Yet Wim is not a genetic freak or Tibetan monk. He is a 52 year old Dutch man without much body fat. He believes that anyone can adapt to the cold and learn to control body temperature.

In this article, I will try to answer two questions:

• How does he do it, and can anyone really do the same?
• Is this basically an impressive stunt, or is there any benefit to learning Wim’s methods?

No stunts.  First, just to be clear about what Wim has been able to accomplish,  take a look at these two short videos:

1. Wim running a half marathon in the north of Finland:

2. Wim swimming 50 meters under arctic ice:

An enjoyable account of Wim’s remarkable adventures and methods is detailed in the book Becoming the Iceman, co-authored by Wim Hof and Justin Rosales.  Rosales is a college student who became so intrigued with Wim’s abilities that he managed to earn enough money washing dishes–while still attending classes–to travel to Europe and learn Wim’s methods.  The chapters alternate between those written by Wim and those by Justin. While their account suffers from a lack of editing and is sprinkled with grammatical errors, the excitement of Wim’s remarkable sense of fearless adventure and Justin’s learning process make this book a real page-turner.

Changing how body temperature is regulated.  How does Wim Hof manage to keep his core body temperature elevated, maintain peripheral circulation, and avoid frostbite and hypothermia?  Nobody knows for sure, but there is no doubt that he does it.  Dr. Kenneth Kamler, an expert on hypothermia, frostbite and high-altitude medicine, who has himself climbed up Everest, has observed that Wim’s trained body responds differently than yours or mine.

The normal response to extreme cold exposure starts in the peripheral blood vessels in the extremities  – the ears, nose, fingers and toes.  Blood flow in the extremities at first increases, in order to stimulate warming.  If the cold exposure is prolonged more than a few minutes, goosebumps and shivering kick in to induce warming of muscles and skin.  But if the exposure continues beyond that, a process of biological “triage” takes place.  To preserve the high priority  organs – brain, heart, digestive tract — the body shuts down blood flow to the extremities to prevent further heat loss. The peripheral veins snap shut to segregate warm interior blood from cold peripheral blood. After all, these extremities have a lot exposed surface area, so cutting them off greatly conserves heat.  But the cost of doing this is frostbite and the irreversible tissue damage that often results if the cold exposure is sustained for more than a brief time.  Finally, when the core temperature falls below 95 F, the various stages of hypothermia set in, ultimately leading to death if sufficiently prolonged.

But Wim, and Tibetan practioners of the ancient art of Tummo, are able to significantly alter this normal process.  As Kamler explains, the key adaptation occurs within the brain during meditation–specifically the yoga and controlled breathing exercises that Wim and the tumo practitioners follow.  Of these exercises, breath retention exercises are key.  As a result, there is a significant activation of blood flow and electrical activity in his frontal cortex and hypothalamus — areas that regulate peripheral nerves and veins involved in the regulation of body temperature.   Normally, the circuit between the hypothalamus and these temperature control circuits is involuntary, governed by the autonomic nervous system. Kamler reasonably speculates that,  through meditation, Wim is able to override the normal function of the hypothalamus, allowing the peripheral veins to remain open and heat the extremities, preventing injury.  He points out that Wim must be generating heat and distributing it more efficiently, but he admits having no idea mechanistically how Wim’s meditative techniques accomplish this.

The monks who practice Tummo are able to tolerate cold, but they do so in a meditative pose, while sitting. They speak of being able to generate an “inner fire”.  Wim Hof’s method has diverged from that of classical Tummo. He has innovated significantly, since he is able to control his body temperature while moving about, in fact while exerting himself under conditions of running, swimming, or high altitude climbing which would be challenging for most people even at ambient temperatures! Yet, while Wim is certainly a one-of-a-kind personality, he is insistent that anyone can apply his techniques. His success in teaching Justin Rosales and others seems to bear that out. More recently, Wim  has devoted himself to training others through seminars and training expeditions.

Other abilities.  Wim’s ability to voluntarily control what what we consider to be automatic, involuntary responses does not stop at tolerance of extreme cold.  He has also learned to tolerate extreme heat, consciously overcome pain and cramping, and even moderate his immune response to endotoxin.  A fuller discussion of these abilities is given in Becoming the Iceman.

Possible benefits.  I’m particularly interested in Wim Hof, because of my own positive experience taking daily cold showers.  As I discussed in my post, Cold Showers, making a daily habit of cold showering results in a remarkable degree of adaptation.  The initial intense discomfort of cold shock rapidly shrinks in both intensity and duration, and the self-heating process of thermogenesis becomes more prominent after only a few weeks of the daily habit.  I’ve found benefits in weight control, mood enhancement, and generalized stress resistance.  I’ve not had any colds since starting cold showers. When my family was suffering with a stomach flu that lasted several days, the net effect on me was a 12 hours of achiness which I slept off on a single night, with none of the nausea that they had.

Could more aggressive exposure to the cold provide benefits that go beyond that of daily cold showers?  Hof and Kamler have suggested that the ability to open up peripheral veins and capillaries may help to enhance more than just temperature regulation.  It likely improves blood circulation overall, particularly in the smaller peripheral vessels. Because there are so few individuals that do what Wim Hof does, there is not yet any body of clinical science regarding the benefits to circulation.  But it is not hard to speculate that cold exposure could be a great way to fend of a wide range of cardiovascular and circulatory maladies.  So it intrigues me.

Total cold water submersion.   Cold showers are great, but what Wim Hof does is far more extreme.  Not only is the temperature of the water significantly colder — 32 F vs. the 55-60 F of my showers — but the total body immersion involves much more extensive skin surface area contact, meaning more rapid heat loss. A few times a year, I go for a brisk 10 minute swim in the ocean.  Here where I live in northern California, the ocean temperatures range between 53 and 60 F, similar to my shower water, and ocean swims are definitely more bracing than the cold showers.

My first experiments.  I want to see if I can up the game beyond cold showers. I first read Tim Ferriss’s account of cold water exposure in his book, The 4-Hour Body.  In his chapter “Ice Age”, he recounts the method of Ray Cronis, a NASA scientist who was able to lose almost 30 pounds of fat — fat, not weight — in 6 weeks, by taking cold walks, cold swims, and by drinking cold water.  Ferris himself tried immersing himself in cold baths — with added ice — for 20 minutes.  But he first heated himself to the point of sweating by consuming a thermogenic cocktail of ephedrine, caffeine and aspirin.  So what Conise and Ferris did doesn’t really approach the level of unmediated cold exposure undertaken by Wim Hof.

I want to see how much I can directly adapt to the cold.  My first effort will be to attempt this without any special meditative technique or breathing method, and certainly without taking any thermogenic medications or supplements, as Ferriss did.  So I did my first experiment today, and here is what I did and what I experienced:

I filled a bath with cold water, which I measured at 58 F (14 C).  I first submerged my legs.  It was painful, so I decided to allow myself to adjust before filling the tub with more water. Fortunately, after about 2.5 minutes, my legs no longer hurt and by 4 minutes they felt a kind of paradoxical warmth and I could wiggle my toes again. So I filled the cold water up to my chest when laying back. I was completely submerged at 9 minutes.  At first, this was very uncomfortable, and I started shivering. I felt some numbness, but that went away and I was comfortable again at  14 minutes. I could easily flex my toes and fingers. I continued laying in the tub, submerged up to my neck. The sensation alternated between shivering and coolness. I stayed in until 20 minutes had passed from the initial plunge.

After I got out of the bath, I felt warmer and tingly at first. But 5 minutes after getting out and drying off, I started feeling very cold and shivering uncontrollably. I was not really expecting that; I thought I would instantly feel warmer, just as I always do after stepping out of a cold shower. But in the book Becoming the Iceman, Justin Rosales and Wim Hof describe a phenomenon they refer to as “the afterdrop”, an experience of getting colder after you emerge from cold water. This is exactly what was happening to me. I needed to  put on warm clothes and move around to fight off the shakes. I was still cold and shivering 30 minutes after emerging from the cold bath, and my fingers were stiff, making it hard to type up my notes.

However, a full hour after finishing the bath I started to feel great. I became warmer throughout the evening, even though it has been a chilly evening. Psychologically, I have been quite alert all evening long. So there is some evidence of adaptation, even though the experience has been quite different than what I would have predicted from my familiar habit of cold showers.

I plan to continue experimenting with cold baths over the coming weeks, varying both the duration and the water temperature.  I’m interested to see how readily I adapt, and what other benefits or problems occur along with the adaptation.

Many of the questions I get on this website and the forums are of this type.  People understand the general concept of hormesis, namely that exposure to controlled amounts of stress can be beneficial, because it elicits beneficial adaptive responses in the organism.  They understand that weight lifting builds muscles, and that intermittent fasting and calorie reduction can be healthful. But too much of any stressor — weight lifting, caloric restriction, sunlight, allergens  – can have adverse consequences.  With hormesis, it seems, the Goldilocks principle applies: to get a benefit, the level of stress must be “just right”.  And because it’s so easy to veer into overload, many people seek to avoid even mild stress:  Avoid allergens. Cover up with sunscreen. Eat frequent small meals. Don’t exert yourself. But if you choose this path, you forgo the possible hormetic benefits.

So how do you determine the optimum level and frequency of exposure to a stress?  And how much rest or recovery between exposures is optimal?

These are important questions, difficult to answer with certainty.  Of course, all over the Internet you will find those who tell you exactly how many days each week is optimal for lifting weights, how much sun tanning is safe or dangerous, what level of dietary carbohydrate or food restriction is optimal or unhealthy.  In some cases, they will cite studies to support their position. But there is one big problem with all this advice, even the advice based upon careful scientific studies:

Individual responses to hormetic stressors can vary significantly.

Just as responses differ between individuals, a given individual’s ability to tolerate and benefit from hormesis changes over time, and as a function of previous exposures to stressors.  This makes it virtually impossible to reduce hormesis to a simple formula. And yet, the situation may not be so hopeless.  There are actually some tools and metrics we can use to quantifiably determine whether hormesis is helping or hurting us, and thus to “adjust” the dose.

Allostasis. There is a general biological principle that can help us dial in the right level of hormesis.  The principle is called “allostasis”.  Most people are familiar with the related concept of homeostasis, the tendency of a system to maintain a constant internal state, such as the pH, temperature, or oxygen concentration of the blood, within a fairly narrow range.  This concept was developed by the famous nineteenth century biologist, Claude Bernard, who observed that organisms strive to control their internal environment, or milieu interieur, within tight physiological constraints, through physiological processes that resist disturbances from the external environment and quickly restore normal operating conditions.   This notion was later formalized by Walter Canon as “homeostasis”, the tendency of a biological system to regulate its internal environment within a stable range.

While the concept of homeostasis has some validity, in actuality it is of fairly limited application.  In fact, most biological systems do not self-regulate physiological variables within a narrow range, but tolerate a fairly wide range of variation.  During the course of a typical day, blood glucose and insulin levels rise and fall by as much as 50% or more.  Blood pressure, heart rate, and adrenaline surge upon waking and standing in the morning, and increase to further heights when engaging in vigorous exercise, or responding to threatening or emotional situations.

Bernard and Cannon developed the concept of homeostasis to apply only to regulation of the internal environment, particularly that of the cell or circulatory system. It was not intended to describe the external condition of organs or whole organisms.  Yet others have extrapolated this concept and applied it to the misleading notion of “set points”.  For example, some have advanced the idea that each of us is born with a body weight set point from which we can only deviate transiently and in a futile manner through diet and exercise, but which we are doomed to return to.  But body weight or body fat is not an “internally” regulated physiological variable, despite the efforts of some to tie this to the hormone leptin.  Rather, it is the result of a number of interacting systems, which frequently lead to a relatively stable output.  I’ve provided a more detailed critique of the set point concept in my post, Change your receptors, change your set point.

On the contrary, when you consider the whole organism, you are struck more by its variability over time than by its constancy.  Sterling, Eyer and McEwen have contrasted the stability of homeostasis with what they call “allostasis” or “stability through change”. “Stability” here does not mean a static state, but rather a dynamic physiological process which allows the organism to sustain itself in the face of external challenges.  For example, hormones like cortisol, adrenalin and catecholamines, and mediators like cytokines, allow us to adapt to changes in activity level. Digestive hormones like insulin and glucagon, and secreted digestive enzymes like proteases, amylases and lipases, allow us to effectively respond to the sudden ingestion of food, otherwise known as “meals”.  On longer time scales, major morphological changes in the overall shape and and size of the body allow animals to handle episodic changes like pregnancy, migration, or hibernation.  While organisms and physiology are stable enough to survive, they do not maintain or even strive for a state of constancy.

Allostasis, not homeostatsis, better describes how we deal with changing circumstances.

Changes which are beneficial in the short term to handle an external stress, may be harmful or pathological if maintained chronically.  So for example, glucocorticoid and catecholamine hormones such as cortisol and adrenaline are helpful, even essential, for gearing the body up to handle acute stress.  Without such hormones would we be unable to get up in the morning, much less deal with emergencies. But these same hormones become harmful or deadly when chronically elevated, causing significant damage to the cardiovascular system and neurodegenerative conditions such as depression and memory loss.  The “biphasic” effect of cortisol and other arousal hormones and catecholamines is encapsulated by the Yerkes-Dodson Law, illustrated in the figure at the right, which holds that performance increases with physiological or mental arousal, but only up to a point. When levels of arousal become too high, performance decreases.

Similarly, insulin, which is essential for the short term digestion of carbohydrates and protein, and for facilitating tissue growth, can likewise be harmful if elevated chronically, leading to obesity, cardiovascular disease, inflammatory diseases, and possibly cancer.  McEwen refers to the elevation of these stress related hormones and effectors as “allostatic load” and their chronic elevation as “allostatic overload”.

Hormones are neither good nor bad in and of themselves.  They are helpful at the right time and for the right length of time.

Alternating states and opponent processes.  I’ve written about opponent processes as an explanation for psychological adaption in my post on The opponent-process theory of emotion.  Here I would like to go further and generalize the opponent process theory to more broadly characterize our adaptive physiology.

Our natural allostatic variability typically manifests itself in an oscillation between two states or “extremes” which alternate or fluctuate over some characteristic interval of time that can range from seconds, to hours, days, months, or years.   These two states are often thought of as “high” and “low” levels of some variable hormone, enzyme or effector. But I think they are better considered merely as opposing conditions.  That’s because what appears to be “states” are really the results of underlying processes that move the organism in opposite directions — opponent processes. These processes typically come in pairs and act to balance each other, like yin and yang. It is important not to confuse the states and the opponent processes.  These alternating states are the resultant outcomes of the opponent processes; the visible “state” reflects the dominant process, but both processes are always in play to greater or lesser extents.

This concept of may be confusing, so here are a few examples of alternating states and associated opponent processes, with widely varying temporal scales. In each case “State A” exists when “Process a” dominates over “Process b”, and “State B” exists when process b dominates:

State A     State B            Process a        Process b                     Frequency

Eating      Fasting             Anabolism       Catabolism                    3-24 hrs
Waking    Sleeping           “C” process      ”S” process                   24 hrs
Exercise   Rest                Sympathetic     Parasympathetic            varies

Eating and fasting. You could attempt to characterize the A and B states as “active vs. passive”, “stressful vs. restful” or “bad vs. good” but that is not quite right. Take eating and fasting, for example.  You might argue that eating is the active or stressful state, because it places a demand on the digestive system, and the fasting period between meals allows the digestive system to recover.  However, if the fast is continued beyond a certain point, it becomes the stressor.  After about 12 hours, the stress of fasting causes a rise in catabolic “breakdown” processes, upregulates the neuroprotective hormone BDNF, and the process of autophagy activates the breakdown of intracellular materials to fuel the mitochondria. Utilized in moderation, the “stress” of fasting thereby activates beneficial processes that protect and defend us.  Once you resume eating, the “stress” of fasting is relieved and the anabolic “building” process kick in with the rise of insulin.  This has its own benefits, in repair and growth.  It is important to note that the anabolic hormones like insulin and the catabolic ones like glucagon or adrenaline are always present at some level; they never “go to zero”.  Yet one or the other is dominant at a given time, depending on the state of digestion.

Wake and sleep. Similarly, you could say that wakefulness is active and stressful, whereas sleep is passive and restorative.  But again, this would be misleading. Wakefulness and sleep are the outcome of a dynamic, alternating balance between two essential processes, the “C process” and the “S process”. The “C process” generates a wakeful state based upon activation of  the ascending arousal system, including cholinergic, noradrenergic, serotoninergic, dopaminergic, and histaminergic neurons located in the hypothalamus and other brain nuclei.  These neurons release corticotropin-releasing factor (CRF),  ACTH, and cortiosol on a regular diurnal cycle. This arousal system interacts with inhibitory “sleep-active” neurons in the ventrolateral preoptic nucleus (VLPO), releasing GABA and other sleep-inducing neurotransmitters.   These sleep promoting neutrons and neurotransmitters represent the “S” process. The result is a “flip-flop switch”  producing distinct sleep and wake states with abrupt transitions.  The “C” and “S” processes each never actually stop, but they continuously wax and wane, with one of the two becoming dominant and leading to either wakefulness and sleep. Even within the states of wakefulness and sleep there are many regular oscillating subcycles; for example REM sleep, deep sleep and light sleep. Disruptions in this process can lead to insomnia, and can be corrected by Sleep Restriction Therapy, as I’ve described in my post A cure for insomnia.

The reality is that for each basic physiological process we need both A and B states and the underlying a and b processes.  The opponent processes represent polarities of an indivisible “yin-yang” pair.  They balance each other, but not in a constant ratio.  The a and b processes cannot be indefinitely sustained, but each have within themselves the seeds of their own demise, by inducing their complementary, inhibitory process.  Biological organisms are constructed out of complementary and opposing physiological process, which naturally give rise to  an alternation between the A and B states.  This is a phenomenon I will refer to as stress oscillation.

Stress oscillation builds dynamic range.  So what does allostatis and the opponent processes have to do with hormesis?  Sometimes hormesis is thought of unidimensionally:  lift weights to build muscle.  Fast or reduce carbohydrates to lower insulin and reduce weight.

But in reality, hormesis should be thought of as a binary process of alternating stress and recovery.

Lifting weight builds muscles because it induces “catabolic” microtrauma to the muscles; it is the rest between workouts, in combination with adequate diet, that leads to the “anabolic” rebuilding of the muscle.  Both stress and recovery are necessary.  For the same reasons, weight loss through insulin lowering should be balanced with sufficient periodic insulin raising to maintain lean body mass, and maintain the healthy function of the insulin producing system, including the pancreatic secretory islets and the insulin receptors in the brain and muscle tissues.  One risk of an unremitting “insulin sparing” diet, such as a very low carbohydrate diet without periodic insulinogenesis is the induction of a state of physiological insulin resistance. This is indeed a paradoxical outcome of a diet which many pursue in order to improve their insulin sensitivity!

In the wake-sleep cycle, the ascending arousal system or “C-process” is stimulated by the secretion of CRF (corticopin releasing factor) by the hypothalamic-pituitary-adrenal (HPA) axis.  But a state of interminable wakefulness or insomnia results in cognitive deterioration. Both the “C” and “S” processes are necessary, and they must oscillate:  An unvarying simultaneous activation of both processes would not lead to cognitive stability, but rather mental deterioration.  Stress and renewal must follow one another as night follows day.

For any physiological function like digestion, muscle synthesis, or the wake-sleep cycle, the oscillation between State A and State B produces a dynamic stability that exhibits a certain dynamic range between stress and rest.   The cycle of eat-fast-eat leads to a cycling of digestive hormones such as insulin, glucagon, and adrenaline.  The cycle of wake-sleep-fast leads to a cycling between the arousal system and the sleep system.

And here is the takeway:  By exposing ourselves to alternating A and B states of increasing intensity, we build tolerance and dynamic range for the opponent processes.  We should strive to increase the magnitude of contrast between the opponent states.  I believe that we can generalize the use of dynamic capacity between allostatic states as a marker of fitness.  This can be illustrated by several examples:

Example 1.  Aerobic capacity.  Exercise phyiologists understand that athletes are able to build aerobic capacity (so-called VO2 max) by exerting themselves at or near maximal heart rate.  Their state of fitness is manifest in a reduced resting heart rate or pulse, and a higher ratio between peak VO2 and resting VO2.  This ratio or difference is sometimes referred to as VO2 reserve or VO2R, and it represents a good measure of aerobic fitness, a kind of dynamic capacity to oscillate between rest and exertion. Yet another measure of dynamic capacity is the rate at which heart rate or VO2 return to normal, after exertion

What is interesting is that training harder does not necessarily increase VO2R or dynamic capacity.  A study by the Navy Seals showed that overtraining can actually decrease VO2R, and can elevated resting heart rate by as much as 10-15 beats per minute.  Monitoring your resting heart rate is an excellent way to know if you are overtraining.  (Caveat: the heart rate measure must be used with judgement, as severe overtraining can lead to extreme exhaustion and an abnormally low heart rate).

More generally, high intensity interval training (HIIT), whether it be in the form of weight lifting, sprinting, or other metabolic training, is based on the very same premise.  Maximal exertion, into the anaerobic range, activates the full range of muscle fibers, including the ever-important fast-twitch muscle fibers, empties muscle glycogen, and activates the glycolytic pathway, resulting in an upregulation of insulin receptors (GLUT4 transporters), and improved insulin sensitivity.  But for HIIT to work effectively, it is equally important to allow adequate time for rest and recovery.  (I’ve discussed this in more detail on the Fitness page of this blog, with particular emphasis on the physiological analysis of Doug McGuff in his book, Body by Science).

For sports as varied as running and weight lifting, the well known principle of periodization recognizes the importance of variation in intensity and proper rest. In short, both high intensity training and aerobic training, if carried out with adequate rest and recovery, build dynamic range.

Example 2.  Digestive or metabolic fitness can be measured by a low basal insulin level in combination with a pattern of sharp, but brief insulin secretion in response to ingested carbohydrates or insulinogenic protein.  Low basal insulin level is seen, for example in non-industrialized populations such as the Kitavins, whose average basal insulin levels of about 4 mIU/ml are about half those of Western populations.  And yet the Kitavans consume meals with a high percentage of carbohydrates and have good insulin sensitivity.   So low basal insulin levels alone are not the whole story. The optimal pattern seems to involve an alternation between feast and fast, allowing the digestive hormones and enzymes to cycle between anabolic (insulin) and catabolic (glucagon, adrenaline, and cortisol).

This is also the premise behind the concept of intermittent fasting.  By training yourself to cut out snacks and go for longer periods of time between meals, the metabolic system — which includes not only digestive hormones and enzymes, but neurotransmitters and hypothalamic receptors — adapts to increase its dynamic capacity.  The resulting benefits are lower basal levels of anabolic hormones like insulin and catabolic hormones like glucagon and adrenaline. But just as importantly, intermittent fasting develops improved sensitivity and the ability to both ramp up and reduce these hormones quickly and responsively.

The benefits of spending time in the fasting state are numerous, including a natural detoxification and nutrient recycling process known as autophagy, and the upregulation of brain-protective growth factors such as Brain-Derived Neurotrophic Factor (BDNF).  Fasting allows for the upregulation of fat-liberating enzymes and hormones and a significant and glucose transporters, thereby improving insulin sensitivity. McEwen has compiled research showing that an appropriate level of “stress” or allostatic load will increase markers of brain plasticity. By contrast, following the conventional wisdom to eat six small meals a day of controlled glycemic foods, in the misguided attempt to “regulate” blood glucose at a constant level, deprives your body of these important restorative and protective processes.

But at the other extreme, extensive fasting or strict low carbohydrate dieting can leave the pancreas underutilized and thereby lead to a reduction in glucose transporters in the cells, since these are no longer “demanded”.  Our cells and organs tend to “economize” by synthesizing only the machinery they really need: use it or lose it.  People who abstain from or never consume milk will lose the ability to produce the enzyme lactase, so they become lactose intolerant.  Similarly, we need to regularly “exercise” our ability to secrete insulin on demand and the ability of cells to utilize glucose. This doesn’t necessarily have to occur every day, but several glucose loadings a week are probably necessary.

So the wise course is to apply “stress oscillation” to diet, and alternate judiciously between fasting and nutritious, balanced meals with a variety of macronutients and micronutrients.   Remember that the “stress” is binary: fasting represents recovery from the “stress” of eating; and eating relieves the “stress” of fasting.   A dynamic approach of hormesis involves stretching the ability to move between these two poles, increasing “allostatic capacity”.

Example 3.  Stress, health and cortisol.  Of all the hormones, cortisol has acquired a reputation as “the bad guy”.  It is well known that elevated cortisol levels are the mark of chronic stress and adrenal fatigue.  It has been suggested that higher levels of cortisol are linked to disregulated or high blood glucose levels and predispose one to diabetes. Chronically elevated cortisol also damages neurons in the hippocampus, leading to memory loss and cognitive decline. As a result, some practitioners mistakenly advise trying to minimize stress and even eat frequent meals, in order to keep cortisol at bay and avoid “stressing” the adrenal glands. But this is a one-sided perspetive.  Cortisol is necessary to normal alertness and mental function, as well as our ability to respond to sudden demands like exercise or threats. The problem comes when cortisol does not exhibit a normal morning peak level, followed by a steady decline through the day, but instead remains flat or even increases in the evening.  Chinook et al. classified four different cortisol patterns, shown below.  Pattern 1 (Graph A) is normal; Patterns 2, 3 and 4 show the flattening or later peaks that characterize dysregulation:

Diurnal or event-related elevations in cortisol are not problematic, so long as cortisol levels return to baseline at a decent rate, as in Pattern 1. According to Lovell et al., higher percieved stress levels are reflected not so much in average cortisol levels, but rather as higher basal or evening cortisol levels, and flatter diurnal fluctuations in cortisol levels. Matthews et al found that individuals with the flattest cortisol pattern (slowest rate of decline to baseline) were most at risk of coronary calcification.  Sephton et al found that flatter cortisol patterns were predictive of suppressed immunity and lower survival rates in women with metastatic breast cancer.

In short, we should be less concerned with absolute cortisol levels, than with the pattern of cortisol secretion.  As with other hormones, increased dynamic range and a robust cyclical pattern are indicative of fitness, stress-hardiness, and health.

The larger lesson.  James Loehr (about whom I wrote in my earlier post on Stress management and toughness training) has written eloquently about the use of “stress oscillation” to build athletic capicity and resilience in the corporate world in his book The Power of Full Engagement:

Balancing stress and recovery is critical not just in competitive sports, but also in managing energy in all facets of our lives. When we expend energy, we draw down our reservoir. When we recover energy, we fill it back up.  Too much energy expenditure without sufficient recovery eventually leads to burnout and breakdown…Too much recovery without sufficient stress leads to atrophy and weakness….Oscillation occurs even at the most basic levels of our being. Healthy patterns of activity and rest lie at the heart of our capacity for full engagement, maximum performance, and sustained health. Linearity, by contrast, ultimately leads to dysfunction and death. (TPOFE, pp. 29-31).

How to apply stress oscillation to your life. Let’s return to the question at the beginning of this post: How much of any kind of stress is enough, but not too much, to generate a hormetic benefit? The answer is: This is the wrong question!  You should not be striving for some magic optimum level of constant stress. Rather, you should strive to oscillate stress, by exposing yourself to intermittent, but intense sources of stress.  This builds dynamic capacity or strength. The amount and frequency of the stress are variables you can experiment with, but younow have a way to measure the benefit and know whether you are on track. The key metric is dynamic capacity. The appropriate measures of dynamic capacity depend upon what our goals are:

• For physical fitness:  a high VO2 max during exertion combined with a low resting VO2, resting pulse, and blood pressure.
• For dietary or metabolic health:  a rapid insulin and blood glucose response to food and low basal insulin and blood glucose levels
• For stress hardiness:  peak cortisol levels upon waking, followed by steady decline to low evening (basal) levels.

These may be imperfect measures, and they are subject to exceptions and interpretations based upon special health circumstances. Some of these measures are easy to implement at home; others are less convenient because they require blood or saliva analysis (which can be purchased online). But the general principle is valid:  Don’t look for average biometric values, but look for the dynamic range between high and low. And look for an oscillatory pattern that demonstrates periods of testing and building capacity, alternating with periods of rest and recovery.  I’ve discussed only three applications here in detail: digestion, exercise, and general stress tolerance.  But the principle of stress oscillation can be applied to many other applications of hormesis:  suntanning, allergen immunotherapy, cold showers or plus lens therapy.  I leave it to the curious reader to think about the physiological processes at work, and the appropriate measures of improved dynamic capacity.

The goal of hormetic stress should be to increase dynamic capacity to handle allostatic load — variable stresses — in a measureable way.  The precise level and frequency of stress exposure will vary from person to person. This is not a one-size-fits all path to health, but rather a journey that each of us must take for ourselves.  But on this journey, our engine is stress oscillation and our compass is increased dynamic capacity.

Why is it so hard to make permanent changes to your habits, your health, and your happiness?  Some of the most difficult struggles in life involve losing weight (and keeping it off), overcoming addictions, and recovering from depression. Many diets and therapies deliver great short term results, but the most common pattern appears to be relapse.  It often seems that you are destined to fulfill some biological program — that you are stuck with a high body weight set point or an addictive or depressive personality that cannot be escaped in the long run.

This pessimistic message is prevalent among those who have investigated the track records of the “helping” industries: the weight loss companies, the addiction recovery centers, and the various schools of psychology and psychiatry. Unlike the advocates, those who investigate them often find the results are less than what the practitioners might want you to believe.  In the arena of dieting and weight loss, books such as “The Dieter’s Dilemma” (Bennett and Gurin, 1982), and  ”Rethinking Thin”  (Kolata, 2008) echo the original set point theory first propounded by Gordon C. Kennedy in the 1950s; they conclude that your body weight is largely predetermined by a biological set point that is handed to you at birth, plus or minus about ten pounds. I do agree that sustained weight loss cannot be achieved through sheer will power alone, or simply by using diet and exercise in order to create a calorie deficit. Yet, while there is some plausibility to the set point theory, I am convinced that it is wrong because it overlooks some important factors. I’ve already given some of my reasons for my disagreement with set point theory in other posts on this blog (Flavor control diets, How to break through a plateau). But in this post I’ll present some strong evidence for an alternative theory, based on the homeostatic regulation of cellular receptors for hormones and neurotransmitters. This is a variable set point theory which I call the receptor control theory. This theory proposes a mechanism that controls appetite and body weight, as well as regulating the balance of  energy and pleasure in your life. It provides practical tools to lose weight and keep it off, overcome addictions without relapse, and move out of depression into happiness.

But first, let’s consider some common approaches for dealing with three different  health issues:

1. Obesity/Diabetes. To lose weight, reducing diets are employed that create an energy deficit.  The most effective of these diets work by actively modulating the levels hormones such as insulin or leptin, by modifying the type of food we eat (low glycemic or low carbohydrate are best), or the size and timing of meals.  In the case of advanced diabetes (an insulin deficiency), exogenous insulin is administered periodically in a controlled manner. Alternately, diet pills or other appetite suppressants are used to moderate certain hormones and peptides involved in satiety.  The back-up strategy is to learn how to cope with always being somewhat hungry.
2. Addiction. Addictive cravings from cocaine, alcohol, or other substances or activities have been associated with overstimulated dopamine “reward” circuits.  Some  treatments involve the use of antidepressants to elevate baseline dopamine levels, The back-up strategy is to counsel abstinence to avoid triggering the dopamine circuits in the first place.
3. Depression. To counteract depression, antidepressant drugs (typically SSRIs) are prescribed to boost levels of neurotransmitters such as serotonin or dopamine. Or, we may try non-drug supplements or dietary options to increase the level of these neurotransmitters: for example, serotonin precursors such 5-HTP,  tryptophan-rich food such as turkey and carbohydrates such as potatoes, which allow dietary tryptophan to readily produce serotonin in the brain. The back-up strategy is psychotherapy to provide insight or coping skills to better deal with the underlying depression.

The organic imbalance model. These three seemingly different treatments share a common thread: they are all based on conceiving health problems as intrinsic organic imbalances in our metabolism or neurochemistry that you are either born with or develop early in life, and over which you have little control.   Once you accept this model, there are two basic strategies: an “active” strategy to rebalance internal biochemistry, usually by means of drugs, supplements, or diet. And a “passive” back-up strategy of accepting that you are biochemically different, and counseling ways to cope with these organic conditions as best youe can, while trying to minimize the risk of triggering flare-ups due to relapse, bingeing, or depressive episodes.

Signaling compounds. I’ll focus here more on the “active” interventions which involve trying to directly rebalance the levels of “biochemical messengers” or signaling compounds circulating in our bodies. I’m referring to hormones like insulin and leptin, glucagon, or adrenaline; or neurotransmitters like serotonin or dopamine, which are produced in response to external stimuli.  According to the imbalance model, the levels of these signaling compounds are out of balance: there is a surplus or deficiency of “communication” that needs to be adjusted. The resulting “message” conveyed by the signaling compound is “too loud” or “too soft” for normal bodily function.  So to correct this, a therapeutic intervention is devised which attempts to restore our health by adjusting the amount of the signalling compound in our system.  In effect, the treatment attempts to turn up or turn down the “volume” of the message by adjusting the amount of signaling compound, in order to re-normalize our response to external stimuli.

These active medical or dietary interventions should work, if the imbalance model is correct.  But in many cases the treatments backfire:  after perhaps seeing a short term benefit the effect dissipates, and in some cases symptoms actually worsen, or side effects develop.  After some initial weight loss, the weight is regained.  Attempts to overcome addiction frequently end with relapse and failure. And depression returns. The problem is that we are not mechanical machines, we’re adaptive organisms, regulated by homeostasis. Trying to control message intensity may work for a short time, but the body outsmarts us and compensates for the intervention. Our wonderful, adaptive bodies react to the increased level of signaling compounds by becoming less responsive to them, just as we learn to tune out a dog that constantly barks for attention.  When the message volume is turned up, the receiver volume is turned down.

Our efforts to change seem to be hampered by biological programs that resist these efforts at biochemical rebalancing. Some will explain this by arguing that’s because we are born with a biological set point that our body will “defend” or an addictive or depressive personality that we can’t shake.  Try as we might to fight this in the short term, it’s almost impossible to succeed in the long run.  A lucky few may prevail, but the vast majority are doomed to their biology destiny.

Even if you manage to normalize the level of signaling compounds, you are now stuck with another problem:  you are dependent on some drug, supplement, or special dietary restriction for the long term — maybe even for the rest of your life. Drug companies and dietary supplement suppliers are happy to provide you with a lifetime supply of these compounds for a price.  I don’t know about you, but I’d rather not be dependent long term on drugs or supplements, or even restrictive diets, if it doesn’t have to be that way.

There are grounds for pessimism here.  But there may be a better solution that gives us back control of our fate:  Receptor regulation.

Receptor regulation. Receptors are “message receivers” located throughout our bodies. They are typically transmembrane proteins located on the surfaces of cells, and they bind with hormones and neurotransmitters to “receive” the signal and initiate a sequence of changes in our bodies — often profound system-wide changes in energy utilization, tissue growth, or the perception of pleasure and pain. For some reason, receptors don’t get the public attention that gets showered on the communication chemicals — the hormones and neurotransmitters.  And yet, as I shall argue, the receptors may be far more important than the signaling compounds that they interact with, because they do not change by the minute or hour, but are long-lasting parts of the control systems of our bodies.  If hormones and neurotransmitters are the “software”, receptors are the “hardware”.

The key process to understand is called receptor regulation, the process which controls the number, location and sensitivity of receptors. There are two forms: upregulation (an increase in the number and/or sensitivity of receptors in each cell) and downregulation (the reverse process). Wikipedia explains downregulation by describing how insulin resistance develops in response to elevated insulin levels:

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell’s surface without doubts. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it varies only in the receptor hormone complex. (Italics added by me for emphasis).

So not only are the insulin receptors drawn inside the cell (like a turtle into its shell); they are also actively digested and degraded, making them less available to readily redeploy when glucose and insulin levels drop again.  New receptors are always being synthesized, but they are degraded more quickly than they can be replenished if insulin levels remain high. The resulting downregulation of insulin receptors forms the basis for the condition of insulin resistance, in which insulin at normal levels loses its ability to efficiently shuttle glucose from the bloodstream into liver, muscle, brain, adipose or other tissues; the body responds by further increasing insulin, resulting in a vicious cycle of hyperinsulinemia. Reversing this process — growing new insulin receptors — takes time and requires sustained periods with low circulating levels of insulin in order to foster the growth of new receptors.

It is quite revealing to look at how how receptor regulation can undermine “message control” treatments,  due to the way the body adapts. Let’s take a look again at how this plays out in the above three examples of obesity, addiction, and depression:

1.  Obesity. Obesity is associated with high levels of two hormones: insulin and leptin. Normally, an increase in the level of either of these two hormones induces satiety upon reaching the hypothalamus in the brain. Leptin levels in the body increase with the amount of body fat, so leptin has been proposed as a physiological correlate for our “set point” weight: when body fat falls below a certain level, appetite induces us to eat more; when body fat increases, the associated rise in leptin levels leads to satiety. Insulin plays a similar but different role; it tends to regulate appetite on a shorter timescale than leptin, varying during each meal, and is more closely associated with visceral fat of the type more commonly found in men, whereas appetite regulation by leptin operates on more of a daily timescale and responds more closely to subcutaneous fat of the type more common in women. Insulin, of course, is directly involved with the storage and release of metabolic fuels. There are also many other regulatory hormones and sensory peptides, such as ghrelin, CCK and PYY, which adjust appetite based upon meal timing, gut sensations, and other inputs.  But insulin and leptin are key drivers of appetite.

The discovery of leptin, the “satiety hormone” by Jeff Friedman at Rockefeller University in 1993 provoked great excitement and expectations.  A well written account of this discovery is detailed in “Rethinking Thin“, the above-mentioned book by Gina Kolata. Studies in leptin-deficient ob mice and humans showed that individuals with defective production of leptin became ravenous and obese.  So the logical conclusion was leptin itself may be the magical “set point” compound that determines our weight.  Therefore, we should be able to provide leptin to the overweight to help them shed pounds. And in fact, adminstering leptin does work to counteract obesity in mice and humans that are genetically incapable of producing normal leptin, as Kolata describes poignantly in her chapter “The Girl Who Had No Leptin”.  It even works initially in normal or lean mice to reduce body fat. Amgen acquired the rights to leptin from Rockefeller University for $20 million plus royalties in anticipation of imminent commercialization. But after a long-term study in humans, the October 1999 issue of  JAMA reported disappointing results indicating very little weight loss, and even that in only in a small percentage of subjects. As Kolata observes:

The question, though, was, Why didn’t the obese people in Amgen’s study respond to leptin? The possibiity, or perhaps the likelihood, was that leptin was not their problem. These people were making plenty of leptin–they were not the human equivalent of the ob mice. And since adding more leptin did not make them lose weight, it must be that the hormone was being blocked from acting somewhere along its passage from the fat cells to the appetite-controlling pathways in the brain…Then [scientists] discovered that leptin can do something else. It can actually change the brain’s wiring diagram, strengthening circuits that inhibit eating and weakening the ones that spur the appetite. It can exert this effect at a critical period early in life, perhaps influencing appetite and obesity in adults.  And, in adulthood, leptin can again alter the brain’s wiring, permanently changing an animal’s appetite and weight. (RT, pp. 163-165).

The problem is often that excessive sustained levels of leptin, common in the overweight or obese,  can cause “leptin resistance” in which the leptin receptors are downregulated, so that they are fewer in number and become less sensitive to the leptin signal. As Byron Richards indicates in The Leptin Diet:

In overweight people, the communications involving insulin and leptin are inefficient. It is like making a phone call where no one answers. Insulin resistance and leptin resistance mean that the hormones don’t communicate efficiently in response to food. Thus a person has to overeat in order to get enough leptin into the brain to get a full signal. The pancreas may not hear the leptin signal to stop making insulin, which leads to excess insulin, fatigue, and possibly even more hunger within a few hours of eating…Several hours following the meal the extra insulin ends up taking too much sugar out of the blood, making a person hungry and tired-headed. (TLD, p 36)

With leptin resistance, adding more leptin no longer effectively inhibits appetite, because the brain and body have a reduced ability to respond to the extra leptin.  Conversely, lean individuals typically have more leptin receptors and greater leptin sensitivity, so their appetite is satisfied even at reduced leptin levels.  In short, the leptin system adapts so that the number of leptin receptors adjusts to the amount of leptin.

Interestingly, obesity is also associated with reduced number of receptors for dopamine, a neurotransmitter associated with pleasure or reward circuits in the brain. In 2001, Gene Jack Wang and Nora Volkow of the U.S. Department of Energy’s Brookhaven National Laboratory used Positron Emission Tomography (PET) brain scans to look at dopamine receptors in the brains of obese and normal individuals:

Obese individuals, the scientists found, had fewer dopamine receptors than normal-weight subjects. And within this obese group, the number of dopamine receptors decreased as the subjects’ body mass index, an indicator of obesity, increased.  That is, the more obese the individual, the lower the number of receptors.

A 2008 study of women and adolescent girls in New Zealand showed that this receptor deficit is at least partly genetic. The overweight females had the Taq1A1 gene that is associated with fewer dopamine receptors. This receptor deficit in the obese led them to overeat to achieve the level of pleasure or satiety that normal individuals reached with less food. This reduced level of dopamine receptors tends to make life a bit less pleasant for the obese when they are hungry and without food. Ingestion of food, particularly carbohydrates, temporarily raises the level of dopamine, eliminating the “pleasure deficit” and rewarding eating behavior.  Excessive eating or bingeing raises the dopamine levels even higher than normal, which can lead to a further downregulation of dopamine receptors, only worsening the craving problem. This effect is not only influenced by genes, but by diet; a 2010 study of rats fed a supermarket “junk food” diet showed raid desensitization of dopamine receptors a significant increase in appetite, and an unwillingness to return to eating “healthy” food.

The connection between obesity and the number and sensitivity of dopamine receptors is perhaps not so surprising, given how highly rewarding food can be for the obese; for many of the overweight, food becomes an addiction.  It is still quite striking that this translates to such a significant decline in the number of dopamine receptors, while the baseline level of dopamine actually increases.  Here, as with insulin and leptin, we have yet another example of reduced receptor levels being associated with obesity.  By analogy with insulin resistance and leptin resistance, we might say that the strong appetite of the obese is a direct result of “dopamine resistance”.

2. Addiction. What is particularly interesting is that these low levels of dopamine receptors are also characteristic of drug addicts and alcoholics.  Nora Volkow, one of the directors of the Brookhaven study, subsequently became director of NIDA, the National Institute of Drug Abuse. part of NIH, but her research on addiction actually predates the study she did on brain activity in the obese. She used PET brain scans to study dopamine receptors levels in alcoholics, cocaine addicts, and addicted smokers.  And, as you might guess, the same pattern of reduced levels of dopamine receptors was observed in addicts vs. non-addicted controls.  This is illustrated in the PET scan to the right, which shows dopamine binding activity for addicts (top row) vs. non-addicts (bottom row). Regions of greatest dopamine receptor activity are indicated with a color scale starting from red (most active), descending through yellow and green to blue and purple (least active).

The mechanism downregulation of dopamine receptors by cocaine has been elucidated:

Cocaine binds tightly at the dopamine transporter forming a complex that blocks the transporter’s function. The dopamine transporter can no longer perform its reuptake function, and thus dopamine accumulates in the synaptic cleft. This results in an enhanced and prolonged postsynaptic effect of dopaminergic signaling at dopamine receptors on the receiving neuron. Prolonged exposure to cocaine, as occurs with habitual use, leads to homeostatic dysregulation of normal (i.e. without cocaine) dopaminergic signaling via down-regulation of dopamine receptors and enhanced signal transduction. The decreased dopaminergic signaling after chronic cocaine use may contribute to depressive mood disorders and sensitize this important brain reward circuit to the reinforcing effects of cocaine (e.g. enhanced dopaminergic signalling only when cocaine is self-administered). This sensitization contributes to the intractable nature of addiction and relapse.

3.  Depression. A reduced number or sensitivity of neurotransmitter receptors has also been linked to mood disorders such as major depression. Depression has been associated with shortages of at least two neurotransmitters:  dopamine (which is associated with drive, motivation and pleasure), and serotinin (which is associated with a sense of well-being and pleasure).  While dopamine receptors are located largely in the brain, a little known fact is that only about 20% of serotonin receptors are in the brain, most of the other 80% are in the gut, blood platelets, and other organs.  That might help explain why serotonin is also associated with food and satiety.   Different types or depression are often associated with a different imbalance of neurotransmitters, so despite the prevalence of SSRIs, which are intended to restore serotonin levels, some forms of depression respond better to antidepressants which boost dopamine levels.

While antidepressants work for many people, a surprising number — some estimates put it at 50% or higher — are unresponsive. Furthermore, long term use of SSRI’s can have the effect of downregulating serotonin (5-HT2A) receptors with adverse results:

Another adaptive process provoked by SSRIs is the downregulation of postsynaptic serotonin 5-HT2A receptors. After the use of an SSRI, since there is more serotonin available, the response is to decrease the number of postsynaptic receptors over time and in the long run, this modifies the serotonin/receptor ratio. This downregulation of 5-HT2A occurs when the antidepressant effects of SSRIs become apparent. Also, deceased suicidal and otherwise depressed patients have had more [presynaptic] 5-HT2A receptors than normal patients. These considerations suggest that 5-HT2A overactivity is involved in the pathogenesis of depression

The last sentence in the above quote again points to the fact that a deficiency of post-synaptic serotonin receptors, in combination with  an excess of serotonin from diet, antidepressants, or elsewhere,  may play a role in both the genesis and worsening of depression.  The same phenomenon of receptor downregulation together with excess neurotransmitter has been noted with other antidepressants, such as MAO inhibitors and buproprion, that stimulate the production or prolong the lifetime of dopamine in the synapse.  This can lead to tolerance and withdrawal effects.

In short, in all these cases — obesity, addiction, and depression — receptors are becoming less sensitive to a signaling compound as a reaction to excessive levels of that compound.  So too much insulin and leptin lead to insulin and leptin resistance, too much dopamine to a downregulation of dopamine receptors.

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HOW TO UPREGULATE YOUR RECEPTORS. So if directly changing the amount of signaling compounds is frequently frustrated by receptor downregulation, is there anything you can do to upregulate the receptors?  Fortunately, the answer is yes.  There are a number of measures that have proven particularly effective for deliberately increasing the number and sensitivity of key classes of receptors:

Step 1:  Strenuous exercise. Regular, intense exercise can upregulate your insulin receptors. In Dr. Bernstein’s Diet Solution, Richard Bernstein explains the role of exercise in actually reversing insulin resistance by growing new muscle tissue, and by increasing the density of glucose transporter receptors in muscle and other tissues.  While his advice is directed primarily towards diabetics, it applies more broadly to anyone with some degree of insulin resistance That includes most of us.  According to Dr. Bernstein:

The higher your ratio of abdominal fat to muscle mass, the more insulin-resistant you’re likely to be. As you increase your muscle mass, your insulin needs will be reduced…Long-term, regular strenuous exercise also reduces insulin resistance independently of its effect upon muscle mass…In my experience, it takes about two weeks of daily strenuous exercise to bring about a steady, increased level of insulin sensitivity…via increased production of glucose transporters in muscle cells. (DBDS, p. 170-1).

Furthermore, the exercise must be strenuous and “anaerobic” – not aerobic.  There are two reasons for this:

First, the blood sugar drop during and after continuous anaerobic exercise will be much greater than after a similar period of aerobic exercise. Second, to accomplish efficient transport of glucose into muscle cells, as muscle strength and bulk develop, glucose transporters in these cells will greatly increase in number. Glucose transporters also become more numerous in tissues other than muscle, including the liver.  (DBDS, p. 180)

Glucose transporter (GLUT4) receptors are upregulated by intense exercise.  A study reported in the New England Journal of Medicine showed that this upregulation begins to happen within hours, but significant and sustained improvement requires repeated exercise sessions over several weeks.  When insulin levels are kept low, the glucose transporters migrate from a location inside the cell to protrude beyond the cell surface, becoming more available to bind glucose and shepherd it into the interior of the cell.  With time, the cells can actally express or “grow” additional receptors, increasing the overall rate of glucose transport.  This increased response rate is synonymous with “insulin sensitivity”.

The benefits of anerobic exercise extend not only to upgregulation of insulin receptors, but also to maintaining high levels of dopamine “reward” receptors. A study of exercised rates by McRae et al at University of Texas showed that regular exercise has a protective effect on D2 dopamine receptors, while keeping levels of dopamine (DA) and dopamine metabolite (DOPAC) low.  Unexercised rats saw both a decrease in D2 receptor density and an increase in circulating dopamine.

Step 2:  Calorie restriction and intermittent fasting. Another brain scan study at Brookhaven National Laboratory showed that restricted eating led to higher numbers of dopamine receptors in obese rats:

The scientists found that genetically obese rats had lower levels of dopamine D2 receptors than lean rats. They also demonstrated that restricting food intake can significantly increase the number of D2 receptors, partially attenuating a normal decline associated with aging.

This research corroborates brain-imaging studies conducted at Brookhaven that found decreased levels of dopamine D2 receptors in obese people compared with normal-weight people,” said Brookhaven neuroscientist Panayotis (Peter) Thanos, lead author of the current study, which will be published online in the journal Synapse on Thursday, October 25, 2007.

One of the essential points to understand here is that if calorie restriction and intermittent fasting are effective, it is not for the reason that most people think explains this (that you are creating a calorie deficit).  Rather, intense exercise and fasting work because they resensitize and grow your insulin and dopamine receptors in a way that allows you to get enough energy and pleasure from eating less food.   This means that not only are the receptors upregulated, but you also get the energy and pleasure when you need it.  So restricting calories is not good enough.  You must eat foods that maximize insulin senstivity (e.g. containing adequate essential fatty acids, protein, magnesium, etc.) and foods which give you enough pleasure so as to satisfy your “pleasure budget”, but not so much as to downregulate your dopamine receptors.  My experience is that intermittent fasting, using a varied diet, is the best way to do this.  One reason that pure “starvation diets” like that used in the Minnesota Starvation Experiment may have failed is that the diet failed to supply adequate nutrients that to support receptor function for cellular energy and pleasure.  (The 1560 calorie/day regimen consisted only of potatoes,  rutabagas,  turnips,  bread and macaroni — so go figure!)

A particularly effective protocol for improving insulin sensitivity and upregulating glucose transporter receptors is called “fasted workouts”: a combination of intense exercise and intermittent fasting, in which eating is postponed until after one works out.  One of the foremost practioners of this approach is Martin Berkhan, who I’ve referenced on the Fitness page of this blog, and whose Leangains blog I’ve listed under the Diet links.  Martin summarizes the research by DeBock et al. and Cluberton et al. that documents the physiological beneifts of fasted workouts, including enhanced insulin sensitivity based upon a six-week study with four 60-90 minute workouts per week. The study controlled for dietary intake, and compared results of those who fasted (F) with the control group (C) that ate prior to working out. Among other variables, the study compared changes in the levels of the GLUT4 transporter, a type of insulin receptor in the muscles, between the F and C groups:

Glucose transporter type 4 is a protein responsible for insulin-regulated glucose transport into the muscle cell. It increased by a whopping 28% in F but only 2-3% in C (not mentioned in the paper but this is my estimate based on the graphs). This partly explains why F saw superior results in regards to glucose tolerance and insulin sensitivity. Since GLUT4 is triggered by AMPK, which is increased when glucose availability is low, i.e. during fasted training, one would assume the GLUT4 increase could then be explained by an increase in AMPK. This was found to be true: AMPK increased by 25% in F, which correlated closely with the increase in GLUT4 content.

Step 3: Deconditioning and extinction. Pleasure reward circuits do not change overnight.  But the good news is that there is plenty of evidence that these reward circuits can be extinguished by classical conditioning techniques.  I’ve discussed these deconditioning techniques in depth on the Psychology and Diet pages of this blog, and I’d recommend looking there for details.  Extinction involves merely refraining from the undesired behavior (eating, addictive drugs) and allowing the cravings to happen without reinforcing them.  It may surprise you how quickly your reward circuits recover, and it is very likely that this involves upregulation of dopamine receptors, so that the brain is more easily “satisifed” without the previously craved behavior. Deconditioning is more active than extinction; it requires actively exposing yourself to cues which normally set off the addictive response.  This may sound extremely difficult, but is attested to by extensive research, as well as the personal experience of several people who have posted here on the Forum, including myself.   One of the more successful appliations of active deconditioning is the Sinclair Method, which has been used successfully to extinguish alcoholism while training the former alcoholic to drink moderately. The key is the use of a dopamine blocker, naltrexone, to block the reward circuits during exposure.

Any type of extinction should benefit from simultaneous reinforcement of healthy alternative sources of pleasure, while engaging in exercise and intermittent fasting to rebuild the density and sensitivity of receptors.  Unless you increase your level of dopamine receptors, you’ll always be vulnerable to the temptation of any pleasure that can “fill your pleasure deficit”.

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THE RECEPTOR CONTROL THEORY. Based upon a synthesis of extensive evidence, I’m putting forward in this post an alternative to the classic set point theory of Gordon Kennedy:  the receptor control theory.  This is a general hypothesis of biological regulation which applies to more than just weight control; it applies to any homeostatic variable that is controlled by cellular receptors — even, for example, pleasure and motivation. Whereas the classic set point theory of body weight posits a fixed genetic set point for each individual,

the receptor control theory postulates that our set points for regulating weight, energy, or pleasure are variable; they are directly related to the number, sensitivity and location of cellular receptors in our bodies, and can be modified by changing the number and sensitivity of these receptors.

For example, the set point for your body fat is controlled by insulin and leptin sensitivity, which is determined by the number and functional sensitivity of insulin and leptin receptors throughout your body.  As the number and sensitivity of insulin and leptin receptors decreases, body weight set point goes up. But unlike the set point theory, body fat set point can also go down by increasing the number and sensitivity of these receptors — for example by the use of strenuous exercise, intermittent fasting, and extinction.

If you don’t change the number and sensitivity of your receptors, your set point will not change.  Under these circumstances, the receptor control theory agrees with the classic fixed set point theory. However, the receptor control theory provides a way to change your set point by upregulating your receptors.

The pleasure budget. The receptor control theory goes beyond weight management to explain more generally the regulation of pleasure in your life.  If you have ample dopamine receptors, then a wide variety of stimuli– including food, social interactions, work, and other interests– should provide you with sufficient pleasure to make life not just bearable, but interesting.  However, if you end up with an undersupply of dopamine receptors — whether it be from birth, addictions or unremitting stress — then your baseline pleasure “set point” will be low and you’ll be vulnerable to depression, low self-esteem and other aspects of unhappiness. Addictive escapes may provide temporary (but unsustainable) bursts of dopamine, serotonin, and other feel-good neurotransmitters, but at the cost of further downregulating dopamine receptors and feeling worse later on.

It may be the case that all of us have a certain “pleasure budget” — perhaps we need a certain amount of pleasure every week, and we’ll find a way to get it, one way or another.  One of the commenters (zdd) to my earlier post on The opponent-process theory of emotion expressed this point well, when speculating about why diets like Shangri-La and Atkins work so well initially, but eventually become less effective:

If there is a set point, I believe it’s not a weight set point but rather a pleasure set point. When you don’t reach the set point, cravings start and when you go over the set point (staying too long at the fair) you get feelings of aversion.

I doubt if the pleasure set point changes very much. People simply switch sources of pleasure. Stop smoking, and you start eating more. Much of the pleasure of being on this diet comes from the pleasure of feeling in control. Once the novelty of control wears off people will have to look for other sources of pleasure or they will go back to getting pleasure from food.

I think this insightful comments carries a useful warning: that behavioral changes such as diets which cut off one source of pleasure may require us to find a way to replace that source of pleasure, or else risk rebounding from the diet and regaining the weight we lost.

The good news here is that there are proven ways to raise our “pleasure” set point.  The bad news is that they require significant and sustained effort – no quick fixes.  And yet it is the most sustainable way to increase pleasure in life.  To paraphrase a saying about fishing sometimes attributed to the Bible: “Give someone a neurotransmitter and they’ll feel good for an hour; teach someone to grow more receptors and they’ll feel good all the time.”

Explanations. The receptor control theory explains a number of observations that cannot be accounted for by classical set point theory:

1. Biology is not destiny. Individuals do differ genetically in their tendency to gain weight or to be prone to addiction or depression.  You are born with a certain density of receptors and this can be influenced further during prenatal and postnatal development.  But it is not the end of the story. The types of foods you eat and the frequency of eating have strong effects on insulin and leptin sensitivity.  Likewise, exercise, hard work and a stoic practices can sensitize your dopamine receptors and make you happier and less prone to depression.
2. Obesity is not a constant. Both the weight gain of individuals as they age, and the obesity epidemic of recent decades are often blamed on “calorie imbalance”: eating too much and exercising too little. But this doesn’t explain why this caloric imbalance is happening now as opposed to earlier. Sometimes the uptick in obesity is blamed on the increasing availability of tasty high-calorie food and a less active lifestyle. But that explanation cannot be right, because there has always been tasty food. And as Kolata has shown, controlled interventions to reduce calories and enforce more activity have a poor track record.  The reason that body weight set points are rising has more to do with changes in the amounts of food and exercise, as it does with specific types of food, eating patterns and exercise–and the long term hormonal influences of these changes on receptor sensitivity.
3. Permanent weight loss is still possible. Granted, most diets don’t work. Quick weight loss diets don’t work because they don’t allow a biologically realistic amount of time for receptors to upregulate; receptor upregulation is a gradual process that requires persistence and effort. Certain diets are quite effective in the short term, including low carbohydrate diets, low glycemic diets, and the Shangri-La Diet (which temporarily suppresses appetite). These diets will temporarily change levels of hormones, neurotransmitters and other signalling compounds to induce satiety and weight loss. However, unless appetite circuits are permanently “re-wired” by upregulating hormonal and neural receptors, weight loss will be temporary.  Appetite will remain vulnerable to coming back like a tiger, and you may return to your old set point weight — perhaps even plus a few pounds.  The best way to upregulate metabolic and appetite receptors is by strenuous exercise, intermittent fasting or deconditioning.  Given enough time, persistent and habitual dietary changes can lead to permanent weight loss, particularly when combined with reduced eating frequency, intense exercise, and deconditioning.

Biological basis for Hormetism. The receptor control theory also provides us with a some biological underpinnings for Hormetism and Stoicism, as advocated in this blog. Hard work –tough, uncomfortable and challenging activities–can lower our metabolic and pleasure set points, helping us to lose weight and making us less vulnerable to addictions, cravings and depression.  What is exciting to me is that this theory may provide a possible biological basis for the psychological Opponent-Process Theory of Richard Solomon.  The basis is located not in transient chemical messengers like neurotransmitter and hormones, but rather in the adpatable receptors located throughout our body on every cell.  These receptors are part of the hardware or firmware of our bodies and brains.   Receptors are a part of us that cannot be changed overnight, but can only be changed with persistent effort.  (And they will not disappear so readily either).

I will be the first to acknowledge that at this point the receptor control theory is just that — a theory.  It has support by scientific evidence, but many questions remain.  And yet it is a productive theory which generates many testable hypotheses.  It provides us with a possible basis for understanding the benefits of less-studied hormetic or Stoic practices such as showering or swimming in cold water, radiation hormesis, or allergen immunotherapy.  Do these types of stress also result in upregulation or downregulation of specific cellular receptors involved in pain perception, cellular repair, inflammation or immune response? Can we measure and better understand these responses at the level of receptors? Are there practical ways to measure the number and sensitivity of our receptors, so that we can track progress? Receptor change is probably only one of many mechanisms that explain hormesis, but it may be an important and underappreciated one.  These questions make good topics for future posts.

Finally, unlike the classic set point theory, the receptor control theory is not fatalistic, but is optimistic:  By combining insights as old as ancient Stoic philosophy with a contemporary scientific understanding of psychological conditioning and the plasticity of cellular signal receptors and receptor circuits, we can work to achieve fitness and weight loss, freedom from addictive compulsions, and chart other major changes in our metabolic and psychological well being.

And then…progress stalls. You’re still eating the same foods, faithfully completing your workouts, but your weight loss stalls, perhaps the scale even goes up a few pounds. The progress you make at the gym similarly maxes out…you can’t lift any more weight, your running speed or distance maxes out…maybe even some soreness or injury sets you back a bit. You’ve hit the dreaded plateau.  Sometimes it lasts a few weeks and progress resumes. But it can last months. And it saps your morale because you are not getting any more return on your invested effort. In all likelihood, you give up or cut back, your discipline withers. Your weight goes back up, maybe adding a few pounds on top of where you started, and you cut back on or cut out your exercise program. The genie is back in the bottle.

What causes plateaus?  Are they inevitable endpoints in any effort to make progress? Or are they at best temporary way-posts or resting points that you can move beyond with the right approach?  The school of thought that says that plateaus are unavoidable indicators of biological limits is called the Set Point theory. I think that the Set Point theory is wrong, and that there is a reliable way to push past plateaus to bring about substantial weight loss and improved fitness.

Conventional plateau busting suggestions. Before we get into the Set Point theory, let’s take a look some typical suggestions you’ll get if you google “plateau busting” or “break through plateau”:

To break through exercise plateaus:

1. Increase exercise intensity
2. Take a break – don’t overtrain
3. Try new exercises
4. Mix up your routine, change the order of exercises
5. Wait out the plateau

To break through diet plateaus:

1. Eat more frequently, don’t skip meals
2. Eat different foods
3. Drink more water
4. Wait it out

Many of these are good suggestions, and they can work to jump start progress. But I suspect that more often than not, these approaches at best result in temporary progress, lasting perhaps a few days or weeks. Progress is soon reversed and you are right back on the original plateau. Eating more frequent small meals might lead to a temporary boost in metabolism and better blood glucose control, but it is unlikely to result in any permanent weight loss, once the body adapts. The least effective of the above suggestions is to wait it out. If you don’t change the input, you can’t expect the output to change. So while these recommendations might help get you started, they are unlikely to lead to permanent, long term change.  But where does that leave us?  Are we doomed to stay on the plateau forever?

The ‘Set Point’ theory. I discussed the Set Point theory in a previous post on the Shangri-La Diet, just one of many diets based upon the set point theory. (See:  Flavor Control Diets). Set point theories trace back to the lipostatic (“constant fat”) weight control theory of Gordon C. Kennedy, based upon research he did on rats in the 1950s. Kennedy found that when he varied the caloric density of rat chow, his rats initially gained or lost weight, but they eventually adjusted how much food they ate, or their physical activity levels, so as to re-establish their original weight. Kennedy took this to be evidence that rats have an internal set point, a “natural weight” which their physiology acts to maintain against external changes to environment. The set point concept was later extended to explain the persistence of stable weights in human, in the face of variation in dietary intake and energy expenditure. The physiological explanation is that your metabolism slows when you attempt to diet and your weight drops below its set point; this also typically makes you less inclined to be active.  Conversely, overeating leads to a ramped up metabolism, which puts the brakes on weight gain; it also often gives you the extra energy to be active and burn off calories.  In the end, try as you might, you just can’t budge your set point weight.

The set point theory is ultimately a rather pessimistic view. (For a typical popular portrayal of the theory, take a look at this discussion of set point theory in the context of eating disorders). The underlying assumption is that each of us is born with a natural weight (or more accurately, a weight “program” that specifies a weight set point that changes as a function of age).  We can temporarily deviate from our pre-programmed set point weight by extreme diets, intense exercise, emotional events or illness, but eventually we will return to equilibrium, to our intrinsic, biologically predestined set point weight.  We best off not to fight our set point, but to accept it. Some adherents of the Set Point theory believe that the set point can be changed, but only by means of a sustained intervention.  For example, Seth Roberts, in his Shangri-La Diet, prescribes the use of “flavorless calories” (such as oil or sugar water) to break associations between flavor and calories and trick the metabolism into lowering set point.  Set point can also be changed by other interventions such as diet pills or special appetite suppressing foods.  However, once the dietary or medical intervention is stopped, the set point will return to its “natural” level, and the weight will creep back on.  Permanent, lasting change is impossible without the intervention, according to this Set Point theory, since progress requires lifelong dependence on some external crutch, some substance which hopefully is healthful, but nevertheless which we can never afford to go without for very long.

If you think about it and look around, it soon becomes clear that the Set Point theory can’t be right, or at least it is too simple, because it can’t explain certain undeniable facts.  Despite the numerous people who have failed to keep the weight off, we all know people who have lost huge amounts of weight — and kept it off. One of the most remarkable stories is that of Jon Gabriel, who dropped from 400 pounds to a very muscular 189 pounds and published his story and his insights in a best-seller called The Gabriel Method. Many people have replicated Gabriel’s type of “non-dieting” weight loss, to varying degrees.  We also know that various ethnic populations, such as Pacific Islanders and the Pima, who are healthy and trim on their native foods and in their native environment, frequently become morbidly obese and diabetic when they transition to a Western diet and lifestyle. And the American population as a whole is experiencing skyrocketing rates of obesity since the 1970s, which cannot be explained in terms of genetic programs. So the experience of both individuals and populations testifies against the Set Point theory.

And yet, there is at least some plausibility to the Set Point theory, or it would never have taken hold so strongly.  There are undoubtedly periods in our lives where our weight is remarkably stable, and where we experience resistance at our efforts to lose weight or get fit. Even outside of weight control and fitness, whenever we try to change ingrained habitual behaviors, there is a strong tendency to return to where we started.  In both physiological and psychological terms this is called “homeostasis” — the strong tendency of an organism to resist change. Homeostasis is generally beneficial because it helps us to maintain a healthy stability in the face of environmental changes that could be potentially detrimental or even lethal, if not resisted.  But at the same time, homeostasis can sometimes be the enemy of positive changes, such as losing excess weight, or becoming more fit.

If the Set Point theory is based upon a recognition of homeostasis, a well established biological reality, what could possibly be wrong with it?  Well, upon looking more closely, it turns out that the Set Point theory is based upon a serious misunderstanding of homeostasis.

What homeostasis really is and how it really works.  The big mistake in the Set Point theory is that it fails to realize that homeostasis applies only to our internal environment, not to our external physical condition. The organism does not inherently defend any particular macroscopic bodily features such as total fat or muscle mass, or external fitness. What the organism defends is the internal environment, the so-called “milieu interieur“, as Claude Bernard called it in the nineteenth century. Homeostasis appropriately applies to certain essential internal physiological variables, at the level of the cell or the bloodstream:  pH, the concentration of glucose (or more accurately, glucose+fatty acids+ ketones), electrolytes, and certain other essential physiological metabolites. These essential physiological parameters must be tightly controlled within narrow bounds — not as a constant, but as a range — in order to support cellular function. For example, blood glucose should be kept within the range of about 70-150 mg/dL; if it drifts outside of this range, hormones like insulin, glucagon or epinephrine will normally act to bring it back within range. If the body is unable to successfully regulate these key parameters, it may enter a state of shock and tissue damage, loss of consciousness, or death may ensue.

So if there is a “set point”, it applies not to body weight, fat, muscle, conditioning, or other outward characteristics; rather, it applies only to the inner environment of our cells and the bloodstream that nourishes them and supplies their energy.  Our brain and endocrine systems don’t directly detect our weight or muscularity — they sense only what is present in the immediate cellular environment.  There are certain hormones, such as leptin, which do to some extent vary as a function of body composition, but they do not do so in an absolute way, and can alter their response over time in a dynamic fashion. Body weight and fitness tend to act “as if” there is a set point only because they are influenced strongly by energy metabolism, and are linked to them in the short term. So in the short term, weight loss does tend to produce an energy deficit that is reflected by blood metabolites, cellular response, and even hunger. And in the short term, if nothing is done to change this connection, the set point theory seems to work. However, this is at best a temporary type of stability which is not centrally controlled, but rather results from a “balance of forces” that can be dynamically altered over time. Gary Taubes expressed this point well in his critique of the lipostatic set point theory:

Life is dependent on homeostatic systems that exhibit the same relative constancy as body weight, and none of them require a set point, like the temperature setting on a thermostat, to do so. Moreover, it is always possible to create a system that exhibits set-point-like behavior or a settling point, without actually having a set-point mechanism involved. The classic example is the water level in a lake, which might, to the naive, appear to be regulated from day to day or year to year, but is just the end result of a balance between the flow of water into the lake and the flow out. When Claude Bernard discussed the stability of the milieu interieur, and Walter Cannon the notion of homeostasis, it was this kind of dynamic equilibrium they had in mind, not a central thermostatlike regulator in the brain that would do the job rather than the body itself.  (Good Calories, Bad Calories, p. 428).

Once you grasp this point, it becomes obvious that you can have a stable, sustainable inner environment whether you are fat or skinny, fit or flabby.  On the other hand, the good news is that you can significantly change your body composition and fitness — and maintain the new state — so long as you can do so while maintaining internal homeostasis.  In fact, you can make major, lasting changes to your body and fitness by understanding how homeostasis works.

A stepwise evolutionary model of plateau busting. So if we are not constrained by arbitrary set points, if our body weight, fat, and muscle composition are not predetermined at birth, why is it so hard to make progress, and how can we progress to a new state? I think the best way to answer this question is to think about how systems evolve and adapt.  Adaptation is typically not a smooth, continuous process, but moves from one relatively stable state to another through a series of discrete, quantum steps.  Mathematical analysis of complex adaptive systems — such as cells, individual organisms, biological species, and human organizations and economies–shows that they typically display stable “nodes” or “attractors”– states which tend to resist change — until the change is big enough, and in the right direction, to move them to a new stable state or “orbit”.

A useful analogue for how this works comes from the Darwinian explanation of how biological species evolve.  Species are typically very stable in the short term (which can be thousands or millions of years on the timescale of evolution).  Species resist genetic change because a common breeding population exerts conservative forces that tend to keep variation within a limited range, so the population traits remain stable.  But every so often, new or divergent traits appear within sub-populations in response to environmental pressures.  If such a sub-population becomes reproductively isolated for long enough, perhaps by due to geographic separation, it can continue to grow far enough apart genetically that the new sub-population can no longer interbreed with the original breeding population.  In this way, a new differentiated species is born, with no “bridge” back to the original species.

Individual adaptation is of course not the same thing as species adaptation. But there is at least this much similarity:  if the adaptation is large enough, and if there arise new forces which act to stabilize the adaptation, then a stable change is possible.  If the stability persists long enough for the balance of forces to change, the adaptation will be “permanent”, with no easy reversion to the original state.  However, some sort of “separation”, analagous to geographic isolation, is needed to prevent reversion or “backsliding” to the original state.  Just as a river or ocean separating two islands can keep two sub-species from rejoining, there needs to be some type of “habit separation” between new and old patterns to prevent us from going back to where we started.

A good mental model for this is crossing a stream which is broken up by a series of large boulders. Getting from one side to the other may seem like an impossible task. It certainly cannot be done with a single bounding leap.  But if the task is broken down into a series of small steps, each of which is a stable “boulder”, then it can be done.  If the boulders are far apart, you may hang out for quite a while on each boulder, getting your footing and balance. But then at the right time, with enough confidence, you decide to make your move to the next boulder. Each step is still a challenge and takes some preparation, but with preparation and sufficient strength, it is within your reach.  By the time you are to the other side, it is equally hard to return to where you started. Just as biological evolution proceeds stepwise, and generally without reversion, to a new space, so can individual adaptation evolve to a new stable state through a series of intermediate “resting points”, each stable in their own right. And if these resting points are far enough apart, it will be hard to return to the original place you started.  But, applying this to “plateau evolution”,  a stream with well spaced boulders is preferable to a stream crossed by a continuous foot bridge, because the bridge makes it too easy to re-cross the river back to where you started.

How does this look in practice? The stepwise evolutionary model is not mere theory, but something I have experienced myself. And I think it may provide a more general model of how we can adapt and bust out of plateaus that appear (but only appear) to be holding us back.  The figure below shows the most recent 8 months of my weight loss.  I started out at 185 pounds several years ago and just recently reached my goal of 150 pounds.  But only since February 2010 did I keep an almost daily record of weights. I annotated my weight log with comments regarding various changes I made to my eating or habits, including both sustained and individual events:

When you look closely at the day by day weight measurement in any period of a few weeks, you tend to see only a lot of fluctuation over a range of about 4-6 pounds.  These are plateaus.  A plateau does not mean a constant weight, but rather what stock investors might call a “trading range” — a normal range of variation around some average weight.  But periodically there is a move of 3-4 pounds that seems to endure, to “take”.  And then there is a new average weight with a range of variation around it. These shifts may not become apparent immediately as permanent shifts in the average, because the magnitude of the shift (3-4 pounds in my case) can actually be smaller than the “trading range” variation around the old average (4-6 pounds in my case).  Only after several weeks have passed, does it become clear that a new “plateau” has been established, because the weight is not going back up.

What causes the shifts? The key question is how to explain the moves to the new plateaus.  From my limited analysis, I think I have an answer:

1. Single, unique events are incapable of establishing new plateaus.
2. Gradual, continuous changes are generally not likely to lead to new plateaus.
3. Step changes in behavior are the main driver in new plateaus.

So, to look at my example, preparing for (and running) a challenging two-day relay race in late April did cause a brief and significant loss in weight, but the pounds came back quickly over the following week, even exceeding the starting point. What did cause a lasting shift to the first new plateau was permanently cutting back my consumption of alcohol from 5 times to 2 times a week. Eating a big birthday dinner in June spiked my weight, during that phase, but the effect was transient. But what had a significant and lasting effect in July was increasing the frequency of my intermittent fasting from once a week (on average) to about 2-3 times a week. Most recently, I used an extended fast of between 2 1/2 to 3 days to reach my goal weight of 150 pounds, dropping 4 pounds from my last plateau of 154 pounds. I now realize that a single big move like that will not by itself produce a permanent change.  So my plan is to further extend my use of intermittent fasting so that I limit my eating to only 1 or 2 meals per day, going forward. So I will simply give up eating 3 meals a day; it will be either 1 or 2 meals (still giving me some freedom).  That may have seemed extreme several months ago.  But because I have approached this gradually, in small increments, I believe it will not be difficult at all.

The secret to plateau busting. To summarize, I think there are three important principles to keep in mind:

1. Make a deliberate, discrete step–and write it down! One of the most important aspects of this strategy is to define permanent changes based upon discrete quantum steps, not tiny moves along a continuum. For example, rather than gradually increasing the intervals between meals, make a one-time decision to cut out afternoon snacks. Or to skip lunches on certain days. Or add an extra workout each week. Write down the change on paper in clear language.  The value of doing this is that the change is conscious and deliberate, not something you slide into without awareness. Just as you pause on each boulder when crossing a stream and carefully plan your hop to the next boulder, be sure to deliberately and carefully plan each move to a new plateau, to be sure it is a step you think you can commit to. Look before you leap!
2. Keep records and establish a range of variation for each plateau. Any step to a new stable plateau is not a step to a fixed and unvarying behavior. There should be a certain range of “freedom”, allowing for natural variation. You will first need a little time after each change to “discover” what the new range of variation is. And the change will be more apparent if you are keeping good records of your weight, your speed, or whatever you are trying to change. (If you see no change within a week, you probably did not make a significant change). It’s best to chart the results graphically so that you can see the plateaus and the shifts. But once you see some results, it is equally important to establish firm limits to this range and stay within them.  In my last plateau, where my average weight dropped from 158 to 154 pounds, I was careful to stay in the range between 152 and 156 pounds.  Whenever I got close to the high end of the range, I consciously cut back on my eating to allow the weight to drift lower. I had just enough freedom to make this new plateau comfortable, but not enough to make it meaningless. Likewise I never pushed hard to get below 152 pounds during this period. These limits or bounds provide essential “habit separation” to isolate the new plateau or habit from backsliding into a previous plateau range.  Enjoy the freedom of the range, but strictly enforce the limits!
3. Allow yourself adequate time on each plateau. It is very important to allow yourself enough time to “get comfortable” at each new step. Don’t push too hard or move too quickly to the next step.  Habits take time to consolidate, both physiologically and psychologically. In the case of weight loss, what is really happening is that your hormones, enzymes, and other modulators of metabolism need time to re-balance, to provide the same level of homeostatic control of key energetic variables such blood glucose and fats as they did on the previous plateau.  If you are using intermittent fasting to lose weight, you must allow time to up-regulate the catabolic hormones and enzymes so that they can more readily mobilize fatty acids and glucose from storage, keeping your cells and your brain happy. This adaptation can take weeks, and you might be wise to stay on the new plateau for a few months!  Similarly, if you are adapting to lifting heavier weights or running faster miles, your body needs time to grow muscle tissue or increase aerobic capacity in response to the newly added stress. These changes are often imperceptible to you, but they are going on “behind the scenes”. To use the river-crossing analogy, allow time to catch your balance before you make the jump to the next boulder!  But don’t stay there forever…keep your ultimate goal in mind and make the next move when you feel ready.

Understanding that it takes time to adjust to a new plateau is, I think, a key point to being psychologically prepared to handle the inevitable resistance to change that is experienced whenever we “stretch” ourselves in the effort to grow physically, mentally or spiritually. Learning to appreciate your time on the plateau — even to love it — was one of George Leonard’s great insights that can help all of us who are on the path of change, as I discussed in another post about his book, “Mastery”. But the good news is that we don’t have to stay on a plateau forever, if we understand how it works. Armed with this knowledge, we can judiciously make our move to the next plateau in the right way and at the right time.

Other than recommending this book as a great vacation read or a way to rekindle your passion for running, I’d like to concentrate here on one of its central claims about the biomechanics of barefoot running, because it resonates so strongly with the thesis of Hormetism and Edward Tenner’s theories about the “revenge effects” of technology — and because it has implications that extend well beyond the sport of running. McDougall’s seemingly paradoxical assertion is that running without shoes makes one less susceptible to injury than using modern engineered running shoes, with their high-tech cushioning. Says McDougall: “Running shoes may be the most destructive force ever to hit the human foot.” (BTR, p. 168)   …How can this possibly be true?

Perhaps the most controversial thesis of McDougall’s book is that humans evolved to be long distance runners, and that at some point in our evolution as hunters we exploited this ability to actually run down large game such as antelope–animals that could outsprint us for short spurts, but would eventually tire and give up.  McDougall cites some archeological and biometric evidence, but I’m not so sure I buy this, and I’m somewhat skeptical and weary of the constant invocation of evolutionary arguments to explain just about everything related to diet, health and fitness. It’s just that it is so difficult to verify these speculations, so  I happen to prefer more testable explanations based upon physiology. And in the area of physiology, I believe that McDougall is onto something. The idea that adding padding or protection can hurt or injure us seems to be a paradox–at first glance.  But if we can understand why protective armor has this effect, perhaps it can teach us something about human adaptation that extends beyond the domain of running.

Shoes and foot injuries. Among the many experts McDougall cites, Stanford track coach Vin Lananna has a certain credibility when he states: “I can’t prove this, but I believe when my runners train barefoot, they run faster and suffer fewer injuries…We’ve shielded our feet from their natural position by providing more and more support…If you strengthen the foot by going barefoot, I think you reduce the risk of Achilles and knee and plantar fascia problems.” (BTW, p. 169-170).  Dr. Barry Bates, who directs the University of Oregon’s Biomechanical/Sports Medicine lab, gathered data showing that the cushioning on shoes does not reduce impact on the legs, but may actually promote injuries. To gain insight into why this should be so, consider another study reported by McDougall, this time from McGill University, showing that gymnasts landing on a mat instinctively adjust their landings based on the thickness and softness of the mat in order to achieve balance upon landing. The same thing happens when we run with cushioned soles: “your legs and feet instinctively come down hard when they sense something squishy underfoot. When you run in cushioned shoes, your feet are pushing through the soles in search of a hard, stable platform.” (p. 173). These adjustments are part of the proprioceptive or “body awareness” sensory system that is built into our neuro-muscular physiology. The story is otherwise when running barefoot on a hard surface:

To see pronation in action, kick off your shoes and run down the driveway. On a hard surface, your feet will briefly unlearn the habits they picked up in shoes and automatically shift to self-defense mode; you’ll find yourself landing on the outside edge of your foot, then gently rolling from little toe to big until your foot is flat. That’s pronation–just a mild, shock-absorbing twist that allows your arch to compress.  (BTW, p. 176)

And according to Dr. George Hartmann, a physical therapist trainer to long-distance runners, pronation is a actually good thing, not the defect it has been made out to be by many:

Your foot’s centerpiece is the arch, the greatest weight-bearing design ever created. The beauty of any arch is the way it gets stronger under stress; the harder you push down, the tighter its parts mesh. No stonemason worth his trowel would ever stick a support under an arch; push up from underneath, and you weaken the whole structure. Buttressing the foot’s arch from all sides is a high-tensile web of twenty-six bones, thirty-three joints, twelve rubbery tendons, and eighteen muscles, all stretching and flexing like an earthquake-resistant suspension bridge…I’ve worked with over a hundred of the best Kenyan runners, and one thing they have in common is marvelous elasticity in their feet. That comes from never running in shoes until you’re seventeen. (BTW, pp. 176-177).

So the explanation here is clear: Our skeletons, musculature and nervous systems are highly refined and well-coordinated adapative systems which adjust both instanteously and by means of longer term adjustments to in order handle the terrain.  These “proprioceptive” adjustments take place virtually beneath the level of consciousness, through the exquisite feedback systems of our body and brain. Try to circumvent these systems, and the protective mechanisms will weaken, exposing us to injury.

I’ve checked this out, and McDougall doesn’t seem to be cherry-picking the research to support his biomechanical thesis.  My informal survey of other research found additional supporting evidence:

• A study by Harvard’s Daniel Lieberman et. al, in the prestigious journal Nature, entitled “Foot strike patterns and collision forces in habitually barefoot versus shod runners“. The study found that “habitually barefoot endurance runners often land on the fore-foot (fore-foot strike) before bringing down the heel, but they sometimes land with a flat foot (mid-foot strike) or, less often, on the heel (rear-foot strike). In contrast, habitually shod runners mostly rear-foot strike, facilitated by the elevated and cushioned heel of the modern running shoe. Kinematic and kinetic analyses show that even on hard surfaces, barefoot runners who fore-foot strike generate smaller collision forces than shod rear-foot strikers. This difference results primarily from a more plantarflexed foot at landing and more ankle compliance during impact, decreasing the effective mass of the body that collides with the ground.”  To see how this works in action, take a look at blogger Karen Given’s interview of Lieberman, who teaches her how to run barefoot and demonstrates how dramatically this reduces the collision forces on her foot and body:
• A review by Warburton in the Australian journal Sportscience, of foot injuries, which found that “Wearers of expensive running shoes that were promoted as correcting pronation or providing more cushioning experienced a greater prevalence of these running-related injuries than wearers of less expensive shoes (Robbins and Gouw, 1991). In another study, expensive athletic shoes accounted for more than twice as many injuries as cheaper shoes, a fact that prompted Robbins and Waked (1997) to suggest that deceptive advertising of athletic footwear (e.g., “cushioning impact”) may represent a public health hazard. Anthony (1987) reported that running shoes should be considered protective devices (from dangerous or painful objects) rather than corrective devices, as their capacity for shock absorption and control of over-pronation is limited. The modern running shoe and footwear generally reduce sensory feedback, apparently without diminishing injury-inducing impact–a process Robbins and Gouw (1991)  described as the “perceptual illusion” of athletic footwear. A resulting false sense of security may contribute to the risk of injury (Robbins and Gouw, 1991).  Yessis (2000, p.122) reasoned that once the natural foot structures are weakened by long-term footwear use, people have to rely on the external support of the footwear, but the support does not match that provided by a well functioning foot.
• Additional studies and commentary, summarized in an article “Should you be running barefoot?” in Runner’s World, by the aptly named Amby Burfoot.  Burfoot’s article has a nice historical overview of great barefoot runners over the past century.
• Barefoot Ken Bob, a somewhat whimsical website devoted to barefoot running as an avocation, which includes research, practical advice, and announcements of upcoming barefoot races.

Finally, here is short video clip that gives a fairly simple explanation of barefoot running technique, featuring aficionado Barefoot Ted, who will be familiar to readers of Born to Run:

This research regarding the adaptive capacity of the foot coheres nicely with the overall thrust of Hormetism, in its confirmation that strengthening of our capabilities proceeds by progressive, periodic exposure to stress, to an appropriate degree and at a rate that allows us to adapt. It may seem paradoxical to some, but the fact remains that our strength is frequently compromised when we resort to crutches or corrective devices in the (misguided) attempt to shield or cushion ourselves from discomforts and shocks.

Technology and paradox. These findings about barefoot running are actually part of a much larger lesson about the paradox of injury, muscular weakening and other adverse consequences that come from an over-reliance on the protective technologies. This larger thesis is in fact the story of a much larger book published originally in 1996 by Edward Tenner: “Why Things Bite Back: Technology and the Revenge of Unintended Consequences“. You might think that a book with that title would be an anti-technology rant. But this book is not that, it is rather an insightful and even amusing look at technology, written by a technophile who does appreciate the benefits of technology, but at the same time was drawn to probe this puzzling downside to our over-reliance on technology. He has pulled together a wide-ranging survey and analysis of what he calls the “revenge effects” of technology, attempting to explain why it is that technologies often backfire in ironic and unexpected ways that tend to undermine their effectiveness. Such a book could go on for volumes if one wanted to catalogue every possible instance of the perverse effects of technology, but Tenner wisely limits his focus to several probing chapters on a handful of especially illuminating fields: medicine, environmental engineering, pest control, the computerized office, and sport. And while he has interesting things to say in all these areas, I would like to pick up specifically on his discussions of sports injuries, which are particularly relevant to generalizing our understanding of the paradox of barefoot running.

Tenner’s discussion covers a wide range of different sports, from high contact sports like boxing, rugby and football, to seemingly benign recreational sports, like running, skiing and tennis.  Football is illustrative of the evolution of a once intensely violent sport. In 1905, a year when there were 23 deaths in intramural collegiate play, President Theodore Roosevelt threatened to ban the sport unless the rules were changed regulating allowable conduct. Later, in 1939, plastic helmets were introduced and after World War II they entirely replaced the thin padded leather helmets used until that point. But this had an unexpected effect:

Where plastic helmets were adopted, players intent on using maximum force to stop an opponent began to use their headgear, with the mouth guard that soon accompanied it, as a battering ram. This intensifying tactic all too often had its own unintended consequence: spinal fracture and paralysis…What seemed to be a technological solution had become an extension of the medical problem…The NCAA banned aggressive use of the helmet in 1976, and injuries dropped…Spearing, the use of a helmet in place of the shoulders to knock down an opponent, is now banned but is still widespread, and not just in professional play.  (WTBB, p. 217)

So protection led to intensification of injury, but this was moderated by additional rule changes. So far, so good. But this reduction in acute injuries was replaced by a more insidious problem, chronic injuries:

While there are fewer catastrophes, most of which result from spearing and other dangerous practices, serious injuries have actually increased with the spread of better protective equipment. From the First World War through the 1950s, only four in ten professional players per season reported injuries that needed surgery or resulted in prolonged absence from the game. By the 1980s, seven in ten were seriously hurt each season, according to a study by the NFL Players Association…The game’s “ballistic” style calls for brief but powerful bursts expressed as joint- and vertebra-jarring collisions far more severe than those of Theodore Roosevelt’s day. The helmets, face shields, mouthpieces, and padding are better than ever, and deaths may be rare, but neither protective nor conditioning technology can prevent damage to the joints. Since massive injections of anti-inflammatory drugs and painkillers make it possible for battered athletes to return to play, the new intensity means trading immediate relief for long-term disability…Knee and hip surgery can extend players careers, but usually only at the price of later pain, inflammation, and repeated rounds of surgery. (WTBB, pp. 218-219)

Football is certainly not unique in this regard.  For example, Tenner makes a similar points about skiing:

The replacement of wood by plastics and composites in the 1950s changed and extended the sport just as dramatically as lifts had done earlier in the century. Gone were the rituals of waxing. And on the way out, it seemed at the time, were the broken bones that once formed part of the folklore of skiing. At first, the new equipment shifted some of the injury from ankle fractures (common with lower prewar boots) to twisting fractures of the tibia. A fall often led to this spiral break of the bone. Then came further improvements. New, rigid plastic boots and bindings employing strong, lightweight alloys were designed to release the legs of skiers at a predetermined level of force…To the extent that skiers are risk seekers, they will respond to safer equipment and more carefully maintained slopes by seeking more dangerous runs and increasing their speed….Protection also leads to greater risk-taking in the slalom event, where skiers voluntarily use protective gear, including helmets, to take a straighter course down the slope…In the days of wooden skiis, the cast-encased leg was a cartoonist’s cliche, but with some reason….ACL sprains now account for up to six injuries a day at large resorts and up to 100,000 annually in the United States. Surgeons can usually repair a torn MCL by stitching ends together: a sprained ACL demands much more difficult techniques, including tendon grafts. (WTBB, p. 224).

The basic message in all of the above is that as protections have increased, injuries have not gone away, but have shifted from the acute to the chronic, and in many cases chronic injuries that are more enduring and difficult to deal with. This message is consistent with the point made on the Rehabilitation page of this blog about the downside of “crutches” such as canes, orthodics, and even eyeglasses.  The difference, in this case, is that these protective aids defeat our intentions in a different context than that of rehabilitation. Instead of impairing our recovery from disability, these protective aids instead make us vulnerable to injury.  (While the distinction between prevention and recovery is important, there is actually the interesting case of Michael Sandler whose RunBare blog documents his story of how he used barefoot running to overcome a serious shattered leg injury, transforming himself from being unable to walk, to running barefoot 80-100 miles per week!)

Protections such as extra support or cushioning no doubt make us safer in certain respects. But while guarding against the strong shocks that can cause acute injury, these very protections can mask the sensory inputs that our body uses to adjust and adapt internally–both in the instant and over time. In doing so, we are making ourselves vulnerable to repetitive stress or other low level chronic injuries that, over time, can become at least as serious, if not more so, than acute injures, because the healing process is not as straightforward.

Lessons. So where does this leave us, and what should we do about it?  Should we always run barefoot and forgo all the protections of padding and modern protective technology when we engage in challenging physical activities like sports? I certainly would not advocate that. But I think the key point here is to be conscious of what we give up by relying on artificial external protections, especially if it means decreasing our reliance on our own internal musculature and nervous system.  We should be wary of getting too far away from contact with our raw senses and physical exertions whenever we pick up a piece of protective athletic equipment, clothing or footwear, and we might consider how to make internal strengthening and perceptual sharpening an essential part of our conditioning when we train and prepare for athletic performance or even to enhance our ability to navigate the ordinary physical challenges of daily life, such as climbing stairs, or lifting groceries or children. In short: beware of “labor saving” devices; the labor you end up saving may actually be have been useful or necessary to your well being!

What do you think?  Please leave your comments below, or visit the Discussion Forum.

Biological markers. After these ordeals, Dr. Andy Morgan of Yale Medical School found that the top performers had very different physiological responses from those who couldn’t hack it. He did extensive physiological monitoring and found that those who passed these tough tests had much higher levels of NPY (a neuropeptide) and DHEA (a hormone that buffers the effects of cortisol, a stress hormone).  In addition, those who did best also had “metronomic heartbeats” — very little heart rate variability (HRV), compared to most normal people, who show a lot of variability in the intervals between heartbeats.

These biological markers of stress-resistant individuals show that they are somehow different than most of us.  Perhaps this is worth looking for what it can teach the rest of us.   Certainly, there are other health known health benefits that have been reported for NPY and DHEA.

Autonomic nervous system. Regarding HRV, however, Sherwood raises a caveat, noting that numerous studies have associated metronomic heartbeats (low HRV) with cardiovascular disease, diabetes, and even sudden death.  However, other research into the HRV paints a more complex picture.  A paper on the Intellewave Method,  by Dr. Alexander Riftine,  indicates that low HRV may have different implications for the state of the autonomic nervous system, depending on the frequency of the heartbeat variability, derived from heart rhythmograms.  When spectral analysis (a mathematical technique based upon Fourier Transforms) is applied to the heart rhythmograms, the heartbeat frequency variations are resolved into high frequency (HF) and low frequency (LF) patterns.  The LF variations are associated with the sympathetic nervous system (SNS), where as high frequency HF variation correlate with the parasympathetic nerous system (PSNS).  The balance between SNS and PSNS states predicts much about an individual’s fitness.  According to Dr. Riftine, these states cluster into nine typical combinations.  The ninth state–an elevated PSNS with a reduced SNS state–is “rather unusual because normally an increase in PSNS is accompanied by an increase in SNS.  This rare condition is found in water polo athletes, long-distance runners, navy seals and persons with special heart training for deep sea diving.”

The physiological analysis of individuals who have successfully adapted to tolerate stress is a promising area ripe with lessons for the rest of us, as it could be used to assess, predict, and track our progress in getting stronger and more stress-hardy.

Tennis. Loehr gleaned some of his most perceptive insights by using telemetry to observe the behaviors that separated the top tennis players from the lower ranks. Specifically, he found that the best tennis players are intense and focused during play, but show a remarkable ability to recover during “between-point” time, following routines that allowed them to pause and recover their energy for the next point. During these brief periods–approximately 25 seconds–between points, “top competitors were much more skillful oscillators during competition. The rhythmic increases in heart rate during points, and decreases in heart rate between points, meant that a competitor was adapting to the stress.” (SFS, p. 167). By contrast, poor competitors did not use their downtime wisely, not relaxing or even exacerbating the stress by disputing calls or showing emotion.

Toughening. The best of Loehr’s ideas are encapsulated in Part III of “Stress for Success”, entitled “Life Skills and the Toughening Process: Targeting Stress Exposure”. This section presents what I believe are the key concepts for effective toughness training based upon deliberate and controlled exposure to stress. Loehr takes research from sport science and applies it to training for toughness in everyday life.  ”For decades, sport science researchers have been diligently investigating the relationships between stress and growth.  The optimal frequency, duration, and intensity of stress exposure for improving strength, speed agility, endurance, stamina, and toughness of all kinds have been vigorously pursued. The most important confirmation in all the research is simple and direct:  STRESS IS THE STIMULUS FOR ALL GROWTH.”  (SFS, P. 145).

Oscillation. Loehr goes on to describe training routines whereby one can increase stress tolerance by deliberately using intermittent intervals of stress exposure, oscillating with periods of recovery and rest. One of the most effect means of doing this is excercise, specifically interval training. According to Loehr, “exercise is really stress practice,” and he cites the training principle of “specificity” to argue that the exercise stress should oscillate, so that they resemble the up-and-down of stresses in real life. The intermittent stresses should be intense to the point of discomfort, but never painful. And the use of intervening periods of “active rest” and sleep are equally important for recharging.

The benefits of this approach to oscillatory stress training have biochemical correlates. Loehr cites research indicating that, whereas chronic, sustained stress leads to depletion of the stress hormone norepinephrine and elevation of cortisol, intermittent acute stress, followed by recovery, allows for increased tolerance and resistance to norepinephrine depletion.

Although Loehr mentions that sports scientists have studied the optimum intensity, duration, and frequency of applied stresses in exercise, he does not provide in his book any specific guidelines for optimizing these variables, beyond noting that they will vary based on the nature of the stress and subjective factors such as discomfort and pain thresholds. While being aware of one’s own thresholds is no doubt good advice, it seems to me that turning exploring the quantitative aspects of this science would be useful in helping to reveal more objective factors.

Beyond exercise. I believe that the application of stress and recovery cycles for training can be generalized beyond the use of physical exercise. Following the principle of specificity, why not train for life using more  specific stresses encountered in life, specific distractions or irritants, including physical stresses such noise, heat, or hunger; or interpersonal irritants such as yelling, nagging, or insulting. In fact, such deliberate exposure to stress and hardship is a techniques going back to the Stoics, who recommended training oneself to tolerate increasing levels of physical stress and discomfort by means of cold baths, sleeping on the floor, fasting, and learning to tolerate insults. Extreme forms of such exposures to stress have been used by the Army and Navy to harden their special forces (See my previous post on The Physiology of Stress), but I believe there is a lot of opportunity for both creativity and the use of proven behavioral science in developing and optimizing specific and effective techniques to help us become more resistant to a variety of life’s everyday stresses.