Wednesday, June 30, 2010

Anxiety and Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a condition characterized by the chronic experience of abdominal pain, cramping, bloating, gas, constipation, diarrhea, and/or mucous. 1 in 7 people suffer from it, but only half of those have sought treatment. And since there aren't any FDA approved treatments, a lot of people are struggling with irritable guts out there. 61% of people with IBS have anxiety disorders (1), and IBS sufferers report more stressful life events, and their bowel symptoms worsen with stress.

Anxiety itself is the result of an evolutionary adaptation to help us survive during times of extreme duress. Imagine you are hanging out with your buddies by the campfire, and a large animal suddenly joins you, looking for a meal. Your heart begins to race, your breathing picks up, your pupils dilate, blood is shunted from your digestive organs to give you more oxygen in your heart and large muscles, and your senses become acute. Steroids pump out of your adrenal glands to give you increased strength, stamina, and speed, at the cost of fatigue later on. Even your platelets can change shape to become stickier, just in case you are wounded.

Acutely, these changes can help you survive some pretty dire circumstances. But jack up the anxiety response on a chronic basis, and you end up with a classic anxiety disorder - hypervigilance, fatigue, insomnia, panic symptoms, muscle tension, gastrointestinal distress, and worry.

IBS patients have increased startle responses and increased vigilance compared to controls (2), and they have increased cortisol levels at baseline and in response to stress (3). Once again, we have two highly correlated conditions (IBS and Anxiety Disorders) with a similar pathophysiology - for both, possible disregulation of the Hypothalamic-Pituitary-Adrenal axis.

What is the HPA axis? Well, in layman's terms, it comprises three glands in the body that all send messages to each other. These glands control stress response, oversee metabolism, mineral and salt regulation, and basically a whole lot of important stuff, from blood pressure to growth to psychological states. Having that system disregulated is not good. HPA system breakdown is implicated in a dozen disorders, including PTSD, depression, fibromyalgia, and chronic fatigue.

What causes HPA axis dysfunction? Chronic stress, of course, as our body keeps trying to juice us with cortisol to help us battle a perceived threat. But another key cause of HPA axis dysfunction is inflammation. Yup, good old inflammation, the super secret cause of all diseases of civilization. Steroids like cortisol are antiinflammatory, so if our bodies perceive too much inflammation burning out of control, it will send out a wave of cortisol to quench the flames.

Whole books have been written about stress and modern life. Compared to hunter gatherers, we work too hard, play too little, exercise infrequently, hide from the sunlight, and don't sleep enough. And our modern diet, I believe, is highly inflammatory, particularly with regards to linoleic acid (4), fructose (5), and refined flour (5).

But let's step back to the brain, IBS, and anxiety for a moment and check out how they are connected more closely. Corticotropin releasing factor (CRF) is a molecule that works in both the periphery and the central nervous system, and is released in response to stress. CRF, when administered in the brain, causes anxiety and fear behaviors (at least in animals), and when administered in the body, changes the rate of gastric emptying, colonic motility, and increases gut permeability (so all the nasty things we want kept within our GI tract, such as wheat lectin, have an easier time floating through, theoretically, when we are stressed). Rats who are made more sensitive to the effects of CRF have higher rates of anxiety and more sensitivity to colon discomfort (1). For the neuroscience geeks out there - different neurochemicals and neurocharacters implicated in the whole cascade of stress to anxiety and gut issues include BDNF, the NMDA receptor, TrkB and TrkA, 5-HT, monoamine oxidase A, GABA, and the NGF receptor. Most of these activities happen within the amygdala, which is a region of the brain that is highly responsive to sex hormones (which may also explain why women have IBS about twice as often as men.)

Interestingly, sometimes antidepressants help IBS and anxiety. It might help the psychiatric symptoms, the physical symptoms, both, or neither - my definition of a toss-up.

Finally, Peter at Hyperlipid (as always) has an interesting theory about IBS and wheat opiates. Opiates (like heroin, morphine, and percocet) are well known to cause constipation while they are active, and diarrhea and overall discomfort and a lot of anxiety as they come out of your system. It would stand to reason that if someone is sensitive to wheat exorphins, the alternating exposure and withdrawal of wheat through differing meals throughout the day and week might cause alternating constipation and diarrhea, along with abdominal discomfort, the cardinal signs of IBS. Not to mention the anxiety factor. No proof other than anecdotes - but an idea to chew on.

Tuesday, June 29, 2010

Genes Are Not Destiny

We are the products of our mother's and father's genes (more Mom than Dad), but a modern understanding of genetics and biology shows us that how our genes are expressed are the product of our environment and what we do. How can that be, when we are allotted a certain genetic hand of cards at conception?

The science of epigenetics explains a lot (and leaves us with a lot of questions too). It turns out that genes can be silenced or turned on depending on how we live, and how we are treated. The body is not just a complicated jelly bag of enzymes and muscle and protein regulation; the very genetic material that directs all the regulation can change shape and redirect what goes on in the first place. So our genes regulate our proteins, but our proteins also regulate our genes.

Following the study of epigenetics, we also end up with the idea that what we do (and breathe and eat) affects our children and grandchildren, too. For example, in a small European community during World War II, babies were born smaller than usual. It makes sense. There was less to eat. But the children who were born smaller then grew up and had smaller babies themselves. Even more bizarre, epigenetic studies show that if your paternal grandfather had plenty to eat between the age of 9-12, your average lifespan is likely to be shorter than someone whose paternal grandfather didn't have enough to eat during that same critical age (1).

Why is this whole concept important to psychiatry? It's all about the brain. The brain has 100 billion neurons. 1.25 terrabyte memory capacity. 100,000 kilometers of connecting neuronal cables (2). Our human brains require many years of careful nuturing and protection as they reach maturity. The wiring process as we grow up depends upon a multitude of factors - nutrition, appropriate social attachment, education. Even after we are fully mature, the brain is still capable of change, or else we could never learn anything new.

Humans are all very closely related. There appears to have been a genetic bottleneck about 2000 generations ago, so that all of us are descended from a small family group that lived 50,000 years ago (3). Two randomly chosen humans have closer genetic similarities than two chimpanzees chosen from the same social group (2). There have been a number of changes over the last 2000 generations, but we are still so much more the same than different. The contention that "all men are created equal" has more scientific truth to it than one might think.

Let's pull all these separate threads together - we are born with a certain genetic hand. We can alter that hand for ourselves, our children and grandchildren by how we live. The brain is the most complicated organ in existence, and the interplay between our genes and how we live will affect the brain in countless ways. Finally, we are all brothers and sisters, and, with few exceptions, have enormous genetic potential for success.

Hardly any of us are doomed by our genes to be obese, diabetic, or depressed. There are simply too many other factors at play to make that flat statement. Yes, if your parents are obese, and you eat and do the same things your parents do, you are more likely to be obese yourself. The logic follows that if we eat and do similar things to what our lean ancestors did, we will be lean. We can't just wait for a new diet pill, a new surgery, a new exercise contraption to solve our problems for us. There are too many factors at play.

With the brain, the factors expand a thousand fold. Lifestyle, nutrition, and proper nurturing are more important for the brain than for any other organ. Hopefully, now, we can finally use medical science to address the whole picture, instead of looking for a single magical chemical or pill. We're all meant to be strong, smart homo sapiens - and we can be, if we work at it. And if genes are our destiny, then we are meant to be that small, intrepid band of humans who conquered the world, for good or ill.

Sunday, June 27, 2010

Depression 3 - Not Quite What It Used to Be

The first written records we have of depression are from Mesopotamia, in 2000 B.C. Those who were depressed were thought to be possessed by spirits, and thus treated by priests. The same was true of mental illness in other records in Babylonia, Egypt, and China, and often a type of exorcism was used as treatment, such as beatings, starvation, and restraint (1). The Greeks and Romans felt "melancholia" had spiritual and physical causes, and thus bathing, gymnastics, special diets, poppy extract, and donkey's milk were used as remedies. Hippocrates himself used bloodletting to help fix an excess of "black bile." Hippocrates described the symptoms of melancholia as persistent sleeplessness, lack of appetite, and depressed mood, along with occasional aggressive behavior, sometimes leading to suicide.

Cicero, a prominent statesman, argued that melancholia was "violent rage, fear, and grief," a similar explanation to Sigmund Freud's (anger turned inward) a few thousand years later. There was even a Persian doctor who recorded use of behavior therapy (rewards for positive actions). Then came the Middle Ages, and we were back to demonic possession again. Some doctors locked the mentally ill away in asylums, but many of the afflicted were thought to be contagious and were burned or drowned. Towards the end of the Renaissance, we were back to baths, humane treatment, and even music therapy.

The Age of Enlightenment brought the idea that mental illness was an inherited weakness of character, so we went back again to shunning and locking people away. However, scientists and doctors were experimenting more and more with different treatments, such as water immersion, a spinning chair, and Benjamin Franklin even came up with an early version of electroshock therapy (2). In the mid 1800s, we begin to get much more detailed descriptions of the symptoms of people admitted to asylums (3). Melancholia was still depressed mood, suicidal thoughts, worse in the morning, with prominent appetite loss and insomnia - very similar to the descriptions of the Greeks and Romans. In the late 1800s, as I remarked upon in my last post, the admissions to asylums skyrocketed. The author of (3) noted that syphilis was often blamed, however, only 14 cases were recorded in the asylum they studied, and that number did not explain the large increase in admissions overall.

Studies of human nutritional history show that rickets (a bone disease caused by severe vitamin D deficiency) became pandemic (especially in urban areas) in the 19th century (4). Here's a description of a common diet in working class England around the end of the 19th century: "The diets of working class women and children too often consisted largely of bread and tea, with sugar and the occasional smear of jam or margarine. Babies of all social classes were generally weaned on ‘pap’—bread and water or bread and milk." (4). Prior to this time, the vast majority of people lived on a farm, with (one would assume) access to fruits, vegetables, fresh meat, and the like. Weston Price found physical and mental deterioration in peoples as they abandoned their traditional diets and began to depend on sugar and refined flour. He also considered appropriate amounts of animal fat critical to good health (5).
I suspect that poor nutrition and deficient vitamin D may have led to quite a bit of mental illness in the 19th century (and today). Deficiency in B vitamins is also well known to cause psychiatric and neurological illness, and much of the cultural worry about physical and mental "racial degradation" disappeared after flour began to be enriched with B vitamins during WWII.

However, even in the early 20th century, the symptoms of depression were consistent with "melancholia." That is, intense sad mood, insomnia, agitation, suicidal thoughts, and appetite suppression. Then, and it is hard to say exactly when (maybe the 50s or 60s?), another type of depression began emerging, called "atypical depression." The symptoms include a milder depressed mood, poor energy, increased sleepiness, and increased appetite and weight gain (via carbohydrate craving). These symptoms are very similar to those of hypothyroidism (though usually thyroid tests are normal) and atypical depression responds to different classes of medication than old-fashioned melancholia. Chromium, a dietary supplement which is thought to suppress carbohydrate craving and speed metabolism, was found to be helpful for atypical depression in one trial. (6). Thyroid hormone (T3) is also used by psychiatrists for adjunctive treatment of depression. Atypical depression sufferers are also much more likely to have anxiety. While I've seen several textbooks quote the prevalence of atypical depression as 40% of depression subtypes overall, I would say in my clinic, the vast majority of my depressed patients have the atypical subtype. I only have two or three patients with classic melancholia. There is argument that atypical depression is actually a subtype of bipolar disorder, but I'm not convinced.

Atypical depression is generally considered milder than melancholia, and may not have shown up in the earlier asylum records for that reason. I've read quite a few novels over the years, and while I recall many literary descriptions of melancholia, I don't recall a whole lot of anxious characters with fluctuating depressed moods gorging on sugar. (That is obviously not a scientific sampling.) But in any event, the United States has done cohort studies every ten years, checking the incidence of mental illness in each successive generation. And in every generation, especially since 1950, depression has increased (increased diagnosis and awareness were, supposedly, statistically accounted for and do not explain the increase). Here's a link to the last cohort study. A woman today who has lived to old age has a 30-40% chance of having major depressive episode sometime in her lifetime. A man's risk is around 20-30% (7). As I stated in the first depression post, major depression and dysthymia (all subtypes included) afflict nearly 10% of us every single year.

Why is depression both changing and increasing? Well, Hibbeln and Salem * note that the dietary omega 6 to omega 3 ratio has also been increasing in the past century (yes, vegetable oils again!) And recall how atypical depression has similar symptoms to hypothyroidism? Whole Health Source has a terrific post linking linoleic acid (the predominant fatty acid in corn oil and other vegetable oils except olive and canola) to suppression of thyroid function at the liver. This would suggest that one could experience metabolic symptoms of hypothyroidism if one had a lot of linoleic acid in the tissues with normal serum thyroid hormone levels. I couldn't find an article noting T3 receptor suppression by linoleic acid in the brain - and this study seems to indicate that it doesn't happen in rat brains (8). Also, in my post on omega 3 fatty acid treatment for major depressive disorder, the depression with anxiety subtypes only trended towards doing better on omega 3s, whereas the treatment of plain depression showed significant positive effects. Since the modern, atypical depression is notable for its prominent anxiety, that may suggest the link to an overconsumption of omega 6 isn't the whole story behind the increase and alteration of depressive symptoms in the past decades.

There are other diet and depression theories also, related to that other "neolithic agent of disease" - sugar (or large amounts of processed carbohydrates in the form of starch.) Rob Faigin, a bodybuilder and lawyer looking for ways to build muscle without using steroids, wrote his book Natural Hormonal Enhancement in 2000. He postulates that a mechanism for modern depression is overall serotonin depletion caused by a diet high in processed carbohydrates (9). Each bolus of carbohydrate would cause a flush of serotonin (and thus good feelings and cravings for more while the carbohydrates are still working in your system), then a fall in serotonin and relative depletion once the sugar rush was over. Thus, in the short term, a switch from a high carbohydrate to low carbohydrate diet might cause depression, but in the long term, staying on a low carbohydrate might free one from mood swings and irritability (10).**

Any of you on low-carb diets? Do you feel depressed compared to how you were on a more traditional diet? While I am not extremely low-carb myself, on a primal style diet (lots of meat and fish, fruits, veggies, and rarely rice and potatoes for carbs, low in omega 6 and no wheat or refined sugars), I am personally more serene, more motivated, and more energetic. These rapid, painless, positive changes piqued my interest in the effects of diet on mood in the first place.

I suspect that depression, like other chronic disease states of Western Civilization, has a multifactorial dietary cause. Linoleic acid to increase the inflammatory soup, and some other factor (sugar rushes and crashes, perhaps?) to fuel the fire. I'll keep looking for more definitive information.

* Hibbeln's paper is extremely interesting, in that he brings up the contradiction between the findings that lower serum cholesterol levels are associated with increased depression and suicide, yet cardiovascular disease (and the higher cholesterol levels associated with that) is highly correlated with depressive disorders (p < 0.0000001!). It's also important to know that Hibbeln quotes a 1985 study by Eaton et al to suggest that saturated fat intake is higher today than it was in hunter-gatherers (9). According to Gary Taubes, Eaton repudiated his previous results in 2000, saying that he had not accounted for the hunter-gatherers eating organ meats and marrow, all high in fat and saturated fat.

**Judith Wurtman at MIT appears to be the major detractor of low carb diets due to possible depressive mood effects, but there is also this quote by her, which doesn't make any sense to me: ""When serotonin is made and becomes active in your brain, its effect on your appetite is to make you feel full before your stomach is stuffed and stretched." The researchers explain that people may still feel hungry after eating a large steak-their stomachs may be full but their brains may not be producing enough serotonin to shut off their appetites." In your experience, are you more likely to eat 5,000 calories worth of steak in one sitting, or 5,000 calories worth of potato chips or candy?? I think the fat/carb combo is far more likely to result in binging than steak. Or butter.

Saturday, June 26, 2010

The Evolution of Psychiatry

In the West a few centuries ago, mental illness was considered the result of personal or spiritual failure. Those who suffered were often considered punished by God, and incarcerated or otherwise treated cruelly (think of Bertha Antoinetta Mason locked away in Thornfield Manor.) In France in the early 1800s, Phillipe Pinel and Jean Etienne Esquirol introduced the idea of the traitement morale, that is, using empathy and compassion as treatments, and they began to develop basic diagnostic categories. A few years later, in Germany, Kahlbaum and Kraepelin, who worked in mental asylums, began documenting and describing psychotic and cycling mood illness. Some of their descriptions are still used as diagnostic criteria in the DSMIV today.

It's important to note that these doctors felt psychiatric illness was biological, that is part of an organic disorder of the brain, much like a stroke or epilepsy. Some of the disorders, such as hebrephrenia (a giddy type of schizophrenia found more often in young people) were extremely common back then, but incredibly rare now. Catatonia (a type of movement disorder associated with schizophrenia - either frozen movement or frenzied, uncontrolled movement) was also much, much more common in Kraepelin and Kahlbaum's catalogs than today.

Towards the end of the 19th century and the beginning of the 20th century, there was a large-scale increase in the number of psychiatric inpatients. Thousands upon thousands of people ended up in psychiatric hospitals. There was speculation at the time that the human race was "degenerating" as a result of some unknown natural selection process. Kraepelin traveled to Java and noted that mental illness was rare there, and felt the "domestication" of the human race was to blame. Unfortunately, he ignored the effects of poverty, poor hygiene, poor nutrition, and lack of education as possible causes of mental illness. His ideas were very influential, and since there was no pharmacological treatment at the time, many countries began measures such as sterilizing anyone with mental illness to stop the decline of the human race. Psychiatric authorities saw themselves as advocates of the mental health of the population (and some advocates of racial purity), rather than as medical doctors who treated individuals. (It is toward the end of this time that Weston Price made his famous journeys, and thus the name of his book, Nutrition and Physical Degeneration, and his preoccupation with the decline of physical, moral, and mental fiber, as it were, in the 1930s.)

We know what happened next. In Germany, the eugenics movement became the systematic extermination of millions of people, all for the sake of a non-existent and meaningless racial purity. Among those murdered were the mentally ill.

One who fled Nazi persecution was Sigmund Freud, and his ideas as to the cause of psychiatric illness were almost entirely different than the psychiatrists of the 18th and 19th centuries. He theorized that mental illness was caused by unconscious and repressed desires, and exacerbated by family situations (particularly problems with mothering) and coping patterns. The treatment, therefore, was therapy (back then, psychoanalysis). A large group of psychiatrists and psychologists were influenced by his ideas, and London and New York became centers of psychoanalytic thinking in the 1950s and 60s. In the next decades, psychotherapy advanced by leaps and bounds, and today there are 10 or 20 different kinds (in my opinion, the best book about the history of psychotherapy is Freud and Beyond). By the 1980s, it became clear that mental illness had both biological and psychological underpinnings. However, even to this day, there remains a false dichotomy - that all psychiatric illness can be cured if one works hard enough and has a good enough therapist, and that psychiatrists don't care about psychology or therapy and only want to stuff you full of pills. Truth be told, social, biological, and psychological underpinnings are all extremely important, and all must be kept in mind when recommending appropriate treatment.

I believe that all psychiatric illness is biologic, meaning rooted in neurotransmitters and membrane potentials, but that genetics, environment, nutrition, and psychotherapy impact how the brain works. The brain is better understood now than ever, which is to say it is still poorly understood in many respects. The vast complexity is nearly unfathomable. In my mind, the study of nutritional and evolutionary paradigms which may predispose us to psychiatric illness have been neglected in favor of psychology and the psychiatric medications. In the next post, I'll focus more on the changes in major depressive disorder over the last century, and speculate as to some nutritional causes.

Friday, June 25, 2010

Diet and Depression Again

Now I'll review the other major dietary observational studies regarding depressive disorders.

Dietary patterns and depressive symptoms among Japanese men and women: 521 men and women filled out dietary surveys and mental health questionnaires. Once again three dietary patterns were identified - and those who ate fruits, vegetables, mushrooms, and soy (called the "healthy Japanese diet" group) were less depressed.

Vegetarian diets are associated with healthy mood states: a cross-sectional study in Seventh Day Adventist adults
: 60 vegan Seventh Day Adventists were compared with 78 omnivorous Seventh Day Adventists. The vegans reported a much higher intake of flax oil (an omega 3 fatty acid, ALA) and linoleic acid (omega 6 fatty acid). The plasma and tissue if the participants were not measured for their fat content, but vegans generally have a red blood cell phospholipid ratio (omega 6 to omega 3) of 18.6 compared to 9.9 in omnivores. Also, the vegans were generally happier! (see table).

Association of the Mediterranean dietary pattern with the incidence of depression: 10,094 Spanish men were followed for an average of 4.4 years. Participants were each given a Mediterranean Diet Compliance score based on positive points for consuming vegetables, fruit and nuts, cereal, legumes, and fish, a good monounsaturated- to saturated-fatty-acids ratio, and moderate alcohol consumption. Participants got a negative score for "meat" and whole-fat dairy. Over those 4.4 years, 480 new cases of depression were identified (as in the other two studies, anyone with depression or taking an antidepressant medication at the beginning was excluded from the study.) In general, the higher the diet compliance score, the less depressed the participants were, with intake of monounsaturated fats, nuts, fruits, and legumes seeming to be especially protective.

Anxiety and depression in adult patients with celiac disease on a gluten-free diet:
Germans (primarily women) with Celiac Disease on a gluten-free diet were compared with a group of Germans with inflammatory bowel disease (Crohn's or Ulcerative Colitis) and a group of normal controls. Women with IBD and celiac disease were both more anxious than the controls. Men seemed to be serene no matter what. Adherence to the gluten-free diet didn't seem to matter much with regards to level of anxiety. In a related study, anxiety improved in patients with celiac disease in a year on a gluten-free diet, but not depression.

In summary - we get the usual mish-mash with the observational studies. Vegan Seventh Day Adventists are happy folks. German women with celiac disease tend to be anxious, and the Mediterranean Diet appears to be protective against depression, at least in Spanish men! The most surprising finding for the researchers in any of the studies appeared to be the happy vegans, given the strong evidence in prospective trials for an antidepressant effect from fish oils. While limiting the study to Seventh Day Adventists was meant to be a control, it may mean that you can't generalize the results to the rest of the vegans and omnivores in the world. I know very little about Seventh Day Adventists, but maybe eating vegan every day as a religious practice is self-affirming and has an antidepressant effect of its own, for example. Clearly, though, the omega 6 to omega 3 ratio is not the end all, be all factor in the brain. Stuff to keep in mind!

Thursday, June 24, 2010

Diet, Depression, and Anxiety

This post will focus on a single paper, published in March 2010 in the American Journal of Psychiatry: Association of Western and Traditional Diets With Depression and Anxiety in Women. (Thank you to Dr. Hale for pointing out the study). In the introduction, the authors make note that depression and anxiety are highly prevalent with other chronic dietary-related illnesses such as cardiovascular disease, obesity, and type 2 diabetes. At the same time, psychiatry lacks evidence-based prevention and treatment strategies based on dietary modification. That may be for the best, considering what has happened with obesity and type II diabetes over the past 30 years, but that is, in part, why I'm trying to get the information out, blog-wise.

So - the study! Well, these researchers in Australia hijacked an ongoing study, called the "Geelong Osteoporosis Study." Thousands of intrepid women were randomly picked from compulsory voting rolls, and all told, 1046 women ages 20-93 were followed for roughly 10 years for the diet and depression part. Each participant filled out yearly questionnaires about her diet. (Problem number one - imagine I gave you a questionnaire about your usual consumption of 74 foods, 6 alcoholic beverages, and the type of bread, dairy products, and fat spreads you used? How accurate could it be? The researchers say the "comprehensive food frequency questionnaire" was a validated instrument, but one must keep limitations in mind.)

Then, all participants were given a SCID (that's a standard structured clinical interview used to diagnose psychiatric disorders in research), and they looked for current diagnoses of major depressive disorder, dysthymia (a low-grade, ongoing depression), and anxiety disorders. Also, a wide variety of statistical analysis tools were used to account for so-called "covariates" such as socioeconomic status, physical activity, alcohol consumption, and smoking. (Problem number two - which is the major problem with any observational study - one can never really account for all the covariates. For example, people who drink moderate amounts of wine have less heart disease. Wine could be a factor in that. Or perhaps people who drink wine happen to exercise more. Or maybe people who drink wine also have magical hearts. We really don't know. If you take a group of people and force-feed some a glass of wine or two a day, and then tell another group to abstain, then see if there is a difference in heart disease between the two groups, then you have a prospective trial, and that's not the kind of data we're talking about with the current study I'm examining, which is an observational study. We end up with associations and correlations with such studies, which are interesting, but could be meaningless. Tom Naughton brings up this issue and the 2010 US dietary guidelines in this blog post. Don't click that link if you have extremely delicate sensibilities.) The researchers weighed and measured the height of all the participants also.

Results! Everyone's diet was analyzed and segregated into three basic groups - traditional, Western, and modern. Traditional diets were comprised of vegetables, fruit, beef, lamb, fish, and whole grain foods. A Western pattern was associated with meat pies (Australian fast food), processed meats, pizza, chips (I seriously do not know if they mean french fries or potato chips here - Australian readers, help me out!), hamburgers, white bread, sugar, flavored milk drinks, and beer. The "modern" diet consisted of fruits, salads, fish, tofu, beans, nuts, yogurt, and red wine (in other words, the people who read the news reports on all the observational studies out there...).

And the punch line? A traditional dietary pattern "was associated with a lower likelihood of depressive and anxiety disorders."

Traditional fruit, veggie, lamb, beef, fish and whole grain eaters had a 25% lower risk for major chronic disease (cardiovascular disease and cancer) after 10 years. They had 35% reduced odds for having major depression or dysthymia, and 32% reduced odds for anxiety disorders. The "Western" (junk) and "modern" (bean, fish, wine, and tofu) eaters fared about the same, but the Western eaters were slightly more depressed.

So there you have it! Beans and tofu and meat pies are correlated with depression and anxiety! Well, the authors of the study are pretty fair about the limitations of their design in the discussion. The do mention another study and how high-fat, high-sugar diets caused decreased hippocampal BDNF in animals, and that diets high in refined carbohydrates are associated with more inflammation. They also made note that a Mediterranean-style diet (which would roughly correspond to the traditional and modern diets) tends to decrease inflammatory markers.

I wonder what the data would look like without the whole grain eaters? Also, full fat dairy versus low fat dairy. Why do researchers never present the really interesting stuff to a paleolithic diet-inspired psychiatrist?

(A sobering thought is that I may be the only paleolithic-diet inspired psychiatrist).

Tuesday, June 22, 2010

Depression 2 - Inflammation Boogaloo

It is well known that symptoms of clinical depression are likely mediated by inflammation in the brain. A number of lines of evidence support this idea, including that depressed people, old and young, have elevated levels of certain inflammatory proteins in the plasma and cerebrospinal fluid. Anti-inflammatory agents treat depression, and pharmacologic agents such as interferon-alpha, that cause depression, also lead to increases in the inflammatory proteins IL-6 and TNF-alpha. In addition, when someone who is depressed responds to antidepressant treatment, these same inflammation markers decrease (1). People with generalized inflammatory syndromes (such as acute viral illness, rheumatoid arthritis, insulin resistance, and cardiovascular disease) have higher rates of depression than the general population too. I also notice in my clinic that people who have had bone surgery tend to get depressed for a few weeks after the operation, more so than people who had other kinds of surgery. I always wonder if sawing through the bones releases an enormous wave of inflammatory cytokines.

There are several suspected mechanisms of how this inflammation leads to depression, many of them very cute. Here's one - the amino acid tryptophan is a precursor to Eli Lilly's second favorite neurotransmitter, serotonin*. Turns out that tryptophan is also the precursor to kynurenic. When the inflammatory cascade is activated, more tryptophan is made into kynurenic, which leaves less tryptophan around to make into Eli Lilly's second favorite neurotransmitter, serotonin. And everyone knows that without serotonin, we're unhappy (and angry). SSRIs work, in part, by undermining the effect of the inflammatory cytokines, pushing more tryptophan to be made into serotonin.

Here's another mechanism - inflammatory cytokines also interfere with the regulation of another neurotransmitter, glutamate. Glutamate is an excitatory neurotransmitter that, if left to go wild, can pound our NMDA receptors in the brain and wreak major havoc. No one wants overexcited NMDA receptors, and clinical depression is one among many nasty brain issues that can be caused by overexcitement. Astrocytes, little clean-up cells in the brain, are supposed to mop up excess glutamate to keep it from going nutso on the NMDA. Turns out inflammatory cytokines interfere with the clean-up process (2). The horse tranquilizer (and club drug) ketamine, when administered IV, can eliminate symptoms of severe depression pretty much immediately in some cases (do NOT try this at home) (3). Ketamine helps the astrocytes mop up glutamate, and it is assumed that this is how ketamine instantly cures depression. Unfortunately, the effects of ketamine don't last, otherwise it would be a nifty psychiatrist's tool, indeed.

Finally, inflammatory cytokines also push the brain from a general environment of happy "neuroplasticity" (mediated finally by our old friend, BDNF) towards an environment of neurotoxicity (sounds bad, and it is!).

In my post on vegetable oils, I made note of a popular theory that a relative imbalance between the consumption of anti-inflammatory omega 3 fatty acids (fish oil) and inflammatory omega 6 fatty acids (vegetable oil, such as corn oil) predisposes us to inflammation. The omega 6 fatty acids are the precursors for many of the nasty, depressing cytokines mentioned above (such as IL-6). Well, an absolute flurry of research has been done in this area in the last decade or so, because omega 3 fish oils would be a nifty, low side effect, cheap treatment for depression, if it worked. Some studies have been disappointing (4)(5). However, the largest study yet, hot off the presses, does show benefit (equal to a prescription antidepressant) for those who have depression, but not concurrent anxiety, at a daily dose of 150mg DHA and about 1000mg EPA. (DHA and EPA are fish oil omega 3 fatty acids).

Well, neat! But adding extra omega 3 is just one half of the omega 6/omega 3 balancing act. What if we decreased dietary omega 6 at the same time? Researchers looked at the blood levels and tissue levels of all the different kinds of fatty acid in this recent paper. Turns out that depressed people had higher amounts of omega-6 fatty acids, but the amounts of monounsaturated fats, saturated fats, and omega 3 fats were about the same between depressed and non-depressed individuals. (Other studies showed a decreased amount of omega 3 and an increased amount of omega 6 (6)).

As far as I know, there haven't been any major studies testing both a dietary decrease in omega 6 and supplementation with omega 3 for depression, but it would be an interesting intervention. Dr. Guyenet uses the work of Dr. Lands to make a case that reducing omega 6 PUFAs to less than 4% of calories would be a great way to reduce overall inflammation, and lots of Western disease. Hunter gatherers, such as the Kitavans, consume less than 1% of calories from omega 6 fatty acids. Right now, in the US, about 7% of our calories are omega 6 PUFAs.

In summary - inflammation is depressing! Fish oil may make it better, but avoiding corn/safflower/sunflower/soybean oil (theoretically) makes it all better still, and is the natural state for which we are evolved.

*Eli Lilly's favorite neurotransmitter is, of course, dopamine.

Monday, June 21, 2010

Cravings and Processed Food Woo Woo

David Kessler wrote an interesting book last year called The End of Overeating, in which he examined the nature of the food industry in America today and how it might contribute to overeating and obesity. Kessler's book takes up where Fast Food Nation left off - Fast Food Nation will make you never want to eat at a fast food restaurant again, (and also, since reading it I've used as much sterile technique as I can in handling industrial beef and chicken in my own kitchen.) The End of Overeating examines many of the menu items and advertising for our favorite chain restaurants (Chilis, TGI Fridays, those sorts of places), noting that most of the food is purposefully made "hyperpalatable" with generous heapings of fat, salt, and sugar. He contends that this combination short-circuits our appetite regulatory system, so we eat more and more, and begin gaining weight, when weight gain has been such an unusual problem historically for the human species.

I agree that the types of food (particularly wheat, sugar, vegetable oils, and other highly refined carbohydrates) seem to drive us into addictive behaviors when it comes to eating (and as I mentioned in the Wheat and Schizophrenia post, there is some biological evidence that gluten and beta casein A1 activate opiate receptors). All the pretty, pretty advertising with those short ribs dripping in sugar and doesn't help get the message across that those short ribs (or really, the sugary sauce) should be a special treat, rather than a daily indulgence. But at the heart of the idea that the industry is manipulating our food and our eating is still that idea that we are weak, that we are gluttons, and if only we could get ourselves in hand, we wouldn't be fat. That the food industry is playing to our weakness and leading us along the path to disease and obesity.

We aren't weak. And guess what, if you are obese, it is not because you are a glutton. It really is your glands (if one can use 'glands' in a broad sense to encompass the hormonal environment and appetite regulatory systems). Really. And the only way that obesity is genetic is that some people will be more vulnerable to the hormonal impact of all the trashy food we eat that is not actually, truly, fit for human consumption. Stick to whole, real food and ditch the wheat, vegetable oil, and sugar (and if you are obese, cut down your carbohydrates in general), and you don't have to worry about bowing to food industry's every whim.

"Naturally" skinny folks - even you (unless you are extremely lucky) will slowly, inevitably put on visceral fat over the years on a Western diet. Half the people who die of heart attacks aren't obese. At least those of us who tend to put on a bit of fat have an early warning sign and, perhaps, a bit more motivation to get cracking on cleaning up our foods.

But there is that little niggling fact that there are addictive qualities to processed modern foods. And when you are newly breaking the habit, or if you are feeling emotionally overwhelmed, it can be easy to slip back into the happy world of drippy sugar sauce and shiny, shiny glazed doughnuts.

The End Of Overeating's most interesting message, I think, is in the idea of "food rehab." He recommends the most effective behavioral method around (and an ancient method designed to keep us from eating poisonous things!) for conquering cravings - disgust. What has helped for me is a reading/educational program (hardly sexy - it's not a 5 day diet or a juice fast - it's a reading/educational program!). Fast Food Nation, Michael Pollan's books, Food Inc., The End of Overeating, Good Calories, Bad Calories, and The Unhealthy Truth will get you hopping mad, and sickened. When you get the idea drilled into your head that processed sugar/vegetable oil bombs are actually poison, and that little bit of bile rises to the back of the throat when you think about eating them, the cravings ain't so bad. Read about The Lady's Brunch Burger, preferably after you have eaten a large, satisfying meal. If you are the kind who gets fired up about corporate conspiracy and the government's seeming lack of protection of our interests (for example, our health), then these books are the books for you.

And if you are the kind of person who must have what you "cannot" have, remember, the paleo way of eating is not about being a martyr. It's about eating food we're evolved to eat most of the time to hopefully reduce the risks of western disease. It doesn't mean you can never have a shiny, shiny glazed doughnut again. It will throw your hormones out of whack for a bit, and if you are trying to lose fat, it will slow the process down. But in the whole scheme of the million calories we consume over the year, that Sunday morning doughnut is not such a big deal. Don't be surprised, however, if it doesn't appeal to you after a while. And that's okay too.

(And now a little side rant about what the nutritional guidelines have done to our food - all those sad skinless chicken breasts and "lite" vegetable oil dressings... they made real food the enemy, when it has nurtured and sustained us for thousands of generations. Science is a powerful tool, but if you don't have common sense, it will lead you very far astray.)

Off to have a square of chocolate now. Remember, chocolate is a vegetable (70% cacao and higher, that is).

Sunday, June 20, 2010

Vegetable Oils and our Brave New World

A quick review of the basic premise, this new lens through which I examine nutrition, general health, and mental health: humans beings will have the best chance of good physical and mental health by staying true to the diet and activities that we are evolved for. Let's get back to diet for the moment and focus on some of the differences between what we eat today, and what physically healthy peoples and cultures ate. Much of the following information is taken from Food and Western Disease (never leave home without it).

We know from several hundred years of good observation and anthropology that healthy peoples ate a wide variety of different foods, with vastly differing percentages of macronutrients (primarily differences in carbohydrates and fats - protein is usually around 15-30% of calories). The types and quality of the food they ate, however, universally differed from our current diet in the following ways:

1) no wheat, and if grain-based the grains are carefully prepared to minimize antinutrients
2) minimal amounts of omega 6 fatty acids balanced with omega 3 fatty acids (or vast amounts of omega 3)
3) reliance on whole foods with no industrial processing (therefore no highly refined carbohydrates or sugar other than perhaps seasonal raw honey and wild fruits)

In my opinion, one doesn't need to understand the science or biochemistry of these differences to go forward with a paleolithic-style diet based on the time-tested diets of healthy cultures. However, I'm interested in what it is about these differences that might cause Western disease.

I'm going to focus on #2 at the moment, and introduce a fading star of the "heart-healthy diet," vegetable oils. (Or not so fading star - this recent article trumpets vegetable oil as the second coming, though, as always, Stephan at Whole Health Source has a reasoned review.)

Corn oil, safflower oil, sunflower oil, peanut oil and/or soybean oil are ingredients in pretty much all processed food. Just check the list on the back. They are in breakfast cereal, bread and other baked goods, and also in fried items, salad dressings, mayonnaise, sauces, and are used (along with canola oil) in the fryers at most restaurants. They are cheap and relatively tasteless, which makes them perfect for certain industrial and restaurant food applications. They are also universally high in omega 6 fatty acids, and therefore we eat a ton of them in the Western diet, especially since throwing out butter, lard, and beef tallow 30-40 years ago.

How could this possibly matter? Omega 6 fatty acids are a type of PUFA (polyunsaturated fatty acid), which are required by the body to make certain hormones and signaling molecules. Omega 6 PUFAs are "essential" fatty acids - we can't make these signaling molecules without them, and we need them to live. PUFAs are made into HUFAs (highly unsaturated fatty acids - which isn't all that vital to this discussion but I like to say 'HUFA'), and omega 6 PUFAs (in particular linoleic acid) are made into the HUFA arachidonic acid. Arachidonic acid (AA) is the precursor for all sorts of *inflammatory* signaling molecules, including (as an example) COX-1 and COX-2 (which are blocked by ibuprofen and other NSAIDS that decrease pain and inflammation). (Here is a very understandable review of eicosanoids.)

Too much inflammation mediated by a high dietary percentage of the omega 6 fatty acid linoleic acid (the predominant fatty acid in corn oil) can be reasonably associated with coronary vascular disease, insulin resistance, cancer, hypothyroidism and other autoimmune diseases, thrombotic stroke, headaches, asthma, arthritis,(1) melanoma, depression, and psychosis.

But why do I keep harping on "balance" and those omega 3 PUFAs? Well, turns out the omega 3s (wild fish oil is the best source, but it is also available in grass-fed animal fat, other kinds of seafood, flax, and in more balanced levels with omega 6 in walnuts and macadamia nuts) compete in the body with the omega 6s in every which way. Omega 3s are precursors for anti-inflammatory signal molecules (which, obviously, counteract the inflammatory signal molecules). We can only store so much of either, so if we eat omega 3, we displace some of the omega 6 from our systems. Supplementing with omega 3 fatty acids has been shown to be beneficial in a number of major diseases (2). Again, we need both to survive, but if we max out on the omega 6 without any omega 3, we end up with a highly inflammatory soup of chemicals stored and floating around in our bodies predisposing us to that list again - cancer, diabetes, obesity, depression, heart disease, and autoimmune diseases.

Here are some numbers from Food and Western Disease about ratios of of omega 6 to omega 3 fatty acids in different populations (from page 46):

Omega 6/ Omega 3 ratio
Coastal fishing populations: <1
Hunter-gatherers: 2-3
Greece in the 1900s: 2
Japan today: 4
Northern Europe today: 15
USA today: 17

And here's the real kicker about the modern diet - first we load ourselves up with vegetable oils to create a large reservoir of pro-inflammatory molecules, and then add a soup of what are thought to be highly allergenic and pro-inflammatory proteins (gluten, gliadin, beta casein A1, proteins from peanuts and similar proteins from genetically modified soy, etc. etc.). Our modern diseases can almost always be linked back to inflammation of some kind. In my mind, this combination explains why my schedule is full every day.

How can you eat less omega 6 and more omega 3? One way is to eat more paleo. Get rid of the processed food. Use olive oil and vinegar instead of supermarket salad dressing. Balance out nuts (relatively high in omega 6 too) with some fish oil from wild caught fish. Poultry fat is relatively higher in omega 6, so eat grass fed beef and wild caught fish in a nice balance with your chicken and turkey.

And here's where I really part ways with the Grand Poohbahs of nutritional recommendations - you can eat more saturated fat. (Really. It won't kill you.) Instead of baking with industrial seed oils, use butter or coconut oil. They are neutral players in the omega 3 omega 6 fat war, and plenty of healthy cultures eat a reasonable or even high amount of saturated fat (the Masai, the Kitavans, the Tokelau) and they don't drop dead of heart attacks at age 50. Or 75. Pastured butter, bone marrow, and other yummy, more traditional treats are high in saturated fats are also the best sources of some vitamins we need but just don't get in our modern diet. But more on that later.

See, here's what has happened with the nutritional recommendations over the years. First we were told not to eat saturated fat and foods high in cholesterol. It was figured out almost immediately that foods high in cholesterol (such as eggs) don't cause heart disease or even elevated cholesterol in humans, but that was deemed confusing, so the message changed to don't eat saturated fat. At first everyone was moved over to the PUFAs - vegetable oils, including all that deadly trans fat margarine, but then it was discovered that PUFAs cause cancer and trans fats are horrible, so the message switched to 'eat low fat!' We're fairly restricted in the amount of protein we can eat anyway, so a low fat diet is therefore very high in carbohydrates (our particularly vicious mix of sugar and wheat). Then everyone following this advice got REALLY fat and diabetes incidence exploded. So THEN there was more backpedaling, and the message has changed to "healthy fats" (the omega 3s and olive oil), and "whole grains" (which when eaten without careful preparation as we eat them now *may* contribute to the problem) of a Mediterranean diet. (Though a true Mediterranean diet has plenty of saturated fat too. Cheese. Butter. France. Synonymous.) And consider that most of the disease states I'm looking at require two hits from the diet to make them happen - for example, wheat lectins to open the gut, and casein protein in the blood to predispose beta cells to autoimmune destruction in type one diabetes.

But one can see that all these nutritional recommendations backflip over themselves to catch up with science, and everyone is confused, sick, fat, and unhappy. But one doesn't need to stress over food, or make food the enemy. All one has to do is to go to a basic, default paleo style diet and then add in more modern foods (such as dairy) based on observations from other cultures (like the Masai) who ate them and don't have the diseases of modern civilization. All the work has already been done for us! We just have to pay attention.

Saturday, June 19, 2010

Wheat and Schizophrenia

I'm in the middle of an introduction to vegetable oils post, but in the midst of tweaking that one, my youngest woke up from her nap, and I moved to the family room to observe her toddling about while I glanced at this seriously interesting paper, Genetic Hypothesis of Idiopathic Schizophrenia: It's Exorphin Connection. Free full text! Click the gray box on the upper right.

Schizophrenia is an unfortunate brain disease. Inherited often, progressive, presents usually with social withdrawal, paranoia, hearing voices, that sort of thing. After a while you get a kind of "burnout" effect where the voices and whatnot lessen, but the afflicted is left with all the negative symptoms of social withdrawal, thought blocking, and an inexpressiveness known as "flat affect." MRI of the brain will show "large ventricles" at this point, meaning cell death (brain damage) has caused the active, lively part of the brain to shrink. Dementia, basically. You'll see schizophrenia in any large public park in any major city. Go ask the guy on the bench with holey shoes if he wants a sandwich, and see what he says. If it's paranoid meaningless word salad, that's schizophrenia, most likely. He had parents, brothers, sisters, maybe even a college degree. There aren't enough group homes, even if he were willing to stay.

Anyway, most of the research is focused on dopamine and genetic polymorphisms of the receptor (yawn), some on acetylcholine, histamine, serotonin. The usual questions about ineffective brain chemistry. The usual treatment is neuroleptic medication (hopefully decreases excess dopamine in the right place and leaves it well enough alone in other corners of the brain). Read a popular press book called "The Food-Mood Connection" which sounds like my sort of book, really, until the the author (who has a PhD of some sort!) explained that schizophrenia in a certain case was caused by childhood teasing. Poor man was treated with horrible prescription medicine and his genetics were examined, but I suppose some serious teasing psychoanalysis would have cured that schizophrenia must have been his mother, come to think of it.

Anyway, there's a funny thing about schizophrenia, turns out that quite a few of the adult schizophrenics on Handford's inpatient unit in 1967 happened to have a major history of celiac disease (gluten/wheat intolerance) as children. As in 50-100 times the amount of celiac disease that one would expect by chance. Celiac doctors also noticed their patients were schizophrenic about 10X as often as the general population. That's a lot!

Allow me to paraphrase and expand on Table 1 of this paper, "Major Evidence that Peptides from Grain Glutens Evoke Idiopathic Schizophrenia in Those with Its Genotype"

1) In the 1960s, many observations suggested celiac disease and schizophrenia shared some genes. The role of gluten in schizophrenia was examined.
2) Epidemiologic studies showed a strong, dose-dependent relationship between grain intake and schizophrenia (Pacific islanders who ate no wheat had extremely rare occurence of schizophrenia - 2 in 65,000 rather than about 1 in 100 as we have in the grain-eating West. Then the same islanders changed their diet and began eating wheat - and schizophrenia became common).
3) Clinical trials and showed that gluten made new-onset acutely ill schizophrenics worse. Only occasional long-term patients responded to gluten restriction (remember, the affected brain cells of the long-term schizophrenics are already dead, so getting rid of the possible poison that killed the cells won't make much difference).
4) NIH investigators looked for poisonous protein fragments derived from gluten, gliadin, and casein. They found them - potent opiate (yes, opiate as in morphine. Or heroin) analogs they called "exorphins." They did these studies in rats, and I've read several of them. Very creepy. Turns out, you take wheat gluten, add stomach enzymes, and you end up with fragments of proteins that are potent opiates (1). The cute thing is these fragments aren't digested by the small intestine and definitely end up in the body and brain of rats that are fed gluten orally. Inject these same proteins directly into the brains of poor unfortunate rats, and you get rat seizures.
5) People with schizophrenia have a lot of these opioid-like small gluten-derived peptides in their urine. Way more than people without schizophrenia.

Let me review what is perhaps the most important part of the paper - a gluten-free diet definitely improved some of the new-onset schizophrenics on the inpatient unit. Not all of them. But 2 out of 17 or so. Putting back the wheat made the affected a lot worse. 115 patients on a locked ward were all given a gluten free milk free diet (remember the casein issue). They were released into the community (got better?) on average twice as fast as the similar patients on another, diet as usual ward (p=.009). It is of note that repeat studies didn't show the same thing, but instead of 17 or 115 patients, these studies had 4 or 8 patients, and they used chronic schizophrenics (end stage, when the brain cells are already gone).

Historically, prior to WWII, when grain consumption was super-high and neuroleptics (those medications, as you recall, which affect brain dopamine levels and are used to treat schizophrenia) did not yet exist, there are reports of schizophrenics having marked, unexplained fluctuations in weight and gut symptoms, poor iron absorption just like celiac sufferers, and "post-mortem abnormalities like those subsequently discovered in celiac patients." Why aren't these found now? Well, it turns out that a side effect of neuroleptics is that they decrease the permeability of the gut. Meaning gluten may not be able to weasel through quite so easily.

Which begs the question, is that the side effect? Or perhaps the principle effect?
Who knows?

Not psychiatrists in 2010. The paper (from 1988) finishes by suggesting a number of methods to investigate this connection further. One of the suggestions was morally bankrupt (feed the identical twins of schizophrenics a high gluten diet to see what happens!), but intriguing. That study wasn't done (fortunately). Nor, looking at pubmed (via eCommons), were any others (that I could find. I'm not the wiliest research paper discoverer so I might have missed one). The article is mentioned in a few review articles, and schizophrenics were left to eat wheat in peace.

Edit: I shouldn't be such a cynic, and I should search harder before I post - Here are more recent studies, including one from last month (Thanks to the commenter for the link - why I love blogging. Interactive! Editable! We can all stand on eachother's shoulders and the shoulders of past giants). All told, they throw out some more "biochemical smoke" about the link between schizophrenia and gluten:

Markers of Gluten Sensitivity and Celiac Disease in Recent-Onset Psychosis and Multi-Episode Schizophrenia: Conclusions - Individuals with recent-onset psychosis and with multi-episode schizophrenia who have increased antibodies to gliadin may share some immunologic features of celiac disease, but their immune response to gliadin differs from that of celiac disease.

Novel immune response to gluten in individuals with schizophrenia: The researchers here looked at all sorts of different anti-gliadin antibodies and celiac disease associated biomarkers (meaning some different antibodies and also specific celiac MHC genes - basically genetic predispositions to have autoimmune response to wheat). They also did some fancy chromatography to find if the schizophrenic's blood reacted to other wheat proteins, and then it sounds like they used "peptide mass mapping" to figure out what the wheat proteins were that the schizophrenics were reacting to - and the results were... schizophrenics of the wheat-reactive subtype had lots of anti-wheat protein immune response, and a lot of them were completely different than those found in celiac disease.

A Case Report of the Resolution of Schizophrenic Symptoms on a Ketogenic Diet That link is to the full text. It doesn't need much translating to make it more understandable - the title says it all.

This article from 2006 is also cited often, and I did look at it before I posted the first time, but it doesn't add that much: The gluten connection: the association between schizophrenia and celiac disease. Basically it says there are case reviews in the literature that show dramatic improvements in schizophrenia on a gluten-free diet (these studies were the same ones commented on in the original paper that I reviewed in detail at the top of the post) and that only a subset of schizophrenics are affected. (The researchers in residency would always refer to them as "the schizophrenias" rather than "schizophrenia." It is several different diseases, lumped into a similar symptom cluster because we don't fully understand the pathology, and in psychiatry, lumping is done by symptoms, as that made the most sense for research purposes.)

I would love to take a look at this one, but my institutional access won't get me there for the moment - A PILOT STUDY OF THE KETOGENIC DIET IN SCHIZOPHRENIA
PACHECO et al. Am J Psychiatry.1965; 121: 1110-1111. We'll track it down eventually.

The bottom line? Schizophrenia is a progressive and destructive psychotic mental illness that, at the moment, can sometimes be managed with medications and community therapeutic support, but does not have a cure. Some people with schizophrenia are bound to have the gluten-sensitive variety, and a few lucky souls apparently have been cured among the case reports. A gluten-free diet is safe and doesn't have side effects - I don't see a good argument against giving it a try for anyone with schizophrenia who is willing to give it a go, at least for a few months (how long? 3? 5? I'll look more into that one), while more data is being gathered. (You *might* get even better results with stabilizing your GABA receptors and whatnot via a ketogenic (very low carbohydrate) diet. More on this later! Very little research in psychiatry...) The worst thing that happens is you find you are not one of the gluten-sensitive schizophrenics, and you've gone without bread for a little while. The best thing that happens is that your symptoms get better, possibly quite a lot better.

Friday, June 18, 2010

Depression 1

I realize this blog is titled "Evolutionary Psychiatry," and I have yet to actually mention much psychiatry. In part because my job is to stick my nose where it doesn't belong, such asking you about your relationship with your father, or smack in the middle of metabolic syndrome and weight loss. In part we began with the paleolithic theories because I wanted to describe a basis of healthy eating, and put out some more information to say I'm not coming completely out of left field, though some of my perspectives aren't exactly conventional (though perhaps they are exceedingly conventional, seeing as how I prefer to eat as my ancestors did). I'm happy to be proven wrong about my ideas and perspectives if I find something that changes my mind along the way.

But let's talk about depression for a bit. It's a blockbuster, after all. In any given year, approximately 9% of the adult population is suffering from major depression or dysthymia (1). Women are afflicted about 2-3 times as often as men, and 10-15% of women will become depressed after having children.

What is depression? Well, one must have a certain number of the following symptoms for a certain period of time - depressed mood, lack of interest, appetite changes (increased or decreased), sleep changes (increased or decreased), a generally negative outlook, suicidal thoughts, feelings of hopelessness, helplessness, worthlessness, poor energy, poor motivation, poor concentration, feelings of guilt... you get the picture. What causes depression? Well, it isn't zoloft deficiency. (That doesn't mean that zoloft won't help...) But it is obviously a combination of factors, including genetic predisposition, adaptive versus maladaptive coping skills, levels of stress, and sometimes biological or iatrogenic (i.e. caused by other medical treatments) factors.

To appropriately treat depressive disorders, one must obviously address all these these factors, and the generally accepted procedure nowadays is to combine a thorough medical work-up, psychotherapy, and medication if needed. In that respect the treatment for depression is extremely similar to the treatment for obesity and diabetes - which involves medical monitoring, nutritional counseling, psychological counseling if needed, and medication if needed.

But what *really* causes depression? Biologically speaking? Having a clinical depression means your brain isn't working as it should, and number of factors have been implicated. Among them serotonin system dysfunction, and problems with norepinephrine regulation. But the heart of the matter may be way down in the hippocampus, where stress may interact with genetic predisposition and other factors to create a deficiency in a brain fertilizer of sorts, brain-derived neurotrophic factor (BDNF). It is thought that antidepressant medication actually helps depression by increasing the production of BDNF.

Well, what else can increase BDNF? What other commonly recommended treatment works just as well for depression as antidepressant medication? Exercise, of course. How would exercise increase BDNF in the hippocampus, of all places? There are a number of ways, but the most interesting to me right now is via nitric oxide. Nitric oxide is a gas we make in our red blood cells, especially during exercise and meditative-type breathing. Nitric oxide does all sorts of happy things in our bodies, including relaxing blood vessels and lowering blood pressure, and it is also necessary for erections in men.

Perhaps I have gone far afield of depression at the moment. We psychiatrists, always getting distracted. (Did you know that impotence is related to diabetes and insulin resistance?) But back to the brain! See, antidepressants have to be absorbed in the GI tract, then the active molecules have to somehow make it to the blood brain barrier, and then find the right part of the brain, where a whole cascade of membrane proteins, second messengers, vitamins, and neurotransmitters have to work in concert to increase the production of BDNF to cause the antidepressant effect. Whew. But good old nitric oxide, it is a tiny little molecule, a gas. It doesn't have to rely on all these other players. It can just float through membranes and bind directly to the promoter region of the gene for BDNF, and help the brain make more.

Great! Everyone go out and get some exercise, or meditate. But wait a minute.

It turns out that depressive disorders are a lot more common in people with type II diabetes, and that people with depressive disorders have a 65% greater chance than unaffected adults of developing diabetes. The correlation is so strong, in fact, that for a while researchers were trying to figure out if antidepressant medication actually caused diabetes. (Don't panic - unless the medicine is also making you gain weight, it is probably not adding to your risk of diabetes). As it turns out, successfully treating the depression doesn't improve the increased risk of diabetes. Hmmm, why would that be? Maybe because something else is causing diabetes and the depression, and zoloft isn't FDA-approved to treat insulin resistance?

Well, what does that have to do with the price of tea? I don't know, not 100%. But I have a sneaking suspicion about several factors. Here's one. You see, insulin resistance is associated with endothelial dysfunction (damage to the inner walls of the blood vessels). This means that nitric oxide isn't able to float through the blood vessels (where it is made) into the cells (where it is used). In a nutshell, the nitric oxide of people with insulin resistance cannot do all the things it needs to do. Such as help with sexual activity, reduce blood pressure, and perhaps, just perhaps, help the spectacular brain fertilizer, BDNF, repair the oxidative and inflammatory damage thought to be characteristic of a depressed brain.

So it turns out that maybe it is important for psychiatrist to know a little something about what causes insulin resistance and diabetes, and what an appropriate and effective dietary intervention might be for the whole metabolic derangement in the first place (hint - it's not a high carbohydrate diet).

Thursday, June 17, 2010

Eat What You Want**, Lose Fat, and Keep it Off Forever

** except for a few foods which currently constitute 60% of the standard American diet

(disclaimer again - I'm not your doctor - you may have a particular medical condition so that this information does not apply to you. Talk to your doctor if you have questions, but make sure he/she knows what the Friedewalde equation is!)

All you have to do is follow a few dietary rules to be more hunter gatherer in your eating:

1) Eat veggies. May substitute fruits sometimes, but most of the time it should be veggies. Prepare the veggies any way you like, and most people can use coconut oil and butter (from pastured sources is preferred).
2) Eat protein several times a day, too. It is preferable for it to be wild caught fish, organic poultry (or pork, for most people), shellfish and shrimp, omega 3 or organic eggs or grass fed beef, bison, buffalo, goats, venison, etc.
3) Snacks can be nuts, veggies, fruit, veggies with almond butter - that sort of thing.
4) Avoid (for the most part) soy, peanuts, grains, corn, and any processed food or added sugar.
5) Avoid all processed vegetable oils (watch those salad dressings, and "real" mayonnaise at the store is soybean oil! Use olive oil and lemon juice or vinegar!)
6) Keep your dairy high fat, fermented if possible, and try not to have it for every single meal.
7) Avoid alcohol (for the most part)

*Now a few simple lifestyle rules:

1) Get plenty of sleep
2) Move around (I'll have another post on exercise with more details)
3) Don't get too stressed (Build anti-stress/enjoyable time into your daily life)

*A few specifics on medical conditions/medications which may affect these rules:

1) Antihypertensive medication: Most people who start to eat this way decrease their salt consumption dramatically (no processed food), and the weight loss can lead to lower blood pressures fairly quickly. Keep your pressure monitored and consult your doctor.

2) Diabetes - especially type II, on any sulfonylurea medications (glipizide (glucotrol) and glyburide (micronase) are the most common, but there are several more): Dropping your carbohydrates like this can lead to low blood sugars if you are on these medicines, which cause your pancreas to secrete more insulin. So again, consult with your doctor!

3) Any condition for which you have to be on coumadin (warfarin) - A diet high in veggies can increase vitamin K, which will make your coumadin less effective. A diet high in omega 3s relative to omega 6 fatty acids will make you more likely to bleed (omega 6 fatty acids are pro-thrombic and omega-3s tend to displace them in the diet and in tissues). So again, go slowly (see below), keep the INR in check, and CONSULT WITH YOUR DOCTOR.

4) Advanced Ischemic Heart Disease and Severe Type II Diabetes - *some* evidence suggests saturated fats may actually be bad for you. Focus on the olive oil and fish oil, and keep in mind that most animal fats (the fat on your steak and in your chicken skin) are actually very high in oleic acid (same fat as olive oil) and other "cholesterol neutral" fats. Plain old saturated fat would include: coconut and palm oil, high fat dairy, butter, beef tallow, lard. This advice may change as the science on this subject is expanding far more rapidly than the "official" advice. But even Staffan Lindeberg, my paleonutrition guru, advises against loads of saturated fat with these conditions. I'll have a whole post on this once I do more research and wrap my head around the theory of lipotoxicity. However, I must admit I am exasperated with the cognitive dissonance between the official recommendations and what might actually work to help improve insulin resistance and reduce atherosclerosis. As near as I can tell, the official way to eat recommended to diabetics is moderate or low carb, lots of fiber, and low in animals and animal fat. This means you are pretty much limited to salad, skinless chicken breasts, olive oil, and wood chips (fiber), with some token whole grains, potato, or fruit thrown in. But the truth of the matter is, we can either be low carb OR low fat. Protein can't really change that much. Wood chips are not a viable substitution for fat. Sigh. I'm a psychiatrist, and this kills me. I'm not sure how the heads of nutritionists, cardiologists, and endocrinologists just don't explode.

*How to Start Slowly:

Not ready to take the full plunge? Still have lots of pasta in the pantry?

1) Start by ditching the processed food, meaning anything with 10 zillion ingredients and anything with high fructose corn syrup in it. Get rid of fruit juice, soda, and other added sugars. Take your coffee black or with cream, switch to a touch of honey (preferably raw) instead of sugar. Reduce the amount of honey over time. Use real maple syrup on your pancakes. You'll use less because it costs more.

2) After you're comfortable with that, then reduce the grains/sugars to one meal a day. The other meals should follow the simple dietary rules. Your best bet is to have the high-carb meal happen within a two hour window after you exercise. Your worst bet is to have your high-carb meal every morning for breakfast. If you want a sugary treat, eat it within 30 minutes after exercise.

3) Then clean up your grains. Wheat is probably the worst offender, wild rice and quinoa are the least, though you can pack on quite a carb load with an anemic-looking amount of rice. Get rid of any non-organic sources (the others will be genetically modified which *may* have autoimmune implications - until they are more thoroughly tested, why risk it?). Corn may be more or less okay, but in processed food usually comes with a lot of corn oil, which is horrible. Sorry.

*I'm following all your rules and I'm still not losing weight!!

1) What is your insulin status? You may be sensitive to too many carbohydrates (if you have excess abdominal fat, love handles, high blood pressure, have trouble losing weight, and you've been eating the standard American diet, you're probably a bit insulin resistant). First, ditch any remaining grains. Then decrease the amounts of more sugary fruits like apples, oranges, bananas, pineapples - you're better off with lower carb fruits like plums, peaches, figs, those kinds of things, and then only once a day or every few days.

2) Are you intolerant to lactose or casein? Get rid of the dairy (except eggs) and see what happens.

3) Are you following the lifestyle rules too? Diet is probably only 80% of fat loss.

4) Are you vitamin D deficient?

5) Are you eating too much protein? If you are packing in five pounds of porterhouse a day, you could be making glucose via gluconeogenesis, resulting in fat gain.

*I'm following all your stupid rules, and I feel like crap!!

1) A sudden drop in carbohydrates can cause some people to feel sick and tired and grouchy. This can happen even without ketosis (which won't generally happen with the amount of carbohydrates you would eat from having lots of veggies and fruit). This usually passes within a couple of days, (after which you will tend to feel energetic, clear-headed, and fabulous) but go to the "How to Start Slowly" section if you like.

*Wait a minute - where are the portion sizes and calorie counts?

1) Hunter gatherers did not have FitDay. And many modern hunter gatherer societies have plenty of food about - no malnutrition, and yet still they are effortlessly slim. Our appetites regulate themselves, as long as we don't have foods about which likely throw off our hormonal appetite regulation (added sugar and wheat are the most likely culprits). Don't go hungry. If you are hungry, eat. If you aren't hungry, you don't have to eat. If you're like me, you might not trust your natural appetite after watching your food closely for a long time. Then go for a pile of veggies and a palm-sized amount of protein. The rest will take care of itself.

*I want a cookie!!!!!

Eat a cookie.

No, seriously, eat a cookie. The way of eating detailed above puts us into a fat-burning metabolic mode. As long as you spend the majority of your time eating according to the rules, you should be in fat-burning mode most of the time, and a cookie ain't gonna hurt much. You will be out of fat-burning mode for a few hours. Big deal. If you are insulin resistant, it will be harder to get into fat-burning mode, and harder to get out of fat-storing mode. So a cookie is going to do your diet more harm than someone who is insulin sensitive.

* The American Heart Association Or Other Official Grand Poohbas say that vegetable oils are fine and are preferred to animal fats! Why is that?

They are trying to get you to decrease the amount of saturated fat you eat by replacing it with vegetable oil. Corn oil will lower your total cholesterol lickety split, but here's a gem of an old study dug up on Hyperlipid showing it may also kill you and cause diabetes (1). I personally think it is unfortunate advice, as the seed oils such as corn oil are high in omega-6 and will cause your omega-3s and omega-6s to be out of balance, and this is most likely very bad for both your health and your brain. I'll do another post on the specifics of the PUFA fat balance.

* Won't I be missing vital vitamins and minerals if I am not eating grains?

No. You won't be. Tells you how important grains are to good health. If you drop grains, you don't need a single vitamin or mineral supplement to make up for it. Not the same story if you drop all animal foods! Speaking of...

* I'm a vegetarian

Why? Is it strictly for improved health? Then you might want to look into it some more and consider other approaches. Adult vegetarians are generally healthier than the average American on the standard American diet, but you will be missing some major vitamins and minerals (especially if you are a vegan), and you will find it very difficult to keep your omega 6 and omega 3 in balance. Is it for environmental, sustainability, or spiritual reasons? All those are very valid and important reasons to some people, though I would argue that if you consume conventional grains, that the environment suffers a great deal (2). Consider adding dairy, and especially consider adding fish. Flax oil is an okay omega-3 additive, though it is high in phytoestrogens, and many people have poor conversion from flax oil (ALA) to the shorter-chain omega 3 acids we need to use in our bodies (found in fish oil). Watch your corn oil and omega 6 intake like a hawk. Soak/use traditional methods to prepare your grains and beans. Nuts can be pretty high in omega 6, so steer towards macadamia nuts which are somewhat higher in omega 3s.

Tuesday, June 15, 2010

Beans and Grains: A Brief Introduction

In previous entries, I made mention of a paleolithic-style diet being optimal for human consumption. By "optimal" I meant you can rely on your appetite to direct you to stay lean (if you are already lean), or be a tad more careful about what you eat and lose the extra fat (in a later post I will explain exactly how to lose the fat!), and, it seems pretty scientifically clear from epidemiological and observational studies (and from a few small studies on people with actual disease) that if you spend your whole life eating this way, also get plenty of sleep, a moderate amount of exercise, and appropriate social interaction, your chances of getting Western diseases such as ischemic heart disease, type II diabetes, many autoimmune diseases, stroke, acne, depression, hypertension, obesity, osteoporosis, and tooth decay are very small. Ooo ooo cool! Sign me up!

There's just one *little* caveat which I will elucidate more fully today - the strict paleo folks avoid grains (including corn, wheat, rye, buckwheat, oats, quinoa, spelt, rice - except maybe wild rice). Or beans and legumes - including chickpeas, peanuts, and especially soy. Or sometimes cow's or goat's milk (though I will go into more detail about milk in a separate post). Also, some will avoid potatoes, tomatoes, eggplants, and other nightshades. Hmm. Kind of a drag, really. (Though once you've gone over to the dark side of paleo, those large pants and type II diabetes seem like way more of a drag than giving up your daily dinner roll).

How could beans and grains be bad for you? Well, let me count the ways:

Lectins: Lectins sit on the outside of plants, attached to sugar molecules. Their roll in nature is thought to be to protect the plant from plant-eating animals. While lots of plants have lectins, the highest concentrations are in seeds, soybeans, beans, potatoes, and peanuts. Normal cooking doesn't destroy the lectins, though pressure cooking will (except for wheat agglutinin - that nasty bugger is impossible to kill), and your stomach and digestive tract don't seem to break them down completely either. (Well, who cares?) Turns out these lectins can penetrate your gut and fly around willy nilly within your body, and there is a mounting body of scientific evidence that lectins play a role in atherosclerosis, insulin resistance, cancer, and autoimmune disease (1). Wheat agglutinin has been shown to bind leptin receptors, which could explain leptin resistance (the first step on the road to obesity). Unfortunately, the theoretical biochemical mechanisms of these things in each separate disease state are becoming clear, and it ain't pretty. Oh. (Now there's no way to get away from lectins - tons of plants have them! But if you vary your plant consumption you'll be exposed to less of the same ones all the time. And seeds and beans, the plant's precious resource for future plant generations, have the most concentrated versions.) To add to the problem, post-modern genetically modified wheat and soy have enhanced lectin activity. Lectins are pesticides, after all, and these superwheats and supersoybeans are more resistant to pests and/or Roundup pesticide. This means the wheat we eat today is very different than the wheat we grew up with 30 years ago, and GMO soybean is questioned as a cause in the rise of peanut allergies in children.

Protease inhibitors: Live in beans and seeds and cereals. They keep the gut from breaking down protein entirely. That means if you eat protein + cereal, your absorption of the protein can be diminished.

Phytoestrogens and isoflavones: These are plant-made hormones that can disrupt the endocrine system. They also might be powerful antioxidants, but that isn't entirely clear. Soy is chock-full of them.

Glycoalkaloids: on the skins of potatoes - can be poisonous in large quantities - probably fine in small quantities.

Plant sterols: thought to decrease the absorption of cholesterol, these guys have been added to margarine recently. Seeing as how margarine is not exactly a health food, adding plant sterols to it seems to me like sprinkling lipitor on your pizza. A certain cardiologist blogger makes a convincing argument to steer clear of sterols.

Phytic Acids: Found on all grains, and while you can get rid of these with warm soaking and fermenting, the phytic acids in oats won't reduce that way, as oats have no natural phytases. These bind dietary minerals, such as calcium, magnesium, zinc, iron, you name it. So if you consume the unreduced phytic acids with every meal, a lot of the minerals in your food will go down the toilet. Literally.

The kicker is, humans have been consuming grains for 10,000 years. Over time we developed a million ways to reduce the toxic effects of these grains via various traditional harvesting and cooking techniques. Without these techniques (hand milling, soaking, sprouting, long fermentation times rather than quick-rise yeast) and getting a lot of our calories from wheat (whose giladins and glutens are among the toughest to get rid of), cereals and beans become sources of nutrient depleting, empty calories, and vectors of biochemical mayhem within the body. Take a grain and smash it flat to mix all the phytic acids and lectins together, then puff it and oxidize the seed oils, add sugar and sell it as chocolate puff cereal - we aren't exactly evolved to eat that.

It's not that a little bit will be all that bad (unless, perhaps, you have autoimmune disease, which I will go into later). It's that massive exposure in every meal day in day out... well...

(Information from this post was taken almost entirely from Staffan Lindeberg's Food and Western Disease. In addition, some of the thoughts about genetically modified wheat and soy come from The Unhealthy Truth.)

Monday, June 14, 2010

The Fat Post: For Heaven's Sake, Eat the Skin on your Chicken

A hundred dieters just turned their heads. "What? The SKIN? That's where all the FAT is!"

Well, let me regale you with a tale of ego, bias, and misdirected good intentions.* Back mid-twentieth century or so, public health officials and doctors were trying to figure out what caused heart disease. At the time, there was only a blood test available for total cholesterol, and investigations of atherosclerotic plaques showed that they were made of cholesterol! Also, excess fat on your body is saturated fat, pretty much. So these researchers decided 1+1 = 2, because people with high total cholesterol did seem to have more heart attacks.

Dr. Ancel Keys, made famous for his conscientious objectors study in WWII, inventing the K ration, and also for feeding institutionalized schizophrenics different diets and monitoring their cholesterol, came up with the Dietary Fats Hypothesis. Which is, basically, that eating a diet high in fat causes heart disease. For evidence, he produced his (also famous) Seven Countries Study, where countries where people ate low amounts of fat (such as Japan), had less heart disease than countries where people ate more fat (such as the U.S.). Unfortunately, he hand-picked these countries, leaving out the troublesome ones (such as places in Finland, Crete, Newfoundland, France, Switzerland, etc. etc. etc.(1)) where people ate plenty of fat, and had low incidence of heart disease. For various reasons, this dietary fat hypothesis took off, and before you know it, Time magazine had a cover with fried egg eyes and a bacon frown, and none of us were allowed to eat the skin on our chickens anymore. We were told to substitute "bad" animal fats with "good" vegetable fats (seed oils, like corn and soybean and safflower) and eat more carbohydrates in lieu of fats.

This recommendation was basically an unregulated experiment on the population of the United States, because there was never good evidence that this would prevent heart attacks or, perhaps more importantly to most of us, lessen overall mortality, though cholesterol will get lower if you lower your intake of saturated fat. Though really, if you look at the data, it doesn't matter.

The lone famous outlier was Dr. Atkins, who really did some brilliant work. Unfortunately, he was apparently something of a jerk, and people in the scientific community would go out of their way to prove him wrong and discredit him. Alas. (In my opinion, Atkins didn't get it completely right either, but he wasn't completely wrong).

Now let's fast forward to the 21st century, and look at all the scientific data we have accumulated over the years to show that dietary fat (especially saturated fat) causes heart disease and early death: Um, well, there isn't any (2). Well, okay, a few studies in people with advanced ischemic heart disease or diabetes showed worse outcomes with high amounts of saturated fat, but these studies weren't controlled for the kinds or amounts of carbohydrates the study subjects were eating, and in one of the studies the 'animal fats' involved included sausages and processed deli meats and the like (3). In fact, the Framingham Heart Study (perhaps the most famous heart disease study in history) has studied the dietary habits if three generations of people, and found no link between total dietary fat consumption and ischemic heart disease. Worse, though the Nurse's Health Study shows no correlation between total dietary fat consumption and heart disease in women (4), other epidemiological studies show a higher risk of cancer in women who consume low fat diets (5)(6).

Don't believe me? Check out this article in Scientific American about a meta-analysis of ALL the major dietary studies, comparing the daily food intake of some 350,000 people.

I'm not trying to promote a silly blood type or food combining diet, folks! I'm a mother and a doctor who wants to not worry about her weight and keep my kids from becoming the next diabetes statistic, so I have done a bit of homework.

All right, back to the main point. Yes, Fat (in general) = Not Bad (or, in some cases, V. Good!). Before you say, "Suweet! I'm off to Cinnabon!" please remember, fat+sugar = kiss your pancreas good-bye. And unfortunately, ladies and gentleman, all those fast "food" joints serve up their industrial meat with special sauces loaded with sugar on sugary buns with sugar sprinkles, more or less, so the KFC Double Down is still not a good idea. However, there is no consistent medical literature to back the AHA Recommended Diet limiting fat consumption to 30% of calories daily.

The whole fat story is more complicated, and I'm about to bring back the biochemistry, so if you are still interested, keep reading (at the very end will be a summary about what to eat), because, guess what, there are good fats and bad fats (7), but they just aren't the ones you might think:

1) The Good Fat: Monounsaturated fats, such as olive oil. Everyone pretty much agrees on this one. Olive oil is good for you. Hooray! In fact, the new healthy diet du jour is the Mediterranean Diet with its focus on healthy fats - olive oil! (Did you know that while the people in Crete had low incidence of heart disease, they have similar incidence of type II diabetes to the rest of Europe (8)? But I digress...) Another famous monounsaturated fat is canola (or rapeseed) oil. Unfortunately, canola oil is highly processed and some of it is even loaded with trans fats, which brings me to...

2) The Bad Fat: Trans Fats (boo!). What are trans fats? Well, unsaturated fats have chemical bonds that are, in nature, shaped like little boats. If you take an unsaturated fat and then heat it and use a chemical catalyst to make it hydrogenated (think margarine - boo!), then some of the chemical bonds are trans bonds, which are like little boats if they were cleaved by lightning and the stern flipped over and all the people on board were doomed to death by drowning. Trans fats are also unnaturally high in industrial grain-fed beef, according The Primal Blueprint. Trans fats are yet another example of the industrial process creating frankenfood that we just aren't able to metabolize correctly, and it killed us in droves. And be careful about those "0g trans fat" labels on food nowadays - up to 0.5g trans fat per serving can be rounded down to 0, so if you eat 5-6 servings of chips, you could be consuming up to 3 grams of deadly trans fats. Read the label and pass on ANY food with hydrogenated or partially hydrogenated oils in it. Do you know how to get an animal to develop atherosclerosis? Feed it something it doesn't normally eat, like red meat to rabbits.

3) The Fat that Will Make You Pull Your Hair Out: Polyunsaturated Fats (PUFAs). PUFAs are vegetable seed oils and fish and nut oils that we were told to eat in lieu of saturated animal fats. Ditch the butter, eat margarine! Ditch the lard - fry in vegetable oil! It turns out there are two kinds of PUFAs, omega 6 and omega 3. In general, most seed and nut oils are omega 6 (though macadamia nuts are pretty high in omega 3), and fish oil and flax oil are omega 3. Who cares? Well, the balance between omega 3 and 6 is important. In our modern diet LOADED with soy and corn oil (seriously, look on the ingredients of ANY processed food), we have a huge imbalance between omega 6 and omega 3. Omega 3 is only high in things like wild caught fish (NOT farm raised - those fish are fed corn/grain, and the actual omega 3 fats in salmon come from the little diatoms and algae they munch on in the wild) and grass-fed beef. So who cares if our ratio is off? Well, PUFAs (especially omega 6) are definitely linked to cancer (9). Yup. Different kinds of cancer. And fatty liver and insulin resistance. (sorry, chip lovers. sorry, infant formula drinkers, etc. etc. etc.). Oh, and corn-fed beef is also higher in omega 6 and almost missing omega 3, whereas grass-fed is reasonably more balanced between the two. Truth is, you don't want to ingest a high amount of PUFAs (though we need some to survive), but they are almost impossible to avoid. If you take some extra omega 3s, though, you can diminish the impact. Fat is important. Your brain is 60% fat - and it needs to be the right kind, or things don't work properly (more details on fats and the brain in another post).

4) The Fat of Kings: Saturated Fat. Poor saturated fat. That's animal fats and a few tropical oils (lard, beef tallow, eggs, butter, the skin on your chicken, etc. and palm and coconut oils) Did you know that the cell membranes of every cell in your body require saturated fat to work properly? Ingesting saturated fats will definitely raise your total cholesterol. It increases your LDL ("bad" cholesterol) - which I am going to go out on a limb a bit and say probably doesn't matter in the slightest, as long as you have a low number of "small, dense" LDL which are associated with high carbohydrate diets. Saturated fat also increases your HDL (hooray! "Good" cholesterol!), thus, total cholesterol will go up. You know who has been proven to do poorly with total cholesterol over 250? Men with known ischemic heart disease under the age of 50 (10). You know who hasn't been proven to do poorly with high cholesterol? Anyone else. In fact, in Japan they ask people to eat more of certain kinds of fats because it lowers risk of stroke. Did you know that a large percentage of the fat in a porterhouse steak is the same monounsaturated fat as in olive oil? Yeah, the Good Fat! Did you know that the only saturated fat to be linked to issues with ischemic heart disease and insulin resistance is palmitic acid, which is found only in small amounts in coconut oil, for example, which we have been told to avoid? Did you know that the young Masai warriors and the Tokelau eat diets of 33% and 50% or their total calories from saturated fat respectively, and have no appreciable atherosclerosis, diabetes or ischemic heart disease while they are eating their traditional diets?

(But why is everyone on lipitor? Ah, statins. They have been proven to help men with ischemic heart disease or people with hereditary hypercholesterolemia lower their risk of further heart disease. And they do lower cholesterol, which is likely not the reason they help. They are also thought to decrease inflammation, which is the real devil (along with small, dense LDL which are increased, again, in high sugar diets) - and statins can have a high cost.

This is a long one. Let's wrap it up: Telling everyone to cut the animal fat and exchange it for vegetables oils, high carbohydrates and saying sugar wasn't a major health problem was an unmitigated public health disaster leading to record obesity and failed diets for 30 years. I'm not going to pull any punches here, because doctors should know biochemistry, and a lot of this is basic, basic stuff.

You want to eat fat? Go olive oil, wild fish oil, and some nuts. Organic eggs have 5-7 times the DHA (an omega 3) of conventionally grown ones, and 1/5 of the omega 6 (11). Get a lovely steak derived from a cow that spent its life eating what it was supposed to eat - grass, not corn! Eat the skin on your chicken.

Bold? Not about to take a (in my opinion, hopelessly outdated) cholesterol test for a life insurance policy or disability policy, and unafraid to tell your doctor that you don't care about your total cholesterol or your LDL as much as whether you have a negligible percentage of small, dense LDL, your triglycerides are low and your HDL is high? Fry your eggs and organic ground turkey in coconut oil. Stir-fry with pastured butter. Yum Yum! Some individuals with certain genetic profiles may need to watch their saturated fats more closely than most of us. I'll go into this in more detail in a later post.

Don't go nuts and eat your fats with a lot of sugar or a huge pile of pasta, at least not very often.

*all meticulously documented in Good Calories, Bad Calories by Gary Taubes. He is the secondary source for much of my information. Dr. Stephan Guyenet has examined many of the primary sources on his blog, Whole Health Source