Voluntary stress

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Tags: Angela Patmore, cold showers, Epictetus, exhaustion, exposure and response prevention, exposure therapy, fight
or flight, GAS, General Adaptation Syndrome, Hans Selye, Hormesis, Hormetism, immunity, intermittent fasting, learned
helplessness, Martin Seligman, psychoneuroimmunology, resignation, Stoicisim, Viktor Frankl, voluntary stress
Posted 22 Sep 2011 in Hormesis, Psychology, Stoicism

When does stress help you and when does it hurt

you? There is no doubt that stresses of the wrong sort can lead to anxiety, emotional turmoil — and
eventually depression and diseases like atherosclerosis and cancer. Yet a central theme of this blog
is that certain stresses are “hormetic”: at the right dose and frequency, stress can actually make you
stronger and more resilient. The many posts on this blog illustrate how stress can be channelled to
build muscle, retrain appetite, improve eyesight, strengthen immunity, defeat allergies, and tame
addictions and anger. Judicious exposure to stress can even promote joy and excellent health.
But one can come away from the study of hormesis with the misleading impression that it’s all about
adjusting the level and timing of stressors to induce an appropriate adaptive or defensive response. In
this article, I would like to focus on a frequently overlooked ingredient in hormesis: the role of
intention, attitude and voluntary choice. If you omit this ingredient, you are leaving out an important
element of the way that stress helps you become stronger.

Voluntary, deliberate exposure to stress can be particularly effective in providing psychological

benefits, including overcoming anxieties, obsessions and phobias, and vanquishing appetite cravings,
addictions. Beyond overcoming such self-defeating tendencies, deliberate exposure works to unleash
confidence and generate a sense of joy and accomplishment.

Hans Selye

General Adaptation Syndrome. Our modern understanding of stress can be traced in large part
to Hans Selye, the Hungarian-born endocrinologist whose detailed studies of animals and humans
under stress led to a model of stress as a generalizable force capable of causing disease. Selye
distinguished between good stress, which he called “eustress”, and bad stress, which he called
“distress”. While acknowledging that some stress is good because it is energizing and activates our
defenses, Selye spent most of his career studying the negative effects of exposure to stress, which he
fit into a pattern called GAS or General Adaptation Syndrome. Selye claimed that GAS proceeds
through three stages:
 Stage 1: Alarm reaction is what is often called “flight or fight” syndrome — a quickening of the
heartbeat, tensing of the muscles, release of adrenaline and a cascade of other
neurochemicals. This is typically a short term galvanizing response, reversible once the source
of stress is removed.
 Stage 2: Resistance or adaptation occurs when the stressor is sustained. Glucocorticoid
hormones and catecholamines are ramped up to maintain alertness and provide a continued
supply of blood glucose, and blood pressure increases to sustain tonicity of the muscles and
other organs. Positive coping and adaptation during this stage can increase resistance and
immunity, although not indefinitely. With time, and if continued unimpeded without periods or rest
and relaxation, this stage leads to mental fatigue, overtaxing of the adrenal glands and immune
system, and vulnerability to disease
 Stage 3: Exhaustion, in which the organism becomes depleted of energy energy reserves and
immunity. Mentally, it leads to emotional withdrawal and depression. If sustained, this third stage
leads to grave illness and eventual death.
While Selye did acknowledge some positive aspects of stress during Stage 1 and the Stage 2, he did
not leave much room in his model to account for the beneficial biological aspects of stress. Looked at
this way, only relatively mild and short-term stresses can be considered useful and positive, insofar as
they activate readiness and resistance. But even here, Selye held that repetition of Stage 1 and Stage
2 stresses can weaken and degrade resilience. He saw chronic, repetitive, and sustained stress as
uniformly damaging to both the psyche and the body. The possibility that routine or frequent stress
could significantly and sustainably build resilience was something he did not address.

Learned helplessness. Angela Patmore, in her illuminating book, The Truth About Stress, points out
that Selye’s model has led to an emphasis on “stress management”, which is largely about stress
prevention and strategies for coping and relaxation. While acknowledging Selye’s contributions,
Patmore believes that he overlooked a key factor which can make a very big difference in whether
stress is beneficial or detrimental:
In animal experiments using inescapable threat (prolonged and repeated tail shock, forced swim,
water restraint, hot plate contact and other ordeals dreamed up by researchers), long-term inability to
respond to perceived danger results in a syndrome that is the biological opposite of the galvanizing
stress response. In this quite different response, which has nothing at all to do with survival, the
subject gives up the struggle for its life and resigns itself to its fate. This is the so-called ‘third phase’ of
Selye’s GAS, but it is important to realize, as Selye evidently did not, that the animal may do this in
return for a degree of neural tranquilization, and that its brain may now release pentapeptides and
other opiate-like substances to dull the pain and horror of its situation. The resigned animal then
succumbs to morbid physiological changes…Giving up may buffer you from reality, but at considerable
cost. Resignation causes the suppression or shutting down of the immune system. If you’ve given up,
why would you need an immune system anyway? (TTAS, pp. 110-111)
The act of “giving up” or resignation literally turns a switch and redirects the entire physiology of the
animal’s response into a downward spiral of depression and failing health. This is seen not only with
animals, but also in human studies. Patmore describes experiments by Martin Seligman that
demonstrate much the same phenomenon:

…Seligman and his colleagues turned their attention to students, shutting them in a room with loud
unpleasant noise, and various knobs that might or might not control the volume. Some continued to
alter the sound levels. Others gave up. By now Seligman had developed a model of depression based
on his experimental work. His concept of learned helplessness — resigned failure to act in the face of
threat — has become of fulcrum of psychological research. (TTAS, p. 113)

The concept of learned helpless highlights the importance of looking beyond the type and extent of
stress alone, to consider the internal mental state of the subject. The essential factor is the perception
of control and self-determination:

A number of key studies in the stress literature have highlighted the importance of control in the
vulnerability to illness from distressing experiences. Here we plainly see why this is so. Those who act
to help themselves assume control. Those who fail to act requlinquish it…Viktor Frankl studied [first
hand] the behavior and susceptibilities of the victims of Auschwitz and Dachau, and formulated a
theory of survival that he called the ‘will to meaning’. Of immense significance was self-determination.
As Frankl observes: ‘Everything can be take from a man but one thing: the last of the human freedoms
– to choose one’s own way.’ Taking action based on personal choice..may also send vital messages
from the brain to the body to keep fighting and not fall sick. (TTAS p. 116)
Countering Selye’s GAS theory, Patmore puts forward an alternative theory of stress:

The distress-disease link that he formulated was not the direct, simple bond that he envisaged, but a
complex sequence of events dependent on each individual’s psychological make-up, courage and
coping skills. According to this alternative theory, disease strikes not a direct result of the response to
threat, but as a result of resignation, helplessness and failure to act. (TTAS, p. 118)

Learned control and mastery. We can take these learnings about the negative effects of learned
helplessness and turn them around: Perhaps we can enhance the effectiveness of adaptation and
resistance to stress by enhancing our sense of intentionality or deliberate control when we are
exposed to stress. One way to do this is to train ourselves to become more resilient to stress by
deliberately exposing ourselves. This is well recognized in the case weight lifting or athletic training to
become physically stronger and more skilled. But I’m talking here about something more fundamental:
our attitude towards facing life’s challenges and hardships.
In contrast to the modern ideology of stress management, which teaches us to avoid stress in order to
stay healthy and sane, Patmore recalls that

…there was a far different school of thought, dating back to the Romans, based not
on avoidingnegative emotions such as fear and tension, but on rehearsing them. Children were taught
resourcefulness and mental strength by ‘character-forming pursuits’ that developed fortitude and self-
mastery. By using the opposite of stress management – emotional rehearsal…our ancestors made
themselves psychologically more robust….Childhood dares, games and contests, sport and adventure
activities — all provide emotionally challenging experiences that help people to understand and
season their own sensations and feelings, and take them through unpleasant emotions in order to
achieve a resolution…
This attitude goes back at least to the Stoic philosophers such as Epictetus, Seneca and Marcus
Aurelius. William Irvine, in his excellent modern reinterpretation of Stoicism, A Guide to the Good Life,
notes:
Indeed, by practicing Stoic self-denial techniques over a long period, Stoics can transform themselves
into individuals remarkable for their courage and self-control. They will be able to do things that others
dread doing, and they will be able to refrain from things that others cannot resist doing. They will, as a
result, be thoroughly in control of themselves.

By rehearsing or training techniques such as these, you can substantially improve your resilience in
handling everyday stressors, whether they be physical or social and emotional. But what about
situations in which we actually have no real control, or where the outcome is highly
uncertain? Perhaps ironically, I think that fostering a sense of control can be helpful even when we
may not or do not actually have much control over the situation. By “making the involuntary voluntary”,
we can transform the way the way we respond to stress at the deepest levels of both our biology and
our psyche.

I think this attitude of voluntarily embracing unavoidable stress is most articulately expressed by
Epictetus, the Greek Stoic and slave whose teachings have inspired two millennia of philosophical and
religious thought. Epictetus distinguished between externals — the events and actions of others
which we cannot control — and internals — our values and attitudes. A slave for much of his life,
Epictetus realized how much freedom he nevertheless retained in choosing how to react to his fate. A
Stoic “sage”, he said, never finds life intolerable, but sees in every challenge as an opportunity to test
and improve oneself:

You should look to the faculties that you have, and say as you behold them, ‘Bring on me now, O
Zeus, whatever difficulties you will, for I have the means and the resources granted to me by yourself
to bring honour to myself through whatever may come to pass.’ (TD, Book One, Ch. 6, p. 18).

Furthermore, it is by how we handle the challenges in life that our character is revealed and built:
Difficulties are the things that show what men are. Henceforth, when some difficulty befalls you,
remember that god, like a wrestling-master, has matched you with a rough young man. (TD, Book
One, Ch. 24, p. 53).

By deciding to accept the hardships that come your way, as if you had deliberately chosen them, your
reactions are transformed. What may otherwise have been a stress that leads to resignation, giving
up, and Selye’s third phase of exhaustion, now becomes a challenge deliberately embraced. This
does not mean deceiving oneself and pretending that you can control the uncontrollable. Rather, it
means embracing the challenge as an opportunity to demonstrate your ability to handle a physically or
emotionally difficult situation with courage and grace, to grow from it, and to actually become stronger,
not weaker. Whether or not the stressor eventually diminishes or resolves, with or without your
intervention, you are left more resilient as a result.

For a more detailed discussion of Stoicism and its similarity to Hormetism, the philosophy advocated in
this blog, I would encourage you to read my page on Stoicism.
Real world applications. Many of you who have read this far may be wondering: “Interesting
philosophy, but how do I actually apply this to my life?”. I’d like to answer that by illustrating with three
very different examples. Cold showers, intermittent fasting, and exposure therapy for anxiety and
phobias.

Cold showers. The single most popular page on this blog is the
March 2010 article on Cold Showers. Initially, it surprised me that so many people would show an
interest in something that is without any question uncomfortable. And for some people: terrifying.
The article recites a number of health benefits that have been shown or claimed to result from taking
cold showers or baths.
But the article goes beyond the objective physical health benefits to describe my subjective experience
of taking cold showers. In particular, I noted that cold showers are initially quite uncomfortable,
provoking an involuntary reactions like rapid breathing, a pumping heart and even laughing. While the
shock and discomfort becomes less the more cold showers you take, my experience is that–unless the
weather outside is hot–there is almost always hesitation and discomfort when first stepping into the
cold shower. It takes an act of will to force myself to do this. But I do it willingly because I’ve come to
understand the benefits that result. Beyond that initial hesitation upon jumping into the cold shower
each morning, I embrace it and enjoy it.
The intentional, voluntary attitude makes a big difference to the experience. Consider the case of
those who must take cold showers unwillingly, perhaps because they have no hot water for a period of
their lives, or perhaps were forced to take cold showers at camp or school dormitories. I get
comments from such people, and their attitude towards cold showers is typically very negative. It is
likely that they did not receive much physical or psychological benefit from taking cold
showers. Perhaps the experience even had an adverse effect on them, at least psychologically.

Intermittent fasting. Going without food some days, or eating only one meal per day is the
involuntary fate of millions of people living in poverty or near-poverty. It can also happen to you if you
become lost, stranded or trapped in a place without ready access to food. This experience of hunger
can be quite uncomfortable, even painful.
It’s entirely different matter, however, to abstain from eating periodically for 12-24 hours as a
deliberate, voluntary practice. I’m not talking about eating disorders hear, but rather the practice of
intermittent fasting (IF), undertaken to achieve not merely for healthful weight management, but for the
well-documented health and longevity benefits, which I’ve discussed in my video article, Intermittent
fasting for health and longevity. When you engage in IF voluntarily, you’ll surely experience
moments and periods of hunger cravings. But in just knowing that hunger cravings are expected and
are possible to
“ride out” without adverse effects, you gain a sense of control over your urges. You soon come to
recognize the difference between a conditioned craving that can be extinguished by training, and true
biological hunger that deserves attention. The sense of achievement in mastering your appetite,
rather than being its slave, can be empowering.
I’ve found that intermittent fasting works best for me when I am the one who controls the eating
schedule. Rather than follow someone else’s rigidly prescribed diet or eating schedule, I like the
flexibility that IF affords. I can choose which days to fast and which meals to skip, adapting the
schedule to the demands of my week. But once I make a decision, for example to skip breakfast and
lunch tomorrow, I am very disciplined about sticking to my plan. Here again, I believe that feeling “in
control” plays an important role in the outcome. A prisoner forced to follow a fasting regimen against
his would be much less likely to reap the benefits — unless perhaps he decided to “own” the imposed
diet in the manner of Epictetus.

Exposure therapy for anxiety, obsessions, and phobias. One of the most common and successful
approaches to treating anxiety, fear and obsessive-compulsive disorder (OCD) is the use of exposure
therapy. Often this involves both a cognitive and a behavioral component, in which a therapist works
with the patient to identify beliefs, emotions and responses relating to stimuli that provoke anxiety,
fear, obsessive thoughts and compulsive behaviors. Cognitive Behavioral Therapy (CBT) emphasizes
the cognitive component and proceeds by demonstrating that the underlying beliefs are false or
irrational.

My personal view is that the changing the

behavioral component by controlled exposure to the problematic stimulus is the most important aspect
of exposure therapy, and may be sufficient even without examining your beliefs. The essential element
of treatment is progressive exposure to stronger stimuli until habituation or extinction occurs. The
theory of Pavlovian extinction and deconditioning is discussed in more detail on the Psychology page
of this blog.
So if you have a fear of height, snakes, or social situations, you should progressively–and very
gradually–expose yourself to tougher situations. To counteract acrophobia, you could start by
ascending very small elevations. Walk to a height that just begins to make you anxious and hold there
for a while, but retreat before it becomes too uncomfortable. If you fear snakes, start by looking at
photographs of snakes, then handle fake rubber snakes, or observe real snakes cages at
zoos. Eventually, work on handling real, but harmless snakes for increasing amounts of time For
social situations, start with small groups of friends, and build from there. A related version of this
exposure therapy, called exposure and response prevention, has been found useful in treating
OCD. The key is to recognize the obsessive thoughts or compulsive behaviors as “escape responses”
or “safety behaviors” in response to stressful stimuli, while learning to prevent the escape response to
progressively stronger stimuli.
It is especially important with exposure therapies that you stay in control of the situation at all
times. There must always be an “exit hatch” that allows you to back down and escape or stop the
stressful stimulus before real panic sets in. Being forced by a therapist or third party to go beyond the
edge of your comfort zone can be extremely counterproductive and anxiety-inducing. The therapist, if
any, should be at best a “guide” or coach. If you are strongly motivated to succeed, exposure therapy
may be quite effective if you do it yourself, without a therapist.

Psychology and hormesis. What all the above practices and treatments have in common is an
important psychological dimension. In each situation, the extent to which the exposure process
is voluntary is the key to successful hormesis. When stress exposure is voluntary, the gains in
resilience can be substantial, even when the stress faced is sustained or repeated over the long
term. Contrary to Selye, chronic and repeated exposure to stress does not invariably lead to impaired
health and depression. What is perceived as stress can be turned into an energizing stimulus, when it
is approached with a willing and inviting attitude. Just as you can decide to “give up” in the face of
stress, you can make the opposite choice: to persevere and embrace mastering what challenges you.
Voluntariness is not an essential component of all types of hormesis. For example, it is likely that low
level exposures to radiation, chemical toxins and allergens build biological resilience by activating
DNA and mitochondrial repair mechanisms, endogenous antioxidant enzymes, and immune
responses that involve no psychological or neurological mediation. But a surprisingly large realm of
human biology, including digestive, metabolic, immune processes — has a significant psychological or
neurological dimension. An entire field — psychoneuroimmunology — has been laboring to elucidate
the mechanisms of such neurologically-mediated processes. Human intentionality — or what is
sometimes called “will”– must be considered a key factor in the successful application of hormesis to
improve your health.
At points, paradoxically in spite of his focus on the detrimental aspects of stress, Selye himself came
close to appreciating the importance of this. I was particularly struck by one statement attributed to
Han Selye, that succinctly crystallizes the essential insight of this entire article:

“Adopting the right attitude can convert a negative stress into a positive one.”

Does insulin make you fat?

68 Comments
Tags: ASP, carbohydrate/insulin hypothesis, CarbSane, fat loss, HSL, insulin, insulin resistance, insulin
sensitivity, intermittent fasting, Kitavans, Krieger, low carbohydrate, LPL, obesity, Okinawans, Taubes, weight loss
Posted 03 Feb 2011 in Diet

Whether or not insulin is to blame for the obesity epidemic is one of the hot questions being debated
on heath and diet blogs. On the surface, this seems like an arcane question that would mainly interest
physiologists and diet researchers. After all, who really cares about the underlying mechanisms of fat
storage and release? Most of us just want to know some practical steps we can take to lose excess
weight and keep it off and, beyond that, to stay healthy.

It seems like a simple yes-or-no question of fact that you could settle by studying populations and
doing lab studies. But it’s not so much a question about facts as one about causation. Questions of
causation are often the thorniest ones. This particular question has taken on almost political or
religious overtones, provoking emotion and acrimony in the diet blogosphere. On one side are
defenders of the Carbohydrate/Insulin Hypothesis, like Gary Taubes and Michael Eades. This is laid
out in detail in Taubes’ book Good Calories, Bad Calories (2007), and more compactly in “Why We
Get Fat: And What To Do About It” (2010). On the other side are opponents such as James Krieger
and CarbSane, who find the Carbohydrate/Insulin Hypothesis to be oversimplified and deeply flawed,
citing recent scientific advances. People tend to chose up sides in this debate. I’ve been participating
in this debate myself (while still learning a lot) on the websites of Jimmy Moore, James Krieger,
and CarbSane. I won’t rehash all the technical details here. Instead, I’d like to propose a “frameshift”
that recognizes and integrates the strong points from each side, attempting to overcome their
shortcomings.
First, here’s an overview of what each side has to say:
Proponents of the Carbohydrate/Insulin Hypothesis, as articulated by Taubes, posit four main
points:
1. Obesity is a disorder of excess fat accumulation, not voluntary overeating or inactivity, caused by
an imbalance in hormonal regulation of adipose tissue and fat metabolism.
2. Insulin is the primary regulator of fat storage. When insulin levels are elevated–either chronically
or after a meal–we accumulate fat in adopose tissue. When insulin levels fall, we release fat and
oxidize it for fuel.
3. Elevated blood insulin levels increase hunger and the drive to eat, while decreasing energy
expenditure and activity
4. By stimulating insulin secretion, carbohydrates make us fat and ultimately cause obesity
In short: Carbohydrates drives insulin, which drives fat.
Opponents of the Carbohydrate Hypothesis challenge each of the above points. I’ve paraphrased
four main counterpoints here:
1. Fat accumulation and obesity result from positive caloric balance (more calories consumed than
expended), without regard to the macronutrient class of calorie (carbohydrate, protein, or fat).
2. Your body can store fat even when insulin is low, via the action of the hormone ASP (acylation
stimulating protein)
3. Insulin doesn’t make you hungry; rather, it suppresses appetite. (The critics proffer that low carb
diets may work because protein is more satiating than carbohydrates, but they merely report this
observation and don’t attempt to explain it).
4. Carbohydrate doesn’t uniquely stimulate insulin; many proteins are equally or more insulinogenic.
In short: Calories in minus calories out drives fat.
On the surface of it, these two models of fat metabolism appear to be diametrically opposed. But are
they really? There is at least one large point on which both sides appear to agree:

Obesity, particularly of the abdominal type, is associated with insulin resistance.

What that means is that people with abdominal obesity (the characteristic “apple” or pot belly shape,
rather than those with “pear” shaped backsides or extra subcutaneous fat) tend to secrete more
insulin after eating and have high basal insulin levels, ultimately leading to elevated blood glucose,
triglycerides, elevated blood pressure, unfavorable cholesterol ratios, and a host of other issues
associated with metabolic syndrome or “Syndrome X”. Nobody seems to deny this. Sometimes leptin
resistance is also cited as an independent or alternative marker of obesity. But I’ll focus here primarily
on insulin resistance, because it seems to be more closely involved with regulation of nutrient
partitioning than is leptin.

Where the two sides disagree, however, is on the causal chain behind the association between
obesity and insulin resistance. Advocates of the carbohydrate/insulin hypothesis tend to arrange the
causal the order, from causes to effects, as:

carbohydrates > insulin spikes > hyperinsulinemia > insulin resistance > obesity

Whereas Krieger and CarbSane argue that the order of causality should be:

positive caloric balance > obesity > insulin resistance > hyerinsulinemia

When you look more deeply, however, there is acknoweldgement on both sides that insulin resistance
is not a simple monocausal condition, but is likely multifactorial. There is evidence of many
contributing factors, including:
  specific dietary components: fructose, sucrose, saturated fats, gluten, lectins, dairy, allergens
 micronutrient deficiencies: vitamin D, magnesium, omega-3 fatty acids
 metabolites: triglycerides, free fatty acids (“FFA”, also called non-esterified fatty acids or “NEFA”)
 inflammatory conditions
 lack of physical activity and exercise (particularly strenuous exercise)
 genetics
There is as yet no broad scientific consensus as to the relative importance of each of these factors in
causing insulin resistance. But it is almost certain that there is no single cause. Regardless of the
cause, however, it is important to understand what insulin resistance is on a cellular level: a reduction
in the number and sensitivity of insulin receptors, such as GLUT4 receptors. Different tissues can
experience different degrees of insulin resistance. Typically, muscle tissues are the first to become
insulin resistance and fat tissue is one of the last. Insulin resistance in different organs like the brain
or the skin can have different effects. Some have argued that certain pathologies such as Alzheimer’s
disease and acne are associated with organ-specific insulin resistance. I’ve proposed elsewhere on
this blog (“Change your receptors, change your set point“) that receptor number and sensitivity can
serve as a kind of dynamic “set point” for weight and other physiogical states governed by hormone-
receptor and neurotransmitter-receptor balances.
So here is where I think that a frameshift in the debate about insulin can reconcile the two sides, at
least in good measure:

Insulin resistant (IR) individuals respond in a qualititatively different way to carbohydrates and
fats in their diet.
Let’s see what that means specifically:

First, consider insulin resistant (IR) individuals, regardless of how they got that way. IR individuals
have elevated basal insulin levels, usually defined as a fasting insulin of at least 15 μIU/mL, or
perhaps higher. If you have a protruding belly, high triglycerides and a high blood pressure, you are
probably in this category. Under these conditions, dietary carbohydrate, and to a lesser extent protein,
add fuel to the fire by spiking an already elevated insulin level. And let us grant here the point of
Krieger and CarbSane that ASP is a potent faciliator of fat storage. It is known than insulin
significantly enhances the action of ASP. In addition, insulin upregulates lipoprotein lipase (LPL) a fat-
storage promoting enzyme and inhibits the action of hormone sensitive lipase (HSL) an enzyme that
favors hydrolysis of stored lipids to free fatty acids. Combine all three effects and we should expect
that IR individuals store dietary fat easily, even with moderately low carbohydrate diets.
For these individuals, the elevated levels of basal insulin will tend to shift the balance of glucose and
fatty acids from the blood stream into the tissues. (Krieger and CarbSane are correct that insulin may
not play a big direct role in driving fat sequestration, but its indirect stimulatory effects on ASP and
LPL and inhibitory effect on HSL are quite significant, reducing the concentration of fatty acids in the
blood stream by shifting the equilibrium towards the adipocytes). This will also tend to stimulate
appetite and eating, leading to more fat storage and a worsening IR condition. Sugarholics and those
with carbohydrate cravings tend to be insulin resistant. Appetite has a large conditioned component,
whereby preprandial levels of insulin, ghrelin, and other hormones are secreted based upon temporal
cues and specific sensory cues. It has been found that this pre-prandial secretion is much more
pronounced in overweight, IR individuals.
One of the best ways to break this cycle is to go on a very low carbohydrate diet, something like the
Atkins induction diet. Since there is no insulin response to dietary fat, a high fat, very low carb,
moderate protein diet will allow basal insulin level to gradually drift down. This will shift the balance,
reducing (but not eliminating) the actions of ASP and LPL, and disinhibiting the action of HSL. This will
increase release of glucose and fatty acids, supplying energy and providing satiety, further lessening
the drive to eat. The vicious cycle is replaced by a virtuous one. Unfortunately, a reduced calorie, high
carb diet will not work for IR individuals, because their appetite is so easily triggered by any increase in
insulin, which leads to a faster than normal drop in blood glucose. Note that blood glucose does not
have to be “low” to induce hunger. There is evidence that hunger is triggered merely by a rapid drop
in glucose levels. On the Deconditioning Diet page of this blog, I describe a method for
extinguishing this conditioned pre-prandial insulin response.
Claims that insulin suppresses appetite is based on studies involving central administration of insulin
while artificially infusing glucose. Krieger is correct about the “central” effect of insulin within the
hypothalamus and upon the vagal afferent fibers. However, as with many hormones, insulin can have
opposing effects at different locations and times. We need to consider the important appetite-inducing
effect of insulin secreted into the “periphery”, without the simultaneous supplementation of glucose or
other nutrients. This is a particular issue for IR individuals who are vulnerable to insulin-induced
cravings, and less of an issue for those with good blood sugar control.

Now let’s consider insulin sensitive (IS) individuals. These are people with less than 10 μIU/mL,
ideally less than 5 μIU/mL insulin. The situation is quite different for these folks. As a result of much
lower basal insulin levels, they have more stable blood glucose and fatty acid levels, because the
lower insulin levels reduce inhibition of glucose and fatty acid release from glycogen and adipose
tissue. So IS individuals are less prone to hunger cravings, because they can access their own
energy stores more easily. They are much better able to tolerate higher levels of carbohydrate in the
diet, because their insulin response is well controlled and glucose readily gets to the cells and brain
after eating.
This may also provide a plausible explanation for why certain populations such as the Okinawans, the
Kitavans, and other cultures remain lean on a relatively high carbohydrate diet: their low basal insulin
levels and high insulin sensitivity permit them to handle carbohydrates easily. According to Stephan
Guyunet’s Whole Health Source blog:
Grains, refined sugar, vegetable oils and other processed foods are virtually nonexistent on Kitava.
They get an estimated 69% of their calories from carbohydrate, 21% from fat, 17% from saturated fat
and 10% from protein. Most of their fat intake is saturated because it comes from coconuts. They have
an omega-6 : omega-3 ratio of approximately 1:2. Average caloric intake is 2,200 calories per day
(9,200 kJ). By Western standards, their diet is high in carbohydrate, high in saturated fat, low in total
fat, a bit low in protein and high in calories.

While this is a “high carbohydrate” diet, the carbohydrates are not typical western foods: The Kitavan
diet consists mainly of foods like tubers, fruit, coconut, fish and vegetables. Even with the high
carbohydrate levels, their insulin levels are much lower than that of typical Westerners. One could
argue that these foods have low levels of fructose and sugars, and are generally quite non-
inflammatory, so they should promote insulin sensitivity. According to Lindeberg, their fasting insulin
levels averaged 3.12 and 3.29 IU/ml for males and females, respectively. This is about half the basal
insulin levels of Swedes: 6.98 and 6.65 IU/ml for males and females, respectively. Fasting blood
glucose levels for the Kitavan’s were about 27% lower than that of the Swedes.
Furthermore, IS individuals should be able to lose fat quite easily by restricting carbohydrate,
intermittent fasting and/or exercise. With resulting very low basal insulin levels, it should be even
easier to release fat from adipose tissue and oxidize it for energy, or to go into ketosis. It is known that
Type 1 diabetics, who have no insulin, shed fat readily and have trouble holding onto it without
injections. But someone with low basal insulin can achieve a naturally lean state easily, while also
being able to handle insulinogenic meals without difficulty. Based on my own experience over time, as
my fasting insulin level has dropped, intermittent fasting and even fasted workouts become easy, and
this does not preclude a reasonable level of carbohydrates in my diet.

Now let’s ask the question of whether insulin sensitive (IS) individuals can accumulate body fat on a
high-fat, low carb diet. According to Krieger and CarbSane, this should be no more difficult than on a
high-carb diet. You just have to eat a “caloric surplus” of fat, with no or little carbohydrate, and ASP
will do the job, even without insulin. But will this really have the predicted effect? Without doing the
study, it is hard to know for sure. But my prediction would be that it is unlikely to play out as they
suggest, for several reasons:

1. Despite the claims that ASP works without any insulin, the primary sources don’t show this. For
example in the paper by Saleh et al., which CarbSane cites in support, there is still some insulin
and carbohydrate present to stimulate ASP, with or without the action of chylomicrons.
2. Even assuming that the ASP could drive fat accumulation without insulin present, the lack of
insulin would also favor downregulation of LPL and activation of HSL, which will tend to balance
ASP’s action by liberating fatty acids from the adipocyte.
3. Under low insulin conditions, even with excess fatty acids being fixed within the adipocytes, one
would expect a reasonably high equilibrium level of free fatty acids in the blood stream. This
would favor satiety, so that eating the fat meal would be self-limiting. This contrasts with the
action of insulin which, when elevated, will tend to deplete the blood stream of glucose and fatty
acids.
I will conclude with the following synthesis between the above opposing positions:
 1. Obesity is a disorder of excess fat accumulation resulting from insulin resistance (and leptin
resistance), which stimulates appetite and naturally leads to caloric imbalance, including
overconsumption of both carbohydrates and fats.
2. Insulin and ASP together regulate fat storage and release. While ASP acts directly to transport
and fix fatty acids within fat cells, insulin acts to induce fat storage via ASP and LPL, and to
inhibit fat release via HSL and epinephrine and norepinephrine. Reduced levels of both insulin
and ASP favor lipolysis and fat loss. The synergy of insulin and ASP further explain why the
combination of dietary carbohydrate and fat is particularly fattening.
3. In insulin resistant individuals, elevated blood insulin levels stimulate hunger and the drive to eat;
this effect is largely absent for insulin senstive individuals due to superior blood glucose control
4. In insulin resistant individuals, the pancreas compensates for reduced receptor sensitivity by
secreting more insulin, leading to hyperinsulinemia.
So the answer to the question is to shift the blame from the hormone insulin to the condition of the
insulin receptors. Insulin spikes at meal time are no problem, so long as basal insulin remains low.
Restriction of dietary carbohydrate is one very effective strategy, which should be chosen not for the
short term benefits in weight loss, so much as the longer term benefits in improving insulin sensitivity
and reducing basal insulin. With the focus on “regrowing” and “reconditioning” insulin receptors, we
should look at the full arsenal of tools, including intermittent fasting, nutrients such as vitamin D,
magnesium and fish oil, and high intensity interval training.

Let me emphasize here that my proposed explanation is meant as a tentative conceptual framework
rather than a conclusive scientific analysis. I’m still learning about the details and I fully expect that
our understanding of the underlying mechanisms of fat metabolism will continue to be revised and
evolve. But I do think that there has been too much emphasis placed on hormones and
neurotransmitters, which fluctuate every day, and not enough on receptor health, which is something
we can can influence over the long term by commitment to scientifically informed practices.

If you are interested in this general framework for diet and how it fits into my overall philosophy of
Hormetism, check out my podcast interview with Jimmy Moore which just went live today.

Is it dangerous to skip breakfast?

20 Comments
Tags: blood glucose, calorie restriction, cancer, cardiovascular
disease, cortisol, dementia, dopamine, Hormesis, hormone balance, hunger, insulin sensitivity, intermittent fasting, meal
frequency, obesity
Posted 08 Dec 2014 in Diet, Health, Hormesis

There is increasing evidence from recent human and animal

studies that intermittent fasting — refraining from food or caloric beverages for at least 12 hours a day,
several days a week — reduces the risks of cardiovascular disease, dementia and cancer. Those
benefits are well-documented in the hyperlinked articles, so I won’t repeat them here. Yet many
nutritionists hold that skipping breakfast or other meals and snacks can lead to weight gain and
metabolic imbalance. Several recent articles have suggested that IF and breakfast skipping is a
particularly bad idea for women. Much to my chagrin, this view been even embraced recently by a
number of ‘Paleo’ advocates whom I respect, such as Chris Kresser and Mark Sisson.
In this post I’d like to address three main objections that have been raised against skipping breakfast
and other forms of intermittent fasting:

1. It spurs hunger cravings, leading to compensatory overeating and obesity

2. It causes cardiovascular disease and metabolic dysregulation of blood glucose and hormone
levels
3. It’s bad for women, leading to hormone imbalance, disrupted menstrual cycle, and heightened
stress response
I believe these concerns with breakfast skipping are overblown, based on an incorrect interpretation of
a few animal and human studies, and flawed personal implementation. To the contrary, adaptation to
meal skipping can actually help boost stress tolerance and improve blood sugar control. If practiced
correctly, intermittent fasting (IF) can actually be a powerful tool to overcome hypoglycemic symptoms,
and regain control over a harried lifestyle. And it can be particularly useful for women who are
struggling with cravings, weight management and stress management.
Opposition to intermittent fasting arises from both published research and anecdotal reports. I’d like to
address both in this post. I’ll first point out some significant flaws in the interpretation of several recent
studies purporting to show negative effects of reduced meal frequency on women and other
groups. And I’ll end by pointing out how to avoid common mistakes made by many who try
intermittent fasting find it to be unpleasant and unsustainable.

Approached correctly, IF can provide major health benefits for most us.

Let’s dig in to the arguments that have been made in support of these three myths about breakfast
skipping and intermittent fasting:

Myth 1: It spurs hunger cravings, leading to compensatory overeating and obesity. A number of
observational studies report a correlation between breakfast skipping and obesity. For example,
a 2010 study of 9659 teenagers found that self-reporting breakfast skippers had higher BMI, and waist
size than those who ate breakfast.

Some have attempted to explain this

association in terms of overcompensation for hunger. The idea is that skipping the first meal of the
day is counterproductive because it backfires, stoking hunger and leading to a high net intake of
calories later in the day. This view seems to find support in a 2014 CDC study of eating behavior
among overweight young adult women. The participants were screened to include only those who
already habitually skipped breakfast and were overweight (BMI 25-35 kg/m2). The study measured
dopamine levels (using homovanillan, a dopamine metabolite) and subjective cravings in response to
different breakfasts, or skipping breakfast. It was found that, compared to eating breakfast, skipping
breakfast resulted in a gradual increase in cravings and lower dopamine levels over a 4-hour morning
sampling period.
According to Heather Leidy, the lead author,
Our research showed that people experience a dramatic decline in cravings for sweet foods when
they eat breakfast. However, breakfasts that are high in protein also reduced cravings for savory – or
high-fat – foods. On the other hand, if breakfast is skipped, these cravings continue to rise throughout
the day….It used to be that nearly 100 percent of American adults, kids and teens were eating
breakfast, but over the last 50 years, we have seen a decrease in eating frequency and an increase in
obesity.
It’s not really surprising that eating breakfast would reduce hunger and increase dopamine levels
relative to not eating breakfast, is it? The more important question is whether skipping breakfast and
the increased mid-day appetite leads to obesity or long term weight gain via compensatory eating later
in the day. The CDC study didn’t specifically address that question. It could not answer the question
of progression to obesity, because it started out with a pre-selected group of already overweight
teenagers who were already breakfast skippers.
So who knows what led to their initial weight gain prior to the study. We don’t know whether their
breakfast skipping was the cause of their high BMI. It is entirely possible that their breakfast skipping
was a consequence of their BMI or something related to it. In fact, the authors of the study end by
acknowledging these uncertainties:
Specifically, reduced breakfast frequency (i.e., breakfast skipping) is inversely associated with
increased BMI, weight gain, and obesity in young people. However, due to the lack of long-term
randomized controlled trials, a causal link between breakfast skipping and obesity has not been
substantially identified.
It’s certainly far from proven that breakfast skippers overcompensate due to hunger cravings and eat
more as a result of skipping the first meal of the day. A 2013 study by Levitsky and Pacanowski found
that while skipping breakfast does lead to increased hunger by lunch time and eating of larger
lunches, by the end of the day the breakfast skippers had spontaneously consumed 400 less calories
per day than the non-breakfast skippers. Overcompensatory eating did not occur.
If skipping breakfast doesn’t lead directly to overeating and obesity, what explains the observed
association? Perhaps eating late in the day “causes” breakfast skipping the next morning. That
may not be as strange as it sounds. It could be that a large number of those who are obese skip
breakfast because they overeat late into the night and wake up still feeling full from the previous night,
delaying their eating until later in the day.
Myth 2: It causes cardiovascular disease and metabolic dysregulation of blood glucose and
hormone levels. There is indeed some evidence that those who skip breakfast and also consume
most of their calories after 6 pm put on more weight and are less healthy. But is it the breakfast
skipping or the late night eating that drives this? Let’s take a look at a few studies that examined
breakfast skipping and late night eating.
A 2014 study of 1245 adults by Bo et al. found that consuming more of the daily energy intake at
dinner is associated with an increased risk of obesity , metabolic syndrome and non-alcoholic fatty
liver disease.
A 2013 study by Jakubowicz et al. found that when daily intake was fixed at 1400 calories, eating the
larger 700 calorie meal for breakfast resulting in more weight loss and better metabolic markers than
consuming the 700 calorie meal between 6 and 9 pm at night.
A 2013 study by Cahill et al. at Harvard followed the eating patterns and cardiovascular health of over
26,000 men for 16 years. The men all started out free of Coronary Heart Disease. But the men who
skipped breakfast were found to have a 27% higher “risk” of CHD. This alarming conclusion got a lot
of press!

But such a bold headline deserves closer scrutiny. Buried within the Cahill study are a number of
surprises. It turns out that the “risk” analysis was based on complex modeling that attempts to correct
for numerous differences between the subgroups in order to tease out the “true” risks. In fact,
the actual incidence of CHD “events” over the course of the 16 year study was….drumroll:
 5% among the breakfast skippers
 6% among the breakfast eaters.
So CHD events were actually 20% more frequent (6% vs.5%) among the breakfast eaters than
the breakfast skippers!
Then why did Cahill et al calculate a higher “risk” for the breakfast skippers? Answer: they “corrected”
the results using a statistical model. They did in an attempt to account for the fact that in
their particular sample of study participants, breakfast skippers were different from the breakfast
eaters in a number of key respects. For example:
  Breakfast skippers were 5 years younger on average than breakfast eaters
 15% of the breakfast skippers smoked vs. only 5% of the breakfast eaters
 Breakfast skippers consumed 37% more alcohol than breakfast eaters
 Cholesterol levels and other biomarkers differed between the two gropus
Through the magic of statistics and multivariate modeling, Cahill et al. “adjusted” for a large
number of other health and demographic factors, converting the absolutely lower CHD
incidence of the breakfast skippers into a 27% higher risk! Magic! Yet the adjustment is
paradoxical because — other than being younger — the breakfast skippers had a number of strikes
against them, such as higher smoking and drinking rates. So you would think the fact that their actual
incidence of CHD was lower, would mean that the breakfast skipping behavior was protective, not risk-
enhancing.
The “corrections” made by Cahill’s team of modelers led to another head-scratcher:

In stratified analyses, among men ≤60 years of age, those who skipped breakfast had a 50% higher
risk of CHD compared with men who ate breakfast (multivariate RR, 1.55; 95% CI, 1.09–
2.22), whereas this association was not significant in the older half of participants (RR, 1.06;
95% CI, 0.84–1.33; P for interaction=0.01;
Huh? If you believe the Cahill analysis, skipping breakfast increases your risk of CHD if you are
younger than 60, but that risk suddenly disappears entirely after you reach age 60! It seems to me
that the Cahill analysis is an example of placing undue faith in a model, rather than taking the
unvarnished incidence data at face value. Data massaging for risk analysis is often warranted, but it
can sometimes lead to perverse and nonsensical results, especially when the risk relationships are
complex and non-linear, and when the absolute risks are relatively small and similar in magnitude.

If you still have confidence in the Cahill

multivariate models, there is yet an even more alarming result: Those who ate late at night or through
the night had a 55% higher CHD risk than others, and this higher risk was mediated by body mass
index, hypertension, hypercholesterolemia, and diabetes. Unlike the analysis for the breakfast
skippers, a key point is that this difference persisted even independently of the statistical risk
model. In absolute terms, over the 16-year study, fully 9% of the late night eaters had CHD, vs. 6% of
the non-late night eaters — more significant than the impact of breakfast habits.
In addition, Cahill found a 25-30% increase in CHD risk among those who ate more than 5 times a
day. Snacker and grazers take note.

A 2014 study by Kutsuma et al. examined the eating habits of 14,068 Japanese adults with a variety of
eating patterns. Multivariate analysis showed that the combination of late night dinner eating and
breakfast skipping was associated with obesity and metabolic syndrome, and yet this association
was absent in the case of either breakfast skipping alone or late night eating alone.
Looking at all these studies, we can ask: What’s the real problem: breakfast skipping, or
eating frequently and late into the night?
We need to be careful not to link intermittent fasting with effects that may originate from a very
different pattern of eating — in which breakfast skipping is associated with a common cultural pattern
of eating late at night and snacking frequently. Many such breakfast skippers may start eating around
lunchtime, and continues snacking and eating through the afternoon and evening, culminating in the
midnight snack. Maybe even “healthy” snacks. Know anyone like that? By contrast, most who
practice IF deliberately confine their eating to an interval of about 5-7 hours. Typically, they skip
breakfast, eating lunch and an early dinner, or perhaps just an early dinner, going to sleep on an
empty stomach.

Going to bed on a full stomach eliminates the nighttime fasting that kicks in for those who partake of
lighter or earlier dinners. Late eating may prevent the benefits of fasting and low insulin levels during
sleep brought on by autophagy — the process of nutrient recycling that reverses the accumulation of
metabolic damage and underlies many of the health benefits of intermittent fasting. If eating a big
meal at night is followed by eating breakfast again early in the morning, there is not much of a “fast” to
break, even if one waits until lunch for the next meal. Autophagy kicks in only when you don’t eat for
about 12 hours. (It can also be activated by severely restricting protein and/or carbohydrates).

Myth 3: It’s bad for women, leading to hormone

imbalance, disrupted menstrual cycle, and heightened stress response. Recent articles
by Stefani Ruper and the Poliquon blog cite animal and human studies to substantiate this claim. In
her blog post, “Shattering the myth of fasting for women”, Ruper cites a combination of biological
research, anecdote and personal experience to buttress her main thesis:
Many women find that with intermittent fasting comes sleeplessness, anxiety, and irregular periods,
among a myriad of other symptoms [and] hormone dysregulations. I have also personally experienced
metabolic distress as a result of fasting, which is evidenced by my interest in hypocretin
neurons. Hypocretin neurons have the ability to incite energetic wakefulness, and to prevent a person
from falling asleep, should his body detect a “starved” state. Hypocretin neurons are one way in which
intermittent fasting may dysregulate a woman’s system…the mere fact of being more sensitive to the
strains of fasting simply by being a woman is, I would assert, pretty important for a woman who is
contemplating or already practicing IF.
Ruper’s reference to hyopcretin neurons draws upon a rat study by Martin et al., showing that 6
months of calorie restriction was beneficial for male rats but detrimental to female rats, causing them
to “masculinize”. The fasting female rats stopped ovulating, exhibited heightened alertness and
memory, and slept less. The authors showed that these changes came about by activating the
hypocretin “arousal” system in the brain’s hippocampus. These arousal and food-seeking behaviors
are presumably beneficial as an evolutionary adaptation to starvation. Chronic activation of these
arousal systems could interfere with reproductive capacity and cause other health problems.
However, a closer look at the Martin et al. study makes it clear that none of the diets examined was
a reasonable model of breakfast skipping or intermittent fasting. The five diets studied were:
1. ad libitum (control diet)
2. 20% CR (calorie restriction)
3. 40% CR (calorie restriction)
4. IF (intermittent fasting)
5. HFG (high fat / high glucose)
 Restricting calories by 20-40% is really quite severe, and it is
not surprising that it could lead to loss of ovulation. But what about the so-called “IF” diet? The article
makes it quite clear that the IF diet was also a forced calorie restriction diet. Unfortunately,
few details are provided regarding the precise degree of calorie restriction or the feeding schedule.
However, the authors do give us this clue:
Whereas males on the HFG diet showed a greater increase in weight than those on the control diet,
females on HFG and control diets gained similar amounts of weight. Males and females exhibited
similar body weight responses to 20% CR and IF diets (i.e. a small increase in body
weight). Both male and female rats responded to 40% CR by losing a significant amount of body
weight during the study.
From this, together with the fact that the researchers explicitly state that the IF diet was calorie
restricted, it is reasonable to infer that the IF diet was probably in the range of 20% calorie restriction.

Here’s the problem: Nothing about intermittent fasting mandates or even recommends net calorie
restriction! With IF, you eat all you want — you just eat it within a restricted time window. True IF is
more like an “ad libitum” diet than a calorie-restricted diet, in that it allows your appetite to be fully
sated. The neat thing about IF is that it has been shown to provide many of the health benefits of
calorie restriction without any actual net reduction in calories! Quite a few IF practitioners
do spontaneously reduce calorie intake over time, as their appetite adjusts. But many IFers do not
significantly cut back on calories — they just alter the temporal pattern of intake. In either case, IF has
been shown to provide health benefits.
In short, the Martin et al. rat study cited by Ruper fails to say anything about intermittent fasting the
way most people practice it: without forced calorie restriction. It’s certainly not the way I practice or
advocate it.

Ruper does seem to acknowledge the difference between calorie restriction and IF, but she appears
to confute IF with longer term fasting:

It is well-known in both the research and the nutritional communities that caloric restriction
is horrible for female reproductive health. This is not news. But what of fasting regimes? Should
women go long periods without eating, even if maintaining normal caloric input?

Long periods without eating? Intermittent fasting involves short term breaks from eating of 12-24
hours, and the the degree of net calorie restriction can be modest to none. We are not talking about
“long periods” of going without food or any significant amount of calorie restriction.

On that note, Ruper cites a 2005 study by Heilbronn et al. showing that alternate day fasting improved
insulin sensitivity men, but slightly impaired glucose tolerance in women. The study had a very small
sample size (eight men and eight women) and the effects were slight, but even granting its validity, the
protocol involved so-called Alternate Day Fasting (ADF). This involves continuously alternating
between 12-hour eating windows and 36-hour fasts for two weeks. In my view, this is starting to push
the fast a bit long. I certainly wouldn’t recommend ADF to anyone as an “introductory” version of
IF. Longer fasts require a period of adaptation. I occasionally do longer fasts myself. But my
recommendation to newbies is always to start out gradually, by skipping snacks and then a few meals,
rather than taking a heady plunge into longer fasts.
One of the most common misunderstandings of hormesis that I encounter on this blog is a failure to
appreciate the dramatic difference between modest, intermittent stress and intense, chronic
stress. Hormesis is all about the benefits of low dose, intermittent stress. This applies to
exercise, diet, immune response, vision therapy and even psychology. People think that if a little is
good, a lot is better. Moderation and gradualism are essential to reaping the benefits of hormesis.
Hormones out of whack? The posts by Ruper and the Poliquon Group also both cite a 2007 study of
meal frequency by Stote et al, comparing consumption of three meals a day with consumption of the
same amount of food once daily for dinner. The results were a mixed bag: Those eating a single daily
meal lost body fat, and saw their cortisol levels decline. However, they apparently also experienced
greater hunger, less satiety, and modest elevations in blood pressure and LDL and HDL cholesterol
levels. Ruper’s verdict:
In sum: patients on the one meal/day regiment were unhappy, hungry, lost a little bit of weight,
increased cholesterol. This was a small sample, included ~menopausal women, and all people of
normal body weight.
A closer read, however, pinpoints some telling details. First, how was hunger measured? “Subjective
satiety and hunger were assessed daily before consumption of the evening meal“. Well
duh! Obviously this is going to be precisely the high point of hunger for those eating one meal per
day, and hunger will obviously be much more attenuated for those who ate lunch just a few hours
earlier! Seems to me that it would have been fairer to do the hunger assessment after the dinner, or
perhaps upon waking in the morning, for both treatments. Personally, some increased hunger is a
good thing, particularly if it makes food tastier and the meal leaves you satisfied.
The Poliquon article interprets the Stote article as evidence that intermittent fasting causes hormone
dysregulation:
The effect of intermittent fasting on hormones and circadian rhythms is devastating. First, the entire
hormonal cascade (metabolic hormones like insulin, anabolic hormones like testosterone and growth
hormone, and energizing hormones of the adrenal glands) is interrelated. When one hormone-
producing gland gets out of whack, you can bet that others will be negatively affected. This can
produce any of the following: Poor metabolism and body composition, inability to build muscle,
infertility, chronic fatigue, sleep disorders, a pro-inflammatory state, and increased risk of disease.

A glimpse of this with intermittent fasting comes from an 8-week study [Stote et al.] in which middle-
aged people went on a 1-meal-a-day diet or a regular 3 meal-a-day diet—calories were not restricted.
Results showed that the 1-meal-a-day group diet lost 2 kg of fat compared to the 3-meals-a-day group,
however they also had a significant increase in blood pressure. Elevated blood pressure is indicative
of altered circadian rhythms.

In addition, cortisol, which was measured in the late afternoon before eating the 1 meal, was 48
percent lower than at baseline. This is further evidence of diurnal dysregulation. Yes, you want to
minimize cortisol for health and body composition, but that doesn’t mean you want irregular cortisol,
which is a symptom of adrenal fatigue.

Quite an indictment! But this is taking a few tidbits out of context and wildly speculating about them.

First of all, the slight blood pressure elevation that Stote saw in the once-a day eaters was most
likely an artifact of the time of day at which blood pressure measurements were made, as Stote et al
themselves suggest:

In animal models, intermittent fasting without caloric restriction has been shown to decrease blood
pressure and heart rate (15). The observed increase in blood pressure in our subject population
consuming 1 meal/d may be due to a circadian rhythm in blood pressure (23). Diurnal changes may
have occurred, because blood pressure measurements were obtained in the late afternoon in the
1 meal/d diet versus early morning in the 3 meals/d.
Second, the concern about the 48% drop in cortisol over the day is misplaced. This is not
dysregulation or a sign of “adrenal fatigue”. To the contrary, it is perfectly healthy! According
to Chinnock et al. a normal cortisol pattern starts with a rise in the morning, followed by a gradual
decline throughout the day, precisely as was found in the once-a-day eaters. Later in this article, I’ll
reference another study by Taylor et al., confirming normal levels of cortisol and other hormones in
intermittent fasters, and no impact on the menstrual cycle.
The Poliquon article’s charges of adverse hormonal effects of intermittent fasting are unfounded.
Another anomaly of the Stote study is that subjects eating once daily were required to eat the same
amount of food as the three-meal-per-day group in a single setting. All 2400 calories, whether they
wanted to or not. In other words, appetite was not allowed to control eating. Yet they still lost
weight. Imagine if it had been an ad libitum study. Yet I think this is a big defect of the study and may
be responsible for some of the negative effects on blood lipids and blood pressure. It is not a natural
way to eat. And it may have been responsible for the high dropout rate of the study. As the authors
note,
Our study withdrawal rate was 28.6%. Typical rates of withdrawal from human feeding studies at our
facility are ≈4–7% (18–20). We can hypothesize that subject withdrawals increased because the
subjects were asked to consume all food for the day in 1 meal; however, only 1 subject specifically
stated this reason for withdrawing.
So far from stoking hunger, the authors worry that their once-a-day feeding protocol made subjects
feel too full!

Stote concludes with the view that IF might be OK for overweight women, but not for women of normal
weight, light sleepers, those with irregular menstrual periods or conditions like acne.

The solution, then, in moving forward, is to look at options, to be honest about priorities, and to listen
to one’s body with awareness and love. Is fasting worth trying if a woman is overweight and trying to
improve her metabolic markers, and so far hasn’t had much success? Perhaps. Should it be
undertaken if a woman is of normal weight? What if she is a light sleeper? What if her periods begin
to dysregulate? Or stop? What if she starts getting acne, getting a stronger appetite, or losing her
appetite altogether? These things happen, and I see them in women who fast and contact me time
and time again.

These fears about intermittent fasting seem unfounded. Hormonal dysregulation might be associated
with longer term fasting or other lifestyle or dietary conditions that raise cortisol. But that is not the
situation with IF, which was even shown to reduce cortisol levels.

By failing to distinguish intermittent fasting from extreme calorie restriction and long term fasting, I
think that Ruper and others do a disservice to women in particular. I know quite a few women who
have adapted to IF quite well and swear that it has improved their health and their lives. That fact that
it works for some women quite well should be enough to refute the idea that IF is only suitable for
men. I do not doubt that the transition to IF may be difficult for some women — but that is also true
for some men. I’ll deal with the practicality of how do adapt to IF towards the end of this article.
True intermittent fasting. Now let’s look at a few studies that actually looked at real intermittent
fasting — eating less frequently (but generally at least once a day) and within a confined time window,
but without any attempt to limit or equalize net daily calorie intake.
A 2014 Salk Institute study published in Cell looked at true non-calorie-restricted intermittent fasting in
mice. Unlike the Martin et al. study, these mice were allowed to eat all they wanted, but just within a
restricted eating window. Mice that ate within a 9-12 hour window ended up weighing significantly
less than control mice allowed to eat as much as they wanted around the clock — even though they
ended up consuming the same net amount of daily calories! The reduced weight gain was true
even for rats given diets high in fat and sugar. Even more impressively, the IF rats maintained good
lipid profiles and insulin sensitivity, unlike control rats that could feed ad libitum. Interestingly, the
strong weight control and metabolic benefits persisted even when the rats were allowed to go off the
diet on weekends! A slightly longer 15-hour eating window provided more modest benefits.
Great for rats, but how about humans, and specifically women?
 A 1998 study of meal frequency
in women by Taylor et al. compared the metabolic effects of eating 3 daily meals plus a snack versus
a single daily dinnertime meal of equal daily caloric, macronutrient and micronutrient composition. The
same seven women were studied eating these two different patterns for two separate 3-day study
periods. It should be pointed out that the investigators approached this study with the mindset that
“the ingestion of fewer large meals may be metabolically worse than the ingestion of frequent small
meals.” The fact that the authors labelled the eating of one daily meal as “binge eating” rather than
“intermittent fasting” tells you something about the investigators’ presumptions! With that said, it’s
worth looking at what this study actually found:
Ingestion of an entire day’s calories at dinner resulted in a significant increase in fasting glucose levels
and a dramatic increase in insulin responses to the evening meal. The diurnal pattern of leptin
secretion was altered, such that the gradual rise in leptin from 0800 h observed during the normal diet
was abolished, and leptin did not begin to rise during the binge diet until at least 2 h after the evening
meal.

This is of course not at all surprising. The question is whether it a more concentrated peak rise in
glucose and insulin, and change in the timing of the leptin peak could result in hypothesized insulin
resistance or hormonal dysregulation, based on prior studies associating these problems with “binge
eating”. It turns out that those fears were not actualized:

No changes were demonstrated in insulin sensitivity, follicular growth, or ovulation between the two
diets….Importantly, there was no difference in cortisol excretion between the two diets.

It is also worth pointing out that despite higher morning (“fasting”) blood glucose levels on the once-
daily pattern (94 mg/dL) vs. multi-meal (86 mg/dL), the average blood glucose over the day for the
once-daily pattern (97 mg/dL) was significantly lower than for the multi-meal pattern (107
mg/dL). It seems to me that average blood glucose is a better indicator than a single morning reading
of what your brain and peripheral tissues are seeing most of the time. And 97 is definitely better than
107! Eating once a day may cause bigger “spikes” in blood sugar but average blood glucose levels
are lower, and remain lower for a more sustained, uninterrupted time. Adaptation to this pattern can be
especially valuable for people with blood sugar issues, because elevated blood sugars can cause all
sorts of problems.
Somewhat surprised that their study found no problems with one meal per day, Taylor at al. ended
their paper with the suggestion that perhaps something more is involved with true binge eating than
merely reduced meal frequency:

as most binge eating episodes in the population are associated with the ingestion of excess calories, it
is hypothesized that binge eating behavior is associated with even greater metabolic
dysfunction than that described herein.
Indeed. Binge eating, like bulimia and anorexia, is a true eating disorder. Eating disorders typically
arise from issues associated with body image and self-control, perhaps exacerbated by a poor diet or
metabolic dysfunction. But binge eating should not be confused with intermittent fasting. Practitioners
of IF are motivated by its documented health benefits and additionally by the freedom to offers from
cravings and food obsessions.

Conclusions and recommendations. The purpose of this post was not to make the positive case for
intermittent fasting. For that, you can check out the hyperlinks in the first sentence of this post, or
watch my talk on Intermittent Fasting for Health and Longevity. Rather, this post attempts to
examine and respond to some recent claims that IF can cause obesity, cardiovascular disease, and
disordered glucose, hormone levels, and menstrual cycles. I believe that these criticisms hinge upon
several fundamental misunderstandings of IF and misinterpretations of a number of
scientific studies. By closely examining the evidence, we can draw two main conclusions.
 Many breakfast skippers are indeed overweight or unhealthy, but this most likely reflects other
associated habits such as frequent snacking and eating late at night. IF is best practiced by
confining eating to a 4-6 hour window, and preferably eating dinner early and well before
bedtime.
 While dysregulation of hormones and menstrual cycles can be disrupted by severe calorie
restriction and very long fasts, there is no evidence that such problems result from shorter daily
fasts of about 12-24 hours.
While I believe that intermittent fasting is generally safe for most people, including women, I think there
are better and worse ways to implement it. Many have stated that IF is not suitable for people with
diabetes, hypoglycemia or other metabolic issues. However, I’ve heard and read of many instances of
people who used IF to reverse those conditions — to normalize blood glucose and lipids and to bring
hunger and hypoglycemia under control. For just one instance of this, read this inspiring post by Lee
Shurie, who reversed his diabetes using IF:

How I defeated Type II Diabetes

Of course, I have no doubt many of you reading this have had very negative personal experiences
trying intermittent fasting. But I suspect that many of the negative experiences that some individuals
have had with IF stem from making a very common and understandable mistake: moving too
quickly.
If you are habituated to a pattern of eating three or more meals a day plus snacks, trying to suddenly
switch to one meal a day may be a bad idea. While some people can do that (I did), many will find it to
be both psychologically and physically intolerable. Eating and appetite are under the control of a
complex system of hormones and enzymes. It can take weeks to change the timing of induction and
secretion of these modulators. Symptoms can range from hunger pangs and unbearable cravings to
headaches, hypoglycemic light-headedness, sweating and fainting. Not a good idea.

I strongly advise gradualism. Make small changes each week and allow them to set in before
proceeding further. First, eliminate between-meal snacks and avoid eating for at least an hour before
bedtime. Those changes can be hard enough and may take weeks to adjust to. But even that first
step is already beneficial. Once snacking is eliminated, try delaying breakfast rather than skipping
it. Eventually you may be able to skip breakfast. You can also try to finish eating dinner earlier and
avoid eating after 8 p.m.
Interestingly, the benefits of intermittent fasting can be significant even if you can manage a 12-18
hour mini-fast once or twice a week. You don’t have to do it every day to see health
improvements. Of course, if you can skip breakfast 5 or more days a week, more power to you.
 Your appetite will adjust, as your hormone and
enzyme levels gradually change to the altered eating schedule. Just as Pavlov trained his dogs by
repetition, you can train your mind and digestive apparatus to learn a new pattern. Hunger is much
more susceptible to conditioning that you may think — read this New Yorker article and my page on
Appetite the Deconditioning Diet. And be patient!
I’ve summarized my recommendations on transitioning to intermittent fasting in an earlier
post, Learning to Fast. It includes a lot of useful tricks, such as the use of “training snacks”. Learned
correctly, intermittent fasting doesn’t ramp up hunger — it tames hunger. Many people have told me
that post was very helpful in helping them adjust to intermittent fasting with a minimum of effort and
discomfort. I’d be interested in additional feedback and comments from others regarding what has or
has not worked for you in your efforts at intermittent fasting.
Happy (and gradual) intermittent fasting…just in time for the Holidays!