Bioactive Compounds and Probiotics

[link to the mp3 amigos!]

Many moons ago I read a little book called On the Road by one Jack Kerouac. There’s a short passage in there where Kerouac finds himself in Loveland, Colorado and he only has about an hour’s ride to Denver. He hitches a ride with a nutty guy to take him the last leg of his journey, and while they are driving down I-25 the nutty guy tells Kerouac that he hasn’t eaten in three days because he’s on this new calorie-restricting diet that is supposed to make him healthier and live longer. I remember thinking “Oh the crazy stuff people did in the 40s! How could anyone think that eating next to nothing would help you live longer?” As it turns out this claim is not that unreasonable. In fact, the science appears to back up this bizarre notion.

It kinda makes sense if you think about it. In terms of health the less food particles you have circulating through your blood the less damage can be done. You see whenever you eat your body breaks down and absorbs everything it can: all the fats, cholesterol, sugars, protein, and what-not. Then it all gets dumped into your bloodstream and tissues pick up what they can. Diseases like atherosclerosis come about when too much LDL is circulating through your blood vessels and end up damaging the vessel walls.1 Furthermore if you eat just enough food to get by then your chances of getting maladies like type 2 diabetes, hypertension, metabolic syndrome, and obesity are significantly reduced.2

If you subscribe to the free radical theory of aging, calorie-restriction can also play a role there as well. What is the free radical theory of aging? You can read the Wikipedia article on it if you want a more detailed explanation, but in short natural biological processes like aerobic respiration generate superoxide and other free radicals as a by-product of producing energy. These free radicals can damage cells, and according to the theory this is what causes aging and eventual death. The thinking here regarding calorie-restriction is that less flux through the electron transport chain = fewer free radicals = less disease and longer lifespan.

This is not just due to less food floating around in your veins; there are genetic implications as well.3 Evidently there is a fair amount of evidence that suggests a low-calorie diet can “activate” specific genes (e.g. the “sirtuins” that Sridhar mentions such as Sir2 or SIRT1) that lead to longer life. It’s a pretty interesting idea. 60 Minutes produced a piece a few years ago discussing this very idea with some biochemists. It does a pretty good job of presenting a nice snapshot of the whole concept.

A representation of some of the studies that investigate resveratrol and lifespan. It looks promising! This was taken from the Baur and Sinclair article I link to below. It was published in 2006, and since then I think we can say that it works in mice to some degree, too.

This is where resveratrol comes in. Resveratrol apparently activates these sirtuins without having to restrict calories. There’s a nice review article published by Nature in 2006 on the topic. Suffice it to say not only is there growing evidence that resveratrol might prolong life but it also has anti-cancer properties, can prevent or delay heart disease, helps with chronic inflammation, and possibly more. There was one neat study4 that took three groups of mice and fed them a standard diet, a high-calorie diet, or a high-calorie diet supplemented with resveratrol. The high-calorie mice wound up like you might expect: fat, insulin resistant, high fasting glucose levels, performed poorly on physical tests, had fatty & enlarged livers, and died sooner than the other mice. However, the mice fed the high-calorie diet plus resveratrol performed as well or better than the control mice fed a standard diet. With the exception of being just as fat as the high-calorie only mice, the mice supplemented with resveratrol tested as good as or better than the control mice on everything I just mentioned. Crazy, right? The only caveat is that it takes a fairly large amount of the stuff to work its magic. In other words if you think a couple of bottles of wine per night will have enough resveratrol to turn you into a badass, think again. It would take more than three hundred bottles of red wine per day to get your resveratrol intake into the ballpark of what the researchers fed those mice.

We also discussed a little bit of the burgeoning field of probiotics. To wit, diet plays a big role in the composition of our gut microbiome and that microbiome plays a much bigger role in things like disease and nutrient metabolism than most people ever imagined.

Here is an image recently taken from a review article5 on the subject:

The interrelationship between diet, intestinal microbial ecology, and energy homeostasis was investigated in a mouse model of diet-induced obesity. The Western diet was associated with an increased body weight, a lower relative abundance of Bacteroidetes, and a higher relative abundance of Firmicutes. The overall diversity of the Western diet-associated gut microbiota dropped dramatically. (Tilg, et al.)

As you can see the type of diet one follows has profound effects on the composition of one’s gut bacteria. The bacteria, in turn, will have profound effects on its host. That article details some of the recent animal studies done with mice where researchers manipulated the mice’s gut microflora. We touch on this in the podcast, too, but you can colonize lean and germ-free with “obese gut microflora” and the mice will become fatter even though diet and calorie intake remains the same. This is partially due to the fact that the bacteria from obese mice are far more efficient at extracting nutrients from foods so the mouse can absorb more sugars, fats, vitamins, etc. It’s quite remarkable.

In addition to extracting nutrients the authors illustrate that some strains of bacteria in the gut have metabolites that activate G-protein-coupled receptors in intestinal epithelium which triggers a cellular cascade that promotes fatty acid storage in the adipose tissue, induces triglyceride production by the liver, and inhibits fatty acid oxidation in muscle tissue. In other words if you are trying to lose weight some types of bacteria are really gonna work against you.

Anyways if you want read more about this strange field of gut bacteria there is always a Wikipedia article. In addition Scientific American recently devoted some server space to the subject as well; you can read their series The Bacteria in Your Belly: Part 1, Part 2, and Part 3. Plus Science Talk did a two part podcast on fecal transplants and antibiotic resistance.

1. It is kind of a complicated process, but that’s the long-and-the-short of it.

2. Chances of other conditions related to malnutrition, however, are significantly increased. See: Anorexia or Marasmus

3. I did use to work in a genetics lab, but my grasp of the whole enterprise is still very basic. Don’t expect a detailed explanation of how it works.

4. Baur JA, et al. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 444:337-342

5. TIlg H, et al. (2009) Obesity and the Microbiota. Gastroenterology. 136:1476-1483


One thought on “Bioactive Compounds and Probiotics

  1. And I thought I was the only person who recalled that Kerouac line and marvelled at the prescience of the driver – and Kerouac’s reportage.
    They’re always out there!

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