Saturday, August 25, 2012

Goals, Salt and Viromes

Here's an update on what's been going on here at megafauna central. Health goals, salt sensitivity, and the microvirome.

Eagle-eyed readers will have noticed that the quote in the mast-head has changed. The original version was "science is the disbelief in the authority of experts." I heard this quoted by Michael Vassar on the Bulletproof Executive podcast (episode 14). A reader told me that he was researching the quote and was unable to find a reliable attribution to Feynman. The closest Feynman quote he could find was "science is the belief in the ignorance of experts." This version appears in an essay called "What is Science?", which is included among other places in a collection called "The Pleasure of Finding Things Out" (Perseus, 1999). Now I like the original, wrong version better, since it is less confrontational and fits my personality. So I imagined myself going all Jonah Lehrer and sticking with it. However reason prevailed and I changed the quote to the one I'm pretty sure Feynman actually said. Getting a quote wrong in a podcast interview is understandable, but I should have done a better job of fact checking. As it is, it looks like I may have permanently polluted the Internet. Sorry!

Health Goals

I took a break from experimentation while on the home stretch for my 2012 health goal, which I mentioned at the end of my last butter post. Last week I completed that goal with a 415 pound deadlift, thanks in part to high butter consumption which allows me to keep my calorie intake high and maintain my bodyweight (twitter subscribers have already seen the video, which is low quality and not terribly interesting).

My next health goal is to achieve a reasonably fast one mile run. I don't run and never really have, so I'm hoping to find some "low hanging fruit" by exploring another fitness domain. I also have no idea what a reasonable goal might be, so I'll just muddle around for a few months and see where I end up. I'll be closely watching my resting heart rate and expect some short-term improvements there. I will be writing about my protocol and progress.

Now that my 2012 health goal is complete, I have a little time for experiments.

Salt Sensitivity

For a while I have been interested in lifestyle modifications that might affect blood pressure. While my blood pressure is considered normal, my systolic (the high number) is at the high end of the normal range.

It seems clear that salt raises blood pressure significantly for some people, and in those people, excess salt consumption is associated with a host of bad effects. These folks are called "salt sensitive." For others, blood pressure seems to be unaffected or even decrease when excess salt is added to the diet. These folks are called "salt resistant." I would like to find out which category I fall into.

The following graph from Sanada et al (Clinical Chemistry 2006) gives a good picture of what's going on with short-term changes in salt intake. It shows the daily sodium excretion of salt sensitive and salt resistant individuals during a dietary protocol in which salt is first decreased, then increased, and then returned to baseline (note, since the molecular mass of sodium is about 23, multiply the mmol values by 23 to determine milligrams of sodium per day).

It appears that salt resistant individuals rapidly increase their sodium excretion when the salt content of the diet goes up (this is accomplished through a reduction in renal sodium reabsorption, hence excess urinary sodium excretion). The net effect should be that the body maintains sodium homeostasis notwithstanding the rapid change in intake. Salt sensitive individuals appear to be slower to make that adjustment, as evidenced by the lag in the sodium excretion curve during the salt loading phase. Given the lag, it would appear that salt sensitive individuals might accumulate sodium in the body on a high salt diet, though it is unclear if this normalizes over a longer term (I haven't gone deep enough into the research to see if that is the case).

Effect of dietary sodium on sodium excretion in SR (○) and SS (▪) hypertensive Japanese. From Sandana et al (Clinical Chemistry 2006).
One recent paper suggests that salt resistance confers advantages in maintaining body temperature homeostasis (see Muller et al, Hypertension Research 2011). I had always assumed that salt sensitivity was the ancestral state and that salt resistance traits were associated with agricultural cultures that used salt to preserve food. However, the Muller paper suggests to me that salt sensitivity might actually be an adaptation for persistence hunting in hot climates by allowing improved thermoregulation. I have no idea if the genomics work on that question has been done.

Are You Salt Sensitive?

If your blood pressure is more than 100-110 over 70-75 (the norms reported for hunter-gatherers), perhaps it makes sense to find out if you are salt sensitive.

I reviewed the medical protocols for diagnosing salt sensitivity and found them to be fairly intensive. They seem to be confined to clinical research settings at this point. In other words, doctors don't know, and can't find out, if their patients are salt sensitive.

There seem to be two recognized approaches for diagnosing salt sensitivity in research settings. In the first, a low salt diet (~1g of sodium per day) is followed for two weeks followed by a high salt diet for another two weeks. A second standardized approach, described by Weinberger et al in 1986, is much quicker. It uses IV saline solution for the loading phase, followed by a low salt diet and the administration of furosemide, a diuretic that decreases renal reabsorption of sodium.

At least one study has shown that the two techniques are not well correlated with each other (see de la Sierra 2002, Journal of Human Hypertension). Since I am not interested in my response to diuretics, I am running myself through the dietary version of the test. I am one week into the low salt phase and have seen no noticeable change in blood pressure thus far. That's not unexpected though, since my baseline diet was pretty low in salt. I'll know much more once salt loading kicks in at the end of this week. What is most interesting to me so far is that I have had absolutely no cravings for salt.

In the mean time, health authorities strongly advise everyone to restrict salt, despite the fact that they have no idea what effect this will have on you in particular. Lemmings will jump. Ostriches may hide their heads from the truth.* I prefer to get the information I need to make good decisions.

* Yes, I understand that neither of these statements is true. I am lying about animals for rhetorical effect.


In microbiome news, I received the results of my Metametrix stool profile. It is pretty interesting but I believe this type of data is of very limited usefulness at this point. The profile works by sequencing the ribosomal RNA of the bacteria in your stools. This gives you an idea of the mix of "species" of bacteria that are present and in what quantities they appeared in your stools on that particular day. What information is missing given current technology?
  • Changes in the microbiome over time
  • Presence and expression of genes. Microbes are exceptionally promiscuous and share DNA via plasmids, phage, and other mechanisms. 16S ribosomal RNA does not tell us what genes are there or to what degree they are expressed
  • Where the bacteria are located. Bacteria can colonize multiple niches (e.g. lumen vs. mucosal layers) and these differences can have meaningful effects
  • Behavior of the bacteria that are there. Microbes communicate with each other and with the immune system. What are they saying?
I mentioned phage above. While it is well known these days that bacteria form an important part of the human digestive tract, it is not as widely appreciated that viruses are also a significant component. Viruses that infect bacteria, known as bacteriophages or "phages" for short, are the most abundant life forms on earth. If they were so inclined, they could link hands and stretch from one end of the galaxy to the other. And back. By comparison, humans could get 1/10 of the way to Mars, and would almost certainly be accompanied by terrible music.

Phage seem to represent the majority of all genetic variability on the planet. They associate with our gut microbiota and change in response to dietary interventions (see Minot et al, Genome Research 2011). Scientists seem to be at the very early stages of figuring out what phages are out there, what they look like, and what they might be doing. I don't think anyone has a clue about the impact they have on human health. So until these questions are answered, keep plenty of salt grains at the ready for the next time you hear a definitive-sounding pronouncement about the microbiome.