Salt Experiment Results

As previously reported, I spent a few weeks this summer conducting a self-experiment on salt sensitivity and blood pressure. The experiment included a three week phase on a low carb whole foods diet with no added salt, followed by a moderately extreme salt loading phase. This post is a summary of my results.

I learned a lot from the experiment and came out of it with at least one bit of useful information. Will I try to restrict salt in my diet? Na (sorry, couldn't resist). I don't think salt restriction can work for me. From now on I will ensure that I get sufficient salt on a daily basis.

Executive Summary

Cutting to the chase, these are the main points I learned over the course of the experiment, roughly sorted from most to least interesting.

1. Salt restriction caused impaired thermoregulation. In hot weather, my cardiovascular system was not able to sufficiently lower my body temperature. This resulted in an elevated heart rate and hypethermia (up to 101.5 degrees in one instance). This can be dangerous, so be careful if you try this at home.

2. No clinically meaningful change in blood pressure. Systolic pressure was unchanged, though salt loading may have caused a small rise in diastolic pressure. This does not rule out long term negative effects from chronic salt loading (see discussion below), but it does show that, as previously discussed, my kidneys seem to basically work and can regulate my blood pressure through the maintenance of fluid and electrolyte balance in response to changes in my sodium intake.

3. Possible susceptibility to skin infections. Three days into the salt restriction phase, I came down with what was probably a staph infection in my right eyelid. This responded to antibiotics but it came back once I went off them. Since adding back salt I have had no problems with skin infections and no more antibiotics.

4. Possible strength loss. I did not perform well in the gym on my usual strength training program.

5. My taste for salt adapts quickly to restriction and loading. I experienced no cravings even when my sodium intake was too low. I can't just "listen to my body". Likewise, while the salt loading phase was difficult for the first two or three days, my taste rapidly adjusted to the added salt.

6. Bodyweight changes. I experienced substantial changes in body fluid levels (e.g. 6 pound weight gain within two hours of the transition from the salt restriction to the salt loading phase).

Conclusion: A low carb paleo diet must include added salt (for me). Can others do without? Perhaps, and some scientists such as Loren Cordain and Tim Noakes (e.g. this podcast episode 18 at 1:03:50) seem to think they can. Skip ahead to read my further musings on this question.

Study Design

The experiment was conducted in three phases. First, I did a one week lead-in phase (phase I) where I made no changes to diet or salt consumption. The purpose of phase I was to establish a blood pressure baseline through daily morning measurements (see Measurement Methods below).

This was followed by a three-week sodium restricted phase (phase II) during which I did not add any salt to my food. In addition, during phase II only, I avoided naturally salty foods such as shellfish. My sodium intake during phase II was limited to the sodium in the foods I was eating. Note however that there were one or two restaurant meals per week during this time where I was not able to strictly control for added salt. Sodium consumption on phase II was estimated to be between 800mg and 1000mg per day. phase II was originally scheduled for two weeks, but was extended due to the aforementioned infection and antibiotic use.

Finally, phase III was a salt-loading phase during which I added an additional 5 grams of sodium to my diet, for a total of nearly 6 grams of sodium per day including the sodium naturally occurring in my food. The supplemental salt during phase III consisted of hand harvested French Celtic sea salt (Eden Foods, Inc.) and was measured daily on an AMW-1000 digital scale. Because the Eden French Celtic sea salt is approximately 1/3 sodium by weight according to the label, the 5 grams of supplemental sodium per day was provided by approximately 15 grams of sea salt. Note that different varieties of salt will contain different percentages of sodium by weight. Sea salts vary significantly due to variations in residual water content (not, as commonly assumed, by the presence of other minerals). Please consult the label or a friendly analytical chemist for guidance.

The diet throughout this experiment consisted of meat, fish, eggs, coconut oil, butter, and non-starchy vegetables. In addition, I typically consumed a banana, an ounce (28g) of almonds and a bit of dark chocolate each day. Potassium intake was fairly consistent at around 4 g/day. Table 1 shows a typical day's macronutrient intake. Given the macronutrient ratio, I believe it is likely that the diet was ketogenic.

Table 1. Approximate daily macronutrient intake.

Macronutrient	grams	calories	percent (calories)
Carbohydrate	50	200	6.6%
Protein	155	620	20.5%
Fat	245	2205	72.9%
Total		3025	100%

Measurement Methods

Blood pressure was measured daily first thing each morning while seated, with the cuff of an Omron HEM-711 placed on the left upper arm over the brachial artery. I followed guidelines described by Agena et al (see Chart 2 of the linked paper). Each day's blood pressure value was determined by averaging the first three measurements taken that morning.

My first measurement of the day was typically higher than the average of the second and third measurements (systolic: +5, diastolic: +4, average over all three phases). This is referred to as the "alarm reaction" and is related to the more commonly known "white coat syndrome", where the presence of a doctor elicits a stress response and therefore an innacurately high blood pressure reading. My alarm reaction seems to be due to the fact that I get slightly stressed out about seeing what my blood pressure is, even when I measure it myself. Therefore I experience a slight rise in blood pressure while waiting to see the first reading each day. I kept all three readings for this experiment. My "true" normal blood pressure is on average slightly lower than these results which include the first "alarm" reading.

Results

I summarized my qualitative findings in the executive summary above. If you skipped that because you are not an executive, you can go back and read it now. Below are graphs showing my blood pressure and bodyweight during the three phases.

Figure 1: Possible mild elevation in diastolic blood pressure during the salt loading phase. Each point is the average of the three morning blood pressure readings for the day. Red = phase I, green = phase II, blue = phase III. Curves from ggplot2 "geom_smooth()" using default parameters.

Figure 2. No change in systolic blood pressure.

Figure 3: Bodyweight.

Figure 3 shows my daily bodyweight, measured each morning before consumption of any food or fluids. Note that my previous health goal (the 415 deadlift) involved an intentional increase in bodyweight and therefore significant excess calorie consumption. My current diet is lower in calories and Figure 3 therefore should show a long term downward trend in bodyweight.

Salt restriction clearly resulted in a rapid decrease in bodyweight over the first few days of phase II. There appears to be a stabilization towards the end of the salt restricted phase. The salt loading in phase III produced a very large initial weight gain, followed again by stabilization around the same level seen at the end of the salt restriction phase. As salt is primarily stored in bones and extracellular fluids, an increase in salt would be expected to correspond to an increase in extracellular fluid (since the body's bone mass should change slowly). The bodyweight changes shown in Figure 3 therefore reflect changes in extracellular fluid levels. While salt loading at the levels used in phase III produced a large acute change in body fluids, this was restored to normal over approximately 5 days.

Since my extracellular fluid volume was evidently restored within 5 days, it is not surprising that salt loading had no significant effect on my blood pressure. What is somewhat surprising was that there was no evidence of a temporary increase in blood pressure during the few days in which my extracellular fluid volume was in fact elevated. This suggests that there is an additional regulatory element working to restore blood pressure homeostasis at a shorter time scale than the dominant kidney-fluid mechanism previously discussed on the blog here.

Thanks to Mako Hill for guidance with ggplot2, without which these plots would look less nice.

Discussion

This experiment demonstrated to me that a low carb paleo diet with no added salt is potentially dangerous for me. Impaired thermoregulation is a big deal and would have been a life-threatening issue if I had to hunt for my food in a hot climate. Not only was my body temperature elevated in warm weather, but my pulse was elevated as well, suggesting my cardiovascular system was unable to restore my body temperature to normal. I'm clearly not salt sensitive, and I do not function well with a low salt diet. However, genetic studies suggest the ancestral human genotype is associated with high levels of salt sensitivity and ability to function with very low sodium intakes. How did humans evolve these traits? And why don't I seem to have them?

A Faustian Kidney Bargain

Susumo Watanabe has proposed in interesting hypothesis about the evolution of sodium metabolism in hominids. The theory is laid out in a 2002 paper called "Uric Acid, Hominid Evolution, and the Pathogenesis of Salit-Sensitivity," published in the journal Hypertension. It goes something like this. At some point during the evolution of our common ancestor with gorillas and chimpanzees, a series of mutations inactivated the gene for urate oxidase, an enzyme that breaks down uric acid. As a consequence, we have much higher blood levels of uric acid than other mammals. These mutations seem to have occurred between 24 and 8 million years ago, during the miocene, when our ancestors were believed to be subsisting primarily on fruits and leaves. This diet would have been exceptionally low in sodium. Since there is evidence of multiple independent mutations in this gene in multiple primate lineages, it is thought that mutations deactivating urate oxidase were strongly selected.

In rats, uric acid raises blood pressure acutely, but also causes renal vascular disease via renin/angiotensin systems. This over time makes the rats more salt sensitive. If there is very little salt available, salt sensitivity can be a good thing. Watanabe argues that, where salt is scarce, high uric acid is beneficial (via multiple pathways) for preventing blood pressure from going too low.

In addition to causing kidney disease, high uric acid causes other problems, like gout, and is associated with heart disease. So this looks like an engineering tradeoff with a number of downsides, but some benefits in the context of a miocene diet that was even lower in sodium than the lowest current estimates for paleolithic diets. The organism with this adaptation is supposed to partially destroy its kidneys on purpose in order to maintain sufficiently high blood pressure. This miocene environment is long gone. However, it is much easier to break a gene than to put it back together. Our urate oxidase gene has been broken more than once and it would take quite a long time to fix it.

It's kind of a crazy theory. I'm not sure I believe it but it is interesting to think about.

Some Hypotheses

During this experiment, I was eating almost exclusively meat, fish (often with bones), eggs and vegetables, plus added calories from butter, coconut oil and olive oil. The diet was grain, legume and dairy free and, as mentioned, possibly ketogenic. This would be considered by many online diet and health personalities to be a good low carb paleo diet, even though of course processed fats like butter and coconut oil are not Paleolithic foods.

So I want to discuss a few possible ways to resolve the apparent impossibility of eating this way without added salt.

Hypothesis 1: Low Carb, Low Crab, or Low Salt: choose any two

I have been eating a low carb diet, and my experiment suggests that, in that context, low salt is not a good idea. It is possible that a healthy human diet can be either low in carbohydrates or low in salt, but not both.

A great deal of evidence suggests that ketosis was not the norm for our paleolithic ancestors (see e.g. Kuipers et. al. 2012 for a thorough review of paleolithic diet research). In fact it would have been quite a struggle for me to eat this sort of macronutrient ratio without modern refined fats such as butter and coconut oil. Or ready access to marine mammal blubber (but then again the Inuit are not my paleolithic ancestors).

In contrast to the online paleo diet scene, most low carb diet advocates seem to line up behind the recommendation for ample supplementary salt. My result accord with that clinical experience. Low carbohydrate diets are usually said to have a diuretic effect in this community, at least in the initial stages (e.g. M.R. Eades, Jenny Ruhl). It is possible that my problems were caused by the interaction between diet-induced ketosis and salt restriction, and I would have done just fine without salt if I had some more carbohydrates. This hypothesis would be straightforward to test.

In order to keep my sodium intake sufficiently low during the salt restriction phase, I had to remove shellfish such as oysters and mussels from my diet. Crab is also salty and makes for a handy pun. It seems likely that daily shellfish consumption would have pushed my sodium intake into the healthy range. While shellfish does not get much attention these days in the paleo club, there is ample support (again see Kuipers et. al.) that it was an important contributor to actual paleolithic nutrition.

Hypothesis 2: Humans must drink blood. Or eat salt.

File this one in the "teen paranormal romance" department. This hypothesis states that the ancestral human diet was not as low in salt as commonly assumed.

Sodium is the body's primary extracellular cation, and most of it is located in the blood and other extracellular fluids. A pint of blood contains about 1.6 grams of sodium (see, e.g., these livestock reference ranges for blood sodium). That much blood per day should have been more than enough to push me into the healthy range of sodium consumption. On the other hand, salt depletion set in pretty quickly for me (probably 3-4 days), so this hypothesis assumes that fresh blood was consistently available to inland populations that did not have ready access to shellfish or sea water.

I find this hypothesis intriguing because of the fact that my putative ancestors were commanded not to drink blood (Genesis 9:4, Leviticus 17:13, Deuteronomy 12:15-16), and that salt is used in this tradition specifically to remove blood from meat before it is eaten. Presumably blood drinking was outlawed because it was thought to spread diseases and not because of tacky pop-culture connotations. Were my ancestors salting their meat not just for its preservative qualities, but also to make up for the reduction in sodium intake due to their prohibition on drinking blood?

Hypothesis 3: I'm Not (Genetically) a Paleolithic Human

Some say the human genome has hardly changed in the past 10,000 years. However, the hard evidence points to a number of significant evolutionary changes since the advent of agriculture, the classic example being lactase persistance (see Cochran and Harpending 2009 for a thorough argument on the rapidity of recent human evolution). Genes associated with hypertension and salt sensitivity are also apparently under strong evolutionary pressure. Alan Weder discusses this in an article published in 2007 in the journal Hypertension about evolution and hypertension. It is worth reading as an example of excellent science writing.

My experiment clearly demonstrates that I am not salt sensitive. This is not surprising given my European ancestry. As discussed by Weber, the genetics of salt resistance seem to correlate with adaptations to colder climates. It seems possible that in the course of such adaptation, my ancestors lost the ability to function optimally on a low salt diet.

Is a High Salt Diet Safe?

It is possible that, as much of mainstream medicine believes, a high salt diet actually is unhealthy over the long term. There is nothing in this experiment that contradicts that belief. Just because I am resistant to the short term blood pressure effects of salt loading, that does not mean I am immune to whatever long term negative effects a high salt diet may have. While epidemiological studies have their problems, it seems unwise to discount their findings altogether.

Edward Frohlich has argued that, notwithstanding the fact that most people's blood pressure does not respond to acute increases in sodium intake, sodium is nevertheless responsible long-term for increases in blood pressure. He argues that excess salt causes kidney damage over time (as with uric acid this is mediated by renin/angiotensin systems), resulting long-term in an increase in blood pressure. While much of this research is based on studies done on rats (including those of the "spontaneously hypertensive" variety), this line of thought is worth looking into and I will continue to do so.

Further Research is Needed

Studies always end with the statement that further research, and therefore research funding, is required. Well, I don't need funding but I will go a little further than a call for further research. Here are some ideas for areas of study and self experimentation.

• High carb low salt diet -- measure bodyweight and thermoregulation (e.g. via controlled hot baths or showers) over 5 day intervention period.
• Anthropological studies of salt and carbohydrate consumption among hunter-gatherers. Including seasonal variation. Genetics would be expected to play a significant role as there is ample evidence for recent evolution of salt sensitivity.
• Theories and evidence for salt use among paleolithic people. Support for consistent blood and/or shellfish consumption? Evidence for use of natural salt deposits?
• Sodium consumption and skin infections. Is salty sweat bacteriostatic within in sweat glands? Is low sodium consumption associated with skin infections? How salt sensitive is staph aureus? How about p. acnes? Have comensal skin bacteria evolved higher or lower levels of salt sensitivity? Are there differences between human populations (e.g. African vs. European skin flora)?
• Evidence for genetic selection of salt sensitivity in neanderthals. Is it possible I inherited some of my salt-related genetics from my neanderthal ancestors? If salt resistance is associated with adaptation to cold environments (see Weber), neanderthals would be expected to show these adaptations, and if they conferred a selective advantage, they should have been propagated if passed to human populations.

Computational Hemodynamics

This is a quick update on salt, and a digression about computation and blood pressure control. Read all the way to the end for a grain of salt advisory on the carbohydrate-insulin hypothesis.

My salt experiment is progressing and I've completed a 6 day baseline period, followed by a 3 week salt restriction period during which I consumed approximately 800-1,000 mg of sodium per day. I am now half way through a 2 week salt loading phase where I am consuming about 6,000 mg of sodium per day. It is quite a challenge to eat this much salt, though my taste buds have now gotten used to it.

Results? There has not really been a noticeable change in blood pressure between the three phases. Blood pressure during salt loading is almost certainly the same as the baseline diet, which was fairly low in salt to begin with. I'm still reviewing the data on the salt restriction phase, as there may have been a small drop there. I will report in more detail later.

Severe salt restriction had some negative side effects, most significantly an impairment in my body's ability to maintain a stable core temperature. In a warm environment, I might experience an increase in heart rate, and ultimately an elevated core temperature (up to 100.5 in one case). I also noticed a substantial drop in exercise performance. I was clearly dehydrated during this period, as evidenced by a drop in body weight. According to a google book called The Interface of Neurology and Internal Medicine (2007), salt restriction and dehydration can result in impaired thermoregulation possibly leading to heat stroke. I believe dehydration and the resulting drop in blood volume limits cardiac output, thereby preventing the cardiovascular system from performing its temperature regulatory functions.

Infinite Gain

In a former incarnation I was an electrical engineer.

Beloved of electrical engineers the world over, the operational amplifier (a.k.a. the "op amp") has been a mainstay of circuit design at least since the mid-1960s, when the first integrated circuit operational amplifier was introduced. An op amp has two inputs and one output, with the output dependent on the difference in voltage between the inputs, multiplied by a gain factor.

An ideal op amp by itself has effectively an infinite gain. This means it is not going to make a very useful amplifier unless it is built into a circuit that incorporates negative feedback. In this configuration, as articulated by Paul Horowitz and Winfield Hill in "The Art of Electronics," the op amp will do "whatever is necessary to make the voltage difference between the inputs zero."

An operational amplifier in the inverting closed-loop configuration. Rf provides negative feedback such that the voltages at the (+) and (-) inputs become equal. The circuit designer can manipulate Rin and Rf to produce the desired relationship between Vin and Vout.

Since the op amp is so useful in engineering, one might expect to find something like it in evolved biological systems that incorporate regulatory elements and negative feedback. In fact, there does appear to be an "infinite gain" element in the human blood pressure regulation system.

Computational Hemodynamics

In 1966, Arthur Guyton and Thomas Coleman developed a computer model of blood pressure regulation. The model was put together based on prior research on the various systems that work together to regulate blood pressure, including hormones (renin, angiotensin, aldosterone, antidiuretic hormone), heart pumping parameters (including pulse and stroke volume), fluid dynamics, electrolytes, local blood flow control, and various other factors. In a paper published in 1990 in the journal Hypertension, Guyton discusses the discovery he made using this computer model of an infinite gain regulatory element.

1966 was a long time ago in the computing world. Guyton and Coleman may have needed one of these to program their blood pressure model. Image from "Introductory Computer Programming" by Fredric Stuart, John Wiley & Sons, Inc. 1966.

After Guyton and Coleman started playing around with their computer model (did I mention it was 1966!), they saw some unexpected results. They increased one variable -- namely total peripheral resistance -- that "everyone already understood" would cause chronic hypertension. Instead, as Coleman reported to Guyton, "the patient developed hypertension all right, but the pressure came back to normal after a few days." Guyton and Coleman saw that the kidney's ability to regulate fluid and electrolytes was effectively an infinite gain feedback system: like an op amp, the kidney would do whatever was necessary to maintain stable blood pressure. While this surprised them at first, they found that this property could explain earlier observations that had been difficult to understand.

As Guyton stated in the 1990 paper, "the infinite gain property of the kidney-fluid mechanism for pressure control is so dominating that it will not allow a factor from outside this mechanism to alter the blood pressure permanently unless the kidney-fluid mechanism is itself altered at the same time." In other words, if you are looking for a cause for a long term change in blood pressure, look for something that is affecting kidney function.

Here is an except of a schematic diagram of Guyton's 1972 blood pressure model (this may be a revised version of the original 1966 model). A shrunken version of the full diagram is included at the end of this post. It's so big that it is worth checking out the fill size image, which you can get here.

A small segment of the Guyton 1972 schematic.

Biology as Computation

I think this story is a good example of a successful computational approach to a biological question. We can view the human blood pressure regulatory system as a computational system. It reads a variety of inputs and "computes" the organism's blood pressure. If we can accurately model the system's individual elements (based on lots of reductionist basic science) we can try to simulate the whole thing in a computer.

This story also shows that a reductionist approach to biology can mislead. Viewed in isolation, it seemed obvious to everyone that an increase in "total peripheral resistance" would result in a long-term rise in blood pressure. This was consistent with the fact that patients with hypertension typically also show an increased total peripheral resistance. However, in other cases where there is a clear primary cause for a rise in total peripheral resistance (e.g. multiple amputations), scientists frequently observed no long term increase in blood pressure.

The computer model helped provide an answer to these riddles. Instead of relying on an intuitive understanding of a single element, it let us watch what happens when all of the computational elements are allowed to interact. It then became obvious to Guyton and Coleman that the kidney's fluid regulation mechanism was powerful enough to override other factors that might try to drive blood pressure up or down. It could then be hypothesized that the increased total peripheral resistance seen in hypertensives was in fact a consequence, and not a cause, of elevated blood pressure. Work could then proceed on how exactly this came about.

Beyond Blood Pressure

Some complex systems may sometimes exhibit simple and comprehensible behaviors, while other complex systems will not. Computational approaches might help us figure out which is which. Computational approaches may be required when purely reductionist thinking is not enough. In other cases, when the basic "computational units" of the system being modeled are not individually well understood, a computational approach might lead us absolutely nowhere. And as anyone who has ever tried to build a complex system can tell you, if it is not extensively validated, it is almost guaranteed to break.

Blood pressure regulation is complex, though it is probably quite simple compared to many other biological systems. To me the diagram below looks about as complex as this schematic for the Intel 4004 microprocessor, introduced in 1971. The infinite gain property of kidney fluid regulation, discovered because of a computer model, allows for a powerful simplification. If the kidney is really driving the blood pressure boat, we could safely ignore most of the complexity of the total system and look only at the kidney's health and its specific regulatory drivers. Many other complex systems will not be reducible in this way.

Grain of salt advisory.

Consider this next time someone says carbs drive insulin which drives fat storage. Insulin works in a complex web of biological computational elements, including the mother of all biological computers, the human brain. Insulin viewed in isolation may or may not give us the answer. This is why my ears glaze over a bit when I hear someone start talking about "<hormone du jour> resistance." I'm not interested in the behavior of a single wire in a complex web. I want to know how the whole thing works.

Blood pressure regulation. It's complicated. From Guyton 1972.

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.

Microbiome

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.