mine to 50-100 grams of chocolate per day.

For more information on chocolate, sugar, fat, and health, see these posts:

Tea, Coffee and Cocoa: All Good for Your Teeth
SAs, MUFAs vs. PUFAs: Fat Storage Depends on Type of Fatty Acid in Rabbits
Fats and AGEs: PUFAs Are Even Worse than Fructose
Low-Carb vs. Low-Fat: Effects on Weight Loss and Cholesterol in Overweight Men

Which Oils and Fats Are Best for Cooking?

Avocado oil has the highest smoking point. (Photo by Muffet)

If you've wondered which oils and fats are the best choices for cooking your meals, this post is for you.

The first question we need to ask is what makes an oil good or bad for cooking? Putting the cholesterol issue aside for a moment, we can say that perhaps the most important thing is how well the oil tolerates heat. We are using it for cooking, after all.

Two factors that affect heat tolerance are smoking point and oxidation. Smoking point is, as you might have guessed, the temperature at which the oil begins to smoke. It's also the point the oil starts to break down chemically. This is something you generally want to avoid, so it's usually recommended that you don't heat the oil to its smoking point. This, of course, rules out using oils with a low smoking point for cooking at high temperatures.

The second factor, oxidation, is related to smoking point in the sense that both are affected by temperature. However, oxidation also happens at lower temperatures than are needed for the oil to start smoking. Oxidation is problematic because the lipid peroxidation end-products (ALEs) it creates can wreak havoc inside the body. These products have been shown to accumulate with aging and cause problems such as liver spots on the skin.

So which oils are most susceptible to oxidation? If you've read this blog before then you already know the answer: polyunsaturated fats. In fact, polyunsaturated fatty acids (or PUFAs) tolerate heat very poorly. Not only do they oxidize when you heat them on a frying pan, they do so inside the body as well. On the other hand, monounsaturated fats are much more resistant to oxidation than polyunsaturated fats. Saturated fats are the most resistant.

This gives us a good rule of thumb when looking for fats to use in cooking: avoid oils high in polyunsaturated fatty acids. Because of their potential to undergo lipid peroxidation inside the body, I tend to restrict their consumption altogether, but even if you are a fan of vegetable oils and omega-3, using them for cooking is not a very good idea.



The table above shows the relative percentages of saturated (SA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) in various cooking oils and fats (data from US and Finnish food databases). They are in a decreasing order of PUFA content, meaning that the oils moist suitable for cooking are on the left and the least suitable oils are on the right.

As you can see, coconut oil has the highest SA content and the lowest PUFA content of all oils, making it very resistant to oxidation. Ghee and butter also have very little PUFA and lots of saturated fat. Based on this, butter is actually one of the best choices for cooking, although the high AGE content of butter and its tendency to brown quickly suggest to me that perhaps ghee is a better option. The reason might be that butter also contains some protein and a small amount of carbohydrate.

Palm oil and lard are somewhat lower in saturated fat than the first three, but since their MUFA content is quite high, they still make good choices for cooking. The rest to the right of these five are less than optimal. Corn oil, sesame oil, rapeseed oil, peanut oil, and canola oil are all high in polyunsaturates, making them prone to lipid peroxidation. And unless you buy them cold-pressed, they will have been heated during refining anyway, so some oxidation has probably happened before you even use them.

What about olive oil then? Even though everyone seems to love olive oil in general, there's something of a debate going on over whether it should be used for cooking purposes. My opinion is that, like the graph suggests, it's not the worst choice but it's not the best either. The smoking point of extra virgin olive oil seems to vary from 160 to 190 °C, depending on the free fatty acid content. Virgin olive oil, however, has some properties that make it more heat-tolerant than most other oils (link).

In general, the less refined the oil, the lower the smoke point. Unrefined oils high in PUFAs have the lowest smoking points (link), but high saturated fatty acid content does not necessarily guarantee a high smoking point. Coconut oil, for example, has a fairly low smoking point (177 °C, about the same as butter and lard) compared to peanut oil (227 °C). Refined avocado oil, which is mostly monounsaturated fat, appears to have one of the highest smoking points at 255-270 °C (link). Ghee is another oil with a very high smoking point (252 °C).

So which oils should you use for cooking? For sautéing and cooking at light to medium temperatures, my choice would be the ones on the left of the graph: coconut oil, ghee, butter, palm oil, and lard. If you stay below 170 °C, you're in pretty safe waters in terms of oxidation regardless of which one of them you choose. Virgin olive oil seems like a viable choice, too; just make sure the particular olive oil you're using it doesn't start smoking.

For searing, browning and other methods of cooking requiring higher temperatures, ghee and avocado oil seem like the best choices. When it comes to resistance to oxidation, ghee might take the cake, but avocado oil appears to have the highest smoking point of all oils, even though it does have 13.5% PUFAs. Still, keep in mind that when cooking at very high temperatures, some advanced glycation end-products (AGEs) are bound to be generated.

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

Coconut Lowers LDL, VLDL and Triglycerides, Raises HDL
My Current Health Regimen
Blood Test Analysis: The Cholesterol and Saturated Fat Issue Revisited
Should Saturated Fat Be Avoided in Low-Carb Diets?

Fore! Gators in S.C. News

Golf in South Carolina (which proclaims itself "First in Golf" because the Palmetto State claims to have more golf courses per capita than any other state and/or because they're just so damn good) made headlines today. I noticed these headlinees while catching up on the news over my eggs and bacon this morning.

Headline One from The State: "SC golfer loses arm in alligator attack"

Headline Two from USA Today: "Second homes: Golf, sun and sand for less in Myrtle Beach"

Let's hope the readers of Headline Two don't see Headline One. I don't mean to make light of this poor fellow. It made headlines because it's actually quite rare. Just ten minutes from my house is a lake with several gators. I helped with the fishing station at Cub Scout camp there and we just steered clear of them. Once a kid snagged one by accident (the gator gobbled the bobber) and we just cut the line. Generally, the gators leave you alone.

And to friends who want to come for some fun in the sun with me, I promise you we'll golf at alligator-free courses. Or I'll take advantage of South Carolina's generous gun sales policy (I'm sure a nice gator rifle could fit in my bag between my driver and three-wood) and if we're confronted with a gator, you can go home with some sweet alligator golf shoes.

Fats and AGEs: PUFAs Are Even Worse than Fructose

Olive oil is mostly monounsaturated fat. (Photo by Splat Worldwide)

While the exact role AGEs play in aging is still unclear, it seems that reducing their accumulation in the body is a useful goal. And if for no other reason, how about being superficial: liver spots, for example, are a visible sign of AGEs in the skin. If you want to look youthful, glycation is not the way to go.

The question of how to avoid AGEs has proven to be more difficult than one might think, however. If it was merely a matter of reducing the formation of advanced glycation end-products during cooking, we could just cook our foods at lower heat and use water instead of frying at high temperatures. But as we've seen, the AGEs we get directly from food may not be as important as the AGEs that form inside our body as a result of internal glycation.

The term 'advanced glycation end-product' is somewhat misleading in the sense that they are not formed only by glycation, which refers to glucose molecules binding to protein or lipid molecules, but also by fructation, which is essentially the same thing but this time with fructose. In fact, fructose is much more prone to form these products than glucose. Since there's no such term as 'advanced fructation end-product', they're also referred to as AGEs (other sugars like galactose go through a similar process too; more on that in another post).

To complicate this further, similar products are also formed during cooking when fats alone are exposed to high heat and air. This process is known as lipid peroxidation. The end results of lipid peroxidation are referred to as either AGEs or ALEs, short for advanced lipoxidation end-products. For the sake of simplicity, I will refer to all of them as AGEs, unless the difference is important.

So we now have several different ways to accumulate AGEs: eating cooked foods that contain sugars heated with protein or fats, eating uncooked foods that contain sugars, or eating oxidized fats. And, like glycation, lipid peroxidation can also happen endogenously. That is, even if the fats you eat do not contain any AGEs, they can still form AGEs inside the body if they are unstable and prone to oxidation.

The bad news is that not only does lipid peroxidation lead to AGEs, it appears to do so more rapidly than glycation does. CML, a product of the oxidative degradation of glycated protein and a common measure of AGE levels, is actually formed through the oxidation of arachidonic acid in much higher quantities than from glycation (link). CML is a handy way to compare things, because it can be formed through glycation, fructation or lipid peroxidation.

The reason you should keep your fish oil and flax seed oil in the fridge is precisely because they, like other highly unsaturated fats, are easily oxidized (link). Cooking with these oils is a really bad idea. Through lipid peroxidation, polyunsaturated fats or PUFAs are more prone to form AGEs. Below is a comparison of CML formation from three different fatty acids and glucose (link):



The left graph shows that arachidonic acid forms CML at about twice the rate as linoleic acid. The formation of CML from oleic acid is close to zero. Compared to glucose in the right graph, the two PUFAs here are at least 10 times as prone to AGE formation – very much like fructose, except that if you look at the fructose graphs, the 10-fold increase is not seen as early as it is in these graphs.

The explanation for the differences is that lipid peroxidation increases exponentially as a function of the number of double bonds (link), i.e. the degree of unsaturation. Arachidonic acid is a 20-carbon chain PUFA with four double bonds and linoleic acid is an 18-carbon chain PUFA with two double bonds. Oleic acid, like all MUFAs, has one double bond. Note that this equation makes the omega-3 fatty acids DHA and EPA (with their 6 and 5 double bonds, respectively) the worst offenders.

So oils high in PUFAs seem to have the ability to raise the AGE burden much more than glucose, or even fructose. This could potentially explain some of the differences in AGE levels between omnivores and vegetarians – maybe vegetarians eat more vegetable oils than omnivores, since glucose and fructose intakes alone are insufficient to explain the results. The authors of the paper state:

Oxidation of fatty acid is clearly a more efficient source of CML, despite the fact that the glucose is in solution throughout the course of the experiment, while the PUFA are only progressively solubilized. Further, after 6 days of incubation, a large fraction of the arachidonate was oxidized based on its solubilization in the aqueous phase, while less than 2% of the glucose is oxidized during this same time period.

In the same study, arachidonic acid produced more than 10 times the amount glyoxal than it did CML. Glyoxal is another inflammatory compound, which in food is created by heating unstable (i.e. polyunsaturated) oils to high temperatures but which, again, can also be formed inside the body. Some of this glyoxal goes on to form AGEs, but the rest that doesn't isn't exactly life elixir either.

Unfortunately, the problems don't end with CML. Polyunsaturated fats also quite easily form other AGEs, such as malondialdehydelysine (MDA-lys) and carboxyethyllysine (CEL). Indeed, rats fed a diet high in PUFAs have over twice the level of MDA-lys in their brains compared to rats fed a diet high insaturated fat diet (link). Their levels of CEL and CML in the brain and MDA-lys in the liver are also significantly higher (although CEL and CML are lower in the liver). Unsurprisingly, MDA and CML deposits in the brain are implicated in Alzheimer's disease (link).

As I mentioned before, simply avoiding cooking with oils rich in PUFAs is probably not enough, because exposing them to high heat and air in the frying pan isn't the only thing that causes them to form AGEs. Reactive species such as radicals, transition metals, other electrophiles, and enzymes can also cause their oxidation inside the body (link).

In fact, it's not certain based on the studies mentioned here just how bad food-derived ALEs are. Perhaps ALEs from food are less important than ALEs formed endogenously. Endogenous AGEs certainly appear to play a bigger role than exogenous AGEs, although consuming excess amounts of AGEs is probably not a good idea either.

Personally, I'm trying to limit both endogenous and exogenous AGEs and ALEs by avoiding cooking at high temperatures and using saturated fats for frying. Stay tuned for more posts on the issue. Meanwhile, see these posts on glycation and fats:

AGE Content of Foods
The 7 Types of Aging Damage That End up Killing You
Green Tea Reduces the Formation of AGEs
Should Saturated Fat Be Avoided in Low-Carb Diets?

Hair Growth with Ayurveda – The Nutrich Oil Experiment

Licorice is used in Ayurvedic medicine for hair growth. (Photo by Pikaluk)

Now that my previous hair growth battle has come to its disappointing conclusion, it's time to start a new experiment. In this one, I'm going to take a plunge into the strange world of Ayurveda, the ancient Indian system of traditional medicine.

There are probably hundreds of plants used in Ayurvedic medicine that are claimed to promote hair growth. Some of them may be effective to a degree, while the majority of them probably do nothing, at least not for hair loss. The fact that there are so many balding Indians – including Ayurvedic practitioners – should make anyone suspicious of any wild claims about growing your hair back.

The product I've chosen is something called Nutrich oil. This hair growth tonic contains a number of oils and herb extracts, all meant to either treat male-pattern baldness, stimulate hair growth, or prevent graying. The oils and their proportions are:

• Sesame oil (sesamum indicum): 80%
• Coconut oil (cocos nucifera): 10%
• Castor oil (ricinus communis): 9.5%
• Almond oil (prunus amygdalus): 0.5%

All of these are mentioned as hair growth promoters in Ayurvedic literature, but scientific evidence is severy lacking. While coconut oil is antibacterial on the skin and has been shown to protect the hair from protein loss when used as a conditioner (link), there's not much reliable information out there on the other three. Sesame oil is apparently a common massage oil and is said to "remove toxins from the body", which immediately raises alarm bells in my mind, because nobody ever seems to know exactly what these "toxins" are. I couldn't find any data on almond oil as a hair growth promoter. Same thing with castor oil, though it does increase the luster of hair (link).

So not much going on in the oil department. Perhaps the more interesting part of the ingredient list are the herb extracts:

• Bhrungraj (Ecplita alba)
• Jatamansi (Nardostachys jatamansi)
• Brahmi (Centella asiatica)
• Nilpushpa (Indigofera tinctoria)
• Ratanjyot (Onosoma echiodes)
• Nagarmotha (Cyperus scariosus)
• Triphala (Emblica officinalis, Terminalia bellirica & Terminalia chebula)
• Gunja (Abrus precatorius)
• Chameli (Jasminum officinale)
• Dhatura
• Henna (Lawsonia inermis)
• Sankpushpi (Convolvulus pluricaulis)
• Khaskhas (Vetiveria zizanioides)
• Yashtimadhu (Glycyrrhiza glabra)
• Rasanjan (Berberis aristata)
• Ratanjali (Pterocarpus santalinus)

Out of these, Bhrungraj or Eclipta alba has actually been shown to grow hair in mice – even quicker than minoxidil, provided that the extract is not made with ethanol. Unfortunately, there's no mention on the label as to how the extracts were made. Even the absolute amount of the extracts is unclear, since only the relative quantities are stated.

Emblica officinalis, one of the components of Triphala, has been shown to increase cell proliferation, improve wound healing (link), and induce procollagen production (link), which may actually make it useful for hair growth. There's not much info on the other two, except that they're antibacterial (link). All three components together improve wound healing (link). Rasanjan (Berberis aristata) and Ratanjali (Pterocarpus santalinus) may also speed up wound healing (link, link).

Yashtimadhu, which is the Ayurvedic name for Licorice, is known to be antiandrogenic (link) and to suppress prostate cancer (link). These effects may be due to beta-sitosterol, which reduces 5-alpha-reductase (link). There are no in vivo studies showing that licorice topically or orally grows hair in animals or humans, however.

Jatamansi (Nardostachys jatamansi) and Sankpushpi (Convolvulus pluricaulis) are apparently good for the brain when taken orally, but a pubmed search gives nothing on hair growth. Brahmi, also known as Gotu kola or Centella asiatica also has a range of health benefits, but again, nothing related to hair. Jasminum officinale is anti-inflammatory (link), and some of the other ingredients are antioxidants, but that's about it.

With this in mind, I'm going to apply the oil on my right temple & hairline and also on my right eyebrow. The left side, meanwhile, is getting the tretinoin treatment. The bottle (100 ml) looks like it's going to last me quite a while, so the $20 I paid for it is not cheap but not overexpensive either.

The odour is not too bad, but it is really strong and reminds me of incense. Unless you want to smell like an Indian bazaar, massaging your entire scalp with this stuff seems like a potential hazard to me. A nightly application and then washing it off in the morning might work, but the color is green and absorption less than perfect, so be careful.

For more information on Ayurveda, consult your local yoga instructor. For more information on hair growth, see these posts:

North African Plant Extract (Erica multiflora) Increases Hair Growth
Capsaicin and Soy Isoflavones Promote Hair Growth
Do Flax Lignans Reduce Hair Loss from MPB?
Soy Protein Isolate Reduces DHT in Healthy Young Men

Anti-Aging in the Media: The Independent on Immortality

This is so much more peaceful than immortality. (Photo by net efekt)

Most of the anti-aging articles I've written about on this blog have ranged from neutral to positive, but every now and then there's a columnist out there with a different kind of mission.

A mission to tell the world that living longer is bad, that death is good, and that we should stop spending so much effort on trying to change things. This time it's E Jane Dickson from The Independent showing her true colors as someone who apparently sees no problem with masses of people dying from old age every day. Her message? 'Immortality isn't all it's cracked up to be'.

She begins by describing how future doesn't look like we imagined it would 20 years ago. Where are the flying cars and robots doing our housework for us? Clearly, then, all predictions about the future must be wrong. And who could be more wrong than Ray Kurzweil, the lord of all predictors:

"I believe, he says, "that in around 20 years we will have the means to reprogram our bodies' stone-age software so we can halt, then reverse ageing. Then nanotechnology will let us live for ever."

I've said before that Kurzweil's vision of immortality in 20 years seems optimistic (though not completely impossible) to me, but I see the reversal of aging – be it through nanotechnology or some other means – as inevitable, whether it takes 20 or 100 years. But Dickson doesn't see it quite like that:

There is, of course, a considerable gulf between theoretical science and its universal application. God knows the non-theoretical stuff is problematic enough. Video recorders have been round for more than 20 years and not all of us know how to work them. But even if, for the sake of argument, immortality were technically possible, what would we do with it?

So not only is it going to be ridiculously difficult to apply the theory – which obviously must be faulty itself – into practice, we shouldn't even try! I guess we should've just skipped inventing video recorders in the first place, because not everyone on the planet can use them properly. While we're at it, let's get rid of televisions, computers, iPods, cars, microwaves, and everything else that might pose a technical challenge.

But, even if it were possible to use rejuvenation therapies to extend lifespan, we shouldn't. Why? A couple of lame jokes later Dickson lays down her main arguments against immortality. Number one:

How will we fit the extra people on the planet? (Indeed, if nobody ever dies, is it desirable – or even possible – for new people to be born?)

Ah, yes. The inevitable overpopulation argument, always thrown out there without much contemplation. Perhaps it has not occurred to her that the more developed a nation, the slower the population growth. It's the poor countries where population growth is a problem. And why do these people have so many children? As an insurance against old age. Apparently maintaining the status quo and having lots of kids who are more or less destined to the same fate is a better solution than actually making people healthier and less reliant on the next generation.

As for new people being born into a world where people are immortal, I don't see why it would be impossible. I just don't see much reason for it. Let's face it: the main reason why any living thing reproduces is to spread its genes; to make them immortal. But this is poor man's immortality. This is nothing but a diluted version of yourself remaining alive, while you, the unfortunate carrier, vanish into the great big void.

If we have true immortality of the self, who needs immortality of the genes? For those who wish to reproduce for other reasons – say, having children to keep you company – there's still lots of room on this planet. Besides, since immortality in the sense that absolutely nothing can kill you is very difficult (if not impossible), some new people would need to be created just to keep the population count where it is. And if we do run out of space here on this earth, we can head for other planets.

But, perhaps the most important question to ask those who put forth the overpopulation argument is this: Are you really willing to let masses of people die now just to reduce the changes of a hypothetical scenario where some people yet to be born might have to live in a more crowded world?

Enough about overpopulation. As I mentioned, Dickson has another ace up her sleeve. Reasons against living forever, take two:

Our fascination with the notion of eternal life is instinctive and atavistic. Every morality tale we tell ourselves, from the grail legend to science fiction (not forgetting most world religions), is wound about the notion of human mortality. Death is traditionally the leveller, the absolute against which all else is measured. Take away that absolute and you take away the reason, or at least some good reasons, for living.

This is a twist of the old "only death gives meaning to life" nonsense. But look at how Dickson herself dilutes it even further by saying that immortality wouldn't take away all the reasons for living, just some. I wonder what those reasons are – fear of dying, decrepitude in old age, too little time to pursue all your dreams, loss of loved ones? Because those are all fabulous aspects of the human life we just couldn't do without, right?

And, finally, even if immortality itself were good (just see how the article kind of goes from "immortality is bad" to "it might be pretty cool" to "let's not do it anyway"), there would still be thousands of good reasons not to do it. Well, okay, maybe just one. But a very important one. I call it the argument from jealousy, which states that not everyone might achieve immortality at the same time:

A world where only the poor grow old and die is not most people's idea of progress. And it's a short leap to the Huxleian nightmare of a New Order where the young and lovely are serviced by a subspecies of ageing drones.

Dickson is afraid that only the rich will be able to afford these treatments, while the poor will have to stick with mortality. Not only that, but the immortals will turn them into some kind of slaves with their newly-acquired powers. Into ageing drones.

As much as this scenario keeps me up at night, I would suggest that Dickson take a closer look at who might be to blame if only a priviledged few were to get their hands on rejuvenation therapies. If you have a business that offers anti-aging therapies, who would you rather have as your customers, a couple of rich kids or the entire world? And if you're foolish enough to choose the first option, others would soon rush in to offer similar services at a cheaper price to fill demand. This is basic economics. TV's, cars, and computers were all once luxury items, and now they're nearly ubiquitous.

The only instance that really can prevent access to these therapies is your friend the government. Regulation is the thing I'd watch out for when major breakthroughs in anti-aging science become a reality. The rhetoric will no doubt include the very same things Dickson is talking about, with the results of regulation of course being completely opposite to what is said and intended. The obvious consequence of "rejuvenation should not be available only to the rich" is "the government must produce rejuvenation therapies through a monopoly".

And given the horrible track record of government services, I can only imagine what "government immortality" looks like. But enough ranting, let's end all this on a lighter note. Here's an uplifting quote from very end of the article:

We need to fight down the herd panic on the issue of ageing and its natural consequence. Because immortality is not the answer. It is the only and original fate worse than death.

Okay, so I was lying. That's a terrible quote. What the hell was she thinking when she wrote this article?

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

Why Aging Is a Global Disaster That Needs to Be Solved
Who Wants to Live Forever? Results from a Global Survey
Anti-Aging in the Media: Daily Telegraph on Curing Aging
How to Live Forever: My 5 Steps to Immortality